The pseudogenes of Mycobacterium leprae reveal the functional relevance of gene order within operons

Almost 50 years following the discovery of the prokaryotic operon, the functional relevance of gene order within operons remains unclear. In this work, we take advantage of the eroded genome of Mycobacterium leprae to add evidence supporting the notion that functionally less important genes have a tendency to be located at the end of its operons. M. leprae’s genome includes 1133 pseudogenes and 1614 protein-coding genes and can be compared with the close genome of M. tuberculosis. Assuming M. leprae’s pseudogenes to represent dispensable genes, we have studied the position of these pseudogenes in the operons of M. leprae and of their orthologs in M. tuberculosis. We observed that both tend to be located in the 3′ (downstream) half of the operon (P-values of 0.03 and 0.18, respectively). Analysis of pseudogenes in all available prokaryotic genomes confirms this trend (P-value of 7.1 × 10−7). In a complementary analysis, we found a significant tendency for essential genes to be located at the 5′ (upstream) half of the operon (P-value of 0.006). Our work provides an indication that, in prokarya, functionally less important genes have a tendency to be located at the end of operons, while more relevant genes tend to be located toward operon starts

Measuring Active Living Environments: An international comparison between Canada and Wales

Background The impacts of the built environment on health is a widely studied international area of research. One area of research is how urban morphology (e.g. active living environments, also known as neighbourhood walkability) may promote healthy behaviour within a population. However urban morphology and data relating to the built environment varies across different countries. Objectives One of the challenges in international studies is producing consistent, comparable measures of the built environment, in this case active living environments. As part of a study which compares the impact of neighbourhood environments on health outcomes for patients with type 2 diabetes (T2D), neighbourhood-level measures for walkable environments were derived for Canada and Wales using Geographic Information Systems (GIS). Methods Using method based upon the Canadian Active Living Environments Database (Can-ALE) we created walkability indicators for Wales, UK. We created GIS models using OpenStreetMap and Office for National Statistics (ONS) Open Data to produce walkability metrics for each Lower Layer Super Output Area (LSOA) in Wales for linkage into the SAIL databank. We compared the GIS generated walkability metrics for Wales with those produced for Canada to evaluate whether the GIS methods are internationally transferable in the context of generating walkability indictors and associations with T2D. Findings This work highlights the challenges in creating internationally comparable environmental exposure metrics. The differences in urban morphology and scale in Canada and Wales are significant, however this work demonstrates how with considered methodological choices these differences can be overcome to generate comparable built environment indicators. Conclusions The generation of comparable walkability indicators for the built environment has allowed subsequent analysis into hospital admissions for people living with T2D in Caranda and Wales. This study has wider implications for international research into the impacts of the built environment on population health and are reproducible on future studies

International comparison in walkable environments and hospital burden in type 2 diabetes patients

Introduction While some comparative work has provided evidence for a universally positive impact of built environment features that promote physical activity, less is known about chronic diseases and hospitalization among different social contexts and health care systems. Parallel international linkage efforts present an opportunity to study health impacts of the built environment. Objectives and Approach This study compares the impact of neighbourhood environments on health outcomes for patients with type 2 diabetes (T2D) in two countries. Neighborhood-level measures for walkable environments were derived for Canada and Wales using Geographic Information Systems. Hospitalization admissions from routine data sources and linked survey data responses (from the Welsh Health Survey and Canadian Community Health Survey) allow for the generation of population-based descriptive statistics on socio-demographic information, self-reported health, diagnostic patterns, and health care use. We examine the feasibility of investigating contextual differences in walkable environments, T2D, and hospitalization between Wales and Canada. Results Data linkage in respective privacy protecting safe havens in the Canada Research Data Centre Network (CRDCN) and the Wales Secure Anonymised Information Linkage (SAIL) Databank show promise for a comparative study, enabling parallel modelling of environmental and socio-demographic factors with hospitalization data. Both the Canadian and Welsh surveys ask respondents about their current diabetes status, allowing us to compare hospitalization rates and neighborhood effects of those who report having diabetes with the those who do not. Moreover, the linking of survey responses and similarity in geographic scale permitted consistent measurement of walkable environments across countries. Key administrative variables have been identified relating to health and behaviors, such as socio-demographic information, smoking status, and body mass index, and hospitalization metrics in both countries are commensurable. Conclusion/Implications The generation of comparable linked datasets, built environment indicators and comparative research for T2D patients will have wider implications for international assessment of the impacts of environment on chronic diseases, and the hospital burden associated with these conditions

Childbirth-Related Hospital Burden by Socioeconomic Status in a Universal Health Care Setting

Introduction Hospital utilization varies across socioeconomic and demographic strata in Canada, which has a universal health care system that grants essential services to everyone. Rates of adverse birth outcomes are known to differ among high and low SES women, but less is known of the excess burden attached to those outcomes across Canadian provinces. Objective To examine length of stay for childbirth relative to women’s socio-demographic characteristics, in the context of the Canadian universal health care system. Methods A population-based record linkage between the Canadian Community Health Survey (CCHS) cycles 3.1 (2005) and 4.1 (2007/8), and the Discharge Abstract Database (DAD) allowed the tracking of hospital utilization for linked survey respondents between 2005 and 2009. Hourly length of stay for delivery was modeled by socio-demographic factors, controlling for other clinical and individual-level characteristics. Results There were 7,166 complete delivery records from 5,570 female CCHS respondents who agreed to link and share their information. Women with the lowest income had on average, four-hour longer stays for vaginal delivery as compared to high-income women (IRR 1.07, 95% CI 1.02-1.13, p=0.01), and eight-hour longer stays for Caesarian delivery (IRR 1.08, 95% CI 0.95-1.22, p=0.23). A greater proportion of teenage pregnancy was seen for Aboriginal girls. Aboriginal status and rural area of residence were co-determinants of elevated length of stay. Conclusion The absence of egregious socio-demographic differences regarding childbirth is reassuring for the Canadian health care system. However, the persistence of marginally longer, and in turn, costlier visits for low-income and rural Aboriginal women is suggestive that policies of cash transfers during the prenatal period might be highly cost-effective if they achieve population-wide reductions in length of stay

Neighbourhood built environments as correlates of hospital burden and premature mortality in Canada

Introduction The built environment can shape modifiable risk factors such as obesity, poor diet, and physical inactivity, and could be a policy lever for the reduction of chronic disease. In Canada, the health care costs related to chronic disease continue to rise and there have been few policy options offered. Objectives and Approach We examine the role of the built environment in hospital burden and premature mortality, with an emphasis on one of the highest burden diseases, Type 2 Diabetes (T2D). Neighbourhood built environment measures for active living were derived using geographic information systems for respondents of the Canadian Community Health Survey, for whom we have linked hospitalization and mortality records. A combination of ICD codes, self-reported diabetes status, as well as a population-based algorithm identifying those at higher risk of developing diabetes were used to identify cases. Differences in hospitalization frequency, cumulative length of stay, and mortality are investigated. Results Over half a million hospitalization records were identified in our cohort of roughly 450,000 survey respondents. Key factors such as age, gender, race, and socioeconomic status are accounted for in modelling the association between neighborhood environment and hospitalization. Hospital burden and mortality in T2D patients are much higher than that of patients who do not report having the condition, and those at elevated risk of T2D display intermediate levels of hospitalization. Two-part hurdle models show evidence of an association between more walkable neighborhoods and lower hospitalization risk in non-T2D patients as well as those at elevated risk of developing T2D. The relationship between neighborhoods and the volume of chronic-disease related episodes as well as mortality is unclear, and under further investigation. Conclusion/Implications Elucidating the role of neighbourhood built environments on hospital burden and premature mortality for individuals with diabetes will provide insight as to the full range of clinical and non-clinical interventions that could feasibly address the needs of some the highest health care system users

Access to stem cell data and registration of pluripotent cell lines: the Human Pluripotent Stem Cell Registry (hPSCreg)

The value of human pluripotent stem cells (hPSC) in regenerative medicine has yet to reach its full potential. The road from basic research tool to clinically validated PSC-derived cell therapy products is a long and winding one, leading researchers, clinicians, industry and regulators alike into undiscovered territory. All stakeholders must work together to ensure the development of safe and effective cell therapies. Similarly, utilization of hPSC in meaningful and controlled disease modeling and drug screening applications requires information on the quality and suitability of the applied cell lines. Central to these common goals is the complete documentation of hPSC data, including the ethical provenance of the source material, the hPSC line derivation, culture conditions and genetic constitution of the lines. Data surrounding hPSC is scattered amongst diverse sources, including publications, supplemental data, researcher lab books, accredited lab reports, certificates of analyses and public data repositories. Not all of these data sources are publicly accessible nor associated with metadata nor stored in a standard manner, such that data can be easily found and retrieved. The Human Pluripotent Stem Cell Registry (hPSCreg; https://hpscreg.eu/) was started in 2007 to impart provenance and transparency towards hPSC research by registering and collecting standard properties of hPSC lines. In this chapter, we present a short primer on the history of stem cell-based products, summarize the ethical and regulatory issues introduced in the course of working with hPSC-derived products and their associated data, and finally present the Human Pluripotent Stem Cell Registry as a valuable resource for all stakeholders in therapies and disease modeling based on hPSC-derived cells

Stepwise reprogramming of liver cells to a pancreas progenitor state by the transcriptional regulator Tgif2

The development of a successful lineage reprogramming strategy of liver to pancreas holds promises for the treatment and potential cure of diabetes. The liver is an ideal tissue source for generating pancreatic cells, because of its close developmental origin with the pancreas and its regenerative ability. Yet, the molecular bases of hepatic and pancreatic cellular plasticity are still poorly understood. Here, we report that the TALE homeoprotein TGIF2 acts as a developmental regulator of the pancreas versus liver fate decision and is sufficient to elicit liver-to-pancreas fate conversion both ex vivo and in vivo. Hepatocytes expressing Tgif2 undergo extensive transcriptional remodelling, which represses the original hepatic identity and, over time, induces a pancreatic progenitor-like phenotype. Consistently, in vivo forced expression of Tgif2 activates pancreatic progenitor genes in adult mouse hepatocytes. This study uncovers the reprogramming activity of TGIF2 and suggests a stepwise reprogramming paradigm, whereby a ‘lineage-restricted’ dedifferentiation step precedes the identity switch

A Manually Curated Database on Clinical Studies Involving Cell Products Derived from Human Pluripotent Stem Cells

The last 5 years have witnessed a significant increase in the number of clinical studies based on human pluripotent stem cells (hPSCs). In parallel, concern is increasing about the proliferation of unregulated stem cell treatments worldwide. Regulated clinical testing is a de facto standard to establish the safety and efficacy of new cell therapies, yet reliable information on clinical studies involving hPSCs is scattered. Our analysis of a multitude of resources found 54 clinical studies involving several types of hPSCs, which are performed in ten countries. While the majority of those studies is based on human embryonic stem cells (hESCs), clinical studies involving human induced pluripotent stem cells increased more strongly in the past 2 years than the number of hESC-based studies. A publicly accessible database was created using the human pluripotent stem cell registry (https://hpscreg.eu) platform, providing a steadily updated comprehensive overview on hPSC-based clinical studies performed worldwide

Detection of condition-specific marker genes from RNA-seq data with MGFR

The identification of condition-specific genes is key to advancing our understanding of cell fate decisions and disease development. Differential gene expression analysis (DGEA) has been the standard tool for this task. However, the amount of samples that modern transcriptomic technologies allow us to study, makes DGEA a daunting task. On the other hand, experiments with low numbers of replicates lack the statistical power to detect differentially expressed genes. We have previously developed MGFM, a tool for marker gene detection from microarrays, that is particularly useful in the latter case. Here, we have adapted the algorithm behind MGFM to detect markers in RNA-seq data. MGFR groups samples with similar gene expression levels and flags potential markers of a sample type if their highest expression values represent all replicates of this type. We have benchmarked MGFR against other methods and found that its proposed markers accurately characterize the functional identity of different tissues and cell types in standard and single cell RNA-seq datasets. Then, we performed a more detailed analysis for three of these datasets, which profile the transcriptomes of different human tissues, immune and human blastocyst cell types, respectively. MGFR’s predicted markers were compared to gold-standard lists for these datasets and outperformed the other marker detectors. Finally, we suggest novel candidate marker genes for the examined tissues and cell types. MGFR is implemented as a freely available Bioconductor package (https://doi.org/doi:10.18129/B9.bioc.MGFR), which facilitates its use and integration with bioinformatics pipelines

Findings of the WMT 2020 Biomedical Translation Shared Task: Basque, Italian and Russian as New Additional Languages

Machine translation of scientific abstracts and terminologies has the potential to support health professionals and biomedical researchers in some of their activities. In the fifth edition of the WMT Biomedical Task, we addressed a total of eight language pairs. Five language pairs were previously addressed in past editions of the shared task, namely, English/German, English/French, English/Spanish, English/Portuguese, and English/Chinese. Three additional languages pairs were also introduced this year: English/Russian, English/Italian, and English/Basque. The task addressed the evaluation of both scientific abstracts (all language pairs) and terminologies (English/Basque only). We received submissions from a total of 20 teams. For recurring language pairs, we observed an improvement in the translations in terms of automatic scores and qualitative evaluations, compared to previous years