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Background: This study analyzed data from two consecutive protocols for children newly diagnosed with acute lymphoblastic leukemia (ALL) to determine the clinical impact of minimal/measurable residual disease (MRD) and recently identified tumor genetic subtypes. Methods: Genetic subtypes were determined by sequential approaches including DNA indexing, reverse transcriptase–polymerase chain reaction, multiplex ligation‐dependent probe amplification, and RNA‐sequencing. MRD was assessed by flow cytometry. The Taiwan Pediatric Oncology Group TPOG‐ALL‐2013 study enrolled patients who received MRD‐directed therapy. Results: The 5‐year event‐free survival (EFS) and overall survival rates in the 2013 cohort were 77.8% and 86.9% compared to those of the 2002 cohort, which were 62.4% and 76.5%. Among patients treated with MRD‐guided therapy, those with ETV6‐RUNX1 fusion and high hyperdiploidy had the highest 5‐year EFS (91.4% and 89.6%, respectively). The addition of dasatinib improved outcomes in patients with BCR‐ABL1 ALL. Recently identified subtypes like DUX4‐rearranged, ZNF384‐rearranged, MEF2D‐rearranged, and PAX5alt subtypes were frequently positive for MRD after remission induction, and these patients consequently received intensified chemotherapy. Treatment intensification according to the MRD improved the outcomes of patients presenting DUX4 rearrangements. In high‐risk or very‐high‐risk subtypes, the TPOG‐ALL‐2013 regimen did not confer significant improvements compared to TPOG‐ALL‐2002, and the outcomes of BCR‐ABL1‐like, MEF2D‐rearranged, and KMT2A‐rearranged ALL subtypes (in addition to those of T‐cell ALL) were not sufficiently good. Novel agents or approaches are needed to improve the outcomes for these patients. Conclusions: The TPOG‐ALL‐2013 study yielded outcomes superior to those of patients treated in the preceding TPOG‐ALL‐2002 study. This study provides important data to inform the design of future clinical trials in Taiwan. Plain language summary: MRD‐directed therapy improved the outcomes for pediatric ALL, especially standard‐risk patients.Genomic analyses and MRD might be used together for risk‐directed therapy of childhood ALL.Our work provides important data to inform the design of future clinical trials in Taiwan Genomic analyses and minimal/measurable residual disease together might be the best fit for risk‐directed therapy of childhood acute lymphoblastic leukemia to improve outcomes. [ABSTRACT FROM AUTHOR]

Philadelphia chromosome-like (Ph-like) acute lymphoblastic leukaemia (ALL), a high-risk subtype characterised by genomic alterations that activate cytokine receptor and kinase signalling, is associated with inferior outcomes in most childhood ALL clinical trials. Half of the patients with Ph-like ALL have kinase rearrangements or fusions. We examined the frequency and spectrum of these fusions using a retrospective cohort of 212 newly diagnosed patients with childhood B-cell ALL. Samples without known chromosomal alterations were subject to multiplex reverse transcription polymerase chain reaction to identify known Ph-like kinase fusions. Immunoglobulin heavy chain locus (IGH) capture and kinase capture were applied to samples without known kinase fusions. We detected known kinase fusions in five of 212 patients, comprising EBF1-PDGFRB, ETV6-ABL1, ZC3HAV1-ABL2, EPOR-IGH, and CNTRL-ABL1. Two patients with P2RY8-CRLF2 were identified. Patients with non-Ph kinase fusions had inferior 5-year event-free survival and overall survival compared with patients with other common genetic alterations. The prevalence of non-Ph kinase fusions in our Taiwanese cohort was lower than that reported in Caucasian populations. Future clinical trials with tyrosine kinase inhibitors may be indicated in Taiwan because of the inferior outcomes for B-cell ALL with kinase fusions. [ABSTRACT FROM AUTHOR]

Currently, the coronavirus disease 2019 (COVID-19) crisis has rapidly spread worldwide. As the earliest outbreak area of the pandemic, Wuhan, People's Republic of China, is gradually recovering to its normal state under the effective control of government authorities. Outpatient services in major hospitals are now being restored. An accumulation of asymptomatic infections is a potential risk for medical personnel, especially when there is crowding in hospitals. As the biggest center for orthopaedic patients in Wuhan, our orthopaedic outpatient department admits >300 patients per day. Optimal guidelines on how to handle this huge number of patients during the post-outbreak stage of the COVID-19 pandemic, particularly with regard to potential asymptomatic infection, are urgently needed for orthopaedic surgeons. We have developed and proposed applicable guidelines to fill this knowledge gap, including the necessary protective strategies for medical personnel in orthopaedic outpatient and inpatient wards as well as during surgery. We also have provided mental health recommendations for health-care workers. To the best of our knowledge, these guidelines are the first of their kind for orthopaedic surgeons who are slowly reestablishing medical activity following the pandemic. [ABSTRACT FROM AUTHOR]

Glycidyl esters (GEs) and 3-monochloropropanediol esters (3-MCPDEs) are process contaminants commonly found in refined edible oils which are often added to infant formulas. The Taiwan Food and Drug Administration (TFDA) launched regulations for GEs in infant formulas that went into effect on 1 July 2021. To investigate levels of GEs and 3-MCPDEs in infant formula powder, 45 products were sampled and analysed during 2020-2021. The contents of GEs and 3-MCPDEs in formulas of different brands significantly varied, but their concentrations in all of the formulas complied with European Union (EU) regulations. Infant formulas containing palm oil had significantly higher 3-MCPDE levels in both extracted oils and milk powder than those without palm oil. Concentrations of GEs and 3-MCPDEs in infant formula powder and extracted oils were significantly lower in products from Europe than those from Australia and New Zealand. Infants aged 0-1 years in Taiwan who consumed only infant formula showed a margin of exposure (MoE) exceeding 25,000. Mean consumer exposures to 3-MCPDEs stayed below the tolerable daily intake (TDI), while high exposures at the 95th percentile (P95) exceeded the TDI by 1.7-fold. Herein, we present the changing trends in the risk assessment results of infant formula across various countries in the decade. Implementation of regulations and mitigation strategy effectively reduced the risk of infants being exposed to GEs and 3-MCPDEs through infant formula.

Glycidyl esters (GEs) and 3-monochloropropane-1,2-diol esters (3-MCPDEs) are carcinogenic contaminants found in refined oils. This study aimed to determine levels of GEs and 3-MCPDEs in packaged foodstuffs, and estimate daily exposure levels using food consumption data. The analysis involved Soxtec extraction and gas chromatography-mass spectrometry, and the recovery of spiked GEs and 3-MCPDEs was within the range of 80%∼110%. Results showed that GEs and 3-MCPDEs were almost ubiquitous in food products (95%), with the highest concentrations found in processed fats, followed by cookies and spreads. Food products containing palm-derived oils had significantly higher levels of contaminants (p < 0.05), with up to 58.1% of palm oil-containing foodstuffs exceeding the upper limits of either GEs or 3-MCPDEs set by the European Union. Cookies and instant noodles were identified as the main sources of exposure to GEs and 3-MCPDEs, with potential daily intake levels exceeding the tolerable daily intakes in children aged 0 ∼ 12 years., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Wei-Ju Lee reports financial support was provided by National Science and Technology Council., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Antrodia cinnamomea, a polyporus mushroom of Taiwan, has long been used as a remedy for cancer, hypertension, and hangover, with an annual market of over $100 million (US) in Taiwan. We obtained a 32.15-Mb genome draft containing 9,254 genes. Genome ontology enrichment and pathway analyses shed light on sexual development and the biosynthesis of sesquiterpenoids, triterpenoids, ergostanes, antroquinonol, and antrocamphin. We identified genes differentially expressed between mycelium and fruiting body and 242 proteins in the mevalonate pathway, terpenoid pathways, cytochrome P450s, and polyketide synthases, which may contribute to the production of medicinal secondary metabolites. Genes of secondary metabolite biosynthetic pathways showed expression enrichment for tissue-specific compounds, including 14-α-demethylase (CYP51F1) in fruiting body for converting lanostane to ergostane triterpenoids, coenzymes Q (COQ) for antroquinonol biosynthesis in mycelium, and polyketide synthase for antrocamphin biosynthesis in fruiting body. Our data will be useful for developing a strategy to increase the production of useful metabolites.