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Infectious diseases have been continuously and increasingly threatening human health and welfare due to a variety of factors such as globalisation, environmental, demographic changes, and emerging pathogens. In order to establish an interdisciplinary approach for coordinating R&D via funding, it is imperative to discover research trends in the field. In this paper, we apply machine learning methodologies and network analyses to understand how the European Union (EU) and the United States (US) have invested their funding in infectious diseases research utilising an interdisciplinary approach. The purpose of this paper is to use public R&D project data as data and to grasp the research trends of epidemic diseases in the US and EU through scientometric analysis. [ABSTRACT FROM AUTHOR]

Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy, with relapse being a major obstacle to successful treatment. Our understanding of the mechanisms driving chemotherapy resistance and ultimately relapse in leukemia remains incomplete. Herein, we investigate the impact of the tumor microenvironment on leukemia cell drug responses using human plasma-like media (HPLM), designed to mimic physiological conditions more accurately ex vivo . We demonstrate that while most chemotherapeutics maintain an efficacy in HPLM comparable to standard tissue culture media, the thiopurines 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) exhibit significantly reduced potency and efficacy against both B- and T- leukemia cells in HPLM. By merging our understanding of thiopurines' mechanism of action with the metabolites supplemented in HPLM compared to standard media, we proposed and subsequently validated the hypothesis that hypoxanthine, a purine derivative, is responsible for conferring resistance to the thiopurines. Importantly, the concentration of hypoxanthine required for resistance is comparable to physiological levels found in vivo , supporting clinical relevance. Our findings demonstrate the utility of a more physiologic media in identifying and characterizing mechanisms by which the microenvironment can enable resistance. Understanding such interactions may inform strategies to overcome drug resistance and improve therapeutic outcomes in pediatric leukemia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Wang, Ostergaard, Kang, Sagong, Twite, Vargas-Morales and Gordon.)