Sensitive cluster-free differential expression testing.

Comparing molecular features, including the identification of genes with differential expression (DE) between conditions, is a powerful approach for characterising disease-specific phenotypes. When testing for DE in single-cell RNA sequencing data, current pipelines first assign cells into discrete clusters (or cell types), followed by testing for differences within each cluster. Consequently, the sensitivity and specificity of DE testing are limited and ultimately dictated by the granularity of the cell type annotation, with discrete clustering being especially suboptimal for continuous trajectories. To overcome these limitations, we present miloDE - a cluster-free framework for differential expression testing. We build on the Milo approach, introduced for differential cell abundance testing, which leverages the graph representation of single-cell data to assign relatively homogenous, 'neighbouring' cells into overlapping neighbourhoods. We address key differences between differential abundance and expression testing at the level of neighbourhood assignment, statistical testing, and multiple testing correction. To illustrate the performance of miloDE we use both simulations and real data, in the latter case identifying a transient haemogenic endothelia-like state in chimeric mouse embryos lacking Tal1 as well as uncovering distinct transcriptional programs that characterise changes in macrophages in patients with Idiopathic Pulmonary Fibrosis. miloDE is available as an open-source R package at https://github.com/MarioniLab/miloDE.

A reference human induced pluripotent stem cell line for large-scale collaborative studies.

Human induced pluripotent stem cell (iPSC) lines are a powerful tool for studying development and disease, but the considerable phenotypic variation between lines makes it challenging to replicate key findings and integrate data across research groups. To address this issue, we sub-cloned candidate human iPSC lines and deeply characterized their genetic properties using whole genome sequencing, their genomic stability upon CRISPR-Cas9-based gene editing, and their phenotypic properties including differentiation to commonly used cell types. These studies identified KOLF2.1J as an all-around well-performing iPSC line. We then shared KOLF2.1J with groups around the world who tested its performance in head-to-head comparisons with their own preferred iPSC lines across a diverse range of differentiation protocols and functional assays. On the strength of these findings, we have made KOLF2.1J and its gene-edited derivative clones readily accessible to promote the standardization required for large-scale collaborative science in the stem cell field.

Narrative trajectories of disaster response: ethical preparedness from Katrina to COVID-19.

While COVID-19 brings unprecedented challenges to the US healthcare system, understanding narratives of historical disasters illuminates ethical complexities shared with COVID-19. In 2005, Hurricane Katrina revealed a lack of disaster preparation and protocol, not dissimilar to the challenges faced by COVID-19 healthcare workers. A case study of Memorial Hospital during Hurricane Katrina reported by journalist-MD Sheri Fink reveals unique ethical challenges at the forefront of health crises. These challenges include disproportionate suffering in structurally vulnerable populations, as seen in COVID-19 where marginalised groups across the USA experience higher rates of disease and COVID-19-related death. Journalistic accounts of Katrina and COVID-19 offer unique perspectives on the ethical challenges present within medicine and society, and analysis of such stories reveals narrative trajectories anticipated in the aftermath of COVID-19. Through lenses of social suffering and structural violence, these narratives reinforce the need for systemic change, including legal action, ethical preparedness and physician protection to ensure high-quality care during times of crises. Narrative Medicine-as a practice of interrogating stories in medicine and re-centering the patient-offers a means to contextualise individual accounts of suffering during health crises in larger social matrices.

COVID-19 impacts and adaptations in Asia and Africa's aquatic food value chains.

The COVID-19 pandemic is a shock affecting all areas of the global food system. We tracked the impacts of COVID-19 and associated policy responses on the availability and price of aquatic foods and production inputs during 2020, using a high frequency longitudinal survey of 768 respondents in Bangladesh, Egypt, India, Myanmar, Nigeria. We found the following: (1) Aquatic food value chains were severely disrupted but most effects on the availability and accessibility of aquatic foods and production inputs were short-lived. (2) Impacts on demand for aquatic foods, production inputs, and labor have been longer lasting than impacts on their supply. (3) Retail prices of aquatic foods spiked briefly during March-May 2020 but trended down thereafter, whereas prices of production inputs rose. These trends suggest a deepening 'squeeze' on the financial viability of producers and other value chain actors. (4) Survey respondents adapted to the challenges of COVID-19 by reducing production costs, sourcing alternative inputs, diversifying business activities, leveraging social capital, borrowing, seeking alternative employment, and reducing food consumption. Many of these coping strategies are likely to undermine well-being and longer-term resilience, but we also find some evidence of proactive strategies with potential to strengthen business performance. Global production of aquatic food likely contracted significantly in 2020. The importance of aquatic food value chains in supporting livelihoods and food and nutrition security in Asia and Africa makes their revitalization essential in the context of COVID-19 recovery efforts. We outline immediate and longer-term policies and interventions to support this goal.

Mapping out epistemic justice in the clinical space: using narrative techniques to affirm patients as knowers.

Epistemic injustice sits at the intersection of ethics, epistemology, and social justice. Generally, this philosophical term describes when a person is wrongfully discredited as a knower; and within the clinical space, epistemic injustice is the underlying reason that some patient testimonies are valued above others. The following essay seeks to connect patterns of social prejudice to the clinical realm in the United States: illustrating how factors such as race, gender identity, and socioeconomic status influence epistemic credence and associatively, the quality of healthcare a person receives.After describing how epistemic injustice disproportionately harms already vulnerable patients, I propose a narrative therapy intervention. This intervention can help providers re-frame their relationships with patients, in such that they come to view patients as valuable sources of unique knowledge. Though I identify this intervention as a valuable step in addressing clinical epistemic injustice, I call upon medical educators and practitioners to further uplift the voices, perspectives, and stories of marginalized patients.

Seasonal changes in diet and chemical defense in the Climbing Mantella frog (Mantella laevigata).

Poison frogs acquire chemical defenses from the environment for protection against potential predators. These defensive chemicals are lipophilic alkaloids that are sequestered by poison frogs from dietary arthropods and stored in skin glands. Despite decades of research focusing on identifying poison frog alkaloids, we know relatively little about how environmental variation and subsequent arthropod availability impacts alkaloid loads in poison frogs. We investigated how seasonal environmental variation influences poison frog chemical profiles through changes in the diet of the Climbing Mantella (Mantella laevigata). We collected M. laevigata females on the Nosy Mangabe island reserve in Madagascar during the wet and dry seasons and tested the hypothesis that seasonal differences in rainfall is associated with changes in diet composition and skin alkaloid profiles of M. laevigata. The arthropod diet of each frog was characterized into five groups (i.e. ants, termites, mites, insect larvae, or 'other') using visual identification and cytochrome oxidase 1 DNA barcoding. We found that frog diet differed between the wet and dry seasons, where frogs had a more diverse diet in the wet season and consumed a higher percentage of ants in the dry season. To determine if seasonality was associated with variation in frog defensive chemical composition, we used gas chromatography / mass spectrometry to quantify alkaloids from individual skin samples. Although the assortment of identified alkaloids was similar across seasons, we detected significant differences in the abundance of certain alkaloids, which we hypothesize reflects seasonal variation in the diet of M. laevigata. We suggest that these variations could originate from seasonal changes in either arthropod leaf litter composition or changes in frog behavioral patterns. Although additional studies are needed to understand the consequences of long-term environmental shifts, this work suggests that alkaloid profiles are relatively robust against short-term environmental perturbations.

Food stories: Unraveling the mechanisms underlying healthful eating.

The biomedical model of health (BMH) studies the causes and origins of disease. When applied to nutrition research, eating is studied as a behavior that supports physical health. However, the lack of attention the BMH pays to social and historical circumstances in which health behaviors are constructed has been widely addressed in literature. When people are studied without considering contextual influences, the relevance to everyday life is limited. As a result, how individuals actively deal with their context to manage healthful eating is poorly understood. This research applies a complementary model, salutogenic model of health (SMH), and uses life course research methodology to study a group of healthy eaters. The purpose of this research is to unravel how healthful eating develops in everyday life. Healthy eaters (n = 17) were identified and recruited from the NQplus research panel at Wageningen University, the Netherlands. Life course experiences were examined through narrative inquiry. Participants recalled and visually explored life experiences with food and health using timelines. Results indicate that healthful eating results from exposure to individual- and context-bounded factors during childhood and adulthood and involves specific mental and social capacities relevant to coping including amongst others, critical self-awareness; flexibility, craftiness, and fortitude. Through life-course learning moments, participants were able to develop proactive coping strategies which strengthened their sense of agency and helped them in overcoming stressors and challenges. Findings show that nutrition strategies should not only focus on strengthening food-specific factors like cooking skills and nutrition knowledge, but other factors like stress management, empowerment, and participation. Such factors support the development of adaptive skills and behaviors, enable individuals to deal with the demands of everyday life, and are building blocks for health promotion.