"Like an umbrella, protecting me from the rain until I get to my destination": Evaluating the implementation of a tailored primary care model for urban marginalized populations.

Background: Improving health equity and access to the highest possible standard of health care is a key issue of social accountability. Centretown Community Health Centre in Ottawa, Canada has iteratively developed a program to target and serve marginalized and complex populations since 1999. The program implementation was evaluated using a validated implementation framework.

Loss of MMR and TGFBR2 Increases the Susceptibility to Microbiota-Dependent Inflammation-Associated Colon Cancer.

Background And Aims: Mutations in DNA mismatch repair (MMR) genes are causative in Lynch syndrome and a significant proportion of sporadic colorectal cancers (CRCs). MMR-deficient (dMMR) CRCs display increased mutation rates, with mutations frequently accumulating at short repetitive DNA sequences throughout the genome (microsatellite instability). The TGFBR2 gene is one of the most frequently mutated genes in dMMR CRCs.

Invasive Assessment of Microvascular Resistance in Hypertrophic Cardiomyopathy With Echocardiographic Correlates.

Introduction: Hypertrophic cardiomyopathy (HCM) is often associated with ischaemia despite lack of focal epicardial coronary stenosis. Our aim was to assess invasive coronary microvascular circulation and correlate findings with echocardiography.

Methods: We prospectively enrolled patients with HCM and controls who were referred for diagnostic coronary angiography.

Making every death count: institutional mortality accuracy at Ola During Children's Hospital, Sierra Leone.

Introduction: health care data accuracy feeds the development of sound healthcare policy and the prioritisation of interventions in scarce resource environments. We designed a retrospective study at the sole paediatric government hospital in Sierra Leone to examine mortality statistics, specifically: the accuracy of mortality data collected in 2017; and the quality of cause of death (CoD) reporting for 2017.

Methods: the retrospective audit included all available mortality statistics collected at the hospital during the 2017 calendar year.

Evidence-informed interventions and best practices for supporting women experiencing or at risk of homelessness: a scoping review with gender and equity analysis.

Introduction: While much of the literature on homelessness is centred on the experience of men, women make up over one-quarter of Canada's homeless population. Research has shown that women experiencing homelessness are often hidden (i.e.

Lessons learned from expanded reproductive carrier screening in self-reported Ashkenazi, Sephardi, and Mizrahi Jewish patients.

Background: Next-generation sequencing (NGS)-based panels have gained traction as a strategy for reproductive carrier screening. Their value for screening Ashkenazi Jewish (AJ) individuals, who have benefited greatly from population-wide targeted testing, as well as Sephardi/Mizrahi Jewish (SMJ) individuals (an underserved population), has not been fully explored.

Methods: The clinical utilization by 6,805 self-reported Jewish individuals of an expanded NGS panel, along with several ancillary assays, was assessed retrospectively.

The impact of interventions for youth experiencing homelessness on housing, mental health, substance use, and family cohesion: a systematic review.

Background: Youth often experience unique pathways into homelessness, such as family conflict, child abuse and neglect. Most research has focused on adult homeless populations, yet youth have specific needs that require adapted interventions. This review aims to synthesize evidence on interventions for youth and assess their impacts on health, social, and equity outcomes.

Whole-Exome Sequencing (WES) for Illumina Short Read Sequencers Using Solution-Based Capture.

Next-generation sequencing (NGS) is transforming clinical research and diagnostics, vastly enhancing our ability to identify novel disease-causing genetic mutations and perform comprehensive diagnostic testing in the clinic. Whole-exome sequencing (WES) is a commonly used method which captures the majority of coding regions of the genome for sequencing, as these regions contain the majority of disease-causing mutations. The clinical applications of WES are not limited to diagnosis; the technique can be employed to help determine an optimal therapeutic strategy for a patient considering their mutation profile.

The Impact of Peripheral Nerve Stimulation on Coronary Blood Flow and Endothelial Function.

Purpose: The geko™ device is a small transcutaneous nerve stimulator that is applied non-invasively to the skin over the common peroneal nerve to stimulate peripheral blood flow. The purpose of this study was to investigate the effect of peripheral nerve stimulation on coronary flow dynamics and systemic endothelial function.

Methods: We enrolled 10 male patients, age 59 ± 11 years, with symptomatic obstructive coronary disease undergoing percutaneous coronary intervention (PCI).

Regulation of SPRY3 by X chromosome and PAR2-linked promoters in an autism susceptibility region.

Sprouty proteins are regulators of cell growth and branching morphogenesis. Unlike mouse Spry3, which is X-linked, human SPRY3 maps to the pseudoautosomal region 2; however, the human Y-linked allele is not expressed due to epigenetic silencing by an unknown mechanism. SPRY3 maps adjacent to X-linked Trimethyllysine hydroxylase epsilon (TMLHE), recently identified as an autism susceptibility gene.

DNA demethylation by 5-aza-2'-deoxycytidine is imprinted, targeted to euchromatin, and has limited transcriptional consequences.

Background: DNA methylation can be abnormally regulated in human disease and associated with effects on gene transcription that appear to be causally related to pathogenesis. The potential to use pharmacological agents that reverse this dysregulation is therefore an attractive possibility. To test how 5-aza-2'-deoxycytidine (5-aza-CdR) influences the genome therapeutically, we exposed non-malignant cells in culture to the agent and used genome-wide assays to assess the cellular response.

The Wasp System: an open source environment for managing and analyzing genomic data.

The challenges associated with the management, analysis and interpretation of assays based on massively-parallel sequencing (MPS) are both individually complex and numerous. We describe what we believe to be the appropriate solution, one that represents a departure from traditional computational biology approaches. The Wasp System is an open source, distributed package written in Spring/J2EE that creates a foundation for development of an end-to-end solution for MPS-based experiments or clinical tests.

The Einstein Genome Gateway using WASP - a high throughput multi-layered life sciences portal for XSEDE.

Massively-parallel sequencing (MPS) technologies and their diverse applications in genomics and epigenomics research have yielded enormous new insights into the physiology and pathophysiology of the human genome. The biggest hurdle remains the magnitude and diversity of the datasets generated, compromising our ability to manage, organize, process and ultimately analyse data. The Wiki-based Automated Sequence Processor (WASP), developed at the Albert Einstein College of Medicine (hereafter Einstein), uniquely manages to tightly couple the sequencing platform, the sequencing assay, sample metadata and the automated workflows deployed on a heterogeneous high performance computing cluster infrastructure that yield sequenced, quality-controlled and 'mapped' sequence data, all within the one operating environment accessible by a web-based GUI interface.

Automated computational analysis of genome-wide DNA methylation profiling data from HELP-tagging assays.

A novel DNA methylation assay, HELP-tagging, has been recently described to use massively parallel sequencing technology for genome-wide methylation profiling. Massively parallel sequencing-based assays such as this produce substantial amounts of data, which complicate analysis and necessitate the use of significant computational resources. To simplify the processing and analysis of HELP-tagging data, a bioinformatic analytical pipeline was developed.

Late-replicating heterochromatin is characterized by decreased cytosine methylation in the human genome.

Heterochromatin is believed to be associated with increased levels of cytosine methylation. With the recent availability of genome-wide, high-resolution molecular data reflecting chromatin organization and methylation, such relationships can be explored systematically. As well-defined surrogates for heterochromatin, we tested the relationship between DNA replication timing and DNase hypersensitivity with cytosine methylation in two human cell types, unexpectedly finding the later-replicating, more heterochromatic regions to be less methylated than early replicating regions.

Optimized design and data analysis of tag-based cytosine methylation assays.

Using the type III restriction-modification enzyme EcoP15I, we isolated sequences flanking sites digested by the methylation-sensitive HpaII enzyme or its methylation-insensitive MspI isoschizomer for massively parallel sequencing. A novel data transformation allows us to normalise HpaII by MspI counts, resulting in more accurate quantification of methylation at >1.8 million loci in the human genome.

The Einstein Center for Epigenomics: studying the role of epigenomic dysregulation in human disease.

There is increasing interest in the role of epigenetic and transcriptional dysregulation in the pathogenesis of a range of human diseases, not just in the best-studied example of cancer. It is, however, quite difficult for an individual investigator to perform these studies, as they involve genome-wide molecular assays combined with sophisticated computational analytical approaches of very large datasets that may be generated from various resources and technologies. In 2008, the Albert Einstein College of Medicine in New York, USA established a Center for Epigenomics to facilitate the research programs of its investigators, providing shared resources for genome-wide assays and for data analysis.

Mouse pregnancy-specific glycoproteins: tissue-specific expression and evidence of association with maternal vasculature.

The pregnancy-specific glycoproteins (Psg) are secreted hormones encoded by multiple genes in rodents and primates, and are thought to act as immune modulators. The only Psg receptor identified is CD9, through which Psg17 induces cytokine production from macrophages cultured in vitro. We examined temporal and spatial aspects of Psg and CD9 expression during mouse pregnancy to determine whether their expression patterns support a role in immune modulation.

Identification of a novel group of evolutionarily conserved members within the rapidly diverging murine Cea family.

The carcinoembryonic antigen (CEA) family comprises a still actively evolving populous group of proteins that are involved in controlling tissue homeostasis, immune responses, and host/pathogen interactions. The genes identified to date in rodents and primates exhibit low sequence similarity and an extremely variable domain composition. Among the 22 murine Cea-related genes, only for Ceacam1 has an ortholog been assigned.

Conservation of pregnancy-specific glycoprotein (PSG) N domains following independent expansions of the gene families in rodents and primates.

Background: Rodent and primate pregnancy-specific glycoprotein (PSG) gene families have expanded independently from a common ancestor and are expressed virtually exclusively in placental trophoblasts. However, within each species, it is unknown whether multiple paralogs have been selected for diversification of function, or for increased dosage of monofunctional PSG. We analysed the evolution of the mouse PSG sequences, and compared them to rat, human and baboon PSGs to attempt to understand the evolution of this complex gene family.

Structure and evolution of the mouse pregnancy-specific glycoprotein (Psg) gene locus.

Background: The pregnancy-specific glycoprotein (Psg) genes encode proteins of unknown function, and are members of the carcinoembryonic antigen (Cea) gene family, which is a member of the immunoglobulin gene (Ig) superfamily. In rodents and primates, but not in artiodactyls (even-toed ungulates / hoofed mammals), there have been independent expansions of the Psg gene family, with all members expressed exclusively in placental trophoblast cells. For the mouse Psg genes, we sought to determine the genomic organisation of the locus, the expression profiles of the various family members, and the evolution of exon structure, to attempt to reconstruct the evolutionary history of this locus, and to determine whether expansion of the gene family has been driven by selection for increased gene dosage, or diversification of function.

An abundant placental transcript containing an IAP-LTR is allelic to mouse pregnancy-specific glycoprotein 23 (Psg23): cloning and genetic analysis.

Several families of endogenous retroviruses (ERVs) are expressed in mammalian placental tissues, and are implicated in aspects of placental development and function. We characterized the structure of abundant ERV-related transcripts in mouse placenta. In addition to the 7 kb full-length type I and 5 kb type I deleted intracisternal A-particle (IAP) transcripts, we identified and cloned an abundant 2 kb transcript encoding a novel member of the pregnancy-specific glycoprotein (Psg) gene family, which contains an IAP long terminal repeat (LTR) in the 3' untranslated region (UTR).

Exhaustive identification of human class II basic helix-loop-helix proteins by virtual library screening.

Cellular proliferation, specification and differentiation in developing tissues are tightly coordinated by groups of transcription factors in response to extrinsic and intrinsic signals. Furthermore, renewable pools of stem cells in adult tissues are subject to similar regulation. Basic helix-loop-helix (bHLH) proteins are a group of transcription factors that exert such a determinative influence on a variety of developmental pathways from C.