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Tumors are phenotypically heterogeneous and include subpopulations of cancer cells with stemlike properties. The natural product salinomycin, a K+-selective ionophore, was recently found to exert selectivity against such cancer stem cells. This selective effect is thought to be due to inhibition of the Wnt signaling pathway, but the mechanistic basis remains unclear. Here, we develop a functionall
Bayesian decision analysis is a useful method for risk management decisions, but is limited in its ability to consider severe uncertainty in knowledge, and value ambiguity in management objectives. We study the use of robust Bayesian decision analysis to handle problems where one or both of these issues arise. The robust Bayesian approach models severe uncertainty through bounds on probability dis
Background A clustering of cardiovascular risk factors is denoted the metabolic syndrome (MetS), but the mechanistic underpinnings of this clustering is not clear. Using large-scale metabolomics, we aimed to find a metabolic profile common for all five components of MetS. Methods and findings 791 annotated non-xenobiotic metabolites were measured by ultra-performance liquid chromatography tandem m
BACKGROUND: Caveolin-1 (CAV1) is associated with cholesterol-rich membrane raft domains and is a master regulator of cell signaling and membrane transport. Here, we investigated CAV1's role in cellular compartments of breast cancer in relation to signaling pathways, clinicopathological features, and clinical outcomes.METHODS: CAV1 levels were evaluated with immunohistochemistry in cytoplasm of inv
Context: There is a dispute whether obesity without major metabolic derangements may represent a benign condition or not. Objective: We aimed to compare the plasma metabolome in obese subjects without metabolic syndrome (MetS) with normal-weight subjects without MetS and with obese subjects with MetS. Methods: This was a cross-sectional study at 2 academic centers in Sweden. Individuals from 3 pop
Legal persons have traditionally been understood as entities with legal rights and/or duties. This traditional concept of legal personhood has been challenged during the last decades: In legal practice through the global development in law where previous legal non-persons such as different non-human natural entities, non-human animals, fetuses and artificial intelligences have been ascribed, or be
At the emergency department (ED), it is important to quickly and accurately determine which patients are likely to have a major adverse cardiac event (MACE). Machine learning (ML) models can be used to aid physicians in detecting MACE, and improving the performance of such models is an active area of research. In this study, we sought to determine if ML models can be improved by including a prior
Introduction: Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease affecting multiple organs in the human body, including the central nervous system. Recently, an artificial intelligence method called BrainAGE (Brain Age Gap Estimation), defined as predicted age minus chronological age, has been developed to measure the deviation of brain aging from a healthy population us
Haematopoietic stem cell (HSC) self-renewal is a process that is essential for the development and homeostasis of the blood system. Self-renewal expansion divisions, which create two daughter HSCs from a single parent HSC, can be harnessed to create large numbers of HSCs for a wide range of cell and gene therapies, but the same process is also a driver of the abnormal expansion of HSCs in diseases
Background: Systemic lupus erythematosus (SLE) often presents with neuropsychiatric (NP) involvement, including cognitive impairment and depression. Past magnetic resonance imaging (MRI) research in SLE patients showed smaller hippocampal volumes but did not investigate other medial temporal lobe (MTL) regions. Our study aims to compare MTL subregional volumes in SLE patients to healthy individual
A naturalistic view should make us appreciate the rich possibilities of nature. This naturalistic point of departure, as formulated by Willem B. Drees, invites reflection on the relationship between nature and spirituality. Today, the concept of sustainability occupies a key role in what has come to be the greatest challenge ever that humankind has faced together at the same moment in history. Usu
Focusing on three initiatives of the United Nations Framework Convention on Climate Change (UNFCCC) Secretariat – the Momentum for Change Initiative, the Lima–Paris Action Agenda, and the Non-state Actor Zone for Climate Action – this chapter studies how an international environmental bureaucracy can evolve from a low-key and servant-like secretariat to an actor in its own right. It argues that in
