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Abstract The gut microbiota of paediatric oncology patients undergoing a conditioning regimen before hematopoietic stem cell transplantation is recently considered to play role in febrile neutropenia. Disruption of commensal microbiota and evolution of opportune pathogens community carrying a plethora of antibiotic-resistance genes play crucial role. However, the impact, predictive role and association of patient´s gut resistome in the course of the therapy is still to be elucidated. We analysed gut microbiota composition and resistome of 18 paediatric oncology patients undergoing hematopoietic stem cell transplantation, including 12 patients developing febrile neutropenia, hospitalized at The Bone Marrow Transplantation Unit of the National Institute of Children´s disease in Slovak Republic and healthy individuals (n = 14). Gut microbiome of stool samples obtained in 3 time points, before hematopoietic stem cell transplantation (n = 16), one week after hematopoietic stem cell transplantation (n = 16) and four weeks after hematopoietic stem cell transplantation (n = 14) was investigated using shotgun metagenome sequencing and bioinformatical analysis. We identified significant decrease in alpha-diversity and nine antibiotic-resistance genes msr(C), dfrG, erm(T), VanHAX, erm(B), aac(6)-aph(2), aph(3)-III, ant(6)-Ia and aac(6)-Ii, one week after hematopoietic stem cell transplantation associated with febrile neutropenia. Multidrug-resistant opportune pathogens of ESKAPE, Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae and Escherichia coli found in the gut carried the significant subset of patient’s resistome. Over 50% of patients treated with trimethoprim/sulfamethoxazole, piperacillin/tazobactam and amikacin carried antibiotic-resistance genes to applied treatment. The alpha diversity and the resistome of gut microbiota one week after hematopoietic stem cell transplantation is relevant predictor of febrile neutropenia outcome after hematopoietic stem cell transplantation. Furthermore, the interindividual diversity of multi-drug resistant opportunistic pathogens with variable portfolios of antibiotic-resistance genes indicates necessity of preventive, personalized approach.

The magnetic properties of core/shell nanoparticles (NPs) depend on the various parameters, including the magnetic interactions, but these effects have not been well studied. Here, we systematically investigated the structure and magnetic properties of Fe3O4@CoFe2O4 core/shell NPs. X-ray diffraction (XRD), scanning electron microscopy (SEM), and scanning transmission electron microscopy (STEM) confirmed the formation of Fe3O4@CoFe2O4 core/shell NPs. Magnetic measurements of the core/shell NPs were performed on both dried-pressed and well-dispersed in wax states. For the dried-pressed NPs, we found that the temperature-dependent magnetization curves of core/shell NPs vary significantly compared to that of core NPs due to spin interactions at the core/shell interface. Besides, the hysteresis loops of the core/shell NPs at 10 K are constricted, probably due to the interparticle interaction. For the core/shell NPs dispersed in wax, the hysteresis loops were smooth at all temperatures between 10 and 300 K due to the attenuated interparticle interaction. The high HC of 9.14 kOe (at 10 K) of the dispersed NPs is twice larger than that of the dried-pressed powders (4.23 kOe). Our study provides new insights into the effects of shell thickness and interparticle interaction on the magnetic properties of Fe3O4@CoFe2O4 core/shell NPs.

Graft-versus-host disease (GvHD) is a severe complication after hematopoietic stem cell transplantation (HSCT). Our study focused on identifying multidrug-resistant (MDR) gut bacteria associated with GvHD-prone guts and association with gut microbiota (GM) diversity, bacteriome, and mycobiome composition in post-HSCT patients. We examined 11 pediatric patients with acute lymphoblastic leukemia (ALL), including six with GvHD, within three time points: seven days pre-HSCT, seven days post-, and 28 days post-HSCT. The gut microbiome and its resistome were investigated using metagenomic sequencing, taxonomically classified with Kraken2, and statistically evaluated for significance using appropriate tests. We observed an increase in the abundance of MDR bacteria, mainly Enterococcus faecium strains carrying msr(C), erm(T), aac(6′)-li, dfrG, and ant(6)-la genes, in GvHD patients one week post-HSCT. Conversely, non-GvHD patients had more MDR beneficial bacteria pre-HSCT, promoting immunosurveillance, with resistance genes increasing one-month post-HSCT. MDR beneficial bacteria included the anti-inflammatory Bacteroides fragilis, Ruminococcus gnavus, and Turicibacter, while most MDR bacteria represented the dominant species of GM. Changes in the gut mycobiome were not associated with MDR bacterial monodominance or GvHD. Significant α-diversity decline (Shannon index) one week and one month post-HSCT in GvHD patients (p < 0.05) was accompanied by increased Pseudomonadota and decreased Bacteroidota post-HSCT. Our findings suggest that MDR commensal gut bacteria may preserve diversity and enhance immunosurveillance, potentially preventing GvHD in pediatric ALL patients undergoing HSCT. This observation has therapeutic implications.

Previously, the outcome of paediatric Philadelphia-chromosome–positive (Ph+) ALL treated with conventional chemotherapy alone was poor, necessitating the use of haematopoietic stem cell transplantation (HSCT) for the best outcomes. The recent addition of tyrosine kinase inhibitors (TKIs) alongside the chemotherapy regimens for Ph+ ALL has markedly improved outcomes, replacing the need for HSCT for lower risk patients. An additional poor prognosis group of Philadelphia-chromosome–like (Ph-like) ALL has also been identified. This group also can be targeted by TKIs in combination with chemotherapy, but the role of HSCT in this population is not clear. The impact of novel targeted immunotherapies (chimeric antigen receptor T cells and bispecific or drug-conjugated antibodies) has improved the outcome of patients, in combination with chemotherapy, and made the role of HSCT as the optimal curative therapy for Ph+ ALL and Ph-like ALL less clear. The prognosis of patients with Ph+ ALL and persistent minimal residual disease (MRD) at the end of consolidation despite TKI therapy or with additional genetic risk factors remains inferior when HSCT is not used. For such high-risk patients, HSCT using total-body-irradiation–containing conditioning is currently recommended. This review aims to provide an update on the current and future role of HSCT for Ph+ ALL and addresses key questions related to the management of these patients, including the role of HSCT in first complete remission, MRD evaluation and related actions post HSCT, TKI usage post HSCT, and the putative role of HSCT in Ph-like ALL.

Total-body irradiation (TBI) based conditioning prior to allogeneic hematopoietic stem cell transplantation (HSCT) is generally regarded as the gold-standard for children >4 years of age with acute lymphoblastic leukaemia (ALL). Retrospective studies in the 1990's suggested better survival with irradiation, confirmed in a small randomised, prospective study in the early 2000's. Most recently, this was reconfirmed by the early results of the large, randomised, international, phase III FORUM study published in 2020. But we know survivors will suffer a multitude of long-term sequelae after TBI, including second malignancies, neurocognitive, endocrine and cardiometabolic effects. The drive to avoid TBI directs us to continue optimising irradiation-free, myeloablative conditioning. In chemotherapy-based conditioning, the dominant myeloablative effect is provided by the alkylating agents, most commonly busulfan or treosulfan. Busulfan with cyclophosphamide is a long-established alternative to TBI-based conditioning in ALL patients. Substituting fludarabine for cyclophosphamide reduces toxicity, but may not be as effective, prompting the addition of a third agent, such as thiotepa, melphalan, and now clofarabine. For busulfan, it's wide pharmacokinetic (PK) variability and narrow therapeutic window is well-known, with widespread use of therapeutic drug monitoring (TDM) to individualise dosing and control the cumulative busulfan exposure. The development of first-dose selection algorithms has helped achieve early, accurate busulfan levels within the targeted therapeutic window. In the future, predictive genetic variants, associated with differing busulfan exposures and toxicities, could be employed to further tailor individualised busulfan-based conditioning for ALL patients. Treosulfan-based conditioning leads to comparable outcomes to busulfan-based conditioning in paediatric ALL, without the need for TDM to date. Future PK evaluation and modelling may optimise therapy and improve outcome. More recently, the addition of clofarabine to busulfan/fludarabine has shown encouraging results when compared to TBI-based regimens. The combination shows activity in ALL as well as AML and deserves further evaluation. Like busulfan, optimization of chemotherapy conditioning may be enhanced by understanding not just the PK of clofarabine, fludarabine, treosulfan and other agents, but also the pharmacodynamics and pharmacogenetics, ideally in the context of a single disease such as ALL.

The dataset presented in this article represents the pre-processed web server log file of the commercial bank. The source of data is the web server of the bank and keeps access of web users starting the year 2009 till 2012. It contains accesses to the bank website during and after the financial crisis. Unnecessary data saved by the web server was removed to keep the focus only on the textual content of the website. Many variables were added to the original log file to make the analysis workable. To keep the privacy of website users, sensitive information in the log file were anonymized. The dataset offers a way to understand the behavior of stakeholders during and after the crisis and how they comply with the Basel regulations. The behavior of users can be modeled using the multinomial logit model, which is in detail described in the research article [1] related to this data article.

The methods presented in this article were created to model and describe the behaviour of the web users of a bank institution web portal. The source dataset is represented by a log file of the commercial bank web server. The analysis is oriented on examining the behaviour of visitors over an extended period (2009-2012). The years 2009-2010 represent the years of the financial crisis, and the years 2011-2012 represent the years after the financial crisis. The following method describes the sequence of steps necessary to pre-process the raw log file and model the web user behaviour using the multinomial logit model. The introduced methods can be used also for other domains in the case of appropriate data preparation. • Data preparation- data cleaning, user/session identification, path completion, variables determination; • Data analysis- model definition, parameters estimation, logits estimation, probabilities estimation; • Results evaluation- comparison of empirical and theoretical values in term of counts, probabilities and logits.

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.

Magnusiomyces capitatus (previously known as Geotrichum capitatum or Blastoschizomyces capitatus or Trichosporon capitatum) is a rare cause of fungal infection in immunocompromised patients. Most of these cases (87%) have been reported from the Mediterranean region, as it is extremely rare to recognize it in other regions. Here we report a first case of disseminated M. capitatus infection in Slovakia. The patient – 19 year old woman with myelodysplastic syndrome was diagnosed with M. capitatus fungemia after allogeneic stem cell transplantation. The infection occurred despite antifungal prophylaxis with micafungin, which was in vitro sensitive to the yeast. The treatment according to minimal inhibitory concentrations (micafungin, voriconazol) and granulocyte transfusions were administered. M. capitatus was cleared out from the bloodstream. However, patient died of multiple organ failure. Autopsy showed multiple lesions in organs, but did not prove presence of yeast by histopathology. M. capitatus was confirmed by polymerase chain reaction from all tested organs: heart, brain, lungs, spleen, liver and kidneys. We present the post mortem pictures showing the yeast lesions in affected organs. 2012 Elsevier Ltd. All rights reserved.

In this study, the non-isothermal kinetics of the martensitic transition from 14M modulated martensite to austenite phase in Ni55Fe19Ga26 ribbons obtained by melt-spinning has been analyzed. The proximity of the martensitic transition to room temperature makes it very sensitive to pressure and subtle differences for different pieces of the ribbon (ascribed to stresses stored in the ribbon during its rapid solidification process). Despite the dispersion in the characteristic parameters of the transition, a general behavior is observed with a decreasing activation energy as the heating rate increases due to the nucleation driven character of the transition. It has been shown that a first-order autocatalysis can describe the temperature evolution of the austenite fraction using only two experimental temperatures. Predicted curves are in good agreement with experimental data.

Phase transformations and composition of Al-Fe-Si, Al-Co-Si and Al-Ni-Si based rapidly quenched ribbons have been investigated. Different Al-Si based alloys with varying Si content and additions of third metallic element, namely Al80Si20, Al60Si40, Al75Fe5Si20, Al70Fe10Si20, Al75Co5Si20, Al70Co10Si20, Al75Ni5Si20, Al70Ni10Si20 were analyzed. Variation of phase composition with elemental composition was observed. Evolution of phases was determined by resistometry, differential scanning calorimetry (DSC). In situ X-ray diffraction (XRD) and transmission electron microscope (TEM) records were observed during isothermal and isochronal annealing.

(Fe1-xCox)79Mo8Cu1B15 amorphous alloys ware prepared in the form of ribbons by rapid quenching for x=0. 0.25 and 0.5. The effect of variation of Co/Fe ratio is analyzed with respect to the formation of amorphous state and to transformation of the structure into nancrystalline phases formed after subsequent thermal treatment. Selected properties and atomic structure in as-quenched state are studied by TEM, AFM, XRD any by measurement of magnetoresistance characteristics. The influence of heat treatment on transport and magnetic properties is shown on temperature dependencies of electrical resistivity and magnetization. It was founf that while the increase of Co content leads to the increase of Curie temperature of as-quenched structure, transition to nanocrystalline state is not affected in a significant manner. The as-quenched state for alloy without Co was found to contain thin crystal-containing layer which, however, was observed, contary to general behavior, at the side of the ribbon exposed to higher quenching rates.

Clinical and genetic heterogeneity renders confirmation or exclusion of autoimmune lymphoproliferative syndrome difficult. To re-evaluate and improve the currently suggested diagnostic approach to patients with suspected FAS mutation, the most frequent cause of autoimmune lymphoproliferative syndrome, we prospectively determined 11 biomarkers in 163 patients with splenomegaly or lymphadenopathy and presumed or proven autoimmune cytopenia(s). Among 98 patients sequenced for FAS mutations in CD3+TCRα/β+CD4−CD8− “double negative” T cells, 32 had germline and six had somatic FAS mutations. The best a priori predictor of FAS mutations was the combination of vitamin B12 and soluble FAS ligand (cut-offs 1255 pg/mL and 559 pg/mL, respectively), which had a positive predictive value of 92% and a negative predictive value of 97%. We used these data to develop a web-based probability calculator for FAS mutations using the three most discriminatory biomarkers (vitamin B12, soluble FAS ligand, interleukin-10) of the 11 tested. Since more than 60% of patients with lymphoproliferation and autoimmune cytopenia(s) in our cohort did not harbor FAS mutations, 15% had somatic FAS mutations, and the predictive value of double-negative T-cell values was rather low (positive and negative predictive values of 61% and 77%, respectively), we argue that the previously suggested diagnostic algorithm based on determination of double-negative T cells and germline FAS sequencing, followed by biomarker analysis, is not efficient. We propose vitamin B12 and soluble FAS ligand assessment as the initial diagnostic step with subsequent decision on FAS sequencing supported by a probability-calculating tool.

New nanocrystalline materials for the applications in the power electronics systems are developed and tested.These materials are intended to be used in the magnetic circuits of switching-mode power supplies (SMPS). The aim was toachieve extremely low hysteresis and non-linearity in operating region resulting in increased efficiency and decreased weightand size whilst keeping low price of the high-power frequency converters for SMPS.

A relationship between the tensile yield stress and grain size i.e., Hall-Petch (H–P) law, for an ultrafine-grained (UFG) Zn was experimentally evaluated for the first time. In reality, it is problematic to assess this prediction using experimental results due to the low recrystallization temperature of a pure Zn. In order to do so, three Zn bulk materials with the intercept grain size (dl) ranging from 0.6 to 1.1 μm, stabilized with a small portion of nanoscale ZnO dispersoids positioned at high angle grain boundaries (HAGB), were fabricated from fine pure Zn powders. The material with the finest grain size of 0.6 μm, ever reported for unalloyed Zn, also exhibited the highest ultimate tensile and 0.2% strain offset yield strengths (YS0.2), ever reported for unalloyed Zn. The strengths were accompanied by a reasonably high ductility. Deformation in the presented materials was attributed to the grain boundary sliding (GBS) mechanism. The experimental data were compared with a theoretical model of the deformation behavior of UFG metals based on GBS through dislocation glide. We confirmed, that the linear H–P relation YS0.2=40.8+104.8dl−0.5 remained in force in the range of dl = ∼400–0.6 μm. A grain refinement softening in UFG region predicted by the theoretical model and other experimental works was avoided. This was attributed to the presence and an effective stabilizing effect of the nano-metric ZnO at HAGB, which impeded GBS. The practical implications of the presented concept of Zn-based bioresorbable material are discussed from the point of view of potential applications in implantology.

In addition to its use as a lightweight material, pure magnesium is a promising candidate for prospective bioimplants considering its excellent biocompatible properties. Regardless of what Mg application is used, the ultimate goal is to improve magnesium's mechanical properties and degradation behaviour. Because of the high affinity for oxygen native oxide layer of gas-atomized powders is naturally formed in contact with the atmosphere. S/TEM investigation of the native oxide of the Mg powder particles revealed a nonhomogeneous nano-crystalline MgO layer. MgO is relatively soluble in water and does not provide sufficient corrosion protection. Among various surface treatment methods, conversion of the non-protective magnesium oxide to carbonate products is possible depending on the environmental conditions. This work used a simple experimental method using CO2 and water vapour to achieve surface carbonation of Mg powders. Two carbonated samples and pure magnesium were prepared by direct extrusion. The samples after carbonation retained good mechanical properties and the layer of carbonates had a significant impact on corrosion resistance. 1 day carbonation resulted in transformation of native oxide into amorphous layer and reduction of corrosion rate. Longer carbonation (10 days) revealed layer growth and transformation of native oxide to crystalline nesquehonite structure.