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PubMed2002

Tools for clinical toxicology on the World Wide Web: review and scenario.

Clinical toxicologists are entrusted with the health and safety of humans and animals exposed to toxic substances. To do their jobs well they need a solid knowledge of toxicological principles, an ability to handle emergent situations, a "bedside" manner that results in a good rapport with patients, and the ability to access current and accurate information in order to properly care for the afflicted. An information armamentarium that is increasingly digital and Web-based is becoming a necessity. This article reviews Web resources that can assist the toxicologist. A case scenario is presented to provide a practical perspective to the information tools outlined.

Chemical Phenomena↗
PubMed2003

What can digital transcript profiling reveal about human cancers?

Important biological and clinical features of malignancy are reflected in its transcript pattern. Recent advances in gene expression technology and informatics have provided a powerful new means to obtain and interpret these expression patterns. A comprehensive approach to expression profiling is serial analysis of gene expression (SAGE), which provides digital information on transcript levels. SAGE works by counting transcripts and storing these digital values electronically, providing absolute gene expression levels that make historical comparisons possible. SAGE produces a comprehensive profile of gene expression and can be used to search for candidate tumor markers or antigens in a limited number of samples. The Cancer Genome Anatomy Project has created a SAGE database of human gene expression levels for many different tumors and normal reference tissues and provides online tools for viewing, comparing, and downloading expression profiles. Digital expression profiling using SAGE and informatics have been useful for identifying genes that have a role in tumor invasion and other aspects of tumor progression.

Antigens, Neoplasm↗
PubMed2003

Visible Human 2.0--the next generation.

The National Library of Medicine has initiated the development of new anatomical methods and techniques for the acquisition of higher resolution data sets, aiming to address the anatomical artifacts encountered in the development of the Visible Human Male and Female and to insure enhanced detection of structures, providing data in greater depth and breadth. Given this framework, we acquired a complete data set of the head and neck. CT and MR scans were also obtained with registration hardware inserted prior to imaging. The arterial and venous systems were injected with colorized araldite-F. After freezing, axial cryosectioning and digital photography at 147 microns/voxel resolution was performed. Two slabs of the specimen were acquired with a special tissue harvesting technique. The resulting tissue slices of the whole specimen were stained for different tissue types. The resulting histological material was then scanned at a 60x magnification using the Virtual Slice technology at 2 microns/pixel resolution (each slide approximately 75,000 x 100,000 pixels). In this data set, for the first time anatomy is presented as a continuum from a radiologic granularity of 1 mm/voxel, to a macroscopic resolution of .147 mm/voxel, to microscopic resolution of 2 microns/pixel. The hiatus between gross anatomy and histology has been assumed insurmountable, and until the present time this gap was bridged by extrapolating findings on minute samples. The availability of anatomical data with the fidelity presented will render it possible to perform a seamless study of whole organs at a cellular level and provide a testbed for the validation of histological estimation techniques. A future complete Visible Human created from data acquired at a cellular resolution, aside from its daunting size, will open new possibilities in multiple directions in medical research and simulation.

Computer Simulation↗
PubMed1999

Interactive web-based radiology teaching file.

This multimedia radiology teaching file was developed for medical students, residents, physicians, and researchers to present teaching components related to clinical studies. Patient studies are used to create teaching cases, user can also create lecture series and custom presentations (catalogs) by linking related text and images. The user is able to make and preserve his/her own notes related to reviewed information. From the computer workstation, the user can perform search our case library by American College of Radiology (ACR) codes, keywords, modalities, or text. Results are presented in custom pages and include text lists, thumbnails lists, rescaled images, and full-size images. Text can be easily printed in custom format or exported to an ASCI file. To preserve the privacy of the student, access to our database is granted to the web browser by log-in panel. Image and text can be imported from Digital Imaging and Communications in Medicine (DICOM)-compatible devices or entered by using web forms. In conclusion, we developed a multifunctional interactive teaching environment accessible for multiplatform internet users.

Computer Security↗
PubMed2000

Variability of molecular descriptors in compound databases revealed by Shannon entropy calculations

A method is introduced to calculate and compare the variability of molecular descriptors in compound databases. Descriptor variability analysis is based on histograms recording the distribution of molecular descriptors and calculation of Shannon entropy (SE), a metric originally applied in digital communication. SE values reflect the variability of descriptor settings. We have calculated a total of 92 molecular descriptors in the ACD and NCI databases and ranked them according to their variability. Significant differences in entropy are observed for a number of descriptors. However, the most variable descriptors are similar in the ACD and NCI databases. Such high-entropy descriptors are preferred tools to discriminate between compounds or account for the diversity of chemical libraries.

Journal Article↗
PubMed2003

Biomedical informatics: precious scientific resource and public policy dilemma.

Biomedical informatics includes the application of computers, information networks and systems, and a growing body of scientific understanding to a range of problems. As skill in this field increases and as progress in virtually all modern biomedical science becomes more data intensive, informatics becomes a precious resource. Applications areas include access to knowledge, discovery in genomics, medical records, mathematical modeling, and bioengineering. At the same time, progress in informatics is deeply dependent on resolution of four major public policy issues: digital intellectual property rights, genetic testing protection, medical data privacy, and the role of biomedical data in the context of information warfare and homeland security.

Anatomy, Cross-Sectional↗
PubMed2026

Integrating structure and experimental data annotations with computational modeling framework for predicting micro-nanoplastics toxicities.

The wide use of plastic materials leads to increased emissions of micro-nanoplastics (MNPs) into the environment, raising significant concerns about their impact on human health. Traditional experimental approaches for assessing MNPs toxicity are costly, time-consuming, and there are no experimental protocols that are universally acceptable. Computational modeling using machine learning (ML) approaches provides an efficient alternative to MNP toxicity assessment. However, most modeling studies of MNPs are limited due to the lack of high-quality data and there are few previous modeling studies considering complex structures of MNPs for model training. To address this challenge, we constructed three MNP datasets with popular toxicity endpoints from various resources and used nanostructure annotation techniques to create virtual MNPs (vMNPs) for all MNP structures. The MNP structures were digitalized from annotated vMNPs, and geometrical descriptors were calculated using the Delaunay Tessellation approach. Moreover, important experimental information, such as concentrations and cell lines, were transformed into extra training variables. Partial least squares regression (PLSR) models were built using both experimental and geometrical descriptors and validated through a leave-one-out cross validation procedure. The resulting models showed reasonable performance in predicting toxicity potentials of MNPs for the three endpoints in the present datasets. Moreover, an additional library of vMNPs with their predicted properties and bioactivities was constructed, directing further research of new MNPs. This study provides three novel ML models for MNPs by integrating geometrical and experimental descriptors, which have the potential to assess new MNPs for their toxicity. The modeling strategy developed in this study can be easily expanded to model other MNP toxicity endpoints and create promising new models for MNP toxicity assessments.

Data annotation↗
PubMed2004

Bayesian model accounting for within-class biological variability in Serial Analysis of Gene Expression (SAGE).

BACKGROUND: An important challenge for transcript counting methods such as Serial Analysis of Gene Expression (SAGE), "Digital Northern" or Massively Parallel Signature Sequencing (MPSS), is to carry out statistical analyses that account for the within-class variability, i.e., variability due to the intrinsic biological differences among sampled individuals of the same class, and not only variability due to technical sampling error. RESULTS: We introduce a Bayesian model that accounts for the within-class variability by means of mixture distribution. We show that the previously available approaches of aggregation in pools ("pseudo-libraries") and the Beta-Binomial model, are particular cases of the mixture model. We illustrate our method with a brain tumor vs. normal comparison using SAGE data from public databases. We show examples of tags regarded as differentially expressed with high significance if the within-class variability is ignored, but clearly not so significant if one accounts for it. CONCLUSION: Using available information about biological replicates, one can transform a list of candidate transcripts showing differential expression to a more reliable one. Our method is freely available, under GPL/GNU copyleft, through a user friendly web-based on-line tool or as R language scripts at supplemental web-site.

Astrocytoma↗
PubMed1997

SIGIF: a digital signal interchange format with application in neurophysiology.

In this paper, the authors describe a biomedical digital-signal interchange format. The format supports both raw and processed data, multiple segments, several signal structures and representations, and an open architecture. Its versatility and adaptability allows the software to take advantage of any particular features of the acquisition hardware. The format has been used and improved in routine work during a five-year period involving the cooperation between two hospitals and one engineering research center. In order to support the format, an object oriented C language library has been developed and is also shortly described.

Electrophysiology↗
PubMed1999

Application of multilayer feed-forward neural networks to automated compound identification in low-resolution open-path FT-IR spectrometry.

A drawback of current open-path Fourier transform infrared (OP/FT-IR) systems is that they need a human expert to determine those compounds that may be quantified from a given spectrum. In this work, multilayer feed-forward neural networks with one hidden layer were used to automatically recognize compounds in an OP/FT-IR spectrum without compensation of absorption lines due to atmospheric H2O and CO2. The networks were trained by fast-back-propagation. The training set comprised spectra that were synthesized by digitally adding randomly scaled reference spectra to actual open-path background spectra measured over a variety of path lengths and temperatures. The reference spectra of 109 compounds were used to synthesize the training spectra. Each neural network was trained to recognize only one compound in the presence of up to 10 other interferences in an OP/FT-IR spectrum. Every compound in a database of vaporphase reference spectra can be encoded in an independent neural network so that a neural network library can be established. When these networks are used for the identification of compounds, the process is analogous to spectral library searching. The effect of learning rate and band intensities on the convergence of network training was examined. The networks were successfully used to recognize five alcohols and two chlorinated compounds in field-measured controlled-release OP/FT-IR spectra of mixtures of these compounds.

Neural Networks, Computer↗
PubMed2003

A functional analysis of the spacer of V(D)J recombination signal sequences.

During lymphocyte development, V(D)J recombination assembles antigen receptor genes from component V, D, and J gene segments. These gene segments are flanked by a recombination signal sequence (RSS), which serves as the binding site for the recombination machinery. The murine Jbeta2.6 gene segment is a recombinationally inactive pseudogene, but examination of its RSS reveals no obvious reason for its failure to recombine. Mutagenesis of the Jbeta2.6 RSS demonstrates that the sequences of the heptamer, nonamer, and spacer are all important. Strikingly, changes solely in the spacer sequence can result in dramatic differences in the level of recombination. The subsequent analysis of a library of more than 4,000 spacer variants revealed that spacer residues of particular functional importance are correlated with their degree of conservation. Biochemical assays indicate distinct cooperation between the spacer and heptamer/nonamer along each step of the reaction pathway. The results suggest that the spacer serves not only to ensure the appropriate distance between the heptamer and nonamer but also regulates RSS activity by providing additional RAG:RSS interaction surfaces. We conclude that while RSSs are defined by a "digital" requirement for absolutely conserved nucleotides, the quality of RSS function is determined in an "analog" manner by numerous complex interactions between the RAG proteins and the less-well conserved nucleotides in the heptamer, the nonamer, and, importantly, the spacer. Those modulatory effects are accurately predicted by a new computational algorithm for "RSS information content." The interplay between such binary and multiplicative modes of interactions provides a general model for analyzing protein-DNA interactions in various biological systems.

Algorithms↗
PubMed1977

Cytomat-R: a computer-controlled multiple laser source multiparameter flow cytophotometer system.

A multiple illumination wavelength multiparameter flow cytophotometer system, using laser sources and controlled by a small, general-purpose digital computer, has been produced for use in the development of new flow cytometric techniques. Three different laser wave-lengths can be used simultaneously to illuminate different regions of the flow chamber; as many as five measurements of light scattering at various angles, extinction, and fluorescence at one or more wavelengths can be made at each illuminated station. Cells in suspension may be examined at rates of 1000 cells/sec, with seven correlated optical measurements being recorded for each cell. A library of programs for data manipulation and statistical analysis make it possible to use the system to develop and implement cell characterization, counting and classification procedures for basic and clinical research applications.

Blood Cells↗
PubMed2006

Antenatal perineal massage for reducing perineal trauma.

BACKGROUND: Perineal trauma following vaginal birth can be associated with significant short- and long-term morbidity. Antenatal perineal massage has been proposed as one method of decreasing the incidence of perineal trauma. OBJECTIVES: To assess the effect of antenatal perineal massage on the incidence of perineal trauma at birth and subsequent morbidity. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group Trials Register (30 January 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 1, 2005), PubMed (1966 to January 2005), EMBASE (1980 to January 2005) and reference lists of relevant articles. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials evaluating any described method of antenatal perineal massage undertaken for at least the last four weeks of pregnancy. DATA COLLECTION AND ANALYSIS: Both review authors independently applied the selection criteria, extracted data from the included studies and assessed study quality. We contacted study authors for additional information. MAIN RESULTS: Three trials (2434 women) comparing digital perineal massage with control were included. All were of good quality. Antenatal perineal massage was associated with an overall reduction in the incidence of trauma requiring suturing (three trials, 2417 women, relative risk (RR) 0.91 (95% confidence interval (CI) 0.86 to 0.96), number needed to treat (NNT) 16 (10 to 39)). This reduction was statistically significant for women without previous vaginal birth only (three trials, 1925 women, RR 0.90 (95% CI 0.84 to 0.96), NNT 14 (9 to 35)). Women who practised perineal massage were less likely to have an episiotomy (three trials, 2417 women, RR 0.85 (95% CI 0.75 to 0.97), NNT 23 (13 to 111)). Again this reduction was statistically significant for women without previous vaginal birth only (three trials, 1925 women, RR 0.85 (95% CI 0.74 to 0.97), NNT 20 (11 to 110)). No differences were seen in the incidence of 1st or 2nd degree perineal tears or 3rd/4th degree perineal trauma. Only women who have previously birthed vaginally reported a statistically significant reduction in the incidence of pain at three months postpartum (one trial, 376 women, RR 0.68 (95% CI 0.50 to 0.91) NNT 13 (7 to 60)). No significant differences were observed in the incidence of instrumental deliveries, sexual satisfaction, or incontinence of urine, faeces or flatus for any women who practised perineal massage compared with those who did not massage. AUTHORS' CONCLUSIONS: Antenatal perineal massage reduces the likelihood of perineal trauma (mainly episiotomies) and the reporting of ongoing perineal pain and is generally well accepted by women. As such, women should be made aware of the likely benefit of perineal massage and provided with information on how to massage.

Delivery, Obstetric↗
PubMed2001

Spectral imaging of multi-color chromogenic dyes in pathological specimens.

We have investigated the use of spectral imaging for multi-color analysis of permanent cytochemical dyes and enzyme precipitates on cytopathological specimens. Spectral imaging is based on Fourier-transform spectroscopy and digital imaging. A pixel-by-pixel spectrum-based color classification is presented of single-, double-, and triple-color in situ hybridization for centromeric probes in T24 bladder cancer cells, and immunocytochemical staining of nuclear antigens Ki-67 and TP53 in paraffin-embedded cervical brush material (AgarCyto). The results demonstrate that spectral imaging unambiguously identifies three chromogenic dyes in a single bright-field microscopic specimen. Serial microscopic fields from the same specimen can be analyzed using a spectral reference library. We conclude that spectral imaging of multi-color chromogenic dyes is a reliable and robust method for pixel color recognition and classification. Our data further indicate that the use of spectral imaging (a) may increase the number of parameters studied simultaneously in pathological diagnosis, (b) may provide quantitative data (such as positive labeling indices) more accurately, and (c) may solve segmentation problems currently faced in automated screening of cell- and tissue specimens.

Carcinoma, Transitional Cell↗
PubMedDate not supplied

VIPER: a general-purpose digital image-processing system applied to video microscopy.

This paper describes VIPER, the video image-processing system Erlangen. It consists of a general purpose microcomputer, commercially available image-processing hardware modules connected directly to the computer, video input/output-modules such as a TV camera, video recorders and monitors, and a software package. The modular structure and the capabilities of this system are explained. The software is user-friendly, menu-driven and performs image acquisition, transfers, greyscale processing, arithmetics, logical operations, filtering display, colour assignment, graphics, and a couple of management functions. More than 100 image-processing functions are implemented. They are available either by typing a key or by a simple call to the function-subroutine library in application programs. Examples are supplied in the area of biomedical research, e.g. in in-vivo microscopy.

Animals↗
PubMed2001

Expression patterns of Fgf-8 during development and limb regeneration of the axolotl.

Fgf-8 is one of the key signaling molecules implicated in the initiation, outgrowth, and patterning of vertebrate limbs. However, it is not clear whether FGF-8 plays similar role in development and regeneration of urodele limbs. We isolated a Fgf-8 cDNA from the Mexican axolotl (Ambystoma mexicanum) through the screening of an embryo cDNA library. The cloned 1.26-kb cDNA contained an open reading frame encoding 212 amino acid residues with 84%, 86%, and 80% amino acid identities to those of Xenopus, chick, and mouse, respectively. By using the above clone as a probe, we examined the temporal and spatial expression patterns of Fgf-8 in developing embryos and in regenerating larval limbs. In developing embryos, Fgf-8 was expressed in the neural fold, midbrain-hindbrain junction, tail and limb buds, pharyngeal clefts, and primordia of maxilla and mandible. In the developing axolotl limb, Fgf-8 began to be expressed in the prospective forelimb region at pre-limb-bud and limb bud stages. Interestingly, strong expression was detected in the mesenchymal tissue of the limb bud before digit forming stages. In the regenerating limb, Fgf-8 expression was noted in the basal layer of the apical epithelial cap (AEC) and the underlying thin layer of mesenchymal tissue during blastema formation stages. These data suggest that Fgf-8 is involved in the organogenesis of various craniofacial structures, the initiation and outgrowth of limb development, and the blastema formation and outgrowth of regenerating limbs. In the developing limb of axolotl, unlike in Xenopus or in amniotes such as chick and mouse, the Fgf-8 expression domain was localized mainly in the mesenchyme rather than epidermis. The unique expression pattern of Fgf-8 in axolotl suggests that the regulatory mechanism of Fgf-8 expression is different between urodeles and other higher species. The expression of Fgf-8 in the deep layer of the AEC and the thin layer of underlying mesenchymal tissue in the regenerating limbs support the previous notion that the amphibian AEC is a functional equivalent of the AER in amniotes.

Ambystoma↗
PubMedDate not supplied

The fetal imaging workstation demonstration project.

Congenital birth defects are a leading cause of infant mortality. Early detection of fetal anomalies by prenatal ultrasound may improve clinical outcome in selected cases. However, many training programs are hindered by curriculum weaknesses which include: (1) limited physician exposure to ultrasound anomalies; (2) inadequate postnatal correlation with prenatal findings; (3) constraints imposed by static images for ultrasound training; and (4) difficulty with understanding complex three-dimensional anatomy. The Fetal Imaging Workstation Demonstration Project addresses these problems by illustrating how computers can supplement traditional prenatal ultrasound training through interactive multimedia. The project uses a laserdisc library of ultrasound video images as source material for a variety of interactive software tutorials. An educational testing module has been developed that can evaluate diagnostic skills through simulated ultrasound studies provided by the laserdisc library. An interactive three-dimensional fetal heart model also provides a new way for physicians to better understand their two-dimensional ultrasound studies. A survey suggests that this prototype has been widely accepted by housestaff physicians and that there is a perceived need for this supplementary training. Future work will address the educational effectiveness of these materials and will consider cost-effective ways to disseminate the software for other institutions. However, future development must be implemented against a background of rapidly emerging technologies involving faster computers, digital video, and virtual reality applications.

Computer Systems↗
PubMed2006

Utilization of digital differential display to identify novel targets of Oct3/4.

Embryonic stem (ES) cells proliferate infinitely while maintaining pluripotency. The POU family transcription factor Oct3/4 is specifically expressed in ES cells and early embryos and plays a critical role in self-renewal of ES cells. However, only a few examples of Oct3/4 target genes have been identified. In this chapter, we describe our strategy to isolate novel Oct3/4 target genes. We first identify genes that are specifically expressed in ES cells by means of digital differential display of expressed sequence tag databases. Reporter gene and gel mobility shift assays are used to confirm the role of Oct3/4. Identification of novel Oct3/4 targets will facilitate our understanding of pluripotency.

Animals↗