Smoker’s paradox usually refers to the common observation of a favourable outcome of smoker patients in acute myocardial infarction. The interpretation of this phenomenon is still controversial and not fully explained. We aimed at assessing whether smoking could be associated with mortality in a large cohort of prospectively enrolled patients with ST segment elevation myocardial infarction (STEMI) referred to primary percutaneous coronary intervention (pPCI). From April 2006 to December 2018 a population of 2456 STEMI patients treated with primary PCI were prospectively enrolled in the MATRIX registry. Ischemic time, clinical, demographics, angiographic data and 1-year follow-up were collected. Among 2546 patients admitted with STEMI 1007 (41%) were current smokers. Smokers were 10 years younger and had lower crude in-hospital and 1-year mortality (1.5% vs 6%, p<0.0001 and 5% vs 11%, p<0.0001), shorter ischemic time (203 [147-299] vs 220 [154-334] minutes, p=0.002) and shorter decision time (60 [30-135] vs 70 [36-170] minutes, p=0.0063). After propensity-matching, age, cardiogenic shock and low TIMI score were associated with in-hospital mortality, while smoking habit was still associated with reduced mortality. Smoking was also associated with reduced death rate at 1-year follow-up (HR 0.54, 95% CI [0.37 - 0.78]; p<0.001). Our data show a protective link between smoking status and mortality in patients with STEMI, the so called “smoker’s paradox”. This could be explained not only by the shorter ischemic time and younger age of the smoking population but also by a specific pathogenetic effect of smoking underlying the onset of STEMI and response to therapies.

New series of compounds containing both heterocycle moieties and pseudo-symmetric hydroxyethylamine core were obtained using a simple synthetic path that can provide a library of compounds in few steps and high yields. Furthermore, diversity-oriented synthesis was studied to change different functionalities according to needs. The in vitro inhibition activity against recombinant HIV-1 protease was evaluated. A beneficial effect of this class of compounds can be obtained either for the presence of a bis-benzyl group into the core and for the heterocyclic moiety in P1, specifically the indole ring. Docking analysis was also reported.

Somatosensory tactile experience is a key aspect of our interaction with the environment. It is involved in object manipulation, in the planning and control of actions and, in its affective components, in the relationships with other individuals. It is also a foundational component of body awareness. An intriguing aspect of sensory perception in general and tactile perception in particular is the way in which stimulation comes to consciousness. Indeed, although being aware of something seems a rather self-evident and monolithic aspect of our mental states, sensory awareness may be in fact modulated by many different processes that impact on the mere stimulation of the skin, including the way in which we perceive our bodies as belonging to us. In this review, we first took into consideration the pathological conditions of absence of phenomenal experience of touch, in the presence of implicit processing, as initial models for understanding the neural bases of conscious tactile experience. Subsequently, we discussed cases of tactile illusions both in normal subjects and in brain-damaged patients which help to understand which high order processes impact tactile awareness. Finally, we discussed the observations reported in the review in light of some influential models of touch and body representation.

The remote monitoring of clinical parameters plays a fundamental role in different situations, like pandemic health emergencies and post-surgery conditions. In these situations, the patients might be impeded in their movements and it could be difficult to have a specific health monitoring. In recent years, technological advancements in smartphones have opened up new possibilities in this landscape. The present work aims to propose a new method for respiratory kinematics monitoring via smartphone sensors. In particular, a specific application was developed to register Inertial Movement Unit (IMU) sensors data from the smartphone for respiratory kinematics measurement and to guide the user through a specific acquisition session. The session was defined to allow for the monitoring of the respiratory movement in five prescribed positions. The application and the sequence were successfully tested on a given population of 77 healthy volunteers. The resulting accelerometers and gyroscope signals were processed to evaluate the significance of differences according to participants sex, vector components and smartphone positioning and, finally, to estimate the respiratory rate. The emerged statistical differences revealed the significance of information in the different acquisition positions.

The ability of S. aureus to infect humans and cause a wide range of infections so efficiently is a consequence of the many variant virulence factors that it can produce. Superantigens (SAgs) make up a group of them and include staphylococcal enterotoxins (SE). The main objective of this study was to detect enterotoxin gene cluster (EGC) in S. aureus isolates that caused infections in Paraguayan children in the year 2017, through an observational and cross-sectional study. The detection of the EGC including the seg, sei, sem, sen, seo, and seu genes, was carried out by end-point PCR. 181 S. aureus isolates were collected, most of them caused skin and soft tissue infections (SSTI, n=140, 77%) and came from children under 6 years 50% (n=90). At least one SE gene was detected in 96% (174/181) of isolates and 24% (44/181) carried the entire EGC. An association between methicillin resistance and seg, sei, seo, and seu gene carriage (p ≤0.05) was observed. A high prevalence of EGC was detected in S. aureus isolates collected from infected children attending the main health care centers in Paraguay, its importance is due to the potential of these toxins to aggravate staphylococcal infections.

Anomalous waves and rogue events are closely associated with irregularities and unexpected events occurring at various levels of physics, such as in optics, in oceans and in the atmosphere. Mathematical modeling of rogue waves is a highly actual field of research, which has evolved over the last decades into a specialized part of mathematical physics. The applications of the mathematical models for rogue events is directly relevant to technology development for prediction of rogue ocean waves, and for signal processing in quantum units. In this survey, a comprehensive perspective of the most recent developments in methods for representing rogue waves is given, along with discussion of the devised and forms and solutions. The standard nonlinear Schrödinger equation, the Hirota equation, the MMT equation and further to other models are discussed, and their properties highlighted. This survey shows that the most recent advancement in modeling rogue waves give models which can be used to establish methods for prediction of rogue waves at open seas, which is important for the safety and activity of marine vessels and installations. The study further puts emphasis on the difference between the methods, and how the resulting models form a basis for representing rogue waves in various forms, solitary or with a wave-background. This review has also a pedagogic component directed towards students and interested non-experts, and forms a complete survey of the most conventional and emerging methods published until recently

Previous studies on the mechanisms underlying willed actions reported that the premotor cortex may be involved in the construction of motor awareness. However, its exact role is still under investigation. Here we investigated the role of the dorsal premotor cortex (PMd) in motor awareness by modulating its activity applying inhibitory rTMS to PMd, before a specific motor awareness task (under three conditions: without stimulation, after rTMS and after sham stimulation). During the task, subjects had to trace straight lines to a given target, receiving a visual feedback of the line trajectories on a computer screen. Crucially, in most trials the trajectories on the screen were deviated and to produce straight lines, subjects had to correct their movements towards the opposite direction. After each trial, participants were asked to judge whether the line seen on the computer screen corresponded to the line actually drawn. Results show that participants in the no stimulation condition did not recognize the perturbation until 14 degrees of deviation. Importantly, active, but not sham, rTMS significantly modulated motor awareness, decreasing the amplitude of the angle at which participants became aware of the trajectory correction. These results suggest that PMd plays a crucial role in action self- monitoring.

In this paper, we propose a quantitative definition of emergence from the density matrix framework as a state of knowledge of the system and its generalized probability formulation, in order to detect emergent properties. We propose the use of a descriptor based on the difference of von Neumann entropy, to calculate if subsystems of systems have inner correlations by defining emergent systems in terms of emergent information.

Two wild-type field populations of root-knot nematodes (Mi-Vfield, Mj-TunC2field), and two isolates selected for virulence in laboratory on resistant tomato cultivars (SM2V, SM11C2), were used to induce a resistance reaction in tomato to the soil-borne parasites. Epigenetic and metabolic mechanisms of resistance were detected and compared with those occurring in partially or fully successful infections. The activated epigenetic mechanisms in plant resistance, as opposed to those activated in infected plants, were detected by analysing the methylated status of total DNA, by ELISA methods, and the expression level of key genes involved in the methylation pathway, by qRT-PCR. DNA hypo-methylation and down-regulation of two methyl-transferase genes (CMT2, DRM5), characterized the only true resistant reaction obtained by inoculating the Mi-1.2-carrying resistant tomato cv Rossol with the avirulent field population Mi-Vfield. On the contrary, in the roots into which nematodes were allowed to develop and reproduce, total DNA was generally found to be hyper-methylated and methyl-transferase genes up-loaded. DNA hypo-methylation was considered to be the upstream mechanism that triggers the general gene over-expression observed in plant resistance. Gene silencing induced by nematodes may be obtained through DNA hyper-methylation and methyl-transferase gene activation. Plant resistance is also characterized by an inhibition of the anti-oxidant enzyme system and activation of the defence enzyme chitinase, as opposed to the activation of such a system and inhibition of the defence enzyme glucanase in roots infested by nematodes.

American secularisation is considered a exceptional case in the Western world because of, on the one hand, the softer way it seems to have occurred in relation to other Western countries and, on the other, the fusion it seems to have been done among Judeo-Christian traditions into what is known as American civil religion. The point proposed before is problematic and needs to be called into questions under the light of both the revisions made to the secularization theory by scholars such as Casanova through the interpretation of empirical data collected through the world about the religiosity of people and the multiple works made about the use of “sacred” language in American public life. However, this paper takes those problematic dimensions for granted in order to deepened into what can be considered another secular human endeavour endowed with a religious spirit, namely: the spirit of Silicon Valley. This new secular-sacred narrative is not just American but is being exported as a narrative with “Messianic” traces that seems to aspire to embrace the whole world. Thus, this article explores the origins and evolution of this narrative in the United States, on the one hand, and the expansion of what can be considered a “salvation” ideology abroad that country, on the other.

While some researchers have suggested that the self-employment (SE) sector is a haven during a financial Crisis, others believe that SE is not necessarily the desired outcome, but an indicator that the labor market is tightening for some groups. Few researchers have compared the SE sector before and after the occurrence of a significant financial Crisis, especially in developed countries. This paper analyzes the determinants of entry into self-employment during the 2008 Spanish Crisis. Using data from the Encuesta de Presupuesto Familiar (EPF), results show that although the rate of SE did not experience a significant change during this time the Crisis affected people differently based on gender, with being females more affected than males. Results also suggest differences between Comunidades Autonomas in how the self-employment sector behaved during the Crisis.

In this article the galactic rotation curve is analyzed as an effect of an accelerated reference frame. This phenomenon is the strongest evidence for the so called dark matter. We show that a non-inertial reference frame could explain the experimental data. We also show that general relativity is not enough to complete explain that which encouraged alternatives paths such as the MOND approach. Considering the effect of dark matter as a realization of accelerated reference frames is a simple but powerful hypothesis.

The paper will examine in detail (a) the norms that can be featured under the category "Green Deal" connected to the European Commission, (b) their application to Spain and (c) the different patterns of action and development models that have been shaped by this framework over the last 20 years. These patterns are particularly relevant currently, as the Covid crisis has highlighted the importance of advancing towards new patterns of local sustainability endowed with higher resilience. The notion of cognitive sustainability will be one of the added value to current reflections on sustainability in general and energetic sustainability in particular.

Sport has the potential to support psychosocial development in young people. However, extant studies have tended to evaluate purpose-built interventions, leaving regular organised sport relatively overlooked. Moreover, previous work has tended to concentrated on a narrow range of outcomes. To address these gaps, we conducted a season-long ethnography of a youth performance sport club based on a novel Realist Evaluation approach [1]. We construed the club as a social intervention within a complex system of agents and structures. In this - Part 1 - account we detail the perceptions of former and current club parents, players and coaches, using them to build a set of programme theories. The resulting network of outcomes (i.e. self, emotional, social, moral and cognitive) and generative mechanisms (i.e., the attention factory, the greenhouse for growth, the personal boost, and the real-life simulator) spanning across multiple contextual layers provides a nuanced understanding of stakeholders’ views and experiences. This textured perspective of the multi-faceted process of development provides new insights for administrators, coaches and parents to maximise the developmental properties of youth sport, and signposts new avenues for research in this area.

Commercial formulates of beneficial microbes have been used to enrich the rhizosphere microbiome of tomato plants grown in pots located in a glasshouse. These plants have been subjected to attacks by soil-borne parasites, such as root-knot nematodes (RKNs), and herbivores, such as the miner insect Tuta absoluta. The development of both parasites and the symptoms of their parasitism were restricted in these plants with respect to plants left untreated. A mixture, named in the text as Myco, containing plant growth promoting rhizobacteria (PGPR), opportunistic biocontrol fungi (BCF), and arbuscular mycorrhizal fungi (AMF) was more effective in limiting pest damages than a formulate containing the sole AMF (Ozor). Therefore, Myco-treated plants inoculated with RKNs were taken as a model to further study which biocontrol agent (BCA) was specifically responsible of plant immunization and the molecular pathways exploited to achieve such an immunization. The PGPR contained in Myco were not able to reduce nematode infection, rather, they worsened symptoms on plants, compared with those observed on untreated plants. When plants were treated with suspensions of Bacillus subtilis at concentrations similar to those provided with Myco and then inoculated with RKNs, infection was actually more severe than that on untreated plants. Therefore, it was argued that both BCF and AMFwere the microorganisms that, colonizing roots, synergistically stimulate plant immune system against RKNs. Beneficial fungi lowered the activities of the defense supporting enzymes endochitinases and β-1,3-glucanase to be able to colonize the roots. However, as early as three days after nematode inoculation, these enzyme activities, and the expression of the encoding pathogenesis related genes (PR-2, PR-3) were found to be enhanced in roots with respect to not inoculated plants, thus indicating that plants had been primed against RKNs. Addition of paclobutrazol, which reduced salicylic acid (SA) levels in cells, and of diphenyliodonium chloride, which inhibits superoxides generation, completely abolished the repressive effect of Myco on nematode infection and presumably plant immune reaction. Inhibitors of copper enzymes and of the alternative cyanide-resistant respiration did not significantly alter resistance induction by Myco. When Myco-treated plants were subjected to a moderate water stress and inoculated with nematodes, they retained numbers of developed individuals in the roots similar to those present in regularly watered plants, in contrast to what occurred in roots of untreated stressed plants that hosted very few individuals because of poor nutrient availability.

The Virus HIV-1 infection still represents a serious disease even if actually it is transformed in chronic pathology. Considering the crucial role of the enzyme Protease in life cycle of HIV many efforts have been made in the research of new organic compounds showing inhibitory activity. After development of several series of non peptidic inhibitors we report here the synthesis of novel simple HIV-Protease inhibitors containing heteroaryl carboxamides and their antiviral activity in vitro and in HEK293 cells. Benzofuryl- benzothienyl- and indolyl rings as well as aryl sulfonamides with different electronic properties have been introduced by efficient synthetic procedures. All compounds showed inhibitory activity similar to the commercial drug Darunavir, effective against both wild-type HIV-1 protease and that containing the V32I or V82A mutations. ADME properties were also evaluated, showing the potential of such compounds to be developed as drugs.

⦁ Introduction: The challenging context, resulting from a post-pandemic scenario, wars, and various natural disasters, does not allow for the ideal assurance of efficiency in the Agri-food supply chain. ⦁ Research significance Currently, Agri-food supply chains and Reverse logistics show critical characteristics such as centralization, limited flexibility, distrust, bureaucratization, Border and Documentary Compliance and there are problems about efficiency, security, and safety Agri-Food. using the Supply Chain Operations Reference (SCOR) framework, with the purpose of achieving Sustainable Development Goals, promoting transparency, traceability, and non-linearization of the agri-food supply chain. ⦁ Methodology The methodology is combined, the first part uses Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) identifying 72 articles with the principal contribution in the literature. The second part combines the application of Supply Chain Operations References (SCOR) and the Blockchain Technology aiming to decentralize the linear Agri-food Supply Chain and Reverse logistics. ⦁ Results/findings The results revealed a transformation of the traditional Agri-food Supply Chain, transitioning from linear management to a circular one. Additionally, after application it is possible to know a new way to manage the Reverse Logistic with more decentralization, flexibility, traceability, and reducing the unnecessary activities, which include Border and Documentary Compliance. The originality of this research is the novel combination of SCOR Model and Blockchain showing a priority about the key activities that add value and come close to the Sustainable practices. ⦁ Conclusion / Implications Based on the results is possible to conclude that the synergy between Blockchain and SCOR Model enables a new way to manage the Agri-food supply chain, improving efficiency and reducing activities without value. Also, it is possible to ensure that the practices of Reverse Logistics are improved based on terms of cost and time, and the reduction of the exposition on the Defective Product Risk. ⦁ Social Implications This paper could enhance confidence in all operations of the Agri-food supply chain as there are numerous issues regarding the security and safety of food. Additionally, it will aid in diminishing unnecessary activities and inefficient resource consumption practices, thereby accomplishing objectives 2 "zero hunger", 9 "Industry, Innovation, and Infrastructure", and 12 "Responsible consumption and production", along with their respective indicators. ⦁ Practical implications Regarding the practical implications, this research could contribute to analyses of the application of technology Blockchain in different sectors and identify the possible limitations when the main objective is to apply it on a big scale.

Part 1 of this 2-paper series identified a wide and deep network of context, generative mechanisms and outcomes responsible for psychosocial development in a performance basketball club. In this – part 2 – study, the stakeholder’s programme theories were tested during a full-season ethnography of the same club. The findings confirm the highly individualised nature of each young person’s journey. Methodologically, immersion in the day-to-day environment generated a fine-grain analysis of the processes involved, including: i) sustained attentional focus; ii) structured and unstructured skill building activities; iii) deliberate and incidental support; and iv) feelings indicating personal growth. Personal development in and through sport is thus shown to be conditional, multi-faceted, time-sensitive and idiosyncratic. The findings of this two-part study are considered to propose a model of psychosocial development in and through sport. This heuristic tool is presented to support sport psychologists, coaches, club administrators and parents to deliberately create and optimise developmental environments.

In his best-selling book An Introduction to Probability Theory and its Applications, W. Feller established a way of ending the St. Petersburg Paradox by the introduction of an entrance fee, and provided it for the case in which the game is played with a fair coin. A natural generalization of his method is to establish the entrance fee for the case in which the probability of head is θ (0 < θ < 1/2). The deduction of those fees is the main result of Section 2. We then propose a Bayesian approach to the problem. When the probability of head is θ (1/2 < θ < 1) the expected gain of the St. Petersburg Game is finite, therefore there is no paradox. However, if one takes θ as a random variable assuming values in (1/2,1) the paradox may hold, what is counter-intuitive. On Section 3 we determine a necessary and sufficient condition for the absence of paradox on the Bayesian approach and on Section 4 we establish the entrance fee for the case in which θ is uniformly distributed in (1/2,1), for in this case there is paradox.

The prevalence of patients on buprenorphine therapy presenting for elective surgery has increased. Buprenorphine is a widely used medication for management of patients with chronic pain. It is also used for maintenance therapy for patients with a history of opioid use disorder (OUD). Due to lack of standardized protocol for managing patients on buprenorphine peri-operatively, we performed a retrospective analysis to compare pain score outcomes and post-operative opiate requirements between patients who continued versus discontinued buprenorphine. We identified 35 patients, 11 continued buprenorphine and 24 discontinued buprenorphine. The average Post-Anesthesia Care Unit (PACU) pain score was 7.54 for those who discontinued pre-operative buprenorphine and 5.59 for those who continued (P value 0.0339). The average post-operative Morphine Milligram Equivalent (MME) use was 86.13 for those who continued pre-operative buprenorphine and was 107.70 for those who discontinued buprenorphine (P value 0.6439). The results from our study correlate with several previous studies which showed lower PACU pain scores in patients who continued buprenorphine. There is a benefit of decreased pain post-operatively when pre-operative buprenorphine is continued and having a decrease in relapse in those with a history of OUD.

In Mexico, the evaluations of environmental flows are regulated by the Mexican Norm NMX-AA-159-SCFI-2012 and they warrant the establishment of water reserves for the environment. Yet, the pressure for water use limits the establishment of said reserves. This research aimed to evaluate the changes through time of the variables that serve as a basis for the implementation strategy by the Mexican government. A geographical information system was built with updated variables, the desired conservation status was analyzed, and the potential reserves were estimated based on the reference values for all basins nationwide. The results were examined according to their historical, current, and potential contribution to the conservation of natural protected areas and their connectivity. The outcomes point towards an administrative implementation strategy with positive outcomes despite the growing pressure for water use, with a change rate higher than the one for the creation of new protected areas. Currently, basins with low pressure and high conservation value have the potential to contribute to 86–88% of the goal set by the present administration without affecting water availability. Finally, reserving water in the priority basins would guarantee the legal protection of the flow regime in 48–50% of the hydrographic network in a desired conservation status, 45–49% of wetlands of international importance, and other natural protected areas in 85–89% of the global ecoregions represented in Mexico.

While the role of safe riding behavior as a safety contributor for cyclists has been increasingly studied in recent years, there have been few studies analysing cycling behavior in relation to crash-related outcomes in Baltic countries. Indeed, to the best of our knowledge, this is the first time this issue has been addressed in the case of Latvia. Aim: The objective of this study was to assess the relationships among self-repotted cyclists’ behavior, traffic safety literacy, and their cycling crash involvement rates. Method: A total of 299 cyclists aged M=32.8 from across Latvia (42% females) participated in an online survey, which comprised questions regarding respondents’ demographics, frequency of riding, and the number of crashes in the past five years. The Cycling Behavior Questionnaire (CBQ) and the Cyclist Risk Perception and Regulation Scale (RPRS) were applied to assess cyclists' behavior patterns and traffic safety literacy. Results: According to the findings, it can be inferred that cyclists frequently engage in riding errors and traffic violations while cycling. Those who exhibit more antisocial behavior patterns are also more likely to be involved in road crashes. Conversely, cyclists with greater positive behavior rates more often also tend to possess better knowledge of traffic rules and exhibit a heightened risk perception, indicating a greater awareness of road traffic safety. Conclusion: All in sum, this study underscores key age differences, with older individuals significantly less involved in riding crashes, exhibiting fewer driving errors and a higher level of risk perception, which serves as a crucial factor in road safety. At the practical level, these results stress the need to address both traffic safety literacy and protective cycling factors of cyclists, in a manner to improve overall road safety and promote active transport modes in Latvia.

There is evidence of constitutional rank in Chile, and not only a sectoral rank, to estimate that the regulation of digital media is in an initial and insufficient phase to properly protect information pluralism as political pluralism. The study aims to investigate the forms of concentration, such as the communicational flow of digital media, to determine the opportunities and information defects of these media due to regulatory deficiencies in this sector. Data collection will be carried out through a qualitative and quantitative methodology. The prospect of the imminent constituent process in Chile provides the opportunity to the evaluate the possibilities to propose changes not only at the legislative level but also at the constitutional level, which are likely to benefit freedom of expression with greater guarantees to such as the pluralism of digital media. The latter also means assessing the relevance of enshrining the right to communication in the future.

Toxoplasma gondii, a protozoan parasite with the ability to infect various warm-blooded vertebrates, including humans, is the causative agent of toxoplasmosis. This infection poses significant risks, leading to severe complications in immunocompromised individuals and potentially affecting the fetus through congenital transmission. A comprehensive understanding of the intricate molecular interactions between T. gondii and its host is pivotal for the development of effective therapeutic strategies. This review emphasizes the crucial role of proteomics in T. gondii research, with a specific focus on host-parasite interactions, post-translational modifications (PTMs), PTM crosstalk, and ongoing efforts in drug discovery. Additionally, we provide an overview of recent advancements in proteomics techniques, encompassing interactome sample preparation methods such as BioID, APEX, and Y2H, as well as various proteomics approaches, including single-cell analysis, DIA, targeted, top-down, and plasma proteomics. Furthermore, we discuss the integration of proteomics with other omics technologies, highlighting its potential in unraveling the intricate mechanisms of T. gondii pathogenesis and identifying novel therapeutic targets.

Within the context of sustainable material development for the construction sector, this study explores the viability of panels composed of recycled newspaper-derived cellulose (9%), rice husk (14%), borax (15%), and polyvinyl acetate-based glue (62%). The methods employed involve water absorption and density tests, following ASTM C-1763 and C-303 standards. The fire resistance test conforming to the European standard UNE 23-725-90, and a mold growth test using AOAC 2002.11. The composite is prone to absorbing a significant amount of water when exposed to humid conditions. However, the incorporation of rice husk and borax can provide benefits such as improved moisture resistance compared to other cellulitic insulators, which may be advantageous in specific climates. Also, the developed composite has an intermediate density compared to other polymeric materials. This characteristic presents advantages in applications that demand a balance between strength and lightness. During the fire resistance tests, the samples with borax presented less fire propagation, and superficial damage compared with the specimens without borax. This is important, considering the fireproofing property, required in building materials. The presence of borax in the composite has an inhibitory effect on the growth of fungi and yeasts. These findings are consistent with previous research. Nevertheless, further research and testing are imperative to assess its viability and performance for commercial applications.

The use of biolubricants as an alternative for petroleum-based products has played an important role in the last decade. Thus, due to the encouragement of global policies, which mainly support green chemistry and circular economy, there has been an increasing interest in bio-based products, including biolubricants, from scientific and industrial points of view. Due to the different applications of biolubricants for a wide range of practical uses, the raw materials, production, and characteristics might vary, making this field a continuously changing subject of study by researchers. The aim of this research work was to focus on biolubricant production from vegetable oil crops in a bio-refinery perspective, paying attention to the main raw materials used, the corresponding production methods (with special focus on double transesterification), the role of catalysts and techno-economic studies. Thus, the main factors affecting quality parameters such as viscosity or oxidative stability have been covered, including catalyst addition, reaction temperature or the use of raw materials, reagents or additives were also analyzed. The latest research trends were included, updating previous studies about this matter, considering current conclusions and future research.

High redshift blazars are among the most powerful objects in the Universe. Although they represent a significant fraction of the extragalactic hard X-ray sky, they are not commonly detected in gamma-rays. High redshift (z>2) objects represent <10 per cent of the AGN population observed by Fermi so far, and gamma-ray flaring activity from these sources is even more uncommon. The characterization of the radio-to-gamma-ray properties of high redshift blazars represents a powerful tool for the study of the energetics of such extreme objects and the Extragalactic Background Light. This contribution will present results of multi-band campaigns, from radio to gamma-rays, on PKS 0836+710, PKS 2149-306, and TXS 0536+145. The latter is the highest redshift detection of a flaring gamma-ray blazar so far. At the peaks of their respective flares these sources reached an apparent isotropic gamma-ray luminosity of about 10^50 erg/s, which is comparable with the luminosity observed from the most powerful blazars. The physical properties derived from the multi-wavelength observations of these sources are then compared with those shown by the high redshift population.

We propose a novel moving median estimator specifically designed for online detection of threshold crossings in multi-channel signals, such as extracellular neural recordings. This estimator offers two key advantages: a reduced sensitivity to outliers and the elimination of memory requirements for storing arrival times. Furthermore, its design facilitates parallel implementation on FPGAs, making it ideal for real-time processing of multi-channel recordings.

Indoor comfort is a critical determinant of the holistic educational experience, significantly influencing the well-being, concentration, and performance of students within the confines of school environments. Despite the widespread implementation of heating, ventilation, and air conditioning (HVAC) systems in educational institutions, achieving satisfactory thermal conditions, acceptable acoustics, and optimal daylight levels for occupants continues to pose a considerable challenge. In this review, we specifically delves into the parameters characterizing Italian school environments, recognizing their direct impact on students’learning and concentration. The primary objectives of this review are conducting a thorough examination of the current acustic conditions in Italian schools. The initial phase of our search strategy involved retrieving data from key databases, namely, Scopus, Web of Science, ScienceDirect, PubMed, and Google Scholar. Following the elimination of duplicate articles (n = 289), a total of 135 distinct papers remained for analysis. A critical review of the existing literature is presented based on these criteria, offering guidelines and recommendations for forthcoming studies. The critical review underscores various shortcomings in the current design, deployment, and documentation of multi-domain studies, signaling the need for enhanced quality in future research efforts.

This paper is the first of a series of papers which aims to address Islamist violent radicalization from different angles: the nature of violent radicalization in the context of Spain, a comparison between European, North American and Indian violent radicalization, the need to refine territorial radicalization indexes within the context of preventing violent radicalization and the relation between Islamist violent radicalization and other forms of violent radicalization in Europe. This set of articles builds upon the general theoretical framework set by the author on two previous works (García, 2018; 2019). These works are framed under the known conception of three layers of micro, meso and macro factors contributing to violent radicalization processes (McCauley, Moskalenko, 2017). The paper starts by defining Islamist violent radicalization, then it explores different theoretical explanations and finally proposes an explanatory hypothesis that is tested against, on the one hand, data proceeding from different institutional sources in Spain and, on the other, some initial conversations which will become life stories and a in depth interviews to Spanish security officials and people who whether radicalized and regretted or lived very close to others that did it.

The aim of this study was to evaluate the effect of an Athletic Performance Program, performed in addition to teams’ regular training routines, on match performance variables in professional football players. Twenty-nine professional football players (age=27.21±4.95 years; body mass=79.56±5.21 kg) of the Spanish First Division (LaLiga) underwent a 10-week training program focused on the development of mobility, stability, strength, and multidirectional running skills. The APP included 5 indoor sessions per week and on-field micro-dosing stimulus in addition to regular training practices. Match performance variables obtained with GPS devices during official matches and jump performance were measured before and after the APP. The APP increased peak running speed (31.1±1.4 vs 32.1±1.0 km/h, P < 0.001, d=1.88), the number of sprints (0.14±0.03 vs 0.16±0.03 sprint/min, P< 0.001, d=1.44) and the sprint distance (6.45±1.43 vs 8.35±1.22 m/min P< 0.001, d=2.49) during the matches. The intervention also increased countermovement jump height (34.1±2.7vs 35.8±2.5 cm, P< 0.001, d=2.20). The APP was effective to improve intense actions during competitive match play in professional football players. Strength and conditioning coaches may consider the use of multicomponent physical training programs included in the usual training week to enhance players’ match running at high intensity.

In forensic acoustics, a possible area of analysis is represented by unwanted sound that 1 is perceived as a source of intrusion or disturbance within a certain auditory context. This context 2 is defined as the "auditory scene" and refers to the set of sounds present in a specific environment. 3 The presence of unwanted sounds in the auditory scene can cause a wide range of negative effects, 4 including disturbance, discomfort, moral or immoral harm, and other types of negative impact on the 5 health and well-being of individuals exposed to noise. In 2022, the technical specification UNI/TS 6 11844:2022 dedicated to the measurement and analysis of intrusive noise was published. The standard 7 introduces the concept of intrusive noise and defines its calculation methods based on environmental 8 measurements. The purposes of this technical specification is to provide an objective support to 9 methods already in used in acoustic disputes, where the assessment of the annoyance of a noise is 10 often a subjective evaluation of the technician. This work delves into the application to some real 11 cases, identifying the potentiality and the limits of the standardized method.

The main objective was to analyze the influence of silicon content on high-temperature oxidation of low-alloy steels. Samples of AISI 1045, AISI 5160, and AISI 9254 steels, with different silicon contents, were oxidized at an isothermal temperature of 1000°C for times of 20 minutes, 40 minutes, and 60 minutes. The oxide layers formed mainly contain hematite, magnetite wustite, and fayalite. The average thickness of the oxide layer can decrease with an increase in silicon content below 1% but can increase for contents greater than 1% due to the difference in density between fayalite and iron oxides. Silicon tends to accumulate on the surface of steel and form a SiO2 film in the early stages of oxidation, which can control the oxidation process. The eutectic compound FeO+Fe2SiO4 forms at the oxide-steel interface, and its thickness increases with oxidation time and the silicon content present. The SiO2 film tends to decrease with oxidation time and silicon content.

Metastasis is the main cause of anti-cancer therapies failure, leading to unfavorable prognosis for patients. The true challenge to increase cancer patient life expectancy by making cancer a chronic disease with periodic but manageable relapses, relies on the development of efficient therapeutic strategies specifically directed against key targets in the metastatic process. Traditional chemotherapy with classical alkylating agents, microtubule inhibitors and antimetabolites has demonstrated its limited efficacy against metastatic cells due to their capacity to select chemo-resistant cell populations that undergo epithelial to mesenchymal transition (ETM) thus promoting the colonization of distant sites that in turn sustain the initial metastatic process. This scenario has prompted efforts aimed at discovering a wide variety of small molecules as potential anti-metastatic drugs directed against more specific targets known to be involved in the various stages of metastasis. In this short reviews we will give an overview of the most recent advances related to three main large families of antimetastatic small molecules: intracellular tyrosine kinase inhibitors, integrin antagonists and small interfering (siRNAs). Although the majority of these small molecules are not yet approved and not available in the drug market, any information related to their stage of development could represent a precious and valuable tool to identify new targets in the endless fight against metastasis.

In the whole world, including Mexico, the rising prevalence of diabetes poses significant challenges to healthcare systems, with a notable impact on hospital admissions even being an ambulatory care sensitive condition, that means, hospital admissions are avoidable. Traditional healthcare methodologies have been instrumental in managing diabetes and preventing complications, yet they often face limitations such as merging, cleansing, and outlier analysis of health data to identify and address diseases effectively. This paper aims to address this gap by conducting a comprehensive comparison of the methodologies used in healthcare and data science for this purpose. This work uses hospital diabetes discharge records from 2010 to 2023, a total of 36,665,793 records, which belong to medical units of the Ministry of Health of Mexico. In this work, we seek to provide the arguments why as a data scientist it is mandatory to learn the field of knowledge of the problem and its implications if this is not done, and therefore to disclose insights that can help in policy decisions and reduce the burden of avoidable hospitalizations. The approach is mainly based on the standardization or adjust rates by sex and age groups. This study provides the foundations for a new way of data scientist must deal with health data.

Artificial neural networks are a powerful tool for managing data that is difficult to process and interpret. This paper presents the study of artificial neural networks for information processing generated by an optical encoder based on the polarization of light. A machine learning technique is proposed to train the neural networks, such that the system can predict with remarkable accuracy the angular position in which the rotating element of the neuro-encoder is located, based on information provided by light’s phase shifting arrangements. The proposed neural designs show excellent performance in small angular intervals, and a methodology is proposed to avoid losing this remarkable characteristic in measurements from 0 to 180o or even to 360o. The neuro-encoder is implemented in simulation stage to obtain performance results. This study can be useful to improve capabilities of resolvers or other polyphasic sensors.

Abstract: Objective: analyze the effectiveness of the implementation of the Lean Healthcare sys-tem at the emergency room of the Clinical Hospital of the Federal University of Uberlândia (HC-UFU), based on a comparison of hospital indicators obtained over the three phases corre-sponding to the period of one year before the implementation (T1), the year during the imple-mentation (T2) and one year after implementation (T3). Material and Methods: this is applied research, classified as a case study, exploratory, descriptive that is developed in stages. Based herein on the search for hospital indicators, as occurred in the implementation process of Lean in Emergencies at the HC-UFU and a description of the implemented Lean system. Results and Discussions: during the period where it was possible to collect data relevant to the NEDOCS and LOS indicators, the motivation of the teams grew, but with a notable tension between municipal management and hospital management. It was found that, despite the fluctuations, the patient length of stay in the Emergency Room remained high. Noteworthy here is that with the excep-tion of the variable of female deaths before 24 hours of hospitalization, all other variables showed percentage increases before and after the intervention. Conclusion: the methodology followed for the implementation of Lean in Emergencies in the emergency sector of the hospital did not produce an improvement in hospital indicators.

The increasing number of registered road crashes involving cyclists during the last decade, and the high proportion of road crashes resulting in severe injuries and fatalities among cyclists constitutes a global issue for community health, urban development, and sustainability. Nowadays, the incidence of many risk factors for road crashes of cyclists remains largely unexplained. Given the importance of this issue, the present study has been conducted with the aim of determining relationships between infrastructural, human factors and safety outcomes of cyclists. Objectives: This study aimed, first, to examine the relationship between key infrastructural and human factors present in cycling, bicycle-user characteristics, and their self-reported experience with road crashes. And second, to determine whether a set of key infrastructural and human factors may predict their self-reported road crashes. Methods: For this cross-sectional study, a total of 1064 cyclists (38.8% women, 61.2% men; M = 32.8 years of age) from 20 different countries across Europe, South America and North America, participated in an online survey composed of four sections: demographic data and cycling-related factors, human factors, perceptions on infrastructural factors, and road crashes suffered. Results: The results of this study showed significant associations between human factors, infrastructural conditions and self-reported road crashes. Also, a logistic regression model found that self-reported road crashes of cyclists could be predicted through variables such as age, riding intensity, risky behaviors, and problematic user/infrastructure interactions. Conclusions: The results of this study suggest that self-reported road crashes of cyclists are influenced by features related to the user and their interaction with infrastructural characteristics of the road.

Firms are increasingly organized around the client. At the same time, there is customer pressure on green and sustainable organizations. The purpose of this paper is to map the current state of the research in the domain of customer-centric organizations from a sustainable perspective. We conducted a bibliometric analysis from published documents between 1990 and 2020. Key findings indicate that research on customer centricity and sustainability has increased in recent years and that the topic is structured into 3 clusters: (1) Sustainability; (2) Customer-Centric Perspective, and Sustainable Development; and (3) Customer Experience and Sales. Moreover, new concepts and technologies have been introduced during the last three years. The implementation of a bibliometric methodology and the focus given to the definition, the relationships, and the evolution of the three main clusters within the topic are the characteristics that differentiate our study from other publications or reviews in the field of research. This paper is beneficial for practitioners who aim to deploy the customer centricity approach in their firms from a sustainable perspective.

In music, the role of the interpreter is to play her/his part manipulating the performance parameters in order to offer a sonic rendition of the piece capable of conveying specific expressive intentions. Since the 1980s there has been a growing interest in computational expressive music performance (EMP). This research field has two fundamental objectives: the understanding of the phenomenon of human musical interpretation and the automatic generation of expressive performances. Rule based, statistical, machine and deep learning approaches have been proposed, most of them devoted to the classical repertoire, in particular to piano pieces. On the contrary, we present an introduction to the role of expressive performance within popular music and to the contemporary ecology of pop music production, based on the use of Digital Audio Workstations (DAWs) and virtual instruments. After an analysis of the tools related to expressiveness commonly available to modern producers we propose a detailed survey of research into the computational EMP field, highlighting the potential and limits of what is present in literature with respect to the context of popular music, which by its nature cannot be completely superimposed on the classical one. In the concluding discussion we suggest possible lines of future research in the field of computational expressiveness applied to pop music.

The Azores bullfinch (Pyrrhula murina Godman, 1866) is a rare Passeriformes endemic from the eastern part of São Miguel Island. This bird was almost considered extinct in the first half of the 20th century and, due to recent conservation measures, it has experienced a recovery since the beginning of the 2000s. Despite the attention given to this bird, the size of its population is still controversial, and the most recent studies present significant divergences on this behalf. The pur-pose of the present study is to present data from the long-term monitoring of the Azores bullfinch to update the information about the population size and range of this species. In addition, we performed a literature review to highlight the limitations and advantages of the different ap-proaches for monitoring this species. In this study, we conclude that the most likely size of the Azores bullfinch population is 500 to 800 couples, with a slow population growth tendency, and an area of distribution of 130 Km2.

Wellness tourism is a growing segment that destinations can rely on to increase tourism flows and revive underdeveloped rural areas. This study elicits tourists' preferences for wellness tourism products and the redevelopment of a wellness destination in a depopulated rural area. The re-search included 595 participants in Central Greece using on-site, face-to-face surveys. The survey data was analyzed using a two-step process. First, conjoint analysis was applied to determine the combination of wellness tourism product attributes that maximize visitors’ utility. In the second step, we elicited visitors' willingness to pay (WTP) for improvements in tourism product attributes using the contingent valuation method. Findings indicate that the combination of attributes that maximizes the preference structure of respondents includes time of visit from September to Oc-tober, duration of visit from 1 to 7 days, wellness tourism as the primary purpose of the visit, and wellness activities that contain both physical activities and training as well as spiritual and emo-tional enhancement. Using binary logistic regression, the analysis indicates that respondents are willing to pay 47.33€ per visit on average further to develop wellness tourism products in the study area. Empirical results confirmed that sustainability issues, quality, and entrepreneurship factors positively impact visitors' WTP for revitalizing wellness products. In contrast, a longer duration of stay in the area and respondents' age negatively impact their WTP. These findings suggest that structuring a customer-driven tourism product will enhance the rural destination's efforts to attract high-yield visitors and advance the rural economy. Furthermore, practical im-plications reveal that Destination Management Organizations will benefit from research results to foster targeted management plans.

The classical Rotational Isomeric State (RIS) model, originally proposed by Flory, has been used to rationalize a wide range of physicochemical properties of neutral polymers. However, many weak polyelectrolytes of interest are able to regulate their charge depending on the conformational state of the bonds. Recently, it has been shown that the RIS model can be coupled with the Site Binding (SB) model, for which the ionizable sites can adopt two states: protonated or deprotonated. The resulting combined scheme, the SBRIS model, allows to analyse ionization and conformational equilibria on the same foot. In the present work this approach is extended to include pH-dependent electrostatic Long Range (LR) interactions, ubiquitous in weak polyelectrolytes at moderate and low ionic strengths. With this aim the original LR interactions are taken into account by defining effective Short Range (SR) and pH-dependent parameters, such as effective microscopic protonation constants and rotational bond energies. The new parameters are systematically calculated using variational methods. The machinery of statistical mechanics for SR interactions, including the powerful and fast transfer matrix methods, can then be applied. The resulting technique, to which we will refer as Local Effective Interaction Parameters (LEIP) method, is illustrated with a minimal model of a flexible linear polyelectrolyte containing only one type of rotating bonds. LEIP reproduces very well the pH dependence of the degree of protonation and bond probabilities obtained by semi-grand canonical Monte Carlo simulations, where LR interactions are taken explicitly into account. The reduction in the computational time in several orders of magnitude suggests that the LEIP technique could be useful in a range of areas involving linear weak polyelectrolytes, allowing direct fitting of the relevant physical parameters to the experimental quantities.

Mn-promoted bulk iron catalysts with high specific surface area (82-211 m2.g-1) were synthesized by coprecipitation followed by drying under supercritical conditions. The catalysts were tested in the CO2 hydrogenation reaction. The Mn-promoted iron catalysts showed better textural properties than the bare Fe2O3 catalyst, allowing better dispersion of the active phase, easier reduction of iron oxide, better carburization of iron oxides and higher catalytic activity than the bare Fe2O3 catalyst. The best activity results were obtained by catalyst promotion with a very low amount of Mn (Mn/Fe ratio of 0.05). Upon steady-state conditions (T=340 ºC, total pressure of 20 bar and H2/CO2=3), this catalyst showed high CO2 conversion (44.2%) and selectivity to C2-C4 hydrocarbons (68%, olefin to paraffin ratio of 0.54), while the selectivity to C5+ hydrocarbons, CH4 and CO was about 3.2, 38.5 and 5%, respectively. A close correlation was found between catalyst textural properties and CO2 conversion. The most active MnFe-0.05 catalyst shows high stability during 72 h of reaction related to low amount of soft coke formation and catalyst activation through the formation of χ-Fe5C2 phase during the on-stream reaction.

Inspired by the forward and the reverse channels from the image-size characterization problem in network information theory, we introduce a functional inequality which unifies both the Brascamp-Lieb inequality and Barthe's inequality, which is a reverse form of the Brascamp-Lieb inequality. For Polish spaces, we prove its equivalent entropic formulation using the Legendre-Fenchel duality theory. Capitalizing on the entropic formulation, we elaborate on a "doubling trick" used by Lieb and Geng-Nair to prove the Gaussian optimality in this inequality for the case of Gaussian reference measures.

Road Safety Education (RSE) is widely known as a reliable determinant of future results for what concerns health and welfare, and as an undisputable factor which contributes to the social behavior of individuals and to their mid and long-term road safety outcomes. However, its development has been relatively scarce in most countries, fact which has contributed to letting matters as delicate as traffic crashes produced by road misbehaviors continue to be a prevalent problem, thus affecting the health of the community. Objective: The aim of this study was to describe the relationship between demographic and RSE-related variables and the self-reported road risky behavior of Spanish students. Methods: For this cross-sectional study, a representative sample of 4,062 (51.5 males and 48.5% females) participants attending primary (47.5%), secondary (40.7%) and high school (11.7%) was gathered through a national survey on RSE and road behaviors. Results: A set of significant associations between demographic factors, RSE variables and self-reported road behaviors was found. Furthermore, the SEM modelling allowed us to establish that age, observed misbehaviors, attitudes towards road safety and risk perception keep a direct link with the road risky behavior of children and young people. The knowledge of traffic rules was not a significant predictor of road behavior. Conclusions: The results of this study show that, together with demographic factors such as age, RSE-related variables have an effect on the road behavior of children and young people. They also suggest the need of strengthening actions to be implemented in road safety (Road Safety Education), into scholar and community levels.

In recent years, the need to make the built environment more resilient and adaptable to climate change has become increasingly evident. In Europe, this aspect concerns the vast majority of existing buildings, which present several deficiencies from the energy-efficiency point of view, considering they were designed before the introduction of modern energy codes. Nowadays, it is possible to retrofit existing buildings using advanced and high-efficient technologies such as Double Skin Façades (DSFs). The research aims to evaluate the use of properly designed DSFs for the energy restoration of existing buildings. In detail, various DSF configurations are applied to a residential building located in central Italy and investigated under present and future climate conditions, estimated through regional climate models. The results underline that all the analysed Double Skin Façades confirm to be a useful option, and, in particular, the Multi-Storey typology allows drastic energy needs decrement. Moreover, the general increase in temperatures and solar radiations could affect the building energy performance, and the insertion of DSF can mitigate the climate change effects, reducing the predicted energy consumption and ensuring better behaviours than the building in its original state.

The SARS-Cov-2 virus, which causes COVID 19, uses the cell surface protein ACE2 as receptor for entry into cells. Critically ill COVID-19 patients often require prolonged mechanical ventilation which can cause mechanical stress to lung tissue. In vitro studies have shown that expression of ACE2 in alveolar cells is increased following mechanical stretch and inflammation. Therefore, we analyzed transcriptome datasets of 480 (non-COVID-19) lung tissues in the GTex tissue gene expression database. We found that mechanical ventilation of the tissue donors increased the expression of ACE2 by more than two-fold (p<10^-6). Analyses of transcriptomes of mechanically ventilated mice in the GEO database indicate that this alveolar cell response to stretch and inflammation is mediated by the chemokine midkine. Using a novel big knowledge network approach (SPOKE) we also found in transcriptomes of pharmacological perturbations (LINCS) that corticosteroids down-regulate midkine in pulmonal cells, and confirmed this in GEO transcriptomes of animal studies. Thus, mechanical ventilation of patients with COVID-19 pneumonia may eo ipso facilitate viral propagation in the lung, further accelerating the pulmonal pathology that has necessitated mechanical ventilation in the first place. This vicious cycle presents a rationale for the temporary treatment with corticosteroids to modulate the midkine-ACE2 axis in ventilated COVID19 patients and for gentler ventilation protocols.

Understanding the dynamics of Organic Carbon mineralization is fundamental in forecasting biosphere to atmosphere Net Carbon Ecosystem Exchange (NEE). With this perspective, we developed 3D-CMCC-PSM, a new version of the hybrid Process Based Model 3D‐CMCC FEM where also heterotrophic respiration (R_h) is explicitly simulated. The aim was to quantify NEE as a forward problem, by subtracting Ecosystem Respiration (R_eco) to Gross Primary Productivity (GPP). To do so, we developed a simplification of the Soil Carbon dynamics routine proposed in DNDC [1]. The method calculates decomposition as a function of soil moisture, temperature, state of the organic compartments, and relative abundance of microbial pools. Given the pulse dynamics of soil respiration, we introduced modifications in some of the principal constitutive relations involved in phenology and littering sub-routines. We quantified the model structure related uncertainty in NEE, by running our training simulations over 1000 random parameter-sets extracted from parameters distributions expected from literature. 3D-CMCC-PSM predictability was tested on independent time series for 6 Fluxnet sites. The model resulted in daily and monthly estimations highly consistent with the observed time series. It showed lower predictability in Mediterranean ecosystems, suggesting that it may need further improvements in addressing evapotranspiration and water dynamics.

This paper presents the design and implementation of a remote supervision and control system for a gunpowder drum filling plant. The use of technologies such as SCADA (Ignition), IoT (Node-RED), ERP (Odoo) and digital twins (Factory I/O) to achieve remote monitoring and operation of the plant is described. The solution allows full control of the production process from any location through customized graphical interfaces. The challenges encountered in integrating multiple systems and platforms are discussed, along with the security measures implemented within the Azure cloud environment. The results demonstrate the effectiveness of 4.0 technologies in automating and digitizing critical industrial processes. This research will lay the groundwork for the adoption of these approaches in companies seeking greater efficiency, traceability and safety in their operations. The experience gained allows us to successfully face the digital transformation in modern manufacturing.

Glioblastoma is a central nervous system cancer type with a poor prognosis. One of its main features is the constant change of metabolism phenotype to support its development and progression. Mitochondria play a critical role in cellular metabolism. Acetylation on lysine residues of mitochondrial enzymes is a mechanism for regulating protein function. This modification negatively affects the mitochondrial proteome function and is counteracted by the enzyme sirtuin 3 (SIRT3). To better understand how SIRT3 regulates mitochondrial metabolism, we inhibited SIRT3 and examined by high-resolution mass spectrometry analysis the proteome and acetylome of two glioblastoma cell lines with different metabolic preferences. Our results indicate that protein synthesis machinery is regulated by lysine acetylation and plays a role in the metabolic phenotype. We also identified new SIRT3 targets not previously associated with specific functions, highlighting their potential as future targets for further study. This study shed light on the role of SIRT3 in mitochondria and its implication for cellular metabolism. We have generated knowledge at the proteome and acetylome levels on the dynamics between two glioblastoma cell lines with opposing metabolic phenotypes. Our results might guide in searching for biomarkers at both proteome and acetylome levels in glioblastoma.

Recently, we demonstrated the validity of anomalous numbers law, known as Newcomb-Benford´s law, at the mammalian neuromuscular transmission, considering different extracellular calcium concentrations . The present work continues to examine how alterations in extracellular solution modulate the first digit law in the context of the spontaneous release of acetylcholine from the neuromuscular junction. We investigated if the intervals of miniature potentials collected at the neuromuscular junction obey the law in a hyperkalemic environment. The analysis showed that the interval between the miniature potentials at high potassium concentrations follows Newcomb-Benford´s law. Also, our data allowed us to uncover a conformity fluctuation as a function of the number of intervals of the miniature potentials. Finally, we discuss the biophysical implications of the present findings.

A Robust Optimization framework with original concepts and fundamentals also admitting a fusion of ideals from relative regret models and static robust optimization, containing conservatism concepts is disclosed. The algorithm uses a fine-tune strategy to tune the model so the robustness and a target ideality can be mutually achieved with a specified risk. The framework comprises original concepts, a mathematical approach and an algorithm. The statistical treatment of the data with the original concepts from the framework make it able to make short, middle or long-term decision-making setting. The framework has high tractability since the algorithm forces the creation of a setting that makes a robust optimization with the specified risk. The framework can be applied in linear and nonlinear mathematical models since that the objective function is monotonic in the domain of the active convex region. Several examples are solved to best understand the framework and all results demonstrated high tractability and performance. There is a wide range of applications. Along all the text, there is a profound discussion about its philosophy, objective, original concepts, fields of application, statistical and probabilistic fundamentals.

A workplace sleep health promotion program was implemented in an Italian police unit from 2016 to 2017. Of the 242 police officers in the unit, 218 (90%) agreed to take part in the program. A crossover trial was made in which the police officers were divided into two groups that performed sleep health promotion activities in the first and second year, respectively. The first group of officers showed significant sleep improvements at the end of the first year, while the second group had similar or worse parameters than at baseline. At follow-up, a significant improvement in the quantity and quality of sleep was reported in both groups. Sleep improvements at follow-up were associated with a marked reduction in the frequency of accidents at work and near-misses. All sleep parameters showed a significant association with injuries and near-misses in univariate logistic regression analyses. Before the intervention, sleepiness was the best predictor of injuries (aOR 1.220; CI95% 1.044-1.426) and near-misses (aOR 1.382; CI95% 1.182-1.615). At follow-up, when sleep conditions had improved, insomnia symptoms were the most significant predictors of work accidents (aOR 13.358; CI95% 2.353-75.818). Sleep health promotion can be useful in police officers.

A general framework for inference in dynamical systems is described, based on the language of Bayesian probability theory and making use of the maximum entropy principle. Taking as fundamental the concept of a path, the continuity equation and Cauchy's equation for fluid dynamics arise naturally, while the specific information about the system can be included using the Maximum Caliber (or maximum path entropy) principle.

High-density olive groves, despite their interesting production potential, have several limitations, also due to the high fruit load and the irrigation requirements.The study aimed to evaluate the effects of fruit load and deficit irrigation on oil yield and fruit quality, and on olive chemical composition in a high-density olive grove (cv Sikitita). Our main hypothesis was that the primary metabolism, as influenced by crop load and stress, could modify the accumulation of different phenolic classes.Different fruit loads were generated through flower thinning (66%, 50%, 33%, 0%) and two deficit irrigation treatments (-60%, -75%) were compared to the well-watered control (920 m3/ha).Thinning treatments had a limited effect on oil yield, on the other hand, deficit irrigation caused considerably less oil accumulation in the fruit on all sampling dates.Thinning 66% and deficit irrigation 75% were considered with the control for untargeted metabolomic analysis, considering three sampling dates. 233 different phenolic compounds were annotated. Multivariate HCA results indicated the impact of harvest time on the phenolic profile of olive fruits, yielding two separate clusters grouping t1 and t2 together and apart from t3. Regarding agronomic techniques, they played a differential role in the phenolic profile (supervised OPLS – DA). Fruit load mostly affected flavonoid glycosides. In contrast, the phenolic response to deficit irrigation is more heterogeneous, with phenolic acids (35%), flavonoids (25%), LMW, and other phenols (25%).

In the coming years, digital applications and services that continue to use the country's native cloud systems will be huge. By 2023, that will exceed 500 million, according to IDC. This corresponds to the sum of all applications developed in the last 40 years. If you are the one you answered, yes! This article is for you!

Breast cancer is the most common cause of death for women worldwide. Thus, the ability of artificial intelligence systems to predict and classify breast cancer is very important. In this paper, a hybrid ensemble method classification mechanism is proposed based on a majority voting mechanism. First, the performance of different state-of-the-art machine learning classification algorithms for the Wisconsin Breast Cancer Dataset (WBCD) were evaluated. The three best classifiers were then selected based on their F3 score. F3 score is used to emphasize the importance of false negatives (recall) in breast cancer classification. Then, these three classifiers, simple logistic Regression learning, stochastic gradient descent learning and multilayer perceptron network, are used for ensemble classification using a voting mechanism. We also evaluated the performance of hard and soft voting mechanism. For hard voting, majority-based voting mechanism was used and for soft voting we used average of probabilities, product of probabilities, maximum of probabilities and minimum of probabilities-based voting methods. The hard voting (majority-based voting) mechanism shows better performance with 99.42% as compared to the state-of-the-art algorithm for WBCD.

Lithium rich layered oxides (LRLO) are a wide class of innovative active materials for positive electrodes in lithium-ion (LIB) and lithium-metal secondary batteries (LMB). LRLOs are over-stoichiometric layered oxides rich in lithium and manganese, with general formula Li1+xTM1-xO2, where TM is a blend of transition metals comprising Mn (main constituent), Ni, Co, Fe and others. Due to the very variable composition and the extended defectivity their structural identity is still debated among researchers being likely an unresolved hybrid between a monoclinic (mC24) and a hexagonal lattice (hR12). Once casted in composite positive electrode films and assembled in LIBs or LMBs, LRLOs can delivery reversible specific capacities above 220-240 mAhg-1, thus beyond any other available intercalation cathode material for LIBs, with mean working potential above 3.3-3.4 V vs Li for hundreds of cycles in liquid aprotic commercial electrodes. In this review we critically outline the recent advancements in the fundamental understanding of the physico-chemical properties of LRLO as well as the most exciting innovations in their battery performance. We focus in particular on the elusive structural identity of these phases, on the complexity of the reaction mechanism in batteries as well as on practical strategies to minimize or remove cobalt from the lattice while preserving the outstanding performance upon cycling.

The satisfaction of basic psychological needs leads students to engage in a sport modality on their own initiative. In the Spanish public educational system, mixed and heterogeneous, the gender and sport experience of students influence the teaching and motivation of invasion sports. This study investigated whether students' gender and sport experience, and method influence the psychological variables (basic psychological needs and sport adherence) when teaching school soccer and basketball. Furthermore, correlations were calculated between these psychological variables. The study involved 165 fifth and sixth grade students (age, 11.27 ± 0.68 years old) from several Spanish state schools in the same autonomous community. A non-random convenience sample was used. The needs for autonomy, perceived competence and social relationships were measured using the Basic Psychological Needs in Physical Exercise Scale. Sport adherence was measured using the Measure of Intentionality to be Physically Active. A Confirmatory Factor Analysis and Cronbach's alpha were used to analyze the psychometric properties of the scales. Descriptive and inferential analyses were performed with the Mann-Whitney U and Kruskal-Wallis H tests. There were significant differences in the needs for autonomy and perceived competence according to the students’ gender (boys &gt; girls). Attending to sport adherence, there were also significant differences according to the students’ gender (boys &gt; girls) and sport experience (experienced students &gt; inexperienced students). Likewise, a regression analysis (structural equation model) revealed that the autonomy need showed low association with sport adherence. Higher perceived competence (β = 0.52) and social relationships (β = 0.36) were associated with greater adherence to sport (R2 = 0.65). Increased sport adherence will have health benefits.

The use of sustainable energy sources is a feasible alternative for fossil fuel products, which can represent a positive factor to alleviate many current environmental issues. In that sense, not only the sustainable industrial development is important, but also sustainable practices at local level, including households. Specifically, heating and cooking are one of the most important activities that require energy in households, where the role of biomass could be interesting, as it can provide an energy source with lower environmental impact. However, there is room for improvement in biomass stoves, whose adaptability to specific wastes, as well as their improvement in efficiency, should be accomplished. The aim of this work was to assess the improvement of combustion performance of a domestic stove by the implementation of a programmable logic converter for a better adaptation to different biomass samples (holm oak, pear tree, poplar and sugarcane bagasse pellets). Thus, the working regime of the stove was controlled, especially concerning the screw conveyor (to regulate pellet feeding) and flue gas fan (to change oxygen supply). As a result, better combustion performances were obtained, heat capacities from 5.66 to 8.67 kW for the selected samples. On the other hand, different improvements of the combustion stove to avoid blockages, for instance, are proposed as further steps.

Crimean-Congo hemorrhagic fever virus is one the most important and wide spread tick-borne viruses. Very little is known about the transmission from the tick and the early aspects of pathogenesis. Here, we generate human cutaneous antigen presenting cells: dermal dendritic cells and Langerhans cells, from umbilical cord progenitor cells. In order to mimic the environment created during tick feeding, tick salivary gland extract was generated from semi-engorged Hyalomma marginatum ticks. Our findings indicate that human dermal dendritic cells and Langerhans cells are susceptible and permissive to Crimean-Congo hemorrhagic fever virus infection, however, to different degrees. Infection leads to cell activation and cytokine/chemokine secretion, although these responses vary between the different cell types. Hyalomma marginatum salivary gland extract had minimal effect on cell responses, with some synergy with viral infection with respect to cytokine secretion. However, salivary gland extract appeared to inhibit antigen presenting cell (APC) migration. Based on the findings here we hypothesize that human dermal dendritic cells and Langerhans cells serve as early target cells. Rather affecting Crimean-Congo hemorrhagic fever virus replication, tick saliva likely immunomodulates and inhibits migration of these APC from the feeding site.

The present study evaluates the response to betahistine in patients who presented vestibular drops attacks in the context of Ménière's disease (MD) and the factors that can predict an unfavorable response to it. A total of 43 patients were analyzed, out of which 33 were diagnosed with MD. It is a descriptive, cross-sectional study with retrospective data collection. Data as regards age, accompanying symptoms, etiological diagnosis and response to MD treatment were collected. A statistical analysis was carried out, and we found that the disease evolution time and specific alterations in the vestibulospinal and oculomotor physical examination present an unfavorable response to betahistine, as opposed to the use of intratympanic gentamicin, with which symptomatic control is achieved in 100% of the cases.

Energy transitions are reshaping the global energy system. Such shift has taken the power system to become a critical infrastructure for achieving economic development of every nation in the planet, therefore, guaranteeing its security is crucial, not only for energy purposes but as a part of a national security strategy. This paper presents a multi-dimensional index developed to assess energy security of electrical systems in the long term. This tool, named Power System Security Index (PSIx), and which has been previously used for the evaluation of a country in two different time frames, is applied to evaluate the member countries of the Latin American Energy Organization, located within the Latin America and the Caribbean region, in order to measure their performance on energy security. Mixed results were obtained from the analysis, with clear top performers in the region such as Argentina, while there are others with broad areas of opportunity, as it is the case of Haiti.

This work addresses the role of charge regulation (CR) and the associated fluctuations in the conformational and mechanical properties of weak polyelectrolytes. Due to CR, changes in the pH-value modifies the average macromolecular charge and conformational equilibria. A second effect is that, for a given average charge per site, fluctuations can alter the intensity of the interactions by means of correlation between binding sites. We investigate both effects by means of Monte Carlo simulations at constant pH-value, so that the charge is a fluctuating quantity. Once the average charge per site is available, we turn off the fluctuations by assigning the same average charge to every site. A constant charge MC simulation is then performed. We make use of a model which accounts for the main fundamental aspects of a linear flexible polyelectrolyte i.e. proton binding, angle internal rotation, bond stretching and bending. Steric excluded volume and differentiated treatment for short-range and long-range interactions are also included in the model. It can be regarded as a kind of "minimal'' model in the sense that contains a minimum number of parameters but still preserving the atomistic detail. It is shown that, if fluctuations are activated, gauche state bond probabilities increase, and the persistence length decreases, so that the polymer becomes more folded. Macromolecular stretching is also analyzed in presence of CR (the charge depends on the applied force) and without CR (the charge is fixed to the value at zero force). The analysis of the low force scaling behavior concludes that Pincus exponent becomes pH-dependent. Both with and without CR, a transition from 1/2 at high pH-values (phantom chain) to 3/5 to low pH-values (Pincus regime), is observed. Finally, the intermediate force stretching regime is investigated. It is found that CR induces a moderate influence in the force-extension curves and persistence length (which in this force regime becomes force-dependent). It is thus concluded that the effect of CR on the stretching curves is mainly due to changes in the average charge at zero force. It is also found that, for the cases studied, the effect of steric excluded volume is almost irrelevant compared to electrostatic interactions.

With the continuous growth of electric and electronic appliances’ usage, the waste produced with obsolete material (e-waste) has an increasing environmental impact. Also, the production of such appliances bears to increased consumption of natural resources and produces a multitude of toxic and hazardous substances, which typically are not properly treated. One of the approaches that may be adopted to reduce such problems relies on the circularization of the current linear model, commonly adopted in the EEE value chain. This includes recovering eol products and reintroducing its parts, components, or raw materials into the value chain (e.g. semiconductors, circuit boards, raw metals, etc.), thus contributing to a more sustainable value chain. In this article, we present a state-of-art review that focuses on approaches and solutions for the EEE value chain traceability, and analyses the technologies that may be beneficial for promoting and implementing the CE model in this value chain.

We propose a new statistical analysis of the Acoustic Emissions (AE) produced in a series of triaxial deformation experiments leading to fractures and failure of two different rocks, namely, Darley Dale Sandstone (DDS) and AG Granite (AG). By means of q-statistical formalism, we are able to characterize the pre-failure processes in both types of rocks. In particular, we study AE inter-event time and AE inter-event distance distributions. Both of them can be reproduced with q-exponential curves, showing universal features which are observed here for the first time and could be important in order to understand more in detail rock fractures dynamics.

Worldwide, hypoxia-related conditions, including cancer, COVID-19, and neuro-degenerative diseases, often lead to multi-organ failure and significant mortality. Oxygen, crucial for cellular function, becomes scarce as levels drop below 10 mmHg (<2% O2), triggering mitochondrial dysregulation and activating hypoxia-induced factors (HiFs). Herein, Oxygen nanoBubbles (OnB), an emerging versatile oxygen de-livery platform, implies to offer a novel approach to address hypoxia-related pathologies. This review explores OnB oxygen delivery strategies and systems, including diffusion, ultrasound, photodynamic, and pH-responsive nanobubbles. It delves into the nanoscale mechanisms of OnB, elucidating their role in mitochondrial metabolism (TFAM, PGC1alpha), hypoxic responses (HiF-1alpha), and their interplay in chronic pathologies including cancer and neurodegenerative disorders, amongst others. By understanding these dynamics and underlying mechanisms, this article aims to contribute to our accruing knowledge of OnB and the developing potential in ameliorating hypoxia- and metabolic stress-related conditions and fostering innovative therapies.

Sewage sludge is an organic waste generated in waste-water treatment plants with certain content of nutrients, what may potentially be used as a source of slow release fertilizer, especially as phosphorus (P) source, but it demands some pre-treatment and the content of P is much lower compared to soluble mineral fertilizers. For these reasons, composted sewage sludge was used to manufacture pelletized organomineral fertilizers, mixing it with the inorganic sources monoammonium phosphate (MAP) and AshDec® (ASD) (thermochemically incinerated sewage sludge). The fertilizers were physiochemically characterized and evaluated as to the dynamics of soil P solubilization, and the forms of P remaining according to its lability. The sources evaluated were: organic compost of sewage sludge powder (SSC), pelletized SSC (SCP), pelletized organominerals SSC+MAP (S+MAP) and SSC+ASD (S+ASD), ASD alone, all compared to a soluble mineral fertilizer (MAP), and a control without P fertilizer. A test was conducted in leaching columns with 50 g of soil (Oxisol), where the fertilizers were applied at a dose of 100 mg P/column, and 30 mL of water or 2% citric acid were added daily for 30 consecutive days. The collected leachates had pH measured and P content determined. Pelletizing process resulted in denser products and promoted more gradual P release. The organomineral S+MAP was the most water-soluble recycled source, solubilizing about 70% of the total P, while the others presented much lower solubilization (&lt;20%). In contrast, all fertilizers showed high solubility in 2% citric acid (except for S+ASD). After leaching, the greatest amount of P remaining in the soil as labile and moderately labile. Composting and the AshDec process produced materials with slow P solubilization, which would be favoured to solubilize in acidic soils and acidic rhizosphere conditions. In turn, the organomineral mixture of SSC with a highly soluble mineral fertilizer (MAP) resulted in a promising product with intermediate nutrient solubility, better synchronized with crop demand, thus increasing efficiency in P use.

Simulation tools capturing the interactions of communication and electrical system operation represent a powerful support for fully assessing the potential benefits and impacts of ICT in future smart power distribution network. A strong interest is upon the possibility of exploiting the last generation communication systems for supporting the transition of distribution network towards a smart grid scenario. Having in mind the above, the authors propose a numerical co-simulation tool useful to thoroughly understand the impact of the communication networks on the performance of whole power system dynamics. The co-simulation tool has been purposely developed to simulate the highly time-critical smart grid application of fault management and network reconfiguration and permits reproducing and evaluating the behavior of the public mobile telecommunication system 4G Long Term Evolution (LTE), as communication technology for smart grid applications. Results of the paper demonstrates that LTE provides good performances for supporting the data communication required to perform fault location, extinction and a subsequent network reconfiguration in smart power distribution networks.

Concrete production requires a significant amount of natural resources, with aggregates comprising between 55% and 80% of the total volume. However, over-exploitation of natural aggregates has led to the exploration of alternative materials for use in concrete production. In this study, crushed hazelnut shells were investigated as a partial replacement for fine aggregate, addressing the problem of natural resource depletion and offering a second use for this important agricultural waste product available in Chile. Hazelnut shells were incorporated in percentages of 2.5%, 5%, and 10% by weight of sand for water-cement ratios of 0.4 and 0.5. The compressive strengths at 7 and 28 days and bending tensile strengths at 28 days were determined, alongside physical properties such as workability, temperature, air content, fresh density, and hardened density of the concrete. Our findings show that replacing 2.5% of the fine aggregate with hazelnut shells led to higher compressive strength at 28 days, exceeding the strength of the standard specimens by 9.5%, whereas replacing 5% of the fine aggregate led to the highest bending tensile strength, exceeding the resistance of the standard specimens by 3.5%. Moreover, the 0.4 w/c ratio consistently led to better results for both compressive and bending tensile resistances, with fewer and lower reductions in mechanical resistances compared to the standard mixture. Our results suggest that concrete mixes with hazelnut shells as a replacement for fine aggregate at a percentage of up to 2.5% can be used in constructive systems with compression strengths lower than 17 MPa, and mixtures with up to 10% hazelnut shell replacement can be used in structures with tensile bending stress requirements lower than 6 MPa. Overall, the use of hazelnut shells as a partial replacement for fine aggregate in concrete production presents an environmentally-friendly and cost-effective solution for the construction industry.

As a result of the growing demand for foods with reduced animal protein content, many new alternative diets are now emerging. Nevertheless, recent studies have shown that the Western population is unprepared for drastic changes and is disinclined to accept foods based on alternative proteins. However, hybrid products might become a good transitional offer. This study used a desirability-based mixture design to model hybrid spreadable cheese analogues (SCAs). The design combined the dairy protein (MPC), Tenebrio molitor (IF) and faba bean (FBP) flours. Nine SCAs with different MPC/FBP/IF ratios were formulated, representing 0, 50 and 100% MPC replacement (7.1% of the formula). Incorporating the IF negatively impacted the desirable texture properties. The FBP flour improved the texture (achieving increased firmness and stickiness and decreased spreadability), but only when combined with MPC. Changing the MPC/FBP/IF ratio affected the colour of SCAs. Sensory analysis showed that hybrid SCAs (≤ 50% MPC) had a more characteristic cheesy flavour than the commercial plant-based reference, and sample C2 had a texture profile similar to the dairy reference. Samples containing IF showed a better flavour profile than the products without IF. The SCAs had higher protein and lower saturated fat, starch and sugar con-tent than commercial analogues.This study demonstrates that the inclusion of alternative proteins can be effective as a strategy to reduce dairy protein content in hybrid product formulations.

Coronavirus 19 disease (COVID-19) may be complicated by thrombotic events, particularly venous thromboembolism (VTE), which have been reported both in critically ill hospitalized patients and in individuals with mild symptoms. It is known that the chronic use of oral contraceptive pills (OCPs) is associated with higher risk of VTE. To date, there are only few reports concerning the association of OCPs and VTE/pulmonary embolism (PE) in COVID-19 patients. Given that during the convalescent phase of disease, a state of endothelial dysfunction, hypercoagulability and a low-grade inflammation may be persistent, the occurrence of thromboembolic events following acute COVID-19 infection may be not surprising. Herein, we report a case of high-risk PE detected in a post-COVID-19 young woman under hormonal contraception, which required thrombolytic treatment. A number of prothrombotic phenomena, such as overweight, hormonal contraceptive therapy, recent COVID-19 infection and prolonged immobilization, might have synergically contributed to the development of a sublethal thromboembolic event.

Currently, there is no effective antiviral therapy recommended for the new coronavirus disease 2019 pneumonia (COVID-19). The purpose of this pilot study was to evaluate the safety of Ozonized Saline Solution (O₃SS) used as a complementary therapy in adult patients COVID-19. Twenty-five adult patients who were hospitalized with mild to severe COVID-19 symptoms, who met the inclusion criteria and were being treated from April 18^rd to April 26th, 2020, at the Viamed Virgen De La Paloma Hospital, Madrid, Spain were included in this study. Patients were allocated to receive standard care (SC) that included 200-400 mg hydroxychloroquine twice daily for 5-7 days plus Tocilizumab 400 mg twice daily for 5 days, low molecular weight heparin (LMWH) and 40 mg-60 mg metil-prednisone plus O₃SS, 200 mL, 3-5 µg/mL daily for 10 days. No control group was included, data were compared to clinical trials in this subject. Primary outcomes of treatment with O₃SS were an improvement of clinical symptoms and a reduction in mortality. Secondary end points evaluated included participant clinical status, laboratory examinations, and duration of viral shedding. None of the patients treated with SC + O₃SS died. Improvements in symptoms such as dyspnea, weakness, and reduction in body temperature were observed and corresponded with an improvement of laboratory finding including D-dimer, fibrinogen, LDH, and CRP. No side effects from the O₃SS treatment were observed. Conclusions: COVID-19 patients with mild to severe symptoms who received intravenous O₃SS as a complementary therapy demonstrated no side effects. This preliminary data will be served as base for a future study of the efficacy of this therapy.

Elastic properties of materials and their changes with temperature are important for their applications in engineering. A study on the influence of phase composition of AISI 4130 alloy on Young's modulus (Ed), shear modulus (Gd), and damping (Q-1) was carried out by Impulse Excitation Technique (IET). The material characterization was carried out using confocal microscopy, XRD, MET, HV, and dilatometry. A stable structure, composed of ferrite (BCC) and pearlite (α-Fe+Fe3C), was obtained by annealing. Metastable structure of martensite (BCT) was obtained by quenching. The Ed, Gd, and Q-1 were measured, varying the temperature from RT to 900 °C. The values of Ed and Gd, at RT, were determined as 201.5 and 79.2 GPa (annealed), and 190.13 and 76.5 GPa (quenched), respectively. In the annealed steel, the values Ed and Gd decrease linearly on heating up to 650 °C, with the thermal expansion. In the quenched steel, weak changes in the dilatometric curve, Ed, Gd, and Q-1, in the range of 350-450 °C, indicated decompositions of the martensitic phase. Sharp decrease in the moduli and high peak of Q-1, was observed for both samples around 650-900 °C, revealing low lattice elastic stability of the phases during transformations α(BCC)+Fe3C↔γ(FCC).

Orthognathic surgery is used to modify anomalies in maxillomandibular position; this process can significantly affect the anatomy of the airway and cause functional changes. This study aims to define the impact of mandibular maxillary movement on the airway of subjects with dentofacial deformity. A retrospective study was conducted on subjects with Angle class II (CII group) and Angle class III (CIII group) dentofacial deformities. The subjects were treated by bimaxillary surgery; for all of them, planning was performed with software and 3D printing. Cone beam computed tomography (CBCT) was obtained 21 days before surgery and 6 months after surgery and was used for planning and follow-up with the same conditions and equipment. Was used the superimposition technique to obtain the maximum and minimum airway areas, and total airway volume. The data were analyzed with the Shapiro-Wilk test and Student’s t-test, while Spearman's test was used to correlate the variables, considering a value of p&lt;0.05. Seventy-six subjects aged 18 to 55 years (32.38 ± 10.91) were included: 46 subjects were in CII group, treated with a maxillo-mandibular advancement, and 30 subjects were in the CIII group, treated with a maxillary advancement and a mandibular setback. In CII group, a maxillary advancement of +2.45 mm (±0.88) and a mandibular advancement of +4.25 mm (±1.25) were observed, with a significant increase in all the airway records. In the CIII group, a maxillary advancement of +3.42 mm (±1.25) and a mandibular setback of -3.62 mm (±1.18) was noted, with no significant changes in the variables measured for the airway (p&gt;0.05). It may be concluded that maxillo mandibular advancement is an effective procedure to augment the airway area and volume in the CII group. On the other hand, in subjects with mandibular prognathism and Angle class III operated with the maxillary advancement and mandibular setback lower than 4 mm it is possible to not reduce the areas and volume in the airway.

The MAP kinase ERK5 contains an N-terminal kinase domain and a unique C-terminal tail including a nuclear localization signal and a transcriptional activation domain. ERK5 is activated in response to growth factors and stresses, and regulates transcription at the nucleus by either phosphorylation or interaction with transcription factors. MEK5-ERK5 pathway plays an important role regulating cancer cell proliferation and survival. Therefore, it is important to define the precise molecular mechanisms implicated in ERK5 nucleo-cytoplasmic shuttling. We previously described that the molecular chaperone Hsp90 stabilizes and anchors ERK5 at the cytosol, and that ERK5 nuclear shuttling requires Hsp90 dissociation. Here, we show that MEK5 or Cdc37 overexpression -mechanisms that induce nuclear ERK5- induced ERK5 SUMO-2 modification at residues Lys6/Lys22 in cancer cells. We also show that overexpression of the SUMO protease SENP2 completely abolished endogenous ERK5 nuclear localization in response to EGF stimulation. Furthermore, mutation of these SUMO sites abolished the ability of ERK5 to translocate to the nucleus and to promote prostatic cancer PC-3 cell proliferation. These results allow us to propose a more precise mechanism: in response to MEK5 activation, ERK5 SUMOylation favors the dissociation of Hsp90 from the complex, allowing ERK5 nuclear shuttling and activation of transcription.

Asthma is a prevalent disease that around 300 million worldwide, resulting in substantial morbidity, mortality, and economic burden on a global scale. New clinical and laboratory research has shed light on the immunology causing asthma. Asthma is now recognized as a heterogeneous disease. A personalized medicine is based on the classification of asthma by endotype by linking observable characteristics to immunological mechanisms. Identifying endotype mechanisms is essential for better characterizing patients and personalizing therapeutic approaches with novel biological agents that target specific immune pathways. This article provides a summary of the major immunological mechanisms involved in the pathogenesis and emergence of the disease's phenotypic features, as well as the individualized treatment for severe asthma subtypes

The c-Jun N-terminal Kinase (JNK) signalling pathway is a conserved response to a wide range of internal and external cellular stress signals. Besides the stress response, the JNK pathway is involved in a series of vital regulatory mechanisms during development and adulthood that are critical to maintain tissue homeostasis. These mechanisms include the regulation of apoptosis, growth, proliferation, differentiation, migration and invasion. The JNK pathway has such a diverse functionality and cell-tissue specificity, that it has emerged as a key player in regeneration, tumorigenesis and other pathologies such as neurodegenerative diseases. The JNK pathway is highly active in the central nervous system (CNS), and plays a central role for the cells to cope with pathophysiological insults during both development and adulthood. Among the many mechanisms described in the literature, in this review we focus on the JNK pathway functions in pathologies of the CNS. More specifically, we discuss some newly identified examples and mechanisms of JNK-driven tumor progression in glioblastoma, regeneration/repair after an injury in the CNS, neurodegeneration, and neuronal cell death. Recent studies have shown that the JNK pathway regulates matrix metalloproteinases (MMPs) production in response to cytoneme/tumor microtubes formation and Wingless (Wg)/WNT pathway activation in glioblastoma cells. Thus, JNK pathway is essential for glioblastoma progression, infiltration and non-autonomous induction of neurodegeneration. In regeneration, the JNK pathway controls Draper (Drpr) expression in glial cells that mediate engulfment and regeneration of the CNS upon injury.

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.

Non-alcoholic fatty liver disease (NAFLD), a frequent complication of metabolic syndrome and visceral obesity, is characterized by marked accumulation of lipids in hepatocytes, accompanied by oxidant stress. In a substantial minority of cases, this progresses to steatohepatitis, which in turn can lead to life-threatening hepatic fibrosis and/or hepatocarcinogenesis. This essay analyzes the molecular biology underlying fat accumulation and oxidant stress in NAFLD, and identifies targets that can be addressed by nutraceutical or dietary measures. Nutraceuticals with potential for prevention or control of NAFLD – as suggested on theoretical grounds, and borne out by experience in rodent studies and/or clinical trials - include ferulic acid, melatonin, methylnicotinamide, tetrahydrocurcumin, nicotinamide riboside, carnosic acid, urolithin A, quercetin, high-dose biotin, citrulline, astaxanthin, long-chain omega-3 fatty acids, berberine, lipoic acid, silibinin, N-acetylcysteine, taurine, capsaicin, spermidine, spirulina, and carnitine. Some of these agents can also address the NLRP3 inflammasome activation and transforming growth factor-β signaling that play a role in driving the transition to steatohepatitis and fibrosis. In addition, soy isoflavones, via estrogen receptor-beta agonism, have anti-fibrotic potential, and supplemental glycine may blunt the contribution of Kupffer cells to the progression of NAFLD. Whole-food plant-based diets of modest protein content, owing to their impact on hormones such as fibroblast growth factor 21 and adiponectin, as well as on the obesity and metabolic syndrome underlying NAFLD, may also be protective in this syndrome. There is considerable potential for complex medical foods or nutraceutical supplementation regimens of rational design to aid prevention and control of NAFLD.

Optoacoustic imaging is an emerging technology that holds great promise for improving general clinical practice since it offers a unique combination of optical absorption contrast, high resolution, and high penetration depth. This combination of factors provides a distinct advantage over alternative imaging modalities in oncology, cardiology, dermatology, or endocrinology among other medical fields. Optoacoustic technology affords the medical practitioner the possibility of visualizing light-absorbing biomolecules like water, lipids, oxy/deoxy hemoglobin, or melanin in deep tissue with relatively cheap and small form factor instruments, without the need of contrast agents or ionizing radiation. Moreover, exogenous fluorescent contrast agents like indocyanine green or methylene blue can also be observed. Driven by its potential for new applications in the clinic, the field has experienced intense changes in the last 20 years. Continuous technological advancements in instrumentation, image formation methods, or acquisition geometries, have led to the development of numerous clinical devices also motivating the creation of several startup companies that aim to translate the technology from the lab to the clinic. Thus, the question arises: how far are we from clinical adoption? In this article, we aim to shed light on such question by reviewing the clinical studies that have been performed in the last 10 years. Our intention is to go beyond the classical review format by providing a brief general overview of the steps that new imaging methods undergo on their journey from the lab to clinical adoption. Then we examine the progress that optoacoustic technology has made on such a journey.

Power converter technologies have become increasingly vital in various applications due to their efficient management of electrical energy. With the growing prominence of renewable energy sources like solar and wind, the high penetration of power electronic converters has been justified. However, ensuring power quality has emerged as a significant challenge for grid-connected power converters. The divergence from the ideal sinusoidal waveform in terms of magnitude and frequency impacts both grid-side currents and voltages. Several studies have proposed solutions to address power quality issues at the load side. The advancement of power converters has been fueled by the development of high-performance microprocessors and the emergence of high-speed switching devices, such as SiC-MOSFETs. This paper focuses on the design of voltage source converters, particularly those based on SiC-MOSFET semiconductor devices. The article presents the design of H-Bridge cells, discusses two-level voltage source converters based on cascade H-Bridge cells in parallel configuration with experimental fault analysis, addresses the seven-level voltage source converters topology, and explores the design and experimental results of the matrix converter. The findings underscore the importance of considering the entire converter design for improved performance at high switching frequencies. The article concludes by summarizing the main outcomes and implications of this research.

Explaining the emergence of behavior and understanding on the basis of neuronal mechanisms is still elusive. One renowned proposal is the Free Energy Principle (FEP), which uses an information-theoretic framework derived from thermodynamic considerations to describe how behavior and understanding would emerge. FEP starts from a whole organism approach, based on mental states and phenomena, mapping them into the neuronal substrate. An alternative approach, the Energy Homeostasis Principle (EHP), initiates a similar explanatory effort, but starting from single neuron phenomena and building up to the whole organism’s behavior and understanding. In this work, we develop the EHP as an alternative but complementary vision to FEP and try to explain how behavior and understanding would emerge from the local requirements of the neurons. Based on EHP and a strict naturalist approach that sees living beings as physical and deterministic systems, we explain scenarios where learning would emerge without the need for volition or goals. Given these starting points, we state several considerations of how we see the nervous system, particularly the role of function, purpose, and the conception of goal-oriented behaviors. We problematize these conceptions, giving an alternative teleology-free framework in which behavior and, ultimately, understanding would still emerge. We reinterpret neural processing explaining basic learning situations up to simple anticipatory behavior. Finally, we end the work with an evolutionary perspective of how this non-goal-oriented behavior appears. We acknowledge that in the current form of our proposal, we are still far from explaining the emergence of understanding. Still, we set the ground for an alternative neuron-based framework to ultimately explain understanding.

Interactions of soil moisture with plant root systems are very important for plant growth. For non-invasive determination of volumetric soil moisture in a rhizobox, a microwave system based on transmittance of electromagnetic waves in the microwave frequency range was developed using microstrip patch antennas. Vector Network Analyzers (VNAs) were used to measure the S-parameters at frequency ranges close to 5 GHz. A transmission system with microstrip patch antennas was developed. The result of this attenuation is in the frequency domain. The antennae were designed as resonant microstrip antennae. The antennae were placed on both sides of a rhizobox, which allowed non-invasive measuring soil moisture in the box. The attenuation (S21(dB)) was used to measure the effect of temperature, and different types of soil; as well as sensitivity, reproducibility and repeatability of the system. In this work we present quantitative results of soil moisture in rhizobox. The microwave technique, using microstrip patch antennas, is a reliable and accurate system, and showed very promising potential applications for rhizobox-based investigations of root performance.

In this article we presented an application of the quantum cosmological model in teleparallel gravity. Working with a vacuum solution, the gravitational energy density is quantized with the Weyl procedure and we obtain a discrete expression for the gravitational energy. As an immediate consequence the empty space exhibits an expansion for an early universe.

The aim of this paper is to explore the watertightness behaviour for high pressure applications using Multijetfusion technology and polyamide 12 as a material. It reports an efficient solution for manufacturing functional prototypes and final parts for water pressure applications. It provides manufacturing rules to engineers in the pressurized product development process up to 10 MPa of nominal pressure. The research findings show manufacturers the possibility of using additive manufacturing as an alternative to traditional manufacturing. Water leakage was studied using different printing orientations and wall thickness for a range of pressure values. An industrial ball valve was printed and validated with the ISO 9393 standard also meeting tolerance requirements. This paper is a pioneering approach to the additive manufacturing of high performance fluid handling components. This approach solves the problem of leakage caused by porosity in additive manufacturing technologies

Background: Though tyrosine kinase inhibitors managed to reach outstanding responses in the treatment of Chronic Myeloid Leukemia, resistance is still a challenging point, occurring in approximately 10–20% of the cases, due to several mechanisms. STAT5 expression has been strictly linked to resistance and disease progression and may thus represent a significant target to overcome resistance to TKI in CML. The aim of the study is to explore the in vitro antineoplastic role of the STAT5 inhibitor Pimozide in association with 2nd and 3rd generation inhibitors on chronic myeloid leukemia cells. Methods: The cytotoxic effect was evaluated by the Trypan blue dye exclusion test. K562 cell lines were exposed to pimozide alone and in association with ponatinib and dasatinib at different concentrations to explore the drugs association effect and the in vitro cytotoxic concentrations. Conclusions: Pimozide showed a synergic effect when associated with ponatinib and dasatinib in survival inhibition of K562 cell lines. This results are of note and pave the way for a possible in vivo associations.

Then the purposes of this study were to compare and correlate the aerobic threshold (TH_aer) and anaerobic threshold (TH_anaer) measured during a new single judo specific incremental test and Treadmill Test for aerobic demand evaluation. Eight well-trained male competitive judo players (24.3±7.9 years; height of 169.3±6.7cm; fat mass of 12.7±3.9%) performed a maximal incremental specific test for judo mimicking the UchiKomi drills and on treadmill in different days. There was difference between specific and general TH_aer (P=0.0006) as well as weak correlation for TH_aer (r=0.32; R²=0.1; P=0.2) and TH_anaer (rs=-0.31; R²=0.1; P=0.12). When correlation was applied with normalized data (percentage of peak load) we observed moderate correlation for TH_aer (r=0.76; R²=0.58; P=0.027), but the same was not observed for TH_anaer. We conclude that there is a need of TH_aer and TH_anaer evaluation through a specific test for Judo.

The high consumption of firewood in Honduras requires the search for alternatives that reduce its negative effects on health, economy, and the environment. One of these alternatives has been the promotion of improved cooking stoves, which achieve a large reduction in firewood consumption. This paper shows a cost-benefit analysis for an improved cooking stove adoption strategy for Honduras. The methodology uses the Long-range Energy Alternatives Planning System, LEAP, a tool globally used in the analysis and formulation of energy policies and strategies. The energy model considers the demand for firewood as well as the gradual introduction of improved cooking stoves, according to premises of a National Strategy. Hence, it is demonstrated that the costs of implementing this adoption strategy are lower than the costs of not implementing it, taking into consideration various scenarios up to and including the year 2030.

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.

Non-homologous end joining (NHEJ) is the main DNA repair mechanism for the repair of double strand breaks (DSBs) throughout the course of the cell cycle. DSBs are generated in developing B and T lymphocytes during V(D)J recombination to increase the repertoire of B and T cell receptors. DSBs are also generated during the class switch recombination (CSR) process in mature B lymphocytes, providing distinct effector functions of antibody heavy chain constant regions. Thus, NHEJ is important for both V(D)J recombination and CSR. NHEJ comprises core Ku70 and Ku80 subunits that form the Ku heterodimer, which binds DSBs and promotes the recruitment of accessory factors (e.g., DNA-PKcs, Artemis, PAXX, Mri) and downstream core factors (XLF, Lig4 and XRCC4). In recent decades, new NHEJ proteins have been reported, increasing complexity of this molecular pathway. Numerous in vivo mouse models have been generated and characterized to identify the interplay of NHEJ factors and their role in development of adaptive immune system. This review summarizes the currently available mouse models lacking one or several NHEJ factors, with a particular focus on early B cell development. We also underline genetic interactions and redundancy in the NHEJ pathway in mice.

Given that evaluating suspected child maltreatment is a challenging task, we aimed to begin to explore how laboratory test results may assist in its detection. Hence, we have examined biomarker differences between 137 children entering out-of-home care and 126 children living in their own homes. Each child entering Majorcan institutionalized care was randomly matched for gender and age with children living in their homes and the same health area. Concerning basic hematological and biochemical values, children placed in out-of-home care differed significantly from children remaining at home in four distinct ways. Children at care entry had significantly higher eosinophil counts than children at home; and also had significantly lower levels of transaminase, thyroid-stimulating hormone, triglycerides and LDL-Cholesterol than children living at home. Oxidative stress linked to anxiety disorders and underweight are common features found in children at entry into the care system. The present study shows a relationship between some underweight or oxidative stress biomarkers and the risk of entry into out-of-home care. Medical diagnoses require physicians to select and assemble relevant data from all available information. Accordingly, we should consider the implementation of laboratory checkups in order to identify the abused from the non-abused child better.

The Covid-19 infodemic can be countered by scientific evidences, clear and consistent communication and improved health literacy of both individuals in need of information and those providing it. A rapid online survey was carried out to evaluate vaccine literacy (VL) skills in the general population and perceptions about candidate Covid-19 vaccines, as well as behavior and beliefs about current vaccinations. Observed VL levels were sufficiently high and consistent with previous observations - where comparable self-reported tools were administered face-to-face and paper-and-pencil - the mean functional score being =2.92, while the interactive-critical one was =3.27, on a maximum of 4. Perceptions regarding future Covid-19 vaccines, along with beliefs about vaccination, were mostly positive and significantly associated with functional and interactive-critical VL scales. Despite obvious limitations, the study confirms that rapid surveys via web are a suitable method to evaluate and trail attitudes during infectious disease outbreaks, and to assess health literacy skills about vaccination, which can be useful to adapt medical communication strategies, for a better understanding of the value of immunization.

A Tangible User Interface (TUI) is a new interaction option that uses nontraditional input and output elements. A tangible interface thus allows the manipulation of physical objects using digital information. The exploration and manipulation of physical objects is a factor to be considered in learning in children, especially those with some kind of disability such as hearing, who maximize the use of other senses such as vision and touch. In a tangible interface, three elements are related - physical, digital and social. The potential of IoT for children is growing. This technology IoT integrated with TUI, can help for that parents or teachers can monitoring activities of the child. Also to identify behavior patterns in the child with hearing impairment. This article shows four case studies, where had been designed different products of Internet of Things Tangible applied a several contexts and with products of low cost.

Because this issue journal is dedicated to Gelatin here we present a few applications of gelatin in the field of optics. It is understood that optics is the science that studies the production, propagation, interaction and detection of light. Regarding the detection there are some materials sensitive to light (photosensitive) that are used like photomultipliers, CCD’s, crystals, two dimension (2D) materials and more. Among the 2D materials the most popular through several centuries has been gelatin based photographic emulsion that records spatial distributions of light. More recently (1970) films made of Gelatin with Dichromate (DCG) and dyes have been used. We describe some characteristics and applications of these two photosensitive materials. Also we describe examples where gelatin is used as Relative Humidity (RH) sensor and in the fabrication of optical elements based on gelatin. This article is intended to researchers outside the optics community.

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

The Textile and Clothing (T\&C) value chain is one of the most polluting in the world and one that produces the most waste. It is, therefore, important to encourage the Circular Economy (CE) model in this sector, to reduce pollution and mitigate the effects of waste production, and consequently increase environmental sustainability. For that, the involvement of the final consumer is essential. And, the final consumer's use of an Eco-gamified application for registering and promoting Consumer-to-Consumer (C2C) and Consumer-to-Business (C2B) activities, which extends the life time of textile products, is of utmost importance. In this article, we survey gamification frameworks for analyzing system design level techniques that enable engaging the final consumer in the CE process. Then, we select and use one of such frameworks, Gameful Design Heuristics (GDH), for defining the gamification structure needed to implement on a Business-to-Consumer-to-Consumer (B2C2C) context of a circular economy. As result, we present a B2C2C circular business process model for the T\&C value chain, and propose the design model of a gamified platform for the final consumers, which allows them to register the C2B and C2C activities, from the circular value chain's business process, and benefit from a game-like experience. All model features have been mapped to GDH framework heuristics, validating that it is possible to support a set of defined heuristics of applied gamification for promoting CE in the T\&C value chain.

Timber-concrete composite (TCC) systems join the positive aspects of engineered wood products (good seismic behaviour, low thermal conductivity, environmental sustainability, good behaviour under fire if appropriately designed) with those of concrete (high thermal inertia, durability, excellent fire resistance). TCC facades are typically composed by an internal insulated timber-frame wall and an external concrete slab, separated by a ventilated air cavity. However, there is very limited knowledge concerning the performance of TCC facades, especially for what concerns their thermal behaviour. The present paper deals with the development and optimisation of a 2D CFD model for the analysis of TCC ventilated façades thermal behaviour. The model is calibrated and validated against the experimental data collected during the annual monitoring of a real TCC ventilated envelope in the north of Italy. Also, a new solver algorithm is developed to significantly speed up the simulation. The final model can be used for the time-efficient analysis and optimisation of the thermal performance of TCC ventilated facades, as well as other ventilated facades with external massive cladding, avoiding the expensive and time-consuming construction of mock-ups, or the use of comparably slow (conventional) CFD solvers that are less suitable for optimization studies.

Clinical trials often involve new substances characterized or developed for a specific pathology or class of pathologies. At other times, a clinical trial is observational; in other words, a known sub-stance has a range of effects on a given cohort of subjects. The types of trials are different and complex, and often, young clinical novice and the inexperienced researchers may struggle to evaluate how to proceed correctly. In this paper, we aim to create a mini-guide for beginners in clinical trials and provide elements for designing a clinical trial. Our intention is to highlight where to find the materials and how to adapt, even in the absence of sponsors, so that even the most inexperienced and under-resourced researcher can gain an understqanding of the complexi-ty of the process andaddress it appropriately. We do not claim to be exhaustive or cover all ele-ments, but rather, we aim to create a checklist. With this approach, starting discussioms about the experimental phases of the drug and concluding with the clinical trial, we aim to assist those facing this challenging "world."