In 1957, Hillestad et al. defined acute promyelocytic leukemia (APL) for the first time in the literature as a distinct type of acute myeloid leukemia (AML) with a "rapid downhill course" ...characterized with a severe bleeding tendency. APL, accounting for 10-15% of the newly diagnosed AML cases, results from a balanced translocation, t(15;17) (q22;q12-21), which leads to the fusion of the promyelocytic leukemia (PML) gene with the retinoic acid receptor alpha (RARA) gene. The PML-RARA fusion oncoprotein induces leukemia by blocking normal myeloid differentiation. Before using anthracyclines in APL therapy in 1973, no effective treatment was available. In the mid-1980s, all-trans retinoic acid (ATRA) monotherapy was used with high response rates, but response durations were short. Later, the development of ATRA, chemotherapy, and arsenic trioxide combinations turned APL into a highly curable malignancy. In this review, we summarize the evolution of APL therapy, focusing on key milestones that led to the standard-of-care APL therapy available today and discuss treatment algorithms and management tips to minimize induction mortality.
In this research, an optimization methodology was introduced for improving bipedal robot locomotion controlled by reinforcement learning (RL) algorithms. Specifically, the study focused on optimizing ...the Proximal Policy Optimization (PPO), Advantage Actor-Critic (A2C), Soft Actor-Critic (SAC), and Twin Delayed Deep Deterministic Policy Gradients (TD3) algorithms. The optimization process utilized the Tree-structured Parzen Estimator (TPE), a Bayesian optimization technique. All RL algorithms were applied to the same environment, which was created within the OpenAI GYM framework and known as the bipedal walker. The optimization involved the fine-tuning of key hyperparameters, including learning rate, discount factor, generalized advantage estimation, entropy coefficient, and Polyak update parameters. The study comprehensively analyzed the impact of these hyperparameters on the performance of RL algorithms. The results of the optimization efforts were promising, as the fine-tuned RL algorithms demonstrated significant improvements in performance. The mean reward values for the 10 trials were as follows: PPO achieved an average reward of 181.3, A2C obtained an average reward of -122.2, SAC reached an average reward of 320.3, and TD3 had an average reward of 278.6. These outcomes underscore the effectiveness of the optimization approach in enhancing the locomotion capabilities of the bipedal robot using RL techniques.
Ceramic materials are an indispensable part of our lives. Today, ceramic materials are mainly used in construction and kitchenware production. The fact that some deformations cannot be seen with the ...naked eye in the ceramic industry leads to a loss of time in the detection of deformations in the products. Delays that may occur in the elimination of deformations and in the planning of the production process cause the products with deformation to be excessive, which adversely affects the quality. In this study, a deep learning model based on acoustic noise data and transfer learning techniques was designed to detect cracks in ceramic plates. In order to create a data set, noise curves were obtained by applying the same magnitude impact to the ceramic experiment plates by impact pendulum. For experimental application, ceramic plates with three invisible cracks and one undamaged ceramic plate were used. The deep learning model was trained and tested for crack detection in ceramic plates by the data set obtained from the noise graphs. As a result, 99.50% accuracy was achieved with the deep learning model based on acoustic noise.
Background
Dasatinib, a potent Bcr‐Abl tyrosine kinase inhibitor, is approved for the treatment of chronic‐phase chronic myeloid leukemia (CML‐CP) in the frontline and salvage settings. Notable side ...effects include pleural effusions and myelosuppression. Dasatinib at 50 mg daily has previously been reported to be active and better tolerated than the approved 100‐mg daily dose. The aim of this study was to update the long‐term follow‐up results of dasatinib at 50 mg daily as frontline therapy for CML‐CP.
Methods
Eighty‐three patients with newly diagnosed CML‐CP received dasatinib at 50 mg daily. Eligibility and response criteria were standards used in previous protocols.
Results
After a minimum follow‐up of 12 months, 81 patients were evaluable. Two patients came off the study in less than 3 months. The rates of BCR‐ABL1 transcript levels (International Standard) at ≤10% and ≤1% at 3 months were 96% and 77%, respectively. The cumulative rates for a complete cytogenetic response by 6 and 12 months were 77% and 95%, respectively. The cumulative rates for a major molecular response, a molecular response with a 4.0‐log reduction, and a molecular response with a 4.5‐log reduction by 12 months were 81%, 55%, and 49%, respectively. Twenty‐one patients (25%) had treatment interruptions for a median of 13 days (range, 4‐64 days). Five patients (6%) developed pleural effusions; 4 of these patients (80%) required a dose reduction. Two patients (2%) failed to achieve any cytogenetic or molecular response and were taken off the study. At a median follow‐up of 24 months, none of the patients had disease transformation to an accelerated or blastic phase. The 2‐year event‐free and overall survival rates were 100%.
Conclusions
These updated results continue to support 50 mg of dasatinib daily as an effective and safe dose for early CML‐CP.
This study updates the long‐term follow‐up results for dasatinib at 50 mg daily as frontline therapy for chronic‐phase chronic myeloid leukemia. These updated results continue to support 50 mg of dasatinib daily as an effective and safe dose for early chronic‐phase chronic myeloid leukemia.
Abstract During the past 20 y, there has been much interest in sugars and especially fructose in relation to human health. Over the past decade, considerable scientific debate and controversy have ...arisen about the potential health effects of sucrose, high-fructose corn syrup (HFCS), and fructose itself. HFCS increasingly has been used as a sweetener in thousands of food products and soft drinks, leading to the development of obesity, diabetes, dyslipidemia, and metabolic syndrome (MetS) in both rodents and humans, which is associated with an increase in body weight. There is a need for detailed research on the mechanism underlying MetS that could lead to a remedy. This review will first systematically present a definition of MetS, its history, prevalence, and comparative diagnostic criteria. We will then consider fructose and its effects on human health, the diet-induced obesity model (various fat contents), the hypercholesterolemic model, the diabetes model, the hypertensive model, the MetS or insulin resistance model, and biomarkers related to MetS, in light of contemporary data using multiple databases (PubMed, MEDLINE, and OVID).
•Irisin was mainly located in the perimysium and endomysium in skeletal muscle cells.•Fetal skeletal muscle cells also produce irisin.•Testis, pancreas, liver, spleen, stomach, brain, and cardiac ...tissues produce irisin.•Skeletal muscle is not the main source of irisin.
Irisin was first identified in skeletal muscle cells, but its precise location has not yet been demonstrated, and there is limited information about irisin protein in other human and rat tissues. The present immunohistochemical study was undertaken to screen skeletal muscle and other tissues for irisin immunoreactivity. İrisin staining was found in the brain (neurons and neuroglia), cardiac and skeletal muscle (fibers) and skin (sebaceous glands) tissues in male rats. In both human adult and fetal skeletal muscle, the most intense immunohistochemical staining was in the perimysium and endomysium, in the peripheral nerve (epineurium) and axon and nerve sheaths spreading among the cells, in the sarcoplasma and subendomysium. Irisin was also demonstrated in the testis (seminiferous tubules, some spermatogenic cells in fetal and Leydig cells in fetal and adult testis, ductus epididymis in fetal human epididymis); pancreas (islets of Langerhans, serous acini cells, intralobular and intralobular ducts cells); liver (hepatocytes; Kupffer cells and sinusoidal endothelial cells); spleen (subcapsular region and periarterial lymphatic sheets); the stomach (gastric parietal cells, tunica muscularis cells). We conclude that the fat-burning protein irisin locally produced in peripheral and central tissues could act as a gatekeeper of metabolic energy regulation in those tissues, since this myokine converts white into brown adipose tissue, enhancing energy expenditure.
Photovoltaic (PV) panels exhibit a non-linear current-voltage characteristic with a Maximum Power Point (MPP) that varies due to environmental factors such as solar radiation and ambient temperature. ...In this study, an Artificial Neural Network (ANN)-based MPPT method, called the ANN-based Adaptive Reference Voltage (ARV) method, is proposed to determine the optimal operating point of the PV panel. The ANN-based ARV method is a voltage-controlled approach that can adapt to changing atmospheric conditions. The performance of the proposed method is evaluated using both a normal Proportional-Integral (PI) controller and an anti-windup PI controller. Comparative analysis is conducted with the widely used Perturb and Observe (P&O) and Incremental Conductance (INC) methods in the MATLAB/Simulink environment, considering three different atmospheric scenarios with varying radiation levels according to EN50530 standards. The proposed method demonstrates superior efficiency with overall results of 99.4%, 95.9%, and 96% in scenario 1, scenario 2, and scenario 3, respectively. Particularly, the proposed method exhibits notable superiority in rapidly changing atmospheric conditions.
Preclinically, enasidenib and azacitidine (ENA + AZA) synergistically enhance cell differentiation, and venetoclax (VEN), a small molecule Bcl2 inhibitor (i) is particularly effective in IDH2 mutated ...acute myeloid leukemia (IDH2
AML). This open label phase II trial enrolled patients (pts) with documented IDH2
AML. All patients received AZA 75 mg/m
/d x 7 d/cycle and ENA 100 mg QD continuously. Concomitant Bcl2i and FLT3i were allowed (NCT03683433).Twenty-six pts received ENA + AZA (median 68 years, range, 24-88); 7 newly diagnosed (ND) and 19 relapsed/refractory (R/R). In R/R AML patients, three had received prior ENA and none had received prior VEN. The composite complete remission rate (CRc) complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) was 100% in ND AML, and 58% in R/R AML. Median OS was not reached in ND AML with median follow-up of 13.1 months (mo); Pts treated in first relapse had improved OS than those with ≥2 relapse (median OS not reached vs 5.2 mo; HR 0.24, 95% CI 0.07-0.79, p = 0.04). Two patients received ENA + AZA with a concomitant FLT3i, one responding ND AML patient and one nonresponding R/R AML patient. Seven R/R AML pts received ENA + AZA + VEN triplet, and with median follow up of 11.2 mo, median OS was not reached and 6-mo OS was 70%. The most frequent treatment-emergent adverse events include febrile neutropenia (23%). Adverse events of special interest included all-grade IDH differentiation syndrome (8%) and indirect hyperbilirubinemia (35%). ENA + AZA was a well-tolerated, and effective therapy for elderly pts with IDH2
ND AML as well as pts with R/R AML. The addition of VEN to ENA + AZA appears to improve outcomes in R/R IDH2
AML.Clinical trial registration information: https://clinicaltrials.gov/.NCT03683433.
Infinite impulse response (IIR) systems, with their ability to model intricate system behaviors, have proven to be a powerful class of digital filters. However, accurately identifying the optimal ...filter parameters for system emulation remains a challenge. Metaheuristic algorithms have emerged as effective tools for parameter optimization in IIR filter design, allowing for the exploration of parameter spaces and the discovery of suitable filter sets. This paper introduces a novel adaptive algorithm, named simulated annealing aided artificial hummingbird optimizer (AHA-SA), which combines the strengths of the artificial hummingbird algorithm (AHA) and simulated annealing (SA). The synergistic integration of AHA and SA in the AHA-SA optimizer enables efficient search space exploration, rapid convergence, and the attainment of precise solutions. Extensive experiments demonstrate the superiority of the AHA-SA optimizer over competitive algorithms, both in terms of solution quality and convergence speed. The proposed optimizer presents a promising solution for optimization problems in various domains, with its simplicity, intuitive workflow, and potential for widespread adoption.
This paper addresses the design of an optimally executed proportional-integral-derivative (PID) controller, tailored for the speed regulation of a direct current (DC) motor. To achieve this ...objective, we present a novel hybrid algorithm, combining the gazelle optimization algorithm (GOA) with the effective simplex search method known as the Nelder-Mead (NM) technique. The fusion of these algorithms yields an innovative hybridized version, striking the balance between exploration and exploitation. The proposed approach, named the gazelle simplex optimizer (GSO), showcases great promise when applied to the task of controlling the speed regulation of a DC motor using the PID controller. To identify the optimal values for PID gains, we harness the power of a novel objective function as well, which guides the GSO in determining the most favorable controller settings. Rigorous comparative simulations are then undertaken, where we pit the GSO against several other algorithms, namely the reptile search algorithm, prairie dog optimization algorithm, weighted mean of vectors optimization, and the original GOA algorithm. These simulations allow us to assess the system's behavior through various lenses, such as statistical tests, time and frequency domain responses, robustness analysis, and changes in the objective function. The evaluations from these comprehensive tests demonstrate the superiority of the GSO-based PID controlled DC motor speed regulation system. The GSO exhibits better performance than the alternative algorithms, providing solid evidence of its effectiveness. Furthermore, the proposed GSO approach outperforms other reported PID tuning methods, affirming its prowess in achieving superior speed regulation for DC motors.
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