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Background: Mercaptopurine-induced neutropenia can interrupt chemotherapy and expose patients to infection during childhood acute lymphoblastic leukemia (ALL) treatment. Previously, six candidate gene variants associated with mercaptopurine intolerance were reported. Herein, we investigated the association between the mean tolerable dose of mercaptopurine and these genetic variants in Taiwanese patients. Methods: In total, 294 children with ALL were treated at the National Taiwan University Hospital from April 1997 to December 2017. Germline variants were analyzed for NUDT15, SUCLA2, TPMT, ITPA, PACSIN2, and MRP4. Mean daily tolerable doses of mercaptopurine in the continuation phase of treatment were correlated with these genetic variants. Results: Mercaptopurine intolerance was significantly associated with polymorphisms in NUDT15(Pvalue < 0.0001). Patients with SUCLA2variants received lower mercaptopurine doses (Pvalue?=?0.0119). The mean mercaptopurine doses did not differ among patients with TPMT, ITPA, MRP4, and PACSIN2polymorphisms (Pvalue?=?0.9461, 0.5818, and 0.7951, respectively). After multivariable linear regression analysis, only NUDT15variants retained their clinically significant correlation with mercaptopurine intolerance (Pvalue < 0.0001). Conclusion: In this cohort, the major genetic determinant of mercaptopurine intolerance was NUDT15in Taiwanese patients. Impact:

NUDT15causes mercaptopurine intolerance in children with ALL.

The NUDT15variant is a stronger predictor of mercaptopurine intolerance than TPMTin a Taiwanese cohort. This finding is similar with studies performed on Asian populations rather than Caucasians.

Pre-emptive genotyping of the patients’ NUDT15before administering mercaptopurine may be more helpful than genotyping TPMTin Asians.

This article investigates four issues, background (BKG) suppression (BS), anomaly detectability, noise effect, and interband correlation reduction (IBCR), which have significant impacts on its performance. Despite that a recently developed effective anomaly space (EAS) was designed to use data sphering (DS) to remove the second-order data statistics characterized by BKG, enhance anomaly detectability, and reduce noise effect, it does not address the IBCR issue. To cope with this issue, this article introduces band sampling (BSam) into EAS to reduce IBCR and further suppress BKG more effectively. By implementing EAS in conjunction with BSam (EAS-BSam), these four issues can be resolved altogether for any arbitrary anomaly detector. It first modifies iterative spectral–spatial hyperspectral anomaly detection (ISSHAD) to develop a new variant of ISSHAD, called iterative spectral–spatial maximal map (ISSMax), and then generalizes ISSMax to EAS-ISSMax, which further enhances anomaly detectability and noise removal. Finally, EAS-BSam is implemented to reduce IBCR. As a result, combining EAS, BSam, and ISSMax yields four versions: EAS-BSam, EAS-ISSMax, BSam-SSMAX, and EAS-BSam-SSMax. Such integration presents a great challenge because all these four versions are derived from different aspects, iterative spectral–spatial feedback process, compressive sensing, and low-rank and sparse matrix decomposition. Experiments demonstrate that EAS-BSam and EAS-BSam-SSMax show their superiority to ISSHAD and many current existing hyperspectral anomaly detection (HAD) methods.

The purpose of this study was to create a platform for conducting small animal proton FLASH irradiation at a research-specific therapy center using an auxiliary proton beam line. A dose monitoring system was implemented to provide real-time irradiation dose and dose rate time structure information, utilizing a transmission ionization chamber (TIC), a plastic scintillator-based beam position monitor, and a poor man faraday cup (PMFC). Both the TIC and PMFC were equipped with a custom-made fast-reading current integral electronics device, allowing for real-time dose monitoring with a resolution of 0.5 ms. Experimental testing showed that the maximum dose that could be delivered to the target in a single pulse of 230-MeV protons was approximately 20 Gy, during a pulse period of 199 ms, at a dose rate of 100 Gy/s. The establishment of a dedicated proton research platform at Chang Gung Memorial Hospital has enabled investigation of the biological effects of FLASH irradiation on small animals. The final setup data serves as a useful reference for both planning future experiments and improving the facility for beam users. This study’s achievement provides a valuable foundation for further research on proton FLASH irradiation, potentially offering new insights into its applications for cancer treatment.