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Background Multilevel data integration is becoming a major area of research in systems biology. Within this area, multi-‘omics datasets on complex diseases are becoming more readily available and there is a need to set standards and good practices for integrated analysis of biological, clinical and environmental data. We present a framework to plan and generate single and multi-‘omics signatures of disease states. Methods The framework is divided into four major steps: dataset subsetting, feature filtering, ‘omics-based clustering and biomarker identification. Results We illustrate the usefulness of this framework by identifying potential patient clusters based on integrated multi-‘omics signatures in a publicly available ovarian cystadenocarcinoma dataset. The analysis generated a higher number of stable and clinically relevant clusters than previously reported, and enabled the generation of predictive models of patient outcomes. Conclusions This framework will help health researchers plan and perform multi-‘omics big data analyses to generate hypotheses and make sense of their rich, diverse and ever growing datasets, to enable implementation of translational P4 medicine. Electronic supplementary material The online version of this article (10.1186/s12918-018-0556-z) contains supplementary material, which is available to authorized users.

This essay employs Barbara Herrnstein Smith's notion of “contingencies of value,” the idea that evaluations of text vary because our readings take place in specific contexts and are shaped by cultural and historical exigencies. In this study, we apply this notion to the reading of student texts in a college composition portfolio assessment. Through an analysis of taped teacher discussions of students' writing and an examination of student responses to the grading process, we conclude that in every reading of a text (but especially in the reading of the multiple texts of a portfolio) readers posit an “implied author.” That is, based on their reading of a single text or portfolio, teacher-readers construct a persona that represents the author, and this projection can strongly influence the reader's evaluation of student work. Group discussions of portfolios allow teachers to expose and explore the value-laden nature of these judgments.

Immunotherapeutic approaches targeting a single immune checkpoint, programmed death ligand 1, have resulted in unprecedented response rates and survival benefit across multiple cancer histologies. The efficacy of PD-1 blockade is augmented when delivered in combination with other immune checkpoints, specifically anti-CTLA-4, despite a significant increase in toxicity. The current challenge is identification of novel immunomodulatory targets with equivalent efficacy to PD1 blockade as monotherapy, and which can be applied in combination with anti-PD1 with a superior therapeutic index. As the majority of autoimmune toxicity occurs in healthy, non-malignant tissue, we developed a novel high throughput RNA screen to identify new immune checkpoint targets preferentially expressed in the tumor microenvironment. Across numerous tumor types including tumors targeted by monoclonal antibodies (Abs), ie rituximab, trastuzumab, among others, the screen reproducibly identified a list of novel targets for immunotherapy which through a secondary screen were refined for cell surface expression. By this approach we selected a novel type II transmembrane glycoprotein (TIITG) with dual function as an ectoenzyme and in signal transduction. Further experiments in-vitro and ex-vivo from tumor biopsies confirmed upregulation of the target on tumor-infiltrating, activated, immune cells including but not limited to innate immune effectors. In-vitro and in-vivo murine models using agonistic antibodies to the TIITG demonstrated (1) augmentation of natural killer cell spontaneous and antibody-dependent cytotoxicity, (2) inhibition of myeloid derived suppressor cell and regulatory T cell function, and (3) enhancement in depth and breadth of the adaptive response including post vaccination. Antagonistic Abs had minimal to no effect on the immune response, while agonistic Abs augmented type 1-cytokines (IFNg and TNFa) and cytotoxic markers, including CD107a, perforin, and granzyme. Surprisingly, in a murine autoimmune toxicity model established with prior immune checkpoint agonists, agonists of the TIITG elicited no apparent adverse effects, autoimmune or otherwise. Finally, human xenograft models support antitumor activity across over a dozen tumor histologies as monotherapy in addition to synergy with anti-PD1. In summary, using a novel screening technique we uncovered promising immune targets for cancer therapy. The first of which, TIITG, has completed lead selection and is being prepared to enter a first-in-human clinical trial. Citation Format: Narendiran Rajasekaran, Amani Makkouk, Russel K. Pachynski, Aruna Azameera, Cariad Chester, Xing Zhao, Atsushi Yonezawa, Holbrook E. Kohrt. Discovery and validation of a novel checkpoint target preferentially expressed in the tumor microenvironment. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2318.

In response to damage, stress and cell death cardiac muscle undergoes remodeling in which cardiomyocytes de-differentiate and re-differentiate. An understanding of the mechanisms involved in this process may lead to therapies to promote and enhance the repair of damaged cardiac tissue. However, due to the complexity of native environments, it is hard to investigate this remodeling process directly on tissues isolated from the body. Therefore, it is important to construct a cell-culture model that will replicate the most relevant characteristics of that tissue in controlled environments with greater capability to be assessed. Native cardiac myocytes have an aligned arrangement in which neighboring cardiomyocytes are electrically and mechanical coupled through contact junctions. When adult cardiomyocytes are placed into a culture dish, the cells will be randomly oriented and lose their native phenotypes gradually due to the lack of proper aligned cell-cell connections. To address this issue, we have implemented our laser cell micropatterning system to create an adult cardiomyocyte culturing model with aligned rows of cells connected end to end. In this abstract, we describe the experimental procedure to achieve the laser alignment of adult cardiomyocytes and the results of mechanical property testing of the myocytes investigated using Multimode Picoforce Nanoscope Atomic Force Microscope (AFM) (Veeco).

This study analyzed the persuasive essays of high school juniors and seniors to determine the specific rhetorical and linguistic features that contributed to raters' holistic judgments about the overall quality of the essays. Essays written by a random sample of an ethnically, socially, and economically diverse population of high school writers were analyzed using an array of rhetorical and linguistic measures: overall quality, use of a five-paragraph structure, coherence, three types of persuasive appeals, and sentence-level errors. The relationships between the variables and the holistic scores were examined using a correlation analysis. A forward stepwise regression analysis was also used to estimate the amount of variance contributed by each variable. Results indicate that use of logical appeals, five-paragraph structure, coherence, and number of words were strongly correlated with the overall quality ratings.

Study Design. A radiologic assessment of the success of anterior lumbar interbody fusion (ALIF) using thin-section computerized tomography (CT) was performed. Objective. To assess the effect of different types of posterior stabilization on the fusion rate of ALIF. Summary of Background Data. Thin-section CT has shown a higher rate of pseudarthrosis with ALIF than previously reported with standard radiologic methods. Cadaveric studies have shown that posterior stabilization would increase stiffness of the motion segment and is likely to enhance the rate of fusion with ALIF. To our knowledge, the results of thin-section CT of ALIF, with and without posterior stabilization, has not been reported previously. Methods. Patients with discogenic back pain confirmed by diskography underwent ALIF surgery, either as a stand-alone procedure or with posterior stabilization, using translaminar, unilateral pedicle, or bilateral pedicle screws. The 4 cohorts were followed up prospectively, and thin-section CT was used to assess interbody fusion. Results. The fusion rate for stand-alone ALIF was 51%, for patients with supplementary stabilization with translaminar screws 58%, with unilateral pedicle screws 89%, and with bilateral pedicle screws 88%. A significant difference in the fusion rate was found when ALIF was combined with pedicle screw stabilization (P Conclusion. The addition of pedicle screw fixation at ALIF produces a significant increase in the rate of interbody fusion.

Study design A comparative study investigated the use of plain static radiographs, flexion-extension radiographs, and thin-section helical computed tomography (CT) scanning in the assessment of anterior lumbar interbody fusion using carbon fiber cages. Objective To compare plain static radiographs, flexion-extension radiographs, and thin-section helical computed tomography scans in the assessment of lumbar interbody fusion using carbon fiber cages. Summary of background data Lumbar interbody fusion has become a popular procedure for the treatment of discogenic back pain. However, there currently is no universally accepted radiologic assessment tool for determining fusion, and the definitive criteria for diagnosing a successful interbody fusion in the lumbar spine remains controversial. Methods Plain static radiographs, flexion-extension radiographs, and helical computed tomography scans were performed on 32 patients (49 levels) 5 years after anterior lumbar interbody fusion using carbon fiber cages and autologous bone. A radiologist assessed fusion using the Hutter method to detect movement, whereas a spinal surgeon measured movement in degrees using the Simmons method. Helical computed tomography scans were assessed for the presence of bridging trabecular bone. Results The fusion rate was 86% on plain radiographs and 84% with the Hutter method. The fusion rate was 74% with the 2 degrees cutoff, and 96% with the 5 degrees cutoff prescribed by the Food and Drug Administration. Fusion on helical computed tomography scans was observed in 65% of the patients. Conclusions In the radiologic assessment of interbody fusion using carbon fiber cages, the use of plain radiographs and flexion-extension radiographs produced much higher fusion rates than assessment with thin-section helical computed tomography scans. The thin-section helical computed tomography studies clearly demonstrated the radiographic presence or absence of bridging bone, a property that was not seen with plain static radiographs or flexion-extension radiographs.

A prodder for mine detection has been enhanced with sensors and electronics in order to provide the operator with information on the force exerted during the prodding operation and on the type of material that is in contact with the tip of the prodder. The performance of a technology demonstrator version of this Instrumented Prodder is tested under laboratory conditions, as a start of a product development path. For these tests seven different types of objects (inert PMN mines and minelike objects from stone, PVC, wood and metal) were buried in test lanes with six soil types with different hardness and moisture content. The Instrumented Prodder was inserted into the soil in such a way that it was possible to adjust the exerted force. From the test results it is concluded that material identification of buried objects by an instrumented prodder is feasible. The low reliability of the material identification feature of the technologt demonstrator as found in the tests is likely due to incorrect measurement of the contact force between the prodder's tip and the buried object.

Organohalide contaminants such as triclosan and triclocarban have been well documented in municipal wastewater treatment plants (WWTPs), but the degradation of these contaminants is not well understood. One possible removal mechanism is organohalide respiration by which bacteria reduce the halogenated compound. The purpose of this study was to determine the abundance of organohalide-respiring bacteria in eight WWTP anaerobic digesters. The obligate organohalide respiring Dehalococcoides mccartyi was the most abundant and averaged 3.3 × 107 copies of 16S rRNA genes per gram, while the Dehalobacter was much lower at 2.6 × 104 copies of 16S rRNA genes per gram. The genus Sulfurospirillum spp. was also detected at 1.0 × 107 copies of 16S rRNA genes per gram. No other known or putatively organohalide-respiring strains in the Dehalococcoidaceae family were found to be present nor were the genera Desulfitobacterium or Desulfomonile.

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