scholarly journals Automated identification of leukocyte subsets improves standardization of database-guided expert-supervised diagnostic orientation in acute leukemia: a EuroFlow study

2020 ◽  
Author(s):  
Ludovic Lhermitte ◽  
◽  
Sylvain Barreau ◽  
Daniela Morf ◽  
Paula Fernandez ◽  
...  

Abstract Precise classification of acute leukemia (AL) is crucial for adequate treatment. EuroFlow has previously designed an AL orientation tube (ALOT) to guide toward the relevant classification panel and final diagnosis. In this study, we designed and validated an algorithm for automated (database-supported) gating and identification (AGI tool) of cell subsets within samples stained with ALOT. A reference database of normal peripheral blood (PB, n = 41) and bone marrow (BM; n = 45) samples analyzed with the ALOT was constructed, and served as a reference for the AGI tool to automatically identify normal cells. Populations not unequivocally identified as normal cells were labeled as checks and were classified by an expert. Additional normal BM (n = 25) and PB (n = 43) and leukemic samples (n = 109), analyzed in parallel by experts and the AGI tool, were used to evaluate the AGI tool. Analysis of normal PB and BM samples showed low percentages of checks (<3% in PB, <10% in BM), with variations between different laboratories. Manual analysis and AGI analysis of normal and leukemic samples showed high levels of correlation between cell numbers (r2 > 0.95 for all cell types in PB and r2 > 0.75 in BM) and resulted in highly concordant classification of leukemic cells by our previously published automated database-guided expert-supervised orientation tool for immunophenotypic diagnosis and classification of acute leukemia (Compass tool). Similar data were obtained using alternative, commercially available tubes, confirming the robustness of the developed tools. The AGI tool represents an innovative step in minimizing human intervention and requirements in expertise, toward a “sample-in and result-out” approach which may result in more objective and reproducible data analysis and diagnostics. The AGI tool may improve quality of immunophenotyping in individual laboratories, since high percentages of checks in normal samples are an alert on the quality of the internal procedures.

2019 ◽  
Vol 51 (4) ◽  
pp. 345-351
Author(s):  
Mohammad Shahjahani ◽  
Amirreza Abroun ◽  
Najmaldin Saki ◽  
Seyed Mohammad Bagher Mohammadi ◽  
Hadi Rezaeeyan

Abstract Background Based on the results of multiple studies, multiple signaling pathways is a major cause of resistence to chemotherapy in leukemia cells. Signal transducer and activator of transcription 5 (STAT5) is among these factors; it plays an essential role in proliferation of leukemic cells. Methods We obtained the materials used in our study via PubMed search from 1996 through 2019. The key search terms included “STAT5,” “acute leukemia,” “leukemogenesis,” and “mutation.” Results On activation, STAT5 not only inhibits apoptosis of leukemic cells via activating the B-cell lymphoma 2 (BCL-2) gene but also inhibits resistance to chemotherapy by enhancing human telomerase reverse transcriptase (hTERT) expression and maintaining telomere length in cells. It has also been shown that a number of mutations in the STAT5 gene and in related genes alter the expression of STAT5. Conclusion The identification of STAT5 and the factors activated in its up- or downstream expression, affecting its function, contribute to better treatments such as targeted therapy rather than chemotherapy, improving the quality of life patients.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5213-5213
Author(s):  
Yingyu Chen ◽  
Jing Zheng ◽  
Zhenxing Lin ◽  
Jing Li ◽  
Qizhen Shi ◽  
...  

Abstract Leukemia stem cells (LSCs) play central roles in the pathogenesis of acute leukemia and contribute to both disease initiation and relapse. Thus, identification of agents to eradicate LSCs is an important priority. Our previous studies have demonstrated that emodin, an extracted natural compound, might exert anti-leukemic effects in vitro. To improvethe bioavailability and solubility of emodin, we designed and synthesized a family of novel emodin analogs. Among them, E35 has demonstrated greater bioactivity. In this study, we investigated whether E35 may selectively eliminate acute leukemia stem and progenitor cellsand the underlying mechanism involved. We isolated CD34+ cells from leukemic stem-like cell line KG1a and resistant myeloid cell line HARs. Results demonstrated that E35 affected the viability of CD34+ leukemia cells with the average IC50 value of 15.33 ± 3.88 μM in KG1a cells and 9.12 ± 0.08 μM in HARs, respectively. We then performed the biological studies in primary leukemia specimens from 33 acute leukemia patients. All of the primary leukemia cells were sensitive to E35 with the average IC50 value of 13.86 ± 9.35 μM. Treatment with 16 μM and 32 μM E35 resulted in viability of 41.68 ± 3.90% (n = 33) and 16.63 ± 3.09% (n = 21) for overall primary leukemia cells, and 29.68 ± 4.18% (n = 17) and 15.98 ± 6.71% (n = 7) for CD34+ leukemia cells, respectively. However, both normal mononuclear cells and CD34+ cells obtained from healthy donors were not significantly affected by E35. The viability at 16 μM was 79.43 ± 3.73% (n = 6) for overall healthy cells and 88.64 ± 5.00% (n = 4) for CD34+ hematopoieticcells. Around 65% normal hematopoieticcells remained alive even though treated with E35 as high as 32 μM. E35 strongly induced robust apoptosis of LSCs from KG1a and HARs. After exposure to 16 μM E35 for 24 hours, the percentages of apoptotic LSCs in KG1a and HARs significantly increased up to 4.7 and 2.0 folds compared with those of without treatment groups (P < 0.01, n = 3), respectively. The percentage of CD34+ Annexin V+ cells from primary leukemia specimens following E35 treatment was also significantly greater than that in untreated group (27.29 ± 6.29% vs 10.08 ± 2.15%; P < 0.05, n = 15). Consistently, E35 stimuli raised the percentage of CD34+ CD38- LSCs undergoing apoptosis from 19.79 ± 4.91% to 28.36 ± 7.14% (n = 14). Notably, E35 did not trigger apoptosis in normal hematopoietic stemcells on comparison with control group (P > 0.05, n = 5). Western Blotting results showed that activation of Caspase-family proteins (eg, pro-caspase and PARP cleavage) and inhibiton of Akt/mTOR signaling pathway (eg, p-Akt, p-4E-BP1 and p-p-70S6K blockage) might be key steps toward LSC-specific apoptosis by E35. To determine whether E35 targets functionally defined leukemia stem and progenitor cells, colony assays and NOD/SCID xenotransplantation were performed. Primary AML cells versus normal cells were treated with E35 for 18 hours, followed by plating in methylcellulose culture or transplanting into Busulfan preconditioned NOD/SCID mice. Normal hematopoietic cells with E35 treatment did not affect myeloid colony formation relative to untreated control (n = 6). In contrast, E35 treatment strongly inhibited the ability of leukemia cells to form colonies (P < 0 .0001, n = 7). Similarly, primary leukemic cells with with E35 treatment led to a significant decrease in stem cell activity, with reduction engraftment levels from 19.47 ± 4.77 % to 2.92 ± 0.34 % (P < 0.01, n = 7). In contrast, the engraftment levels of E35 preconditioned normal cells were not statistical significant different from those of healthy cells without treatment (28.10 ± 5.30% vs 31.10 ± 6.88%, n = 4). These data demonstrate that E35 specifically ablates leukemic but not normal hematopoietic progenitor- and stem-cell function. In conclusion, E35 has the potential to selectively eradicate primitive leukemic cells, indicating it is a novel therapeutic candidate against hematologic cancers. Disclosures No relevant conflicts of interest to declare.


Author(s):  
A. Martini ◽  
P. V. Kuper ◽  
M. Breunig

<p><strong>Abstract.</strong> A significant advantage of OpenStreetMap data is its up-to-dateness. However, for rural and city planning, it is also of importance to access historical data and to compare the changes between new and old versions of the same area. This paper first introduces into a differentiated classification of changes on OpenStreetMap data sets. Then a methodology for an automated database-supported analysis of changes is presented. Beyond the information already provided from the OpenStreetMap server, we present a more detailed analysis with derived information. Based on this approach it is possible to identify objects with attributive or geometric changes and to find out how they exactly differ from their previous versions. The analysis shows in which regions mappers were active during a certain time interval. Furthermore, a time based approach based on various parameters to determine the quality of the data is presented. It provides a guideline of data quality and works without any reference data. Therefore, an indication about the development of OpenStreetMap in terms of completeness and correctness of the data in different regions is given. Finally, a conclusion and an outlook on open research questions are presented.</p>


Leukemia ◽  
2017 ◽  
Vol 32 (4) ◽  
pp. 874-881 ◽  
Author(s):  
L Lhermitte ◽  
◽  
E Mejstrikova ◽  
A J van der Sluijs-Gelling ◽  
G E Grigore ◽  
...  

1998 ◽  
Vol 2 ◽  
pp. 115-122
Author(s):  
Donatas Švitra ◽  
Jolanta Janutėnienė

In the practice of processing of metals by cutting it is necessary to overcome the vibration of the cutting tool, the processed detail and units of the machine tool. These vibrations in many cases are an obstacle to increase the productivity and quality of treatment of details on metal-cutting machine tools. Vibration at cutting of metals is a very diverse phenomenon due to both it’s nature and the form of oscillatory motion. The most general classification of vibrations at cutting is a division them into forced vibration and autovibrations. The most difficult to remove and poorly investigated are the autovibrations, i.e. vibrations arising at the absence of external periodic forces. The autovibrations, stipulated by the process of cutting on metalcutting machine are of two types: the low-frequency autovibrations and high-frequency autovibrations. When the low-frequency autovibration there appear, the cutting process ought to be terminated and the cause of the vibrations eliminated. Otherwise, there is a danger of a break of both machine and tool. In the case of high-frequency vibration the machine operates apparently quiently, but the processed surface feature small-sized roughness. The frequency of autovibrations can reach 5000 Hz and more.


2020 ◽  
Vol 45 (4) ◽  
pp. 794-801
Author(s):  
Caroline Oliveira Andrino ◽  
Marcelo Fragomeni Simon ◽  
Jair Eustáquio Quintino Faria ◽  
André Luiz da Costa Moreira ◽  
Paulo Takeo Sano

Abstract—We describe and illustrate Paepalanthus fabianeae, a new species of Eriocaulaceae from the central portion of the Espinhaço Range in Minas Gerais, Brazil. Previous phylogenetic evidence based on analyses of nuclear (ITS and ETS) and plastid (trnL-trnF and psba-trnH) sequences revealed P. fabianeae as belonging to a strongly supported and morphologically coherent clade containing five other species, all of them microendemic, restricted to the Espinhaço range. Due to the infrageneric classification of Paepalanthus being highly artificial, we preferred not assigning P. fabianeae to any infrageneric group. Paepalanthus fabianeae is known from two populations growing in campos rupestres (highland rocky fields) in the meridional Espinhaço Range. The species is characterized by pseudodichotomously branched stems, small, linear, recurved, and reflexed leaves, urceolate capitula, and bifid stigmas. Illustrations, photos, the phylogenetic position, and a detailed description, as well as comments on habitat, morphology, and affinities with similar species are provided. The restricted area of occurrence allied with threats to the quality of the habitat, mainly due to quartzite mining, justifies the preliminary classification of the new species in the Critically Endangered (CR) category using the guidelines and criteria of the IUCN Red List.


2020 ◽  
Vol 6 (3) ◽  
pp. 158-164
Author(s):  
Navruza Yakhyayeva ◽  

The quality and content of information in the article media text is based on scientific classification of linguistic features. The study of functional styles of speech, the identification of their linguistic signs, the discovery of the functional properties of linguistic units and their separation on the basis of linguistic facts is one of thetasks that modern linguistics is waiting for a solution. Text Linguistics, which deals with the creation, modeling of its structure and the study of the process of such activity, is of interest to journalists today as a science.


2019 ◽  
pp. 86-88
Author(s):  
R. H. Batirova ◽  
S. S. Tashpulatov ◽  
I. V. Cherunova ◽  
M. A. Mansurova ◽  
S. L. Matismailov
Keyword(s):  

2018 ◽  
Vol 3 (1) ◽  
pp. 1-8
Author(s):  
Desy Damayanti ◽  
Adin Fauzi ◽  
Azizatul Mahfida Inayati

Among some components of effective language classroom, learning materials indisputably play a focal role. They improve the quality of language teaching; facilitate teachers in doing their duties, and lead students to a higher level of understanding in learning. This research aims to discuss the notion of materials in language teaching. It made use of works of literature to outline the importance of materials in language teaching, and to analyze kinds of materials, which are relevant to language teaching. The analysis resulted in the classification of materials into two broad categories namely (1) created materials, which include course book, audio materials, and video materials; and (2) authentic materials, which cover authentic texts, movie/film, radio broadcasting, television program, graphs, maps, tables, and charts. This paper serves as an invaluable resource to facilitate language teachers in selecting appropriate materials for effective language teaching.


Sign in / Sign up

Export Citation Format

Share Document