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Surgical Practices in the Management of Pediatric Renal Tumors in Low- and Middle-Income Countries in the Asia Pacific Region

Othman MY, Emmanuel J, Pamungkas KO, Sutthatarn P, Nguyen TT, Moreno A, et al.

Pediatr Blood Cancer, 2025 Mar 13.
PMID: 40079682 DOI: 10.1002/pbc.31599

PURPOSE: To profile the surgical management of pediatric renal tumors rendered in low- and middle-income countries (LMICs) of the Asia Pacific region, which are not currently affiliated to any pediatric renal tumor cooperative group.
METHODS: An online survey was conducted among surgeons and urologists identified through the St. Jude Global Online Community Asia Pacific Pediatric Surgical Collaborations Group and participants of the St. Jude-VIVA Pediatric Surgical Oncology Symposium 2024.
RESULTS: Ninety-six of 99 respondents provided replies, together representing 11 countries and 51 institutions. The majority (n = 90, 93.8%) were pediatric surgeons, with 26.7% having had subspecialty training in urology or oncology; 60% had experience managing Wilms tumors for more than 5 years, though 64% performed less than three nephrectomies per year. A chemotherapy-first approach was specified by 31% of institutions, but employed by 40% of respondents in actual practice. Of those who practiced a chemotherapy-first approach, 44.8% did so without an initial biopsy. Notably, 38% of respondents and 55% of institutions did not adhere to a consistent protocol. Lymph node biopsy practices varied widely, with only 40.6% sampling routinely and 56.3% had ever experienced a tumor rupture during nephrectomy. Most (90%) perceived that Wilms tumors comprised 90% of all renal tumors in Asian children-contrary to known demographic data.
CONCLUSION: There is substantial variation in the upfront surgical management of renal tumors in Asia Pacific LMICs. Considering the unique epidemiology of renal tumors in Asians and limited surgical capabilities, there is a great need for regional collaboration to better standardize the initial surgical management approach.
Deciphering the mechanism of Annona muricata leaf extract in alloxan-nicotinamide-induced diabetic rat model with 1H-NMR-based metabolomics approach

Zubaidi SN, Wong PL, Qadi WSM, Dawoud EAD, Hamezah HS, Baharum SN, et al.

J Pharm Biomed Anal, 2025 Mar 12;260:116806.
PMID: 40106911 DOI: 10.1016/j.jpba.2025.116806

The leaves of Annona muricata Linn. have long been utilized in traditional medicine for diabetes treatment, and there is no study that has employed a metabolomics approach to investigate the plant's effects in managing the disease. We aimed to explore the antidiabetic effects of the standardised A. muricata leaf extract on diabetes-induced rats by alloxan monohydrate (Ax) and nicotinamide (NA) using a proton nuclear magnetic resonance (¹H-NMR)-based metabolomics approach. Absolute quantification was performed on the leaf extract using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Two different doses of the extract were administered orally for four weeks to diabetic rats induced with Ax + NA, and physical evaluations, biochemical analyses, and ¹H-NMR metabolomics of urine and serum were assessed. The results showed that quercetin 3-rutinoside was the most abundant compound in the 80 % ethanolic extract of A. muricata leaf. The induction of type 2 diabetes mellitus (T2DM) in the rat model was confirmed by the clear metabolic distinction between normal rats, diabetic rats, and metformin-treated diabetic rats. The low-dose of A. muricata leaf extract (200 mg/kg) was found to exhibit better results, significantly reducing serum urea levels in diabetic rats, with effects comparable to those of metformin. Additionally, metabolite analysis from ¹H-NMR metabolomics of serum and urine showed a slight shift toward normal metabolic profiles in the treated diabetic rats. Pathway analysis revealed alterations in the tricarboxylic acid cycle (TCA), pyruvate metabolism, and glycolysis/gluconeogenesis pathways in the diabetic rat model, which were improved following treatment with the A. muricata leaf extract. Overall, this study provides scientific support for its traditional use in diabetes management and offers new insights into the underlying molecular mechanisms.
Fulltext Plasmodium knowlesi Cytoadhesion Involves SICA Variant Proteins

Peterson MS, Joyner CJ, Lapp SA, Brady JA, Wood JS, Cabrera-Mora M, et al.

Front Cell Infect Microbiol, 2022;12:888496.
PMID: 35811680 DOI: 10.3389/fcimb.2022.888496

Plasmodium knowlesi poses a health threat throughout Southeast Asian communities and currently causes most cases of malaria in Malaysia. This zoonotic parasite species has been studied in Macaca mulatta (rhesus monkeys) as a model for severe malarial infections, chronicity, and antigenic variation. The phenomenon of Plasmodium antigenic variation was first recognized during rhesus monkey infections. Plasmodium-encoded variant proteins were first discovered in this species and found to be expressed at the surface of infected erythrocytes, and then named the Schizont-Infected Cell Agglutination (SICA) antigens. SICA expression was shown to be spleen dependent, as SICA expression is lost after P. knowlesi is passaged in splenectomized rhesus. Here we present data from longitudinal P. knowlesi infections in rhesus with the most comprehensive analysis to date of clinical parameters and infected red blood cell sequestration in the vasculature of tissues from 22 organs. Based on the histopathological analysis of 22 tissue types from 11 rhesus monkeys, we show a comparative distribution of parasitized erythrocytes and the degree of margination of the infected erythrocytes with the endothelium. Interestingly, there was a significantly higher burden of parasites in the gastrointestinal tissues, and extensive margination of the parasites along the endothelium, which may help explain gastrointestinal symptoms frequently reported by patients with P. knowlesi malarial infections. Moreover, this margination was not observed in splenectomized rhesus that were infected with parasites not expressing the SICA proteins. This work provides data that directly supports the view that a subpopulation of P. knowlesi parasites cytoadheres and sequesters, likely via SICA variant antigens acting as ligands. This process is akin to the cytoadhesive function of the related variant antigen proteins, namely Erythrocyte Membrane Protein-1, expressed by Plasmodium falciparum.
Hidden Concepts in the History and Philosophy of Origins-of-Life Studies: a Workshop Report

Mariscal C, Barahona A, Aubert-Kato N, Aydinoglu AU, Bartlett S, Cárdenas ML, et al.

Orig Life Evol Biosph, 2019 Sep;49(3):111-145.
PMID: 31399826 DOI: 10.1007/s11084-019-09580-x

In this review, we describe some of the central philosophical issues facing origins-of-life research and provide a targeted history of the developments that have led to the multidisciplinary field of origins-of-life studies. We outline these issues and developments to guide researchers and students from all fields. With respect to philosophy, we provide brief summaries of debates with respect to (1) definitions (or theories) of life, what life is and how research should be conducted in the absence of an accepted theory of life, (2) the distinctions between synthetic, historical, and universal projects in origins-of-life studies, issues with strategies for inferring the origins of life, such as (3) the nature of the first living entities (the "bottom up" approach) and (4) how to infer the nature of the last universal common ancestor (the "top down" approach), and (5) the status of origins of life as a science. Each of these debates influences the others. Although there are clusters of researchers that agree on some answers to these issues, each of these debates is still open. With respect to history, we outline several independent paths that have led to some of the approaches now prevalent in origins-of-life studies. These include one path from early views of life through the scientific revolutions brought about by Linnaeus (von Linn.), Wöhler, Miller, and others. In this approach, new theories, tools, and evidence guide new thoughts about the nature of life and its origin. We also describe another family of paths motivated by a" circularity" approach to life, which is guided by such thinkers as Maturana & Varela, Gánti, Rosen, and others. These views echo ideas developed by Kant and Aristotle, though they do so using modern science in ways that produce exciting avenues of investigation. By exploring the history of these ideas, we can see how many of the issues that currently interest us have been guided by the contexts in which the ideas were developed. The disciplinary backgrounds of each of these scholars has influenced the questions they sought to answer, the experiments they envisioned, and the kinds of data they collected. We conclude by encouraging scientists and scholars in the humanities and social sciences to explore ways in which they can interact to provide a deeper understanding of the conceptual assumptions, structure, and history of origins-of-life research. This may be useful to help frame future research agendas and bring awareness to the multifaceted issues facing this challenging scientific question.