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Measuring scientific success has traditionally involved numbers and statistics. However, due to an increasingly uncertain world, more than ever we need to measure the effect that science has on real-world scenarios. We asked researchers to share their points of view on what scientific impact means to them and how impact matters beyond the numbers.The spread of scientific misinformation is not new but rather has long posed threats to human health, environmental well-being, and the creation of a sustainable and equitable future. However, with the COVID-19 pandemic, the need to develop strategies to counteract scientific misinformation has taken on an acute urgency. Cell editor Nicole Neuman sat down with Walter Quattrociocchi and Dietram Scheufele to gain insights on how we got here and what does-and does not-work to fight the spread of scientific misinformation. Excerpts from this conversation, edited for clarity and length, are presented below, and the full conversation is available with the article online.The first two vaccines proven to be effective for inhibiting COVID-19 illness were both mRNA, achieving 95% efficacy (and safety) among 74,000 participants (half receiving placebo) after intramuscular delivery of two shots, 3-4 weeks apart. To view this Bench to Bedside, open or download the PDF.Conventional thinking in modern drug discovery postulates that the design of highly selective molecules which act on a single disease-associated target will yield safer and more effective drugs. However, high clinical attrition rates and the lack of progress in developing new effective treatments for many important diseases of unmet therapeutic need challenge this hypothesis. This assumption also impinges upon the efficiency of target agnostic phenotypic drug discovery strategies, where early target deconvolution is seen as a critical step to progress phenotypic hits. In this review we provide an overview of how emerging phenotypic and pathway-profiling technologies integrate to deconvolute the mechanism-of-action of phenotypic hits. We propose that such in-depth mechanistic profiling may support more efficient phenotypic drug discovery strategies that are designed to more appropriately address complex heterogeneous diseases of unmet need.Profiling approaches such as gene expression or proteome profiling generate small-molecule bioactivity profiles that describe a perturbed cellular state in a rather unbiased manner and have become indispensable tools in the evaluation of bioactive small molecules. Automated imaging and image analysis can record morphological alterations that are induced by small molecules through the detection of hundreds of morphological features in high-throughput experiments. Thus, morphological profiling has gained growing attention in academia and the pharmaceutical industry as it enables detection of bioactivity in compound collections in a broader biological context in the early stages of compound development and the drug-discovery process. Profiling may be used successfully to predict mode of action or targets of unexplored compounds and to uncover unanticipated activity for already characterized small molecules. Here, we review the reported approaches to morphological profiling and the kind of bioactivity that can be detected so far and, thus, predicted.The use of phenotypic screening was central to the discovery and development of novel thalidomide analogs, the IMiDs (immunomodulatory drugs) agents. With the discovery that these agents bind the E3 ligase, CRL4CRBN, and alter its substrate specificity, there has been a great deal of endeavor to discover other small molecules that can modulate alternative E3 ligases. Furthermore, the chemical properties necessary for drug discovery and the rules by which neo-substrates are selected for degradation are being defined in the context of phenotypic alterations in specific cellular systems. This review gives a detailed summary of these recent advances and the methodologies being exploited to understand the mechanism of action of emerging protein degradation therapies.Human induced pluripotent stem cells (hiPSCs) have emerged as a promising platform for pharmacogenomics and drug development. In cardiology, they make it possible to produce unlimited numbers of patient-specific human cells that reproduce hallmark features of heart disease in the culture dish. Their potential applications include the discovery of mechanism-specific therapeutics, the evaluation of safety and efficacy in a human context before a drug candidate reaches patients, and the stratification of patients for clinical trials. Although this new technology has the potential to revolutionize drug discovery, translational hurdles have hindered its widespread adoption for pharmaceutical development. Here we discuss recent progress in overcoming these hurdles that should facilitate the use of hiPSCs to develop new medicines and individualize therapies for heart disease.
Little is known about the risk of SARS-CoV-2 infection and transmission in educational settings. KI696 cost Public Health England initiated a study, COVID-19 Surveillance in School KIDs (sKIDs), in primary schools when they partially reopened from June 1, 2020, after the first national lockdown in England to estimate the incidence of symptomatic and asymptomatic SARS-CoV-2 infection, seroprevalence, and seroconversion in staff and students.
sKIDs, an active, prospective, surveillance study, included two groups the weekly swabbing group and the blood sampling group. The swabbing group underwent weekly nasal swabs for at least 4 weeks after partial school reopening during the summer half-term (June to mid-July, 2020). The blood sampling group additionally underwent blood sampling for serum SARS-CoV-2 antibodies to measure previous infection at the beginning (June 1-19, 2020) and end (July 3-23, 2020) of the summer half-term, and, after full reopening in September, 2020, and at the end of the autumn term (Nov 23-Dec 18 still participating in the surveillance, and five (four students, one staff member) seroconverted. By December, 2020, 55 (5·1%; 95% CI 3·8-6·5) of 1085 participants who were seronegative at recruitment (in June, 2020) had seroconverted, including 19 (5·6%; 3·4-8·6) of 340 students and 36 (4·8%; 3·4-6·6) of 745 staff members (p=0·60).
In England, SARS-CoV-2 infection rates were low in primary schools following their partial and full reopening in June and September, 2020.
UK Department of Health and Social Care.
UK Department of Health and Social Care.