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Abstract Background Renal cell cancer (RCC) is the most common and highly malignant subtype of kidney cancer. Mesenchymal stromal cells (MSCs) are components of tumor microenvironment (TME) that influence RCC progression. The impact of RCC-secreted small non-coding RNAs (sncRNAs) on TME is largely underexplored. Here, we comprehensively analysed the composition of exosomal sncRNAs secreted by RCC cells to identify those that influence MSCs. Methods Exosomal sncRNAs secreted by RCC cells and normal kidney cells were analyzed using RNAseq, followed by qPCR validation. MSCs were treated by conditioned media (CM) derived from RCC cells and transfected with piRNA, followed by the analysis of proliferation, viability, migration and immunocytochemical detection of piRNA. Expression of MSCs genes was evaluated using microarray and qPCR. TCGA data were analyzed to explore the expression of sncRNAs in RCC tumors. Results RNAseq revealed 40 miRNAs, 71 tRNAs and four piRNAs that were consistently secreted by RCC cells. qPCR validation using five independent RCC cell lines confirmed that expressions of miR-10b-3p and miR-125a-5p were suppressed, while miR-365b-3p was upregulated in exosomes from RCC cells when compared with normal kidney proximal tubules. The expression of miR-10b-3p and miR-125a-5p was decreased, whereas the expression of miR-365b-3p was increased in RCC tumors and correlated with poor survival of patients. Expressions of tRNA-Glu, tRNA-Gly, and tRNA-Val were the most increased, while tRNA-Gln, tRNA-Leu, and tRNA-Lys were top decreased in RCC exosomes when compared with normal kidney cells. Moreover, hsa_piR_004153, hsa_piR_016735, hsa_piR_019521, and hsa_piR_020365 were consistently upregulated in RCC exosomes. piR_004153 (DQ575660.1; aliases: hsa_piRNA_18299, piR-43772, piR-hsa-5938) was the most highly expressed in exosomes from RCC cells when compared with normal kidney cells. Treatment of MSCs with RCC CM resulted in upregulation of piR_004153 expression. Transfection of MSCs with piR_004153 stimulated their migration and viability, and altered expression of 35 genes, including downregulation of FGF2, SLC7A5, and WISP1. Immunocytochemistry confirmed the nuclear localization of piR_004153 transfected in MSCs. Conclusion RCC cells secrete multiple sncRNAs, including piR_004153 which targets MSCs, alters expression of FGF2, SLC7A5, and WISP1, and stimulates their motility and viability. To our knowledge, this is the first study showing that cancer-derived piRNA can enhance MSC migration. Graphical Abstract

BackgroundCytotoxic T lymphocyte–associated antigen-4 (CTLA-4) insufficiency is a rare disease belonging to inborn errors of immunity. Most cases of patients with CTLA-4 insufficiency are diagnosed in adults, therefore it is not a common problem in the clinical practice of pediatricians. However, it is worth noticing that most cases described in the literature show the first symptoms of the disease before the age of 18, but the phenotypic variability of patients complicates and delays the diagnostic process.Case descriptionHerein, we report a case of an almost 4-year-old patient whose first symptom of CTLA-4 insufficiency was thrombocytopenia after an upper respiratory tract infection, suggesting the diagnosis of primary immune thrombocytopenia, often occurring in pediatric patients. Due to the addition of symptoms suggesting a proliferative disease in this patient (pancytopenia, enlargement of lymph nodes, liver and spleen), a bone marrow biopsy was performed 11 months later, which did not confirm a hematopoietic tumor. Two years after the first symptoms appeared, the patient was referred for next-generation sequencing genetic testing, which confirmed the presence of a pathological CTLA-4 variant (c.356T>C). Due to the patient’s lack of response to the pharmacological treatment and the intensification of autoimmune symptoms that threatened the patient’s life, the patient underwent hematopoietic stem cell transplantation (HSCT) 34 months after the first occurrence of symptoms. After HSCT, the patient is alive and does not present any symptoms of autoimmunity.ConclusionsThe first symptoms of some diseases classified as inborn errors of immunity are non-specific and may delay the final diagnosis. Therefore, it seems extremely important that practicing pediatricians should take into account inborn errors of immunity in the differential diagnosis of autoimmune diseases.

Despite significant progress in the treatment of some types of cancer, high-grade gliomas (HGGs) remain a significant clinical problem. In the case of glioblastoma (GBM), the most common solid tumor of the central nervous system in adults, the average survival time from diagnosis is only 15–18 months, despite the use of intensive multimodal therapy. Chimeric antigen receptor (CAR)-expressing T cells, which have already been approved by the Food and Drug Administration for use in the treatment of certain hematologic malignancies, are a new, promising therapeutic option. However, the efficacy of CAR-T cells in solid tumors is lower due to the immunosuppressive tumor microenvironment (TME). Reprogramming the immunosuppressive TME toward a pro-inflammatory phenotype therefore seems particularly important because it may allow for increasing the effectiveness of CAR-T cells in the therapy of solid tumors. The following literature review aims to present the results of preclinical studies showing the possibilities of improving the efficacy of CAR-T in the TME of GBM by reprogramming the TME toward a pro-inflammatory phenotype. It may be achievable thanks to the use of CAR-T in a synergistic therapy in combination with oncolytic viruses, radiotherapy, or epigenetic inhibitors, as well as by supporting CAR-T cells crossing of the blood–brain barrier, normalizing impaired angiogenesis in the TME, improving CAR-T effector functions by cytokine signaling or by blocking/knocking out T-cell inhibitors, and modulating the microRNA expression. The use of CAR-T cells modified in this way in synergistic therapy could lead to the longer survival of patients with HGG by inducing an endogenous anti-tumor response.

Fungal infections constitute a significant challenge and continue to be a predominant cause of treatment failure in pediatric leukemia cases. Despite the implementation of antifungal prophylaxis, these infections contribute to approximately 20% of cases in children undergoing treatment for acute lymphoblastic leukemia (ALL). The aim of this study is to highlight the diagnostic and therapeutic challenges associated with invasive fungal infections (IFIs). We also present a review of the epidemiology, risk factors, treatment, and a clinical presentation of IFI in patients with ALL. This case report details the clinical course of confirmed Candida albicans (C. albicans) and Aspergillus spp. infections during the consolidation phase of ALL treatment in a 5-year-old pediatric patient. This male patient did not experience any complications until Day 28 of protocol II. Then, the patient’s condition deteriorated. Blood culture detected the growth of C. albicans. Despite the implementation of targeted therapy, the boy’s condition did not show improvement. The appearance of respiratory symptoms necessitated a computed tomography (CT) of the chest, which revealed multiple nodular densities atypical for C. albicans etiology. In spite of ongoing antifungal treatment, the lesions depicted in the CT scans showed no regression. A lung biopsy ultimately identified Aspergillus species as the source of the infection. Overcoming fungal infections poses a considerable challenge; therefore, an accurate diagnosis and the prompt initiation of targeted therapy are crucial in managing these infections in patients with leukemia.

Socially responsible investments are a significant element of the global capital market and are becoming increasingly important also in the eyes of Polish investors. ESG ratings are a crucial decisive criterion, as they provide information on the corporate governance (G), and social (S) and environmental (E) activities, of companies. Even though the abovementioned areas differ significantly, the use of ESG ratings by investors is often narrowed down to the total ESG score. Additionally, the literature does not provide unambiguous results on whether the impact of total score as well as the individual pillars of E, S and G on the accounting-based financial performance of companies is statistically significant, and positive or negative. Sparse academic studies concentrate mainly on highly developed markets and accounting-based measures of profitability, leaving aside emerging markets, like Poland, and the other main characteristics of financial performance, like liquidity, efficiency, or leverage. The aim of this paper is therefore to fill the above gap by identifying the dependence of ratings in E, S and G areas and the accounting-based financial performance of companies listed on the Warsaw Stock Exchange. Selected financial parameters and company quotations were taken from the Notoria Serwis SA database, while data on ESG ratings from Refinitiv Eikon were used to perform correlation analysis. The analysis covers the years 2013–2022. The findings indicate a significant positive bi-directional impact of corporate governance (G) and efficiency, as well as of controversies score and efficiency. A linkage has also been revealed between controversies score and profitability. However, the hypothesis of an unequivocally positive impact of ESG factors on financial results, or conversely of financial results on ESG aspects, should be rejected.

The way of disposing of rock mineral material has a significant impact on subsequent spontaneous vegetation succession, soil properties, and respiration. We compared seven spontaneously vegetated samples from a large (2 km2) borrow pit used to dispose of the byproducts of a hard coal mine with seven plots from four coal mine spoil heap piles. We used BIOLOG EcoPlates to assess the microbial catabolic activity of the substrate. The substrate in the borrow pit was characterized by higher water content and lower temperature compared to the heap pile substrate. The borrow pit had a more diverse plant community structure. Higher Rao’s quadratic entropy, functional richness, and functional divergence were also calculated from plant functional traits in borrow pit samples. Although borrow pit samples showed higher total microbial biomass, bacteria/fungi ratio, and gram+/gram− ratio, and heap pile samples showed higher soil enzymatic activity, microbial functional diversity, and catabolic activity, these differences were not significant. Soil respiration from the borrow pit substrate was two folds higher. The borrow pit method of disposing of rock mineral material can be suggested to speed up spontaneous vegetation succession. This research provides new insights into the effects of burying hard coal byproducts in borrow pits and offers guidance for the management of hard coal mining.

According to the World Health Organization, the improvement of people's health literacy is one of the fundamental public health challenges in the 21st century. The key issue in teaching health literacy is to develop critical thinking skills. As health literacy and critical thinking should be developed at school age, we reviewed teaching methods or educational interventions used in empirical studies focused on the development of critical thinking regarding health and implemented by teachers in preschools, primary schools, or secondary schools. We searched seven databases (Medline, Embase, Web of Science, ERIC, ProqQuest, PsycArticles, and CINAHL) from inception to 20 September 2023 for any type of empirical studies. Due to the heterogeneity in interventions and inadequate reporting of results, a descriptive synthesis of studies was performed in addition to quantitative analysis. Of the 15919 initial records, 115 studies were included in the review. Most of the educational interventions focused on lifestyle-related health issues such as substance use, sexual and reproductive health, and nutrition. The popularity of health issues changed over time and depended on the geographical context. Six dimensions that differentiated the teaching methods were identified: central teaching component, central educator, pupils' activity level, teaching context, educational materials, and significance of critical thinking. Many educational interventions did not address the development of critical thinking skills in a comprehensive manner, and the significance of critical thinking varied greatly. Interventions in which critical thinking had high and very high significance applied mainly problem-solving methods and involved pupils' activity. The evidence on the effectiveness of the teaching methods that develop critical thinking is limited because most articles failed to provide detailed information on the teaching methods or did not examine their effects. We recommend that a checklist is developed to facilitate a detailed description of health educational interventions and thus promoting their replicability. Study registration: The protocol of the review was registered in the OSF Registries on 13 January 2022 (doi: https://doi.org/10.17605/OSF.IO/46TEZ).

In this work, we are showing the results of the X- and Q-band electron magnetic resonance measurements of ultra-small Zn1−xMnxFe2O4 nanoparticles (ca. 8 nm) with a very narrow size distribution. The chosen synthetic route allows for precise structural modifications with a broad concentration range (x = 0, 0.2, 0.5, 0.8, 1). The crystal structure was evaluated by means of X-ray diffraction, while cell parameters were calculated using Rietveld refinement. EMR spectral studies indicated that the prepared nanoparticles were superparamagnetic. The linewidth of EMR signal for any ferrite material generally originates from two sources: (a) magnetic dipole–dipole interactions among particles and (b) interparticle superexchange interactions between magnetic ions through oxygen ions. Observed effects are more complex interactions than in pure zinc and manganese ferrites. As a result of the study, a relationship was observed between the composition of the material and the magnetic properties with striking antiferromagnetism and ferrimagnetism change. Hence, by structural modification of materials, the magnetic character (FM–AFM–FiM) can be controlled. [ABSTRACT FROM AUTHOR]

Background: Renal cell cancer (RCC) is the most common and highly malignant subtype of kidney cancer. Mesenchymal stromal cells (MSCs) are components of tumor microenvironment (TME) that influence RCC progression. The impact of RCC-secreted small non-coding RNAs (sncRNAs) on TME is largely underexplored. Here, we comprehensively analysed the composition of exosomal sncRNAs secreted by RCC cells to identify those that influence MSCs. Methods: Exosomal sncRNAs secreted by RCC cells and normal kidney cells were analyzed using RNAseq, followed by qPCR validation. MSCs were treated by conditioned media (CM) derived from RCC cells and transfected with piRNA, followed by the analysis of proliferation, viability, migration and immunocytochemical detection of piRNA. Expression of MSCs genes was evaluated using microarray and qPCR. TCGA data were analyzed to explore the expression of sncRNAs in RCC tumors. Results: RNAseq revealed 40 miRNAs, 71 tRNAs and four piRNAs that were consistently secreted by RCC cells. qPCR validation using five independent RCC cell lines confirmed that expressions of miR-10b-3p and miR-125a-5p were suppressed, while miR-365b-3p was upregulated in exosomes from RCC cells when compared with normal kidney proximal tubules. The expression of miR-10b-3p and miR-125a-5p was decreased, whereas the expression of miR-365b-3p was increased in RCC tumors and correlated with poor survival of patients. Expressions of tRNA-Glu, tRNA-Gly, and tRNA-Val were the most increased, while tRNA-Gln, tRNA-Leu, and tRNA-Lys were top decreased in RCC exosomes when compared with normal kidney cells. Moreover, hsa_piR_004153, hsa_piR_016735, hsa_piR_019521, and hsa_piR_020365 were consistently upregulated in RCC exosomes. piR_004153 (DQ575660.1; aliases: hsa_piRNA_18299, piR-43772, piR-hsa-5938) was the most highly expressed in exosomes from RCC cells when compared with normal kidney cells. Treatment of MSCs with RCC CM resulted in upregulation of piR_004153 expression. Transfection of MSCs with piR_004153 stimulated their migration and viability, and altered expression of 35 genes, including downregulation of FGF2, SLC7A5, and WISP1. Immunocytochemistry confirmed the nuclear localization of piR_004153 transfected in MSCs. Conclusion: RCC cells secrete multiple sncRNAs, including piR_004153 which targets MSCs, alters expression of FGF2, SLC7A5, and WISP1, and stimulates their motility and viability. To our knowledge, this is the first study showing that cancer-derived piRNA can enhance MSC migration. [ABSTRACT FROM AUTHOR]

Background: Cytotoxic T lymphocyte–associated antigen-4 (CTLA-4) insufficiency is a rare disease belonging to inborn errors of immunity. Most cases of patients with CTLA-4 insufficiency are diagnosed in adults, therefore it is not a common problem in the clinical practice of pediatricians. However, it is worth noticing that most cases described in the literature show the first symptoms of the disease before the age of 18, but the phenotypic variability of patients complicates and delays the diagnostic process. Case description: Herein, we report a case of an almost 4-year-old patient whose first symptom of CTLA-4 insufficiency was thrombocytopenia after an upper respiratory tract infection, suggesting the diagnosis of primary immune thrombocytopenia, often occurring in pediatric patients. Due to the addition of symptoms suggesting a proliferative disease in this patient (pancytopenia, enlargement of lymph nodes, liver and spleen), a bone marrow biopsy was performed 11 months later, which did not confirm a hematopoietic tumor. Two years after the first symptoms appeared, the patient was referred for next-generation sequencing genetic testing, which confirmed the presence of a pathological CTLA-4 variant (c.356T>C). Due to the patient's lack of response to the pharmacological treatment and the intensification of autoimmune symptoms that threatened the patient's life, the patient underwent hematopoietic stem cell transplantation (HSCT) 34 months after the first occurrence of symptoms. After HSCT, the patient is alive and does not present any symptoms of autoimmunity. Conclusions: The first symptoms of some diseases classified as inborn errors of immunity are non-specific and may delay the final diagnosis. Therefore, it seems extremely important that practicing pediatricians should take into account inborn errors of immunity in the differential diagnosis of autoimmune diseases. [ABSTRACT FROM AUTHOR]

For a long time, the uterus had been considered a sterile organ, meaning that under physiological conditions the uterus would not be colonized by bacteria. Based on available data, it may be concluded that the gut and uterine microbiome are related, and that the role of this microbiome is greater than expected. Despite being the most common pelvic neoplasms in women of reproductive age, uterine fibroids (UFs) are still poorly understood tumors whose etiology has not been fully determined. This systematic review presents the relationship between intestinal and uterine dysbiosis and uterine fibroids. A systematic review of three medical databases was carried out: the MEDLINE/PubMed, Scopus and Cochrane. In this study, 195 titles and abstracts were reviewed, including only original articles and clinical trials of uterine microbiome criteria. Finally, 16 studies were included to the analysis. In recent years, researchers dealing with reproduction in a broad sense have focused on the microbiome in various locations to study its role in the pathogenesis and, consequently, the prevention and treatment of diseases of the genital organ. Conventional microbial detection methods are not suitable for identifying bacteria, which are difficult to culture. Next-generation sequencing (NGS) provides an easier and faster and more informative analysis of bacterial populations. It seems that gut microbiota dysbiosis has the potential to be a risk factor for uterine fibroids or affect the disease process. Some changes were shown in many types of bacteria, such as Firmicutes, Proteobacteria, Actinobacteria and Verrucomicrobia detected in fecal samples in patients with uterine fibroids. In view of the few results on the link between the microbiome and uterine fibroids, further intensive studies in humans and animal models are necessary, including the possible use of different microbiome modulations in the prevention or treatment of uterine fibroids.

Phase 3 studies combining histone deacetylase inhibitors with bortezomib were hampered by gastrointestinal (GI) intolerance, which was not observed when combined with immunomodulatory drugs. This study is a single-center phase 2 study of panobinostat with lenalidomide and dexamethasone (FRD). Twenty-seven relapsed multiple myeloma patients were enrolled. Twenty-two patients (81%) were lenalidomide refractory and 9 (33%), 14 (52%), and 7 (26%) were refractory to pomalidomide, bortezomib, and carfilzomib, respectively. High-risk molecular findings were present in 17 (63%) patients. Responses included 2 complete responses (CRs), 4 very good partial responses (VGPRs), 5 partial responses (PRs), and 9 minimal responses (MRs) for an overall response rate of 41%, clinical benefit rate of 74%, and a disease control rate of 96%. The median progression-free survival (PFS) was 7.1 months. In the 22 lenalidomide-refractory patients, there were 1 CR, 4 VGPRs, 3 PRs, and 7 MRs, with a median PFS of 6.5 months. Median overall survival was not reached. Grade 3/4 toxicities were primarily hematologic. Gene expression profiling of enrollment tumor samples revealed a set of 1989 genes associated with short (

The aim of the paper is to reconstruct differences between the paleotopography and contemporary topography of the historic centre of Krakow city, Poland, during the last millennium. The paleotopography was reconstructed using published contour-line maps based on archaeological and geoengineering investigations and showing the roof of in situ fossil soil. The preliminary contour-line map represented a digital elevation model (DEM) base map. A DEM from aerial laser scanning (ALS DEM) shows the contemporary topography of Krakow city centre. The application of selected morphometric indices makes it possible to quantitatively describe changes in the spatial dimension with regard to altitude, relative heights, slope, and aspect classes. The analysis of the changes in the values of the elements of topography studied shows that, at the scale of the whole study area, a trend to flattening occurs, however this trend is locally balanced or overridden by an increase of surface unevenness.

Hypoxia-inducible factor 1 (HIF-1) may play a role in mammary gland development, milk production and secretion in mammals. Due to the limited number of scientific reports on the expression of HIF genes in colostrum cells, it was decided to examine the expression of HIF1A, HIF3A and EPAS1 in the these cells, collected from 35 patients who voluntarily agreed to provide their biological material for research, were informed about the purpose of the study and signed a consent to participate in it. The expression of HIF genes was assessed using qPCR. Additionally, the influence of clinical parameters (method of delivery, occurrence of stillbirths in previous pregnancies, BMI level before pregnancy and at the moment of delivery, presence of hypertension during pregnancy, presence of Escherichia coli in vaginal culture, iron supplement and heparin intake during pregnancy) on the gene expression was assessed, revealing statistically significant correlations. The expression of HIF1A was 3.5-fold higher in the case of patients with the presence of E. coli in vaginal culture (p = 0.041) and 2.5 times higher (p = 0.031) in samples from women who used heparin during pregnancy. Approximately 1.7-fold higher expression of the EPAS1 was observed in women who did not supplement iron during pregnancy (p = 0.046). To our knowledge, these are the first studies showing the relationship between HIF expression in cells from breast milk and the method of delivery and health condition of women giving birth. The assessment of HIF expression requires deeper examination in a larger study group, and the results of further studies will allow to determine whether HIF can become biomarkers in pregnancy pathology states. [ABSTRACT FROM AUTHOR]

Fungal infections constitute a significant challenge and continue to be a predominant cause of treatment failure in pediatric leukemia cases. Despite the implementation of antifungal prophylaxis, these infections contribute to approximately 20% of cases in children undergoing treatment for acute lymphoblastic leukemia (ALL). The aim of this study is to highlight the diagnostic and therapeutic challenges associated with invasive fungal infections (IFIs). We also present a review of the epidemiology, risk factors, treatment, and a clinical presentation of IFI in patients with ALL. This case report details the clinical course of confirmed Candida albicans (C. albicans) and Aspergillus spp. infections during the consolidation phase of ALL treatment in a 5-year-old pediatric patient. This male patient did not experience any complications until Day 28 of protocol II. Then, the patient's condition deteriorated. Blood culture detected the growth of C. albicans. Despite the implementation of targeted therapy, the boy's condition did not show improvement. The appearance of respiratory symptoms necessitated a computed tomography (CT) of the chest, which revealed multiple nodular densities atypical for C. albicans etiology. In spite of ongoing antifungal treatment, the lesions depicted in the CT scans showed no regression. A lung biopsy ultimately identified Aspergillus species as the source of the infection. Overcoming fungal infections poses a considerable challenge; therefore, an accurate diagnosis and the prompt initiation of targeted therapy are crucial in managing these infections in patients with leukemia. [ABSTRACT FROM AUTHOR]

Research background: An investment appraisal applies a single discount rate across all effects. However, this may be insufficient for heterogenous environmental impacts, mixing private and public goods as well as use and non-use values, where individuals may have multiple intertemporal preferences due to their duality to act as consumer or citizen.

The incidence and mortality due to neoplastic diseases have shown an increasing tendency over the years. Based on GLOBOCAN 2020 published by the International Agency for Research on Cancer (IARC), leukemias are the thirteenth most commonly diagnosed cancer in the world, with 78.6% of leukemia cases diagnosed in countries with a very high or high Human Development Index (HDI). Carcinogenesis is a complex process initiated by a mutation in DNA that may be caused by chemical carcinogens present in polluted environments and human diet. The IARC has identified 122 human carcinogens, e.g., benzene, formaldehyde, pentachlorophenol, and 93 probable human carcinogens, e.g., styrene, diazinone. The aim of the following review is to present the chemical carcinogens involved or likely to be involved in the pathogenesis of leukemia and to summarize the latest reports on the possibility of detecting these compounds in the environment or food with the use of electrochemical sensors.

Author(s): Monika Boberska [sup.1] , Karolina Zarychta [sup.1] , Nina Knoll [sup.2] , Jan Keller [sup.2] , Diana Hilda Hohl [sup.2] , Karolina Horodyska [sup.1] , Magdalena Kruk [sup.1] , [...], This study investigated whether maternal perceptions of child body mass status would predict child body mass index (BMI) z-score via two sets of sequential mediators: (1) four maternal practices promoting child energy expenditure and (2) children's energy expenditure behaviors. The data of N = 729 mother-child dyads were collected at baseline [T1; n = 495 at 7- to 8-month follow-up (T2)]. Mothers reported perceptions of child body mass status and maternal practices (T1); children reported sedentary screen use and physical activity (T1, T2). Child body mass was assessed objectively (T1, T2). Higher stimulation to be active (T1) was related to a lower child BMI z-score (T2) via higher levels of child physical activity (T2). Higher levels of monitoring of screen use (T1) were associated with higher child BMI z-score (T2) via lower levels of child physical activity (T2). Encouraging parents to stimulate their children to be active may be beneficial for children's weight maintenance.