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Background: Altered T‐cell repertoire with an aberrant T‐cell activation and imbalance of the Th17/Treg cells has been reported in acquired aplastic anemia (aAA). miRNAs are well known to orchestrate T‐cell activation and differentiation, however, their role in aAA is poorly characterized. The study aimed at identifying the profile of miRNAs likely to be involved in T‐cell activation and the Th17/Treg‐cell imbalance in aAA, to explore newer therapeutic targets. Methods: Five milliliters peripheral blood samples from 30 patients of aAA and 15 healthy controls were subjected to flow cytometry for evaluating Th17‐ and Treg‐cell subsets. The differential expression of 7 selected miRNAs viz; hsa‐miR‐126‐3p, miR‐146b‐5p, miR‐155‐5p, miR‐16, miR‐17, miR‐326, and miR‐181c was evaluated in the PB‐MNCs. Expression analysis of the miRNAs was performed using qRT‐PCR and fold change was calculated by 2−ΔΔCt method. The alterations in the target genes of deregulated miRNAs were assessed by qRT‐PCR. The targets studied included various transcription factors, cytokines, and downstream proteins. Results: The absolute CD3+ lymphocytes were significantly elevated in the PB of aAA patients when compared with healthy controls (p < 0.0035), however, the CD4:CD8 ratio was unperturbed. Th17: Treg‐cell ratio was altered in aAA patients (9.1 vs. 3.7%, p value <0.05), which correlated positively with disease severity and the PNH positive aAA. Across all severities of aAA, altered expression of the 07 miRNAs was noted in comparison to controls; upregulation of miR‐155 (FC—2.174, p‐value‐0.0001), miR‐146 (FC—2.006, p‐value‐0.0001), and miR‐17 (FC—3.1, p‐value‐0.0001), and downregulation of miR‐126 (FC—0.329, p‐value‐0.0001), miR‐181c (FC—0.317, p‐value‐0.0001), miR‐16 (FC—0.348, p‐value‐0.0001), and miR‐326 (FC—0.334, p‐value‐0.0001). Target study for these miRNAs revealed an increased expression of transcription factors responsible for Th1 and Th17 differentiation (T‐bet, RORϒt, IL‐17, IL‐6, and IFN‐ϒ), T‐cell activation (NFκB, MYC, and PIK3R2), downregulation of FOX‐P3, and other regulatory downstream molecules like SHIP‐1, ETS‐1, IRAK‐1, TRAF‐6, and PTEN. Conclusion: The study for the first time highlights the plausible role of different miRNAs in deregulating the Th17/Treg‐cell imbalance in aAA, and comprehensively suggest the role of altered NF‐kB and mTOR pathways in aAA. The axis may be actively explored for development of newer therapeutic targets in aAA. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Conclusion Leukemic stem cells (LSCs) are the transcriptionally low/silent cells which are resistant to the tyrosine kinase inhibitor. These have been found to play a pivotal role in disease relapse in chronic myeloid leukemia (CML) cases. The present study evaluated the correlation of absolute CML‐LSC count in the peripheral blood (PB) at diagnosis and achievement of major molecular response (MMR) at 12 months in patients of CML‐CP.This was a prospective, observational, non‐interventional single center study including newly diagnosed adult (>18 yrs) CML‐CP patients. Absolute CD26 + CML‐LSC quantification was done by multiparametric flow cytometry. Patients were treated with Imatinib treatment and subsequently monitored at 3‐month intervals for BCR::ABL transcript levels. MMR was defined as a BCR::ABL1 transcript level of less than 0.1% on international scale.A total of 89 patients were enrolled in the study out of which 40.5% achieved MMR at 12 months. There was a significant difference in the median absolute CML‐LSC count of the patients who achieved MMR at 12 months as compared to those who did not (58.5 vs 368.1 cells/μL; p value <0.001). Using a ROC analysis, a count of <165.69 CML LSC/μL was identified to have a sensitivity of 83.8% and specificity of 72.4%, in predicting the MMR at 12 months.Absolute CML‐LSC count at diagnosis in the PB predicts the MMR achievement at 12 months. An absolute count of less than 165 cells/μL is highly predictive of achieving MMR at 12 months. [ABSTRACT FROM AUTHOR]

The multiphase matrix converter outperforms the conventional three-phase system with higher fault tolerance capability and higher power control competency. This paper discusses the direct control based on different possible switching combinations of a threephase to five-phase matrix converter (MC). The proposed control topology significantly reduces the switching commutations in a switching cycle when compared with its counterpart. The control is based on the modified space vector pulse width modulation (SVPWM) strategy. The proposed space vector scheme intelligently selects the voltage vectors to get the desired output characteristics with the least possible switching transitions in a switching cycle. Three possible cases exist in controlling space vectors based on their magnitude, the number of active switching vectors, and their commutations. The results for three different cases of SVPWM have been presented and compared. The total harmonic distortion (THD) obtained in the output is lower in case 2; however, it suffers from a higher commonmode voltage (CMV). The scheme has been successfully implemented and verified in hardware. [ABSTRACT FROM AUTHOR]

Background: Recently, CD26 have been identified as one of the promising and specific marker for the identification of leukemic stem cells (LSCs) in chronic myeloid leukemia (CML). Methods: This was a prospective, observational validation study. Peripheral blood (PB) samples from suspected cases of CML and other hematolymphoid neoplasm were evaluated for the expression of CD26 on stem cells (SC) (CD45 dim/CD34+/CD38‐) fraction by flow cytometry (FCM) using a single tube four‐color antibodies cocktail: CD45‐V500 /CD26‐PE/CD34‐PerCPcy5.5/CD38‐APC‐H7. The diagnosis of CML was confirmed using cytogenetics and/or molecular studies. Additionally, 12 paired PB and bone marrow (BM) samples of CML cases were compared for the proportion of CD26+ LSCs. Results: Expression of CD26 on the SC fraction was invariably noted in all cases (116/116) of CML, irrespective of the disease phase and transcript type. None of other neoplasm (0/26), including the Ph + ALLs expressed CD26. Proportion of SCs expressing CD26 was variable with a median (range) proportion being 61.3% (7.6%–98.6%). Evaluation of paired PB and BM samples showed similar proportion of CD26 + LSCs (R2: 0.969). Conclusion: We confirmed that FCM evaluation of CD26 expression in the PB LSCs is a rapid and specific tool for CML diagnosis. Its utility as a marker for residual disease evaluation can also be explored in the future. [ABSTRACT FROM AUTHOR]

Objective: To assess the prevalence of early T precursor‐acute lymphoblastic leukaemia (ETP‐ALL), study its clinicopathological features and devise a 'flow score' based on immunophenotypic profiles. Material Methods: This was a retrospective study where clinical and laboratory data of all consecutive T‐ALL cases were analysed to identify features differentiating ETP from non‐ETP‐ALL. The utility of a flow score based on the five commonly used markers in leukaemia panels for T‐ALL (CD34, CD8, CD5, CD13 and CD33) was evaluated to differentiate ETP from non‐ETP‐ALL. Results: Early T precursor‐acute lymphoblastic leukaemia constituted 24.2% (n = 29) of all T‐ALL cases. It was significantly more common in adults (30.2%) as compared to paediatric (17.5%) patients (P =.046). The median age of presentation was significantly higher than the non‐ETP group. (24 vs 19 years; P =.01). Patients with ETP‐ALL usually presented with organomegaly, lymphadenopathy, lower levels of haemoglobin, total leucocyte count, peripheral blood blast proportion and LDH levels as compared to non‐ETP‐ALL. The majority of ETP‐ALL cases had L2 morphology with a moderate amount of cytoplasm showing frequent blebbing. A flow score cut‐off value of ≥3 on ROC curve analysis had a sensitivity and specificity of 100% and 94.6% respectively. Conclusion: Early T precursor‐acute lymphoblastic leukaemia had unique clinical and laboratory features. The prevalence of this entity is more common in the adult population. A flow score based on a minimum of five widely used markers can confidently identify ETP‐ALL and should be included in the primary panel of markers used for flow cytometric analysis. [ABSTRACT FROM AUTHOR]

Background: About 50 different CALR frameshift mutations have been identified in BCR‐ABL1 negative MPN, all leading to the development of common new protein C terminus. Antibody targeting this terminal epitope can be useful to identify this driver mutation using immunohistochemistry. Materials and Methods: CALR mutation analysis was carried out in 51 JAK2V617F negative cases, PMF (n = 22) and ET (n = 29). PCR followed by fragment analysis was performed for molecular detection of CALR mutation. Bone marrow biopsy specimens of corresponding patients were subjected to IHC using mutation specific antibody CAL2. Staining pattern and intensity were observed. Staining of <2% of background nonmegakaryocytic (non‐ MK) cells were regarded as Pattern A, while staining of more than 2% of background nonmegakaryocytic (non‐MK) was regarded as pattern B. Results: CALR mutation was noted in 40.9% (9/22) and 41.4% (12/29) of JAK2V617F negative PMF and ET, respectively. All CALR mutated cases, irrespective of the mutation type, showed a positive IHC staining in the megakaryocytes with moderate to bright intensity. All CALR wild‐type cases were negative on IHC. (Concordance rate‐ 100%). Pattern A was noted in 40% cases, while pattern B was noted in 60% cases. Pattern A staining had significantly higher chances of having type 1 mutation as compared to pattern B. In contrast, pattern B had a nonsignificant trend toward higher bone marrow cellularity and marrow fibrosis. Conclusion: CAL2 IHC detects all types of CALR mutation. This can act as a sensitive, specific, rapid, and cost‐effective screening test for CALR mutation analysis. [ABSTRACT FROM AUTHOR]

Introduction: MicroRNAs (miRNAs) play a critical role in orchestrating T cell differentiation and activation and may thus play a vital role in acquired aplastic anemia (aAA). The study aimed to evaluate the differential expression of selected miRNAs and their relevant target genes in bone marrow samples of aAA patients. Methods: Differential expression of 8 miRNAs viz; hsa‐miR‐126‐3p, miR‐145‐5p, miR‐155‐5p, miR‐150‐5p, miR‐146b‐5p, miR‐34a, miR‐29a, and miR‐29b was evaluated in the bone marrow mononuclear cells of aAA patients. TaqMan microRNA assay was performed for preparing the cDNA of specific miRNA, followed by expression analysis using qRT‐PCR. Data were normalized using two endogenous controls, RNU6B and RNU48. Delta‐delta CT method was used to calculate the fold change (FC) of miRNA expression in individual samples, and a FC of >1.5 was taken as significant. Target genes of these miRNAs were evaluated by qRT‐PCR. Results: Thirty five samples of aAA patients and 20 controls were evaluated. Irrespective of the disease severity, five miRNAs were found to be deregulated; miR‐126 (FC‐0.348; P‐value‐.0001) and miR‐145 (FC‐0.31; P‐value‐.0001) were downregulated, while miR‐155 (FC‐3.50; P‐value‐.0067), miR‐146 (FC‐3.13; P‐value‐.0105), and miR‐150 (FC‐5.78; P‐value‐.0001) were upregulated. Target gene study revealed an upregulation of PIK3R2, MYC, SOCS1, and TRAF‐6, and downregulation of MYB. Conclusion: This is the first study from the Indian subcontinent demonstrating the presence of altered miRNA expression in the bone marrow samples of aAA patients, suggesting their role in the pathogenesis of the disease. A comprehensive study focusing on the effect of these miRNA‐mRNA interactions is likely to open new avenues of management. [ABSTRACT FROM AUTHOR]

Introduction: A prototype of good prognosis, t(8;21)‐positive AML, has diverse clinical and genetic features which affect its outcome. This study aimed at evaluating the clinico‐pathological spectrum of t(8;21)‐positive AML and ascertaining prognostic factors influencing its outcome in the Indian subcontinent. Methods: A retrospective analysis of 75 cases of t(8;21)‐positive AML diagnosed over a period of six years (2013‐2018) was carried out. Detailed clinical and laboratory data of the patients were collected from the electronic medical records and reviewed. Results: Median age was 19.5 years (range 5‐75 years) with a M:F of 1.7. Myeloid sarcoma was observed in 9.3% cases. There were 85% FAB AML‐M2, 8% AML‐M1, and 7% AML‐M4 subtypes. Prominent morphological characteristics included dyspoiesis in maturing myeloid cells (83%), long thin tapered Auer rods (58%), cytoplasmic vacuoles (58%), eosinophilia (50%), and mast cells (22%). Auer rods in maturing granulocytes (4% cases) were highly suggestive of the translocation. Additional cytogenetic abnormalities were present in 53% cases. Seventy‐one percent (25/35) achieved CR. The overall survival (OS) was 40%, with a median follow‐up of 27 months (range 4‐57 months). None of the hematological or cytogenetic factors correlated with OS, except for the presence of myeloid sarcoma which had a trend toward poor survival (P =.07). Conclusion: Outcome of t(8;21) AML is not influenced by any of the clinico‐pathological parameters, except for a myeloid sarcoma, which may herald a poor prognosis. Recognition of this distinct subtype of AML would facilitate further molecular screening for risk stratification in resource‐constrained settings. [ABSTRACT FROM AUTHOR]

The pulse‐width modulation (PWM)‐controlled modern electric drives causes some serious problems such as the generation of common‐mode voltage (CMV) and high dv/dt. The CMV might cause high‐frequency leakage currents that flow through the possible path that is bearing of the motor. Thus, the flow of current through the motor bearing leads to its premature failure. One of the main challenges in developing PWM methods for control of motor drives is the problem of CMV and its reduction/elimination. In this study, a modulation technique based on space‐vector approach is developed to reduce the CMV in a three‐to‐seven‐phase direct matrix converter. CMV reduction becomes possible by selecting suitable zero‐voltage vectors for a specific duration and the use of a selected set of active vectors for the output voltage synthesis. The proposed space‐vector PWM (SVPWM) for the reduction of CMV is performed with a seven‐phase R–L load to show the viability of the proposed technique. The proposed SVPWM technique is implemented experimentally in dSPACE working in conjunction with field‐programmable gate array processor board using a system generator. Hardware results that validate the proposed control algorithm are discussed. [ABSTRACT FROM AUTHOR]

This paper addresses multiphase matrix converter (MPMCs) modulated with Venturini's classical scalar approach. The solution to obtain time-varying modulation functions was limited to 3 × 3 configuration, which was later extended to 3 × n configuration. The equations had four constants that were common to all modulation functions; out of which two were defined arbitrarily and other two were found analytically by reducing the equation to a two-variable optimisation problem. However, in this work, an attempt is made to provide flexibility in finding other solutions by taking all the constants as variables. Thus, Differential Evolution (DE) algorithm is adopted in the proposed modulation approach to solve the complex equations thus obtained. Another aim is to find the solution for the MPMC, where inputs are more than three. It is found that the optimal solutions exist only for 3 × n configuration and are in close approximation with the results of analytical approach. Other solutions were found for certain input and output frequencies and voltage transfer ratios whose results are discussed. It is also found that the solution does not exist for configurations with input phases are other than three. The discussion is supported by simulation and experimental results on a 3 × 7 matrix converter at various values of voltage transfer ratios and input/output frequencies. [ABSTRACT FROM AUTHOR]

The article present a case study of a 67‐year‐old woman with purpuric rashes over her limbs for a week's duration. It mentions a complete blood cell count revealed pancytopenia with hemoglobin; and also mentions based on the morphological and immunophenotypic findings, a final diagnosis of early T‐cell precursor acute lymphoblastic leukemia with Auer rods was favored over an mixed phenotype acute leukemia (MPAL), T/myeloid.

In this study, common mode voltage (CMV) reduction using space vector pulse‐width modulation (SVPWM) technique is proposed for a three‐phase induction motor drive fed by a three‐to‐three phase indirect matrix converter (MC). The proposed SVPWM effectively reduces the peak of the CMV without affecting the output voltage gain. By adopting the proposed SVPWM there is no change in the dv/dt of CMV at the terminal of the machine when compared to the existing method. The proposed control is possible by proper placement of zero vectors in the rectifier stage and discarding zero voltage vectors in the inverter stage of the indirect MC. The control technique is implemented in MATLAB/Simulink environment. Hardware setup is developed and control algorithm is implemented using dSPACE working in conjunction with the FPGA interface board. The results of the proposed SVPWM are compared with the existing method of CMV elimination and the improvement is established. The simulation results obtained are verified with the experimental results. The obtained results confirm a reduction of CMV by 48% (peak) and validate the viability of the proposed scheme in a three‐phase induction motor drive system. [ABSTRACT FROM AUTHOR]

Morphological variants of plasma cells have been described in cases of Plasma cell neoplasm. Presence of these atypical forms poses difficulty in morphological diagnosis and demands the use of ancillary techniques to ascertain the nature of these atypical cells. We hereby report a series of 6 such cases where the bone marrow examination showed plasma cells with atypical morphology, leading to varied differential diagnosis; however immunophenotyping by flow cytometry in adjunct to serum electrophoresis, immunofixation and free light chain assays confirmed the diagnosis. [ABSTRACT FROM AUTHOR]

Background. The objective of this article was to study the role of high frequency ultrasound and color Doppler imaging in the diagnostic evaluation of patients with cervical lymphadenopathy. Methods. The present study was carried out over a period of 18 months and included 64 patients of different age groups presenting with cervical lymphadenopathy. Comprehensive sonographic examination of the neck for cervical lymph nodes was performed using the LOGIQ 500 ultrasound machine (GE Wipro Proseries). The scanning was performed with the patient in the supine position, and with the neck hyperextended using a pad or pillow under the shoulders in order to provide optimum exposure of the neck. The parameters considered in this study included: site, mean long axis (L), mean short axis (S), shape index (S/L), echotexture and homogenicity, margins, ancillary features like calcification, necrosis, posterior enhancement, matting and surrounding tissue changes, vascular pattern, and mean arterial resistive index (RI). These findings were correlated with fine-needle aspiration cytology and excisional biopsy. The nodes were classified as reactive, lymphomatous, and metastatic. The results were subjected to statistical analysis using SPSS software. A p value of <.05 was considered to be significant. Results. The results showed that malignant lymph nodes, especially metastatic nodes, are mostly accompanied with rounded shape, homogenous echotexture, peripheral vascularity, and significantly high RI. Among these sonographic findings, nodal shape (S/L ratio) and RI were more accurate for differentiating benign from malignant lymph nodes. Most of the malignant nodes had well-defined borders. Calcification, necrosis, posterior enhancement, matting, and hilar flow patterns were characteristically found in tubercular lymphadenitis. A combined ultrasound-guided and fine-needle aspiration (FNA) diagnosis had a high sensitivity (95.4%) and specificity (92.3) as compared with situations in which they were used alone. Conclusion. Sonographic findings have a high accuracy in differentiating benign from malignant cervical lymph nodes. An ultrasound scan can be used as the first-line imaging tool in the diagnostic evaluation of cervical lymphadenopathy, especially in developing countries like India due to its ease, noninvasiveness, reproducibility, and cost effectiveness. It can also be used as an imaging tool for theguided aspirations. However, because of some overlapping in sonographic appearances of benign and malignant nodes, this modality may not have definite diagnostic values. But when combined with FNA, it has a very high sensitivity and specificity. [ABSTRACT FROM AUTHOR]