Shared-Task Worklists Improve Clinical Trial Recruitment Workflow in an Academic Emergency Department.

BACKGROUND: Clinical trials performed in our emergency department at Barnes-Jewish Hospital utilize a centralized infrastructure for alerting, screening, and enrollment with rule-based alerts sent to clinical research coordinators. Previously, all alerts were delivered as text messages via dedicated cellular phones. As the number of ongoing clinical trials increased, the volume of alerts grew to an unmanageable level. Therefore, we have changed our primary notification delivery method to study-specific, shared-task worklists integrated with our pre-existing web-based screening documentation system. OBJECTIVE: To evaluate the effects on screening and recruitment workflow of replacing text-message delivery of clinical trial alerts with study-specific shared-task worklists in a high-volume academic emergency department supporting multiple concurrent clinical trials. METHODS: We analyzed retrospective data on alerting, screening, and enrollment for 10 active clinical trials pre- and postimplementation of shared-task worklists. RESULTS: Notifications signaling the presence of potentially eligible subjects for clinical trials were more likely to result in a screen (p < 0.001) with the implementation of shared-task worklists compared with notifications delivered as text messages for 8/10 clinical trials. The change in workflow did not alter the likelihood of a notification resulting in an enrollment (p = 0.473). The Director of Research reported a substantial reduction in the amount of time spent redirecting clinical research coordinator screening activities. CONCLUSION: Shared-task worklists, with the functionalities we have described, offer a viable alternative to delivery of clinical trial alerts via text message directly to clinical research coordinators recruiting for multiple concurrent clinical trials in a high-volume academic emergency department.

ProteoViz: a tool for the analysis and interactive visualization of phosphoproteomics data.

Quantitative proteomics generates large datasets with increasing depth and quantitative information. With the advance of mass spectrometry and increasingly larger data sets, streamlined methodologies and tools for analysis and visualization of phosphoproteomics are needed both at the protein and modified peptide levels. To assist in addressing this need, we developed ProteoViz, which includes a set of R scripts that perform normalization and differential expression analysis of both the proteins and enriched phosphorylated peptides, and identify sequence motifs, kinases, and gene set enrichment pathways. The tool generates interactive visualization plots that allow users to interact with the phosphoproteomics results and quickly identify proteins and phosphorylated peptides of interest for their biological study. The tool also links significant phosphosites with sequence motifs and pathways that will help explain the experimental conditions and guide future experiments. Here, we present the workflow and demonstrate its functionality by analyzing a phosphoproteomic data set from two lymphoma cell lines treated with kinase inhibitors. The scripts and data are freely available at and via the ProteomeXchange with identifier PXD015606.

Use of Multi-Parallel Real-Time Quantitative PCR to Determine Blastocystis Prevalence and Association with Other Gastrointestinal Parasite Infection in a Rural Honduran Location.

To determine whether the presence of Blastocystis is associated with other gastrointestinal parasite infections, stool samples from 95 Honduran rural children were analyzed using multi-parallel quantitative real-time polymerase chain reaction (PCR) and Kato-Katz. Combined results detected the following prevalence: Blastocystis, 71.6%; Trichuris trichiura, 63.2%; Giardia lamblia, 40.0%; Ascaris lumbricoides, 15.8%; and Necator americanus, 4.2%. Age was found associated with the quantity of both Blastocystis DNA (r s = 0.524, P < 0.001) and T. trichiura DNA in the stool (fg/µL) by quantitative PCR (r s = 0.272, P < 0.001). In addition, there was an association with T. trichiura and Blastocystis infection (odds ratio [OR] = 4.72; 95% CI = 1.83, 12.20; P < 0.001). These findings demonstrate a high prevalence of Blastocystis and other intestinal parasites in a rural location in Honduras.

Engineering a stable CHO cell line for the expression of a MERS-coronavirus vaccine antigen.

Middle East respiratory syndrome coronavirus (MERS-CoV) has infected at least 2040 patients and caused 712 deaths since its first appearance in 2012, yet neither pathogen-specific therapeutics nor approved vaccines are available. To address this need, we are developing a subunit recombinant protein vaccine comprising residues 377-588 of the MERS-CoV spike protein receptor-binding domain (RBD), which, when formulated with the AddaVax adjuvant, it induces a significant neutralizing antibody response and protection against MERS-CoV challenge in vaccinated animals. To prepare for the manufacture and first-in-human testing of the vaccine, we have developed a process to stably produce the recombinant MERS S377-588 protein in Chinese hamster ovary (CHO) cells. To accomplish this, we transfected an adherent dihydrofolate reductase-deficient CHO cell line (adCHO) with a plasmid encoding S377-588 fused with the human IgG Fc fragment (S377-588-Fc). We then demonstrated the interleukin-2 signal peptide-directed secretion of the recombinant protein into extracellular milieu. Using a gradually increasing methotrexate (MTX) concentration to 5 µM, we increased protein yield by a factor of 40. The adCHO-expressed S377-588-Fc recombinant protein demonstrated functionality and binding specificity identical to those of the protein from transiently transfected HEK293T cells. In addition, hCD26/dipeptidyl peptidase-4 (DPP4) transgenic mice vaccinated with AddaVax-adjuvanted S377-588-Fc could produce neutralizing antibodies against MERS-CoV and survived for at least 21 days after challenge with live MERS-CoV with no evidence of immunological toxicity or eosinophilic immune enhancement. To prepare for large scale-manufacture of the vaccine antigen, we have further developed a high-yield monoclonal suspension CHO cell line.