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Recent decades have brought global expansion of private supplementary tutoring, widely known as shadow education. Such tutoring consumes considerable resources and is usually viewed by participating households as an investment that will increase the recipients’ academic achievements. However, research on the effectiveness of tutoring has delivered inconclusive and even contradictory findings. Part of the reason lies in definitions and foci of research, since private supplementary tutoring may have many different formats, delivery mechanisms and intensities. As with other types of education, it is important also to investigate the qualities of the instructors and the motivations of the students. This creates a complex research arena, in which practical challenges arise from shortcomings in the instruments for securing data and limitations in methods for analyzing the data. This paper assesses the current state of the literature and makes recommendations for the future research agenda.

Cell Painting is a high-content screening assay that uses multiplexed fluorescent dyes for image-based profiling of ∼1,500 morphological features. Image analysis with CellProfiler automatically identifies and extracts data from individual cells. In morphological profiling, quantitative data are extracted from microscopy images of cells to identify biologically relevant similarities and differences among samples based on these profiles. This protocol describes the design and execution of experiments using Cell Painting, which is a morphological profiling assay that multiplexes six fluorescent dyes, imaged in five channels, to reveal eight broadly relevant cellular components or organelles. Cells are plated in multiwell plates, perturbed with the treatments to be tested, stained, fixed, and imaged on a high-throughput microscope. Next, an automated image analysis software identifies individual cells and measures ∼1,500 morphological features (various measures of size, shape, texture, intensity, and so on) to produce a rich profile that is suitable for the detection of subtle phenotypes. Profiles of cell populations treated with different experimental perturbations can be compared to suit many goals, such as identifying the phenotypic impact of chemical or genetic perturbations, grouping compounds and/or genes into functional pathways, and identifying signatures of disease. Cell culture and image acquisition takes 2 weeks; feature extraction and data analysis take an additional 1–2 weeks.

We hypothesized that human genes and disease-associated alleles might be systematically functionally annotated using morphological profiling of cDNA constructs, via a microscopy-based Cell Painting assay. Indeed, 50% of the 220 tested genes yielded detectable morphological profiles, which grouped into biologically meaningful gene clusters consistent with known functional annotation (e.g., the RAS-RAF-MEK-ERK cascade). We used novel subpopulation-based visualization methods to interpret the morphological changes for specific clusters. This unbiased morphologic map of gene function revealed TRAF2/c-REL negative regulation of YAP1/WWTR1-responsive pathways. We confirmed this discovery of functional connectivity between the NF-κB pathway and Hippo pathway effectors at the transcriptional level, thereby expanding knowledge of these two signaling pathways that critically regulate tumor initiation and progression. We make the images and raw data publicly available, providing an initial morphological map of major biological pathways for future study. Many human diseases are caused by particular changes, called mutations, in patients’ DNA. A genome is the complete DNA set of an organism, which contains all the information to build the body and keep it working. This information is stored as a code made up of four chemicals called bases. Humans have about 30,000 genes built from DNA, which contain specific sequences of bases. Genome sequencing can determine the exact order of these bases, and has revealed a long list of mutations in genes that could cause particular diseases. However, over 30% of genes in the human body do not have a known role. Genes can serve multiple roles, some of which are not yet discovered, and even when a gene’s purpose is known, the impact of each particular mutation in a given gene is largely uncatalogued. Therefore, new methods need to be developed to identify the biological roles of both normal and abnormal gene sequences. For hundreds of years, biologists have used microscopy to study how living cells work. Rohban et al. have now asked whether modern software that extracts data from microscopy images could create a fingerprint-like profile of a cell that would reflect how its genes affect its role and appearance. While some genes do not necessarily carry a code with instructions of what a cell should look like, they can indirectly modify the structure of the cell. The resulting changes in the shape of the cell can then be captured in images. The idea was that two cells with matching profiles would indicate that their combinations of genes had matching biological roles too. Rohban et al. tested their approach with human cells grown in the laboratory. In each sample of cells, they ‘turned on’ one of a few hundred relatively well-known human genes, some of which were known to have similar roles. The cells were then stained via a technique called ‘Cell Painting’ to reveal eight specific components of each cell, including its DNA and its surface membrane. The stained cells were imaged under a microscope and the resulting microscopy images analyzed to create a profile of each type of cell. Rohban et al. confirmed that turning on genes known to perform similar biological roles lead to similar-looking cells. The analysis also revealed a previously unknown interaction between two major pathways in the cell that control how cancer starts and develops. In the future, this approach could predict the biological roles of less-understood genes by looking for profiles that match those of well-known genes. Applying this strategy to every human gene, and mutations in genes that are linked to diseases, could help to answer many mysteries about how genes build the human body and keep it working.

Several countries affected by the COVID-19 pandemic have reported a substantial drop in the number of patients attending the emergency department with acute coronary syndromes and a reduced number of cardiac procedures. We aimed to understand the scale, nature, and duration of changes to admissions for different types of acute coronary syndrome in England and to evaluate whether in-hospital management of patients has been affected as a result of the COVID-19 pandemic. We analysed data on hospital admissions in England for types of acute coronary syndrome from Jan 1, 2019, to May 24, 2020, that were recorded in the Secondary Uses Service Admitted Patient Care database. Admissions were classified as ST-elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), myocardial infarction of unknown type, or other acute coronary syndromes (including unstable angina). We identified revascularisation procedures undertaken during these admissions (ie, coronary angiography without percutaneous coronary intervention [PCI], PCI, and coronary artery bypass graft surgery). We calculated the numbers of weekly admissions and procedures undertaken; percentage reductions in weekly admissions and across subgroups were also calculated, with 95% CIs. Hospital admissions for acute coronary syndrome declined from mid-February, 2020, falling from a 2019 baseline rate of 3017 admissions per week to 1813 per week by the end of March, 2020, a reduction of 40% (95% CI 37–43). This decline was partly reversed during April and May, 2020, such that by the last week of May, 2020, there were 2522 admissions, representing a 16% (95% CI 13–20) reduction from baseline. During the period of declining admissions, there were reductions in the numbers of admissions for all types of acute coronary syndrome, including both STEMI and NSTEMI, but relative and absolute reductions were larger for NSTEMI, with 1267 admissions per week in 2019 and 733 per week by the end of March, 2020, a percent reduction of 42% (95% CI 38–46). In parallel, reductions were recorded in the number of PCI procedures for patients with both STEMI (438 PCI procedures per week in 2019 vs 346 by the end of March, 2020; percent reduction 21%, 95% CI 12–29) and NSTEMI (383 PCI procedures per week in 2019 vs 240 by the end of March, 2020; percent reduction 37%, 29–45). The median length of stay among patients with acute coronary syndrome fell from 4 days (IQR 2–9) in 2019 to 3 days (1–5) by the end of March, 2020. Compared with the weekly average in 2019, there was a substantial reduction in the weekly numbers of patients with acute coronary syndrome who were admitted to hospital in England by the end of March, 2020, which had been partly reversed by the end of May, 2020. The reduced number of admissions during this period is likely to have resulted in increases in out-of-hospital deaths and long-term complications of myocardial infarction and missed opportunities to offer secondary prevention treatment for patients with coronary heart disease. The full extent of the effect of COVID-19 on the management of patients with acute coronary syndrome will continue to be assessed by updating these analyses. UK Medical Research Council, British Heart Foundation, Public Health England, Health Data Research UK, and the National Institute for Health Research Oxford Biomedical Research Centre.

The Anarchist Inquisition explores the groundbreaking transnational human rights campaigns that emerged in response to a brutal wave of repression unleashed by the Spanish state to quash anarchist activities at the turn of the twentieth century. Mark Bray guides readers through this tumultuous era-from backroom meetings in Paris and torture chambers in Barcelona, to international antiterrorist conferences in Rome and human rights demonstrations in Buenos Aires. Anarchist bombings in theaters and cafes in the 1890s provoked mass arrests, the passage of harsh anti-anarchist laws, and executions in France and Spain. Yet, far from a marginal phenomenon, this first international terrorist threat had profound ramifications for the broader development of human rights, as well as modern global policing, and international legislation on extradition and migration. A transnational network of journalists, lawyers, union activists, anarchists, and other dissidents related peninsular torture to Spain's brutal suppression of colonial revolts in Cuba and the Philippines to craft a nascent human rights movement against the \"revival of the Inquisition.\" Ultimately their efforts compelled the monarchy to accede in the face of unprecedented global criticism. Bray draws a vivid picture of the assassins, activists, torturers, and martyrs whose struggles set the stage for a previously unexamined era of human rights mobilization. Rather than assuming that human rights struggles and \"terrorism\" are inherently contradictory forces, The Anarchist Inquisition analyzes how these two modern political phenomena worked in tandem to constitute dynamic campaigns against Spanish atrocities.

Loss of cell-cycle control is a hallmark of human cancer. Cell-cycle checkpoints are essential for maintaining genome integrity and balanced growth and division. They are specifically deregulated in cancer cells and contain regulators that represent potential therapeutic targets. Monopolar spindle 1 (Mps1; also known as TTK protein kinase) is a core component of the spindle assembly checkpoint (SAC), a genome-surveillance mechanism that is important for cell survival, and has emerged as a candidate target for anticancer therapy. Here, we report the cellular and antitumor effects of CFI-402257, a potent (Mps1 K i = 0.09 ± 0.02 nM; cellular Mps1 EC50 = 6.5 ± 0.5 nM), highly selective, and orally active small-molecule inhibitor of Mps1 that was identified through a drug-discovery program. Human cancer cells treated with CFI-402257 exhibit effects consistent with Mps1 kinase inhibition, specifically SAC inactivation, leading to chromosome missegregation, aneuploidy, and ultimately cell death. Oral administration of CFI-402257 in monotherapy or in combination with an anti-programmed cell death 1 (PD-1) antibody in mouse models of human cancer results in inhibition of tumor growth at doses that are well-tolerated. Our findings provide a rationale for the clinical evaluation of CFI-402257 in patients with solid tumors.

Research on shadow education has considerably increased in volume and has helped to improve understanding of the scale, nature, and implications of the phenomenon. However, the field is still in its infancy. Literature on shadow education reflects confusion over terms and parameters, and data suffer from challenges in securing evidence from actors who may be unwilling or unable to respond to enquiries in a clear manner. Particular care is needed in cross-national and cross-cultural comparisons. Nevertheless, the trajectory of improvement in both conceptualisation and instrumentation gives ground for confidence that shadow education will be progressively better documented and better understood.

Background Time-lapse analysis of cellular images is an important and growing need in biology. Algorithms for cell tracking are widely available; what researchers have been missing is a single open-source software package to visualize standard tracking output (from software like CellProfiler) in a way that allows convenient assessment of track quality, especially for researchers tuning tracking parameters for high-content time-lapse experiments. This makes quality assessment and algorithm adjustment a substantial challenge, particularly when dealing with hundreds of time-lapse movies collected in a high-throughput manner. Results We present CellProfiler Tracer, a free and open-source tool that complements the object tracking functionality of the CellProfiler biological image analysis package. Tracer allows multi-parametric morphological data to be visualized on object tracks, providing visualizations that have already been validated within the scientific community for time-lapse experiments, and combining them with simple graph-based measures for highlighting possible tracking artifacts. Conclusions CellProfiler Tracer is a useful, free tool for inspection and quality control of object tracking data, available from http://www.cellprofiler.org/tracer/ .