Nutrient metabolism and cancer in thein vivocontext: a metabolic game of give and take

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Digital health technology used in emergency large-scale vaccination campaigns in low- and middle-income countries: a narrative review for improved pandemic preparedness

Introduction Large-scale vaccination campaigns can benefit from using digital health tools, particularly in low- and middle-income countries (LMICs). Selecting the best tool to fit into a pre-existing digital landscape can be challenging. Areas covered We conducted a narrative review in PubMed and the grey literature for data available within 5 years to provide an overview of digital health tools used in large-scale vaccination campaigns for outbreak response in LMICs. We discuss tools used along the typical steps of a vaccination process. Digital tool functionalities and technical specifications, open-source options, data privacy and security concerns, and lessons learned from the use of these tools are discussed. Expert opinion The landscape of digital health tools for large-scale vaccination processes in LMICs is growing. For efficient implementation, countries should prioritize the appropriate tool(s) depending on their needs and available resources, develop a robust framework around data privacy and security, and select sustainable features. Improving internet connectivity and digital literacy in LMICs will facilitate adoption. This review may aid LMICs still needing to prepare large-scale vaccination campaigns in the selection of supporting digital health tools. Further research on impact and cost-effectiveness is needed

Salicylate activates AMPK and synergizes with metformin to reduce the survival of prostate and lung cancer cells ex vivo through inhibition of de novo lipogenesis

Aspirin, the pro-drug of salicylate, is associated with reduced incidence of death from cancers of the colon, lung and prostate and is commonly prescribed in combination with metformin in individuals with type 2 diabetes. Salicylate activates the AMP-activated protein kinase ( AMPK ) by binding at the A-769662 drug binding site on the AMPK β1-subunit, a mechanism that is distinct from metformin which disrupts the adenylate charge of the cell. A hallmark of many cancers is high rates of fatty acid synthesis and AMPK inhibits this pathway through phosphorylation of acetyl-CoA carboxylase ( ACC ). It is currently unknown whether targeting the AMPK-ACC-lipogenic pathway using salicylate and/or metformin may be effective for inhibiting cancer cell survival. Salicylate suppresses clonogenic survival of prostate and lung cancer cells at therapeutic concentrations achievable following the ingestion of aspirin ( < 1.0 mM ); effects not observed in prostate ( PNT1A ) and lung ( MRC-5 ) epithelial cell lines. Salicylate concentrations of 1 mM increased the phosphorylation of ACC and suppressed de novo lipogenesis and these effects were enhanced with the addition of clinical concentrations of metformin ( 100 μM ) and eliminated in mouse embryonic fibroblasts ( MEFs ) deficient in AMPK β1. Supplementation of media with fatty acids and/or cholesterol reverses the suppressive effects of salicylate and metformin on cell survival indicating the inhibition of de novo lipogenesis is probably important. Pre-clinical studies evaluating the use of salicylate based drugs alone and in combination with metformin to inhibit de novo lipogenesis and the survival of prostate and lung cancers are warranted

The development of an artificial intelligence-based digital pathology for neglected tropical diseases : a platform specific analysis of the World Health Organization diagnostic target product profile for soil-transmitted helminthiasis

The World Health Organization (WHO) recently published target product profiles (TPPs) for neglected tropical diseases (NTDs) to inform and accelerate the development of diagnostics tools necessary to achieve targets in the decade ahead. These TPPs describe the minimal and ideal requirements for various diagnostic needs related to NTD specific use-cases. An early step towards the manufacture and implementation of new diagnostics is to critically review the TPPs and translate these into an initial design and ultimately into user requirement specifications (URS). Artificial intelligence-based digital pathology (AI-DP) may overcome critical shortcomings of current standards for most NTDs reliant on microscopy, such as poor reproducibility and error-prone manual read-out. Furthermore, a digitalised workflow can create opportunities to reduce operational costs via increased throughput and automated data capture, analysis, and reporting. Despite these promising benefits, a critical review of the NTD TPPs with consideration to an AI-DP diagnostic solution is lacking. We present a systematic analysis of one of the WHO TPPs with the aim to inform the development of a URS for an AI-DP solution for NTDs. As a case study we focused on monitoring and evaluation (M&amp;amp;E) of programs designed to control soil-transmitted helminths (STHs). To this end, we start by outlining a brief overview of diagnostic needs for STHs, after which we systematically analyse the recently published WHO TPPs, highlighting the technical considerations for an AI-DP diagnostic solution to meet the minimal requirements for this TPP. Finally, we further reflect on the feasibility of an AI-DP informing STH programs towards the WHO 2030 targets in due time

Salicylate activates AMPK and synergizes with metformin to reduce the survival of prostate and lung cancer cells ex vivo through inhibition of de novo lipogenesis

Aspirin, the pro-drug of salicylate, is associated with reduced incidence of death from cancers of the colon, lung and prostate and is commonly prescribed in combination with metformin in individuals with type 2 diabetes. Salicylate activates the AMP-activated protein kinase ( AMPK ) by binding at the A-769662 drug binding site on the AMPK β1-subunit, a mechanism that is distinct from metformin which disrupts the adenylate charge of the cell. A hallmark of many cancers is high rates of fatty acid synthesis and AMPK inhibits this pathway through phosphorylation of acetyl-CoA carboxylase ( ACC ). It is currently unknown whether targeting the AMPK-ACC-lipogenic pathway using salicylate and/or metformin may be effective for inhibiting cancer cell survival. Salicylate suppresses clonogenic survival of prostate and lung cancer cells at therapeutic concentrations achievable following the ingestion of aspirin ( < 1.0 mM ); effects not observed in prostate ( PNT1A ) and lung ( MRC-5 ) epithelial cell lines. Salicylate concentrations of 1 mM increased the phosphorylation of ACC and suppressed de novo lipogenesis and these effects were enhanced with the addition of clinical concentrations of metformin ( 100 μM ) and eliminated in mouse embryonic fibroblasts ( MEFs ) deficient in AMPK β1. Supplementation of media with fatty acids and/or cholesterol reverses the suppressive effects of salicylate and metformin on cell survival indicating the inhibition of de novo lipogenesis is probably important. Pre-clinical studies evaluating the use of salicylate based drugs alone and in combination with metformin to inhibit de novo lipogenesis and the survival of prostate and lung cancers are warranted