Assessing phenotype order in molecular data.

Biological entities are key elements of biomedical research. Their definition and their relationships are important in areas such as phylogenetic reconstruction, developmental processes or tumor evolution. Hypotheses about relationships like phenotype order are often postulated based on prior knowledge or belief. Evidence on a molecular level is typically unknown and whether total orders are reflected in the molecular measurements is unclear or not assessed. In this work we propose a method that allows a fast and exhaustive screening for total orders in large datasets. We utilise ordinal classifier cascades to identify discriminable molecular representations of the phenotypes. These classifiers are constrained by an order hypothesis and are highly sensitive to incorrect assumptions. Two new error bounds, which are introduced and theoretically proven, lead to a substantial speed-up and allow the application to large collections of many phenotypes. In our experiments we show that by exhaustively evaluating all possible candidate orders, we are able to identify phenotype orders that best coincide with the high-dimensional molecular profiles.

Modularized CRISPR/dCas9 effector toolkit for target-specific gene regulation.

The ability to control mammalian genes in a synergistic mode using synthetic transcription factors is highly desirable in fields of tissue engineering, stem cell reprogramming and fundamental research. In this study, we developed a standardized toolkit utilizing an engineered CRISPR/Cas9 system that enables customizable gene regulation in mammalian cells. The RNA-guided dCas9 protein was implemented as a programmable transcriptional activator or repressor device, including targeting of endogenous loci. For facile assembly of single or multiple CRISPR RNAs, our toolkit comprises a modular RNAimer plasmid, which encodes the required noncoding RNA components.

Complementary and alternative medicine (CAM) providers' views of chronic low back pain patients' expectations of CAM therapies: a qualitative study.

BACKGROUND: Some researchers think that patients with higher expectations for CAM therapies experience better outcomes and that enthusiastic providers can enhance treatment outcomes. This is in contrast to evidence suggesting conventional medical providers often reorient patient expectations to better match what providers believe to be realistic. However, there is a paucity of research on CAM providers' views of their patients' expectations regarding CAM therapy and the role of these expectations in patient outcomes. METHODS: To better understand how CAM providers view and respond to their patients' expectations of a particular therapy, we conducted 32 semi-structured, qualitative interviews with acupuncturists, chiropractors, massage therapists and yoga instructors identified through convenience sampling. Interviews were recorded, transcribed and analyzed thematically using Atlas ti version 6.1. RESULTS: CAM providers reported that they attempt to ensure that their patients' expectations are realistic. Providers indicated they manage their patients' expectations in a number of domains- roles and responsibilities of providers and patients, treatment outcomes, timeframe for improvement, and treatment experience. Providers reported that patients' expectations change over time and that they need to continually manage these expectations to enhance patient engagement and satisfaction with treatment. CONCLUSIONS: Providers of four types of CAM therapies viewed patients' expectations as an important component of their experiences with CAM therapy and indicated that they try to align patient expectations with reality. These findings suggest that CAM providers are similar in this respect to conventional medical providers.