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Abstract Background The BCR::ABL1 is a hallmark of chronic myeloid leukemia (CML) and is also found in acute lymphoblastic leukemia (ALL). Most genomic breaks on the BCR side occur in two regions - Major and minor - leading to p210 and p190 fusion proteins, respectively. Methods By multiplex long-distance PCR or next-generation sequencing technology we characterized the BCR::ABL1 genomic fusion in 971 patients (adults and children, with CML and ALL: pediatric ALL: n = 353; pediatric CML: n = 197; adult ALL: n = 166; adult CML: n = 255 patients) and designed “Break-App” web tool to allow visualization and various analyses of the breakpoints. Pearson’s Chi-Squared test, Kolmogorov-Smirnov test and logistic regression were used for statistical analyses. Results Detailed analysis showed a non-random distribution of breaks in both BCR regions, whereas ABL1 breaks were distributed more evenly. However, we found a significant difference in the distribution of breaks between CML and ALL. We found no association of breakpoints with any type of interspersed repeats or DNA motifs. With a few exceptions, the primary structure of the fusions suggests non-homologous end joining being responsible for the BCR and ABL1 gene fusions. Analysis of reciprocal ABL1::BCR fusions in 453 patients showed mostly balanced translocations without major deletions or duplications. Conclusions Taken together, our data suggest that physical colocalization and chromatin accessibility, which change with the developmental stage of the cell (hence the difference between ALL and CML), are more critical factors influencing breakpoint localization than presence of specific DNA motifs.

Background: Placenta accreta spectrum (PAS) is a clinical entity significantly increasing the risk of a peripartum hemorrhage. Various surgical methods have been described in the literature, which aim to reduce the risk of bleeding, although they often lack reproducibility and have been performed on low numbers of patients. The aim of this study was to evaluate the use of the Foley catheter as a cervical tourniquet during cesarean sections, in patients with PAS. Methods: All patients who underwent peripartum hysterectomy due to PAS in a large single-center registry were included in the present analysis. The general demographics and clinical characteristics of all participants, including blood loss, and maternal and fetal outcomes, were collected and analyzed. Results: Twelve participants were included. The mean blood loss was 1200 ± 760 ml during operation and the mean ± SD procedural duration was 89 ± 17 min. The median (Q1–Q3) length of hospital stay post-procedurally was 5 (4–6) days. None of the patients required subsequent urgent surgical procedures after hysterectomy. The median (Q1–Q3) packed red blood cell units transfused in our cohort was 2 (0–3). Conclusion: Using the Foley catheter as a tourniquet might be an effective method of excessive bleeding prevention in patients with PAS during peripartum hysterectomy.

One of the most perilous complications in obstetrics, often leading to severe bleeding and sometimes a need for urgent hysterectomy, is placenta accreta spectrum, which significantly increases the risk of peri-partum complications, even including the risk of death for the mother and the child. Dealing with excessive bleeding in this situation is paramount. We have found a Foley catheter tourniquet to be useful as a temporary tourniquet to control placental and uterine hemorrhage. We have used this method and find it very useful. In this publication, we describe the last two cases of the use of the Foley catheter as a tourniquet for peri-partum hemorrhage prevention, and we will present a review of the literature in this field.

This study determined the measurable factor responsible for the high rate performance of lithium titanium oxide (Li4Ti5O12, LTO) powders in lithium-ion batteries. The structural and morphological properties of various Li4Ti5O12 materials and their correlation with electrochemical performance were analysed. The results showed that there was a strong correlation between high capacity retention at 10 C and the specific surface area. Other electrochemical and structural factors, such as the crystal size and pore structure, were not correlated with 10 C performance. We found that an increase in the specific surface area of Li4Ti5O12 above c.a. 15 m2 g−1 neither improved the high rate capacity retention nor its specific discharge capacity at high current rates. We also showed that the sol–gel synthesized lithium titanium oxide powders could retain similar or higher discharge specific capacities than materials synthesized via more complex routes.

Nowadays, the transformations of metropolises into smart cities is a crucial factor in improving the living conditions of the inhabitants. The goal of the smart city concept is modern urban management using technical tools that offer state-of-the-art technologies, considering the applicable ecological standards while saving resources and achieving the expected results. The purpose of this article is to identify the areas of research analysed in the international literature in the field of smart cities. The bibliometric analysis was carried out to achieve the purpose. The analysis covered publications on smart cities published in Scopus and Web of Science databases from January 2009 to May 2019. Based on the bibliometric analysis, a bibliometric map was developed using the mapping technique VOS — the visualisation of similarities. Original clusters were created using the VOSviewer software. The bibliometric map visualises the results of the analysis that targeted the word coexistence.

Recently, we described B-cell precursor acute lymphoblastic leukemia (BCP-ALL) subtype with early switch to the monocytic lineage and loss of the B-cell immunophenotype, including CD19 expression. Thus far, the genetic background has remained unknown. Among 726 children consecutively diagnosed with BCP-ALL, 8% patients experienced switch detectable by flow cytometry (FC). Using exome and RNA sequencing, switch was found to positively correlate with three different genetic subtypes: PAX5-P80R mutation (5 cases with switch out of 5), rearranged DUX4 (DUX4r; 30 cases of 41) and rearranged ZNF384 (ZNF384r; 4 cases of 10). Expression profiles or phenotypic patterns correlated with genotypes, but within each genotype they could not identify cases who subsequently switched. If switching was not taken into account, the B-cell-oriented FC assessment underestimated the minimal residual disease level. For patients with PAX5-P80R, a discordance between FC-determined and PCR-determined MRD was found on day 15, resulting from a rapid loss of the B-cell phenotype. Discordance on day 33 was observed in all the DUX4r, PAX5-P80R and ZNF384r subtypes. Importantly, despite the substantial phenotypic changes, possibly even challenging the appropriateness of BCP-ALL therapy, the monocytic switch was not associated with a higher incidence of relapse and poorer prognosis in patients undergoing standard ALL treatment.

Modern technology offers an increasing number of tools for teaching mathematics, but technology adoption in schools encounters many barriers. The Technology Acceptance Model explains that technology usage is dependent on intentions, which rest on perceived ease of use and perceived usefulness. Less is known about the relationship between intentions and actual behavior. In the current study we show that the level of cognitive investment on the part of the teachers, captured by the construct of Need for Cognition (NC), is crucial in the use of technology in mathematical instruction, while controlling for a variety of background factors. Furthermore NC moderates the relationship between intentions and technology use, such that high NC weakens the relationship between the perceived usefulness of technology in pedagogy and its actual use.

Despite improving cure rates in childhood acute lymphoblastic leukemia (ALL), therapeutic side effects and relapse are ongoing challenges. These can also affect the central nervous system (CNS). Our aim was to identify germline gene polymorphisms that influence the risk of CNS events. Sixty single nucleotide polymorphisms (SNPs) in 20 genes were genotyped in a Hungarian non-matched ALL cohort of 36 cases with chemotherapy related acute toxic encephalopathy (ATE) and 544 controls. Five significant SNPs were further analyzed in an extended Austrian-Czech-NOPHO cohort (n = 107 cases, n = 211 controls) but none of the associations could be validated. Overall populations including all nations’ matched cohorts for ATE (n = 426) with seizure subgroup (n = 133) and posterior reversible encephalopathy syndrome (PRES, n = 251) were analyzed, as well. We found that patients with ABCB1 rs1045642, rs1128503 or rs2032582 TT genotypes were more prone to have seizures but those with rs1045642 TT developed PRES less frequently. The same SNPs were also examined in relation to ALL relapse on a case-control matched cohort of 320 patients from all groups. Those with rs1128503 CC or rs2032582 GG genotypes showed higher incidence of CNS relapse. Our results suggest that blood-brain-barrier drug transporter gene-polymorphisms might have an inverse association with seizures and CNS relapse.

ERG-deletions occur recurrently in acute lymphoblastic leukemia, especially in the DUX4-rearranged subtype. The ERG-deletion was shown to positively impact prognosis of patients with IKZF1-deletion and its presence precludes assignment into IKZF1plus group, a novel high-risk category on AIEOP-BFM ALL trials. We analyzed the impact of different methods on ERG-deletion detection rate, evaluated ERG-deletion as a potential marker for DUX4-rearranged leukemia, studied its associations with molecular and clinical characteristics within this leukemia subtype, and analyzed its clonality. Using single-nucleotide-polymorphism array, genomic polymerase chain reaction (PCR) and amplicon-sequencing we found ERG-deletion in 34% (16 of 47), 66% (33 of 50) and 78% (39 of 50) of DUX4-rearranged leukemia, respectively. False negativity of ERG-deletion by single-nucleotide-polymorphism array caused IKZF1plus misclassification in 5 patients. No ERG-deletion was found outside the DUX4-rearranged cases. Within DUX4-rearranged leukemia, the ERG-deletion was associated with higher total number of copy-number aberrations, and, importantly, the ERG-deletion positivity by PCR was associated with better outcome [5-year event-free survival (EFS), ERG-deletion-positive 93% vs. ERG-deletion-negative 68%, P=0.022; 5-year overall survival (OS), ERG-deletion-positive 97% vs. ERG-deletion-negative 75%, P=0.029]. Ultra-deep amplicon-sequencing revealed distinct co-existing ERG-deletions in 22 of 24 patients. In conclusion, our data demonstrate inadequate sensitivity of single-nucleotide-polymorphism array for ERG-deletion detection, unacceptable for proper IKZF1plus classification. Even using more sensitive methods (PCR/amplicon-sequencing) for its detection, ERG-deletion is absent in 22-34% of DUX4-rearranged leukemia and does not represent an adequately sensitive marker of this leukemia subtype. Importantly, the ERG-deletion potentially stratifies the DUX4-rearranged leukemia into biologically/clinically distinct subsets. Frequent polyclonal pattern of ERG-deletions shows that late origin of this lesion is more common than has been previously described.

Novel biological subtypes and clinically important genetic aberrations (druggable lesions, prognostic factors) have been described in B-other acute lymphoblastic leukemia (ALL) during the last decade; however, due to a lack of studies on unselected cohorts, their population frequency and mutual associations still have to be established. We studied 110 consecutively diagnosed and uniformly treated childhood B-other patients using single nucleotide polymorphism arrays and whole exome/transcriptome sequencing. The frequency of DUX4-rearranged, BCR-ABL1-like, ZNF384-rearranged, ETV6-RUNX1-like, iAMP21 and MEF2D-rearranged subtypes was 27%, 15%, 5%, 5%, 4%, and 2%, respectively; 43% of cases were not classified into any of these subtypes (B-rest). We found worse early response to treatment in DUX4-rearranged leukemia and a strong association of ZNF384-rearranged leukemia with B-myeloid immunophenotype. Of the druggable lesions, JAK/STAT-class and RAS/RAF/MAPK-class aberrations were found in 21% and 43% of patients, respectively; an ABL-class aberration was found in one patient. A recently described negative prognostic factor, IKZF1plus, was found in 14% of patients and was enriched in (but not exclusive for) BCR-ABL1-like subtype. PAX5 fusions (including 4 novel), intragenic amplifications and P80R mutations were mutually exclusive and only occurred in the B-rest subset, altogether accounting for 20% of the B-other group. PAX5 P80R was associated with a specific gene expression signature, potentially defining a novel leukemia subtype. Our study shows unbiased European population-based frequencies of novel ALL subtypes, recurrent (cyto)genetic aberrations and their mutual associations. This study also strengthens and widens the current knowledge of B-other ALL and provides an objective basis for optimization of current genetic diagnostics.

This paper is focused on the determination of the physicochemical properties of a composite inorganic–organic modified membrane. The electrical conductivity of a family of glassy protonic electrolytes defined by the general formula (P2O5)x(SiO2)y, where x/y is 3/7 are studied by Alternating Current electrochemical impedance spectroscopy (AC EIS) method. The reference glass was doped with polymeric additives—poly(ethylene oxide) (PEO) and poly(vinyl alcohol) (PVA), and additionally with a titanium-oxide-based filler. Special attention was paid to determination of the transport properties of the materials thus modified in relation to the charge transfer phenomena occurring within them. The electrical conductivities of the ‘dry’ material ranged from 10−4 to 10−9 S/cm, whereas for ‘wet’ samples the values were ~10−3 S/cm. The additives also modified the pore space of the samples. The pore distribution and specific surface of the modified glassy systems exhibited variation with changes in electrolyte chemical composition. The mechanical properties of the samples were also examined. The Young’s modulus and Poisson’s ratio were determined by the continuous wave technique (CWT). Based on analysis of the dispersion of the dielectric losses, it was found that the composite samples exhibit mixed-type proton mobility with contributions related to both the bulk of the material and the surface of the pore space.

The potential therapeutic applications of mesenchymal stem/stromal cells (MSCs) and biomaterials have attracted a great amount of interest in the field of biomedical engineering. MSCs are multipotent adult stem cells characterized as cells with specific features, e.g., high differentiation potential, low immunogenicity, immunomodulatory properties, and efficient in vitro expansion ability. Human umbilical cord Wharton’s jelly-derived MSCs (hUC-MSCs) are a new, important cell type that may be used for therapeutic purposes, i.e., for autologous and allogeneic transplantations. To improve the therapeutic efficiency of hUC-MSCs, novel biomaterials have been considered for use as scaffolds dedicated to the propagation and differentiation of these cells. Nowadays, some of the most promising materials for tissue engineering include graphene and its derivatives such as graphene oxide (GO) and reduced graphene oxide (rGO). Due to their physicochemical properties, they can be easily modified with biomolecules, which enable their interaction with different types of cells, including MSCs. In this study, we demonstrate the impact of graphene-based substrates (GO, rGO) on the biological properties of hUC-MSCs. The size of the GO flakes and the reduction level of GO have been considered as important factors determining the most favorable surface for hUC-MSCs growth. The obtained results revealed that GO and rGO are suitable scaffolds for hUC-MSCs. hUC-MSCs cultured on: (i) a thin layer of GO and (ii) an rGO surface with a low reduction level demonstrated a viability and proliferation rate comparable to those estimated under standard culture conditions. Interestingly, cell culture on a highly reduced GO substrate resulted in a decreased hUC-MSCs proliferation rate and induced cell apoptosis. Moreover, our analysis demonstrated that hUC-MSCs cultured on all the tested GO and rGO scaffolds showed no alterations of their typical mesenchymal phenotype, regardless of the reduction level and size of the GO flakes. Thus, GO scaffolds and rGO scaffolds with a low reduction level exhibit potential applicability as novel, safe, and biocompatible materials for utilization in regenerative medicine.

Graphene (GN) and its derivatives (rGOs) show anticancer properties in glioblastoma multiforme (GBM) cells in vitro and in tumors in vivo. We compared the anti-tumor effects of rGOs with different oxygen contents with those of GN, and determined the characteristics of rGOs useful in anti-glioblastoma therapy using the U87 glioblastoma line. GN/ExF, rGO/Term, rGO/ATS, and rGO/TUD were structurally analysed via transmission electron microscopy, Raman spectroscopy, FTIR, and AFM. Zeta potential, oxygen content, and electrical resistance were determined. We analyzed the viability, metabolic activity, apoptosis, mitochondrial membrane potential, and cell cycle. Caspase- and mitochondrial-dependent apoptotic pathways were investigated by analyzing gene expression. rGO/TUD induced the greatest decrease in the metabolic activity of U87 cells. rGO/Term induced the highest level of apoptosis compared with that induced by GN/ExF. rGO/ATS induced a greater decrease in mitochondrial membrane potential than GN/ExF. No significant changes were observed in the cytometric study of the cell cycle. The effectiveness of these graphene derivatives was related to the presence of oxygen-containing functional groups and electron clouds. Their cytotoxicity mechanism may involve electron clouds, which are smaller in rGOs, decreasing their cytotoxic effect. Overall, cytotoxic activity involved depolarization of the mitochondrial membrane potential and the induction of apoptosis in U87 glioblastoma cells.

A one-step real-time RT-PCR assay (RT-qPCR) with melting curve analysis, using the green fluorescence dye SYBR Green I, was developed to detect and quantify RNA targets from Apple mosaic virus (ApMV), Apple stem grooving virus (ASGV), Apple stem pitting virus (ASPV) and Apple chlorotic leaf spot virus (ACLSV) in infected apple trees. Single PCR products of 87 bp (ApMV), 70 bp (ASGV), 104 bp (ASPV) and 148 bp (ACLSV) were obtained, and melting curve analyses revealed distinct melting temperature peaks for each virus. A dilution series using in vitro synthesized transcripts containing the target sequences as standards yielded a reproducible quantitative assay, with a wide dynamic range of detection and low coefficients of variance. The content of selected viruses in apple plant tissues was stable throughout the year, and their accumulation did not significantly change between different plant tissues. The only minor exceptions were for ApMV and ACLSV, in which noticeable differences in their concentrations in various biological material were observed within the year. This divergence did not influence their year-round detectability. This one-step RT-qPCR assay is a valuable tool for year-round diagnostics, and molecular studies of the biology of ApMV, ASGV, ASPV and ACLSV.

Apple mosaic, rose mosaic, plum and birch line pattern, horse chestnut yellow mosaic, and hazel mosaic are some of many diseases caused by one of the longest-known pome fruit viruses: Apple mosaic virus. The worldwide distribution of Apple mosaic virus and its negative impacts on fruit, nut and hop production are sufficient to cause international interest. This review endeavors to piece together all known information about the virus. We describe taxonomic position, virion structure, the host range and symptoms, modes of transmission and diagnostics for the virus, as well as distribution and control of the diseases it causes.

Climate anxiety discourse focuses predominantly on individualised and potentially mentally disturbing aspects of emotional responses to the awareness of climate change which can silence the mobilising charge of strong emotions in response to climate change. We critically examine this perspective and explore the range, context, and perceived effects of emotional responses to climate change based on 33 in-depth interviews with people self-identified as highly concerned about this issue in the context of oil-wealthy Norway. Thematic analysis revealed that lived emotional experience of concern about climate change is characterised by a complex palette of co-occurring and dynamically linked emotions reported in relation to 16 evocative themes. We analyse the perceived effects of these emotions focusing on five areas: participants' mood and wellbeing, concerns about existing and hypothetical children, feelings of alienation, responsibility for the climate situation, and positive experience in the context of climate change. We discuss the psychological, social and political implications of participants' emotional experience, considering the Norwegian context, and we conclude that it goes beyond potentially debilitating and paralysing feelings, and includes politically charged moral anger and collective guilt, as well as love for nature, and a sense of community around collective climate action. • We critically reflect on the notion of "climate anxiety" • We conduct in-depth interviews with highly concerned people in the privileged context of oil-wealthy Norway • Participants reported experiencing a complex palette of emotions in relation to 16 evocative themes • Beyond fear and grief, participants reported also, e.g., moral anger, collective guilt and excitement around collective action. • We move away from pathologisation of emotional responses to climate change and discuss their mobilising charge. [ABSTRACT FROM AUTHOR]