Characterizing patient compliance over six months in remote digital trials of Parkinson's and Huntington disease.

Background: A growing number of clinical trials use various sensors and smartphone applications to collect data outside of the clinic or hospital, raising the question to what extent patients comply with the unique requirements of remote study protocols. Compliance is particularly important in conditions where patients are motorically and cognitively impaired. Here, we sought to understand patient compliance in digital trials of two such pathologies, Parkinson's disease (PD) and Huntington disease (HD).

Changes in vaginal community state types reflect major shifts in the microbiome.

: Recent studies of various human microbiome habitats have revealed thousands of bacterial species and the existence of large variation in communities of microorganisms in the same habitats across individual human subjects. Previous efforts to summarize this diversity, notably in the human gut and vagina, have categorized microbiome profiles by clustering them into community state types (CSTs). The functional relevance of specific CSTs has not been established.

Epidemiological Models Lacking Process Noise Can Be Overconfident.

Mathematic models of epidemics are the key tool for predicting future course of disease in a population and analyzing the effects of possible intervention policies. Typically, models that produce deterministic are applied for making predictions and reaching decisions. Stochastic modeling methods present an alternative.

Driver gene classification reveals a substantial overrepresentation of tumor suppressors among very large chromatin-regulating proteins.

Compiling a comprehensive list of cancer driver genes is imperative for oncology diagnostics and drug development. While driver genes are typically discovered by analysis of tumor genomes, infrequently mutated driver genes often evade detection due to limited sample sizes. Here, we address sample size limitations by integrating tumor genomics data with a wide spectrum of gene-specific properties to search for rare drivers, functionally classify them, and detect features characteristic of driver genes.

Understanding Deviations from Clinical Practice Guidelines in Adult Soft Tissue Sarcoma.

In recent years we have witnessed the increasing adoption of clinical practice guidelines (CPGs) as decision support tools that guide medical treatment. As CPGs gain popularity, it has become evident that physicians frequently deviate from CPG recommendations, both erroneously and due to sound medical rationale. In this study we developed a methodology to computationally identify these deviation cases and understand their movitation.

A model-driven approach to clinical practice guidelines representation and evaluation using standards.

Clinical Practice Guidelines (CPGs) contain a set of schematic plans for the treatment and management of patients who have a particular clinical condition. CPGs are increasingly being used to support physician decision making. Many groups develop tools for the representation of CPGs.

Analyzing the "CareGap": assessing gaps in adherence to clinical guidelines in adult soft tissue sarcoma.

Clinical decision support systems (CDSSs) are gaining popularity as tools that assist physicians in optimizing medical care. These systems typically comply with evidence-based medicine and are designed with input from domain experts. Nonetheless, deviations from CDSS recommendations are abundant across a broad spectrum of disorders, raising the question as to why this phenomenon exists.

Evicase: an evidence-based case structuring approach for personalized healthcare.

The personalized medicine era stresses a growing need to combine evidence-based medicine with case based reasoning in order to improve the care process. To address this need we suggest a framework to generate multi-tiered statistical structures we call Evicases. Evicase integrates established medical evidence together with patient cases from the bedside.

Cell-to-cell variability of alternative RNA splicing.

Heterogeneity in the expression levels of mammalian genes is large even in clonal populations and has phenotypic consequences. Alternative splicing is a fundamental aspect of gene expression, yet its contribution to heterogeneity is unknown. Here, we use single-molecule imaging to characterize the cell-to-cell variability in mRNA isoform ratios for two endogenous genes, CAPRIN1 and MKNK2.

Visualization of single mRNAs reveals temporal association of proteins with microRNA-regulated mRNA.

Although many proteins are known to function in microRNA (miRNA)-based translational repression, we lack a comprehensive understanding of temporal relationships between the mRNA, miRNA and their constituent proteins. To understand the dynamics of miRNA and protein interactions, we created a synthetic inducible miRNA system in mammalian cells. By visualizing single mRNAs and observing their co-localization with proteins over time, we produced a temporal association map of miRNA-associated factors.

Systems-level engineering of nonfermentative metabolism in yeast.

We designed and experimentally validated an in silico gene deletion strategy for engineering endogenous one-carbon (C1) metabolism in yeast. We used constraint-based metabolic modeling and computer-aided gene knockout simulations to identify five genes (ALT2, FDH1, FDH2, FUM1, and ZWF1), which, when deleted in combination, predicted formic acid secretion in Saccharomyces cerevisiae under aerobic growth conditions. Once constructed, the quintuple mutant strain showed the predicted increase in formic acid secretion relative to a formate dehydrogenase mutant (fdh1 fdh2), while formic acid secretion in wild-type yeast was undetectable.

Engineering a synthetic dual-organism system for hydrogen production.

Molecular hydrogen produced biologically from renewable biomass is an attractive replacement for fossil fuels. One potential route for biological hydrogen production is the conversion of biomass into formate, which can subsequently be processed into hydrogen by Escherichia coli. Formate is also a widely used commodity chemical, making its bioproduction even more attractive.