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In recent decades, researchers have focused on developing less toxic and more precise cancer therapies. Carbon nanodots (CDs) are among the most promising technologies due to their high biocompatibility, tunable fluorescence, and ability to facilitate photothermal and photodynamic therapy. This study explores the synthesis and characterization of two CDs conjugated with Salphen metal complexes, namely, CDs-PEG-M1 and CDs-PEG-M2 , through Sonogashira coupling. Their interaction with G-quadruplex DNA structures (G4s), motifs largely involved in cancer development, was evaluated using various spectroscopic techniques. The results indicate that CDs-PEG-M1 exhibits greater effectiveness in stabilizing G4 structures compared to the metal complex alone or nonfunctionalized CDs. This enhanced stabilization suggests that CDs-PEG-M1 could reduce the concentration of the metal complex needed for potential antitumor applications, thereby minimizing side effects on nontarget tissues. When tested on breast cancer models (MDA-MB-231 as a triple-negative model and MCF-7 as a HER-2 positive model) and on a healthy cell line (HDFa), the CDs-PEG-M1 conjugate reduced cell viability in a concentration- and time-dependent manner, showing greater potency and selectivity against cancer cells compared to virgin CDs and the free M1 complex. This synergistic anticancer effect, driven by the interaction with G4 structures and reactive oxygen species production, underscores the potential of CDs-PEG-M1 as a targeted nanotheranostic tool.

Flavin-like ligands ( L-1 and L-2 ) with extended π-conjugation were synthesized using microwave-assisted techniques. An N , N -chelating fragment was integrated into alloxazine units, providing binding sites for metal ions while retaining redox activity. The complexation capability of L-1 and L-2 with two prototypical Ru-scaffolds was examined to design Ru(II) complexes ( M-1 and M-2 ), whose electronic properties were studied and compared with their corresponding ligands via absorption and emission spectroscopy, computational analysis (density functional theory (DFT) and time-dependent DFT (TD-DFT)), and cyclic voltammetry (CV). The ability of L-1 and M-1 to undergo alloxazine/isoalloxazine tautomerization was demonstrated to play a crucial role in the photocatalytic oxidation of NADH, including under green and red wavelengths. Moreover, the interaction of M-1 and M-2 with B-DNA and G-quadruplex structures was investigated. M-2 showed high stabilization of Kit1 and h-Telo oligonucleotides. Meanwhile, M-1 demonstrated switchable emissive properties with B-DNA and induced conformational changes in the h-Telo G-quadruplex structure.

In this contribution we report the synthesis, characterization and in vitro anticancer activity of novel cyclometalated 4-phenylthiazole-derived ruthenium(II) (2a-e) and osmium(II) (3a-e) complexes. Formation and sufficient purity of the complexes were unambigiously confirmed by 1 H-, 13 C- and 2D-NMR techniques, X-ray diffractometry, HRMS and elemental analysis. The binding preferences of these cyclometalates to selected amino acids and to DNA models including G-quadruplex structures were analyzed. Additionally, their stability and behaviour in aqueous solutions was determined by UV-Vis spectroscopy. Their cellular accumulation, their ability of inducing apoptosis, as well as their interference in the cell cycle were studied in SW480 colon cancer cells. The anticancer potencies were investigated in three human cancer cell lines and revealed IC 50 values in the low micromolar range, in contrast to the biologically inactive ligands.

Abstract Purpose Combined immunomodulatory and antiviral treatment was administered to three patients with newly diagnosed HIV-associated primary central nervous system lymphoma (PCNSL) in an attempt to improve outcomes. Patients and methods Three patients from our institution who were recently diagnosed with HIV-associated PCNSL received intravenous azidothymidine (AZT) 1.6 gr. bid for two weeks, followed by oral AZT 250 mg bid from day 15. In addition, complementary highly active antiretroviral therapy (HAART) with a second nucleoside reverse transcriptase inhibitor (NRTI) plus one protease inhibitor (PI) and interleukin 2 (IL-2) subcutaneously 2 million units twice daily (bid) plus foscarnet 90 mg/kg bid were administered on days 1-14. One patient received anti-EpsteinBarr virus (EBV)-maintenance therapy with ganciclovir, followed by cidofovir 1. Results All patients experienced progressive disease while on induction therapy, and switched early to whole-brain radiation therapy (WBRT) as second linetreatment. No grade 3 or 4 toxicities were observed. Two patients died on days 50 and 166 respectively due to progressive disease. The third patient with histologically proven lymphoproliferation and only suspected PCNSL remained alive at 53 months. He was on HAART and remained clinically and neurologically stable. Conclusion Although IL-2, HAART, high-dose AZT and foscarnet are used for other HIV-related conditions, they did not demonstrate benefit in lymphoma remission for 2 HIVassociated PCNSL patients. The third patient went into delayed remission after additional radiotherapy and was in good clinical and neurological health status over 53 months after diagnosis.

Standard operating procedures for autologous stem cell transplantation (SCT) aim to guarantee best possible engraftment. Three procedures are routinely used for transplant infusion: regular bag infusion (Procedure 1), injection via syringe (Procedure 2), and combination of regular bag infusion and syringe (Procedure 3). We conducted a retrospective analysis of all autologous stem cell transplants done in the hematology department of the Vivantes Clinic Neukoelln in Berlin, Germany, between January 1, 2016 and March 4, 2017. Of the total of 69 patients, 17 underwent Procedure 1, 32 Procedure 2, and 20 Procedure 3. Although speed of transplant reinfusion differed significantly between procedure types, these differences had no effect on duration of leukopenia. However, duration of leukopenia did correlate with need for blood transfusion and use of antibiotics. Our findings contradict the general perception that very rapid reinfusion is necessary. Nevertheless, considering the limitations of this study (retrospective, single center, small sample size) and that longer duration of aplasia is associated with greater need for intervention, efficient transplant reinfusion is advisable. More research is needed regarding timeliness and type of procedure used., (© 2021. Japanese Society of Hematology.)

Patients with acute myeloid leukemia (AML) and a FLT3 internal tandem duplication (ITD) have poor outcomes to current treatment. A phase 2 hypothesis-generating trial was conducted to determine whether the addition of the multitargeted kinase inhibitor midostaurin to intensive chemotherapy followed by allogeneic hematopoietic cell transplantation (alloHCT) and single-agent maintenance therapy of 12 months is feasible and favorably influences event-free survival (EFS) compared with historical controls. Patients 18 to 70 years of age with newly diagnosed AML and centrally confirmed FLT3 -ITD were eligible: 284 patients were treated, including 198 younger (18-60 years) and 86 older (61-70 years) patients. Complete remission (CR) rate, including CR with incomplete hematological recovery (CRi) after induction therapy, was 76.4% (younger, 75.8%; older, 77.9%). The majority of patients in CR/CRi proceeded to alloHCT (72.4%). Maintenance therapy was started in 97 patients (34%): 75 after alloHCT and 22 after consolidation with high-dose cytarabine (HiDAC). Median time receiving maintenance therapy was 9 months after alloHCT and 10.5 months after HiDAC; premature termination was mainly a result of nonrelapse causes (gastrointestinal toxicity and infections). EFS and overall survival at 2 years were 39% (95% confidence interval [CI], 33%-47%) and 34% (95% CI, 24%-47%) and 53% (95% CI, 46%-61%) and 46% (95% CI, 35%-59%) in younger and older patients, respectively. EFS was evaluated in comparison with 415 historical controls treated within 5 prospective trials. Propensity score-weighted analysis revealed a significant improvement of EFS by midostaurin (hazard ratio [HR], 0.58; 95% CI, 0.48-0.70; P < .001) overall and in older patients (HR, 0.42; 95% CI, 0.29-0.61). The study was registered at www.clinicaltrials.gov as #NCT01477606., (© 2019 by The American Society of Hematology.)

An intelligent optimization technology was proposed to mitigate prevalent multi-defects, particularly failure, wrinkling, and springback in sheet metal forming. This method combined deep neural networks (DNNs), genetic algorithms (GAs), and Monte Carlo simulation (MCS), collectively as DNN-GA-MCS. Our primary aim was to determine intricate process parameters while elucidating the intricate relationship between processing methodologies and material properties. To achieve this goal, variable blank holder force (VBHF) trajectories were implemented into five sub-stroke steps, facilitating adjustments to the blank holder force via numerical simulations with an oil pan model. The Forming Limit Diagram (FLD) predicted by machine learning algorithms based on the Generalized Incremental Stress State Dependent Damage (GISSMO) model provided a robust framework for evaluating sheet failure dynamics during the stamping process. Numerical results confirmed significant improvements in formed quality: compared with the average value of training sets, the improvements of 18.89%, 13.59%, and 14.26% are achieved in failure, wrinkling, and springback; in the purposed two-segmented mode VBHF case application, the average value of three defects is improved by 12.62%, and the total summation of VBHF is reduced by 14.07%. Statistical methodologies grounded in material flow analysis were applied, accompanied by the proposal of distinctive optimization strategies for the die structure aimed at enhancing material flow efficiency. In conclusion, our advanced methodology exhibits considerable potential to improve sheet metal forming processes, highlighting its significant effect on defect reduction. [ABSTRACT FROM AUTHOR]

This study investigates the sensitivity of the square cup forming process. It analyses how the uncertainties in the material properties, friction and process conditions affect the results of the square cup, such as equivalent plastic strain, geometry change, thickness reduction, punch force and springback. The cup flange and the die curvature region are identified as highly affected areas, while the cup bottom is least affected by the uncertainties. Two sensitivity analysis techniques, PAWN and Sobol indices, are compared. In particular, the study shows that PAWN indices require a significantly smaller number of simulations than Sobol indices, making them a more efficient choice for sensitivity analysis. While both PAWN and Sobol indices generally give comparable results, discrepancies arise in the analysis of springback, where PAWN indices show superior accuracy, particularly when dealing with multimodal distributions. This observation highlights the importance of selecting the appropriate sensitivity analysis method based on the nature of the data being analysed. These results provide insights for optimizing stamping processes to reduce production time and costs. [ABSTRACT FROM AUTHOR]

This paper presents a review on the formability evaluation of AHSS, enhancing necking-based failure criteria limitations. Complementary fracture/damage constitutive modeling approaches specifically tailored to formability evaluation, validated through numerical and experimental methods, are also subjects of research. AHSS are widely processed through sheet metal forming processes. Although an excellent choice when lightweight, high-strength, and ductility are critical factors, their multi-phase microstructure accentuates forming challenges. To accurately model forming behavior, necking-based failure criteria as well as direct fracture models require improvements. As a necking-based failure model, the conventional forming limit diagram/curve (FLD/FLC) presents limitations in estimating direct fracture (surface cracks, edge cracks, shear cracks), as well as deformation histories under non-linear strain paths. Thus, significant research efforts are being made towards the development of advanced fracture constitutive models capable of predicting fracture scenarios without necking, which are more frequently observed in the realm of AHSS. Scientific community research is divided into several directions aiming at improving the forming and fracture behavior accuracy of parts subjected to sheet metal forming operations. In this review paper, a comprehensive overview of ductile fracture modeling is presented. Firstly, the limitations of FLD/FLC in modeling fracture behavior in sheet metal forming operations are studied, followed by recent trends in constitutive material modeling. Afterwards, advancements in material characterization methods to cover a broad range of stress states are discussed. Finally, damage and fracture models predicting failure in AHSS are investigated. This review paper supplies relevant information on the current issues the sheet metal forming community is challenged with due to the trend towards AHSS employment in the automotive industry. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the prognostic relevance of cytogenetic risk in 9826 adults with acute myeloid leukemia (AML) who underwent allogeneic hematopoietic cell transplantation (HCT) during the first or second complete remission. The 5-year probabilities of overall survival (OS) were 66%, 61%, and 47% (P < 0.001), the cumulative incidences of relapse were 14%, 19%, and 32% (P < 0.001), and the cumulative incidences of non-relapse mortality (NRM) were 23%, 23%, and 25% (P = 0.208) in patients with favorable (n = 1418), intermediate (n = 6747), and poor cytogenetic risk (n = 1661), respectively. The significant effect of cytogenetic risk on OS was strong in all subgroups stratified by age, sex, performance status, disease status, donor type, conditioning intensity, graft-versus-host disease prophylaxis, and transplantation period (P < 0.001 for all). The evaluation of trends in posttransplant outcomes for patients in each cytogenetic risk category indicated that the risk of relapse declined in patients with favorable and intermediate cytogenetics and that the risk of NRM decreased in those with intermediate and poor cytogenetics. Therefore, patients with intermediate cytogenetics experienced the best OS improvement. These results confirm cytogenetic risk as a universal prognostic factor in patients with AML undergoing allogeneic HCT while highlighting the requirement for further improvements in posttransplant OS by reducing NRM in patients with favorable cytogenetics and by reducing relapse in patients with poor cytogenetics., Competing Interests: Declarations Ethical approval This study was approved by the institutional review board of the Aichi Medical University and was conducted in accordance with the Declaration of Helsinki. All patients provided informed consent for the use of their clinical information for research. Competing interests SM received research funding from Hayashikane Sangyo, and AT received research funding from Air Water, lecture fees from Novartis Pharmaceutical, and donated funds from Chugai Pharmaceutical, Kyowa Kirin, and Zenyaku Kogyo., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

During the forming process, variations in noise parameters can negatively impact product quality. To prevent waste from these fluctuations, this study suggests a method for the in-line optimisation of the deep drawing process. The noise parameter considered is the friction coefficient, assuming the variability in lubrication conditions at the blank–tool interface. The proposed approach estimates the noise factor variability during the process by tracking the draw-in of the blank at critical points. Using this estimation, the optimal blank holder force (BHF) is calculated and then adjusted in-line to modify blank sliding and prevent critical issues on the component. For this purpose, a Finite Element (FE) model of a deep drawing case study was developed, and numerical simulation results were used to construct surrogate models while estimating both the friction coefficient and optimal BHF. The FE model's predictive capability was verified through preliminary experimental tests, and the control logic was numerically validated. Results show the effectiveness of this control type. By adjusting the BHF just once, a defect-free component is achieved. This method overcomes the limitations of feedback controls, which often need multiple adjustment steps. The time required to estimate the friction coefficient and the maximum time available for adjusting the BHF without causing defects was identified. [ABSTRACT FROM AUTHOR]

We retrospectively compared baseline laboratory characteristics and PBSC mobilization parameters from these two latter I FLT3 i -mutated AML patient subgroups. Information on peripheral blood stem cell (PBSC) mobilization, at least to obtain autologous back-up harvest, in I FLT3 i -mutated AML patients receiving midostaurin-incorporating consolidation regimens is so far not available. [Extracted from the article]

Summary: The gradual rise in global warming owing to fossil fuels usage is causing massive environmental problems and global temperature rise and countries are focusing on the negative emissions technologies (NETs) to restrict the average global temperature rise to 1.5°C by 2050. As Italy instigates its stable recovery from the coronavirus emergency, the Italian government is offering Italian people financial support of up to €500 to buy a personal bicycle or e‐scooter, to reduce dependence on private cars and global warming issues and people inItaly have greeted this opportunity for new personal e‐scooters. This paper aims to employ a life cycle assessment (LCA) on the personally owned electric scooters (PEOS) that are circulating in Turin. The results are reported for five impact categories: global warming potential (GWP), acidification potential, eutrophication potential, ozone layer depletion, and human toxicity potential. We found that the environmental load associated with the usage and charging of e‐scooters is less compared with the materials and manufacturing burdens of e‐scooters. Regarding the GWP, the results of Analysis methodology of the use of the PEOS generate 21 g of CO2‐eq. per passenger‐kilometer dominated by around 50% from materials processing, 17.5% from Li‐ion battery production, 1.6% from transportation, and 30.9% from usage and charging of e‐scooter. Four scenarios are compared with the base case situation, which are the substitution of alternate materials, use of 50% recycled aluminum, transportation of e‐scooters via plan, and charging with solar power. Results from these scenarios are proved to be highly sensitive to baseline scenarios. Results also revealed that PEOS has higher (21 g CO2 eq./km) environmental consequences on the global warming potential as compared to bicycles (8 g CO2 eq./km) and lower (21 g CO2 eq./km) environmental impacts as compared with electric bicycles (40 g CO2 eq./km) and battery electric vehicles (80 g CO2 eq./km). [ABSTRACT FROM AUTHOR]

The stamping forming quality of high strength steel is poor at ambient temperature, which easily causes defects such as wrinkle, crack and springback. This article aimed at the defects in automotive rocker arm parts and proposed a multi-objective optimization scheme. The parameters of the drawing process are optimized by finite element simulation of parts. The variable blank holder force model was introduced, and the response surface multi-objective optimization functions between process parameters with maximum springback displacement and maximum thinning ratio were constructed by B-Benhnken test. The objective functions were solved by a non-dominated sorting genetic algorithm with elite hierarchy (NSGA-II), and the Pareto optimal solution set of optimization problem was obtained. The optimal solution results were numerically simulated, and qualified parts with good formation were obtained in trial production, which verified the feasibility of the multi-objective optimization scheme. [ABSTRACT FROM AUTHOR]

The plastic forming process involves many influencing factors and has some inevitable disturbance factors, rendering the multi-objective collaborative optimization difficult. With the rapid development of big data and artificial intelligence (AI) technology, intelligent process optimization has become one of the critical technologies for plastic forming. This paper elaborated on the research progress on the intelligent optimization of plastic forming and the data-driven process planning and decision-making system in plastic forming process optimization. The development trend in intelligent optimization of the plastic forming process was researched. This review showed that the intelligent optimization algorithm has great potential in controlling forming quality, microstructure, and performance in plastic forming. It is a general trend to develop an intelligent optimization model of the plastic forming process with high integration, versatility, and high performance. Future research will take the data-driven expert system and digital twin system as the carrier, integrate the optimization algorithm and model, and realize the multi-scale, high-precision, high-efficiency, and real-time optimization of the plastic forming process. [ABSTRACT FROM AUTHOR]

Opinion statement: Treatment of older adults with acute myeloid leukemia (AML) is challenging. Therapy decisions must be guided by multiple factors including aging-related conditions (e.g., comorbidities, functional impairment), therapy benefits and risks, patient preferences, and disease characteristics. Balancing these factors requires understanding the unique, and frequently higher-risk cytogenetic and molecular characteristics of AML in older adult populations, which should caution providers not to reduce therapy intensity on the basis of age alone. Instead, geriatric assessments should be employed to determine fitness for therapy. Treatment options in AML are increasingly targeted to specific mutations or recognized to have differential benefits on the basis of genomics, and representation of older adults and geriatric outcome reporting in clinical trials is improving. Additionally, newer studies have begun to explore personalized therapy strategies on the basis of initial genetic testing. Review and refinement of practice guidelines for older patients on the basis of these advances is needed and is anticipated to remain an important topic in ongoing hematology/oncology clinical education. [ABSTRACT FROM AUTHOR]

The automotive industry has been developed over the years to build lighter and more efficient vehicles; however, the manufacturing processes still have an important environmental impact starting from the acquisition of the raw material until the end of its useful life. In this sense, life cycle engineering contributes to solve the environmental issues produced by the traditional manufacturing industry by considering a process that evaluates the technical aspects of the product but also weights the importance of the environmental impact. However, since there are some alternatives that can be considered as suitable for their technical, environmental, or cost qualities, the multicriteria decision methods used as an engineering tool have been useful to balance all the needed criteria in order to make the best selection. In this sense, this research provided an analysis of five materials that could be used in a rack and pinion system and were submitted to a process of life cycle analysis to consider the environmental parameters as part of the criteria to be assessed by the multicriteria decision methods such as entropy, the Technique of Order Preference Similarity method, the complex proportional assessment method, and the multicriteria optimization and compromise solution, leading to the selection of the best material to be considered for a rack and pinion system. In this sense, the process allowed us to conclude that some materials that are useful can be evaluated by multicriteria decision methods regarding the life cycle analysis, contributing to the application of these methods to make a more environmentally responsible material selection for automotive parts. Furthermore, among all the materials, the best suited for the rack and pinion system was the AISI 4340, which was validated by finite elements simulation, showing that the selection was optimal with a maximum stress of 216.14 MPa, a maximum deformation of 0.0081 mm, and a minimum safety factor of 3.56. In this sense, the simulation validated the selection made before, guaranteeing that the methods used are feasible for automotive applications. [ABSTRACT FROM AUTHOR]

Nowadays, the accuracy and fast result-delivery of numerical simulations allow to perform not simply feasibility and validation tasks but to actually accomplish optimized process designs and solutions for the metal forming industry. This paper present a wide overview of the role of optimization and inverse analysis in the scientific and industrial community of metal forming, including the contribution of the ESAFORM association to this thematic, which is still growing after about three decades of intense research. The number of efficient and effective solutions comprising metal forming and optimization seems to increase year after year. Representative process optimization problems in sheet, bulk, and tube metal forming are presented through significant examples, and the treatment of uncertainty is also shown in stochastic approaches combined with optimization methods. Inverse problems in metal forming, which are solved with the aid of optimization methodologies, are also discussed particularly with emphasis on parameter identification problems and inverse material characterization in mechanical plasticity. The paper also identifies the most recent research trends and formulates some predictions for the future needs of industrial users. This paper shows not only that the relevance of the field of study is still increasing, but also that optimization and inverse analysis in metal forming is playing and will continue to play an important role in the digital transition of the metal forming industry, where simulation still represents the most advanced frontier. [ABSTRACT FROM AUTHOR]

Opinion statement: Treatment options in acute myeloid leukemia (AML) have improved significantly over the last decade with better understanding of disease biology and availability of a multitude of targeted therapies. The use of FLT3 inhibitors (FLT3i) in FLT3-mutated (FLT3mut) AML is one such development; however, the clinical decisions that govern their use and dictate the choice of the FLT3i are evolving. Midostaurin and gilteritinib are FDA-approved in specific situations; however, available data from clinical trials also shed light on the utility of sorafenib maintenance post-allogeneic stem cell transplantation (allo-SCT) and quizartinib as part of combination therapy in FLT3mut AML. The knowledge of the patient's concurrent myeloid mutations, type of FLT3 mutation, prior FLT3i use, and eligibility for allo-SCT helps to refine the choice of FLT3i. Data from ongoing studies will further precisely define their use and help in making more informed choices. Despite improvements in FLT3i therapy, the definitive aim is to enable the eligible patient with FLT3mut AML (esp. ITD) to proceed to allo-SCT with regimens containing FLT3i incorporated prior to SCT and as maintenance after SCT. [ABSTRACT FROM AUTHOR]

The decision-making process during system planning of power systems is something that requires integrated tools that evaluate technical parameters, environmental impact, and overall costs and benefits with various performance indicators (i.e., key performance indicators KPIs). Several cost–benefit analysis approaches have been presented worldwide, providing analytic procedures to quantify the impact and practical effects of specific electricity projects. The implementation of innovation technology into the electricity networks play a critical role to optimizing overall costs. The targets set by the Clean Energy Package have been the main driver for the disruption occurring in the electricity sector, setting electrification of sectors and digitalization as additional emerging challenges. In the present paper, an evaluation approach for the flexibility benefits of smart grid innovations will be presented, as it has been developed and implemented in the context of the Horizon 2020 Research and Innovation project FLEXITRANSTORE. Flexibility is a prerequisite in an effort to achieve an electrical system of low CO2 emissions. Moreover, flexibility contributes to the increase of renewable energy sources penetration, to the network investments deferral and to the enhancement of the efficiency of the system operation, avoiding generation capacity oversizing. Thus, flexibility has been the scope of many projects lately. FLEXITRANSTORE pilot projects are implemented in various sites across Europe and are briefly presented and the respective technologies are propagated on system level approach, evaluating the respective benefits on a specific use case for the power system of Cyprus, where the one of the pilots is located. The paper tries to show the big picture of the project and presents system study use case to highlight the system impacts of the technologies. To this direction, the installation of a BESS to the Cypriot power system is studied, in an effort to examine its impact to the enhancement of the system's flexibility, considering IRRE as an indicator. [ABSTRACT FROM AUTHOR]

Purpose of Review: With the recent approval of multiple new drugs for the treatment of acute myeloid leukemia (AML), the relevance of conventional treatment approaches, such as daunorubicin and cytarabine ("3+7") induction chemotherapy, has been challenged. We review the AML risk stratification, the efficacy of the newly approved drugs, and the role of "3+7". Recent Findings: Treatment of AML is becoming more niched with specific subtypes more appropriately treated with gemtuzumab, midostaurin, and CPX-351. Although lower intensity therapies can yield high response rates, they are less efficient at preventing relapses. The only curative potential for poor-risk AML is still an allogeneic stem cell transplant. Summary: The number of AML subtypes where 3+7 alone is an appropriate therapeutic option is shrinking. However, it remains the backbone for combination therapy with newer agents in patients suitable for intensive chemotherapy. [ABSTRACT FROM AUTHOR]

Several molecular aberrations affect the prognosis of patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) with excess blasts (EB). This study aimed to determine the incidence and clinical impact of molecular genetic aberrations in Thai patients with AML and MDS-EB, detected by the next-generation sequencing (NGS) technique. This prospective, observational study was conducted between 2018 and 2020 on newly diagnosed Thai AML or MDS-EB patients aged above 15 years. NGS was performed using a custom amplicon-based targeted enrichment assay for 42 genes recurrently mutated in myeloid neoplasms. The molecular results were correlated with baseline patient and disease characteristics as well as outcomes. Forty-nine patients were enrolled in this study. The median age was 56 years (interquartile range [IQR], 44–64), with nearly equal proportions of males and females. The median number of mutations was 3 (IQR, 2–4). The most frequent alterations were FLT3 internal tandem duplications (ITD) (28.6%), DNMT3A (24.5%), and WT1 (22.4%) mutations. FLT3-ITD was more frequent in the de novo AML group than in the MDS/secondary AML group, whereas in the MDS/secondary AML group, ASXL1, ETV6, and SRSF2 mutations were more frequent. Patients aged greater than 65 years and patients with mutated TP53 were more likely to have inferior overall survival from multivariate analysis. FLT3-ITD was the most common mutation among newly diagnosed Thai AML patients. TP53 mutation and advanced age were independent adverse factors for survival outcome. The genetic landscapes of AML patients vary between national populations. Thai Clinical Trials Registry identifier: TCTR20190227003. [ABSTRACT FROM AUTHOR]

The plastic deformation included in the technological processes of sheet metal forming allows the production of different components with different geometries. Therefore, the formability of metallic materials is an essential feature in stamping processes. One of the inevitable scattering sources when considering these processes is the variability of material properties, which can change from coil to coil, from batch to batch and from supplier to supplier. This constitutes a significant obstacle in improving the quality of any manufacturing process. The current study investigates the formability and the mechanical characterization of a defined advanced high strength steel grade, considering different suppliers, coils, and batches in order to evaluate its influence on the results of the sheet metal forming process. A microstructure analysis is also considered to understand the impact of micro-scale variables (e.g. grain size) in macro-scale behavior. Additionally, numerical simulations were taken into consideration to evaluate the influence of mechanical characterization in the results. [ABSTRACT FROM AUTHOR]

Purpose: To describe the epidemiology, clinical characteristics, diagnosis and treatment of human immunodeficiency virus (HIV)-related primary vitreoretinal lymphoma (PVRL).Methods: Narrative literature review.Results: HIV-related PVRL occurs in persons who are relatively young and generally have very low CD4+ T-cell counts. Vitritis with subretinal or sub-retinal pigment epithelial infiltrates is typical. Vitreous cytology remains the gold standard for diagnosis, supplemented by flow cytometry and genetic analyses of tumor cells, and measurement of aqueous or vitreous interleukin-10 levels. Concurrent brain involvement also may establish the diagnosis. Treatment includes antiretroviral therapy (ART), systemic chemotherapy (usually methotrexate-based) and local ocular treatment (intravitreal methotrexate, intravitreal rituximab, external beam radiotherapy). Systemic chemotherapy is of uncertain value for PVRL without other central nervous system involvement. Prognosis is poor, but has improved significantly compared to the pre-ART era.Conclusions: Ophthalmologists should consider the diagnosis of PVRL in HIV-positive individuals who present with intermediate or posterior uveitis. [ABSTRACT FROM AUTHOR]

Tubular pumps are widely used in irrigation and water conveyance projects. However, the operating head of most of these pumps is low, and only a few studies have focused on the design of an efficient tubular pump with a head more than 5 m, which is common in long-distance water supply projects. This work aims to improve the operating head and efficiency of tubular pumps while maintaining a low shaft power. The multi-objective orthogonal optimization method was used to determine the critical parameters of the tubular pump, i.e., blade number, airfoil, blade thickness and guide vane distance, and nine design schemes were selected. Next, by using computational fluid dynamics (CFD), a 3D model of the tubular pumps under different schemes was established, and the results were compared. Subsequently, the range method and weighted matrix method were utilized to find the optimized scheme. In addition, an experimental investigation was performed to verify the simulation and the performance of the designed tubular pump. The results indicated that the optimized scheme improved the operating head to 6.9 m with higher efficiency of 84.2% and a lower shaft power of 27.7 kW. The modeling results were in agreement with the experimental measurements, and the designed tubular pump had a wide range of high-efficiency zones. [ABSTRACT FROM AUTHOR]

Primary central nervous system (CNS) lymphoma is an aggressive malignancy which constitutes one of the acquired immunodeficiency syndrome -defining illnesses. Early diagnosis and timely management can increase the chances of cure. Although many times the diagnosis is straightforward, we present a case of primary CNS lymphoma in a human immunodeficiency virus--positive individual which posed as a major diagnostic dilemma with initially normal imaging findings. A 42-year-old male presented with unremitting fever and a perianal ulcer for 3 months. A battery of diagnostic tests were negative, including a positron emission tomography-computed tomography scan and a magnetic resonance imaging brain. With unresolving symptoms and a high index of suspicion as he developed dizziness and loss of balance, the same were repeated which confirmed a space-occupying lesion in the cerebellum. Although treatment was instituted, the patient did not recover and died in the 4th month of treatment. [ABSTRACT FROM AUTHOR]

In the process of hot stamping of steel sheet, there may appear crack and wrinkling defects. Therefore, in the early stage of die design, it is necessary to evaluate the reliability of its quality and optimize the original design. Considering that there are both random and fuzzy factors in the stamping process, the entropy invariance principle is used to transform the fuzzy factors to the random ones, and the equivalent hybrid reliability model of anti-defect is established. Then, the reliability index is taken as constraints in robust optimization. Finally, the stamping process of bulge formed joint is taken as an example, the maximum thinning rate is taken as objective, and the reliability of anti-crack and anti-wrinkle is taken as constraints in reliability-based robust optimization (RRDO). The results show that the standard deviation obtained by robust optimization is 77.5% less than the standard deviation obtained by deterministic optimization and the reliability obtained by RRDO is higher. Compared with the experiment result, the result obtained by RRDO is more in line with engineering practice. [ABSTRACT FROM AUTHOR]

Several small molecule inhibitors (SMIs) have been recently approved for AML patients. These targeted therapies could be more tolerable than classical antineoplastics, but potential drug-drug interactions (DDI) are relatively frequent. Underestimation or lack of appropriate awareness and management of DDIs with SMIs can jeopardize therapeutic success in AML patients, which often require multiple concomitant medications in the context of prior comorbidities or for the prevention and treatment of infectious and other complications. In this systematic review, we analyze DDIs of glasdegib, venetoclax, midostaurin, quizartinib, gilteritinib, enasidenib, and ivosidenib. CYP3A4 is the main enzyme responsible for SMIs metabolism, and strong CYP3A4 inhibitors, such azoles, could increase drug exposure and toxicity; therefore dose adjustments (venetoclax, quizartinib, and ivosidenib) or alternative therapies or close monitoring (glasdegib, midostaurin, and gilteritinib) are recommended. Besides, coadministration of strong CYP3A4 inducers with SMIs should be avoided due to potential decrease of efficacy. Regarding tolerability, QTc prolongation is frequently observed for most of approved SMIs, and drugs with a potential to prolong the QTc interval and CYP3A4 inhibitors should be avoided and replaced by alternative treatments. In this study, we critically assess the DDIs of SMIs, and we summarize best management options for these new drugs and concomitant medications. [ABSTRACT FROM AUTHOR]

With the advent of new targeted drugs in hematology and oncology patient prognosis is improved. Combination with antifungal prophylaxis challenges clinicians due to pharmacological profiles prone to drug-drug interactions (DDI). Midostaurin is a novel agent for FLT3-TKD/-ITDmut-acute myeloid leukemia (AML) and metabolized via cytochrome P450 3A4 (CYP3A4). Posaconazole is a standard of care antifungal agent used for prophylaxis during induction treatment of AML and a strong CYP3A4 inhibitor. Concomitant administration of both drugs leads to elevated midostaurin exposure. Both drugs improve overall survival at low numbers needed to treat. The impact of CYP3A4-related DDI remains to be determined. Severe adverse events have been observed; however, it remains unclear if they can be directly linked to DDI. The lack of prospective clinical studies assessing incidence of invasive fungal infections and clinical impact of DDI contributes to neglecting live-saving antifungal prophylaxis. Management strategies to combine both drugs have been proposed, but evidence on which approach to use is scarce. In this review, we discuss several approaches in the specific clinical setting of concomitant administration of midostaurin and posaconazole and give examples from everyday clinical practice. Therapeutic drug monitoring will become increasingly important to individualize and personalize antineoplastic concomitant and antifungal treatment in the context of DDI. Pharmaceutical companies addressing the issue in clinical trials may take a pioneer role in this field. Other recently developed and approved drugs for the treatment of AML likely inhere potential of DDI marking a foreseeable issue in future treatment of this life-threatening disease. [ABSTRACT FROM AUTHOR]

To high-precision control the springback of high-strength steel (HSS) in cold roll forming, the 3D finite element analysis (FEA) models of hat-shaped sectional HSS roll forming process were built with the professional roll forming software COPRA. Two conventional angle adjusting methods for HSS, i.e., the Namaste-type and the Platform-type applied widely for complex-sectional normal steel, easily lead to the edge waves and asymmetric behavior, respectively, especially high springback that is difficult to control by the FEA simulation and practical production of HSS cold roll forming process. The roll design of the UDT (USTB-Durable T)-type angle adjusting method was developed to significantly reduce springback with the improvement of the edge waves and asymmetric behavior in the hat-shaped sectional HSS roll forming process by the FEA simulation. The proposed angle compensation method based on UDT-type angle adjusting method achieved high-precision springback control by the FEA simulation, which provides a novel approach for springback control effectively in complex-sectional HSS roll forming process. The industrial application gives remarkable results that the hat-shaped sectional HSS product can strictly meet market requirements of less than 0.5° by the proposed angle compensation method based on UDT-type angle adjusting method. [ABSTRACT FROM AUTHOR]

The addition of midostaurin, a FLT3-inhibitor, to intensive chemotherapy (IC) was previously shown to improve outcome of younger patients with FLT3-mutated AML. The toxicity and efficacy of adding midostaurin to IC in patients not originally included in the RATIFY study or with intensified daunorubicin dosing are unknown. We conducted a retrospective, multi-center, historical-control study to characterize the safety and efficacy of adding midostaurin to IC in a "real-world" setting. Sixty-nine adult patients were included in the analysis (midostaurin n = 34, historical controls n = 35) with a mean follow-up of 18.4 (± 15) months. Median age of patients was 60 (range 26-82) years; 32% and 20% of patients were > 65 and 70 years, respectively. No differences in baseline characteristics were noted between the groups. Midostaurin was administered with 90 mg/m2 daunorubicin in 29% of patients; One-third of patients experienced dose reductions/interruptions during midostaurin therapy. Overall toxicity was comparable between the midostaurin and control groups.CR/CRi rates were higher in patients treated with midostaurin compared with controls (80% vs. 57%, p = 0.047) and significantly more patients in the midostaurin group were transplanted in first remission (95% vs. 68%, p = 0.04).Median OS and DFS were higher in the midostaurin vs. control group (not reached vs. 11 months (p = 0.085) and 13 vs. 6 months (p = 0.09), respectively). In our analysis, midostaurin was not associated with increased toxicity including in older patients, in those with secondary AML or when administered with intensified daunorubicin dosage. Higher remission rates in the midostaurin group and increased transplantation rates in first CR were associated with a trend towards better outcomes. [ABSTRACT FROM AUTHOR]

In sheet metal forming, springback represents a major drawback increasing die set-up problems, especially for ultra-high strength steels. Finite Element Analysis is a well-established method to simulate the process during design, and multicriteria optimizations, for example, via surrogate models, are investigated in order to develop integrated design. Since to take into account also springback compensation die design may involve a large number of geometric variables, this paper presents a robust design formulation, based on the adoption of the shape function optimization, to describe springback in terms of weights directly associated to global shape variations of the die shape. Doing so, multicriteria optimization, which involves also die compensation, can be set up in a more intuitive approach, as requested in the preliminary steps of die design. After the introduction of the industrial problem, the mathematical formulation of the shape function optimization is presented together with its novel extension to Robust Design, which is based on the Dual Response Surface. Through a test case derived from the head part of a B-pillar, stamped from a Dual Phase sheet 1.5 mm thick, this novel extension investigates the effect of 6% variation from nominal values of initial yield stress and thickness. Results demonstrate the feasibility of the procedure, underlying that an optimal compensation may not be optimal in terms of process robustness. [ABSTRACT FROM AUTHOR]

Ribs are the forming components of the framework of an airplane wing. The nose ribs studied have a U-shaped geometry that consisted of a flat plate, a curved flange with various radius of curvature, and straight flange, and were produced by a stamping process. During stamping, some defects such as thinning, thickening, wrinkling, and springback may occur. To design a forming tool that produces good quality, it was essential to understand the influence of process variables. This study evaluated the influence of stamping process variables on the formability of the nose rib for prevention of excessive thinning and control of the springback phenomenon. Three important process variables namely, blank holder gap, die corner radius, and clearance between the die and the punch were analyzed during an Al-2024-O nose rib stamping. The stamping simulation was a nonlinear problem in nonlinear behavior of solid materials and contacts, which was applied to an elastic–plastic material employed with contact behavior conditions. A DOE design matrix was generated by a full factorial design with every combination of the design variables. The main process variables affecting the multi-objective function, i.e., thickness reduction ratio and springback amount were suggested through main effect analysis, along with the stamping simulation. An experiment was performed to verify the validity of the simulation results. Results indicated that the thickness reduction rate and the springback amount predicted by the simulation were in good agreement with the experimental results. The locations where the maximum thickness reduction occurred, the maximum deformation amount caused by springback, the blank holder force, and the initial blank shape were suggested in this paper. The influence of the process variables will be considered as a reference for improving the quality of the nose rib. [ABSTRACT FROM AUTHOR]

Warm forming is a very interesting solution to improve formability and reduce springback. Natural aging is an open issue for heat treatable aluminum alloys, since it causes variability in sheet metal forming operations, namely in the parts shape, as well as in-service behavior. Therefore, this work aims to study the contribution of warm forming to minimize the variability caused by natural aging and reduce the springback in sheet metal forming operations. The thermo-mechanical behavior of two Al-Mg-Si alloys, EN AW 6016-T4 and EN AW 6061-T6, is studied in function of temperature (from 22 to 300 °C) using uniaxial tensile tests, cylindrical cup tests and split ring (springback) tests. Moreover, for the EN AW 6016-T4, the study was also performed in function of the storage time (from 1 to 18 months). At 22 °C, the increase of the storage time leads to a clear increase of the yield stress and of the work hardening and, consequently, of the springback. Warm forming at temperatures between 200 and 250 °C, using a short exposure time, reduces the yield stress and the work hardening and, consequently, springback for both alloys. Moreover, the effect of natural aging is minimized. Thus, warm conditions can be used as an effective solution to minimize the variability caused by the natural aging and reduce the springback in forming operations of heat treatable aluminum alloys. [ABSTRACT FROM AUTHOR]

Due to the different chemistries and manufacturing processes applied, the mechanical property of DP780 steel produced by different production lines may be inconsistent. In order to investigate the effect of mechanical property on the forming limit, two representative stamping processes, the round-cup drawing test and the dome test, are conducted separately on two DP780 specimens with different mechanical properties. Finite element models for the round-cup drawing test and the dome test are built to analyze the stress and strain evolutions during the forming process. Based on the results of experiment and the finite element analysis, the deep drawing and bulging forming limit of DP780 steel under different mechanical properties are predicted and compared with the Cockcroft-Latham ductile fracture criterion. The limit stroke and limit strain at fracture are obtained under variations of strength coefficient K, strain hardening exponent n, Lankford coefficient r, and thickness t in a specified range. It is found that an increase in K results in a significant drop in the limit stroke and limit strain for both the drawing and bulging forming processes. The deep drawing forming limit increases while the bulging forming limit decreases as r increases. The variation of n has a positive but not drastic influence on the deep drawing and bulging forming limit. The variation of t affects the limit drawing stroke but has almost no influence on the bulging forming. Due to these considerable effects of mechanical properties, the criteria for evaluating the performance of DP steel should be revised to improve the stamping manufacturability of DP steel. [ABSTRACT FROM AUTHOR]

The Swift test was originally proposed as a formability test to reproduce the conditions observed in deep drawing operations. This test consists on forming a cylindrical cup from a circular blank, using a flat bottom cylindrical punch and has been extensively studied using both analytical and numerical methods. This test can also be combined with the Demeri test, which consists in cutting a ring from the wall of a cylindrical cup, in order to open it afterwards to measure the springback. This combination allows their use as benchmark test, in order to improve the knowledge concerning the numerical simulation models, through the comparison between experimental and numerical results. The focus of this study is the experimental and numerical analyses of the Swift cup test, followed by the Demeri test, performed with an AA5754-O alloy at room temperature. In this context, a detailed analysis of the punch force evolution, the thickness evolution along the cup wall, the earing profile, the strain paths and their evolution and the ring opening is performed. The numerical simulation is performed using the finite element code ABAQUS, with solid and solid-shell elements, in order to compare the computational efficiency of these type of elements. The results show that the solid-shell element is more cost-effective than the solid, presenting global accurate predictions, excepted for the thinning zones. Both the von Mises and the Hill48 yield criteria predict the strain distributions in the final cup quite accurately. However, improved knowledge concerning the stress states is still required, because the Hill48 criterion showed difficulties in the correct prediction of the springback, whatever the type of finite element adopted. [ABSTRACT FROM AUTHOR]

This work presents a numerical study on the influence of variability in the mechanical properties of metal sheets in predicting the occurrence of springback and maximum thinning, for a sheet metal forming process. For this purpose, a mild steel was selected as reference material and the U-channel forming process was considered. The factors selected for this variability study were Young’s modulus, the isotropic hardening law parameters, the anisotropy coefficients and the initial thickness of the sheet metal. The variability of all factors was described by a probabilistic normal distribution, with well-defined mean and standard deviation values. Firstly, one-factor-at-a-time, 1/16th fractional factorial and Plackett-Burman screening designs were tested, using FEA results of the U-channel forming process, at two levels of blank-holder force. Sensitivity studies based on analysis of main effects, index of influence and variance (ANOVA) were performed, for each screening design approach, to identify the most relevant factors concerning the occurrence of springback and maximum thinning in the forming process. The comparison between the different screening design approaches indicates that they can lead to similar results, or to the selection of different factors, depending on the sensitivity analysis procedure selected to determine the most relevant factors. Then, metamodels were established using the most relevant factors to build the response surfaces, i.e. analytical relationships between the identified relevant factors and the responses (springback and maximum thinning); consequently, the responses variability can be expeditiously evaluated. [ABSTRACT FROM AUTHOR]

Springback, which occurs during stamping of shallow-drawn titanium alloy sheets, can negatively influence the stamping accuracy and reliability of follow-up assembly and welding of parts and restrict the application of titanium alloy sheets when high precision is a requirement. Therefore, accurate prediction and control of springback in titanium alloy sheets is an industrial problem that requires urgent attention. In this paper, a TA2M titanium alloy box formed via shallow drawing is used as the research object and springback control during stamping is attempted by varying the magnitude and mode of the blank holder force (VBHF) and height of a controllable drawbead. The influences of drawbead height, VBHF magnitude, and loading mode on the resulting sheet springback are determined by means of finite element simulation and experimentation to determine the best combination yielding the minimum springback. The results of this research provide a reliable reference for future efforts to form tough materials. [ABSTRACT FROM AUTHOR]

Stress of sheet metal forming was analyzed by using the Hill theory, and the moment formula about bending shallow part was derived in sheet hydroforming. The offset distance in the stamping direction is as the size of the springback. The formulas about springback solution were obtained under the action of hydraulic pressure during the stretch bending. According to the formula, with the liquid chamber pressure increased, the force T increased, the moment M decreased, and the springback decreased. The neutral layer of stress moved to the inside of the plate under fluid pressure, and the sections of sheet are mostly in a tensile stress state and less springback after the end of hydroforming. Combined with the results of theoretical analysis and numerical simulation, the experimental method of getting the springback about bending sheet under liquid pressure is proposed, and the 3D model was got by using reverse engineering. It got the springback by comparing the punch surfaces. The test results show that the smaller the springback, the greater the fluid pressure in the forming pressure range about stainless steel metal, which accords with the theory analysis. [ABSTRACT FROM AUTHOR]

The various U-geometry parameters in the U-bending process result in processing difficulties in the control of the spring-back characteristic. In this study, the effects of U-geometry parameters, including channel width, bend angle, material thickness, tool radius, as well as workpiece length, and their design, were investigated using a combination of finite element method (FEM) simulation, and statistical analysis techniques. Based on stress distribution analyses, the FEM simulation results clearly identified the different bending mechanisms and effects of U-geometry parameters on the spring-back characteristic in the U-bending process, with and without pressure pads. The statistical analyses elucidated that the bend angle and channel width have a major influence in cases with and without pressure pads, respectively. The experiments were carried out to validate the FEM simulation results. Additionally, the FEM simulation results were in agreement with the experimental results, in terms of the bending forces and bending angles. [ABSTRACT FROM AUTHOR]

The use of metamodelling techniques in process design has become indispensable to perform faster solutions reducing time to market. This approach allows the implementation of decision support tools which are easier to use than the conventional numerical simulations. In this paper, a robust metamodelling technique has been designed and its feasibility has been validated for the crucial problem of localised thinning in sheet metal forming process. The proposed methodology is based on the innovative integration between the Design of Experimental statistical method and the Kriging one. This approach, in fact, allows to analyse contemporary the continuous and categorical factors and, as a consequence, to define a single tool for changing process conditions (i.e., material and product shape). To test the reliability of the mathematical approach, the same was performed for the case study of Incremental Sheet Forming, a process strongly affected by the not homogeneous distribution of the thickness. Taking advantage of this strategy, a wide experimental investigation has been performed to build the base of knowledge of the problem both for the metamodelling design and for the validation of the decision support tool; moreover, the experimental data were utilized to set and validate a numerical model, which was subsequently used to enrich the dataset. The proposed metamodel, suitably modified according to each process peculiarities, can be generally adapted for sheet thickness prediction. [ABSTRACT FROM AUTHOR]

Epstein Barr virus (EBV) is well known to cause different types of malignancies. In immunocompromised patients, such as those infected with human immunodeficiency virus (HIV), there is a higher likelihood of EBV related malignant transformation. Diagnosis of EBV related malignancies may be difficult and sometimes requires clinical and pathological correlation. It is very rare to have more than one type of EBV related malignancy in a single patient. Until now, there are no specific guidelines for treatment of EBV related malignancies and lymphoproliferative disorders (LPD). We present a patient who developed three different types of EBV related LPD during a sixteen-year course of HIV infection. [ABSTRACT FROM AUTHOR]

It is important to consider variations in material parameters in the design of automotive structures in order to obtain a robust and reliable design. However, expensive tests are required to gain complete knowledge of the material behavior and its associated variation. Consequently, due to time and cost constraints, simplified material scatter modeling techniques based on scatter data of typical material properties provided by the material suppliers are used at early design stages in simulation-based robustness studies. The aim of this paper is to study the accuracy of the simplified scatter modeling methods in representing the real material variation. The simplified scatter modeling methods are evaluated by comparing the material scatter obtained by them to the scatter obtained by complete tensile tests, which are obtained after detailed time-consuming experimental investigations. Furthermore, an accuracy assessment is carried out based on selected responses from an axially-crushed, square tube made from DP600 steel. [ABSTRACT FROM AUTHOR]

This article aims to investigate the means to obtain optimal hot stamping process parameters and the influence of the stochastic variability of these parameters on forming quality. A multi-objective stochastic approach, integrating response surface methodology (RSM), multi-objective genetic algorithm optimization non-dominated sorting genetic algorithm II (NSGA-II) and the Monte Carlo simulation (MCS) method is proposed in this article to achieve this goal. RSM was used to establish the relationship between the process parameters and forming quality indices. NSGA-II was utilized to obtain a Pareto frontier, which consists of a series of optimal process parameters. The MCS method was employed to study and reduce the influence of a stochastic property of these process parameters on forming quality. The results confirmed the efficiency of the proposed multi-objective stochastic approach during optimization of the hot stamping process. Robust optimal process parameters guaranteeing good forming quality were also obtained using this approach. [ABSTRACT FROM PUBLISHER]

Recently, during the fabrication of U-bent parts, increasing levels of precision have been required not only for the bend angle of the part but also for the bend radius and the flatness of its bottom surface. The conventional coined-bead technique is therefore unlikely to be applied to achieve these requirements. As an innovative variation of the coined-bead technique, the centered coined-bead technique is proposed and investigated in this study. The finite element method (FEM) was used to clearly identify the parameters of interest based on a stress distribution analysis. The results show that the centered coined-bead formation could be applied to produce a balance between the bending and reversed bending characteristics and to eliminate these characteristics in the bottom surface. Therefore, a precise bend angle and bend radius and a flat bottom surface could be achieved. The effects of the coined-bead geometry and its positioning are also examined and clearly identified, and laboratory experiments were carried out to validate the FEM simulation results. Each U-bent part could be fabricated with a precise bend angle and bend radius and a flat bottom surface using the centered coined-bead technique. The recommended coined-bead geometry and positioning are also reported. [ABSTRACT FROM AUTHOR]