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Abstract Genomic alterations are the driving force behind pancreatic cancer (PC) tumorigenesis, but they do not fully account for its diverse phenotypes. Investigating the epigenetic landscapes of PC offers a more comprehensive understanding and could identify targeted therapies that enhance patient survival. In this study, we have developed a new promising methodology of spatial epigenomics that integrates multiplexed molecular imaging with convolutional neural networks. Then, we used it to map epigenetic modification levels in the six most prevalent PC subtypes. We analyzed and semi-quantified the resulting molecular data, revealing significant variability in their epigenomes. DNA and histone modifications, specifically methylation and acetylation, were investigated. Using the same technique, we examined DNA conformational changes to further elucidate the transcriptional regulatory mechanisms involved in PC differentiation. Our results revealed that the foamy-gland and squamous-differentiated subtypes exhibited significantly increased global levels of epigenetic modifications and elevated Z-DNA ratios. Overall, our findings may suggest a potentially reduced efficacy of therapeutics targeting epigenetic regulators for these subtypes. Conversely, the conventional ductal PC subtype has emerged as a promising candidate for treatment with epigenetic modulators.

Abstract Hydrogen is crucial for decarbonization efforts due to its abundance, environmental friendliness, and versatility. To maximize its potential, an efficient transportation infrastructure is essential. While utilizing the natural gas pipeline network for transporting hydrogen is cost-effective, hydrogen embrittlement (HE) poses a significant challenge. When hydrogen enters the metal, it significantly compromises its fracture toughness. This study investigates the impact of high-pressure hydrogen on the mechanical properties of API 5L X65 carbon steel through a combined experimental and computational approach. To quantify the extent of HE, tensile tests were performed on identical specimens, one set pre-exposed to high-pressure hydrogen and another set kept in an inert environment for comparison. Finite element modelling, employing the Bai-Wierzbicki material model (BWMM), was used to simulate the material behaviour under large plastic deformations and correlate with experimental results. This synergistic approach integrates experimental data with simulations, creating a framework for predicting and preventing catastrophic failures.

The Wnt/β-catenin pathway contains multiple high-confidence risk genes that are linked to neurodevelopmental disorders, including autism spectrum disorder. However, its ubiquitous roles across brain cell types and developmental stages have made it challenging to define its impact on neural circuit development and behavior. Here, we show that TCF7L2, which is a key transcriptional effector of the Wnt/β-catenin pathway, plays a cell-autonomous role in postnatal astrocyte maturation and impacts adult social behavior. TCF7L2 was the dominant Wnt effector that was expressed in both mouse and human astrocytes, with a peak during astrocyte maturation. The conditional knockout of Tcf7l2 in postnatal astrocytes led to an enlargement of astrocytes with defective tiling and gap junction coupling. These mice also exhibited an increase in the number of cortical excitatory and inhibitory synapses and a marked increase in social interaction by adulthood. These data reveal an astrocytic role for developmental Wnt/β-catenin signaling in restricting excitatory synapse numbers and regulating adult social behavior.

Celem artykułu jest prześledzenie wpływu cenzury na powstawanie zachowanej w rękopisie Bożycy lub teozofii oraz na decyzje wydawnicze Bronisława Trentowskiego, jednego z wiodących polskich filozofów romantyzmu. Ze swego traktatu z zakresu filozofii Boga autor opublikował za życia tylko dwa fragmenty. Stawiam w artykule tezę, że dzieło nie zostało w pełni opublikowane z powodu złej recepcji owych fragmentów pośród polskich odbiorców, których tożsamość narodowa w okresie zaborów zawisła na spójności polskiego Kościoła katolickiego, a nie bezpośrednio z powodu cenzury. Kolacjonowanie opublikowanych fragmentów z rękopisem dzieła ujawnia różnice o charakterze ilościowym i jakościowym specyficzne dla każdej z publikacji: jednej wydanej w Paryżu bez cenzury oraz drugiej opublikowanej w Poznaniu pod cenzurą pruską. Analiza wyników kolacjonowania w zestawieniu z korespondencją Autora z przyjaciółmi i wydawcami pozwala wnioskować o wpływie cenzury na proces twórczy Bożycy pod postacią autocenzury. Pozwala też uznać gotowość Autora do wydania dzieła za cenę kompromisu z cenzurą instytucjonalną, ale nie za cenę odstąpienia od poglądów na kwestię filozofii Boga w celu zdobycia uznania odbiorców.

The aim of the article is to present the use of synodal method in building the family community. The method was developed for the use of the Synod about the synodality, initiated in 2021 in the Catholic Church. Documents of the church indicate the need for using the method within the universal Church as well as the local Churches. However, due to the fact that a Christian family is also a domestic Church, the method can also be used in building the marital-family community. The research conducted for the use of this article was based mainly on the documents of the Catholic Church devoted to the synod on synodality. They became the source of the undertaken analyses. The authors also used the elaborations regarding the research problem and the marriage and family issues. The aim of the article and the nature of the source materials suggest the use of the adapted research methods. The leading method was the monographic method in some of its dimensions. Moreover, the other research methods include: descriptive method, the method of the analysis of documents and the analysis of the contents. The article consists of three parts. The first part presents the novelty and characteristics of the synodal method. The second part was devoted to the applicability of the method in building the community of marriage and the third part was devoted to the applicability of the method in deepening the bond between parents and their children.

Fetal alcohol spectrum disorders (FASD) are a group of permanent birth defects resulting from maternal alcohol consumption during pregnancy, characterized by neurological, somatic, and mental abnormalities. Among them are changes in the organ of vision, including a decrease in visual acuity and other serious effects. FASD encompasses a range of distinct disease entities, each with its own specific symptoms. These are: fetal alcohol syndrome, partial fetal alcohol syndrome, alcohol-related neurodevelopmental disorders, and alcohol-related birth defects. There is no causal treatment for the disease. Maternal abstinence at all stages of pregnancy is a preventive measure. The best results in the treatment of children with FASD are achieved with individualized, personalized supportive therapy provided by interdisciplinary medical teams. The goals are to alleviate existing dysfunctions and to prevent secondary disorders that result from inadequate or absent medical assistance.

This article presents a comprehensive improvement in the experimental analysis of cracking processes in smooth and sharp V-notched samples taken from gas transport pipelines, utilizing the acoustic emission (AE) method. The research aimed to establish a robust correlation between the failure mechanisms of uni-axially tensile samples and the distinct characteristics of AE signals for enhanced quality management in pipeline integrity. The study encompassed materials from two different straight pipe sections, encompassing both long-term used materials and new, unused materials. Through the application of the k-means grouping method to AE signal analysis, we achieved the identification of AE signal parameters characteristic of various stages of the material destruction process. This advancement introduces a significant improvement in monitoring and managing the operational safety of pipeline networks, offering a methodology that leverages advanced acoustic emission signal analysis. The outcomes present significant implications for the pipeline industry by proposing methods to enhance safety systems and more effectively manage the integrity and quality of gas infrastructure.

El objetivo principal de esta investigación ha sido estudiar la alineación del cuerpo del bailaor(a), mientras realiza el zapateado durante el baile, para proporcionar una descripción detallada al servicio de los profesionales del flamenco: profesores, instructores y estudiantes de diferentes niveles. Se analizó la técnica de zapateado de una bailaora profesional. El análisis biomecánico se basó en treinta ciclos de seis secuencias de repeticiones consecutivas de zapateado. Se realizaron mediciones cinemáticas utilizando el sistema Vicon, mientras que la medición de las fuerzas de reacción del suelo (GRF), se realizaron con una plataforma de fuerza Kistler. Se analizaron los siguientes parámetros: el tiempo de cada zapateado; el valor máximo del componente vertical de GRF, en relación al peso corporal (BW), para la secuencia de zapateados; el impulso de GRF; la cinemática de la pelvis y las articulaciones de las extremidades inferiores; y la forma de onda del sonido de los golpes de los zapateados. Los valores medios de la componente vertical de GRF oscilaron entre 0.6 y 2.7 BW. La inclinación pélvica anterior máxima fue de 29º, con un rango de movimiento (RoM). Esta movilidad estuvo acompañada por un RoM de cadera de 20° y un RoM de rodilla de ~40° durante la flexión. Las conclusiones proporcionan información práctica para que docentes y estudiantes de baile flamenco puedan tenerla en consideración.

OBJECTIVE: The study aimed to identify the effects of ground reaction forces (GRF) recorded during landing in typical elements of three dance styles, including classical, modern, and folk dance, on injuries` topography. METHODS: The research involved a survey and measurements of GRF generated during landing after the jump. The survey involved a group of 90 professional dancers. In the questionnaire, the dancers marked areas of the human body that were affected at least once by injuries. Biomechanical tests of the GRF recording were conducted on a group of 15 professional dancers. The analysis focused on the following parameters: a maximum value of the vertical variable of the GRF relative to body weight (maxGRF_z), the time between the moment from first foot contact with the ground to the moment of reaching the maxGRF_z (_tmaxGRFz), and the loading rate of the GRF relative to body weight (LR_GRFz). RESULTS: Regardless of dance style and sex, the lower spine, knee joints, ankle joints and feet were the areas most affected by injuries among professional dancers. The level of maxGRF_z, t_maxGRFz and LR_GRFz during typical jumps in classical, modern, and folk dance was statistically significantly different (P

Reduced muscle strength can affect daily activities, so monitoring is essential. Methods such as isokinetic dynamometers assess maximum muscle force, while hand dynamometers measure hand grip strength. Research has investigated hand grip strength as a predictor of upper, lower and total strength, but the results remain unsystematic. The aim of this study was to systematize the current state of knowledge to test whether hand grip strength can be used as an indicator of overall strength and functional performance. A review of studies from 2000 to 2023 was conducted using: ScienceDirect, PubMed and GoogleScholar. The focus was on articles that examined the relationship between hand grip strength and muscle torque. The following keywords, entered in different configurations, were used in the search: ’hand grip’, ’muscle strength’, ’correlation’ and ’association’. A total of 22 studies were selected for analysis, involving 752 healthy adults, 30 physically active people, 120 ill adults, 2965 older people and 112 ill older people. The analysis looked at associations between hand grip strength and muscle moments of the trunk, limbs and knee joint. The results from the literature indicate that the value of the correlation between hand grip strength and muscle torque varies (from low to high) depending on the test method or group. Therefore, caution should be exercised when using hand grip strength as the sole measure of overall strength and functional performance.

The aim of this article is to present how to build a community consisting of the sighted people and of the blind. Dom Bożego Narodzenia in Niepołomice in Poland is an example of such a community, as its members – the sighted people and the blind – form a community modelled on the family. The community was created out of the religious inspiration and its building is in accordance to the Christian values. In order to realise the aim of this article, the author interviewed 10 community members (both the sighted and the blind). The received answers were subjected to quality research. The article presents the teaching of the Catholic Church which concerns the community life of people with disabilities and those fully able-bodied. The next step was to present the characteristics of the residents of the nursing home in Niepołomice. Building the community was presented in two dimensions: vertical and horizontal. The vertical dimension is connected with creating the community with God, and it is inspired by the Christian values in building the family relations. The horizontal dimension is connected with building the human community in its everyday life and in celebrating. Contribution: The research undertaken on the community well-being of people with visual disabilities has shown that such people are able to participate subjectively in building a home community similar to a family with sighted people.

Analyses of the economic activity of the Polish population indicate that in 2023, about 7% of all employees performed, usually or sometimes, their work in the form of remote work. The purpose of this publication is to analyze the impact of working with screen-monitor devices on computer vision syndromes, musculoskeletal disorders, circadian rhythm, and to identify recommendations for the proper organization of the home office. A narrative review of the existing literature on the impact of work with the use of devices equipped with screen monitors on the health of employees was performed, as well as recommendations in the above-mentioned area were presented. The most important factors determining the load on the visual organs and musculoskeletal system and affecting the overall health and well-being of employees during remote work are the proper arrangement of the workstation (in accordance with ergonomic principles) and the organization of work (limiting the time spent working at the computer/laptop, systematic active breaks) and healthy sleep habits. It is crucial that both employers, occupational health professionals and employees themselves are aware of the importance to their health of correct preparation of the home office, and have adequate knowledge in this regard. Med Pr Work Health Saf. 2024;75(1):69–80

This paper presents the outcomes of quality tests conducted on specimens, both smooth and V-notched, subjected to uniaxial tension, which were extracted from a gas transport pipeline. The introduction of the V-notch introduced variations in the stress and strain component fields near the plane of maximum constriction, consequently leading to their failure through different mechanisms. The process included the implementation of quality management practices such as numerical modeling and simulation of the loading of the specimens using ABAQUS. The material model employed in these calculations was defined and verified to ensure quality control. Subsequent to the numerical calculations, maps of the stress and strain component fields were generated, contributing to the quality assessment of the specimens. It was determined that the quality management process for the smooth specimen identifies the initiation of failure primarily due to the normal stress component in the central region of the plane with the largest constriction. In contrast, in the V-notched specimen, quality management efforts revealed that failure initiation occurs due to the tangential stress component, and failure proceeds through the shear mechanism. These results are valuable in developing a quality-driven methodology for monitoring the operational safety of gas network pipelines, primarily based on the analysis of acoustic emission signals.

Studies investigating the relationship between balance ability and body size, build and proportions tend to concentrate on body mass and height rather than breadth parameters or size of individual body segments. The purpose of this study was to determine a relationship between the ability to keep balance and the size, build and proportions, based on breadth and length dimensions of the body in healthy adult men and women during a position of free standing. This study also aimed to investigate how the lack of visual control affects the analyzed relationship. The study group consisted of 102 adults of both sexes. The investigations encompassed anthropometric measurements of the body and the ability to keep balance. The analysis covered a of series anthropometric parameters, 9 indices of body proportions, mean velocity of the COP movement (MV) and ellipse area (EA). A statistical analysis of the results was carried out taking into consideration the division into groups due to sexes. The results of the Pearson correlation have revealed that there is a statistically significant correlation (weak or moderate degree) between anthropometric parameters of the body and stabilographic values. Results differ between sexes and depend on whether Romberg’s test was performed with open or closed eyes. The obtained results showed that the surface area of ellipse significantly depends on the dimensions of these body elements which relate to the position of the centre of mass. The obtained results, which differ depending on sex, show that the values of the body sways in a position of free standing depend on breadth and length dimensions of the body, visual control and the analyzed parameter of balance.

The paper examines the convergence of tax systems in Central and Eastern European countries (CEECs) over the period 1995–2018. Due to the increasing impact of tax competition, we have focused on income taxes, in particular, corporate ones. We have identified the factors that influence the taxation system and trends in income taxation in the CEECs by adapting the hidden Markov model approach. We find that many CEECs have reduced income taxation in the analysis period, mainly by lowering tax rates. Corporate income taxes have also decreased in many CEECs in the same period; however, the reverse has been observed too. Both convergence and divergence have been identified among the CEECs over the period considered. The speed of these processes based on the used variables varied depending on both exogenous and endogenous factors. These factors have been diagnosed as being specific to the periods of tax reforms, i.e., before and after accession to the European Union (EU) and the global financial crisis.

Due to the complexity of the medical issues connected with cerebral palsy (CP), the classification of gait pathologies seems rather difficult. The aim of this study was to asses the usefulness of the Gait Kinematics Index (GKI) from a clinical point of view in the population of patients with CP. The assessment of the possibilities of using the GKI in a group of patients with CP was conducted on the basis of the correlation of its results with the Gillette Gait Index (GGI) and Gait Deviation Index (GDI) values. The distribution of the index values was also evaluated with attention paid to the CP types and treatment methods. Analyses were performed on the basis of the gait test results in a group of 56 healthy children and 72 patients with CP. The GKI values for patients with CP were 1.55 ± 0.66, as opposed to 0.77 ± 0.17 for the reference group. A strong linear correlation was found between the values of the GKI and GGI (r = 0.8 ÷ 0.85), as well as between the GKI and GDI (r = −0.89 ÷ 0.9), obtained in children with CP. In addition, significant differences were found between the results obtained in all the groups of children with CP divided by treatment method (rehabilitation, botulinum, rhizotomy, p < 0.05), whereas in the groups of children divided by CP type, significant differences (p < 0.05) were found solely between diplegia and hemiplegia and between hemiplegia and quadriplegia. The results obtained were the same in the case of the GKI, GGI and GDI. To conclude, the results presented in this work confirm the clinical utility of the GKI in the population of patients with CP.

Extremity trauma, including ischemia (e.g., prolonged tourniquet application or crush), is common among battlefield injuries. Injured muscle releases toxins leading to rhabdomyolysis and, potentially, acute kidney injury (AKI). The goal of this study was to characterize sequelae of ischemic extremity injury over 72 h, focusing on time courses of rhabdomyolysis and AKI. Male Sprague Dawley rats were placed into two groups. Ischemic injury was produced in anesthetized rats using bilateral tourniquets (TK; n = 10) for 5 h; control (CON; n = 9) rats were treated identically without TK application. Indicators of rhabdomyolysis and renal function were measured in conscious rats 1 day preinjury (baseline, BL) and then at 1.5, 24, 48, and 72 h post-TK release. Prolonged TK application produced necrosis in both muscle and bone marrow but not in kidney. The wet/dry weights indicated edema in injured limbs at 72 h (4.1 (0.5) (TK) vs. 2.9 (0.1) (CON); p < 0.001). TK rats exhibited a 100-fold increase in creatine kinase activity compared to CON at 1.5 h (20,040 (7265) U/L vs. 195 (86) U/L (mean (SD); p < 0.0001). TK decreased the mean glomerular filtration rate (GFR; p < 0.001) at 1.5 h, but these values recovered by 24 h in concert with elevated urinary flow and alkalinization. Prolonged ischemic extremity injury therefore produced severe rhabdomyolysis without irreversible renal damage.

The increasing prevalence of adult obesity is a major global health problem. Causes include sedentary lifestyles and physical inactivity, as well as the place and style of work. This work aimed to assess the impact of an increase in BMI, resulting from a sedentary lifestyle, on the functioning of the human musculoskeletal system during daily activities. Standing and sitting down were analyzed using numerical simulations in the AnyBody Modeling System. The results showed that by 2050, an increase in body weight will lead to an 11% increase in lumbar spine loads and up to 14% increase in knee and hip joint loads compared to 2015. Increased body weight will also increase muscle fatigue, requiring the body to exert more force to perform the same activities. The BMI change prediction model shows that the average man will be overweight or obese in the coming years, which will likely increase musculoskeletal loads.

In the age of globalisation, alternative forms of dispute resolution (ADR) are gaining new importance. In Poland, an increasing number of mediations and arbitrations in international (cross-border) cases are being observed. However, the number and importance of international ADR in Poland is much lower than in other European countries. Polish advocates and legal advisers, experienced in conducting international arbitration and mediation, explain the Polish specificity, genesis, and perspectives of ADR in international disputes. The comparison of lawyers’ experiences with the collected data thoroughly describes the state of out-of-court forms of dispute resolution in these types of situations. The study, based on interviews with Polish jurists, statistical data analysis, and an analysis of nonreactive materials, demonstrates the far-reaching deficiencies and problems of the Polish system of alternative dispute resolution in transnational cases.