Spot the difference: Comparing results of analyses from real patient data and synthetic derivatives

BACKGROUND: Synthetic data may provide a solution to researchers who wish to generate and share data in support of precision healthcare. Recent advances in data synthesis enable the creation and analysis of synthetic derivatives as if they were the original data; this process has significant advantages over data deidentification. OBJECTIVES: To assess a big-data platform with data-synthesizing capabilities (MDClone Ltd., Beer Sheva, Israel) for its ability to produce data that can be used for research purposes while obviating privacy and confidentiality concerns. METHODS: We explored three use cases and tested the robustness of synthetic data by comparing the results of analyses using synthetic derivatives to analyses using the original data using traditional statistics, machine learning approaches, and spatial representations of the data. We designed these use cases with the purpose of conducting analyses at the observation level (Use Case 1), patient cohorts (Use Case 2), and population-level data (Use Case 3). RESULTS: For each use case, the results of the analyses were sufficiently statistically similar ( DISCUSSION AND CONCLUSION: This article presents the results of each use case and outlines key considerations for the use of synthetic data, examining their role in clinical research for faster insights and improved data sharing in support of precision healthcare

Exposure to retinoic acid in the neonatal but not adult mouse results in synchronous spermatogenesis

Retinoic acid (RA) is required for germ cell differentiation, the regulation of which gives rise to a constant production of mature sperm. In testes from 3-day postpartum (dpp) RARE-hsplacZ mice, periodic regions positive for beta-galactosidase activity were observed along the length of the seminiferous tubules. Periodicity was abolished by treatment of neonates with exogenous RA at 2 dpp. To assess the consequences, 2-dpp mice were treated with RA, and the long- and short-term effects were assessed. Long-term effects of neonatal RA exposure included a delay in the appearance of advanced germ cells and the absence of a spermatogenic wave (synchronous spermatogenesis) in the adult. In contrast, RA exposure in vitamin A-sufficient adults did not result in synchronous spermatogenesis but rather induced apoptosis in a subset of spermatogonia. Shortly after (24 h) neonates were exposed, altered expression of known germ cell differentiation and the (Stra8, Kit, Sycp3, and Rec8) meiosis markers and an increase in the number of STRA8 and SYCP3 immunopositive cells were observed relative to those of vehicle controls. However, 48 and 72 h after exposure, a significant reduction in the number of STRA8 and SYCP3 immunopositive cells occurred. Immunohistochemical analysis of a marker for apoptosis demonstrated neonatal exposure resulted in increased germ cell apoptosis, as observed in the adult. Additionally, RA exposure resulted in increased Cyp26a1 expression of the RA-degrading enzyme. Thus, while RA treatment of neonatal and adult mice resulted in apoptosis of spermatogonia, synchronous spermatogenesis occurred only after neonatal RA exposure

Localization and Regulation of Murine Esco2 During Male and Female Meiosis1

Meiosis is essential for generation of healthy gametes in both sexes and involves recombination and segregation of homologous chromosomes to produce haploid gametes. The initiation of meiosis in both sexes relies upon retinoic acid (RA) (Griswold MD, Hogarth CA, Bowles J, Koopman P. Initiating Meiosis: The Case for Retinoic Acid. Biol Reprod 2012; 86(35):1–7). Previous studies have demonstrated that the stimulated by retinoic acid gene 8 (Stra8) was required for meiotic progression in both the mouse ovary and postnatal testis. To identify additional candidates that may play a role during meiosis, we used microarray databases to generate lists of transcripts with expression profiles similar to that of Stra8 in the embryonic ovary and postnatal testis. One such gene, establishment of cohesion 1 homolog 2 (Saccharomyces cerevisiae) (Esco2), has been described as a regulator of sister chromatid cohesion during mitosis. This study describes the first in-depth analysis of ESCO2 localization and regulation during meiosis in both males and females. ESCO2 colocalized with the gamma H2A histone family member X (H2AFX) in pachytene spermatocytes, indicating that ESCO2 is a component of the XY body. In pachytene cells of the embryonic ovary, ESCO2 colocalized with H2AFX, which is consistent with the presence of ESCO2 in areas of double-stranded breaks. In addition, the expression of Esco2 was found to be regulated by RA in the postnatal testis. These data indicate that ESCO2 may play a vital role in meiosis in both males and females

Localization and Regulation of Murine Esco2 During Male and Female Meiosis

Meiosis is essential for generation of healthy gametes in both sexes and involves recombination and segregation of homologous chromosomes to produce haploid gametes. The initiation of meiosis in both sexes relies upon retinoic acid (RA) (Griswold MD, Hogarth CA, Bowles J, Koopman P. Initiating Meiosis: The Case for Retinoic Acid. Biol Reprod 2012; 86(35):1–7). Previous studies have demonstrated that the stimulated by retinoic acid gene 8 (Stra8) was required for meiotic progression in both the mouse ovary and postnatal testis. To identify additional candidates that may play a role during meiosis, we used microarray databases to generate lists of transcripts with expression profiles similar to that of Stra8 in the embryonic ovary and postnatal testis. One such gene, establishment of cohesion 1 homolog 2 (Saccharomyces cerevisiae) (Esco2), has been described as a regulator of sister chromatid cohesion during mitosis. This study describes the first in-depth analysis of ESCO2 localization and regulation during meiosis in both males and females. ESCO2 colocalized with the gamma H2A histone family member X (H2AFX) in pachytene spermatocytes, indicating that ESCO2 is a component of the XY body. In pachytene cells of the embryonic ovary, ESCO2 colocalized with H2AFX, which is consistent with the presence of ESCO2 in areas of double-stranded breaks. In addition, the expression of Esco2 was found to be regulated by RA in the postnatal testis. These data indicate that ESCO2 may play a vital role in meiosis in both males and females

Quantifying the clinical relevance of a laboratory observer performance paradigm

We continue here the study of the recently introduced spiking neural P systems, which mimic the way that neurons communicate with each other by means of short electrical impulses, identical in shape (volt- age), but emitted at precise moments of time. The sequence of moments when a neuron emits a spike is called the spike train (of this neuron); by designating one neuron as the output neuron of a spiking neural P system ¦, one obtains a spike train of ¦. Given a speci¯c way of assigning sets of numbers to spike trains of ¦, we obtain sets of numbers computed by ¦. In this way, spiking neural P systems become number computing devices. We consider a number of ways to assign (code) sets of numbers to (by) spike trains, and prove then computational completeness: the computed sets of numbers are exactly Turing computable sets. When the number of spikes present in the system is bounded, a characterization of semilinear sets of numbers is obtained. A number of research problems is also formulated

Grey-scale inversion improves detection of lung nodules

OBJECTIVE: The current study aims to establish whether detection of solitary pulmonary nodules can be improved by inverting the grey scale of posteroanterior (PA) chests. METHODS: 30 PA chest images were presented on 2 occasions to 16 senior radiologists on either primary or secondary class displays in the standard or inverted mode. 15 images within each group contained a single nodule positioned in a range of anatomical sites. A receiver operating characteristic (ROC) methodology was used to explore differences between the presentation modes. RESULTS: Improved ROC scores were evident with inverted (Az 0.77) compared with standard (Az 0.73) (p=0.02) images; however, this difference was seen only with the primary displays. The benefits seen are most likely owing to increased nodule luminance with the inverted images, particularly when using primary displays. CONCLUSION: This study demonstrates that the inverted image can offer advantages in lung nodule detection over the standard presentation mode when images are viewed on high-specification viewing systems. The study has demonstrated that there is an improvement in the detectability of lung nodules on an inverted image with a primary display monitor that is not evident with secondary displays. This is likely to be the result of increased nodule luminance on primary displays when images are presented in the inverted mode

Gene Expression in the Efferent ducts, Epididymis, and Vas deferens during Embryonic Development of the Mouse

The tissues of the male reproductive tract are characterized by distinct morphologies, from highly coiled to un-coiled. Global gene expression profiles of efferent ducts, epididymis, and vas deferens were generated from embryonic day 14.5 to postnatal day 1 as tissue-specific morphologies emerge. Expression of homeobox genes, potential mediators of tissue-specific morphological development, was assessed. Twenty homeobox genes were identified as either tissue-enriched, developmentally regulated, or both. Additionally, ontology analysis demonstrated cell adhesion to be highly regulated along the length of the reproductive tract. Regulators of cell adhesion with variable expression between the three tissues were identified including Alcam , various cadherins, and multiple integrins. Immunofluorescence localization of the cell adhesion regulators POSTN and CDH2 demonstrated cell adhesion in the epithelium and mesenchyme of the epididymis may change throughout development. These results imply cell adhesion may be modulated in a tissue-specific manner, playing an important role in establishing each tissue’s final morphology