STUDY ON VIROLOGY OF EXPERIMENTAL LEUKEMIA IN CHINA

Since 1960, the Department of Pathophysio-logy of Shanghai Medical University has beenstudying the virology of experimental leukemia,the strains of L6565 mouse viral leukemia, SRSascitic and solid lymphoma and L783 transplan-table leukemia were established successively. Allof these tumor strains originated from the spon-taneous lymphocytic leukemia of Kunmin mouse(Figure 1). Type A and type C virus particlescould be observed in ultrathin sections of thymus,spleen and lymphonode of all these strains mouse

Diphtheria Toxin/Human B-Cell Activating Factor Fusion Protein Kills Human Acute Lymphoblastic Leukemia BALL-1 Cells: An Experimental Study

Objective： This study aimed to express a fusion protein of diphtheria toxin and human B cell-activating factor （DT388sBAFF） in Escherichia coli （E. coli） and investigate its activity in human B-lineage acute lymphoblastic leukemia 1 cells （BALL-1）. Methods： A fragment of DT388sBAFF fusion gene was separated from plasmid pUC57-DT388sBAFF digested with Nde I and Xho I, and inserted into the expression vector pcold II digested with the same enzymes. Recombinants were screened by the colony polymerase chain reaction （PCR） and restriction map. The recombinant expression vector was transformed into BL21 and its expression was induced by isopropyl β-D-1-thiogalactopyranoside （IPTG）. The recombinant protein was identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis （SDS-PAGE） and Western blot, and then purified by Ni2＋-NTA affinity chromatography. The expression level of B cell-activating factor receptor （BAFF-R） on BALL-1 cells was assessed by real-time PCR. The receptor binding capacity of recombinant protein was determined by cell fluorescent assay. The specific cytotoxicity of recombinant protein on BALL-1 cells was detected by 3-（4,5-dimethylthiazolyl-2）-2,5-diphenyltetrazolium bromide （MTT） assay. Results： The expression level of recombinant protein was 50% of total bacterial proteins in E. coli, and the recombinant protein could bind to BAFF-R-positive BALL-1 cells and thereby produce a cytotoxic effect on the cells. Conclusion： The fusion protein expression vector DT388sBAFF was successfully constructed and the recombinant protein with selective cytotoxicity against BALL-1 cells was obtained, providing foundation for further study of the therapy of human B-lineage acute lymphoblastic leukemia.

Experimental study on the inhibitory effect of arsenic trioxide combined with phorbol ester on the proliferation of acute promyelocytic leukemia cell line Kasumi-1

Objective:To study the effect of arsenic trioxide (As2O3) combined with phorbol ester (PMA) on the proliferation of acute promyelocytic leukemia cell line Kasumi-1.Methods:Acute promyelocytic leukemia cell lines Kasumi-1 were cultured and randomly divided into control group (treated with the RPMI1640 medium without drugs or serum), As2O3 group (treated with serum-free RPMI1640 medium containing 20 μmol/L As2O3), PMA group (treated with serum-free RPMI1640 medium containing 160 nmol/L PMA) and As2O3+ PMA group (treated with serum-free RPMI1640 medium containing 20 μmol/L As2O3 and 160 nmol/L PMA). After treatment, the cell proliferation activity, cell cycle ratio and the protein expression of related genes were measured.Results: 12 h, 24 h and 48 h after treatment, the cell proliferation activity of As2O3 group, PMA group and As2O3+PMA group were significantly lower than that of control group, and the cell proliferation activity of As2O3+PMA group was significantly lower than that of As2O3 group and PMA group;48 h after treatment, the G1 phase and S phase ratio as well as CDK1 and CyclinB1 expression of As2O3 group, PMA group and As2O3+PMA group were significantly lower than those of control group while the G2 phase ratio as well as Bax, Caspase-3, Caspase-9, p-Chk1 and p-Cdc25C9 expression were significantly higher than those of control group;the G1 phase and S phase ratio as well as CDK1 and CyclinB1 expression of As2O3+PMA group were significantly lower than those of As2O3 group and PMA group while the G2 phase ratio as well as Bax, Caspase-3, Caspase-9, p-Chk1 and p-Cdc25C9 expression was significantly higher than those of As2O3 group and PMA group.Conclusion:As2O3 combined with PMA can inhibit the proliferation of acute promyelocytic leukemia cell line Kasumi-1 by inducing apoptosis and blocking cell cycle.

Aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders:progress of experimental models based on disease pathogenesis

Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism remains unknown.Therefore,experimental models of neuromyelitis optica spectrum disorders are essential for exploring its pathogenesis and in screening for therapeutic targets.Since most patients with neuromyelitis optica spectrum disorders are seropositive for IgG autoantibodies against aquaporin-4,which is highly expressed on the membrane of astrocyte endfeet,most current experimental models are based on aquaporin-4-IgG that initially targets astrocytes.These experimental models have successfully simulated many pathological features of neuromyelitis optica spectrum disorders,such as aquaporin-4 loss,astrocytopathy,granulocyte and macrophage infiltration,complement activation,demyelination,and neuronal loss;however,they do not fully capture the pathological process of human neuromyelitis optica spectrum disorders.In this review,we summarize the currently known pathogenic mechanisms and the development of associated experimental models in vitro,ex vivo,and in vivo for neuromyelitis optica spectrum disorders,suggest potential pathogenic mechanisms for further investigation,and provide guidance on experimental model choices.In addition,this review summarizes the latest information on pathologies and therapies for neuromyelitis optica spectrum disorders based on experimental models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders,offering further therapeutic targets and a theoretical basis for clinical trials.

Carrimycin in the treatment of acute promyelocytic leukemia combined with pulmonary tuberculosis: A case report

BACKGROUND Pulmonary tuberculosis(PTB)is prevalent in immunocompromised populations,including patients with hematologic malignancies,human immunodeficiency virus infections,and chronic diseases.Effective treatment for acute promyelocytic leukemia(APL)combined with PTB is lacking.These patients show an extremely poor prognosis.Therefore,studies should establish efficient treatment options to improve patient survival and prognosis.CASE SUMMARY A 60-year-old male with pain in the right side of his chest and a fever for 4 d visited the outpatient department of our hospital.Peripheral blood smear revealed 54%blasts.Following bone marrow examinations,variant APL with TNRC18-RARA fusion gene was diagnosed.Chest computed tomography scan showed bilateral pneumonitis with bilateral pleural effusions,partial atelectasis in the lower lobes of both lungs,and the bronchoalveolar lavage fluid gene X-Pert test was positive,indicative of PTB.Carrimycin,ethambutol(EMB),and isoniazid(INH)were administered since he could not receive chemotherapy as the WBC count decreased continuously.After one week of treatment with carrimycin,the patient recovered from fever and received chemotherapy.Chemotherapy was very effective and his white blood cells counts got back to normal.After being given five months with rifampin,EMB and INH and chemotherapy,the patient showed complete remission from pneumonia and APL.CONCLUSION We report a case of PTB treated successfully with carrimycin with APL that requires chemotherapy.

Recent progresses in the development of tubular segmented-in-series solid oxide fuel cells:Experimental and numerical study

Solid oxide fuel cells(SOFCs)have attracted a great deal of interest because they have the highest efficiency without using any noble metal as catalysts among all the fuel cell technologies.However,traditional SOFCs suffer from having a higher volume,current leakage,complex connections,and difficulty in gas sealing.To solve these problems,Rolls-Royce has fabricated a simple design by stacking cells in series on an insulating porous support,resulting in the tubular segmented-in-series solid oxide fuel cells(SIS-SOFCs),which achieved higher output voltage.This work systematically reviews recent advances in the structures,preparation methods,perform-ances,and stability of tubular SIS-SOFCs in experimental and numerical studies.Finally,the challenges and future development of tubular SIS-SOFCs are also discussed.The findings of this work can help guide the direction and inspire innovation of future development in this field.

Impact of comorbid subthreshold depressive symptoms on cancerrelated fatigue and complications in adults with leukemia

BACKGROUND Patients not only experience symptoms caused by cancer but also suffer from the accompanying psychological pain.Therefore,these patients do not have high quality of life.According to the World Health Organization,the incidence of leukemia in China in 2020 was 5.1/100000,the mortality rate was 3.3/100000,and the prevalence rate was 16.7/100000.Therefore,it is important to examine the influence of comorbid subthreshold depressive symptoms on leukemia patients.AIM To determine the impact of comorbid subthreshold depressive symptoms on cancer-related fatigue and complications in leukemia patients,thereby providing a basis for early diagnosis and treatment in clinical practice.METHODS A questionnaire survey was conducted among leukemia patients admitted to a tertiary hospital in Xi'an,Shaanxi Province,China,from August 2022 to December 2023.Patients with a score>16 on the Chinese Classification of Mental Disorders(CCMD-3)and a Hamilton Depression Rating Scale score of 8-17 were classified as the subthreshold depressive group(n=95),while 100 leukemia patients admitted during the same period were classified as the control group.Data were collected using Epidata 3.1 software,and comparisons were made between the two groups regarding general clinical data,the Piper Fatigue Scale(PFS),the Pittsburgh Sleep Quality Index(PSQI),the Numeric Rating Scale for pain assessment,laboratory indicators,and the occurrence of complications.RESULTS In this survey,120 leukemia patients with depression were preliminarily screened,95 patients with subthreshold depression were ultimately selected as the subthreshold depression group,and 100 leukemia patients admitted during the same period were enrolled as the normal group.Comparison of basic clinical data between the two groups revealed no significant differences in age,sex,body mass index,cognitive function,or comorbidity with other chronic diseases.However,there were statistically significant differences in the use of radiotherapy and regular exercise between the two groups(P<0.05).Comparisons of scales and laboratory indicators revealed no significant differences in albumin or PSQI scores between the two groups,but there were statistically significant differences in pain scores,PSQI scores,PFS scores,hemoglobin levels,and C-reactive protein levels(P<0.05).Spearman’s correlation analysis indicated that cancer-related fatigue was correlated with age,hemoglobin levels,C-reactive protein levels,pain,and regular exercise among leukemia patients with subthreshold depression.Multivariate regression analysis revealed that advanced age,combined radiotherapy,pain,and low hemoglobin levels were risk factors for cancer-related fatigue in leukemia patients with comorbid subthreshold depression,while regular exercise was a protective factor against cancer-related fatigue.Follow-up comparisons revealed a significantly lower overall incidence of complications in the control group(4%)than in the depressive group(24.21%;P<0.001).CONCLUSION Leukemia patients with comorbid subthreshold depressive symptoms experience more severe cancer-related fatigue and a higher incidence of complications.These findings may be related to advanced age,combined radiotherapy,pain,and low hemoglobin levels,while regular exercise may effectively alleviate symptoms.

Identification of cell surface markers for acute myeloid leukemia prognosis based on multi-model analysis

Given the extremely high inter-patient heterogeneity of acute myeloid leukemia(AML),the identification of biomarkers for prognostic assessment and therapeutic guidance is critical.Cell surface markers(CSMs)have been shown to play an important role in AML leukemogenesis and progression.In the current study,we evaluated the prognostic potential of all human CSMs in 130 AML patients from The Cancer Genome Atlas(TCGA)based on differential gene expression analysis and univariable Cox proportional hazards regression analysis.By using multi-model analysis,including Adaptive LASSO regression,LASSO regression,and Elastic Net,we constructed a 9-CSMs prognostic model for risk stratification of the AML patients.The predictive value of the 9-CSMs risk score was further validated at the transcriptome and proteome levels.Multivariable Cox regression analysis showed that the risk score was an independent prognostic factor for the AML patients.The AML patients with high 9-CSMs risk scores had a shorter overall and event-free survival time than those with low scores.Notably,single-cell RNA-sequencing analysis indicated that patients with high 9-CSMs risk scores exhibited chemotherapy resistance.Furthermore,PI3K inhibitors were identified as potential treatments for these high-risk patients.In conclusion,we constructed a 9-CSMs prognostic model that served as an independent prognostic factor for the survival of AML patients and held the potential for guiding drug therapy.

Fasudil-modified macrophages reduce inflammation and regulate the immune response in experimental autoimmune encephalomyelitis

Multiple sclerosis is characterized by demyelination and neuronal loss caused by inflammatory cell activation and infiltration into the central nervous system.Macrophage polarization plays an important role in the pathogenesis of experimental autoimmune encephalomyelitis,a traditional experimental model of multiple sclerosis.This study investigated the effect of Fasudil on macrophages and examined the therapeutic potential of Fasudil-modified macrophages in experimental autoimmune encephalomyelitis.We found that Fasudil induced the conversion of macrophages from the pro-inflammatory M1 type to the anti-inflammatory M2 type,as shown by reduced expression of inducible nitric oxide synthase/nitric oxide,interleukin-12,and CD16/32 and increased expression of arginase-1,interleukin-10,CD14,and CD206,which was linked to inhibition of Rho kinase activity,decreased expression of toll-like receptors,nuclear factor-κB,and components of the mitogen-activated protein kinase signaling pathway,and generation of the pro-inflammatory cytokines tumor necrosis factor-α,interleukin-1β,and interleukin-6.Crucially,Fasudil-modified macrophages effectively decreased the impact of experimental autoimmune encephalomyelitis,resulting in later onset of disease,lower symptom scores,less weight loss,and reduced demyelination compared with unmodified macrophages.In addition,Fasudil-modified macrophages decreased interleukin-17 expression on CD4^(+)T cells and CD16/32,inducible nitric oxide synthase,and interleukin-12 expression on F4/80^(+)macrophages,as well as increasing interleukin-10 expression on CD4^(+)T cells and arginase-1,CD206,and interleukin-10 expression on F4/80^(+)macrophages,which improved immune regulation and reduced inflammation.These findings suggest that Fasudil-modified macrophages may help treat experimental autoimmune encephalomyelitis by inducing M2 macrophage polarization and inhibiting the inflammatory response,thereby providing new insight into cell immunotherapy for multiple sclerosis.

Experimental investigation on coal pore-fracture variation and fractal characteristics synergistically affected by solvents for improving clean gas extraction

Chemical solvents instead of pure water being as hydraulic fracturing fluid could effectively increase permeability and improve clean methane extraction efficiency.However,pore-fracture variation features of lean coal synergistically affected by solvents have not been fully understood.Ultrasonic testing,nuclear magnetic resonance analysis,liquid phase mass spectrometry was adopted to comprehensively analyze pore-fracture change characteristics of lean coal treated by combined solvent(NMP and CS_(2)).Meanwhile,quantitative characterization of above changing properties was conducted using geometric fractal theory.Relationship model between permeability,fractal dimension and porosity were established.Results indicate that the end face fractures of coal are well developed after CS2and combined solvent treatments,of which,end face box-counting fractal dimensions range from 1.1227 to 1.4767.Maximum decreases in ultrasonic longitudinal wave velocity of coal affected by NMP,CS_(2)and combined solvent are 2.700%,20.521%,22.454%,respectively.Solvent treatments could lead to increasing amount of both mesopores and macropores.Decrease ratio of fractal dimension Dsis 0.259%–2.159%,while permeability increases ratio of NMR ranges from 0.1904 to 6.4486.Meanwhile,combined solvent could dissolve coal polar and non-polar small molecules and expand flow space.Results could provide reference for solvent selection and parameter optimization of permeability-enhancement technology.

Adaptive Robust Servo Control for Vertical Electric Stabilization System of Tank and Experimental Validation

A tracking stability control problem for the vertical electric stabilization system of moving tank based on adaptive robust servo control is addressed.This paper mainly focuses on two types of possibly fast timevarying but bounded uncertainty within the vertical electric stabilization system:model parameter uncertainty and uncertain nonlinearity.First,the vertical electric stabilization system is constructed as an uncertain nonlinear dynamic system that can reflect the practical mechanics transfer process of the system.Second,the dynamical equation in the form of state space is established by designing the angular tracking error.Third,the comprehensive parameter of system uncertainty is designed to estimate the most conservative effects of uncertainty.Finally,an adaptive robust servo control which can effectively handle the combined effects of complex nonlinearity and uncertainty is proposed.The feasibility of the proposed control strategy under the practical physical condition is validated through the tests on the experimental platform.This paper pioneers the introduction of the internal nonlinearity and uncertainty of the vertical electric stabilization system into the settlement of the tracking stability control problem,and validates the advanced servo control strategy through experiment for the first time.

Overview of novel nanobiosensors for electrochemical and optical diagnosis of leukemia:Challenge and opportunity

Leukemia is one of the ten types of cancer that causes the biggest death in the world.Compared to other types of cancer,leukemia has a low life expectancy,so an early diagnosis of the cancer is necessary.A new strategy has been developed to identify various leukemia biomarkers by making blood cancer biosensors,especially by developing nanomaterial applications so that they can improve the performance of the biosensor.Although many biosensors have been developed,the detection of leukemia by using nanomaterials with electrochemical and optical methods is still less carried out compare to other types of cancer biosensors.Even the acoustic and calorimetric testing methods for the detection of leukemia by utilizing nanomaterials have not yet been carried out.Most of the reviewed works reported the use of gold nanoparticles and electrochemical characterization methods for leukemia detection with the object of study being conventional cancer cells.In order to be used clinically by the community,future research must be carried out with a lot of patient blood objects,develop non-invasive leukemia detection,and be able to detect all types of blood cancer specifically with one biosensor.This can lead to a fast and accurate diagnosis thus allowing for early treatment and easy periodic condition monitoring for various types of leukemia based on its biomarker and future design controlable via internet of things(IoT)so that why would be monitoring real times.

Bone marrow microRNA-34a is a good indicator for response to treatment in acute myeloid leukemia

Background:microRNA 34a(miR 34a)had been reported to have a diagnostic role in acute myeloid leukemia(AML).However,its value in the bone marrow(BM)of AML patients,in addition to its role in response to therapy is still unclear.The current study was designed to assess the diagnostic,prognostic,and predictive significance of miR 34a in the BM of AML patients.Methods:The miR.34a was assed in BM aspirate of 82 AML patients in relation to 12 normal control subjects using qRT-PCR.The data were assessed for correlation with the relevant dinical critenia,response to therapy,disease-free survival(DFS),and overall survival(OS)rates.Results:miR.34a was significantly downregulated in AML patients[0.005(3.3×10^(-6)-1.32)],compared to the control subjects[0.108(3.2× 10^(-4)-1.64),p=0.021].The.median relative quantification(RQ)of miR-34a was 0.106(range;0-32.12).The specifaity,sensitivity,and area under the curve(AUC)for the diagnosis of AML were(58.3%,69.5%,0.707,respectively,p=0.021).patients with upregulated miR-34a showed decreased platelets count<34.5 × 10^(9)/L,and achieved early complete remission(CR,p=0.031,p=0.044,respectively).Similarly,patients who were refractory to therapy showed decreased miR 34a levels in comparison to those who achieved CR[0.002(0-0.01)and 0.12(0-32.12),respectively,p=0.002].Therefore,miR 34a could significantly identify patients with CR with a specificity of 75%and sensitivity of 100%at a cut-off of 0.014(AUC=0.927,p=0.005).There was no considerable association between miR-34a expression and survival rates of the induded AML patients.Condusion:miR-34a could be a beneficial diagnostic biomarker for AML patients.In addition,it serves as a good indicator for response to therapy,which could possibly identify patients who are refractory to treatment with 100%sensitivity and 75%specificity.

Synergistic Effects of Glutamine Deprivation and Metformin in Acute Myeloid Leukemia

Objective The metabolic reprogramming of acute myeloid leukemia(AML)cells is a compensatory adaptation to meet energy requirements for rapid proliferation.This study aimed to examine the synergistic effects of glutamine deprivation and metformin exposure on AML cells.Methods SKM-1 cells(an AML cell line)were subjected to glutamine deprivation and/or treatment with metformin or bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide(BPTES,a glutaminase inhibitor)or cytarabine.Cell viability was detected by Cell Counting Kit-8(CCK-8)assay,and cell apoptosis and reactive oxygen species(ROS)by flow cytometry.Western blotting was conducted to examine the levels of apoptotic proteins,including cleaved caspase-3 and poly(ADP-ribose)polymerase(PARP).Moreover,the human long noncoding RNA(lncRNA)microarray was used to analyze gene expression after glutamine deprivation,and results were confirmed with quantitative RT-PCR(qRT-PCR).The expression of metallothionein 2A(MT2A)was suppressed using siRNA.Cell growth and apoptosis were further detected by CCK-8 assay and flow cytometry,respectively,in cells with MT2A knockdown.Results Glutamine deprivation or treatment with BPTES inhibited cell growth and induced apoptosis in SKM-1 cells.The lncRNA microarray result showed that the expression of MT family genes was significantly upregulated after glutamine deprivation.MT2A knockdown increased apoptosis,while proliferation was not affected in SKM-1 cells.In addition,metformin inhibited cell growth and induced apoptosis in SKM-1 cells.Both glutamine deprivation and metformin enhanced the sensitivity of SKM-1 cells to cytarabine.Furthermore,the combination of glutamine deprivation with metformin exhibited synergistic antileukemia effects on SKM-1 cells.Conclusion Targeting glutamine metabolism in combination with metformin is a promising new therapeutic strategy for AML.

A New Method for Diagnosis of Leukemia Utilizing a Hybrid DL-ML Approach for Binary and Multi-Class Classification on a Limited-Sized Database

Infection of leukemia in humans causes many complications in its later stages.It impairs bone marrow’s ability to produce blood.Morphological diagnosis of human blood cells is a well-known and well-proven technique for diagnosis in this case.The binary classification is employed to distinguish between normal and leukemiainfected cells.In addition,various subtypes of leukemia require different treatments.These sub-classes must also be detected to obtain an accurate diagnosis of the type of leukemia.This entails using multi-class classification to determine the leukemia subtype.This is usually done using a microscopic examination of these blood cells.Due to the requirement of a trained pathologist,the decision process is critical,which leads to the development of an automated software framework for diagnosis.Researchers utilized state-of-the-art machine learning approaches,such as Support Vector Machine(SVM),Random Forest(RF),Na飗e Bayes,K-Nearest Neighbor(KNN),and others,to provide limited accuracies of classification.More advanced deep-learning methods are also utilized.Due to constrained dataset sizes,these approaches result in over-fitting,reducing their outstanding performances.This study introduces a deep learning-machine learning combined approach for leukemia diagnosis.It uses deep transfer learning frameworks to extract and classify features using state-of-the-artmachine learning classifiers.The transfer learning frameworks such as VGGNet,Xception,InceptionResV2,Densenet,and ResNet are employed as feature extractors.The extracted features are given to RF and XGBoost classifiers for the binary and multi-class classification of leukemia cells.For the experimentation,a very popular ALL-IDB dataset is used,approaching a maximum accuracy of 100%.A private real images dataset with three subclasses of leukemia images,including Acute Myloid Leukemia(AML),Chronic Lymphocytic Leukemia(CLL),and Chronic Myloid Leukemia(CML),is also employed to generalize the system.This dataset achieves an impressive multi-class classification accuracy of 97.08%.The proposed approach is robust and generalized by a standardized dataset and the real image dataset with a limited sample size(520 images).Hence,this method can be explored further for leukemia diagnosis having a limited number of dataset samples.

Damage Mechanism of CK2 and IKAROS in Philadelphia Like Acute Lymphoblastic Leukemia

Acute lymphoblastic leukemia (ALL) is characterized by immature and poorly differentiated B lymphocytes in large numbers in the blood. B cells are distinct from the cell types involved in their development (common lymphoid progenitor cells, pro-B cells, pre-B cells, and mature cells). The process of B cell maturation depends on precise communication within the cell: signals activate specific genes that are essential for proper development. Errors in this intricate signaling network can lead to issues with B cell function and contribute to disease. B-lineage acute lymphoid leukemias, malignancies of precursor-stage B lymphoid cells inhibit lymphoid differentiation, leading to abnormal cell proliferation and survival. The process of developing leukemia (leukemogenesis) can be triggered by an overproduction of both hematopoietic stem cells (the cells that form all blood cells) and the immature versions of white blood cells called lymphoblasts. Acute lymphoblastic leukemia (ALL) with the presence of the Philadelphia chromosome (ALL Ph) is classified as a high-risk manifestation of the disease, this chromosome is the product of the reciprocal translocation, whose product is a BCR-ABL fusion protein. It is a highly active tyrosine kinase that can transform hematopoietic cells into cytokine-independent. Hyperphosphorylation cascades inhibit the differentiating function of IKZF1 as a tumor suppressor gene which leads to an abnormal proliferation of B cells due to the presence of the Philadelphia chromosome;it inhibits the differentiating process, leukemogenesis involving immature B cells in the bloodstream can result from the uncontrolled growth and division of hematopoietic stem cells and immature lymphoblasts (the precursors to B cells).

Non-canonical BRAF variants and rearrangements in hairy cell leukemia

Hairy cell leukemia(HCL)is an uncommon mature B-cell malignancy characterized by a typical morphology,immunophenotype,and clinical profile.The vast majority of HCL patients harbor the canonical BRAF V600E mutation which has become a rationalized target of the subsequently deregulated RAS-RAF-MEK-MAPK signaling pathway in HCL patients who have relapsed or who are refractory to front-line therapy.However,several HCL patients with a classical phenotype display non-canonical BRAF mutations or rearrangements.These include sequence variants within alternative exons and an oncogenic fusion with the IGH gene.Care must be taken in the molecular diagnostic work-up of patients with typical HCL but without the BRAF V600E to include investigation of these uncommon mechanisms.Identification,functional characterization,and reporting of further such patients is likely to provide insights into the pathogenesis of HCL and enable rational selection of targeted inhibitors in such patients if required.

Marine Predators Algorithm with Deep Learning-Based Leukemia Cancer Classification on Medical Images

In blood or bone marrow,leukemia is a form of cancer.A person with leukemia has an expansion of white blood cells(WBCs).It primarily affects children and rarely affects adults.Treatment depends on the type of leukemia and the extent to which cancer has established throughout the body.Identifying leukemia in the initial stage is vital to providing timely patient care.Medical image-analysis-related approaches grant safer,quicker,and less costly solutions while ignoring the difficulties of these invasive processes.It can be simple to generalize Computer vision(CV)-based and image-processing techniques and eradicate human error.Many researchers have implemented computer-aided diagnosticmethods andmachine learning(ML)for laboratory image analysis,hopefully overcoming the limitations of late leukemia detection and determining its subgroups.This study establishes a Marine Predators Algorithm with Deep Learning Leukemia Cancer Classification(MPADL-LCC)algorithm onMedical Images.The projectedMPADL-LCC system uses a bilateral filtering(BF)technique to pre-process medical images.The MPADL-LCC system uses Faster SqueezeNet withMarine Predators Algorithm(MPA)as a hyperparameter optimizer for feature extraction.Lastly,the denoising autoencoder(DAE)methodology can be executed to accurately detect and classify leukemia cancer.The hyperparameter tuning process using MPA helps enhance leukemia cancer classification performance.Simulation results are compared with other recent approaches concerning various measurements and the MPADL-LCC algorithm exhibits the best results over other recent approaches.

Experimental investigation on the permeability of gap-graded soil due to horizontal suffusion considering boundary effect

The boundary condition is a crucial factor affecting the permeability variation due to suffusion.An experimental investigation on the permeability of gap-graded soil due to horizontal suffusion considering the boundary effect is conducted,where the hydraulic head difference(DH)varies,and the boundary includes non-loss and soil-loss conditions.Soil samples are filled into seven soil storerooms connected in turn.After evaluation,the variation in content of fine sand(ΔR_(f))and the hydraulic conductivity of soils in each storeroom(C_(i))are analyzed.In the non-loss test,the soil sample filling area is divided into runoff,transited,and accumulated areas according to the negative or positive ΔR_(f) values.ΔR_(f) increases from negative to positive along the seepage path,and Ci decreases from runoff area to transited area and then rebounds in accumulated area.In the soil-loss test,all soil sample filling areas belong to the runoff area,where the gentle-loss,strengthened-loss,and alleviated-loss parts are further divided.ΔR_(f) decreases from the gentle-loss part to the strengthened-loss part and then rebounds in the alleviated-loss part,and C_(i) increases and then decreases along the seepage path.The relationship between ΔR_(f) and Ci is different with the boundary condition.Ci exponentially decreases with ΔR_(f) in the non-loss test and increases with ΔR_(f) generally in the soil-loss test.

Acute Leukemia in Niger: Epidemiological, Diagnostic and Therapeutic Aspects

Objective: Improve the care of patients followed for acute leukemia in the Oncohematology department of the National Hospital of Niamey. Methods: This was a prospective study, over a period of 2 years from January 1, 2018 to December 31, 2019, in patients with acute leukemia in the Oncohematology department of the National Hospital of Niamey (HNN), whose diagnosis was made on a blood smear associated with a myelogram and immunophenotyping and who were consenting. Results: We collected 25 cases of acute leukemia confirmed by myelogram and immunophenotyping. The mean age of the patients was 31.32 years, with a predominance of women, a sex ratio of 0.92. Pupils and students were in the majority with 40% and most came from the Niamey region, i.e. 68%. Anemic syndrome was the most common clinical sign in 96%. ALL predominated in 64% of cases. On the blood count, the hyperleukocytosis was more marked in AML (mean white count: 197256.6 elts/mm3) than in ALL (137891.6 elts/mm3), it was the same for thrombocytopenia which is more marked in AML (75588.89/mm3) than in ALL (52156.25/mm3). Therapeutically, 52% of patients received chemotherapy. The mean overall survival was 16.223 ± 3.191 months, including a mean survival for AML of 6.853 ± 1200 months compared to 21.720 ± 5.920 months for ALL. Conclusion: Acute leukemia still remains a major problem in our context, due to the precariousness of limited financial, diagnostic and therapeutic resources. Thus reflecting in our results, the increasing number of cases, the diagnostic delay and the guarded prognosis. This is the reality in several other countries in the sub-region and even in certain developed countries.