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The results of experimental and numerical studies of plastic forming of sheets made of the difficult-to-deform Hastelloy X, a nickel-based alloy with a thickness of 1 mm, using layered elastomeric punches and steel dies, are presented in this publication. The elastomeric punches were characterized by hardness in the range of 50-90 Shore A, while the dies were made of 90MnCrV8 steel with a hardness of over 60 HRC. The principle of operating the stamping die was based on the Guerin method. The finite-element-based numerical modeling of the forming process for various configurations of polyurethane inserts was also carried out. The results obtained from numerical modeling were confirmed by the results of experimental tests. The drawpieces obtained through sheet forming were subjected to geometry tests using optical 3D scanning. The results confirmed that in the case of forming difficult-to-deform Hastelloy X, Ni-based alloy sheets, the hardness of the polyurethane inserts significantly affected the geometric quality of the obtained drawpieces. Significant nonuniform sheet metal deformations were also found, which may pose a problem in the process of designing forming tools and the technology of the plastic forming of Hastelloy X, Ni-based alloy sheets.

Uveal melanoma (UM), recognized as the most prevalent primary intraocular malignancy in adults, is primarily driven by mutations in the GNAQ and GNA11 genes. These genetic alterations are also implicated in other conditions, which exhibit distinct morphological characteristics. In this article, we investigate the role of GNAQ and GNA11 mutations across varied disorders (e.g., UM, skin blue nevi, and hemangiomas), emphasizing the shared pathogenic mechanisms that connect them despite their differing clinical manifestations. By investigating the molecular pathways affected by these mutations, we provide insights into the potential for targeted therapies that could address not only UM but also other disorders associated with GNAQ / GNA11 mutations. Moreover, we discuss the role of SOX10-positive perivascular cells that may be implicated in the complex pathophysiology of GNAQ/GNA11-related entities. Understanding the common molecular foundation of these conditions opens new ways for research and treatment opportunities, potentially leading to more effective, personalized therapeutic strategies.

Purpose: Chronic obstructive pulmonary disease (COPD) is a prevalent and preventable condition that typically worsens over time. Acute exacerbations of COPD significantly impact disease progression, underscoring the importance of prevention efforts. This observational study aimed to achieve two main objectives: (1) identify patients at risk of exacerbations using an ensemble of clustering algorithms, and (2) classify patients into distinct clusters based on disease severity., Methods: Data from portable medical devices were analyzed post-hoc using hyperparameter optimization with Self-Organizing Maps (SOM), Density-Based Spatial Clustering of Applications with Noise (DBSCAN), Isolation Forest, and Support Vector Machine (SVM) algorithms, to detect flare-ups. Principal Component Analysis (PCA) followed by KMeans clustering was applied to categorize patients by severity., Results: 25 patients were included within the study population, data from 17 patients had the required reliability. Five patients were identified in the highest deterioration group, with one clinically confirmed exacerbation accurately detected by our ensemble algorithm. Then, PCA and KMeans clustering grouped patients into three clusters based on severity: Cluster 0 started with the least severe characteristics but experienced decline, Cluster 1 consistently showed the most severe characteristics, and Cluster 2 showed slight improvement., Conclusion: Our approach effectively identified patients at risk of exacerbations and classified them by disease severity. Although promising, the approach would need to be verified on a larger sample with a larger number of recorded clinically verified exacerbations., (© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Introduction: The term "post-COVID-19 syndrome" describes a range of symptoms persisting beyond the acute phase of the disease. These symptoms predominantly include fatigue, muscle pain, shortness of breath, and psychological issues. Research additionally suggests the possibility of long-term neurological and psychiatric impairment associated with COVID-19., Methodology: The study included patients who visited the post-COVID outpatient clinic between April 2020 and June 2022. The examination included the detailed history taking, including the COVID-19 course, posteroanterior chest X-ray and pulmonary function tests. Anxiety level was assessed using the Beck Anxiety Inventory (BAI). The relationship between anxiety, demographic data, and course of the disease, need for hospital admission during the acute phase, oxygen therapy, post-inflammatory changes on the chest X-ray and lung function parameters was investigated., Results: This study included 1756 patients who experienced COVID-19 and visited a post-COVID outpatient clinic. The majority of individuals experienced a mild form of the infection. The results showed that younger age and female gender were associated with significantly higher anxiety scores. Inpatients had lower BAI values than those who were not hospitalized during acute phase. Patients with post-inflammatory changes on chest X-ray had surprisingly lower BAI values. Lower values of FEV1 (forced expiratory volume in 1 second), DLCO (diffusing capacity of the lungs for carbon monoxide), and KCO (carbon monoxide transfer coefficient) were associated with significantly higher BAI values. Female gender was associated with higher levels of anxiety. In contrast, higher FEV1 values reduced the risk of a pathological level of anxiety., Conclusion: In our study, the influence of age, gender, inpatient care during the acute phase of infection, the presence of post-inflammatory changes on the chest diagram and selected parameters of lung function (FEV1, DLCO, and KCO) were shown to be important factors in the assessment of anxiety symptoms in post-COVID patients., Competing Interests: The authors declare no conflicts of interest in this work., (© 2024 Bocek et al.)

Uveal melanoma (UM) is the most common primary intraocular tumor in adults, with no standardized treatment for advanced disease. Based on preliminary bioinformatical analyses DTYMK and PARP1 were selected as potential therapeutic targets. High levels of both proteins were detected in uveal melanoma cells and correlated with increased tumor growth and poor prognosis. In vitro tests on MP41 (BAP1 positive) and MP46 (BAP1 negative) cancer cell lines using inhibitors pamiparib (PARP1) and Ymu1 (DTYMK) demonstrated significant cytotoxic effects. Combined treatment had synergistic effects in MP41 and additive in MP46 cell lines, reducing cell proliferation and inhibiting the mTOR signaling pathway. Furthermore, the applied inhibitors in combination decreased cell motility and migration speed, especially for BAP1-negative cell lines. Our hypothesis of the double hit into tumoral DNA metabolism as a possible therapeutic option in uveal melanoma was confirmed since combined targeting of DTYMK and PARP1 affected all tested cytophysiological parameters with the highest efficiency. Our in vitro findings provide insights into novel therapeutic avenues for managing uveal melanoma, warranting further exploration in preclinical and clinical settings.

The global prevalence of overweight and obesity is a significant public health concern that also largely affects women of childbearing age. Human epidemiological studies indicate that prenatal exposure to excessive maternal weight or excessive gestational weight gain is linked to various neurodevelopmental disorders in children, including attention deficit hyperactivity disorder, autism spectrum disorder, internalizing and externalizing problems, schizophrenia, and cognitive/intellectual impairment. Considering that inadequate maternal body mass can induce serious disorders in offspring, it is important to increase efforts to prevent such outcomes. In this paper, we review human studies linking excessive maternal weight and the occurrence of mental disorders in children., (© 2024. The Author(s).)

Aim: Schizophrenia involves complex interactions between biological and environmental factors, including childhood trauma, cognitive impairments, and premorbid adjustment. Predicting its severity and progression remains challenging. Biomarkers like glial cell line-derived neurotrophic factor (GDNF) and miRNA-29a may bridge biological and environmental aspects. The goal was to explore the connections between miRNAs and neural proteins and cognitive functioning, childhood trauma, and premorbid adjustment in the first episode of psychosis (FEP)., Method: This study included 19 FEP patients who underwent clinical evaluation with: the Childhood Trauma Questionnaire (CTQ), the Premorbid Adjustment Scale (PAS), the Positive and Negative Syndrome Scale (PANSS), and the Montreal Cognitive Assessment Scale (MoCA). Multiplex assays for plasma proteins were conducted with Luminex xMAP technology. Additionally, miRNA levels were quantitatively determined through RNA extraction, cDNA synthesis, and RT-qPCR on a 7500 Fast Real-Time PCR System., Results: Among miRNAs, only miR-29a-3p exhibited a significant correlation with PAS-C scores (r = -0.513, p = 0.025) and cognitive improvement (r = -0.505, p = 0.033). Among the analyzed proteins, only GDNF showed correlations with MoCA scores at the baseline and after 3 months (r = 0.533, p = 0.0189 and r = 0.598, p = 0.007), cognitive improvement (r = 0.511, p = 0.025), and CTQ subtests. MIF concentrations correlated with the PAS-C subscale (r = -0.5670, p = 0.011)., Conclusion: GDNF and miR-29a-3p are promising as biomarkers for understanding and addressing cognitive deficits in psychosis. This study links miRNA and MIF to premorbid adjustment and reveals GDNF's unique role in connection with childhood trauma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Szwajca, Kazek, Śmierciak, Mizera, Pomierny-Chamiolo, Szwajca, Biesaga and Pilecki.)

Rationale: Persistent respiratory symptoms following Coronavirus Disease 2019 (COVID-19) are associated with residual radiological changes in lung parenchyma, with a risk of development into lung fibrosis, and with impaired pulmonary function. Previous studies hinted at the possible efficacy of corticosteroids (CS) in facilitating the resolution of post-COVID residual changes in the lungs, but the available data is limited., Aim: To evaluate the effects of CS treatment in post-COVID respiratory syndrome patients., Patients and Methods: Post-COVID patients were recruited into a prospective single-center observational study and scheduled for an initial (V1) and follow-up visit (V2) at the Department of Respiratory Medicine and Tuberculosis, University Hospital Olomouc, comprising of pulmonary function testing, chest x-ray, and complex clinical examination. The decision to administer CS or maintain watchful waiting (WW) was in line with Czech national guidelines., Results: The study involved 2729 COVID-19 survivors (45.7% male; mean age: 54.6). From 2026 patients with complete V1 data, 131 patients were indicated for CS therapy. These patients showed significantly worse radiological and functional impairment at V1. Mean initial dose was 27.6 mg (SD ± 10,64), and the mean duration of CS therapy was 13.3 weeks (SD ± 10,06). Following therapy, significantly better improvement of static lung volumes and transfer factor for carbon monoxide (DLCO), and significantly better rates of good or complete radiological and subjective improvement were observed in the CS group compared to controls with available follow-up data (n = 894)., Conclusion: Better improvement of pulmonary function, radiological findings and subjective symptoms were observed in patients CS compared to watchful waiting. Our findings suggest that glucocorticoid therapy could benefit selected patients with persistent dyspnea, significant radiological changes, and decreased DLCO., (© 2023. The Author(s).)