Breast cancer oncologists are challenged to personalize care with rapidly changing scientific evidence, drug approvals, and treatment guidelines. Artificial intelligence (AI) clinical ...decision-support systems (CDSSs) have the potential to help address this challenge. We report here the results of examining the level of agreement (concordance) between treatment recommendations made by the AI CDSS Watson for Oncology (WFO) and a multidisciplinary tumor board for breast cancer.
Treatment recommendations were provided for 638 breast cancers between 2014 and 2016 at the Manipal Comprehensive Cancer Center, Bengaluru, India. WFO provided treatment recommendations for the identical cases in 2016. A blinded second review was carried out by the center's tumor board in 2016 for all cases in which there was not agreement, to account for treatments and guidelines not available before 2016. Treatment recommendations were considered concordant if the tumor board recommendations were designated ‘recommended’ or ‘for consideration’ by WFO.
Treatment concordance between WFO and the multidisciplinary tumor board occurred in 93% of breast cancer cases. Subgroup analysis found that patients with stage I or IV disease were less likely to be concordant than patients with stage II or III disease. Increasing age was found to have a major impact on concordance. Concordance declined significantly (P ≤ 0.02; P < 0.001) in all age groups compared with patients <45 years of age, except for the age group 55–64 years. Receptor status was not found to affect concordance.
Treatment recommendations made by WFO and the tumor board were highly concordant for breast cancer cases examined. Breast cancer stage and patient age had significant influence on concordance, while receptor status alone did not. This study demonstrates that the AI clinical decision-support system WFO may be a helpful tool for breast cancer treatment decision making, especially at centers where expert breast cancer resources are limited.
Linguistic Analysis Puglielli, Annarita; Frascarelli, Mara
2011, 2011-03-29, Letnik:
220
eBook
The series publishes state-of-the-art work on core areas of linguistics across theoretical frameworks as well as studies that provide new insights by building bridges to neighbouring fields such as ...neuroscience and cognitive science. The series considers itself a forum for cutting-edge research based on solid empirical data on language in its various manifestations, including sign languages. It regards linguistic variation in its synchronic and diachronic dimensions as well as in its social contexts as important sources of insight for a better understanding of the design of linguistic systems and the ecology and evolution of language.
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•Aging is accompanied by structural changes of the brain.•Aging affects synaptic plasticity at multiple levels.•Partial overlap exists between aging and Alzheimer’s disease.•Aging ...pathways impact on pathogenesis and/or progression of Alzheimer’s disease.
As the population of people aged 60 or older continues to rise, it has become increasingly important to understand the molecular basis underlying age-related cognitive decline. In fact, a better understanding of aging biology will help us identify ways to maintain high levels of cognitive functioning throughout the aging process. Many cellular and molecular aspects of brain aging are shared with other organ systems; however, certain age-related changes are unique to the nervous system due to its structural, cellular and molecular complexity. Importantly, the brain appears to show differential changes throughout the aging process, with certain regions (e.g. frontal and temporal regions) being more vulnerable than others (e.g. brain stem). Within the medial temporal lobe, the hippocampus is especially susceptible to age-related changes. The important role of the hippocampus in age-related cognitive decline and in vulnerability to disease processes such as Alzheimer’s disease has prompted this review, which will focus on the complexity of changes that characterize aging, and on the molecular connections that exist between normal aging and Alzheimer’s disease. Finally, it will discuss behavioral interventions and emerging insights for promoting healthy cognitive aging.
Abstract The last decade has revealed that the lifespan of an organism can be modulated by the signaling pathway that acts downstream of the insulin/insulin-like growth factor 1 receptors ...(IR/IGF1-R), indicating that there is a “program” that drives the process of aging. New results have now linked the same pathway to the neurogenic capacities of the aging brain, to neurotrophin signaling, and to the molecular pathogenesis of Alzheimer's disease. Therefore, a common signaling cascade now seems to link aging to age-associated pathologies of the brain, suggesting that pharmacologic approaches aimed at the modulation of this pathway can serve to delay the onset of age-associated disorders and improve the quality of life. Work from a wide range of fields performed with different approaches has already identified some of the signaling molecules that act downstream of IGF1-R, and has revealed that a delicate checkpoint exists to balance excessive growth/“immortality” and reduced growth/“senescence” of a cell. Future research will determine how far the connection goes and how much of it we can influence.
Summary
The optimal partitioning theory predicts that plants of a given species acclimate to different environments by allocating a larger proportion of biomass to the organs acquiring the most ...limiting resource. Are similar patterns found across species adapted to environments with contrasting levels of abiotic stress?
We tested the optimal partitioning theory by analysing how fractional biomass allocation to leaves, stems and roots differed between woody species with different tolerances of shade and drought in plants of different age and size (seedlings to mature trees) using a global dataset including 604 species.
No overarching biomass allocation patterns at different tolerance values across species were found. Biomass allocation varied among functional types as a result of phenological (deciduous vs evergreen broad‐leaved species) and broad phylogenetical (angiosperms vs gymnosperms) differences. Furthermore, the direction of biomass allocation responses between tolerant and intolerant species was often opposite to that predicted by the optimal partitioning theory.
We conclude that plant functional type is the major determinant of biomass allocation in woody species. We propose that interactions between plant functional type, ontogeny and species‐specific stress tolerance adaptations allow woody species with different shade and drought tolerances to display multiple biomass partitioning strategies.
The Nϵ-lysine acetylation of cargo proteins in the lumen of the endoplasmic reticulum (ER) requires a membrane transporter (SLC33A1) and 2 acetyltransferases (NAT8B and NAT8). The ER acetylation ...machinery regulates the homeostatic balance between quality control/efficiency of the secretory pathway and autophagy-mediated disposal of toxic protein aggregates. We recently reported that the autophagy pathway that acts downstream of the ER acetylation machinery specifically targets protein aggregates that form within the secretory pathway. Genetic and biochemical manipulation of ER acetylation in a mouse model of Alzheimer disease is able to restore normal proteostasis and rescue the disease phenotype. Here we summarize these findings and offer an overview of the ER-acetylation machinery.
The Nε-amino group of lysine residues can be transiently modified by the addition of an acetyl group. Recognized functions of Nε-lysine acetylation include regulation of activity, molecular ...stabilization and conformational assembly of a protein. For more than forty years lysine acetylation was thought to occur only in the cytosol and nucleus. Targets included cytoskeletal-associated proteins as well as transcription factors, histone proteins and proteins involved in DNA recombination and repair. However, in 2007 we reported that a type I membrane protein involved in the pathogenesis of Alzheimer's disease was transiently acetylated on the ε amino group of seven lysine residues while transiting along the secretory pathway. Surprisingly, the acetylation occurred in the lumen of the endoplasmic reticulum (ER) forcing us to reconsider old paradigms. Indeed, if lysine acetylation can occur in the lumen of the ER, then all the essential biochemical elements of the reaction must be available in the lumen of the organelle. Follow-up studies revealed the existence of ER-based acetyl-CoA:lysine acetyltransferases as well as a membrane transporter that translocates acetyl-CoA from the cytosol into the ER lumen. Large-scale proteomics showed that the list of substrates of the ER-based acetylation machinery includes both transiting and resident proteins. Finally, genetic studies revealed that this machinery is tightly linked to human diseases. Here, we describe these exciting findings as well as recent biochemical and cellular advances, and discuss possible impact on both human physiology and pathology.
► Resident and transiting proteins can undergo Nε-lysine acetylation in the ER lumen. ► Two (or more) acetyl-CoA:lysine acetyltransferases are found in the ER. ► A membrane transporter translocates acetyl-CoA into the ER lumen. ► Influx of acetyl-CoA into the ER controls the induction of ERAD(II). ► Defects in the ER-based acetylation machinery are linked to human diseases.
The multicomponent Petasis borono‐Mannich reaction proceeds via an imine with the boronic acid acting as the nucleophile for the preparation of amines and their derivatives, including amino acids. In ...view of the expansion of the poorly‐exploited carbohydrate chemistry using this reaction, a new α‐hydroxy aldehyde moiety from the terminal diol of d‐glucose diacetonide was synthesized and applied to this multicomponent reaction, demonstrating the scope of this method and the applicability to the convenient preparation of a protected polyfunctional δ‐amino acid in only three synthetic steps from the Petasis reaction intermediate.
The facile synthesis of protected d‐glucodialdofuranoses from d‐glucose diacetonide enabled the multicomponent Petasis borono‐Mannich reaction at C‐6 carbon atom to give corresponding amino sugars, useful intermediates for the convenient preparation of polyfunctional δ‐amino acids.
The developing nervous system is a complex yet organized system of neurons, glial support cells, and extracellular matrix that arranges into an elegant, highly structured network. The extracellular ...and intracellular events that guide axons to their target locations have been well characterized in many regions of the developing nervous system. However, despite extensive work, we have a poor understanding of how axonal growth cones interact with surrounding glial cells to regulate network assembly. Glia-to-growth cone communication is either direct through cellular contacts or indirect through modulation of the local microenvironment via the secretion of factors or signaling molecules. Microglia, oligodendrocytes, astrocytes, Schwann cells, neural progenitor cells, and olfactory ensheathing cells have all been demonstrated to directly impact axon growth and guidance. Expanding our understanding of how different glial cell types directly interact with growing axons throughout neurodevelopment will inform basic and clinical neuroscientists. For example, identifying the key cellular players beyond the axonal growth cone itself may provide translational clues to develop therapeutic interventions to modulate neuron growth during development or regeneration following injury. This review will provide an overview of the current knowledge about glial involvement in development of the nervous system, specifically focusing on how glia directly interact with growing and maturing axons to influence neuronal connectivity. This focus will be applied to the clinically-relevant field of regeneration following spinal cord injury, highlighting how a better understanding of the roles of glia in neurodevelopment can inform strategies to improve axon regeneration after injury.
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