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Purpose: To determine the psychological and neuropsychological status of patients with both blast-related ocular injury and mild traumatic brain injury (TBI) late after the traumatic event. Material and Methods: Thirty patients with blast-related ocular injury, reduced visual function and comorbid mild TBI were included in the study. The following methods of psychological and neuropsychological assessment were used: formalized interview; Suicidality, Post-traumatic Stress Disorder (PTSD), Alcohol Dependence, and Drug Dependence scales of the Mini-International Neuropsychiatric Interview (MINI); Raven’s Progressive Matrix scale; Personal and Social Performance (PSP) scale; PROMIS® Pain-Interference scale; Hospital Anxiety and Depression Scale (HADS); Mazes subtest of the Neuropsychological Assessment Battery (NAB); and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Results: The following significant correlations were found: PSP functioning and support from the family (r = 0.533, p = 0.002); total RBANS score and Mazes subtest score (r = 0.466, p = 0.009); total RBANS score and self-reported stress score (negative correlation, r = -0.492, p = 0.006); HADS depression and self-reported stress score (r = 0.646, p = 0.000114); PROMIS pain scale and PTSD scale (r = 0.482, p = 0.007). No association was found between the number of mild TBI events experienced and neuropsychological and psychological measurements. Conclusion: Blast-related mild TBI concomitant with ocular injury has a substantial and long-term impact on casualty’s cognitive and psychological functions. In such patients, the most prominent cognitive deficits occur in the domain of executive function (including cognitive control and planning and problem-solving skills). In the presence of reduced visual function, these deficits have a substantial impact on total cognitive scores, scores of other psychic functions (namely, attention and memory) and significantly affect the patient’s capacity for independent functioning.

The article examines the application of the concept of legal pluralism to the interaction between the European Union (EU) administrative legal order and the administrative legal orders of associated or candidate States as part of the process of aligning national legislation with EU standards. This process involves multiple sources of integration obligations derived from the Association Agreement, accession negotiations, conditions for economic aid, administrative cooperation, and EU-funded modernization programs. The authors suggest that a pluralistic approach may provide associated or candidate States with a degree of flexibility in choosing specific scopes, models, and time frames to align their national legislation with EU laws. This can help to mitigate and offset the imbalance in States’ relations with the EU resulting from the latter’s normative dominance. At the same time, various sources can lead to conflicts between integration obligations and approaches to harmonizing national administrative rules and practices.

Abstract Background Patient-focused approaches to capturing day-to-day variability in sleep disturbance are needed to properly evaluate the sleep benefits of new treatments. Such approaches rely on patient-reported outcome (PRO) measures validated in the target patient population. Methods Using atopic dermatitis (AD) as an example of a disease in which sleep is commonly disturbed, we developed a strategy for measuring sleep disturbance in AD trials. In developing this strategy, we conducted a targeted literature review and held concept elicitation interviews with adolescents and adults with AD. We subsequently identified potentially suitable PRO measures and cognitively debriefed them. Finally, we evaluated their psychometric properties using data from phase 2b (NCT03100344) and phase 3 (NCT03985943 and NCT03989349) clinical trials. Results The literature review confirmed that sleep disturbance is a key impact of AD but failed to identify validated PRO measures for assessing fluctuations in sleep disturbance. Subsequent concept elicitation interviews confirmed the multidimensional nature of sleep disturbance in AD and supported use of a single-item measure to assess overall sleep disturbance severity, complemented by a diary to capture individual components of sleep disturbance. The single-item sleep disturbance numerical rating scale (SD NRS) and multi-item Subject Sleep Diary (SSD)—an AD-adapted version of the Consensus Sleep Diary—were identified as potentially suitable PRO measures. Cognitive debriefing of the SD NRS and SSD demonstrated their content validity and their understandability to patients. Psychometric analyses based on AD trial data showed that the SD NRS is a well-defined, reliable, and fit-for-purpose measure of sleep disturbance in adults with AD. Furthermore, the SD NRS correlated with many SSD sleep parameters, suggesting that most concepts from the SSD can be covered using the SD NRS. Conclusions Using these findings, we developed an approach for measuring sleep disturbance in AD trials. Subject to further research, the same approach could also be applied to future trials of other skin diseases where itch causes sleep disturbance.

Abstract Transport of macromolecules through the nuclear envelope (NE) is mediated by nuclear pore complexes (NPCs) consisting of nucleoporins (Nups). Elys/Mel-28 is the Nup that binds and connects the decondensing chromatin with the reassembled NPCs at the end of mitosis. Whether Elys links chromatin with the NE during interphase is unknown. Here, using DamID-seq, we identified Elys binding sites in Drosophila late embryos and divided them into those associated with nucleoplasmic or with NPC-linked Elys. These Elys binding sites are located within active or inactive chromatin, respectively. Strikingly, Elys knockdown in S2 cells results in peripheral chromatin displacement from the NE, in decondensation of NE-attached chromatin, and in derepression of genes within. It also leads to slightly more compact active chromatin regions. Our findings indicate that NPC-linked Elys, together with the nuclear lamina, anchors peripheral chromatin to the NE, whereas nucleoplasmic Elys decompacts active chromatin.

La enfermería es la labor que abarca la atención autónoma a personas de todas las edades, familias, grupos y comunidades, la principal característica y esencia es el cuidado, implica establecer una relación de comprensión y acompañamiento de manera integral, convirtiéndolos en los principales cuidadores formales en la asistencia, lo que pone de manifiesto la necesidad de mirar su salud mental y bienestar del personal de enfermería. El objetivo fue describir el impacto en la salud mental de un profesional de la enfermería en la atención a pacientes del área COVID en tiempos de pandemia, en el periodo 2022-2023. Se realizó un estudio cualitativo, primero mediante el análisis documental y posteriormente mediante el método fenomenológico, descriptivo con base en el estudio de caso, considerando la temporalidad en tres momentos, antes, durante y después de la pandemia por COVID. Los hallazgos dan constancia, de cambios e impactos a nivel biológico, psicológico, social y espiritual que derivan en afectaciones en salud mental que se experimentaron, y, por otro lado, de la escasez acciones para dotar a los profesionales de la salud de un acompañamiento, capacitación y sensibilización en salud mental para la mejora de su labor y bienestar personal.

La relación de las emociones y los procesos cognitivos ha posicionado a la educación emocional como un tema relevante en el ámbito educativo; sin embargo, para lograr su plena integración en la educación superior resulta imperativo conocer el estado que guarda en la actualidad. El objetivo del estudio consiste en identificar los principales hallazgos teóricos y empíricos relacionados con la educación emocional en el nivel superior, la educación emocional en el proceso de enseñanza-aprendizaje y la formación del docente universitario en educación emocional. Para ello se realizó una revisión documental con enfoque cualitativo y descriptivo, utilizando repositorios y bases de datos científicas. Se incluyeron artículos en español e inglés publicados en México y en el extranjero, entre los años 2017 y 2022. Se revisaron 67 documentos y se seleccionaron 22 que fueron organizados en tres categorías: a) educación emocional en el nivel superior, b) educación emocional en el proceso de enseñanza-aprendizaje y c) formación docente en educación emocional. Los principales hallazgos evidencian que la educación emocional tiene una influencia positiva en el rendimiento académico y la generación de ambientes propicios en el aula, pero también la urgente necesidad de una formación docente y el afrontamiento de desafíos...

Abstract The phenyl ring is a basic structural element in chemistry. Here, we show the design, synthesis, and validation of its new saturated bioisostere with improved physicochemical properties − 2-oxabicyclo[2.2.2]octane. The design of the structure is based on the analysis of the advantages and disadvantages of the previously used bioisosteres: bicyclo[1.1.1]pentane, bicyclo[2.2.2]octane, and cubane. The key synthesis step is the iodocyclization of cyclohexane-containing alkenyl alcohols with molecular iodine in acetonitrile. 2-Oxabicyclo[2.2.2]octane core is incorporated into the structure of Imatinib and Vorinostat (SAHA) drugs instead of the phenyl ring. In Imatinib, such replacement leads to improvement of physicochemical properties: increased water solubility, enhanced metabolic stability, and reduced lipophilicity. In Vorinostat, such replacement results in a new bioactive analog of the drug. This study enhances the repertoire of available saturated bioisosteres of (hetero)aromatic rings for the use in drug discovery projects.

Abstract Introduction Assessing treatment response is key to determining treatment value in atopic dermatitis (AD). Currently, response is assessed using various clinician- or patient-reported measures and response criteria. This variation creates a mismatch of evidence across trials, hindering the ability of clinicians, regulators, and payers to compare the efficacy of treatments. This review identifies which measures and criteria are used to determine response in clinical trials and health technology assessments (HTAs). Moreover, it systematically reviews the psychometric performance of those measures and criteria to understand which perform best in capturing patient-relevant symptoms and treatment benefits. Methods A scoping review of clinical trials and HTAs in AD identified the following measures for inclusion: the Eczema Area and Severity Index (EASI), the Investigator’s Global Assessment (IGA), the Dermatology Life Quality Index (DLQI) and the Peak Pruritus Numerical Rating Scale (PP-NRS). A systematic search was performed in MEDLINE and Embase to identify studies testing the psychometric performance of these measures in adults or adolescents with AD. Results A lack of consistency in the assessment of response was observed across clinical trials and HTAs. Important gaps in psychometric evidence were identified. No content validations of the EASI and IGA in AD were found, while some quantitative studies suggested that these measures fail to capture itch, a core symptom. The PP-NRS and DLQI performed well. No studies compared the performance of different response criteria. Conclusion Content validation of the PP-NRS confirmed the importance of itch as a core symptom and treatment priority in AD; however, itch is not well covered in the EASI or IGA. Including the PP-NRS in clinical trials and HTAs will better capture patient-relevant benefit and response. Although various response criteria were used, no studies compared the performance of different criteria to inform which were most appropriate to compare treatments in clinical trials and HTAs.

Abstract The fossil vertebrate fauna of Máriahalom contains remains from a wide range of ecologies including terrestrial and aquatic mammals, crocodiles, sharks, and rays among others. All these were found mixed in mollusc-rich, shallow water, coastal deposits. The aim of the study is to trace the origin of the fossils using their rare earth element (REE) content and their respective ecology with stable oxygen isotopic compositions. In addition, marine vertebrates and calcareous marine fossils were analysed for their Sr isotope composition to provide a new age estimate for the locality. The REE content and their distribution in the fossils indicate similar early diagenetic environments and possible contemporaneous fossilization for the entire vertebrate assemblage. Reworked fossils of significantly different age can be excluded. The enamel/enameloid-derived phosphate oxygen isotope composition of selected fossil taxa fit well with previously inferred habitats that include marine, brackish, and terrestrial environments. Notably, the stem-pinniped Potamotherium valletoni is best interpreted as freshwater dweller instead of marine, consistent with the sedimentology of other occurrences. Our novel 87Sr/86Sr data suggest an Aquitanian age (21.4 ± 0.5 Ma) for the Máriahalom site that is younger than the previously proposed Late Oligocene age based on biostratigraphy (MP28–30 European Mammal Paleogene Reference Levels). An Aquitanian age raises the possibility that the index fossil taxon, the anthracothere mammal Microbunodon minimum, may have vanished earlier in Western Europe than in the Central Paratethys region.

Background. The relevance of studying the phenomenon of public catering in the USSR is due to the need to understand the specifics of the Soviet modernity, the implemen-tation of the project of building a new society in the conditions of Stalin’s reconstruction of the national economy. The purpose of the work is to analyze the process of changes in the functioning of public catering in the 1920s – 1930s on the example of Penza region. Materials and methods. Based on the study of a wide range of sources extracted from the central (Russian State Archive of Economics) and local archives (State Archive of Penza region), as well as published documents, the features of the formation of a key branch of the modern economy – public catering in the period of the 1920s – 1930s are revealed. The methodological basis of the study was the concept of social constructionism or con-structivism, in the context of which the main emphasis is placed on the conditionality of the processes of constructing social reality by state ideology and management practice. Com-parative historical and statistical methods were used to identify the regional specifics of the formation of the Soviet public catering. Results. The main principles, features, advantages and disadvantages of the Soviet public catering in various historical periods – the new eco-nomic policy of the 1920s and industrialization of the 1930s – are analyzed on the example of Penza region. Conclusions. In the period of the 1920s – 1930s, continuity in the work of public canteens of Penza province was maintained: class orientation, advantages and problems characteristic of the previous period. A new trend was a temporary relaxation for private capital admitted to the catering sector in the 1920s. During the years of industriali-zation, it became one of the branches of the Soviet economy that contributed to the solution of important state tasks.

Current rail traffic management and control systems cannot be easily upgraded to the new needs and challenges of modern railway systems because they do not offer interoperable data structures and standardized communication interfaces. To meet this need, the Horizon 2020 Shift2Rail OPTIMA project has developed a communication platform for testing and validating the new generation of traffic management systems (TMS), whose main innovative features are the interoperability of the data structures used, standardization of communications, continuous access to real-time and persistent data from heterogeneous data sources, modularity of components and scalability of the platform. This paper presents the main components, their functions and characteristics, then describes the testing and validation of the platform, even when federated with other innovative TMS modules developed in separate projects. The successful validation of the system has confirmed the achievement of the objectives set and allowed a new set of objectives to be defined for the reference platform for the railway TMS/Traffic Control systems.

Introducción: La pandemia por COVID-19 interrumpió abruptamente la modalidad educativa presencial, los docentes se adaptaron a una nueva forma de enseñanza mediada con tecnología como respuesta al confinamiento. Al respecto, la Universidad de Colima, en México, ejecutó un Programa de Continuidad Académica para garantizar la atención del estudiantado en bachillerato, licenciatura y posgrado. Objetivo: El articulo describe la situación tecnológica, pedagógica-didáctica y socioemocional que enfrentaron los docentes del nivel superior, en el desarrollo de este programa universitario, así como las necesidades de capacitación y los principales retos del profesorado en la enseñanza mediada. Metodología: Estudio mixto de tipo exploratorio, resultado de la aplicación de un cuestionario a 1 587 docentes, de los cuales se obtuvieron 1 195 respuestas. R­esultados y discusión: En la investigación se evidenció que, el 63% de los docentes enfrentó complicaciones de tipo didácticas-pedagógicas; el 17% tecnológicas y de logística y el 7% de tipo emocional al tiempo de conducir la «nueva» forma de enseñanza. Conclusiones: Los retos del docente ante la pandemia permiten visualizar las demandas de formación, capacitación, actualización y desarrollo de habilidades del profesorado, así como la apropiación de los recursos tecnológicos que limita el desarrollo de los procesos de enseñanza aprendizaje acordes a la calidad educativa esperada. Asimismo, se propone continuar con esta línea de investigación orientada a identificar prácticas creativas y necesidades de capacitación docente, desde la perspectiva del estudiantado, y con ello, fortalecer la oferta académica del Programa Institucional de Formación Docente en función de la mejora del desempeño del profesorado universitario.

Abstract Proximity ligation approaches, which are widely used to study the spatial organization of the genome, also make it possible to reveal patterns of RNA-DNA interactions. Here, we use RedC, an RNA-DNA proximity ligation approach, to assess the distribution of major RNA types along the genomes of E. coli, B. subtilis, and thermophilic archaeon T. adornatum. We find that (i) messenger RNAs preferentially interact with their cognate genes and the genes located downstream in the same operon, which is consistent with polycistronic transcription; (ii) ribosomal RNAs preferentially interact with active protein-coding genes in both bacteria and archaea, indicating co-transcriptional translation; and (iii) 6S noncoding RNA, a negative regulator of bacterial transcription, is depleted from active genes in E. coli and B. subtilis. We conclude that the RedC data provide a rich resource for studying both transcription dynamics and the function of noncoding RNAs in microbial organisms.

Purpose. The work is aimed to determine the real location in space and conduct possible measurement of the true geometric dimensions of the NPP cooling pond dam, especially its underwater part and to detect the additional and previously unaccounted factors that could affect these parameters, as well as the state of the entire structure in general. Methodology. A comprehensive analysis of all available materials about engineering surveys and geotechnical studies was carried out at the dam of the cooling pond of the Zaporizhzhia NPP. Due to this, a more comprehensive look at the results of engineering and geological surveys was obtained. Findings. The state of soils in the body of the earth dam can be influenced by weakened and poorly studied zones of the dam. These zones were determined based on the analysis of the soil studies data of the dam’s ground. Previously uncovered issues on the operation of the facility were raised and considered. The ways and methods for additional study of the earth dam of the cooling pond were selected, the conditions for their use were substantiated. A numerical relationship between the thickness of loose soils and the amount of surface subsidence were determined for the first time. A generalized geological section of the dam body was compiled for further modeling of geotechnical processes. Originality. For the first time since construction, a comprehensive program was developed for assessing the technical condition of the cooling pond dam using innovative methods from the Laboratory of Research of Nuclear and Thermal Power Plants in Prydniprovska State Academy of Civil Engineering and Architecture (PSACEA). In particular, combined hydrographic-geodetic and aerovisual methods were proposed using specially designed universal leading signs that have no analogues in world practice. Practical value. The application of the developed comprehensive program using innovative methods allows assessing the technical condition of the cooling pond dam of the NPP.

Abstract Background Understanding the role of various factors in 3D genome organization is essential to determine their impact on shaping large-scale chromatin units such as euchromatin (A) and heterochromatin (B) compartments. At this level, chromatin compaction is extensively modulated when transcription and epigenetic profiles change upon cell differentiation and response to various external impacts. However, detailed analysis of chromatin contact patterns within and between compartments is complicated because of a lack of suitable computational methods. Results We developed a tool, Pentad, to perform calculation, visualisation and quantitative analysis of the average chromatin compartment from the Hi-C matrices in cis, trans, and specified genomic distances. As we demonstrated by applying Pentad to publicly available Hi-C datasets, it helps to reliably detect redistribution of contact frequency in the chromatin compartments and assess alterations in the compartment strength. Conclusions Pentad is a simple tool for the analysis of changes in chromatin compartmentalization in various biological conditions. Pentad is freely available at https://github.com/magnitov/pentad .

Ganoderma lucidum exhibits the ability to synthesize a diverse range of biologically active molecules with significant pharmaceutical potential, including xylomannan and fucogalactan, which have demonstrated antitumor activity. However, there exists considerable intra-species variability in the capacity to produce these metabolites at high concentrations, likely reflecting the high genomic diversity observed from a limited number of strains sequenced to date. We employed high-throughput shotgun sequencing to obtain the complete genome sequence of G. lucidum strain 5.1, which is distinguished by its remarkable xylomannan synthesis capabilities. Through the utilization of semi-automatic reordering based on conformation capture (Hi-C) data, we substantially enhanced the assembly process, resulting in the generation of 12 chromosome-level scaffolds with a cumulative length of 39 Mbp. By employing both de novo and homology-based approaches, we performed comprehensive annotation of the genome, thereby identifying a diverse repertoire of genes likely involved in polysaccharide biosynthesis. The genome sequence generated in this study serves as a valuable resource for elucidating the molecular mechanisms underlying the medicinal potential of Ganoderma species, discovering novel pharmaceutically valuable compounds, and elucidating the ecological mechanisms of the species. Furthermore, the chromosome contact map obtained for the first time for this species extends our understanding of 3D fungal genomics and provides insights into the functional and structural organization within the fungal kingdom.

Zygotic genome activation in zebrafish relies on pluripotency transcription factors Pou5f3 and Sox19b. Here the authors investigate how these factors interact in vivo by analyzing the changes in chromatin state and time-resolved transcription in Pou5f3 and Sox19b single and double mutant embryos.

Abstract The Barrovian metamorphism of the Lepontine dome is manifested by isograds that cross‐cut tectonic nappe contacts, which is commonly interpreted as metamorphism that occurred after nappe emplacement. However, the pervasive mineral and stretching lineation in amphibolite facies, associated with top‐to‐foreland shearing, suggests that peak Barrovian conditions are coeval with nappe‐overthrusting. Here, we combine mapping and U‐Pb zircon dating to better constrain the relation between metamorphism and overthrusting. Metamorphic zircon rims show two age populations at 31–33 and 22–24 Ma. The younger population is locally observed in post‐foliation dikes (and associated metasomatism) likely sourced from deep‐migmatites exhuming along the Alpine backstop. The older population occurs regionally and is found in syn‐kinematic migmatites which occur along a crustal‐scale shear zone. Below this shear zone, magmatic and detrital zircon cores suggest that the Cima Lunga unit, previously interpreted as a tectonic mélange with Mesozoic fragments, was a pre‐Variscan metasedimentary sequence intruded by Permian granitic sills, now orthogneisses. This unit was strongly sheared along the top of the Simano nappe during overthrusting of a rock pile here‐termed Maggia‐Adula nappe. This large‐scale nappe emplacement imprinted the regional lineation and peak temperatures until 31–33 Ma. Péclet (1–10) and Brinkman (0.002–1.8) numbers, estimated for the overthrusting, suggest an advection‐dominated heat transfer caused by rock exhumation, with some diffusion (conduction) during nappe emplacement. Diffusion contributed to Barrovian isograds discordant to the thrust. Shear heating was important if stress times shearing rate >∼5·10−6 W·m−3 within the nappe. The thermal evolution after overthrusting was spatially heterogeneous until ca. 22 Ma.

Introducción: la insuficiencia venosa es una afectación en la cual las venas son incapaces de enviar sangre desde las extremidades inferiores al corazón. La gravedad de esta enfermedad radica en sus complicaciones, el grado más leve produce escozor, dolor, pesadez, cansancio y quemazón en la planta de los pies; al complicarse puede presentar edema, calambres en pantorrillas, prurito intenso y coloración oscura de la piel. Objetivo: describir el nivel de conocimiento y cumplimiento del personal de enfermería de área quirúrgica respecto al autocuidado relacionado a la insuficiencia venosa de miembros inferiores. Material y métodos: se trata de un estudio descriptivo, trasversal, prolectivo y observacional; el universo es de 24 profesionales en enfermería y la muestra estuvo conformada por 22 colaboradores adscritos al área quirúrgica de un hospital público de segundo nivel de atención; se utilizaron dos instrumentos: 1) conocimiento y 2) cuestionario para evaluar el autocuidado. Se analizaron los datos mediante estadística descriptiva y prueba exacta de Fisher. Resultados: el 100 % de los participantes en el estudio no cumple con el autocuidado, el criterio para determinar el cumplimiento fue que, al observar las acciones preventivas conocidas como autocuidado, se obtuviera una calificación de 6 ítems completos, lo cual no sucede. Conclusión: existe un factor de riesgo para la insuficiencia venosa en miembros inferiores, donde la antigüedad laboral es la variable que evidencia diferencias significativas con respecto al conocimiento y cumplimiento.