Search

Abstract Background Muscle-infiltrating urothelial carcinoma of the bladder is the most common genitourinary cancer. Immunotherapeutic agents targeting protein-1 programmed death or protein-1 programmed death ligand are currently considered the standard treatment in patients with either inoperable locally advanced or metastatic urothelial carcinoma (MUC) after platinum-based chemotherapy failure. Case presentation Here we report the case of a Caucasian male patient with metastatic urothelial carcinoma treated with second-line atezolizumab within a trial who achieved complete response by computed tomography (CT), but suddenly died due to cardiac tamponade resulting from malignant pericardial infiltration. Histopathology confirmed this as the only site of disease progression. Conclusions Cardiovascular toxicity of atezolizumab was considered within differential diagnoses, however histopathological examination revealed progression of malignancy in the pericardium as the cause of the sudden death. This is the first published case report of a patient treated with second-line atezolizumab in whom the rare disease progression of pericardial infiltration was confirmed. Despite its rarity, the clinicians should always consider the possibility of pericardial metastases.

Abstract The complex shape of embryonic cartilage represents a true challenge for phenotyping and basic understanding of skeletal development. X-ray computed microtomography (μCT) enables inspecting relevant tissues in all three dimensions; however, most 3D models are still created by manual segmentation, which is a time-consuming and tedious task. In this work, we utilised a convolutional neural network (CNN) to automatically segment the most complex cartilaginous system represented by the developing nasal capsule. The main challenges of this task stem from the large size of the image data (over a thousand pixels in each dimension) and a relatively small training database, including genetically modified mouse embryos, where the phenotype of the analysed structures differs from the norm. We propose a CNN-based segmentation model optimised for the large image size that we trained using a unique manually annotated database. The segmentation model was able to segment the cartilaginous nasal capsule with a median accuracy of 84.44% (Dice coefficient). The time necessary for segmentation of new samples shortened from approximately 8 h needed for manual segmentation to mere 130 s per sample. This will greatly accelerate the throughput of μCT analysis of cartilaginous skeletal elements in animal models of developmental diseases.

The goal of this review was to provide an overview of how solitude has been operationally defined and measured since the year 2000 in psychological studies of children, adolescents, and emerging adults. After applying exclusionary criteria, our review of the extant literature identified n = 19 empirical studies, which we grouped into three broad methodological categories: (1) experiments/manipulations (n = 5); (2) retrospective reports (n = 7); and (3) experience sampling measures (experience sampling methodology; n = 7). A review of these studies indicated considerable variation in how solitude is operationalized and measured. There is also a notable lack of studies measuring solitude in childhood. Implications for ‘what matters’ when assessing solitude are discussed, and we provide a series of suggestions for helping this research area move forward.

Gnotobiotic (GN) animals with simple and defined microbiota can help to elucidate host-pathogen interferences. Hysterectomy-derived germ-free (GF) minipigs were associated at 4 and 24 h post-hysterectomy with porcine commensal mucinolytic Bifidobacterium boum RP36 (RP36) strain or non-mucinolytic strain RP37 (RP37) or at 4 h post-hysterectomy with Lactobacillus amylovorus (LA). One-week-old GN minipigs were infected with Salmonella Typhimurium LT2 strain (LT2). We monitored histological changes in the ileum, mRNA expression of Toll-like receptors (TLRs) 2, 4, and 9 and their related molecules lipopolysaccharide-binding protein (LBP), coreceptors MD-2 and CD14, adaptor proteins MyD88 and TRIF, and receptor for advanced glycation end products (RAGE) in the ileum and colon. LT2 significantly induced expression of TLR2, TLR4, MyD88, LBP, MD-2, and CD14 in the ileum and TLR4, MyD88, TRIF, LBP, and CD14 in the colon. The LT2 infection also significantly increased plasmatic levels of inflammatory markers interleukin (IL)-6 and IL-12/23p40. The previous colonization with RP37 alleviated damage of the ileum caused by the Salmonella infection, and RP37 and LA downregulated plasmatic levels of IL-6. A defined oligo-microbiota composed of bacterial species with selected properties should probably be more effective in downregulating inflammatory response than single bacteria.

The primary aim of the present study was to examine the potential moderating role of screen time in the links between shyness and indices of socio-emotional adjustment in young Chinese children. Participants were N = 211 children (112 boys, 99 girls) ages 43–66 months (M = 58.84 months, SD = 5.32) recruited from two public kindergartens in Shanghai, People’s Republic of China. Mothers completed assessments of children’s shyness and screen time, and both mothers and teachers completed measures of indices of children’s socio-emotional functioning (prosocial, internalizing problems, learning problems). Among the results, shyness was positively associated with internalizing problems and negatively associated with prosocial behavior, whereas screen time was positively associated with internalizing problems. However, several significant shyness × screen time interaction effects were observed. The pattern of these results consistently revealed that at higher levels of screen time, links between shyness and indices of socio-emotional difficulties were exacerbated. Results are discussed in terms of the implications of shyness and screen time in early childhood.

Analysis of T lymphocyte proliferation and activation after antigenic or mitogenic stimulation is a vital parameter used in the diagnosis of various immuno-deficiencies and during the monitoring of treatment responses. Most applied techniques are based on the incorporation of tritiated thymidine (3H-TdR) or ELISPOT analysis, both rely on rather time-consuming/-intensive ex vivo protocols or encompass inherent drawbacks such as the inability to distinguish specific cell populations (3H-TdR, ELISPOT) or focus on a single cytokine (ELISPOT). Here we aimed at characterizing the rapid expression of intracellular CD154 (CD40L) as a marker for rare antigen-specific CD4+ T cells in pemphigus vulgaris (PV). Upon stimulation with human desmoglein (Dsg) 3, the major autoantigen in PV, the expression of CD154 was significantly increased in PV patients compared to healthy controls (HC) and correlated with anti-Dsg3 IgG titers. Patients with active disease showed higher numbers of Dsg3-reactive CD4+ T cells in CXCR5+ T follicular helper cells. In remittent PV and HC, CXCR5+CD4+ T cells remained largely unaffected by Dsg3. IL-17 and IL-21 expression were significantly induced only in CD154+CD4+ T cells from PV patients, lending themselves as potential novel treatment targets. Additionally, stimulation with immunodominant Dsg3-derived epitopes strongly induced a CD4+ T cell response via CD40-CD154 interaction similar to the human Dsg3 protein. We here established a rapid ex vivo assay allowing the detection of Dsg3-reactive CD4+ T cells from activated systemically available PBMCs, which further supports the crucial concept of antigen-specific T cells in the pathogenesis of PV.

Abstract Background Patients with advanced disease may not be invited to participate in research based on the assumption that participation would be too burdensome for them. The aim of this study was to explore how patients with advanced disease and their relatives evaluate their experience with research participation. Method This study used data from two parts of a larger project. The first dataset was a cross-sectional questionnaire study focused on priorities at the end of life. The second dataset used a longitudinal design with structured interviews on prognostic awareness. In both studies, participants evaluated their experience on a 5-point Likert scale and specified their motivation in an open-ended question. Data were collected in 6 hospitals in the Czech Republic with patients with advanced disease and life expectancy less than 1 year and their relatives. Data were analysed using non-parametric tests and thematic analysis. Results First dataset consisted of 167 patients and 102 relatives, and second dataset consisted of 135 patients and 92 relatives (in total, 496 respondents). Results were similar in both datasets, with half of the sample (53%, 48%) scoring neutral, and over 30% of the sample identified their experience as interesting. The most significant factors associated with the evaluation were religiosity (p = 0.001) and the type of diagnosis (p = 0.04). Motivation for participation was to improve care, support research, express own opinion, opportunity to talk and trusting relationship. Conclusions Patients with advanced disease and relatives do not mind participating in palliative care research, and it can be even a positive experience for them.

Nanofibrous scaffolds offer significant promise for wound healing due to their ability to absorb exudates, prevent microbial contamination, and enhance oxygen diffusion. However, challenges remain in fully realizing their clinical potential, as previous research has primarily focused on scaffolds made of two polymers or those encapsulating therapeutic agents within nanofibers. Additionally, scaling up fabrication while maintaining functionality presents a significant challenge. This study introduces a novel type of nanofibrous scaffold, combining poly (ethylene oxide) (PEO), poly (caprolactone) (PCL), and chitosan (CS) in various mass ratios, electrospun using Nanospider™ technology. The scaffolds featured fiber diameters ranging from 134 ± 37 to 148 ± 38 nm and exhibit high gram-per-square-meter values between 6.8 and 8.6 g/m2. An optimal balance of hydrophilicity was achieved, and the scaffolds demonstrated superior breathability with moisture vapor transmission rates ranging from 1904.3 ± 28.6 to 2005.7 ± 42.9 g/m2/day, outperforming commercial wound dressings. Additionally, a wide range of hydrolytic degradation rates (3.8 ± 1% to 73.2 ± 0.8%), elongation at fracture (21% to 0.8%), and Young's modulus (106.7 ± 8.5 MPa to 170.7 ± 11.9 MPa) were observed. Surface-immobilized tetracycline (TET) significantly enhanced antibacterial efficacy, with inhibition zones exceeding 20 mm against Escherichia coli. Our findings confirm that scaffold properties can be effectively tailored by adjusting the PEO/PCL ratio, advancing customization for wound care. Post-fabrication soaking in TET solutions further boosts antibacterial performance and allows for tailored post-production adjustments. Compared to existing studies, this approach simplifies customization and improves the practicality of wound care solutions. [ABSTRACT FROM AUTHOR]

Background: Delivering serious news is usually challenging for healthcare professionals and the pandemic of COVID-19 and related restrictions brought additional challenges in this process. Aims: To explore the experience of bereaved relatives with receiving serious news from healthcare professionals during the pandemic COVID-19. Design: A qualitative study using thematic analysis and a codebook approach of data collected in semi-structured interviews with bereaved relatives. Setting/participants: Data were collected from July to August 2022 in person/via phone with bereaved relatives who lost their relatives during the pandemic (from March 2020 to March 2022). Participants were recruited using a convenience sample and snowball method through social media and through one university hospital palliative care unit that invited bereaved relatives of deceased patients treated at the unit to participate in this study. Results: A total of 22 participants, consisting of 4 men and 18 women, were interviewed for this study. Most of the participants were sons or daughters of individuals who had died (5 grandchildren, 14 sons/daughters, 2 spouses, 1 great-niece). Six themes were identified: Burden caused by visit ban, Fear of COVID-19, Inappropriate behaviour and communication of healthcare professionals, High need for emotional support, Need for detailed and honest communication, Tendency to make excuses for mistakes and lapses by healthcare professionals. Conclusions: Delivering serious news during a pandemic was negatively influenced by a lack of contact with patients and a lack of support and empathetic communication with staff. Overcoming these circumstances can be achieved by frequent communication using various communication tools (such as videoconferences or phone calls), and maintaining empathy and honesty in the communication process. Key message: This article describes results from a qualitative study with bereaved relatives focused on their experience with communication with physicians during the COVID-19 pandemic. Relatives lacked empathetic communication, they also experienced fear of getting infected and they tended to express understanding for the challenging circumstances faced by the healthcare staff. [ABSTRACT FROM AUTHOR]

This paper explores the perceptions of Gen Z students at different levels of English proficiency regarding the use of technology, particularly Neural Machine Translation (NMT) and ChatGPT, in second language acquisition. The research aims to understand how these technologies influence language learning and identify how these tools are used across varying proficiency levels. The significance of the study lies in its potential to inform educators and highlight the role of using technologies in language learning. Based on data collected from a survey of 151 students (ranging from A2 to C2 proficiency levels), the findings indicate that students across all proficiency levels actively engage with NMT and ChatGPT. Across all proficiency levels, NMT and ChatGPT are used primarily for word translation. However, higher proficiency students use ChatGPT for complex tasks (such as mistake correction or summary writing). Moreover, the study emphasizes the positive attitudes of Gen Z learners toward technology as a flexible and valuable educational resource. The motivation to use technology stems from the desire to learn new vocabulary, comprehend English content, and enjoy flexible learning. Therefore, the study recommends that educators adapt teaching strategies to include these technologies, considering the different proficiency levels of students. Future research should focus on the long-term impacts of technology use on language acquisition. [ABSTRACT FROM AUTHOR]

Background: To evaluate the outcomes of first‐line imatinib versus nilotinib treatment for chronic myeloid leukemia in the chronic phase (CML‐CP) in real‐world clinical practice. Methods: A propensity score analysis was performed to eliminate imbalances between the treatment groups. In the analysis, 163 patients in the nilotinib group and 163 patients in the matched imatinib group were retrospectively evaluated. Results: Nilotinib‐treated patients achieved complete cytogenetic response (CCyR) and major molecular response more rapidly than imatinib‐treated patients. However, there was no significant difference in 5‐year overall survival (OS) or progression‐free survival (PFS) between the two groups (OS: 94.3% vs. 90.5%, p = 0.602; PFS: 92.9% vs. 88.0%, p = 0.614). Nilotinib‐treated patients had a higher failure‐free survival (FFS) and event‐free survival (EFS) than imatinib‐treated patients (FFS: 71.7% vs. 54.3%, p = 0.040; EFS: 71.7% vs. 53.5%, p = 0.025). Conclusions: This retrospective analysis from clinical practice did not confirm any benefit of frontline nilotinib treatment for OS and PFS; however, it did demonstrate higher FFS and EFS in the nilotinib cohort. [ABSTRACT FROM AUTHOR]

For the design of façade and roof glazing, loads due to dead weight, climatic loads (IGU - pressure differences), wind and snow are well investigated and are considered in engineering practice. However, glass constructions are also ex-posed to thermally induced stresses due to direct solar irradiation. The standards and guidelines available so far, both nationally and at the European level, are partly outdated or contain only simplified instructions and specifications for calculating thermally induced stresses of façade and roof glazing. Within the research project, a variety of façade glazing configurations and additionally building-integrated (BIPV) glass-glass photovoltaic modules, for example as a façade cladding rear ventilated, are being investigated by means of numerical simulation and subsequent experimental validation with up-to-date German meteorological data. The purpose of the project is to reduce or prevent the occurrence of thermally induced glass breakage (thermal breakage) through European standardization. In this way, economic damage can be avoided. The present paper provides an insight into the two-years lasting joint research project, including the current status of science and technology, goals, structure and process, and descriptions of work packages. Results, such as the collection of the various influencing factors, meteorological data, and results from numerical simulations, will be presented after the project has finished at the end of September 2022.

Mobile devices and applications, which have become an integral part of our lives, are gradually used for different purposes, including learning languages in EFL classrooms. Since vocabulary plays an important role in the process of foreign language learning, the aim of this study was to explore the use of the vocabulary mobile learning application and its usefulness in blended English learning. Quantitative and qualitative approach to research was used, since the integration of both approaches created the possibility to solve complex research problem. The case study was based on the use of the developed mobile application called Angličtina Today the content of which corresponded to the language needs of the target group of students. The quantitative approach used a method of quasi-experiment aiming to achieve the pre-tests and post-test results of the students from the experimental and control groups. The results showed that the students facing blended learning, including mobile application in the process of language learning, achieved better results than the students exposed to the traditional, face-to-face education. In addition, the results revealed students’ overall satisfaction with the application. The main reasons for their satisfaction were improved vocabulary knowledge, ease of use, and enhanced motivation. Based on these findings from the current study, it can be argued that the vocabulary mobile learning application proved to be useful in the process of blended English language learning.

At present, emerging technologies, such as machine learning, deep learning, or various forms of artificial intelligence are penetrating different fields of education, including foreign language education (FLE). Moreover, the current young generation was born into the technological environment, and they perceive technologies as being an indispensable part of their everyday life. However, they mainly use technologies in their informal learning, but there is not much research into emerging technologies in FLE, namely in teaching and learning English as an applied language. Therefore, the purpose of this systematic review is to identify, bring together, compare and analyze all of the technologies that are currently efficiently employed in foreign language teaching and learning, and based on the findings of the detected experimental studies, we provide specific pedagogical implications on how to use these technologies in the acquisition of English as an applied language at the university level. The methodology followed the PRISMA guidelines for systematic reviews and meta-analyses. The results of the detected experimental studies revealed that there was a serious lack of the latest technologies, such as chatbots or virtual reality (VR) devices, that are being empirically employed in a foreign language (FL) education. Moreover, mobile apps are merely focused on the development of FL vocabulary. The findings also indicate that although the FL teachers might theoretically know about these latest technological devices, such as neural machine translation, they do not know how to practically implement them in their teaching process. Therefore, this research suggests that teachers must be trained and pedagogically guided on how to purposefully implement them in their FL classes to support traditional instruction in order to identify what skills or language structures could be developed through their use. In addition, it is also claimed that more experimental studies are needed to clearly the evidence and its usefulness in teaching a foreign language as an applied language.