Implementing Cancer Registry Data With the PCORnet Common Data Model: The Greater Plains Collaborative Experience.

Purpose: Electronic health records (EHRs) comprise a rich source of real-world data for cancer studies, but they often lack critical structured data elements such as diagnosis date and disease stage. Fortunately, such concepts are available from hospital cancer registries. We describe experiences from integrating cancer registry data with EHR and billing data in an interoperable data model across a multisite clinical research network.

The Role of Preprocedure Genetic Counseling in Pregnancies Interrupted for Fetal Abnormalities.

Objective: Congenital birth defects affect 3 to 5% of pregnancies. Genetic counseling can help patients navigate the testing process and understand results. The study objective was to identify predictors and utility of genetic counseling at the time of pregnancy termination.

An EMR-Based Approach to Determine Frequency, Prescribing Pattern, and Characteristics of Patients Receiving Drugs with Pharmacogenomic Guidelines.

(1) Background: This retrospective analysis utilizing electronic medical record (EMR) data from a tertiary integrated health system sought to identify patients and prescribers who would benefit from pharmacogenomic (PGx) testing based on Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. (2) Methods: EMR data from a clinical research data warehouse were analyzed from 845,518 patients that had an encounter between 2015 and 2019 at an academic medical center. Data were collected for 42 commercially available drugs with 52 evidence-based PGx guidelines from CPIC.

Implementation of an evidence-based tobacco control intervention for school teachers in India: Evaluating the effects of a capacity-building strategy.

Background: (TFT-TFS) is an evidence-based intervention that promotes tobacco use cessation among teachers and tobacco control policies among schools in India. This study tested an implementation model to build Bihar Department of Education (DOE) capacity to support and deliver TFT-TFS within schools, leveraging DOE training infrastructure.

Method: We used a training-of-trainers (TOT) "cascade" implementation strategy to embed the TFT-TFS program into the Bihar DOE infrastructure.

Factors Associated With Receipt of Molecular Testing and its Impact on Time to Initial Systemic Therapy in Metastatic Non-Small Cell Lung Cancer.

Background: Despite recommendations for molecular testing irrespective of patient characteristics, differences exist in receipt of molecular testing for oncogenic drivers amongst metastatic non-small cell lung cancer (mNSCLC) patients. Exploration into these differences and their effects on treatment is needed to identify opportunities for improvement.

Patients And Methods: We conducted a retrospective cohort study of adult patients diagnosed with mNSCLC between 2011 and 2018 using PCORnet's Rapid Cycle Research Project dataset (n = 3600).

Cellular and Molecular Mechanisms of MEK1 Inhibitor-Induced Cardiotoxicity.

Background: Trametinib is a MEK1 (mitogen-activated extracellular signal-related kinase kinase 1) inhibitor used in the treatment of BRAF (rapid accelerated fibrosarcoma B-type)-mutated metastatic melanoma. Roughly 11% of patients develop cardiomyopathy following long-term trametinib exposure. Although described clinically, the molecular landscape of trametinib cardiotoxicity has not been characterized.

A Transient Mystery: Nucleolar Channel Systems.

The nucleus is a complex organelle with functions beyond being a simple repository for genomic material. For example, its actions in biomechanical sensing, protein synthesis, and epigenomic regulation showcase how the nucleus integrates multiple signaling modalities to intricately regulate gene expression. This innate dynamism is underscored by subnuclear components that facilitate these roles, with elements of the nucleoskeleton, phase-separated nuclear bodies, and chromatin safeguarding by nuclear envelope proteins providing examples of this functional diversity.

Application of Pharmacokinetic Prediction Platforms in the Design of Optimized Anti-Cancer Drugs.

Cancer is the second most common cause of death in the United States, accounting for 602,350 deaths in 2020. Cancer-related death rates have declined by 27% over the past two decades, partially due to the identification of novel anti-cancer drugs. Despite improvements in cancer treatment, newly approved oncology drugs are associated with increased toxicity risk.

Neurogenic Stunned Myocardium: A Review.

Neurogenic stunned myocardium is a form of stress cardiomyopathy. The disorder is sometimes referred to as atypical Takotsubo cardiomyopathy. The pathophysiology of neurogenic stunned myocardium is hypothesized to involve significant overdrive of the sympathetic nervous system after a brain injury.

The effect of number of healthcare visits on study sample selection in electronic health record data.

Introduction: Few studies have addressed how to select a study sample when using electronic health record (EHR) data.

Objective: To examine how changing criterion for number of visits in EHR data required for inclusion in a study sample would impact one basic epidemiologic measure: estimates of disease period prevalence.

Methods: Year 2016 EHR data from three Midwestern health systems (Northwestern Medicine in Illinois, University of Iowa Health Care, and Froedtert & the Medical College of Wisconsin, all regional tertiary health care systems including hospitals and clinics) was used to examine how alternate definitions of the study sample, based on number of healthcare visits in one year, affected measures of disease period prevalence.

Differentiation of Human Intestinal Organoids with Endogenous Vascular Endothelial Cells.

Human pluripotent stem cell (hPSC)-derived intestinal organoids (HIOs) lack some cellular populations found in the native organ, including vasculature. Using single-cell RNA sequencing (scRNA-seq), we have identified a population of endothelial cells (ECs) present early in HIO differentiation that declines over time in culture. Here, we developed a method to expand and maintain this endogenous population of ECs within HIOs (vHIOs).

Genetic counseling student demographics: an empirical comparison of two cohorts.

Genetic counseling student characteristics may be evolving with the expansion and diversification of the genetic counseling field. We compared characteristics and previously accrued experiences of genetic counseling students enrolled in the 2018-2019 academic year with genetic counseling students surveyed by Lega et al. (Journal of Genetic Counseling, 14, 395; 2005).

High-Throughput Screening at the Membrane Interface Reveals Inhibitors of Amyloid-β.

Aggregation and the formation of oligomeric intermediates of amyloid-β (Aβ) at the membrane interface of neuronal cells are implicated in the cellular toxicity and pathology of Alzheimer's disease. Small molecule compounds have been shown to suppress amyloid aggregation and cellular toxicity, but often the presence of a lipid membrane negates their activity. A high-throughput screen of 1800 small molecules was performed to search for membrane active inhibitors, and 21 primary hits were discovered.

Factors associated with successful tobacco use cessation among teachers in Bihar state, India: a mixed-method study.

Although tobacco use is declining in several countries including India (dropping from 35% in 2009-10 to 29% 2016-17 among adults)-it still poses a huge burden on India, as the world's second largest consumer of tobacco products. In Bihar state, with a prevalence of 25%, the Bihar School Teachers Study (BSTS) successfully enlisted teachers as role models for encouraging quitting and changing social norms pertaining to tobacco. The study used a mixed-methods approach to identify factors associated with teachers' quitting.

Structural Interaction of Apolipoprotein A-I Mimetic Peptide with Amyloid-β Generates Toxic Hetero-oligomers.

Apolipoproteins are involved in pathological conditions of Alzheimer's disease (AD), and it has been reported that truncated apolipoprotein fragments and β-amyloid (Aβ) peptides coexist as neurotoxic heteromers within the plaques. Therefore, it is important to investigate these complexes at the molecular level to better understand their properties and roles in the pathology of AD. Here, we present a mechanistic insight into such heteromerization using a structurally homologue apolipoprotein fragment of apoA-I (4F) complexed with Aβ(M1-42) and characterize their toxicity.

Effect of Ice Nucleation and Cryoprotectants during High Subzero-Preservation in Endothelialized Microchannels.

Cryopreservation is of significance in areas including tissue engineering, regenerative medicine, and organ transplantation. We investigated endothelial cell attachment and membrane integrity in a microvasculature model at high subzero temperatures in the presence of extracellular ice. The results show that in the presence of heterogeneous extracellular ice formation induced by ice nucleating bacteria, endothelial cells showed improved attachment at temperature minimums of -6 °C.

I see the light! Fluorescent proteins suitable for cell wall/apoplast targeting in leaves.

Correct subcellular targeting is crucial for protein function. Protein location can be visualized in vivo by fusion to a fluorescent protein (FP). Nevertheless, despite intense engineering efforts, most FPs are dim or completely quenched at low pH (<6).

A cationic polymethacrylate-copolymer acts as an agonist for β-amyloid and an antagonist for amylin fibrillation.

In humans, β-amyloid and islet amyloid polypeptide (IAPP, also known as amylin) aggregations are linked to Alzheimer's disease and type-2 diabetes, respectively. There is significant interest in better understanding the aggregation process by using chemical tools. Here, we show the ability of a cationic polymethacrylate-copolymer (PMAQA) to quickly induce a β-hairpin structure and accelerate the formation of amorphous aggregates of β-amyloid-1-40, whereas it constrains the conformational plasticity of amylin for several days and slows down its aggregation at substoichiometric polymer concentrations.

Dosage considerations in the combined use of ocular-specific vitamins and nutrients and multivitamin products: A systemic review and analysis.

Objectives: To provide guidance for safe and appropriate vitamin and mineral supplementation regimens for patients who use vitamins marketed for ocular use concurrently with general-purpose multivitamin (MVI) supplementation.

Data Sources: Primary and tertiary evidence was compiled from secondary literature reference databases.

Study Selection: Dosage exposure with the use of supplements marketed for the prevention of ocular disease, including those recommended by the Age-Related Eye Disease Studies (AREDS), when used in combination with conventional MVI/nutrient products was determined.

Alzheimer's amyloid-beta intermediates generated using polymer-nanodiscs.

Polymethacrylate-copolymer (PMA) encased lipid-nanodiscs (∼10 nm) and macro-nanodiscs (>15 nm) are used to study Aβ1-40 aggregation. We demonstrate that PMA-nanodiscs form a ternary association with Aβ and regulate its aggregation kinetics by trapping intermediates. Results demonstrating the reduced neurotoxicity of nanodisc-bound Aβ oligomers are also reported.