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A study on two different CAD systems for mammography as an aid to radiological diagnosis in the search of microcalcification clusters.

OBJECTIVE: The aim of the present study was to evaluate the efficacy of two different computer aided detection (CAD) systems for mammography in improving radiological diagnosis in the search of microcalcification clusters. The CAD systems used are: the SecondLooktrade mark (CADx Medical Systems, Canada) commercial system and the CALMA (computer assisted library in MAmmography) research CAD system. Three radiologists were asked to read mammographic images with and without the support of the CAD systems. MATERIAL AND METHODS: Three radiologists with respectively 3, 5 and 7 years of practice in mammogram reading in an Italian public hospital analysed a dataset composed of 120 digitized mammograms of healthy subjects with no lesion (proven by a radiological follow up of at least 3 years) and 70 images of patients with malignant cluster of microcalcification (proven by histopathological examination) both with no CAD support as well as with the help of the SecondLooktrade mark system. After 3 months they were asked to observe the same digitized mammograms with the assistance of the CALMA system. The radiologists worked independently and were unaware of the final diagnosis. The values of the area A(z) under the ROC curve, diagnostic sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy were evaluated with and without the support of the CAD systems. The reading time and qualitative evaluations of each radiologist were also reported. RESULTS: With the support of the two CAD systems an improvement in A(z) area was obtained ranging from 0.01 to 0.04. Sensitivity increased from +8.6 to +15.7% and specificity decreased from 0.8 to 4.2%. CONCLUSION: In our study, not conditioned by the dataset, the CAD systems as second reader produced an increase in overall sensitivity of up to 15.7%, with a little decrease in specificity of up to 4.2%. Based on these results both CAD systems might be used in the current practise to improve the sensitivity values of conventional reading (radiologist alone). The results of this study show that no significant differences exist in term of A(z), sensitivity and specificity between CALMA and CADx.

Breast Diseases↗

Digital expression profiles of the prostate androgen-response program.

The androgen receptor (AR) and cognate ligands regulate vital aspects of prostate cellular growth and function including proliferation, differentiation, apoptosis, lipid metabolism, and secretory action. In addition, the AR pathway also influences pathological processes of the prostate such as benign prostatic hypertrophy and prostate carcinogenesis. The pivotal role of androgens and the AR in prostate biology prompted this study with the objective of identifying molecular mediators of androgen action. Our approach was designed to compare transcriptomes of the LNCaP prostate cancer cell line under conditions of androgen depletion and androgen stimulation by generating and comparing collections of expressed sequence tags (ESTs). A total of 4400 ESTs were produced from LNCaP cDNA libraries and these ESTs assembled into 2486 distinct transcripts. Rigorous statistical analysis of the expression profiles indicated that 17 genes exhibited a high probability (P>0.9) of androgen-regulated expression. Northern analysis confirmed that the expression of KLK3/PSA, FKBP5, KRT18, DKFZP564K247, DDX15, and HSP90 is regulated by androgen exposure. Of these, only KLK3/PSA is known to be androgen-regulated while the other genes represent new members of the androgen-response program in prostate epithelium. LNCaP gene expression profiles defined by two independent experiments using the serial analysis of gene expression (SAGE) method were compared with the EST profiles. Distinctly different expression patterns were produced from each dataset. These results are indicative of the sensitivity of the methods to experimental conditions and demonstrate the power and the statistical limitations of digital expression analyses.

Adenocarcinoma↗

Gene expression profile of human bone marrow stromal cells: high-throughput expressed sequence tag sequencing analysis.

Human bone marrow stromal cells (HBMSC) are pluripotent cells with the potential to differentiate into osteoblasts, chondrocytes, myelosupportive stroma, and marrow adipocytes. We used high-throughput DNA sequencing analysis to generate 4258 single-pass sequencing reactions (known as expressed sequence tags, or ESTs) obtained from the 5' (97) and 3' (4161) ends of human cDNA clones from a HBMSC cDNA library. Our goal was to obtain tag sequences from the maximum number of possible genes and to deposit them in the publicly accessible database for ESTs (dbEST of the National Center for Biotechnology Information). Comparisons of our EST sequencing data with nonredundant human mRNA and protein databases showed that the ESTs represent 1860 gene clusters. The EST sequencing data analysis showed 60 novel genes found only in this cDNA library after BLAST analysis against 3.0 million ESTs in NCBI's dbEST database. The BLAST search also showed the identified ESTs that have close homology to known genes, which suggests that these may be newly recognized members of known gene families. The gene expression profile of this cell type is revealed by analyzing both the frequency with which a message is encountered and the functional categorization of expressed sequences. Comparing an EST sequence with the human genomic sequence database enables assignment of an EST to a specific chromosomal region (a process called digital gene localization) and often enables immediate partial determination of intron/exon boundaries within the genomic structure. It is expected that high-throughput EST sequencing and data mining analysis will greatly promote our understanding of gene expression in these cells and of growth and development of the skeleton.

Bone Marrow Cells↗

Digital archive system for radiologic images.

Use of a picture archiving and communication system (PACS) for clinical review requires rapid access to patient images. The authors have developed a second-generation archive system for a departmental PACS that optimizes access time for both current and historical images. The system is based on a composite staging mechanism that uses multiple storage media: magnetic disks, erasable magneto-optical disks, and write-once-read-many (WORM) disks. A two-tiered communication network composed of a standard Ethernet network and a gigabit bandwidth fiberoptic UltraNet network is used for distributing images to remote display stations. The system currently archives 1.5 Gbytes of radiologic images daily from three magnetic resonance imagers, two computed tomographic scanners, one computed radiographic system, and one laser film digitizer. The system features (a) multiple optical drives and robotic arms, which support concurrent archival and retrieval operations; (b) a stacking mechanism, which provides fast retrieval of current images; (c) a pre-fetch mechanism, which minimizes on-line image retrieval, hence relieving peak-hour workload of the optical disk library and the networks; (d) studies grouping and platter management, which optimize retrieval of a patient's images from multiple examinations; and (e) a job-prioritizing control, which minimizes waiting time for radiologists and referring physicians to review images at the display stations. This system is suitable for a large-scale PACS to serve the clinical and research staff.

Radiology Information Systems↗

Digital image processing for biocompatibility studies of clinical implant materials.

The use of computer vision coupled with scanning electron microscopy (SEM) was used to monitor the platelet adhesion and activation onto blood-contacting materials. The interaction of blood platelets with polyethylene (PE), poly(ethylene terephthalate) (PET), and poly(vinylchloride) (PVC) after contact of the polymeric surfaces with whole blood was studied. The SEM images (SEM Phillips XL 30) were captured using HLImage++ computer vision systems. A library with a considerable number of acceptance or rejection of samples has been conceived and implemented. The obtained results make the developed computational vision system a promising tool for the evaluation of blood compatibility of biomaterials.

Algorithms↗

Large-scale grid-enabled lattice Boltzmann simulations of complex fluid flow in porous media and under shear.

Well-designed lattice Boltzmann codes exploit the essentially embarrassingly parallel features of the algorithm and so can be run with considerable efficiency on modern supercomputers. Such scalable codes permit us to simulate the behaviour of increasingly large quantities of complex condensed matter systems. In the present paper, we present some preliminary results on the large-scale three-dimensional lattice Boltzmann simulation of binary immiscible fluid flows through a porous medium, derived from digitized X-ray micro-tomographic data of Bentheimer sandstone, and from the study of the same fluids under shear. Simulations on such scales can benefit considerably from the use of computational steering, and we describe our implementation of steering within the lattice Boltzmann code, called LB3D, making use of the RealityGrid steering library. Our large-scale simulations benefit from the new concept of capability computing, designed to prioritize the execution of big jobs on major supercomputing resources. The advent of persistent computational grids promises to provide an optimal environment in which to deploy these mesoscale simulation methods, which can exploit the distributed nature of computer, visualization and storage resources to reach scientific results rapidly; we discuss our work on the grid-enablement of lattice Boltzmann methods in this context.

Journal Article↗

E.T. Net for health science education.

E.T.Net electronic conferencing offers biocommunicators opportunities to link with others involved with interactive technology in health sciences education, development, implementation, evaluation, and research. Conferences, or asynchronous message areas, include: AVLINE, CAI, shareware, hardware, digital images, UMLS User, NUCARE, and general. E.T.Net may be accessed, free of charge to users, via Internet, SprintNet, and DATAPAC in the U.S. and in many other countries.

Computer Communication Networks↗

Identification of T cells in early dermal lymphocytic infiltrates in avian scleroderma.

University of California, Davis (UCD) line 200 chickens spontaneously develop a progressive fibrotic syndrome with features similar to those observed in human autoimmune connective tissue diseases, including fibrosis, vascular occlusion, and lymphocytic infiltration of the comb, skin, digits, and viscera. Beginning at 2 weeks post hatch, line 200 chickens develop intense lymphocytic infiltration of the comb and dorsal neck skin. To further characterize the nature of these cellular infiltrates, weekly serial skin biopsy specimens from line 200 and control birds were examined using hematoxylin and eosin staining and indirect immunofluorescence with a library of mouse anti-chicken monoclonal antibodies specific for lymphocyte markers. In situ staining performed on serial skin sections revealed the presence of large groups of T cells beginning at 2 weeks of age. Further characterization of these infiltrates demonstrated the presence of both T helper and T cytotoxic/suppressor cells with a mean +/- SD T4:T8 ratio of 1.44 +/- 0.29 by 4 weeks of age. As the lesions progressed, the infiltrates also contained distinct groups of B cells as characterized by MUI 36. In addition, the lesions were strongly positive for B-L (Ia) antigen, which was noted on B cells, monocytes/macrophages, activated T cells, and fibroblasts. The skin sections were negative for 2 different macrophage monoclonal antibodies at all time-points. Upon extraction from affected skin, 42.0 +/- 13.06% (mean +/- SD) of these cells were positive for B-L, 35.10 +/- 6.51% were T cells, and 31.25 +/- 3.14% were recognized by MUI 36. Although positive staining for IgG was not found in these extracted cells, 7% of the isolated cells were positive for surface IgM.

Animals↗

Finite element analysis of the strain distribution in the humeral head tubercles during abduction: comparison of young and osteoporotic bone.

AIM: The aim of this work was to design an accurate 3D digital model of the humerus and rotator cuff muscles. This model was then used to study strain distribution in humeral tubercles according to bone density. MATERIALS AND METHODS: The geometry of bone and muscle structures was reproduced using SURFDRIVER software, based on anatomical sections, CT scans and MRI images from the Visible Human Project image library. The contours were transferred to PATRAN software to rebuild volumes and mesh them. Calculations of strains and their distribution were performed using NASTRAN software. All the elements were considered to be isotropes. RESULTS: The study of the distribution of stress magnitude according to the type of bone modeled, shows that some stresses in cortical bone are greater than those in cancellous bone and are also greater in old bone, implying more deformation in old bone at constant force. This study also shows that stresses do not penetrate deeply into cancellous tissue. CONCLUSION: Observing the simulation results led understanding of the pathology of certain fractures of the proximal end of the humerus. This study also helped explain why certain types of osteosynthesis fail due to tubercles reconstruction failures.

Bone Density↗

Personal digital assistants.

Personal digital assistant sales are growing exponentially, and as medical technology advances the amount of information available becomes staggering, making a handheld device, with the ability to store a great amount of information, progressively more valuable to health care providers. Mobile computing allows for a great deal of knowledge in a small package, creating a "walking library" with a mobile collection of data always accessible. There are many diverse types of PDAs, and this article discusses the history of PDAs, general purchasing issues, general PDA features, and the most significant differences between the Palm and the Windows CE operating systems.

Computer Communication Networks↗

[Scholarly communication in the digital era: has a new era really begun?].

In this paper the author examines the issue concerning the future direction of scholarly publications. The scholarly community has sufficient expertise and incentive to collaborate on the design of a new model for scholarly communication that takes advantage of networking technology and extends the traditional benefits of print publications. The "multicanality" presents a unique approach that integrates the elements of scholarly communication beginning at the author's keyboard and ending in the library's archives. The "multicanality" simplifies the work of authors, editors and librarians, and reduces related publishing expense. The needed technical expertise is already available to begin it.

Biomedical Research↗

Management of the picture archiving and communications system archive at Texas Children's Hospital.

As hospitals convert from conventional film-based imaging to picture archival and communications systems (PACS), methods for managing an enormous library of images must change considerably. While most hospitals are required to retain general, nonmammographic, radiologic images for 7 years beyond the examination date, our pediatric hospital must maintain images until the child's eighteenth birthday, plus the 5-year statute of limitations. Although the physical extent of an electronic archive is tiny compared with a film archive, a long-range strategy is required to ensure that electronic images acquired today can be retrieved and viewed 23 years in the future. Challenges to the long-term stability of the electronic archive include the limited and uncertain shelf life of high-density electronic storage media, the finite maintainability of the electromechanical systems for reading the media, the short product lifetime of software for accessing the images, rapid development of higher density storage products, and the exponential advancement of computer and networking technology that fuels product obsolescence. Since we cannot assure the function of our current archive in two decades, we are committed to a continual process of migration of old electronic image data to newer media and systems. As an early-adopter of PACS technology, Texas Children's Hospital's (TCH) archive management experience is relevant to others. Although not filled to capacity, our first digital archive, based on phase-change write-once-read-many (WORM) technology, was forced into an inactive status by software and hardware changes. Our second set of archives was partially filled with low-density magneto-optical disk (MOD) media, when the drives were upgraded to high density and then filled to capacity. This undesirable situation forced us into shelf management of media. Our third-generation archive is based on a helical tape library with the capacity to contain 7 years of examinations. We will describe the motivation for data migration, limitations in the methods available to perform the migration, and unanticipated benefits of the migration process.

Computer Communication Networks↗

Expression of Xenopus XlSALL4 during limb development and regeneration.

The multi-C2H2 zinc-finger domain containing transcriptional regulators of the spalt (SAL) family plays important developmental regulatory roles. In a competitive subtractive hybridization screen of genes expressed in Xenopus laevis hindlimb regeneration blastemas, we identified a SAL family member that, by phylogenetic analysis, falls in the same clade as human SALL4 and have designated it as XlSALL4. Mutations of human SALL4 have been linked to Okihiro syndrome, which includes preaxial (anterior) limb defects. The expression pattern of XlSALL4 transcripts during normal forelimb and hindlimb development and during hindlimb regeneration at the regeneration-competent and regeneration-incompetent stages is temporally and regionally dynamic. We show for the first time that a SAL family member (XlSALL4) is expressed at the right place and time to play a role regulating both digit identity along the anterior/posterior axis and epimorphic limb regeneration.

Amino Acid Sequence↗

In situ visualisation of immunoglobulin genes in normal and malignant lymphoid cells.

Aims-To directly visualise immunoglobulin (Ig) heavy (H) and light chain genes (kappa and lambda) in metaphase chromosomes and interphase nuclei of normal and malignant lymphocytes using small genomic probes targeted to intragenic sequences.Methods-Cytogenetic preparations from phytohaemagglutinin stimulated lymphocytes, B-chronic lymphocytic leukaemia (B-CLL) cells, and a B-prolymphocytic leukaemia (B-PLL) cell line, containing a t(11;14), were hybridised in situ using biotin or digoxigenin labelled plasmid probes. The kappa genes were visualised with a combination of probes for the Ckappa, Jkappa, Vkappa1, and Vkappa2 segments, the lambda genes with a probe containing the Jlambda2-Clambda2, Jlambda3-Clambda3 segments and the H genes with a probe for Clambda2. Hybridisation sites were visualised using appropriate fluorochrome conjugates and images were analysed by digital microscopy.Results-In both normal and malignant lymphoid cells, the kappa and lambda genes were visualised as a single dot signal, whereas the H lambda genes were resolved as either two or three separate signals per chromatid in metaphase chromosomes or per allele in interphase nuclei. In the malignant PLL cells, double hybridisation experiments with a painting library specific for the chromosome 11 showed that the lambda region was retained in the translocated chromosome, with an in situ resolution pattern similar to that of the normal allele.Conclusions-This study shows that a high resolution in situ analysis of the three Ig loci can be efficiently performed with small size genomic probes on both normal and malignant lymphoid cells. Such an approach offers a flexible tool for the molecular characterisations of these loci on chromosomes and individual neoplastic cells.

Journal Article↗

The human gene for xanthine dehydrogenase (XDH) is localized on chromosome band 2q22.

Mutations in the xanthine dehydrogenase gene (XDH), which codes for the last enzyme of the purine catabolic pathway in man, cause the autosomal recessive disease xanthinuria. We obtained cDNA clones from a human breast cDNA library and confirmed one of the two different sequences proposed for human XDH. Using a somatic cell hybrid mapping panel and specific primers for human XDH, we assigned the gene to chromosome 2. By fluorescence in situ hybridization, the gene was localized to bands 2p22.3-->p22.2. The FLpter probe location was 0.135 (SD = 0.016), as determined by digital image analysis.

Base Sequence↗

Dynamic documentation of digital dacryocystography.

Digital dacryocystography has proved to be the optimum method of x-ray diagnostics in connection with managing obstructions of the lacrimal pathways. We present 50 patients in whom digital dacryocystography was performed with a computer-controlled x-ray unit and a C-arc coupled to an image intensifier TV-system. A nonionic water soluble contrast medium was used. The bilateral contrast medium filling process appearing on the monitor was simultaneously recorded on videotape. Videocassettes, with patient data attached, were stored in a videotape library, providing repeatable diagnostic documentation and an excellent base for scientific analyses.

Adult↗

Large-scale statistical analysis of secondary xylem ESTs in pine.

A computational analysis of pine transcripts was conducted to contribute to the functional annotation of conifer sequences. A statistical analysis of expressed sequential tags(ESTs) belonging the 7732 contigs in the TIGR Pinus Gene Index (PGI1.0) identified 260 differentially represented gene sequences across six cDNA libraries from loblolly pine secondary xylem. Cluster analysis of this subset of contigs resulted in five groups representing genes preferentially represented in one of the xylem samples (compression wood, plannings, root xylem, latewood) and one group containing mostly genes simultaneously present in compression and side wood libraries. To complement the sequence annotation, 27 cDNA clones representing selected transcripts were completely sequenced. Several genes were identified that could represent putative markers for xylem from different organs, at different stages of development. Several sequences encoding regulatory proteins were over-represented in root xylem as opposed to the other xylem samples. Some of them belonged to known families of plant transcription factors, but two genes were previously uncharacterized in plants. One transcript was homologous to the gene encoding the Smad4 interacting factor, a key co-activator in TGFbeta (transforming growth factor) signalling in animals. Thus, the digital analysis of pine ESTs highlighted a putative gene function of potentially broad interest but that has yet to be investigated in plants. More generally, this study showed that the application of numerical approaches to EST databases should be helpful in establishing priorities among genes to consider for targeted functional studies. Thus, we illustrated the potential of extracting information from conifer sequences already accessible through well-structured public databases.

Amino Acid Sequence↗