Gene reporters for magnetic resonance imaging.

MRI-based gene reporters allow imaging of gene expression at depth (tens of centimetres) and at relatively high resolution (~10-100 μm) and have the potential to be translated to the clinic. The reporters exploit either endogenous contrast mechanisms or they modulate the response to an introduced exogenous contrast agent.

Recommendations for improving statistical inference in population genomics.

The field of population genomics has grown rapidly in response to the recent advent of affordable, large-scale sequencing technologies. As opposed to the situation during the majority of the 20th century, in which the development of theoretical and statistical population genetic insights outpaced the generation of data to which they could be applied, genomic data are now being produced at a far greater rate than they can be meaningfully analyzed and interpreted. With this wealth of data has come a tendency to focus on fitting specific (and often rather idiosyncratic) models to data, at the expense of a careful exploration of the range of possible underlying evolutionary processes.

Optimizing Generation of Stem Cell-Derived Islet Cells.

Islet transplantation is a highly effective treatment for select patients with type 1 diabetes. Unfortunately, current use is limited to those with brittle disease due to donor limitations and immunosuppression requirements. Discovery of factors for induction of pluripotent stem cells from adult somatic cells into a malleable state has reinvigorated the possibility of autologous-based regenerative cell therapies.

In utero origin of myelofibrosis presenting in adult monozygotic twins.

The latency between acquisition of an initiating somatic driver mutation by a single-cell and clinical presentation with cancer is largely unknown. We describe a remarkable case of monozygotic twins presenting with CALR mutation-positive myeloproliferative neoplasms (MPNs) (aged 37 and 38 years), with a clinical phenotype of primary myelofibrosis. The CALR mutation was absent in T cells and dermal fibroblasts, confirming somatic acquisition.

An overview of synthetic administrative data for research.

Use of administrative data for research and for planning services has increased over recent decades due to the value of the large, rich information available. However, concerns about the release of sensitive or personal data and the associated disclosure risk can lead to lengthy approval processes and restricted data access. This can delay or prevent the production of timely evidence.

Islet Biology During COVID-19: Progress and Perspectives.

The coronavirus-2019 (COVID-19) pandemic has had significant impact on research directions and productivity in the past 2 years. Despite these challenges, since 2020, more than 2,500 peer-reviewed articles have been published on pancreatic islet biology. These include updates on the roles of isocitrate dehydrogenase, pyruvate kinase and incretin hormones in insulin secretion, as well as the discovery of inceptor and signalling by circulating RNAs.

PHGDH heterogeneity potentiates cancer cell dissemination and metastasis.

Cancer metastasis requires the transient activation of cellular programs enabling dissemination and seeding in distant organs. Genetic, transcriptional and translational heterogeneity contributes to this dynamic process. Metabolic heterogeneity has also been observed, yet its role in cancer progression is less explored.

Foregone Opportunities? Time to Treatment Intensification Among Adults With Type 2 Diabetes and Elevated Glycated Hemoglobin on Metformin Monotherapy, 2009-2018.

Objectives: In this study, we aimed to characterize time to treatment intensification (TTI) in people on metformin with uncontrolled hyperglycemia, and estimated the frequency of physician visits until intensification.

Methods: This work was a cohort study of Albertan adults with glycated hemoglobin (A1C) of >7.5% after at least 3 months of metformin monotherapy, using administrative databases from 2009 to 2018, with each subject followed for up to 4 years.

Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation.

We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 × 10), which were delineated to 338 distinct association signals.

Mapping the developing human immune system across organs.

Single-cell genomics studies have decoded the immune cell composition of several human prenatal organs but were limited in describing the developing immune system as a distributed network across tissues. We profiled nine prenatal tissues combining single-cell RNA sequencing, antigen-receptor sequencing, and spatial transcriptomics to reconstruct the developing human immune system. This revealed the late acquisition of immune-effector functions by myeloid and lymphoid cell subsets and the maturation of monocytes and T cells before peripheral tissue seeding.

Towards better reporting of the proportion of days covered method in cardiovascular medication adherence: A scoping review and new tool TEN-SPIDERS.

Although medication adherence is commonly measured in electronic datasets using the proportion of days covered (PDC), no standardized approach is used to calculate and report this measure. We conducted a scoping review to understand the approaches taken to calculate and report the PDC for cardiovascular medicines to develop improved guidance for researchers using this measure. After prespecifying methods in a registered protocol, we searched Ovid Medline, Embase, Scopus, CINAHL Plus and grey literature (1 July 2012 to 14 December 2020) for articles containing the terms "proportion of days covered" and "cardiovascular medicine", or synonyms and subject headings.

Transcriptome and fatty-acid signatures of adipocyte hypertrophy and its non-invasive MR-based characterization in human adipose tissue.

Background: The adipocyte-hypertrophy associated remodeling of fat cell function is considered causal for the development of metabolic disorders. A better understanding of transcriptome and fatty acid (FA) related alterations with adipocyte hypertrophy combined with less-invasive strategies for the detection of the latter can help to increase the prognostic and diagnostic value of adipocyte size and FA composition as markers for metabolic disease.

Methods: To clarify adipocyte-hypertrophy associated transcriptomic alterations, fat cell size was related to RNA-Seq data from white adipose tissue and size-separated adipocytes.

Mental health experiences with COVID-19 public health measures in an Alberta First Nations Community.

Background: First Nations (FN) people of Canada experience health, social, and systemic inequities due to colonization. Consequently, COVID-19 has placed further mental health stress on people related to personal finances, employment security and worry over infection, resulting in exacerbated effects of unresolved past medical and physical traumas. This study aims to understand the experiences related to mental health in an Alberta FN community during the early stages of the pandemic.

SpatialExperiment: infrastructure for spatially-resolved transcriptomics data in R using Bioconductor.

Summary: SpatialExperiment is a new data infrastructure for storing and accessing spatially-resolved transcriptomics data, implemented within the R/Bioconductor framework, which provides advantages of modularity, interoperability, standardized operations and comprehensive documentation. Here, we demonstrate the structure and user interface with examples from the 10x Genomics Visium and seqFISH platforms, and provide access to example datasets and visualization tools in the STexampleData, TENxVisiumData and ggspavis packages.

Availability And Implementation: The SpatialExperiment, STexampleData, TENxVisiumData and ggspavis packages are available from Bioconductor.

Phylogenetic and phylodynamic approaches to understanding and combating the early SARS-CoV-2 pandemic.

Determining the transmissibility, prevalence and patterns of movement of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is central to our understanding of the impact of the pandemic and to the design of effective control strategies. Phylogenies (evolutionary trees) have provided key insights into the international spread of SARS-CoV-2 and enabled investigation of individual outbreaks and transmission chains in specific settings. Phylodynamic approaches combine evolutionary, demographic and epidemiological concepts and have helped track virus genetic changes, identify emerging variants and inform public health strategy.

A loss-of-function IFNAR1 allele in Polynesia underlies severe viral diseases in homozygotes.

Globally, autosomal recessive IFNAR1 deficiency is a rare inborn error of immunity underlying susceptibility to live attenuated vaccine and wild-type viruses. We report seven children from five unrelated kindreds of western Polynesian ancestry who suffered from severe viral diseases. All the patients are homozygous for the same nonsense IFNAR1 variant (p.

Genome wide screen of RNAi molecules against SARS-CoV-2 creates a broadly potent prophylaxis.

Expanding the arsenal of prophylactic approaches against SARS-CoV-2 is of utmost importance, specifically those strategies that are resistant to antigenic drift in Spike. Here, we conducted a screen with over 16,000 RNAi triggers against the SARS-CoV-2 genome using a massively parallel assay to identify hyper-potent siRNAs. We selected 10 candidates for validation and found five siRNAs that exhibited hyper-potent activity with IC50<20pM and strong neutralisation in live virus experiments.

The future of early cancer detection.

A proactive approach to detecting cancer at an early stage can make treatments more effective, with fewer side effects and improved long-term survival. However, as detection methods become increasingly sensitive, it can be difficult to distinguish inconsequential changes from lesions that will lead to life-threatening cancer. Progress relies on a detailed understanding of individualized risk, clear delineation of cancer development stages, a range of testing methods with optimal performance characteristics, and robust evaluation of the implications for individuals and society.

An evolutionarily conserved stop codon enrichment at the 5' ends of mammalian piRNAs.

PIWI-interacting RNAs (piRNAs) are small RNAs required to recognize and silence transposable elements. The 5' ends of mature piRNAs are defined through cleavage of long precursor transcripts, primarily by Zucchini (Zuc). Zuc-dependent cleavage typically occurs immediately upstream of a uridine.