"Matching" consent to purpose: The example of the Matchmaker Exchange.

The Matchmaker Exchange (MME) connects rare disease clinicians and researchers to facilitate the sharing of data from undiagnosed patients for the purpose of novel gene discovery. Such sharing raises the odds that two or more similar patients with candidate genes in common may be found, thereby allowing their condition to be more readily studied and understood. Consent considerations for data sharing in MME included both the ethical and legal differences between clinical and research settings and the level of privacy risk involved in sharing varying amounts of rare disease patient data to enable patient matches.

Selenoprotein MsrB1 promotes anti-inflammatory cytokine gene expression in macrophages and controls immune response in vivo.

Post-translational redox modification of methionine residues often triggers a change in protein function. Emerging evidence points to this reversible protein modification being an important regulatory mechanism under various physiological conditions. Reduction of oxidized methionine residues is catalyzed by methionine sulfoxide reductases (Msrs).

Small molecule metalloprotease inhibitor with in vitro, ex vivo and in vivo efficacy against botulinum neurotoxin serotype A.

Botulinum neurotoxins (BoNTs) are the most toxic substances known to mankind and are the causative agents of the neuroparalytic disease botulism. Their ease of production and extreme toxicity have caused these neurotoxins to be classified as Tier 1 bioterrorist threat agents and have led to a sustained effort to develop countermeasures to treat intoxication in case of a bioterrorist attack. While timely administration of an approved antitoxin is effective in reducing the severity of botulism, reversing intoxication requires different strategies.

Associations among body size across the life course, adult height and endometriosis.

Study Question: Are body size across the life course and adult height associated with endometriosis?

Summary Answer: Endometriosis is associated with lean body size during childhood, adolescence and adulthood; tall total adult height; and tall sitting height.

What Is Known Already: The literature suggests that both adult body size and height are associated with endometriosis risk, but few studies have investigated the role of body size across the life course. Additionally, no study has investigated the relationships between components of height and endometriosis.

Discovery of a Small Molecule Probe That Post-Translationally Stabilizes the Survival Motor Neuron Protein for the Treatment of Spinal Muscular Atrophy.

Spinal muscular atrophy (SMA) is the leading genetic cause of infant death. We previously developed a high-throughput assay that employs an SMN2-luciferase reporter allowing identification of compounds that act transcriptionally, enhance exon recognition, or stabilize the SMN protein. We describe optimization and characterization of an analog suitable for in vivo testing.

Somatic copy number alterations in gastric adenocarcinomas among Asian and Western patients.

Gastric cancer, a leading worldwide cause of cancer mortality, shows high geographic and ethnic variation in incidence rates, which are highest in East Asia. The anatomic locations and clinical behavior also differ by geography, leading to the controversial idea that Eastern and Western forms of the disease are distinct. In view of these differences, we investigated whether gastric cancers from Eastern and Western patients show distinct genomic profiles.

Response to a combination of oxygen and a hypnotic as treatment for obstructive sleep apnoea is predicted by a patient's therapeutic CPAP requirement.

Background And Objective: Upper airway collapsibility predicts the response to several non-continuous positive airway pressure (CPAP) interventions for obstructive sleep apnoea (OSA). Measures of upper airway collapsibility cannot be easily performed in a clinical context; however, a patient's therapeutic CPAP requirement may serve as a surrogate measure of collapsibility. The present work aimed to compare the predictive use of CPAP level with detailed physiological measures of collapsibility.

Effects of expanding the look-back period to all available data in the assessment of covariates.

Background: A fixed baseline period has been a common covariate assessment approach in pharmacoepidemiological studies from claims but may lead to high levels of covariate misclassification. Simulation studies have recommended expanding the look-back approach to all available data (AAD) for binary indicators of diagnoses, procedures, and medications, but there have been few real data analyses using this approach.

Objective: The objective of the study is to explore the impact on treatment effect estimates and covariate prevalence of expanding the look-back period within five validated studies in the Aetion system, a rapid cycle analytics platform.

Limitations on the compensation of gamete donors: a public opinion survey.

Objective: To determine public opinion on gamete donor compensation.

Design: Cross-sectional web-based survey.

Setting: Not applicable.

Genetic Signatures of Asthma Exacerbation.

Asthma exacerbation (AE) usually denotes worsening of asthma symptoms that requires intense management to prevent further deterioration. AE has been reported to correlate with clinical and demographic factors, such as race, gender, and treatment compliance as well as environmental factors, such as viral infection, smoking, and air pollution. In addition, recent observations suggest that there are likely to be genetic factors specific to AE.

Interrogating cyclic AMP signaling using optical approaches.

Optical reporters for cAMP represent a fundamental advancement in our ability to investigate the dynamics of cAMP signaling. These fluorescent sensors can measure changes in cAMP in single cells or in microdomains within cells as opposed to whole populations of cells required for other methods of measuring cAMP. The first optical cAMP reporters were FRET-based sensors utilizing dissociation of purified regulatory and catalytic subunits of PKA, introduced by Roger Tsien in the early 1990s.

Knee symptoms among adults at risk for accelerated knee osteoarthritis: data from the Osteoarthritis Initiative.

The purpose of this study was to examine if adults who develop accelerated knee osteoarthritis (KOA) have greater knee symptoms with certain activities than those with or without incident common KOA. We conducted a case-control study using data from baseline and the first four annual visits of the Osteoarthritis Initiative. Participants had no radiographic KOA at baseline (Kellgren-Lawrence (KL) <2).

Long-term dietary quality and risk of developing rheumatoid arthritis in women.

Objectives: To evaluate the association between long-term dietary quality, measured by the 2010 Alternative Healthy Eating Index, and risk of rheumatoid arthritis (RA) in women.

Methods: We prospectively followed 76 597 women in the Nurses' Health Study aged 30-55 years and 93 392 women in the Nurses' Health Study II aged 25-42 years at baseline and free from RA or other connective tissue diseases. The lifestyle, environmental exposure and anthropometric information were collected at baseline and updated biennially.

Glucose homeostasis influences the risk of incident knee osteoarthritis: Data from the osteoarthritis initiative.

We aimed to determine if serum measures of impaired glucose homeostasis (glucose concentrations or glycated serum protein, GSP) or systemic inflammation (high-sensitivity C-reactive protein, CRP) are related to incident typical knee osteoarthritis (KOA) or incident accelerated KOA. We conducted a case-control study using the Osteoarthritis Initiative's baseline and first four annual visits. All participants had no radiographic KOA at baseline (Kellgren-Lawrence [KL] < 2).

Association Between Menopausal Factors and the Risk of Seronegative and Seropositive Rheumatoid Arthritis: Results From the Nurses' Health Studies.

Objective: To investigate whether menopausal factors are associated with the development of serologic rheumatoid arthritis (RA) phenotypes.

Methods: Data were analyzed from the Nurses' Health Studies (NHS; 1976-2010 and NHSII 1989-2011). A total of 120,700 female nurses ages 30-55 years in the NHS, and a total of 116,430 female nurses ages 25-42 years in the NHSII, were followed via biennial questionnaires on lifestyle and disease outcomes.

ClinGen Pathogenicity Calculator: a configurable system for assessing pathogenicity of genetic variants.

Background: The success of the clinical use of sequencing based tests (from single gene to genomes) depends on the accuracy and consistency of variant interpretation. Aiming to improve the interpretation process through practice guidelines, the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) have published standards and guidelines for the interpretation of sequence variants. However, manual application of the guidelines is tedious and prone to human error.

Bisphenol-A exposure and gene expression in human luteinized membrana granulosa cells in vitro.

Study Question: Does bisphenol-A (BPA) affect gene expression in human membrana granulosa cells (MGC)?

Summary Answer: In vitro, short exposure to supra-physiological concentrations of BPA alters human MGC gene expression.

What Is Known Already: Exposure to BPA may interfere with reproductive endocrine signaling. In vitro studies, mostly in animal models, have shown an inverse correlation between exposure to BPA and follicular growth, meiosis, and steroid hormone production in granulosa cells.

A survey of current practices for genomic sequencing test interpretation and reporting processes in US laboratories.

Purpose: While the diagnostic success of genomic sequencing expands, the complexity of this testing should not be overlooked. Numerous laboratory processes are required to support the identification, interpretation, and reporting of clinically significant variants. This study aimed to examine the workflow and reporting procedures among US laboratories to highlight shared practices and identify areas in need of standardization.

Healthcare costs associated with rivaroxaban or warfarin use for the treatment of venous thromboembolism.

Introduction: Rivaroxaban has been shown to have similar efficacy but less major bleeding than warfarin in randomized trials of patients experiencing venous thromboembolism (VTE). This report sought to assess healthcare costs up to 12-months following an index VTE in patients prescribed either rivaroxaban or warfarin.

Materials And Methods: This study analyzed claims from the MarketScan Commercial Claims and Encounters Database from November 2011-July 2015.

Asthma Metabolomics and the Potential for Integrative Omics in Research and the Clinic.

Asthma is a complex disease well-suited to metabolomic profiling, both for the development of novel biomarkers and for the improved understanding of pathophysiology. In this review, we summarize the 21 existing metabolomic studies of asthma in humans, all of which reported significant findings and concluded that individual metabolites and metabolomic profiles measured in exhaled breath condensate, urine, plasma, and serum could identify people with asthma and asthma phenotypes with high discriminatory ability. There was considerable consistency across the studies in terms of the reported biomarkers, regardless of biospecimen, profiling technology, and population age.

Prospective Study of Oral Health and Risk of Primary Open-Angle Glaucoma in Men: Data from the Health Professionals Follow-up Study.

Purpose: Tooth loss or periodontal disease is associated with systemic endothelial dysfunction, which has been implicated in primary open-angle glaucoma (POAG). The relationship between oral health and POAG has received limited attention. Thus, we evaluated the association between oral health history and risk of POAG and POAG subtypes.