Transcriptome-Wide, Unbiased Profiling of Ribonuclease Targeting Chimeras.

Various approaches have been developed to target RNA and modulate its function with modes of action including binding and cleavage. Herein, we explored how small molecule binding is correlated with cleavage induced by heterobifunctional ribonuclease targeting chimeras (RiboTACs), where RNase L is recruited to cleave the bound RNA target, in a transcriptome-wide, unbiased fashion. Only a fraction of bound targets was cleaved by RNase L, induced by RiboTAC binding.

The RNA secondary structure of androgen receptor-FL and V7 transcripts reveals novel regulatory regions.

The androgen receptor (AR) is a ligand-dependent nuclear transcription factor belonging to the steroid hormone nuclear receptor family. Due to its roles in regulating cell proliferation and differentiation, AR is tightly regulated to maintain proper levels of itself and the many genes it controls. AR dysregulation is a driver of many human diseases including prostate cancer.

Identification of MYC intron 2 regions that modulate expression.

MYC pre-mRNA is spliced with high fidelity to produce the transcription factor known to regulate cellular differentiation, proliferation, apoptosis, and alternative splicing. The mechanisms underpinning the pre-mRNA splicing of MYC, however, remain mostly unexplored. In this study, we examined the interaction of heterogeneous nuclear ribonucleoprotein C (HNRNPC) with MYC intron 2.

Applicability of Artificial Societies to Evaluate Health Care Policies.

We propose the use of artificial societies to support health care policymakers in understanding and forecasting the impact and adverse effects of policies. Artificial societies extend the agent-based modeling paradigm using social science research to allow integrating the human component. We simulate individuals as socially capable software agents with their individual parameters in their situated environment including social networks.

ScanFold 2.0: a rapid approach for identifying potential structured RNA targets in genomes and transcriptomes.

A major limiting factor in target discovery for both basic research and therapeutic intervention is the identification of structural and/or functional RNA elements in genomes and transcriptomes. This was the impetus for the original ScanFold algorithm, which provides maps of local RNA structural stability, evidence of sequence-ordered (potentially evolved) structure, and unique model structures comprised of recurring base pairs with the greatest structural bias. A key step in quantifying this propensity for ordered structure is the prediction of secondary structural stability for randomized sequences which, in the original implementation of ScanFold, is explicitly evaluated.

Thermodynamic and structural characterization of an EBV infected B-cell lymphoma transcriptome.

Epstein-Barr virus (EBV) is a widely prevalent human herpes virus infecting over 95% of all adults and is associated with a variety of B-cell cancers and induction of multiple sclerosis. EBV accomplishes this in part by expression of coding and noncoding RNAs and alteration of the host cell transcriptome. To better understand the structures which are forming in the viral and host transcriptomes of infected cells, the RNA structure probing technique Structure-seq2 was applied to the BJAB-B1 cell line (an EBV infected B-cell lymphoma).

Expansion of the RNAStructuromeDB to include secondary structural data spanning the human protein-coding transcriptome.

RNA plays vital functional roles in almost every component of biology, and these functional roles are often influenced by its folding into secondary and tertiary structures. An important role of RNA secondary structure is in maintaining proper gene regulation; therefore, making accurate predictions of the structures involved in these processes is important. In this study, we have expanded on our previous work that led to the creation of the RNAStructuromeDB.

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The interactions between cellular RNAs in MDA-MB-231 triple negative breast cancer cells and a panel of small molecules appended with a diazirine cross-linking moiety and an alkyne tag were probed transcriptome-wide in live cells. The alkyne tag allows for facile pull-down of cellular RNAs bound by each small molecule, and the enrichment of each RNA target defines the compound's molecular footprint. Among the 34 chemically diverse small molecules studied, six bound and enriched cellular RNAs.

Analyses of human cancer driver genes uncovers evolutionarily conserved RNA structural elements involved in posttranscriptional control.

Experimental breakthroughs have provided unprecedented insights into the genes involved in cancer. The identification of such cancer driver genes is a major step in gaining a fuller understanding of oncogenesis and provides novel lists of potential therapeutic targets. A key area that requires additional study is the posttranscriptional control mechanisms at work in cancer driver genes.

Prediction and analysis of functional RNA structures within the integrative genomics viewer.

In recent years, interest in RNA secondary structure has exploded due to its implications in almost all biological functions and its newly appreciated capacity as a therapeutic agent/target. This surge of interest has driven the development and adaptation of many computational and biochemical methods to discover novel, functional structures across the genome/transcriptome. To further enhance efforts to study RNA secondary structure, we have integrated the functional secondary structure prediction tool ScanFold, into IGV.

Analysis of key genes in reveals conserved RNA structural motifs and regions with apparent pressure to remain unstructured.

Buruli Ulcer is a neglected tropical disease that results in disfiguring and dangerous lesions in affected persons across a wide geographic area, including much of West Africa. The causative agent of Buruli Ulcer is , a relative of the bacterium that causes tuberculosis and leprosy. Few therapeutic options exist for the treatment of this disease beyond antibiotics in the early stages, which are frequently ineffective, and surgical removal in the later stage.

A Narrative Review of Ethnic Minority Studies for Faith-Based Health Promotion Interventions with Special Reference to the Contemporary Christian Nurse.

Heart disease, diabetes mellitus (DM) type 2, and obesity are three of the most prevalent diseases in the USA. Some obesity-related comorbidities are disproportionately higher within African-American and Hispanic communities. While governmental and local health programs offer educational opportunities encouraging long-term health behavior changes, the most accessible programs have been through faith-based communities.

Recent Advances in Systems and Network Medicine: Meeting Report from the First International Conference in Systems and Network Medicine.

The gathered together 200 global thought leaders, scientists, clinicians, academicians, industry and government experts, medical and graduate students, postdoctoral scholars and policymakers. Held at Georgetown University Conference Center in Washington D.C.

Policy Flight Simulators: Accelerating Decisions to Adopt Evidence-Based Health Interventions.

In this study, the authors used simulation to explore factors that might influence hospitals' decisions to adopt evidence-based interventions. Specifically, they developed a simulation model to examine the extent to which hospitals would benefit economically from the transitional care model (TCM). The TCM is designed to transition high-risk older adults from hospitals back to communities using interventions focused on preventing readmissions.

Service supply chains for population health: Overcoming fragmentation of service delivery ecosystems.

Introduction: Population health involves integration of health, education, and social services to keep a defined population healthy, to address health challenges holistically, and to assist with the realities of being mortal. The fragmentation of the US population health delivery system is addressed. The impacts of this fragmentation on the treatment of substance abuse in the United States are considered.

Vision for a systems architecture to integrate and transform population health.

Entities involved in population health often share a common mission while acting independently of one another and perhaps redundantly. Population health is in everybody's interest, but nobody is really in charge of promoting it. Across governments, corporations, and frontline operations, lack of coordination, lack of resources, and lack of reliable, current information have often impeded the development of situation-awareness models and thus a broad operational integration for population health.

Modeling research universities: Predicting probable futures of public vs. private and large vs. small research universities.

The future of the American academic research enterprise is considered. Data are presented that characterize the resources available for the 160 best-resourced research universities, a small subset of the 2,285 4-year, nonprofit, higher education institutions. A computational model of research universities was extended and used to simulate three strategic scenarios: status quo, steady decline in foreign graduate student enrollments, and downward tuition pressures from high-quality, online professional master's programs.

Developing a Policy Flight Simulator to Facilitate the Adoption of an Evidence-Based Intervention.

While the use of evidence-based interventions (EBIs) has been advocated by the medical research community for quite some time, uptake of these interventions by healthcare providers has been slow. One possible explanation is that it is challenging for providers to estimate impacts of a specific EBI on their particular organization. To address that concern, we developed and evaluated a type of simulation called a policy flight simulator to determine if it could improve the adoption decision about a specific EBI, the transitional care model (TCM).

Children's toothache is becoming everybody's business: where do parents go when their children have oral pain in London, England? A cross-sectional analysis.

Objectives: To assess the number of parents who visited community pharmacies in London seeking pain medications for their children's pain and specifically for oral pain, to identify which health services parents contacted before their pharmacy visit and to estimate the cost to the National Health Service (NHS) when children with oral pain who visit pharmacies also see health professionals outside dentistry.

Design: A cross-sectional study.

Setting: 1862 pharmacies in London in November 2016-January 2017.

Learning in the health care enterprise.

Introduction: The overall enterprise of health care delivery is considered. The 4 levels of the enterprise include clinical practices, processes that provide capabilities and information, structure that includes the business entities involved, and ecosystem that includes Centers for Medicare and Medicaid Services and Congress, as well as societal values and norms. It is argued that the enterprise of health care delivery needs to be transformed to enable high-quality, affordable care for everyone.

Decentralizing the Team Station: Simulation before Reality as a Best-Practice Approach.

The purpose of this article is to share the logistical planning requirements and simulation experience of one Canadian hospital as it prepared its staff for the change from a centralized inpatient unit model to the decentralized design planned for its new community hospital. With the commitment and support of senior leadership, project management resources and clinical leads worked collaboratively to design a decentralized prototype in the form of a pod-style environment in the hospital's current setting. Critical success factors included engaging the right stakeholders, providing an opportunity to test new workflows and technology, creating a strong communication plan and building on lessons learned as subsequent pod prototypes are launched.

Interactive visualizations for decision support: Application of Rasmussen's abstraction-aggregation hierarchy.

Data visualization has of late received an enormous amount of attention from both researchers and practitioners. Even the popular press often includes impressive visualizations of various data sets. Interactive visualizations frequently include data visualizations, but they differ in that users employ the visualizations to make inferences, reach conclusions, and make decisions that result in changed and/or new visualizations.

Human interaction with policy flight simulators.

Policy flight simulators are designed for the purpose of exploring alternative management policies at levels ranging from individual organizations to national strategy. This article focuses on how such simulators are developed and on the nature of how people interact with these simulators. These interactions almost always involve groups of people rather than individuals, often with different stakeholders in conflict about priorities and courses of action.