MyMedR

Displaying all 4 publications

Abstract:

Sort:

Fulltext The administrative burden on physicians and technicians for organizing international telemedicine conferences: utility of a shared program management system in an international telemedicine network

Kudo K, Kudo T, Ueda S, Antoku Y, Tomimatsu S, Shiaw-Hooi H, et al.

Heliyon, 2022 Nov;8(11):e11297.
PMID: 36338885 DOI: 10.1016/j.heliyon.2022.e11297

BACKGROUND: The use of international telemedicine conferences for doctor-to-doctor education has increased following the coronavirus disease 2019 pandemic to ensure health and safety. Previous studies have shown that administrative tasks are an obstacle to promoting international telemedicine conferences but have not identified the type of system needed to alleviate this burden.
OBJECTIVE: The Asia-Pacific Advanced Network Medical Working Group (APAN-MWG) is an international telemedicine network that includes 1171 medical institutions and 3653 members as of July 21, 2021. The APAN-MWG has supported international telemedicine conferences since 2005 and implemented a program management system in 2014. The present study explores the conference organizers' tasks and evaluates the APAN-MWG management system through a survey of organizers.
METHODS: We developed a system called med-hok for managing conference programs, international medical institutions, and their members. We investigated all event programs using the med-hok system from June 3, 2015 to July 21, 2021. The target samples included 64 conference programs in 12 series hosted by 13 program organizers. The effectiveness of the system was evaluated using a four-point Likert scale (very good, good, poor, and very poor). The User Experience Questionnaire (UEQ) was used to assess user experience.
RESULTS: The survey response rate of the program organizers, who hosted 11 different program series in 7 Asian countries, was 92% (12/13). The administrative tasks for managing the programs were primarily handled by physicians (67%, 8/12), followed by technicians (17%, 2/12). The average program scope encompassed 7 countries, 10 institutions, and 44 members. The largest program comprised 194 members from 49 institutions in 25 countries and was managed by two physicians and one technician. Most program organizers (8/12, 67%) indicated that verifying member information was the most burdensome aspect of organizing teleconferences. Over 90% of respondents positively evaluated med-hok in the following areas: "Confirmation of institution information," "Confirmation of member information," "Confirmation of technical information," "Maintaining the latest status of the program," "Announcing and publicizing the event," and "Formatting and correcting misspellings." They rated user experience positively for all aspects (attractiveness: 1.22; practical quality: 1.42; and hedonic quality: 1.24).
CONCLUSIONS: Many tasks of organizing casual international telemedicine conferences are handled by physicians and technicians with no operating funds or staff, unlike those in large academic conferences. The proposed system was found to help program organizers manage participants and communicate information effectively. These findings suggest that international telemedicine networks should implement an administrative support system to conduct program operations efficiently.
Fulltext Novel variants in NUDT15 and thiopurine intolerance in children with acute lymphoblastic leukemia from diverse ancestry

Moriyama T, Yang YL, Nishii R, Ariffin H, Liu C, Lin TN, et al.

Blood, 2017 Sep 07;130(10):1209-1212.
PMID: 28659275 DOI: 10.1182/blood-2017-05-782383

Prolonged exposure to thiopurines (eg, mercaptopurine [MP]) is essential for curative therapy in acute lymphoblastic leukemia (ALL), but is also associated with frequent dose-limiting hematopoietic toxicities, which is partly explained by inherited genetic polymorphisms in drug metabolizing enzymes (eg, TPMT). Recently, our group and others identified germ line genetic variants in NUDT15 as another major cause of thiopurine-related myelosuppression, particularly in Asian and Hispanic people. In this article, we describe 3 novel NUDT15 coding variants (p.R34T, p.K35E, and p.G17_V18del) in 5 children with ALL enrolled in frontline protocols in Singapore, Taiwan, and at St. Jude Children's Research Hospital. Patients carrying these variants experienced significant toxicity and reduced tolerance to MP across treatment protocols. Functionally, all 3 variants led to partial to complete loss of NUDT15 nucleotide diphosphatase activity and negatively influenced protein stability. In particular, the p.G17_V18del variant protein showed extremely low thermostability and was completely void of catalytic activity, thus likely to confer a high risk of thiopurine intolerance. This in-frame deletion was only seen in African and European patients, and is the first NUDT15 risk variant identified in non-Asian, non-Hispanic populations. In conclusion, we discovered 3 novel loss-of-function variants in NUDT15 associated with MP toxicity, enabling more comprehensive pharmacogenetics-based thiopurine dose adjustments across diverse populations.
Fulltext An international retrospective study for tolerability of 6-mercaptopurine on NUDT15 bi-allelic variants in children with acute lymphoblastic leukemia

Tanaka Y, Yeoh AEJ, Moriyama T, Li CK, Kudo K, Arakawa Y, et al.

Haematologica, 2021 07 01;106(7):2026-2029.
PMID: 33504140 DOI: 10.3324/haematol.2020.266320
Fulltext Whole-transcriptome sequencing identifies a distinct subtype of acute lymphoblastic leukemia with predominant genomic abnormalities of EP300 and CREBBP

Qian M, Zhang H, Kham SK, Liu S, Jiang C, Zhao X, et al.

Genome Res, 2017 02;27(2):185-195.
PMID: 27903646 DOI: 10.1101/gr.209163.116

Chromosomal translocations are a genomic hallmark of many hematologic malignancies. Often as initiating events, these structural abnormalities result in fusion proteins involving transcription factors important for hematopoietic differentiation and/or signaling molecules regulating cell proliferation and cell cycle. In contrast, epigenetic regulator genes are more frequently targeted by somatic sequence mutations, possibly as secondary events to further potentiate leukemogenesis. Through comprehensive whole-transcriptome sequencing of 231 children with acute lymphoblastic leukemia (ALL), we identified 58 putative functional and predominant fusion genes in 54.1% of patients (n = 125), 31 of which have not been reported previously. In particular, we described a distinct ALL subtype with a characteristic gene expression signature predominantly driven by chromosomal rearrangements of the ZNF384 gene with histone acetyltransferases EP300 and CREBBP ZNF384-rearranged ALL showed significant up-regulation of CLCF1 and BTLA expression, and ZNF384 fusion proteins consistently showed higher activity to promote transcription of these target genes relative to wild-type ZNF384 in vitro. Ectopic expression of EP300-ZNF384 and CREBBP-ZNF384 fusion altered differentiation of mouse hematopoietic stem and progenitor cells and also potentiated oncogenic transformation in vitro. EP300- and CREBBP-ZNF384 fusions resulted in loss of histone lysine acetyltransferase activity in a dominant-negative fashion, with concomitant global reduction of histone acetylation and increased sensitivity of leukemia cells to histone deacetylase inhibitors. In conclusion, our results indicate that gene fusion is a common class of genomic abnormalities in childhood ALL and that recurrent translocations involving EP300 and CREBBP may cause epigenetic deregulation with potential for therapeutic targeting.