Drug repurposing is an attractive strategy for developing new antibacterial molecules. Herein, we evaluated the in vitro antibacterial, antibiofilm, and antivirulence activities of eight FDA-approved “non-antibiotic” drugs, comparatively to tobramycin, against selected Pseudomonas aeruginosa strains from cystic fibrosis patients. MIC and MBC values were measured by broth microdilution methods. Time-kill kinetics was studied by the macro dilution method, and synergy studies were performed by checkerboard microdilution assay. The activity against preformed biofilm was measured by crystal violet and viable cell count assays. The effects on gene expression were studied by real-time quantitative PCR, while the cytotoxic potential was evaluated against IB3-1 bronchial CF cells. Ciclopirox, 5-fluorouracil, and actinomycin D showed the best activity against P. aeruginosa planktonic cells and, therefore, underwent further evaluation. Time-kill assays indicated actinomycin D and ciclopirox, contrarily to 5-fluorouracil and tobramycin, have the potential for bacterial eradication, although with strain-dependent efficacy. Ciclopirox was the most effective against the viability of the preformed biofilm. A similar activity was observed for other drugs, although they stimulate EPS production. Ribavirin showed a specific antibiofilm effect, not dependent on bacterial killing. Exposure to drugs and tobramycin generally caused hyperexpression of the virulence traits tested, except for actinomycin D, which downregulated the expression of alkaline protease and alginate polymerization. Ciclopirox and actinomycin D revealed high cytotoxic potential. Ciclopirox and ribavirin might provide chemical scaffolds for anti-P. aeruginosa drugs. Further studies are warranted to decrease ciclopirox cytotoxicity and evaluate the in vivo protective effects.

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

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

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

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

Background: The two-stage technique combining the Endoscopic Retrograde CholangioPancreatography (ERCP) with common bile duct (CBD) clearance carried out before the laparoscopic cholecystectomy represents the most common approach for CBD stones. Over time, different techniques have been proposed to manage cholecysto- choledocholithiasis (CCL) advantageously in one stage. Among these, the laparoendoscopic rendez-vous (LERV) addresses the CCL issue with a laparoscopic cholecystectomy with insertion of a guide wire performed at initial stage of the procedure, followed by the clearance of the bile duct carried out by the endoscopists. The goal of this study was to evaluate the efficacy and safeness of LERV procedure recording results and complications, also making a comparison between our results and current literature. Methods: We reviewed our experience of all consecutive patients with cholecysto-choledocholithiasis managed with LERV between January 2018 and December 2023. LERV success rate, operative time, length of hospital stay, stone recurrence, incidence of endoscopic and surgical complications were analysed. Results: A total of 120 patients underwent LERV in our facilities. We reported a 97% LERV success rate, 1.6% conversion-to-open rate, a median intraoperative time of 122 (range 95-220) min. The median hospital stay was 4 (range 2-38) days. An overall morbidity of 15% was reported (18/120): 15 Clavien-Dindo type 1/2, 2 type 3a and one type 3b. In two cases a re-operation during the hospital stay was necessary. At a median follow-up of 14 months (3-59) five patients experienced stone recurrence requiring redo-ERCP in two cases. Conclusion: LERV offers the significant advantage of a single stage procedure and hospitalisation along with a lower risk of post-ERCP pancreatitis, failed CBD cannulation and complications. Our experience confirms safety and effectiveness of the technique for CCL management.

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

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

The emergence of new methodologies and tools for digitizing objects belonging to the Cultural Heritage (CH) changed the paradigms adopted so far. Traditionally, the process to acquire artifacts required specialized and often costly equipment tailored to specific purposes. However, the development of more generalized, adaptable, and affordable tools led to novel approaches. This manuscript provides a glimpse into the evolving landscape of custom-made tools for digital documentation, both hardware and software, and their transformative impact on the digitization techniques, built to meet requirements of specific case studies, including ancient drawings, manuscripts, paintings, and museum objects. The advent of self-built instruments has revolutionized the way professionals work today, by leveraging a new generation of low-cost, adaptable gears, leading to unprecedented flexibility and efficiency, while facilitating the capture of high-quality digital representations of objects with minimal damage and preserving their integrity. The outcomes of instruments and tools specifically produced for the contexts described in this paper highlight their potential for promoting interdisciplinary collaboration, facilitating scholarly research, enhancing conservation efforts, and fostering cultural exchange. Ultimately, this research contributes to illustrate how custom software, in combination with recent devices such as smartphones and 3D printers, underscores the importance of adopting these innovative approaches to generate an ecosystem of tools and methods able to preserve, document, and promote the richness of our collective past for future generations.

In the last years, new numerical methods have been applied to weather data for water budget es-timation. Geostatistics is one of the most powerful approaches, when it comes to studying spatially relevant natural phenomena, as it takes into account the spatial correlation among measurements over a specific study area and increases the reliability of the estimation by providing the associate uncertainty. In this study, we tested the feasibility of using a geostatistical method called Ordinary Kriging to provide a reliable estimation of the water budget of the Foro river basin (Periadriatic area, Central Italy), by comparing the obtained results with a more traditional yet robust approach based on the Thiessen polygon spatialization method, considered here as a reference. The spatial estimation with the selected geostatistical and traditional approaches was performed on the av-erage monthly rainfall and temperatures derived from 33-year-long time series measured at the weather station of the regional monitoring network. To transform the spatial variables quantities of both rainfall and air temperature into actual runoff estimates that ideally represent the river dis-charge, we used both the Turc and Thornthwaite methods, considering variable Potential Infiltra-tion Coefficients according to the hydrogeological complexes’ distribution. For the geostatistical method, the same procedure was applied to the 95% confidence interval limits, to quantitatively assess the possible impact of the spatial uncertainty on the estimation of the river discharge. The results obtained by both methods, subsequently converted into monthly discharges, were com-pared to the average monthly discharges related to 33-year-long time series measured at different locations along the Foro river. The results obtained with the geostatistical approach proved to be in line with the ones from the traditional method. Additionally, using the rainfall and temperature values obtained with the Ordinary Kriging and the corresponding confidence interval limits, it was possible to quantify the uncertainty associated with the discharge values, making the estimates more reliable than the ones obtained with the traditional approach. However, the yearly distribu-tion of river discharge obtained by both the geostatistical and traditional methods appeared to be dissimilar to the measured ones. In such anthropized and groundwater-dependent river basins, the surface water use as well as the regulatory effect of the alluvial aquifer regime may affect the river discharge variability over the year and then can account for similar discrepancies between the in-flow and outflow water volumes.

Food Neophobia (FN), defined as the reluctance to eat new or unfamiliar foods, mainly concerns fruit, vegetables, and legumes, typical of the Mediterranean Diet (MD). Considering these premises, this study aimed to clarify the relationship between FN and AMD in a sample of Italian children and their association with some socio-demographic factors and children's nutritional status. A sample of 288 children aged 3-11 years, participated to an assessment carried out with a questionnaire evaluating FN and AMD, respectively with Child Food Neophobia Scale (CFNS) and the KIDMED Test. Most of the sample showed an intermediate (67.3%) or high level of FN (18.1%) with high rates among 6-11 years old children (63.9%) and especially in only-child (50%). The AMD was mostly low (29.5%) or medium (54.8%) and reached lower levels among higher neophobic children (51.9%; p value &lt; 0.05). Present results confirm the study hypothesis that FN is a driver of MD abandonment and show the positive effects on children's eating habits of having siblings. Finally, this study proves the relevance of adopting effective feeding strategies against FN to avoid its maintenance in adulthood and detrimental effects on future overall health and well-being.

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.

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

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

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

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

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

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

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

Oral immunization with the choleric toxin (CT) elicits a high level of protection against its enterotoxin activities and can control cholera in endemic settings. However, the complete B-cell epitope map of the CT responsible for protection remains to be clarified. Here, we have mapped the B-cell linear epitopes of the three chains of the CT protein (CTP) prepared by Spot synthesis. The immunoreactivity of sera from mice immunized with an oral, inactivated vaccine (Schankol†™) was measured against membrane-bound peptides for mapping. Results: Eighteen IgG epitopes were identified; eight in the CTA, three in the CTB, and seven in the protein P. Three epitopes, TQTGFVRHDDGYVST (aa 66-77, Vc/TxA-3), KNGAIFQVE VPGSQN (aa 64-78, Vc/TxB-11), and LNDEHK (aa 90-95, Vc/TxP-16), were chosen to synthesize a multiple antigen peptide that was used to coat ELISA plates to screen immunized mouse sera as a test for an in vitro diagnostics for cholera. Conclusion: Vaccination with inactive CT-generated antibodies against multiple linear epitopes and the selected epitopes can be used to construct immunological reagents for rapid serological diagnosis of cholera with high sensitivity and specificity.

Brain imaging studies have recently provided some evidence in favour of covert cognitive processes ongoing in patients with disorders of consciousness (DoC) (e.g., minimally consciousness states, vegetative state/unresponsive wakefulness syndrome) engaged in passive sensory stimulation or active tasks such as motor imagery. In this exploratory study, we used transcranial magnetic stimulation (TMS) of the motor cortex to assess modulations of corticospinal excitability induced by action observation in eleven patients with DoC. Action observation is known to facilitate corticospinal excitability in healthy subjects, unveiling how the observer’s motor system maps others’ actions onto her/his motor repertoire. Additional stimuli were non-biological motion and acoustic startle stimuli, provided that sudden and loud acoustic stimulation is known to lower corticospinal excitability in healthy subjects. Results indicate that some form of motor resonance is spared in a subset of patients with DoC with some significant difference between biological and non-biological motion stimuli. However, there was no covariation between corticospinal excitability and the type of DoC diagnosis (i.e., whether VS/UWS or MCS). Similarly, no covariation was detected with clinical changes between admission and discharge in clinical outcome measures. Both motor resonance and biological/non-biological motion discrimination correlated with the amplitude of the N20 somatosensory evoked potentials following the stimulation of the median nerve at the wrist (i.e., the temporal marker signalling the activation of the contralateral primary somatosensory cortex). Moreover, the startle-evoking stimulus produced an anomalous increase in corticospinal excitability, suggesting a functional dissociation between cortical and subcortical circuits in patients with DoC. Further work is needed to better comprehend the conditions in which corticospinal facilitation occurs and whether and how they may relate to individual clinical parameters.

Alkali Silica Reaction (ASR) is known to be a serious problem for concrete worldwide, especially in high humidity and high temperature regions. ASR is a slow process that develops over years to decades and it is influenced by changes in environmental and loading conditions of the structure. The problem becomes even more complicated if one recognizes that other phenomena like creep and shrinkage are coupled with ASR. This results in synergistic mechanisms that can not be easily understood without a comprehensive computational model. In this paper, coupling between creep, shrinkage and ASR is modeled within the Lattice Discrete Particle Model (LDPM) framework. In order to achieve this, a multi-physics formulation is used to compute the evolution of temperature, humidity, cement hydration, and ASR in both space and time, which is then used within physics-based formulations of cracking, creep and shrinkage. The overall model is calibrated and validated on the basis of experimental data available in the literature. Results show that even during free expansions (zero macroscopic stress), a significant degree of coupling exists because ASR induced expansions are relaxed by meso-scale creep driven by self-equilibriated stresses at the meso-scale. This explains and highlights the importance of considering ASR and other time dependent aging and deterioration phenomena at an appropriate length scale in coupled modeling approaches.

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

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

Mesenchymal stem cells due to their multipotent ability are considered one of the best candidates to be used in regenerative medicine. The most used source of those stem cells long the last decades was the bone marrow, despite its limited cell resources and the painful and very invasive surgical treatment. Therefore, the scientific community investigated many alternative sources for the harvesting of these stem cell subpopulations. Adipose tissue attracted the biggest interest thanks to special features, such as great tissue abundance, easy availability, and in the end the large amount of positive mesenchymal stem cells. Once it was verified that these stem cell subpopulations possess the same bone marrow differentiation potential, it became evident that they would be the ideal candidate to be used in regenerative and tissue engineering applications. Even the regenerative use of these cells long become a sensitive point because not all the acquired phenotypes resulted in the best source for plastic procedures. As documented in the literature, the ideal fillers for regenerative is represented by stem cell population. Therefore, it became crucial to investigate any kind of biological mechanism on the differentiative ability of those mesenchymal stem cells, especially their regulative factors. One of the most studied and important regulators are the miRNAs. Indeed, miRNA play a crucial role in the differentiation process of adipose stem cell cultures isolated from patients or obtained by commercial cell lines toward osteocytes, chondrocytes, and adipocytes differentiated populations.

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

Abstract: Canine ehrlichiosis is a zoonotic disease transmitted by ticks, posing a formidable challenge to both veterinary and public health sectors worldwide. Across continents and regions, the prevalence rates of Ehrlichia canis exhibit significant variation, underlining the necessity for a nuanced and globally informed approach to understanding and combating this disease. The review navigates through this complexity, shedding light on the intricate pathogenesis of the illness. Central to this understanding is the bacterium's adept manipulation of the host's immune response, contributing to the diverse clinical manifestations observed in infected animals. Diagnostic methodologies, crucial for timely intervention and management, are subjected to critical assessment. From traditional microscopy to modern molecular techniques and serology, each approach is scrutinized for its strengths and limitations. By acknowledging these nuances, the review aims to equip practitioners with the knowledge necessary to make informed diagnostic decisions. A central tenet of this review is the advocacy for an integrated "One Health" approach. By leveraging advancements in genomics, proteomics, and artificial intelligence, there is a potential to enhance diagnostic accuracy and develop innovative therapeutic and preventive strategies globally. This collaborative approach recognizes the interconnectedness of human, animal, and environmental health, offering a holistic framework for tackling complex zoonotic diseases like canine ehrlichiosis. In conclusion, this review serves as a beacon of knowledge, illuminating the multifaceted landscape of canine ehrlichiosis. Through its synthesis of scientific literature and emphasis on methodological rigor, it provides a foundation upon which future research and interventions can be built. With a unified commitment to "One Health" principles and the integration of cutting-edge technologies, there exists the potential to mitigate the impact of this disease and safeguard both animal and human well-being worldwide

Pomegranate peel is a natural source of phenolics, claimed to possess healing properties, among which antioxidant and antidiabetic. In line with this evidence, the ethyl acetate PGE extract, obtained by Soxhlet from the peel of Dente di cavallo DC2 variety and characterized by a 4% amount of ellagic acid, has been studied for its hypoglycemic, antiglycation and antioxidative cytoprotective properties, in order to support a possible further nutraceutical interest. The α-amylase and α-glucosidase enzyme inhibition, interference with advanced glycation end-products (AGE) formation and metal chelating abilities were evaluated as hypoglycemic mechanisms. Also, considering that oxidative stress is associated with hyperglycemia complications, PGE antioxidant cytoprotective properties under hyperglycemic conditions were assayed. Phenolic profile was characterized by integrated chromatographic and spectrophotometric methods. Under our experimental conditions, PGE strongly inhibited the tested enzymes, especially α-glucosidase, and exerted chelating and antiglycation properties. Also, it reduced both ROS and GSH levels under hyperglycemic conditions, thus suggesting its ability to support cell functions by counteracting intracellular oxidative stress. Along with ellagic acid, rutin was the major identified flavonoid (about 4 %) of PGE. Present results suggest PGE to be a possible remedy for hyperglycemia management and encourage further studies to exploit its promising properties.

A 68-year-old man with malignant metastatic melanoma in complete remission after Pembrolizumab treatment, developed 10 months after Pembrolizumab cessation due a grade 3 diarrhea, confusion, altered mental status, progressive memory loss, gait disturbance. He was admitted to the neurologic department and comprehensive neurological workup, brain magnetic resonance imaging, cerebral fluid analysis, EEG, blood test allowed the diagnosis of autoimmune encephalitis. The patient was treated with plasmapheresis, high dose of intravenous steroids and intravenous immunoglobulins. The patient improved and he is now well with a performance status 1. This case is interesting since the AE developed approximately 10 months after the cessation of immunotherapy, the underlying cancer was in complete remission and the AE showed a good response to the treatment done.

We consider a constrained optimal control problem and an extension of it, in which the set of strict-sense trajectories is enlarged. Extension is a common procedure in optimal control, used to derive necessary and sufficient optimality conditions for the original problem from the extended one, which usually admits a minimizer and has a more regular structure. However, this procedure fails if the two problems have different infima. It is therefore relevant to identify such situations. Following on from earlier work by Warga but adopting perturbation techniques developed in non-smooth analysis, we investigate the relation between the occurrence of an infimum gap and abnormality of necessary conditions. For a notion of local minimizer based on control distance and an extension including the impulsive one, we prove that (i) a local extended minimizer which is not a local minimizer of the original problem and (ii) a local strict-sense minimizer which is not a local minimizer of the extended problem, both satisfy the extended maximum principle in abnormal form. The main novelty is result (ii), as until now it had only been shown that a strict-sense minimizer which is not an extended minimizer is abnormal for an `averaged version’ of the maximum principle.

: Microplastics and nanoplastics (MNPs) are becoming an increasingly severe global problem due to their widespread distribution and complex impact on living organisms. Apart from their environmental impact, the effects of MNPs on living organisms have also continued to attract attention. The harmful impact of MNPs has been extensively documented in marine invertebrates and larger marine vertebrates like fish. However, the research on the toxicity of these particles on mammals is still limited, and their possible effects on humans are poorly understood. Considering that MNPs are commonly found in food or food packaging, humans are primarily exposed to them through ingestion. It would be valuable to investigate the potential harmful effects of these particles on gut health. This review focuses on recent research exploring the toxicological impacts of micro- and nanoplastics on the gut, as observed in human cell lines and mammalian models. Available data from various studies indicate that the accumulation of MNPs in mammalian models and human cells may result in adverse consequences, in terms of epithelial toxicity, immune toxicity, and disruption of gut microbiota. The paper also discusses the current research limitations and prospects in this field, aiming to provide a scientific basis and reference for further studies on the toxic mechanisms of micro- and nanoplastics.

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

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

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

Simultaneous measurement of different substances from a single sample is an emerging issue to achieve efficient and high-throughput detection in several fields of application. Although immunoanalytical techniques have well-established and prevailing advantages over alternative screening analytical platforms, one of the incoming challenges for immunoassay is exactly multiplexing. The Lateral Flow Immunoassay (LFIA) is a leading immunoanalytical technique for onsite analysis thanks to its simplicity, rapidity and cost-effectiveness. Moreover, LFIA architecture is adaptable to multiplexing and therefore candidates as a possible answer to the pressing demand of multiplexing point-of-need analysis. The review present an overview of diverse approaches for multiplex LFIA, with a special focus on strategies based on new types of magnetic, fluorescent and colored labels

Background According to some authors, a single isolated measurement of serum BNP executed on hospital admission would not be a sufficiently accurate method to predict the outcome of patients with ADHF. Aims For verifying this assumption, a retrospective study was conducted on patients hospitalized for ADHF. Our main objective was to ascertain whether there was any difference in midterm mortality among patients with rising BNP at discharge as compared to those with decreasing BNP at discharge. Methods Medical records were examined so as to make a partition of the ADHF patient population into two groups, the former characterized by a rise in BNP during hospitalization, and the latter exhibiting a decrease in BNP in the measurement taken at hospital discharge. Results 177 patients were enrolled in a retrospective study. Among them, 53 patients (29.94%) had increased BNPs at the time of discharge, whereas 124 (70.06%) showed decreases in serum BNP during their hospital stay. The group with patients who exhibited BNP increases at the time of discharge had higher degree of congestion evident in the higher frequency of persistent jugular venous distention and persistent orthopnea at discharge. Moreover, patients with increased BNP at the time of discharge had a lower reduction in inferior vena cava maximum diameter [1.58 ± 2.2 mm vs. 6.32 ± 1.82 mm; p (one-way ANOVA)=0.001]. In contrast, there was no significant difference in weight loss when patients with increased BNP at discharge were compared to those with no such increase. A total of 14 patients (7.9%) died during the six-month follow-up period. Cox proportional hazard analysis revealed that BNP increase at the time of discharge was an independent predictor of six-month all-cause mortality after adjustment for age, sodium at discharge, creatinine at discharge and New York Heart Association (NYHA) class at discharge (hazard ratio 34.49; 95% confidence intervals: 4.55–261.06; P =0.001). Conclusions Among patients with history of ADHF, more elevated BNP levels at the time of discharge from the hospital compared to those detected at admission identify a patient subset with higher grade of congestion and higher six-month mortality.

The aim of this study was to investigate the parameters affecting the extraction of positive molecules such as chlorogenic acids and antioxidants, as well as potentially carcinogenic substances such as acrylamide, in different coffee brewing methods. Three coffee varieties, each assigned to different roasting degree, were used to prepare coffee brews following eight diverse preparation methods. Acrylamide was quantified by HPLC-MS/MS instrument while chlorogenic acids and caffeine by HPLC-DAD system. Three spectrophotometric analyses were also performed (DPPH, TFC and TPC) to evaluate antioxidant activity as well. The results showed that the main brewing parameters, that have the greatest influence on the final content of these compounds were the volume of water used, more specifically the brewing ratio (coffee to water ratio), the extraction time and the particle size of the coffee powder.

Background:Caregiving for individuals with neurological disease involves providing physical, emotional, and social support, which can be a challenging and stressful experience. This study aims to compare the caregivers' burden, including the impact on mental and physical health, social support, and quality of life, in different neurodegenerative disorders. Methods:Fifty-five primary caregivers (F=41;mean age=53.07±12.29) of patients with Parkinson's Disease (PD=26), Multiple System Atrophy (MSA=16), and Amyotrophic Lateral Sclerosis (ALS=13), took part in the study. Standardized screening scales for the quality of life (EQ-5D/EQ-VAS and PQoL), levels of the caregiving burden (CBI and FSQ), and the assessment of the anxiety-depressive axis (HADS) were administered. Results: The mean CBI score was higher for caregivers of MSA patients (28.81±21.90) and ALS (25.15±16.23) than for caregivers of PD patients (16.08±10.34; p=0.036). Critical burden (cut-off>36) was present in the caregivers of MSA (31.3%), ALS (23.1%), and PD (19.2%) patients. Caregivers of patients with ALS had a worse perception of quality of life (EQ-5D total score) than caregivers of patients with MSA and PD (p

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

The design of biomaterial platforms able to release bioactive molecules is mandatory in tissue repair and regenerative medicine. In this context, electrospinning is a user-friendly, versatile and low-cost technique, able to process different kinds of materials in micro- and nano-fibers with a large surface area-to-volume ratio for an optimal release of gaseous signalling molecules. Recently, the antioxidant and anti-inflammatory properties of the endogenous gasotramsmitter hydrogen sulfide (H2S), as well as its ability to stimulate relevant biochemical processes on the growth of mesenchymal stem cells (MSC), have been investigated. Therefore, in this work, new poly(lactic) acid fibrous membranes (PFM), doped and functionalized with H2S slow-releasing donors extracted from garlic, were synthetized. These innovative H2S-releasing mats were characterized for their morphological, thermal, mechanical and biological properties. Their antimicrobial activity and effects on the in vitro human cardiac MSC growth, either in the presence or in the absence of oxidative stress, were here assessed. On the basis of the results here presented, these new H2S-releasing PFM could represent promising and low-cost scaffolds or patches for biomedical applications in tissue repair.

Neurological involvement following COronaVIrus Disease 19 (COVID-19) is thought to have a neuroinflammatory etiology. Co-ultraPEALut (an antiinflammatory molecule) and luteolin (an antioxidant) yielded promising results as neuroinflammation antagonists. This study aimed at describing cognitive impairment in post-COVID patient treated with co-ultraPEALut. Montreal Cognitive Assessment (MoCA), Prospective-Retrospective Memory Questionnaire (PRMQ), Fatigue Severity Scale (FSS) and a subjective evaluation were administered at baseline and after 10 months. Co-ultraPEALut-treated patients were retrospectively compared with controls. 26 co-ultraPEALut-treated patients showed significant improvement in PRMQ (T0: 51.94±10.55, T1: 39.67±13.02, p

(1) Background: The diphtheria toxoid antigen is a major component in pediatric and booster combination vaccines and is known to raise a protective humoral immune response upon vaccination. Although antibodies are considered critical for diphtheria protection, little is known about the antigenic determinants that maintain humoral immunity. (2) Methods: One hundred twelve 15-mer peptides covering the entire sequence of DTx protein were prepared by Spot-synthesis. Membrane-bound peptides immunoreactivity with sera from mice immunized with triple DTP vaccine allowed mapping of continuous B-cell epitopes, topological studies, MAPs synthesis, and ELISA development. (3) Results: Twenty epitopes were identified, being 2 in the signal peptide, 5 in the CD, 7 in the HBFT domain, and 5 in the RBD. Two 17-mer (CB/Tx-2/12 and CB/DTx-4-13) derived bi-epitope peptides linked by a Gly-Gly spacer were chemically synthesized. The peptides were used as antigens to coat ELISA plates and assayed with human (huVS) and mice vaccined sera (miVS) for in vitro diagnosis of diphtheria. The assay proved to be highly sensitive (99.96%) and specific (100%) either for huVS and miVS and when compared with a commercial ELISA test, demonstrate high performance. (4) Conclusions: Our work displayed the complete picture of the linear B cell IgG response epitope of the DTx responsible for the protective effect and demonstrated the specificity and eligibility to enter phase IIB studies of some epitopes to develop new and fast diagnostic assays.

Purpose: to assess any differences on marginal bone loss between bone-level or tissue-level dental implants through a review of literature until September 2019. Materials and methods: MEDLINE, Embase and other database were searched by two independent authors. The search was limited to articles in English. Results: The search provided 1028 records and, after removing the duplicates through titles and abstracts screening, 45 full-text articles were assessed for eligibility. For qualitative analysis 20 articles were included, 17 articles of them for quantitative analysis. A total of 1161 patients (mean age 54,4 years) and 2933 implants were observed, 1427 (Tissue-level) and 1506 (Bone-level). The survival rate and the success rate were more than 90%, except for 2 studies with a success rate of 88% and 86.2%. No studies reported any differences between groups in term of success and survival rates. Three studies showed that BL-implants had statistically less marginal bone loss (P< 0.05). Only one study reported statistically less marginal bone loss in TL-implants (P< 0.05). In the most part of the studies, differences between implant types in marginal bone loss were not statistically significant. Conclusion: Despite to the peri-implant tissue around transmucosal implants has been reported to be inflammation-free because of the absence of bacterial infiltration in the micro-gap between the fixture and abutment, no clinical and radiological differences were highlighted between groups from the included studies after a variable period of follow-up ranged between 1 to 5 years.

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

The aim of this article is to review hydrogen combustion applications within the energy transition framework. Hydrogen blends are also included, from the well known hydrogen enriched natural gas (HENG) to the hydrogen and ammonia blends whose chemical kinetics is still not clearly defined. Hydrogen and hydrogen blends combustion characteristics will be firstly summarized, in terms of standard properties like the laminar flame speed and the adiabatic flame temperature, but also evidencing the critical role of hydrogen preferential diffusion in burning rate enhancement and the drastic reduction in radiative emission with respect to natural gas flames. Then, combustion applications in both thermo-electric power generation (based on internal combustion engines, i.e., gas turbines and piston engines) and hard-to-abate industry (requiring high temperature kilns and furnaces) sectors will be considered, highlighting the main issues due to hydrogen addition related to safety, pollutant emissions, and potentially negative effects on industrial products (e.g., glass, cement and ceramic).

In this work we demonstrate the proof-of-concept of real-time discrimination between patches of serine or isoleucine monomers in the primary structure of custom-engineered, macro-dipole-like peptides, at uni-molecular level. We employed single-molecule recordings to examine the ionic current through the α-hemolysin (α-HL) nanopore, when hydrophilic serine or hydrophobic isoleucine residues, flanked by segments of oppositely charged arginine and glutamic amino acids functioning as a voltage-dependent ‘molecular brake’ on the peptide, were driven at controllable rates across the nanopore. The observed differences in the ionic currents blockades through the nanopore, visible at time resolutions corresponding to peptide threading through the α-HL’s constriction region, was explained by a simple model of the volumes of electrolyte excluded by either amino acid species, as groups of three serine or isoleucine monomers transiently occupy the α-HL. To provide insights into the conditions ensuring optimal throughput of peptide readout through the nanopore, we probed the sidedness-dependence of peptide association to and dissociation from the electrically and geometrically asymmetric α-HL.

Background and Aims: Liver cirrhosis leads to clinically significant portal hypertension. Transjugular intrahepatic portosystemic shunt (TIPS) has been shown to effectively reduce the degree of portal hypertension and treat its complications. However, poor nutritional status has been shown to be associated with hepatic encephalopathy, acute on chronic liver failure, and mortality following TIPS placement. The purpose of this systematic review is to create another perspective and evaluate the effect of TIPS placement on the nutritional status of patients with liver cirrhosis. Methods: A comprehensive search of four major electronic databases was conducted to identify studies that assessed the nutritional status of cirrhotic patients before and after TIPS placement. The risk of bias was evaluated using ROBINS-I guidelines. Results: Fifteen studies were analyzed in this review. The results indicate that among the 11 studies that evaluated changes in ascites-free weight and body mass index or body cell mass, 10 reported an improvement in one or more measures. Furthermore, all 7 studies that evaluated changes in muscle mass demonstrated an increase in muscle mass. Among the 4 studies that evaluated subcutaneous fat tissue, 3 showed a significant expansion, while 2 out of 3 studies evaluating visceral fat tissue reported a significant reduction. Conclusion: The results of this systematic review suggest that TIPS placement is associated with improvement in the nutritional status of cirrhotic patients, indicated by an increase in ascites-free weight, body mass index, and muscle mass. Additionally, TIPS placement leads to a shift in the distribution of fat mass, with a preference for subcutaneous over visceral adipose tissue. Notably, sarcopenic patients seem to benefit the most from TIPS placement in terms of the nutritional status.

Background: The newly introduced COVID-19 vaccines have reduced disease severity and hospitalizations. However, they do not significantly prevent infection or transmission. In the same context, measuring IgM and IgG antibody levels is important, but it doesn't provide information about the status of the mucosal immune response. This article describes a comprehensive mapping of IgA epitopes of the S protein, its cross-reactivity, and the development of an ELISA-peptide assay. Methods: IgA epitope mapping was conducted using Spot-synthesis and sera from RT-qPCR COVID-19-positive patients. Specific and cross-reacting epitopes were identified, and an evolutionary analysis from the early Wuhan strain to the Omicron variant was performed using bioinformatics tools and a microarray of peptides. The selected epitopes were chemically synthesized and evaluated using ELISA-IgA. Results: 40 IgA epitopes were identified, with 23 in S1 and 17 in the S2 subunit. Among these, at least 23 epitopes showed cross-reactivity with DENV and other organisms and 24 with other associated coronaviruses. Three MAP4 polypeptides were validated by ELISA, demonstrating a sensitivity of 90-99.96% and a specificity of 100%. Among the six IgA-RBD epitopes, only the SC/18 epitope of the Omicron variants (BA.2 and BA.2.12.1) presented a single IgA epitope. Conclusions: This research unveiled the IgA epitome of the S protein and identified many epitopes that exhibit cross-reactivity with DENV and other coronaviruses. The S protein of variants from Wuhan to Omicron retains many conserved IgA epitopes, except for one epitope (#SCov/18). The cross-reactivity with DENV suggests limitations in using the whole S protein or the S1/S2/RBD segment for IgA serological diagnostic tests for COVID-19. The expression of these identified specific epitopes as diagnostic biomarkers could facilitate monitoring mucosal immunity to COVID-19, potentially leading to more accurate diagnoses and alternative mucosal vaccines.

In the Neighborhood Area Network (NAN), the Advanced Metering Infrastructure (AMI) enables a bidirectional connection between the Smart Meter (SM) and the Data Concentrator (DC). Sensors, such as smart meter node or Radio Frequency transceiver, play a crucial role in collecting and transmitting data from meters to central unit for advanced monitoring, management, and analysis of energy consumption. Wired and wireless communication technologies can be used to implement the AMI-NAN. This paper delves into a novel approach for optimizing the choice of communication medium, Radio Frequency (RF) or Power-Line Communication (PLC), between the SM and DC in the context of AMI-NAN. The authors methodically select the specific technologies, RF and NB-PLC (Narrow Band Power-Line Communication), and meticulously characterize their attributes. Then, a comparative analysis spanning rural, urban, and industrial settings is conducted to evaluate the proposed method. The overall reliability performance of the AMI-NAN system requires a Packet Error Rate (PER) lower than 10%. To this end, a comprehensive methodology is introduced to assess and enhance the reliability of NB-PLC and RF for AMI-NAN applications. Simulation results demonstrate that wireless communication is the optimal choice for the rural scenario, especially for Signal to Noise Ratio (SNR) lower than 25 dB. However, in urban environments characterized by higher SNR values and moderately dense networks, NB-PLC gains prominence. In denser networks, it outperforms wireless communication, exhibiting a remarkable 10 dB gain for a bit error rate (BER) of 10-3. Moreover, in industrial zones characterized by intricate network topologies and non-linear loads, the powerline channel emerges as the optimal choice for data transmission, affording a gain surpassing 20 dB.

Rural electrification in remote areas of developing countries has several challenges which hinders energy access to the population. For instance the extension of the national grid to provide electricity in these areas is largely not viable. The Kenyan government has put a target to achieve universal energy access by the year 2020. In order to realize this objective, focus is being shifted to establishing off-grid power stations in rural areas.Among rural areas to be electrified, Habaswein is a settlement in Kenya's North Eastern region without connection to the National Power Grid where Kenya Power installed a stand alone hybrid mini-grid.Based on field observations, power generation data analysis, evaluation of the potential energy resource and simulations, this research intends to evaluate the performance of the Habaswein mini-grid and optimize the existing hybrid generation system to enhance its reliability and reduce the operation costs.The result will be a suggestion of how Kenyan rural areas could be sustainably electrified by using renewable energy based off-grid power stations. It will contribute to bridge the research gap currently existing on that area, and it will be a vital tool to researchers, implementers and the policy makers in energy sector.

Healthcare-associated infections (HAI) worldwide includes infections by ESKAPE-E pathogens. Environmental surfaces and fomites are important components in HAI transmission dynamics, and shoe soles are vectors of HAI. Ultraviolet (UV) disinfection is an effective method to inactivate pathogenic microorganisms. In this study, we investigated whether the SANITECH UVC shoe sole decontaminator equipment that provides germicidal UVC radiation could effectively reduce this risk of different pathogens. Six standard strains and four clinical MDR strains in liquid and solid medium were exposed to a UVC System at specific concentrations at other times. Bacterial inac-tivation (growth and cultivability) was investigated using colony counts and resazurin as meta-bolic indicators. SEM was performed to assess the membrane damage. Statistically significant reduction in cell viability for all ATCCs strains occurred after 10 sec of exposure to the UVC sys-tem, except for S enterica, which only occurred at 20 sec. The cell viability of P. aeruginosa (90.9%), E. faecalis and A. baumannii (85.3%), S. enterica (82.9%), E. coli (79.2%) and S. aureus (71.9%) was re-duced considerably at 20 sec. In colony count, after 12 sec of UVC exposure, all ATCC strains showed a 100% reduction in CFU counts, except for A. baumannii, which reduced 97.7%. A sub-stantial reduction of colonies above 3 log10 was observed at 12 and 20 sec in all bacterial strains tested, except for A. baumannii ATCC 19606 (12 sec). The exposure of ATCCs bacterial strains to the UVC system for only 2 sec was able to reduce 100% in the CFU count in all ATCCs strains, S. au-reus, P. aeruginosa, E. coli, A. baumannii, E. faecalis, except the S. enterica strain which had a statis-tically significant reduction of 99.7%. In ATCC strains, there was a substantial decrease in colonies after 4 sec (sec) of exposure to the UVC system, with a reduction ranging from 3.78-4.15 log10 CFU/mL. This reduction was observed in MDR/ESKAPE-E strains within 10 sec, showing that UVC could eliminate above 3.84 log10 CFU/mL. SEM showed a reduction of pili-like appendages after UVC treatment in all strains except for E. coli (ATCC 25922). The Sanitech UVC shoe sole decontaminator equipment from Astech Co. effectively killed in vitro a series of ATCCs and MDR/ESKAPE-E bacteria of sanitary interest, commonly found in the hospital environment.

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

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

Remote sensing (RS) has been widely adopted as a tool to investigate several biotic and abiotic factors, directly and indirectly, related to biodiversity conservation. European grasslands are one of the most biodiverse habitats in Europe. Most of these habitats are subject to priority conservation measure, and they are threatened by several human induced process. The broad expansions of few dominant species are widely reported as drivers of biodiversity loss. In this context, using Sentinel-2 (S2) images, we investigate the distribution of one of the most spreading species: <i>Brachypodium genuense</i>. We performed a binary Random Forest (RF) classification of <i>B. genuense</i> using a RS image and field sampled presence/absence points. Then, we integrate the occurrences obtained from RS classification into niche models to identify the topographic drivers of <i>B. genuense</i> distribution. Lastly, the impact of <i>B. genuense</i> distribution in the N2k habitats was assessed by overlay analysis. The RF classification process detected <i>B. genuense</i>'s cover with an overall accuracy of 91.18%. The integration of RS and topographic niche models shows that the most relevant topographic variables that influence the distribution of <i>B. genuense</i> are slope, elevation, solar radiation and Topographic Wet Index (TWI) in order of importance. The overlay analysis shows that 74.04% of the <i>B. genuense</i> identified in the study area falls on the semi-natural dry grasslands. The study highlights the importance of the RS classification and the topographic niche models as an integrated approach for mapping a broad-expansion species such as <i>B. genuense</i>. The coupled techniques presented in this work should be applicable to other plant communities with remotely recognizable characteristics for more effective management of N2k habitats.

Traditionally, overnight fasting before elective surgery has been the routine in medical practice for risk reduction of pulmonary aspiration of gastric contents. Several original study and international societies recommend a 2‐h preoperative fast for clear fluids and a 6‐h fast for solids in most elective patients. We conducted a narrative review of the literature, searching electronic databases (Medline and CINAHL). We used PICO approach. The results of our review suggest that nutrition support in the perioperative period is very important to reduce length of hospital stay and reduced postoperative complication.

The RAINBOW Phase III study established the efficacy of the combination of paclitaxel and ramucirumab, a monoclonal antibody targeting VEGF receptor-2 (VEGF-R2), as second-line therapy. We retrospectively analyzed the data of patients treated with ramucirumab plus paclitaxel at our Institution to evaluate the impact of clinical heterogeneous figures on the efficacy and safety of this combination paclitaxel/ramucirumab in a real- life cohort of patients. After a median follow-up of 10.74 months, the median progression-free survival (PFS) was 5.8 months (95% CI: 3.04 - 5,63). Disease control rate (DCR) was 61% and the median duration of response (DOR) was 5.8 months. Median overall survival (OS) was 8.3 months. A trend toward better outcome was observed in HER2 positive patients. In multivariate analysis, nutritional status (p = 0.0001) and number of metastatic sites (p = 0.0266) resulted significantly related with longer PFS. Our analysis confirmed the efficacy and safety of the combination of ramucirumab with paclitaxel also in the real-life practice and the median PFS is significantly longer than that reported for Western population in previous studies. Subgroup analysis confirms the key-role of nutritional status as prognostic factor and suggests a possible interaction between EGF and angiogenesis pathways that deserves further investigations.

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

Acoustic Radiation Forced Impulse (ARFI) is an ultrasound integrated method, measuring stiff-ness by point shear wave elastography. To evaluate the diagnostic performance of ARFI of the liver and of the spleen, combined with spleen dimension and platelet count, in predicting clinical events in cirrhosis, a prospective and cross-sectional study was conducted between February 2017 and February 2021. The following ratio scores with ARFI measurements were performed: ALSDP (ARFI Liver-Spleen Diameter-to-Platelets ratio score), ASSDP (ARFI Spleen-Spleen Diam-eter-to-Platelets ratio score), ASSAP (ARFI Spleen-Spleen Area-to-Platelets ratio score), ALSAP (ARFI Liver-Spleen Area-to-Platelets ratio score). In 100 enrolled subjects, spleen ARFI, ASSDP, ASSAP, were significantly associated with high-risk oesophageal varices (HRVs) in the prospec-tive short- and long-term follow-up and in the cross-sectional study (p 0.7). ARFI-ratio scores can predict, in cirrhotic patients, the risk of developing HVRs in short and long-term period.

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

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

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

Nicastrin (NICT) is a transmembrane protein physically associated with the polytypical aspartyl protease presenilin that plays a vital role in the correct localization and stabilization of presenilin to the membrane-bound γ-secretase complex. This complex is involved in the regulation of a wide range of cellular events including cell signaling and the regulation of endocytosed membrane proteins for their trafficking and protein processing. Mehtods: In Trypanosoma cruzi, the causal agent of the Chagas disease, an NICT-like protein (Tc/NICT) was identified with a short C-terminus orthologous to the human protein, a large ectodomain (ECD) with numerous glycosylation sites and a single core transmembrane domain containing a putative TM-domain (457GSVGA461) important for the γ-secretase complex activity. Results: Using the Spot-synthesis strategy with Chagasic patient sera, five extracellular epitopes were identified and synthetic forms were used to generate rabbit anti-Tc/NICT polyclonal serum that recognized a ~72-kDa molecule in immunoblots of T. cruzi epimastigote extracts. Confocal microscopy suggests that Tc/NICT is localized in the flagellar pocket, which is consistent with data from our previous studies with a T. cruzi presenilin-like protein. Phylogenetically, Tc/NICT was localized within a subgroup with the T. rangeli protein that are clearly detached from the other Trypanosomatidae such as T. brucei. These results, together with a comparative analysis of the selected peptide sequence regions between the T. cruzi and mammalian proteins suggest a divergence from the human NICT that might be relevant to Chagas disease pathology. As a whole, our data show that an NICT-like protein is expressed in the infective and replicative stages of T. cruzi and may be considered further evidence for a γ-secretase complex in trypanosomatids.

The issue of being pro-gender is still a controversial topic to be debated in Indonesian society. However, in the 21st Century, many women have been able to break through barriers and participate in the public sphere. It is a form of self-existence as proposed by Simone de Beauvoir on existentialist feminism. Based on these problems, this study aims to find out and answer questions about how Indonesian women exist in the public sphere in the 21st Century and find out how Indonesian women exist in the public sphere through Simone de Beauvoir's existentialist feminism paradigm. The research method used is descriptive-qualitative through a literature review of 23 journal articles, websites, and data reports with a range of 2019-2021. This study found that based on Simone de Beauvoir's feminist paradigm, Indonesian women in the 21st Century are no longer a figure other than complete. Furthermore, the data collected by the researcher shows that several gender indicators have shown that Indonesian women have been able to occupy public spaces in various aspects. Based on these results, it is hoped that it can provide information about Simone de Beauvoir's existentialist feminism thought and its relevance to the existence of Indonesian women in the public sphere in the 21st Century. However, this research has limitations, those are only about women in Indonesia, and the paradigm of feminism is limited to Simone de Beauvoir's existentialist feminism.

The biological aging, characterized by changing in metabolism and physicochemical properties of cells, has an impact on public health. Environment and lifestyle including factors like diet and physical activity seems to play a key role in healthy ageing. Several studies have shown that regular physical activity can enhance antioxidant defence mechanisms, including the activity of enzymes such as superoxide dismutase (SOD), catalase, and glutathione peroxidase. However, intense or prolonged exercise can also lead to an increase in ROS production temporarily, re-sulting in oxidative stress. This phenomenon is referred as "exercise-induced oxidative stress". The relationship between physical activity and oxidative stress in aging is complex and depends on various factors such as the type, intensity, duration, and frequency of exercise, as well as in-dividual differences in antioxidant capacity and adaptation to exercise. In this review, we ana-lyzed what is reported from several authors regarding the role of physical activity on oxidative stress in aging process as well as the role of hormesis and physical exercise as tools for preven-tion and treatment of sarcopenia, an aging related disease. Finally we reported what has recently been studied in relation to the effect of physical activity and sport on aging in women

In a digitally oriented society, smartphones provide continual online accessibility to daily life, while simultaneously predisposing adolescents to engage in prolonged connections for various purposes, thus escalating the risk of Internet Addiction (IA). Cognitive processes such as multitasking and attentional shifting are frequently associated with smartphone activities. Additionally, online engagements may serve as emotional strategies for regulating negative states (e.g., boredom and distress), redirecting attention towards more gratifying activities, such as social media content. This study delves into cognitive-emotional processes (emotion regulation, attention impulsiveness, online vigilance, and multitasking) and emotional/behavioural factors (emotional problems, conduct problems, hyperactivity/inattention, peer relationships, and prosocial behaviours) that may be implicated in smartphone activities and technology addiction among adolescents. A community sample (N=676) of Italian high school students (42.2% females) completed the Smartphone Distraction Scale (SDS), the Strength and Difficulties Questionnaire for internalizing/externalizing symptoms (SDQ), and the Internet Addiction Test (IAT) to assess the presence and severity of IA. The scores on the Smartphone Distraction Scale were found to be positively associated with IA levels. Furthermore, students exhibiting higher internalizing/externalizing symptoms, particularly those with traits of Attention Deficit Hyperactivity Disorder (ADHD), are more likely to manifest problematic smartphone usage. The implications for screening adolescents more susceptible to developing IA symptoms and for implementing preventive interventions are discussed.

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

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

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

(1) Background: Health Care-Associated Infections (HAIs)are a significant public health problem worldwide favoring multidrug-resistant (MDR) microorganisms. The SARS-CoV-2 infection had a negative association with the increase in antimicrobial resistance, and the ESKAPE group had the most significant impact on HAIs. The study aimed to evaluate the bactericidal effect of high concentration O3 gas on some reference and ESKAPE bacteria. (2) Material and Methods: Four standard strains and four clinical or environmental MDR strains were exposed to high ozone doses at different concentrations and times. Bacterial inactivation (growth and cultivability) was investigated using colony counts and resazurin as a metabolic indicator. Scanning electron microscopy (SEM) was performed. (3) Results: The culture exposure to a high level of O3 inhibited the growth of all bacterial strains tested with a statistically significant reduction in colony count compared to the control group. The cell viability of S. aureus (MRSA) (99,6%) and P. aeruginosa (XDR) (29,2%) was reduced considerably, and SEM showed damage on bacteria after O3 treatment (4) Conclusion: High doses of ozone were able to interfere in the growth of all strains studied, evidencing that ozone-based decontamination approaches may represent the future of hospital cleaning methods.

(1) Background: Disinfection of medical devices designed for clinical use associated or not with the growing area of tissue engineering is an urgent need. However, traditional disinfection methods are not always suitable for some biomaterials, especially those sensitive to chemical, thermal, or radiation. Therefore, the objective of this study was to evaluate the minimal concentration of ozone gas (O3) necessary to control and kill a set of sensitive or multi-resistant Gram-positive and Gram-negative bacteria. The cell viability, membrane permeability, and the levels of reactive intracellular oxygen (ROS) species were also investigated; (2) Material and Methods: Four standard strains and a clinical MDR strain were exposed to low doses of ozone at different concentrations and times. Bacterial inactivation (cultivability, membrane damage) was investigated using colony counts, resazurin as a metabolic indicator, and propidium iodide (PI). A fluorescent probe (H2DCFDA) was used for the ROS analyses; (3) Results: No reduction in the count colony was detected after O3 exposure, compared to the control group. However, the cell viability of E. coli (30%), P. aeruginosa (25%), and A. baumannii (15%) was reduced considerably. The bacterial membrane of all strains was not affected by O3 but presented a significant increase of ROS in E. coli (90 ± 14%), P. aeruginosa (62.5 ± 19%), and A. baumanni (52.6 ± 5%); (4) Conclusion: Low doses of ozone were able to interfere in the cell viability of most strains studied, and although it does not cause damage to the bacterial membrane, increased levels of reactive ROS are responsible for causing a detrimental effect in the lipids, proteins, and DNA metabolism.

Taxanes have been shown to be the most effective treatment for recurrent or metastatic breast cancer. However, for patients pretreated with taxanes, more active and possibly less toxic drugs are needed. In this retrospective study, we investigated on the effectiveness and safety of eribulin mesylate in 91 taxane-refractory subjects, extracted from the ESEMPIO database, which included 497 metastatic breast cancer patients treated with eribulin allover the Italy. This analysis included only those patients who have shown disease progression while receiving taxane therapy (primary refractory), or those who achieved a response followed by progression while still on therapy (taxane failure). Overall, 41/91 patients (45.2%) showed a clinical benefit; 1 complete response (2.2%) and 16 partial responses (17.6%) were observed. The median progression free survival was 3.1 months (95% CI: 2.8–3.5) and the median overall survival was 11.6 months (95% CI: 8.7–16.7). With regard to toxicity, 53 patients (58%) experienced asthenia/fatigue, 23 (25%) showed peripheral neurotoxicity, 18 (20%) alopecia, 12 (13%) mild constipation and 27 (30%) neutropenia. The toxicity related to the treatment led to eribulin dose reduction in 19 (21%) and discontinuation in 9 (10%) patients, respectively. In conclusion, this study suggests that eribulin is effective and well tolerated also in taxane-refractory patient.

Background: The aim of this study has been to investigate if inflammatory biomarkers such as the systemic immune-inflammation index (SII), neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) have any correlation with the recurrence of pleomorphic adenomas (PA) in patients afflicted by this disease. Methods: A retrospective multicentre study involving two Italian centres, the Maxillofacial Sur-gery at the Policlinico Federico II in Naples and the ENT and Maxillofacial Surgery at the IRCCS G. Pascale National Cancer Institute in Naples, has been performed. The study, involving 608 pa-tients who had received a diagnosis of PA, was conducted between January 2000 and January 2020. A Receiver Operating Characteristic (ROC) curve was used to calculate the optimal cut-off values for the SII, PLR and NLR. A linear regression model (LRM) and a non-linear logistic re-gression model (NLRM) were realized with respect to the NLR, PLR and SII. Results: The highest performance was achieved by the NLR (cut-off 2.960) with the AUC = 0.91, with an accuracy of 96.1%, sensitivity of 78.4% and specificity of 97.2%, PPV = 64.4% and NPV = 98.6%. The LRM and NLRM including all the haematological parameters did not increase the per-formance in terms of recurrence detection. Conclusion: The NLR is an excellent support tool in predicting the recurrence of PA with a cut-off of 2.960. It can be a good reference point for surgical decision-making and follow-up in clinical practice.

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

Cow’s Milk (CM) is a healthy food consumed worldwide by individuals of all ages. Unfortunately, 'lactase deficient' individuals cannot digest milk's carbohydrate lactose depriving themselves of highly beneficial milk proteins like casein, lactoalbumin and lactoglobulin, due to lactose intolerance (LI), while other individuals develop cow milk allergy specifically against these proteins (CMPA). The management of these conditions is distinctly different and an inappropriate diagnosis or treatment may have significant implications for the patients, especially if they are infants or very young children, resulting in unnecessary dietary restriction or avoidable adverse reactions. Omics technologies play a pivotal role in elucidating the intricate interactions between nutrients and the human body, spanning from genetic factors to the microbiota profile and metabolites. This comprehensive approach enables the precise delineation and identification of distinct cohorts of individuals with specific dietary requirements, so that tailored nutrition strategies can be developed. This is what is called personalized nutrition or precision nutrition (PN), the area of nutrition that focuses on the effects of the nutrients over the genome, proteome and metabolome, promoting well-being and health, preventing diseases, reducing chronic disease incidence, and so increasing life expectancy. Here, we report the scientific community opinion proposing to replace the approach “one size fits all” with tailor-made nutrition programs, designed by integrating nutrigenomic data together with clinical parameters and microbiota profiles, taking into account the individual lactose tolerance threshold and needs in terms of specific nutrients intake. This customized approach could help LI patients to improve their quality of life, overcoming depression or anxiety, often resulting from the individual perception of this condition as different from a normal state.

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

Food-borne transmission is a recognized route for many viruses associated with gastrointestinal, hepatic or neurological diseases. Therefore, it is essential to identify new bioactive compounds with broad-spectrum antiviral activity is needed to exploit innovative solutions against these hazards. Lately, antimicrobial peptides (AMPs) have been recognized as promising antiviral agents. Indeed, while the antibacterial and antifungal effects of these molecules have been widely reported, their use as potential antiviral agents has not yet been fully investigated. Herein, the antiviral activity of previously identified or newly designed AMPs, was evaluated against the non-enveloped RNA viruses, Hepatitis A virus (HAV), and Murine Norovirus (MNV), a surrogate for human Norovirus. Moreover, specific assays were performed to recognize at which stage of the viral infection cycle the peptides could function. Results showed that almost all peptides displayed virucidal effects with about 90% of infectivity reduction on HAV or MNV. However, the decapeptide RiLK1 demonstrated, together with its antibacterial and antifungal properties, a notable reduction in viral infection for both HAV and MNV, possibly through direct interaction with viral particles or inhibition of the viral bonding to the cell receptors. Hence, RiLK1 could represent a versatile ‘antimicrobial agent effective against various foodborne pathogens including viruses, bacteria, and fungi.

Cardiovascular disease (CVD) is the leading cause of death worldwide. Cardiac rehabilitation (CR) has proven to be effective in reducing the rate of recurrence and disease as secondary prevention (evidence-based intervention) in patients who have suffered from myocardial infarction (MI). CR is a multidisciplinary path in which the patient is followed pharmacologically, from a psychological, nutritional, nursing and physiotherapy point of view. Post-MI patients present a reduction in the performance of the diaphragm muscle, the main inspiratory muscle, and this condition can become a risk factor for further relapses or for the onset of heart failure. Despite the solidity of the international guidelines for CR, the latter are lacking in specifically indicating an evaluation and training path regarding the inspiratory muscles in post-MI patients who have not undergone cardiac surgery. The article reviews the information on the adaptation of the diaphragm post-MI and highlights the need for clearer indications for a rehabilitation process that gives importance to the diaphragm.

The genus Strophantus belongs to the Apocynaceae family of flowering plants which grows primarily in tropical Africa. The plants are widely used in traditional herbal medicine. S. sarmentosus, in particular, is used for the treatment of, e.g., joint pain and rheumatoid arthritis, wound infections, head lice, diarrhoea, snake bite, and eye conditions. Despite the widespread use, dedicated research characterizing bioactive plant components is scarce. Investigations focussed mainly on the cardenolides, because of their cardioactivity and historical use as cardiotonic. There are also studies concerning the antibacterial, antioxidant and anti-inflammatory activity of plant extracts. This review summarizes the present knowledge about the biochemical and analytical reserach on Strophantus, in general, and S. sarmentosus, in particular, and describes the current state-of-the-field based on the available sientific literature.

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

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

Neurodegeneration is a major problem in neuroscience and medicine as it causes and worsens many neurological and psychiatric disorders. It involves gradual loss of neurons at different levels of the brain, affecting cognition, emotion, behavior, consciousness, and attention. Understanding the causes and consequences of neurodegeneration is crucial for identifying the risk factors, biomarkers, and treatments. However, the current therapies are mostly symptomatic and ineffective. Therefore, new and innovative methods, such as noninvasive brain stimulation (NIBS), are needed to modulate brain activity and plasticity in a safe and reversible manner. This field is rapidly developing, with a focus on exploring new clinical applications, mechanisms, and combinations of NIBS and drugs. This special issue covers the latest progress and challenges in the study of neurodegeneration in cognitive impairment and mood disorders from the experimental, clinical, and translational perspectives. It addresses the complexity and diversity of these conditions, the lack of disease-modifying treatments, the ethical and practical issues of conducting research in vulnerable and diverse populations, the integration and interpretation of data from multiple sources and modalities, and the development and validation of novel methods such as NIBS, artificial intelligence, and drug repurposing. Collaborative efforts among various stakeholders are needed to improve our knowledge and treatment of neurodegeneration underlying cognitive impairment and mood disorders.

Coronary optical coherence tomography (OCT) is an intravascular, near-infrared light-based imaging modality capable of reaching axial resolutions of 10-20 µm. This resolution allows for accurate determination of high-risk plaque features, such as thin cap fibroatheroma; however, visualisation of morphological features alone still provides unreliable positive predictive capability for plaque progression or future major adverse cardiovascular events (MACE). Biomechanical simulation could assist in this prediction, but this requires extracting morphological features from intravascular imaging to construct accurate three-dimensional simulations of patients’ arteries. Extracting these features is a laborious process, often carried out manually by trained experts. To address this challenge, numerous techniques have emerged to automate these processes while simultaneously overcoming difficulties associated with OCT imaging, such as its limited penetration depth. This systematic review summarises advances in automated segmentation techniques from the past five years (2016-2021) with a focus on their application to the three-dimensional reconstruction of vessels and their subsequent simulation. We discuss four categories based on the feature being processed, namely: coronary lumen; plaque characteristics and subtypes; artery layers; and stents. Areas for future innovation are also discussed as well as their potential for future translation.

Background: The surgical approach to treating calcaneal fractures, specifically Sanders types II, III, and IV, is still a subject of controversy. The decision to opt for open reduction and internal fix-ation (ORIF) or minimally invasive osteosynthesis (MIOS) remains uncertain owing to varying complication rates. This study intends to examine each treatment’s pros and cons in relation to the incidence of complications. Methods: In this retrospective study, we examined 70 patients treated between January 2018 and September 2022: 50 received ORIF, and 20 underwent MIOS. We evaluated functional outcomes with the Maryland Foot Score and the Creighton-Nebraska Health Foundation Assessment Scale (CNHFAS). We also assessed the amount of anatomical restoration using Böhler’s and Gissane’s angles, determined by radiographic checks, and the frequency of postoperative complications. Results: A significant reduction in the risk of reinter-vention was observed in patients with high anesthetic risks, polytraumatized individuals, and those with comorbidities who underwent MIOS. The chi-square test analysis of postoperative complications highlighted no substantial differences between the ORIF and MIOS groups in rela-tion to tendinitis, chronic pain and swelling, algodystrophy, and surgical wound infections (p > 0.20 for all). Conclusion: ORIF is more suitable for patients who have high motor function re-quirements, a long-term activity schedule and can endure potential additional procedures. This preference is because ORIF provides better anatomical restoration and features a lower osteoar-thritis occurrence rate.

The use of zeolite in agriculture as a soil conditioner is becoming an important field of research in crop growth. To study the effect of synthetic zeolite and deficit irrigation on sweet pepper (Capsicum annuum L.) cultivation, an experiment in a controlled environment was conducted. In particular, sweet pepper was cultivated in a glasshouse using polypropylene pots filled with sandy-loam soil to which 2% of zeolite was added. The zeolite employed in the experiments was obtained using coal fly ash as raw material. The experiment was planned in order to have two main treatments consisting of a) soil with zeolite at 2% (Z) and b) soil without zeolite, as control (C), and three subplot treatments consisting of 1) full irrigation at 100% of available water content (AWC) (100); 2) deficit irrigation at 70% of AWC (70); 3) deficit irrigation at 50% of AWC (50). Sweet pepper cultivation started on the 24th April 2023 and lasted until the 23th June 2023 and during the trial environmental data, such as soil humidity, air temperature and relative humidity, and some crop parameters, such as plant height, leaf number, SPAD index, were monitored. At the end of the trial, fresh and dry plant weight, dry matter content, and leaf water potential were measured. Results showed that for plant fresh weight and dry matter content, no significant differences were observed by treatments and their interactions whereas for the other parameters the statistical analysis returned significant differences. The study suggests that the soil structural benefits, resulting from the zeolite application, are not followed by an equal positive effect in terms of sweet pepper growth under deficit irrigation conditions.

Coronavirus disease 2019 (COVID-19) displays clinical heterogeneity, but little information is available for patients with mild or very early disease. We aimed to characterize biomarkers that are useful in discriminating the hospitalization risk in a COVID-19 cohort from Northern Italy during the first pandemic wave. We enrolled and followed for four weeks 76 symptomatic SARS-CoV-2 positive patients and age/sex-matched healthy controls. Patients with mild disease were discharged (n.42), and the remaining were hospitalized (n.34). Blood was collected before any anti-inflammatory/immunosuppressive therapy and assessed for soluble C5b-9/C5a, H3-neutrophil extracellular traps (NET), calprotectin, DNase plasma levels by ELISA, and a panel of pro-inflammatory cytokines by ELLA. Calprotectin and NET levels discriminate between hospitalized and non-hospitalized patients, while DNase negatively correlates with NET levels; there are positive correlations between calprotectin and both NET and neopterin levels. Neopterin levels increase in patients at the beginning of the disease and more in hospitalized than non-hospitalized ones. C5a and sC5b-9, and other acute phase proteins correlate with neopterin, calprotectin, and DNase. Both NET and neopterin levels negatively correlate with platelet count. We show that calprotectin, NET, and neopterin are important proinflammatory parameters potentially useful in discriminating between COVID-19 patients at risk for hospitalization.

The study of rare diseases is important not only for the individuals affected but also for the advancement of medical knowledge and a deeper understanding of human biology and genetics. The wide repertoire of structural information now available from reliable and accurate prediction methods provides the opportunity to investigate the molecular origins of most of the rare diseases reviewed in the Orpha.net database. Thus, it has been possible to analyze the topology of the missense mutations found in the 2,535 proteins involved in Mendelian rare diseases (MRD), which form the database for our structural bioinformatics study. The amino acid substitutions responsible for MRD show different mutation site distributions at different three-dimensional protein depths. We then predicted the depth-dependent effects of mutations for the 20,248 pathogenic variants that are present in our database. The results of this structural bioinformatics investigation are relevant, as they provide additional clues to mitigate the damage caused by MRD.

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

Background: Facebook represents a new dimension for global information sharing. Suicidal behaviours and attempts are growingly reported on Facebook. This scoping review explores the various aspects of suicidal behaviours associated with Facebook, discussing the challenges and preventive measures. Methods: PubMed, Google Scholar, and Scopus were searched for related articles published in English up to October 2021, using different combinations of "Facebook" and "suicide". A group of consultant psychiatrists screened the records and read the full-text articles to extract relevant data. Results: Facebook impacts suicidal behaviours in different aspects. Announcing suicides through sharing notes or personal information, which can be helpful in prediction of suicide, and harmful since negatively affects audience. Live-streaming videos of suicide is another aspect, which questions the ability of Facebook to monitor shared contents that can negatively affect the audience. Helping bereaved families to share feelings and seek support online, commemorating the lost person by sharing their photos is another positive impact. Moreover, it can provide real-world details of everyday user behaviours, which are helpful to predict suicide risk, primarily through novel machine-learning techniques, and provide early warning and valuable help to prevent it. It can also provide a timeline of the user's activities and state of mind before suicide. Conclusions: Social media can detect suicidal tendencies, provide support for those seeking help, comfort family and friends with their grief, and provide insights via timelining the users' activities leading to their suicide. The lack of quantitative studies on evaluating preventative efforts on Facebook was one of the limitations. The creators' commitment and the users' social responsibility will be required to create a mentally healthy Facebook environment.

The cold-pressed hempseed oil (HO) has been increasingly exploited in human diet for its excellent nutritional and healthy properties. However, it has a high content of polyunsaturated fatty acids (PUFAs) and chlorophylls, which inevitably accelerate its oxidative deterioration, especially in presence of light. In this scenario, the filtration technology may ameliorate the oxidative stability of the oil, with positive effects on its nutritional quality and shelf-life. Therefore, in this study, the oxidative stability and minor compounds of non-filtered and filtered HO (NF-HO and F-HO) were monitored over 12 weeks of storage in transparent glass bottles. F-HO showed a better hydrolytic and oxidative status than NF-HO during storage. As a result, F-HO displayed also a better preservation of total MUFA and PUFA in the autoxidation process. Filtration consistently reduced chlorophylls, thus, causing a variation of the natural color of HO. Accordingly, F-HO not only revealed an increased resistance to photooxidation but was also suitable for storage in clear bottles within 12 weeks. F-HO predictably showed lower carotenoids, tocopherols, polyphenols, and squalene compared to NF-HO. However, filtration appeared to play a “protective role” toward these antioxidants, which had lower degradation rates in F-HO than NF-HO for 12 weeks. Interestingly, the element profile of HO was not affected by filtration and remained stable during the study period. Overall, this study may be of practical use to both producers and marketers of cold-pressed HO.

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

Background: Tetanus is an acute, fatal disease caused by exotoxins released from Clostridium tetani during infections. A protective humoral immune response can be induced by vaccinations with pediatric and booster combinatorial vaccines that contain inactivated tetanus neurotoxin (TeNT) as a major antigen. Although some epitopes in NeNT have been described using various ap-proaches, a comprehensive list of its antigenic determinants that are involved with immunity have not been elucidated. To that end, a high resolution analysis of the linear B-cell epitopes in NeNT was performed using antibodies generated in vaccinated children. Methods: Two hundred sixty-four peptides that cover the entire coding sequence of TeNT protein were prepared in situ on a cellulose membrane by SPOT synthesis and probed with sera from children vaccinated (ChVS) with a triple DTP-vaccine to map continuous B-cell epitopes that were further characterized and validated by immunoassays. Results: Forty-three IgG epitopes were identified. Four (TT-215-218) were chemically synthesized as Multiple Antigen Peptides (MAPs) and used in peptide ELISAs to screen post-pandemic DTP vaccinations. The assay displayed a high performance with high sensitivity (99.99%) and specificity (100%). Conclusions: The complete map of linear IgG epitopes induced by vaccination with inactivated TeNT highlights three key epitopes involved in the ef-ficacy of the vaccine. Antibodies against epitope TT-8/G can block enzymatic activity, and those against epitopes TT-40/G and TT-42/G can interfere with TeNT binding to neuronal cell receptors. We further show that four of the epitopes identified can be employed in peptide ELISAs to assess vaccine coverage. Overall, the data suggest a set of select epitopes to engineer new, directed vaccines

Background: clubfoot is a common congenital deformity. The Ponseti technique, involving early corrective manipulations followed by the application of long leg casts and Achilles tenotomy, is widely accepted as the preferred treatment. Rapid healing of the tendon after surgery has been documented, but the aspect regarding tendon structure and properties is not known. Three cases of Achilles tendon rupture in adolescent previously treated for clubfoot have been described in the literature. Since rupture is a rare event in this age group a possible correlation with previous surgery has been hypothesized. The primary aim of the study was to compare the ultrasound findings of the Achilles tendon, in patients treated for clubfoot, between patients treated with casting alone and the ones who underwent surgery (percutaneous tenotomy or Z-plasty lengthening). Methods: 22 asymptomatic patients, (34 feet) median age 12 years, previously treated for clubfoot, were recruited for this study; the patients underwent an Achilles tendon ultrasound examination during a follow-up outpatient visit. Results: a greater thickness and structural alterations with presence of hypoechoic areas of the operated tendons compared to those treated with plaster alone were observed (p value: 0.0498 and

Recently, pharmaceutical research has been focused on the design of new antibacterial drugs with higher selectivity towards several strains. Major issues concern the possibility to obtain com-pounds with fewer side effects, at the same time effectively overcoming the problem of antimi-crobial resistance. Several solutions include the synthesis of new pharmacophores starting from piperazine or morpholine core units. Mass spectrometry-based techniques offer important sup-port for the structural characterization of newly synthesized compounds to design safer and more effective drugs for various medical conditions. Here, two new piperazine derivatives and four new morpholine derivatives were synthesized and structurally characterized through a combined approach of FT-ICR and LTQ mass spectrometry. The support of both high-resolution and low-resolution mass spectrometric data namely accurate mass measurements, isotopic distribu-tion and MSn spectra, was crucial to confirm the success of the synthesis. These compounds were further evaluated for inhibitory activity against a total of twenty-nine Gram-positive and Gram-negative bacteria to determine the action spectrum and the antimicrobial effectiveness. Results demonstrated compounds’ antimicrobial activity against many tested bacterial species, providing an inhibitory effect linked to different chemical structure and suggesting that the new-synthesized derivatives could be considered as promising antimicrobial agents.

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

Tsunami modeling and simulation has changed in the past few years more than it had in decades, especially so with respect to coastal inundation. Among other things, this change is supported by the approaching era of exa-scale computing, whether via GPU or more likely forms of hybrid computing whose presence is growing across the geosciences. For reasons identified across this review, exa-scale computing efforts will impact the on-shore, highly turbulent r\'egime to higher degree than the 2D shallow water equations used to model tsunami propagation in the open ocean. This short review describes the different approaches to tsunami modeling from generation to impact and underlines the limits of each model based on the flow r\'egime. Moreover, from the perspective of a future comprehensive multi-scale modeling infrastructure to simulate a full tsunami, we underline the current challenges associated with this approach and review the few efforts that are currently underway to achieve this goal. A table of existing tsunami software packages is provided along with an open Github repository to allow developers and model users to update the table with additional models as they are published and help with model discoverability.

Cancer remains one of the main causes of death in the world due to its increasing incidence and treatment difficulties. Although several progresses have been done in this field, innovative approaches are needed to reduce tumor incidence, progression and spreading. In particular, the development of cancer vaccines is currently ongoing like both preventive and therapeutic strategy. This concept is not new, but few vaccines have been approved in oncology. Antigen-based vaccination emerges as a promising strategy, leveraging specific tumor antigens to activate the immune system response. However, challenges persist in finding suitable delivery systems and antigen preparation methods. Exosomes (EXs) are highly heterogeneous bilayered vesicles which carry several molecule types in the extracellular space. The peculiarity is that they may be released from different cells and may be able to induce a direct or indirect stimulation of immune system. In particular, EX-based vaccines may cause anti-tumor immune attack or produce memory cells recognizing cancer antigens and inhibit disease appearance. This review delves into EXs composition, biogenesis, and immune-modulating properties exploring their role as tool for prevention and therapy in solid tumors. Finally, here we describe future research directions to optimize vaccine efficacy and realize the full potential of EX-based cancer immunotherapy.

Background: Sarcoma may show similarities to malignant melanoma in terms of morphologic and immunohistochemical aspects, hence making it difficult to differentiate between these two neoplasms during the diagnostic process. This systematic review aims to summarize available evidence on cases of sarcoma that were initially diagnosed as melanoma. Methods: A comprehensive search was conducted including MEDLINE/Pubmed, EMBASE and SCOPUS through March 2023. We included case series and case reports of sarcoma patients that were initially diagnosed as malignant melanoma. PRISMA guidelines were followed. Results: Twenty-three case reports and four case series with a total of 34 patients were included. The clinical presentation was heterogeneous, and the most involved anatomical regions were lower limbs (24%), head/neck (24%) and upper limbs (21%). IHC positivity was reported for S100 (69%), HMB45 (63%), MelanA (31%) and MiTF (3%). The main reasons for second assessment were unusual presentation (48%) and uncertain diagnosis (28%). EWSR1 translocation was investigated in 17/34 patients (50%) and found positive in 16/17 (94%). The final diagnosis was clear cell sarcoma (50%) or other soft tissue sarcomas (50%). Conclusions: Melanoma and some histotypes of sarcoma share many similarities. In case of atypical lesions, a second diagnosis should be considered, and ESWR1 translocation should be investigated.

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

Despite successful vaccination efforts, the emergence of new SARS-CoV-2 variants poses ongoing challenges to control COVID-19. Understanding humoral responses concerning SARS-CoV-2 infections and their impact is crucial for developing future vaccines that are effective worldwide. Here, we identified 41 immunodominant linear IgG B-cell epitopes in its Spike glycoprotein with a SPOT synthesis peptide array probed with a pool of serum from hospitalized COVID-19 patients. Bioinformatics showed a restricted set of epitopes unique to SARS-CoV-2 compared to other coronavirus family members. Potential crosstalk was also detected with Dengue virus (DENV), confirmed by screening individuals infected with DENV before the COVID-19 pandemic in a commercial ELISA assay for anti-SARS-CoV-2 antibodies. Higher reactivity indices were often measured in individuals with a pre-pandemic dengue infection than those with COVID-19. A high-resolution evaluation of antibody reactivity against peptides representing epitopes in the spike protein identified ten sequences in the NTD, RBD, and S2 domains. Functionally, antibody-dependent enhancement (ADE) in SARS-CoV-2 infection of monocytes was observed with pre-pandemic dengue-positive sera. A significant increase in viral load was measured compared to controls, with no detectable neutralization or considerable cell death, suggesting its role in viral entry. This study highlights the importance of identifying the epitopes generated during the humoral response to a pathogenic infection to understand the potential interplay of previous and future conditions on disease. Vaccine development and optimization strategies should be mindful of the potential for A.D.E. that could differ geographically due to endemic biological risks.

We describe the development and validation of a HPLC-MS/MS method to assess the pharmacokinetics and tumour distribution of fenretinide, a synthetic retinoid chemically related to all-trans-retinoic acid, after administration of a novel oral nanoformulation of fenretinide, called bionanofenretinide (BNF). BNF was developed to overcome the major limitation of fenretinide: its poor aqueous solubility and bioavailability due to its hydrophobic nature. The method proved to be reproducible, precise, and highly accurate for the measurement of the drug and the mains metabolites. The lower limit of quantification resulted 1 ng/mL. The curve range of 1-500 ng/mL and 50-2000 ng/mL, for plasma and tumor homogenate respectively, was appropriate for the analysis, as demonstrated by the accuracy between 96.8% and 102.4% for plasma and 96.6-102.3% for tumor. The inter-days precision and accuracy determined on quality controls at 3 different levels were in ranges of 6.9%-7.5% and 99.3-101.0% and 0.96-1.91% and 102.3-105.8% for plasma and tumour, respectively.