Search

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]

Grid-forming inverters (GFMs) have emerged as crucial components in modern power systems, facilitating the integration of renewable energy sources and enhancing grid stability. The significance of GFMs lies in their ability to autonomously establish grid voltage and frequency, enabling grids to form and improve system flexibility. Discussing control methods for grid-forming inverters is paramount due to their crucial role in shaping grid dynamics and ensuring reliable power delivery. This paper explores the fundamental and advanced control methods employed by GFMs, explaining their operational principles and performance characteristics. Basic control methods typically involve droop control, voltage and frequency regulation, and power-balancing techniques to maintain grid stability under varying operating conditions. Advanced control strategies encompass predictive control, model predictive control (MPC), and adaptive control, which influence advanced algorithms and real-time data for enhanced system responsiveness and efficiency. A detailed analysis and performance comparison of different control methods for GFM is presented, highlighting their strengths, limitations, and suitability for diverse grid environments. Through comprehensive studies, this research interprets the ability of various control strategies to mitigate grid disturbances, optimize power flow, and enhance overall system stability. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Serum erythropoietin (S. EPO) continues to be a minor diagnostic criterion for discriminating polycythemia vera (PV) from other causes of erythrocytosis. However, in the current era of Janus kinase 2 (JAK2) mutation testing, its relevance for establishing the diagnosis of PV is controversial. AIMS AND OBJECTIVES: The study aimed to assess the utility of S. EPO in patients with absolute erythrocytosis and ascertain its sensitivity and specificity for establishing the diagnosis of PV. Further, the clinicopathological features of PV and JAK2-EPOlow erythrocytosis were compared to discriminate the two disease states. MATERIALS AND METHODS: A total of 286 samples had undergone concomitant testing for S. EPO levels and JAK2V617F mutation for various indications over a period of 60 months (January 2017-December 2021). Clinical details and laboratory parameters were retrieved from the electronic medical records. RESULTS: Among 203/286 (70%) patients with erythrocytosis, JAK2 positivity was noted in 49 (24.1%) patients. A subnormal S. EPO level (<3.2 mIU/mL) was noted in only 27/43 (62.7%) cases of de novo PV, while the postphlebotomy PV patients (n = 6) had normal S. EPO levels. The sensitivity and specificity of low S. EPO for establishing the diagnosis of PV were 62.7% and 77.4%, respectively, while the sensitivity and specificity of high Hb levels (>16.5 g/dL) with low S. EPO and for diagnosing PV was 62.7% and 79.0%, respectively, while the sensitivity of high Hb levels with JAK2 positivity was 89.7%. In addition, 14.7% (30/203) of cases of high Hb/hematocrit (median: 18 g/dL and range: 16.3-23.8 g/dL) belonged to the JAK2-EPOlow subgroup. The median age of these patients, red blood cell count, total leukocyte count, and platelet count were, however, significantly lower as compared to the PV (P < 0.05). CONCLUSION: Overall, a low sensitivity and specificity of S. EPO were observed for diagnosing PV as an isolated investigation, thus questioning its diagnostic utility, though high levels had an excellent negative predictive value. However, this simple and inexpensive test remains an important screening tool for evaluating patients with absolute erythrocytosis. [ABSTRACT FROM AUTHOR]