Several studies have demonstrated that monitoring of minimal residual disease (MRD) in childhood and adult acute lymphoblastic leukemia (ALL) significantly correlates with clinical outcome. MRD ...detection is particularly useful for evaluation of early treatment response and consequently for improved front-line therapy stratification. MRD information is also significant for children undergoing allogeneic hematopoietic stem cell transplantation and those with relapsed ALL. Currently, three highly specific and sensitive methodologies for MRD detection are available, namely multiparameter flow cytometric immunophenotyping, real-time quantitative polymerase chain reaction (RQ-PCR)-based detection of fusion gene transcripts or breakpoints, and RQ-PCR-based detection of clonal immunoglobulin and T-cell receptor gene rearrangements. In this review, characteristics, pitfalls, advantages and disadvantages of each MRD technique are critically discussed. The special emphasis is put on interlaboratory standardization, especially in view of the results obtained within the European collaborative BIOMED-1, BIOMED-2, and Europe Against Cancer projects and recent developments by European Study Group on MRD detection in ALL and EuroFlow Consortium. Standardized MRD techniques form the basis for stratification of patients into the risk groups in new treatment protocols mainly in childhood ALL. Only the results of these studies can answer the question whether MRD-based treatment intervention is associated with improved outcome.
Dasypogon is a widely distributed Palearctic genus. This contribution reviews the species from Central Europe. Two species are identified, including one new species-Dasypogon diabolicus sp. nov. An ...identification key of the Central European species and descriptions of the male and female of both species are provided along with illustrations of the habitus and male and female terminalia. An updated map with species distributions is presented, and a new corrected list of synonyms of D. diadema is proposed. The following new synonymy is established: Leptarthrus brevirostris (Meigen, 1804) = Dasypogon caudatus Bigot, 1881 syn. nov.
Abstract
This paper revises the taxonomy and phylogeny of Ropalopus (Coleoptera: Cerambycidae: Callidiini) species belonging to the taxonomically intricate Ropalopus ungaricus/insubricus group from ...the western Palaearctic. Specimens from all taxa were studied and compared. The key characters, including the male terminalia, were examined by means of scanning electron microscopy. High-quality stacked photographs of the habitus of the specimens (dorsal, ventral) are presented. The phylogenetic analyses were based on 34 adult morphological characters. Both the strict and majority consensus trees revealed the monophyly of the revised group. Identification keys are provided for every taxon from this group, and their geographical distributions are also mapped. All European populations are reduced to subspecies of Ropalopus ungaricus. Additionally, a new subspecies from Greece, Ropalopus ungaricus ossae subsp. nov., is described and illustrated. A new synonymy for Ropalopus insubricus fischeri is proposed: Callidium insubricum = Callidium fischeri. Ropalopus nataliyae, which was described based on only a single female, is herein redescribed owing to the collection of abundant new material. Apart from geographical barriers, the main differentiating factor in this group is proved to be the elevation above sea level. Taxa of the R. ungaricus/insubricus group are therefore allopatric or, when parapatric, are isolated by elevation.
Introduction
Nuwiq® (Human‐cl rhFVIII) is a new‐generation recombinant factor VIII (rFVIII) protein, without chemical modification or fusion to any other protein, produced in a human cell line.
...Aim/Methods
This prospective, open‐label, multinational phase III study assessed the efficacy and safety of Human‐cl rhFVIII in 59 previously treated patients (PTPs) with severe haemophilia A aged 2–12 years (2–5 N = 29; 6–12 N = 30) during standard prophylaxis (≥50 exposure days and ≥6 months). Efficacy in treating breakthrough bleeds and during surgical prophylaxis was also assessed.
Results
An initial pharmacokinetic assessment (N = 13 per age subgroup) demonstrated comparable results with the one‐stage and chromogenic assays. Mean (SD) half‐life was 11.9 (5.4) and 13.1 (2.6) hours in children aged 2–5 years and 6–12 years respectively (one‐stage assay). Prophylactic efficacy, based on mean monthly bleeding rate, was ‘excellent’ or ‘good’ in 91.5% of children for all bleeds and in 96.6% of children for spontaneous bleeds. Mean (SD) annualized bleeding rate was 4.12 (5.22) median 1.9 for all bleeds, 1.50 (3.32) median 0 for spontaneous bleeds and 2.34 (3.54) median 1.57 for traumatic bleeds. There were no major, life‐threatening bleeds. Efficacy was ‘excellent’ or ‘good’ in the treatment of 82.4% of breakthrough bleeds. Overall efficacy during five major surgeries was rated as ‘excellent’. There were no FVIII inhibitors or treatment‐related serious adverse events.
Conclusion
These results in paediatric PTPs indicate that Human‐cl rhFVIII is effective for the prevention and treatment of bleeds.
We consider scattering of electrons by magnetic regions in topological insulators characterized by spin-momentum locking. By using perturbation theory and partial wave summation approaches, we ...analyze the role of the system parameters in different scattering regimes. We demonstrate that the specific features of spin-momentum locking lead to strong differences in the scattering cross-section compared to the conventional spin-independent scattering of electrons in semiconductors. The features include, e.g., the scattering anisotropy and the unusual energy dependence of the scattering cross-section. These results can be useful for the understanding of the kinetic effects in topological insulators with magnetic disorder and for the design of magnetization patterns for control of coupled spin and charge density dynamics.
•We consider electron scattering by magnetic regions in topological insulators.•We analyze theoretically different scattering regimes.•The spin-momentum locking qualitatively modifies the scattering.•The scattering becomes anisotropic with unusual energy dependence.•These results are useful for the understanding of kinetic effects.
Chromosomal rearrangements of the human KMT2A/MLL gene are associated with de novo as well as therapy-induced infant, pediatric, and adult acute leukemias. Here, we present the data obtained from ...3401 acute leukemia patients that have been analyzed between 2003 and 2022. Genomic breakpoints within the KMT2A gene and the involved translocation partner genes (TPGs) and KMT2A-partial tandem duplications (PTDs) were determined. Including the published data from the literature, a total of 107 in-frame KMT2A gene fusions have been identified so far. Further 16 rearrangements were out-of-frame fusions, 18 patients had no partner gene fused to 5'-KMT2A, two patients had a 5'-KMT2A deletion, and one ETV6::RUNX1 patient had an KMT2A insertion at the breakpoint. The seven most frequent TPGs and PTDs account for more than 90% of all recombinations of the KMT2A, 37 occur recurrently and 63 were identified so far only once. This study provides a comprehensive analysis of the KMT2A recombinome in acute leukemia patients. Besides the scientific gain of information, genomic breakpoint sequences of these patients were used to monitor minimal residual disease (MRD). Thus, this work may be directly translated from the bench to the bedside of patients and meet the clinical needs to improve patient survival.
Introduction
Nuwiq® (human‐cl rhFVIII, simoctocog alfa) is a 4th generation recombinant human FVIII, without chemical modification or fusion with any other protein, produced in a human cell line.
...Aim/Methods
This study (GENA‐13) was an extension of the GENA‐03 study in which previously treated children aged 2‐12 years with severe haemophilia A received Nuwiq® prophylaxis for ≥6 months. GENA‐13 examined long‐term tolerability, immunogenicity and efficacy of Nuwiq® prophylaxis in children.
Results
Of 59 patients enrolled in GENA‐03, 49 continued Nuwiq® prophylaxis in GENA‐13 for a median (range) of 30.0 (9.5‐52.0) months. No patient withdrew due to drug‐related adverse events or developed inhibitors. Only 2 of 20 518 infusions were associated with possibly related adverse events (dyspnoea, fever). The estimated annualized bleeding rate (ABR) was 0.67 (95% CI: 0.44, 1.02) for spontaneous and 2.88 (95% CI: 1.86, 4.46) for all bleeds. Younger children (2‐5 years) had lower ABRs than children aged 6‐12 years. Annualized bleeding rates were reduced in GENA‐13 vs GENA‐03, especially for spontaneous bleeds in younger children (71% reduction; ABR ratio 0.29 95% CI: 0.11, 0.74). Nuwiq® efficacy was rated as excellent/good in the treatment of 83.0% of 305 evaluated breakthrough bleeds. Surgical prophylaxis with Nuwiq® was rated as excellent for all 17 assessed procedures.
Conclusion
Long‐term treatment with Nuwiq® for the prevention of bleeds in children with severe haemophilia A was well tolerated, effective and reduced spontaneous bleeding by up to 70% compared with GENA‐03.
New data on the distribution, biology, and ecology of the longhorn beetles occurring in Mongolia are presented together with a list of 35 species that were collected during a one-month entomological ...expedition in August 2015. New localities of some rare taxa endemic to Mongolia, such as
(Jakovlev, 1901),
(Faldermann, 1833), and
(Jakovlev, 1889) are given. High-quality photographs of several rather unique species, i.e.,
(Gebler, 1832),
Danilevsky, 2014,
(Jakovlev, 1895),
(Motschulsky, 1859), and
(Pic, 1898) along with images of their habitats or feeding grounds are also presented. Furthermore, the ecological role of the fireweed
(L.) Scop. in the case of boreal anthophilous cerambycid species is highlighted for the first time.
Arthropods play an essential role in steppe ecosystems. However, studies testing the overall response of terrestrial arthropods to overgrazing are scarce. The problem is particularly worrisome in ...Central Asia, while, to date, only a very few broader studies have been conducted in this region. We investigated how epigeic terrestrial arthropod assemblages respond to different livestock grazing pressure in two ecozones in SE Mongolia by examining their structure using pitfall traps. We also assessed which groups can be utilised as the most efficient indicators of grazing intensity. Our analyses demonstrated that the habitat type, grazing intensity, and the interaction of these variables had a significant effect on the overall species composition and abundance. However, the grazing intensity caused different changes in the composition of arthropod communities in both studied ecozones. Contrary to the semi-desert, in the steppe habitat, the grazing had the strongest impact in the moderately grazed site. It is most likely because steppe-dwelling species are more sensitive to loss of plant biomass and changes in habitat structure. We also found that the most representative species within and from different groups can react differently to changing grazing intensities, indicating with their presence the characteristics of the respective habitat. Such differences should also be considered when elaborating the management plan of conserved species but also when applying grazing management in different habitat types. Our survey is one of the most comprehensive in Central Asia and should help implement further, more targeted studies in the corresponding habitats.
In meadow steppes and other arid habitats, livestock grazing is one of the most severe causes of desertification and leads to an overall decline in vegetation cover, plant species richness and aboveground biomass, and, consequently, most often negatively affects arthropod diversity.
Although the impact of grazing on arthropod diversity has already been the subject of numerous studies, most of them were focused only on a single or small number of arthropods and were conducted outside Central Asia (e.g., there is only one paper dealing with analyses of several arthropod groups conducted in Mongolia, where over 40% of the human population depends on pastoral livestock production and up to 90% of its territory belongs to various arid areas).
We hypothesise that the overall diversity of different arthropod groups will change according to the grazing intensities, and these changes will depend on the habitat type and will differ between arthropod groups.
Our analyses demonstrated that the habitat type, grazing intensity, and the interaction of these two variables significantly impacted the overall species composition and abundance.
Our results highlight that the different terrestrial arthropod groups and representative species of the most abundant groups can react differently to changes in grazing intensity, and such differences should be considered when elaborating the management plan of conserved species and when applying grazing management in different habitat types.
Our results also highlight that the species diversity alone cannot indicate the changes in species composition along the grazing intensity, and one should also consider the individual needs of specific species while investigating the impact of grazing on arid habitats.
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