Derived Data Storage and Exchange Workflow for Large-Scale Neuroimaging Analyses on the BIRN Grid

Organizing and annotating biomedical data in structured ways has gained much interest and focus in the last 30 years. Driven by decreases in digital storage costs and advances in genetics sequencing, imaging, electronic data collection, and microarray technologies, data is being collected at an ever increasing rate. The need to store and exchange data in meaningful ways in support of data analysis, hypothesis testing and future collaborative use is pervasive. Because trans-disciplinary projects rely on effective use of data from many domains, there is a genuine interest in informatics community on how best to store and combine this data while maintaining a high level of data quality and documentation. The difficulties in sharing and combining raw data become amplified after post-processing and/or data analysis in which the new dataset of interest is a function of the original data and may have been collected by multiple collaborating sites. Simple meta-data, documenting which subject and version of data were used for a particular analysis, becomes complicated by the heterogeneity of the collecting sites yet is critically important to the interpretation and reuse of derived results. This manuscript will present a case study of using the XML-Based Clinical Experiment Data Exchange (XCEDE) schema and the Human Imaging Database (HID) in the Biomedical Informatics Research Network's (BIRN) distributed environment to document and exchange derived data. The discussion includes an overview of the data structures used in both the XML and the database representations, insight into the design considerations, and the extensibility of the design to support additional analysis streams

Polysaccharide Specific Monoclonal Antibodies Provide Passive Protection against Intranasal Challenge with Burkholderia pseudomallei

Burkholderia pseudomallei is a Gram-negative bacillus that is the causative agent of melioidosis. The bacterium is inherently resistant to many antibiotics and mortality rates remain high in endemic areas. The lipopolysaccharide (LPS) and capsular polysaccharide (CPS) are two surface-associated antigens that contribute to pathogenesis. We previously developed two monoclonal antibodies (mAbs) specific to the CPS and LPS; the CPS mAb was shown to identify antigen in serum and urine from melioidosis patients. The goal of this study was to determine if passive immunization with CPS and LPS mAbs alone and in combination would protect mice from a lethal challenge with B. pseudomallei. Intranasal (i.n.) challenge experiments were performed with B. pseudomallei strains 1026b and K96423. Both mAbs provided significant protection when administered alone. A combination of mAbs was protective when low doses were administered. In addition, combination therapy provided a significant reduction in spleen colony forming units (cfu) compared to results when either the CPS or LPS mAbs were administered alone

Multi-platform Approach for Microbial Biomarker Identification Using Borrelia burgdorferi as a Model

The identification of microbial biomarkers is critical for the diagnosis of a disease early during infection. However, the identification of reliable biomarkers is often hampered by a low concentration of microbes or biomarkers within host fluids or tissues. We have outlined a multi-platform strategy to assess microbial biomarkers that can be consistently detected in host samples, using Borrelia burgdorferi, the causative agent of Lyme disease, as an example. Key aspects of the strategy include the selection of a macaque model of human disease, in vivo Microbial Antigen Discovery (InMAD), and proteomic methods that include microbial biomarker enrichment within samples to identify secreted proteins circulating during infection. Using the described strategy, we have identified 6 biomarkers from multiple samples. In addition, the temporal antibody response to select bacterial antigens was mapped. By integrating biomarkers identified from early infection with temporal patterns of expression, the described platform allows for the data driven selection of diagnostic targets

Experimental and theoretical studies of multiply bonded tellurium compounds

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Computational Radiomics System to Decode the Radiographic Phenotype

Radiomics aims to quantify phenotypic characteristics on medical imaging through the use of automated algorithms. Radiomic artificial intelligence (AI) technology, either based on engineered hard-coded algorithms or deep learning methods, can be used to develop noninvasive imaging-based biomarkers. However, lack of standardized algorithm definitions and image processing severely hampers reproducibility and comparability of results. To address this issue, we developed PyRadiomics, a flexible open-source platform capable of extracting a large panel of engineered features from medical images. PyRadiomics is implemented in Python and can be used standalone or using 3D Slicer. Here, we discuss the workflow and architecture of PyRadiomics and demonstrate its application in characterizing lung lesions. Source code, documentation, and examples are publicly available at www.radiomics.io. With this platform, we aim to establish a reference standard for radiomic analyses, provide a tested and maintained resource, and to grow the community of radiomic developers addressing critical needs in cancer research. (C) 2017 AACR

Survival and gross pathology of mice passively treated with mAbs.

a<p><i>p</i> value vs. controls determined from Kaplan-Meier survival plots by log-rank (Mantel-Cox) test, bold values are statistically significant (<i>p</i><0.05).</p>b<p>positive spleen cfu was determined on survivors and assumed to occur in mice that died before study endpoint.</p>c<p><i>p</i> values vs. controls determined by Fisher's exact test, bold values are statistically significant (<i>p</i><0.05).</p>d<p>spleen cfu was assessed on survivors only; values indicate cfu determined by plating 100 µl from a 1 ml spleen homogenate; T indicates too numerous to count.</p>e<p>determination of abscess formation on internal organs was performed on survivors only.</p

Protection in passively immunized mice following i.n. challenge with <i>B. pseudomallei</i> strain 1026b.

<p>BALB/c mice were administered 1 mg of either CPS IgG3 mAb 3C5 or LPS IgG3 mAb 4C7 alone or 1 mg of each mAb in combination by the i.p. route. Intranasal challenge was performed 18 h later with 15 LD₅₀ of <i>B. pseudomallei</i>. Mice were monitored for 21 days after which gross pathology and spleen cfu were determined on survivors (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0035386#pone-0035386-t001" target="_blank">Table 1</a>). Control mice were treated with 1 mg of an irrelevant IgG3 mAb. <i>p</i> values of survival vs. controls are listed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0035386#pone-0035386-t001" target="_blank">Table 1</a>.</p

Detection of CPS within a splenic abscess by IHC.

<p>Organs were harvested from control BALB/c mice (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0035386#pone-0035386-g003" target="_blank">Fig. 3</a>) that were infected with <i>B. pseudomallei</i> strain 1026b. A tissue section from a spleen that contained multiple large abscesses is shown (left panel). Location of CPS was identified by HRP-labeled mAb 3C5 (brown). Box within the panel on the left indicates the boundary of an abscess and surrounding normal splenic tissue (tissue within box is magnified in right panel). White scale bars indicate 50 µm.</p

Protection in passively immunized mice following i.n. challenge with <i>B. pseudomallei</i> strain K96243.

<p>mAbs were administered by the i.p. route at the doses (µg) listed. Intranasal challenge was performed 18 h later with 2 LD₅₀ of <i>B. pseudomallei</i>. Mice were monitored for 21 days. Control mice were treated with 1 mg of an irrelevant IgG3 mAb. <i>p</i> values of survival vs. controls are listed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0035386#pone-0035386-t001" target="_blank">Table 1</a>.</p

Effect of mAb dose and combination therapy in mice challenged with <i>B. pseudomallei</i> strain 1026b.

<p>Mice were administered mAb(s) by the i.p. route followed 18 h later by i.n. challenge with 15 LD₅₀ of <i>B. pseudomallei</i>. (A) Dose-response experiment in which mice were treated with the doses (µg) listed of each mAb alone. (B) Multiple doses of mAbs 3C5 and 4C7 were administered in combination at the doses (µg) listed. Mice were monitored for 42 days after which gross pathology and spleen cfu were determined on survivors (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0035386#pone-0035386-t001" target="_blank">Table 1</a>). Control mice were not treated with mAb. <i>p</i> values of survival vs. controls are listed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0035386#pone-0035386-t001" target="_blank">Table 1</a>.</p