Psilocybin: From Serendipity to Credibility?
Ontology highlight
ABSTRACT:
SUBMITTER: Rucker JJ
PROVIDER: S-EPMC8096916 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:An account is given of how a sensitive bioassay system for measurement of the neurotransmitter acetylcholine serendipitously led to the identification of adenosine triphosphate (ATP) released in vitro from active skeletal muscle. Subsequent application of the identification procedures to exercising human muscle in vivo, cardiac muscle cells in vitro, and human erythrocytes exposed to hypoxia gave rise to the general concept of ATP as a molecule that could influence cell function from the extracellular direction. Mechanisms of ATP release from cells in terms of "trigger" events such as mechanical distortion of the membrane, depolarization of the membrane, and exposure to hypoxia are discussed. Potential therapeutic uses of extracellular ATP in cancer therapy, radiation therapy, and a possible influence upon aging are discussed. Possible roles (distant and local) of extracellular ATP released from muscle during whole body exercise are discussed.
| S-EPMC2377322 | biostudies-other
Project description:Innovation is to organizations what evolution is to organisms: it is how organizations adapt to environmental change and improve. Yet despite advances in our understanding of evolution, what drives innovation remains elusive. On the one hand, organizations invest heavily in systematic strategies to accelerate innovation. On the other, historical analysis and individual experience suggest that serendipity plays a significant role. To unify these perspectives, we analysed the mathematics of innovation as a search for designs across a universe of component building blocks. We tested our insights using data from language, gastronomy and technology. By measuring the number of makeable designs as we acquire components, we observed that the relative usefulness of different components can cross over time. When these crossovers are unanticipated, they appear to be the result of serendipity. But when we can predict crossovers in advance, they offer opportunities to strategically increase the growth of the product space.
| S-EPMC5722871 | biostudies-literature
Project description:Scientific collaboration has become a common behaviour in academia. Various recommendation strategies have been designed to provide relevant collaborators for the target scholars. However, scholars are no longer satisfied with the acquainted collaborator recommendations, which may narrow their horizons. Serendipity in the recommender system has attracted increasing attention from researchers in recent years. Serendipity traditionally denotes the faculty of making surprising discoveries. The unexpected and valuable scientific discoveries in science such as X-rays and penicillin may be attributed to serendipity. In this paper, we design a novel recommender system to provide serendipitous scientific collaborators, which learns the serendipity-biased vector representation of each node in the co-author network. We first introduce the definition of serendipitous collaborators from three components of serendipity: relevance, unexpectedness, and value, respectively. Then we improve the transition probability of random walk in DeepWalk, and propose a serendipity-biased DeepWalk, called Seren2vec. The walker jumps to the next neighbor node with the proportional probability of edge weight in the co-author network. Meanwhile, the edge weight is determined by the three indices in definition. Finally, Top-N serendipitous collaborators are generated based on the cosine similarity between scholar vectors. We conducted extensive experiments on the DBLP data set to validate our recommendation performance, and the evaluations from serendipity-based metrics show that Seren2vec outperforms other baseline methods without much loss of recommendation accuracy.
| S-EPMC7924530 | biostudies-literature
Project description:1The relationship between the acute effects of psychedelics and their persisting neurobiological and psychological effects is poorly understood. Here, we tracked brain changes with longitudinal precision functional mapping in healthy adults before, during, and for up to 3 weeks after oral psilocybin and methylphenidate (17 MRI visits per participant) and again 6+ months later. Psilocybin disrupted connectivity across cortical networks and subcortical structures, producing more than 3-fold greater acute changes in functional networks than methylphenidate. These changes were driven by desynchronization of brain activity across spatial scales (area, network, whole brain). Psilocybin-driven desynchronization was observed across association cortex but strongest in the default mode network (DMN), which is connected to the anterior hippocampus and thought to create our sense of self. Performing a perceptual task reduced psilocybin-induced network changes, suggesting a neurobiological basis for grounding, connecting with physical reality during psychedelic therapy. The acute brain effects of psilocybin are consistent with distortions of space-time and the self. Psilocybin induced persistent decrease in functional connectivity between the anterior hippocampus and cortex (and DMN in particular), lasting for weeks but normalizing after 6 months. Persistent suppression of hippocampal-DMN connectivity represents a candidate neuroanatomical and mechanistic correlate for psilocybin's pro-plasticity and anti-depressant effects.
| S-EPMC10493007 | biostudies-literature
Project description: Not available
| S-EPMC5509638 | biostudies-literature
Project description:Although preliminary estimates from published literature and expert surveys suggest striking agreement among climate scientists on the tenets of anthropogenic climate change (ACC), the American public expresses substantial doubt about both the anthropogenic cause and the level of scientific agreement underpinning ACC. A broad analysis of the climate scientist community itself, the distribution of credibility of dissenting researchers relative to agreeing researchers, and the level of agreement among top climate experts has not been conducted and would inform future ACC discussions. Here, we use an extensive dataset of 1,372 climate researchers and their publication and citation data to show that (i) 97-98% of the climate researchers most actively publishing in the field surveyed here support the tenets of ACC outlined by the Intergovernmental Panel on Climate Change, and (ii) the relative climate expertise and scientific prominence of the researchers unconvinced of ACC are substantially below that of the convinced researchers.
| S-EPMC2901439 | biostudies-other
Project description:Lung metastases are a common site of spread for many malignant tumours. Pulmonary metastasectomy has been practiced for many years for sarcomas and is now becoming increasingly frequently advocated for patients with many other tumours, especially colorectal cancer. In this article we argue that this procedure is one framed by therapeutic opportunity and not supported by strong evidence. It is potentially harmful and may not be effective. Our argument is based on several important issues: (I) the vagueness of the concept of "oligometastases" and its biological implausibility; (II) the flaws in the often-cited observational evidence, especially selection bias; (III) the lack of any reliable randomised trial evidence of improved survival but evidence of harm; (IV) the failure of strategies to detect metastases earlier to influence overall survival. The introduction of stereotactic radiotherapy and image-guided thermal ablation have made the urge to treat lung metastases stronger but without any good evidence to justify their use. We acknowledge the problems of carrying out randomised trials when there is a clear lack of equipoise in the clinical teams involved but believe that there is an ethical need to do so. Many patients are probably being given false hope of cure or prolonged survival but are at risk of harm from pulmonary metastasectomy or ablation. It is possible that a few patients may benefit but without better evidence we do not know which, if any, do.
| S-EPMC8107549 | biostudies-literature
Project description:A single dose of psilocybin, a psychedelic that acutely causes distortions of space-time perception and ego dissolution, produces rapid and persistent therapeutic effects in human clinical trials1-4. In animal models, psilocybin induces neuroplasticity in cortex and hippocampus5-8. It remains unclear how human brain network changes relate to subjective and lasting effects of psychedelics. Here we tracked individual-specific brain changes with longitudinal precision functional mapping (roughly 18 magnetic resonance imaging visits per participant). Healthy adults were tracked before, during and for 3 weeks after high-dose psilocybin (25 mg) and methylphenidate (40 mg), and brought back for an additional psilocybin dose 6-12 months later. Psilocybin massively disrupted functional connectivity (FC) in cortex and subcortex, acutely causing more than threefold greater change than methylphenidate. These FC changes were driven by brain desynchronization across spatial scales (areal, global), which dissolved network distinctions by reducing correlations within and anticorrelations between networks. Psilocybin-driven FC changes were strongest in the default mode network, which is connected to the anterior hippocampus and is thought to create our sense of space, time and self. Individual differences in FC changes were strongly linked to the subjective psychedelic experience. Performing a perceptual task reduced psilocybin-driven FC changes. Psilocybin caused persistent decrease in FC between the anterior hippocampus and default mode network, lasting for weeks. Persistent reduction of hippocampal-default mode network connectivity may represent a neuroanatomical and mechanistic correlate of the proplasticity and therapeutic effects of psychedelics.
| S-EPMC11291293 | biostudies-literature
Project description:The phylogenetically ancient, pentraxin family of plasma proteins, comprises C-reactive protein (CRP) and serum amyloid P component (SAP) in humans and the homologous proteins in other species. They are composed of five, identical, non-covalently associated protomers arranged with cyclic pentameric symmetry in a disc-like configuration. Each protomer has a calcium dependent site that mediates the particular specific ligand binding responsible for all the rigorously established functional properties of these proteins. No genetic deficiency of either human CRP or SAP has been reported, nor even any sequence polymorphism in the proteins themselves. Although their actual functions in humans are therefore unknown, gene deletion studies in mice demonstrate that both proteins can contribute to innate immunity. CRP is the classical human acute phase protein, routinely measured in clinical practice worldwide to monitor disease activity. Human SAP, which is not an acute phase protein, is a universal constituent of all human amyloid deposits as a result of its avid specific binding to amyloid fibrils of all types. SAP thereby contributes to amyloid formation and persistence in vivo. Whole body radiolabelled SAP scintigraphy safely and non-invasively localizes and quantifies systemic amyloid deposits, and has transformed understanding of the natural history of amyloidosis and its response to treatment. Human SAP is also a therapeutic target, both in amyloidosis and Alzheimer's disease. Our drug, miridesap, depletes SAP from the blood and the brain and is currently being tested in the DESPIAD clinical trial in Alzheimer's disease. Meanwhile, the obligate therapeutic partnership of miridesap, to deplete circulating SAP, and dezamizumab, a humanized monoclonal anti-SAP antibody that targets residual SAP in amyloid deposits, produces unprecedented removal of amyloid from the tissues and improves organ function. Human CRP binds to dead and damaged cells in vivo and activates complement and this can exacerbate pre-existing tissue damage. The adverse effects of CRP are completely abrogated by compounds that block its binding to autologous ligands and we are developing CRP inhibitor drugs. The present personal and critical perspective on the pentraxins reports, for the first time, the key role of serendipity in our work since 1975. (345 words).
| S-EPMC6232782 | biostudies-other
Project description:Background and objectivesThe "credibility ceiling" method was proposed to conduct sensitivity analysis for unmeasured confounding and other forms of bias in meta-analyses and has been used in umbrella reviews to grade evidence strength. However, we explain that the method has fundamental statistical flaws.MethodsWe use statistical reasoning to assess the method's validity, providing intuition for our findings by presenting simple applied examples in which the method yields clearly incorrect conclusions.ResultsThe credibility ceiling is not a valid bias correction, as we show mathematically and illustrate using examples in which, for example, the method incorrectly "adjusts" the meta-analytic point estimate in the wrong direction. Although the originators describe the method as limiting the credibility of any given observational study to a fixed ceiling, we show why this interpretation in fact bears little relation to what the method actually does.ConclusionGiven the fundamental problems with the credibility ceiling method and its demonstrated potential for misleading conclusions, we recommend against its use.
| S-EPMC8159013 | biostudies-literature