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Advanced Therapy Medicinal Products (ATMPs) based on somatic cells expanded in vitro, with or without genetic modification, is a rapidly growing area of drug development, even more so following the marketing approval of several such products. ATMPs are produced according to Good Manufacturing Practice (GMP) in authorized laboratories. Potency assays are a fundamental aspect of the quality control of the end cell products and ideally could become useful biomarkers of efficacy in vivo. Here we summarize the state of the art with regard to potency assays used for the assessment of the quality of the major ATMPs used clinic settings. We also review the data available on biomarkers that may substitute more complex functional potency tests and predict the efficacy in vivo of these cell-based drugs.

Abstract Atmospheric turbulence, irregular fluctuations of the fluid state, is studied on Mars. Universality of the turbulence spectrum underpins atmospheric models where computational requirements preclude full fidelity simulations of the smallest scales. However, there are discrepancies among reports on the existence and spectral location of universal scaling in Martian atmospheric data. Here, results indicate the smallest resolvable structures from Martian wind speed data are still associated with the energetic regime, which may ultimately explain why multiple reports have not found a consistent Kolmogorov-like spectral regime on Mars. Universal spectral scaling of wind data from Perseverance’s Mars Environmental Dynamics Analyzer is used to estimate the thresholds that separate three turbulence regimes: energetic, inertial, and molecular dissipation. Wind measurements at 2-Hz, the fastest sampling rate for direct wind sensor measurements on Mars, resolves turbulence in the energetic regime and approaches the inertial regime, which is consistent with reported Martian dust devil sizes.

La incorporación del alumnado con NEAE en el aula de música supone un importante reto para los docentes especialistas. Esta investigación se concentra en la visión del docente en música en todas sus vertientes: enseñanza generalista, Conservatorio, Escuelas Municipales y Universidad. Los objetivos de este trabajo se han centrado en conocer la experiencia y formación de los docentes en educación inclusiva, cuantificar las destrezas adquiridas por su alumnado y averiguar su percepción sobre sus necesidades formativas al respecto. La muestra está conformada por un total de 94 docentes especialistas en música de la isla de Tenerife (Canarias, España). Se trata de un estudio mixto con diseño selectivo y transversal, la toma de datos se ha realizado mediante un cuestionario ad hoc sometido a criterio de expertos. El cuestionario tiene tres apartados, uno dedicado a aspectos sociodemográficos, otro sobre destrezas adquiridas en el aula de música que se ha diseñado a modo Likert y la última con carácter cualitativo donde se indaga sobre prácticas, actitudes y mejoras en la formación docente. Se concluye con una evidente necesidad formativa para proporcionar mejor atención al alumnado con NEAE, cada vez más frecuente en las aulas de música, coinciden los participantes en la importancia de la formación permanente para incorporar recursos actualizados y efectivos.

Multitasking game does not only impact different cognitive functions but also influences performance and vital signs. This affirmation is key for supporting and monitoring first responders during real-life rescue scenarios, with the aim of improving mission performance and reducing risks for both victims and rescuers. In this manuscript we have developed a game that combines a primary sustained attention task with secondary tasks that target different cognitive functions (focused attention, working memory and short-term memory). 30 first responders participated in the study, completing 18 trials with varying primary and secondary tasks complexities. The results show that concurrent multitasking significantly impacts both primary and secondary task performance, with a clear shift of attention towards the secondary task. Moreover, the performance impact varies depending on the cognitive functions involved. Physiological data show minimal changes during multitasking, but significant changes are observed when task performance is not properly managed. Therefore, the study provides valuable insights into the complexities of multitasking, highlighting the importance of considering both cognitive functions and objective physiological measures for a comprehensive understanding of cognitive demands in real-world operations.

Objective: Management of a skin dimpling due to a chronic periapical lesion may pose challenges. This case report presents a multidisciplinary approach to resolving a persistent cutaneous scar of endodontic origin and also offers a flowchart for the management of similar cases.Case report: A 34-year-old female referred to the Endodontics Department of Mashhad Dental School at Mashhad University of Medical Sciences, complained of a skin dimpling on her face with a history of pus discharge. Diagnostic workup and radiographic examination revealed that the right mandibular first molar had a failing root canal treatment and a defective restoration. The respective tooth underwent endodontic retreatment. Due to palpation of a cord-like tract at the apical region of the tooth, surgical removal of the mentioned structure was planned using a mucoperiosteal flap. After flap elevation, the cord was cut at the base of attachment to the bone, which resulted in immediate correction of facial contour. Finally, the tooth was permanently restored. At the 6-month follow-up visit, the periapical lesion was healing, and the face had a normal contour.Conclusions: Considering the significance of surgical intervention in cases with a cord-like sinus tract and consequent skin dimpling, a flowchart for a step-by-step decision-making process is offered to better restore the normal facial contour.

Antioxidant therapies are of interest in the prevention and management of ocular disorders such as cataracts. Although an active area of interest, topical therapy with antioxidants for the treatment of cataracts is complicated by multiple ocular anatomical barriers, product stability, and solubility. Entrapment and delivery of antioxidants with poly(lactic-co-glycolic acid) nanoparticles is a possible solution to these challenges, however, little is known regarding their effects in vitro or in vivo. Our first aim was to investigate the impact of blank and lutein loaded PLGA nanoparticles on viability and development of reactive oxygen species in lens epithelial cells in vitro. Photo-oxidative stress was induced by ultraviolet light exposure with cell viability and reactive oxygen species monitored. Next, an in vivo, selenite model was utilized to induce cataract formation in rodents. Eyes were treated topically with both free lutein and lutein loaded nanoparticles (LNP) at varying concentrations. Eyes were monitored for the development of anterior segment changes and cataract formation. The ability of nanodelivered lutein to reach the anterior segment of the eye was evaluated by liquid chromatography coupled to mass spectrometry of aqueous humor samples and liquid chromatography coupled to tandem mass spectrometry (targeted LC-MS/MS) of lenses. LNP had a minimal impact on the viability of lens epithelial cells during the short exposure timeframe (24 h) and at concentrations < 0.2 μg LNP/μl. A significant reduction in the development of reactive oxygen species was also noted. Animals treated with LNPs at an equivalent lutein concentration of 1,278 μg /mL showed the greatest reduction in cataract scores. Lutein delivery to the anterior segment was confirmed through evaluation of aqueous humor and lens sample evaluation. Topical treatment was not associated with the development of secondary keratitis or anterior uveitis when applied once daily for one week. LNPs may be an effective in the treatment of cataracts.

Citizenship education is currently a global priority, although it cannot be said to be a new topic. In October 1997 the Council of Europe implemented the Education for Democratic Citizenship project with the aim of giving shape to European citizenship. The aim of this study is to identify the civic competences promoted by supranational organizations and their realization in the Italian context. We will analyze the development of these skills in compulsory education in relation to the Italian situation, starting from the analysis of the latest Eurydice and PISA reports. This analysis will be the basis for deepening the role of music in the advancement of citizenship skills and the use of the musical discipline as a formula for the development of personal and social civic practices from the educational field in the current compulsory school in Italy.

Missed canals pose a potential risk in the treatment of teeth with anatomical variations, even when multi-angled radiographs have been used. Incomplete mechanical and chemical debridement of the root canal system can lead to treatment failure. Therefore, clinicians must have adequate knowledge of normal root canal systems as well as any possible variations in order to prevent any failure during or after the treatment of teeth with anatomical variations. Any case report of such rare variations would add to this critically required body of knowledge. The current case report presents the diagnosis and endodontic treatment of a maxillary first premolar with one root and three canals (one palatal and two buccal canals, all buccolingually positioned, bifurcating in the apical region), which was different from premolars with 3 canals reported up to now. This configuration describes an unusual root canal system for the maxillary first premolar and does not fit into any of the well-known root canal classification systems.

During the last decade, new technological tools have emerged to provide first responders with augmented senses in emergency and disaster situations. Some of these tools focus on providing extra information about their surroundings. However, despite augmenting first responders’ capabilities, the quantity and the way that this information is presented can affect their cognitive load. This manuscript presents an integrated framework that allows real-time biosignals monitoring to analyze physical constants and correlate them with subjective cognitive load tests. Biosignals monitoring allows alarms to be raised related to the physical status while cognitive load values will allow modulation of the amount of information that can be assimilated by the first responder in operation. In-lab and practice experimental tests have been conducted to create a fully functional framework. During the technical validation, a strong dispersion of subjective cognitive load by means of NASA-TLX questionnaires has been found between participants. Nonetheless, the developed framework allows extraction of relationships between biosignals and cognitive load, with special attention to the respiration rate and eye movements.

ABSTRACT Studies involving endophytic fungi isolated from endemic plants and their antibacterial potential are largely unknown in the Pampa biome. In this study, we identified endophytic fungi isolated from Kelissa brasiliensis (Iridaceae), an endemic species of the Brazilian Pampa, and assessed their antibacterial activity. Endophytic fungi were first grouped based on macro-and micro-morphology, and one representative of each morphospecies was analyzed using sequences from the internal transcribed spacer (ITS) rDNA region. We then tested the fungal extracts against laboratory isolates of Staphylococcus aureus and Escherichia coli for antibacterial activity. A total of 30 endophytes were isolated from the tissues of K. brasiliensis, with the majority from the leaves. Endophytes were then grouped into seven morphospecies based on their morphological features and one representative from each was selected for phylogenetic analysis. The inference from the ITS rDNA sequences identified the endophytes of the seven selected morphospecies as belonging to six taxonomic groups: Colletotrichum (two), Diaporthe (one), Epicoccum (one), Fusarium (one), and Pestalotiopsis (one). The endophyte extracts revealed better results against E. coli than S. aureus, although the extracts from Colletotrichum and Pestalotiopsis sp. were statistically similar to the control antibiotic. Our study is a basis for endophytic fungi studies in Pampa.

Improving the resilience of sensor systems in space exploration is a key objective since the environmental conditions to which they are exposed are very harsh. For example, it is known that the presence of flying debris and Dust Devils on the Martian surface can partially damage sensors present in rovers/landers. The objective of this work is to show how data-driven methods can improve sensor resilience, particularly in the case of complex sensors, with multiple intermediate variables, feeding an inverse algorithm (IA) based on calibration data. The method considers three phases: an initial phase in which the sensor is calibrated in the laboratory and an IA is designed; a second phase, in which the sensor is placed at its intended location and sensor data is used to train data-driven model; and a third phase, once the model has been trained and partial damage is detected, in which the data-driven algorithm is reducing errors. The proposed method is tested with the intermediate data of the wind sensor of the TWINS instrument (NASA InSight mission), consisting of two booms placed on the deck of the lander, and three boards per boom. Wind speed and angle are recovered from the intermediate variables provided by the sensor and predicted by the proposed method. A comparative analysis of various data-driven methods including machine learning and deep learning (DL) methods is carried out for the proposed research. It is shown that even a simple method such as k-nearest neighbor is capable of successfully recovering missing data of a board compared to complex DL models. Depending on the selected missing board, errors are reduced by a factor between 2.43 and 4.78, for horizontal velocity; and by a factor between 1.74 and 4.71, for angle, compared with the situation of using only the two remaining boards.