Insufficient attention has been given to the integration of the mediating effect of Internet gaming disorder (IGD) symptoms on loneliness and four components of aggression-physical aggression, verbal aggression, anger, and hostility-in the Malaysian context. In the present study, 410 participants with (a) at least 1 year of Internet gaming experience and (b) between ages 20- to 39 years were recruited using the probability proportional to size sampling method. Participants were undergraduate students and working adults. Self-reported questionnaires (the Internet Gaming Disorder Scale, University of California, Los Angeles Loneliness Scale, and the Buss-Perry Aggression Questionnaire) were used. The present study found that loneliness positively predicted four components of aggression (i.e., anger, hostility, physical aggression, and verbal aggression) and symptoms of IGD. Relationships between loneliness and the four components of aggression were partially mediated by IGD symptoms. The present study enriches and consolidates existing empirical evidence, particularly in the Malaysian context. If the mediating effect is not emphasized, it may lead to spurious conclusions that can significantly diminish the effectiveness of interventions that are meant to manage aggression.
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.