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At least 1,675 records · Page 93Linked to original sources
PubMed2003

Preferential integration of human papillomavirus type 18 near the c-myc locus in cervical carcinoma.

The development of cervical cancer is highly associated with human papillomavirus (HPV) infection. Greater than 99% of all cervical tumors contain HPV DNA. Integration of high-risk HPV has been temporally associated with the acquisition of a malignant phenotype. Recent work from our lab has shown that HPV16, the most common high-risk HPV associated with cervical carcinoma, preferentially integrates at loci containing human common fragile sites (CFSs). CFSs are regions of genomic instability that have also been associated with deletions, translocations, and gene amplification during cancer development. The current work shows that HPV18, the second most prevalent high-risk HPV type found in cervical tumors, preferentially targets the CFSs. We identified 27 unique HPV18 integrations in cervical tumors, of which 63% (P<0.001) occur in CFSs. However, the distribution of HPV18 integrations found were profoundly different from those found for HPV16. Specifically, 30% of all HPV18 integrations occurred within the chromosomal band 8q24 near the c-myc proto-oncogene. None of the HPV16 integrations occurred in this region. Previous low-resolution mapping suggested that c-myc may be a target of HPV integration. Our data at nucleotide resolution confirm that in HPV18-positive cervical tumors, the region surrounding c-myc is indeed a hot spot of viral integration. These results demonstrate that CFSs are preferred sites of integration for HPV18 in cervical tumors. In addition, we have identified multiple cellular genes that have been disrupted by HPV18 integration in cervical tumors. Our results suggest that the sites of HPV18 integration are nonrandom and may play an important role in the development of cervical tumors.

Chromosome Mapping↗
PubMed2026

scATAnno: Automated Cell Type Annotation for Single-cell ATAC-seq Data.

Recent advances in single-cell epigenomic techniques have increased the demand for single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq) analysis. One key analytical task is to determine cell type identity based on epigenetic data. Here, we introduce scATAnno, a Python package designed to automatically annotate scATAC-seq data using large-scale scATAC-seq reference atlases. This workflow generates reference atlases from publicly available datasets, enabling accurate cell type annotation by integrating query data with reference atlases without the use of single-cell RNA sequencing (scRNA-seq) data. To enhance annotation accuracy, we incorporated k-nearest neighbors (KNN)-based and weighted distance-based uncertainty scores to effectively detect cell populations within the query data that are distinct from all cell types in the reference data. We compared and benchmarked scATAnno against five other published cell annotation approaches, demonstrating its superior performance across multiple datasets and metrics. We further showcased the utility of scATAnno across multiple datasets, including peripheral blood mononuclear cells (PBMCs), triple-negative breast cancer (TNBC), and basal cell carcinoma (BCC), and demonstrated that scATAnno accurately annotates cell types across diverse biological conditions. Overall, scATAnno is a useful tool for scATAC-seq reference atlas construction and cell type annotation and can facilitate the interpretation of new scATAC-seq datasets in complex biological systems. scATAnno is publicly available at https://scatanno-main.readthedocs.io/.

Single-Cell Analysis↗
PubMed1995

Dynamic neuroimaging of brain function.

To fully characterize the brain processes underlying sensorimotor and cognitive function, the spatial distribution of active regions, their interconnected regions must be measured. We describe methods for imaging brain sources from surface-recorded EEG and magnetoencephalographic data, called electromagnetic source imaging (EMSI). EMSI provides brain source locations within the common framework of magnetic resonance (MR) images of brain anatomy. This allows integration of data from other functional brain imaging methods, like positron emission tomography and functional MR imaging, which can improve the accuracy of EMSI localization. EMSI also provides submillisecond temporal resolution of the dynamic processes within brain systems. Examples are given of applications to visual perceptual and attentional studies.

Arousal↗
PubMed2003

New three-dimensional echocardiographic system using digital radiofrequency data--visualization and quantitative analysis of aortic valve dynamics with high resolution: methods, feasibility, and initial clinical experience.

BACKGROUND: Common 3D systems have only limited spatial and temporal resolution (frame rate of 25 Hz). Thin structures such as cardiac valves are not imaged exactly; rapid movement patterns cannot be precisely recorded. The objective of the present project was to achieve radiofrequency (RF) data transmission to the 3D workstation to improve image resolution. METHODS AND RESULTS: A commercially available echocardiographic system (5-MHz transesophageal echocardiography probe) with an integrated raw data interface enables transmission of RF data (up to 40 megabytes per second). A 3D data set may contain up to 3 gigabytes, so that all of the high-resolution ultrasound information of the 2D image is available. Frame rates of up to 168 Hz result in temporal resolution 6 times that of standard 3D systems. The applicability of the system and the image quality were tested in 10 patients. The structure of the aortic valve and the dynamic changes were depicted by volume rendering. The changes in the orifice areas were measured in frame-by-frame planimetry. The mean number of frames recorded per cardiac cycle was 122+/-16. The improved structural resolution enabled a detailed imaging of the morphology of the aortic cusps. The rapid systolic movement patterns were recorded with up to 51 frames. The high number of frames enabled creation of precise area-time diagrams. Thus, the individual phases of aortic valve movement (rapid opening, slow valve closing, and rapid valve closing) could be analyzed quantitatively. CONCLUSIONS: A 3D system based on RF data enables high-resolution imaging of cardiac movement patterns. This offers new perspectives for qualitative and quantitative analyses, especially of cardiac valves.

Aortic Valve↗
PubMed2000

[Security services: an overview of the French legislation on cryptography].

This paper deals with the main security services of data protection: integrity, authentication, nonrepudiation and confidentiality. It describes the different tools which may be used to achieve these security objectives: encryption, digital signature, access controls, integrity control, audit and certification. The French legislation concerning encryption has been recently updated in order to simplify the use of encryption techniques for personal data security. This legislation describes different authorization or reporting procedures according to the type of the request (application, equipment, import or export of encryption techniques) and the security level required.

Algorithms↗
PubMed2004

In silico prediction of ADME properties: are we making progress?

The use of computational models in the prediction of ADME properties of compounds is growing rapidly in drug discovery as the benefits they provide in throughput and early application in drug design are realized. In addition, there is an increasing range of models available, as model builders have advanced from the first-generation' models, which were predominantly focused on solubility, absorption and metabolism, to include models of other optimization factors such as HERG, glucuronyl transferase and drug transport proteins. This widening interest is now driving demand for developments in the component elements of model building, namely higher quality datasets, better molecular descriptors and more computational power, and the quality of models is improving rapidly as a consequence. Models generally have very high throughput and can be used with virtual structures. As a consequence, they can generate large quantities of data on large numbers of compounds. Thus, one consequence of the wider choice of models, coupled with their high throughput, is a growing need to integrate their output into collective analyses of molecules against pre-set criteria. This article comments on some of the recent developments in ADME models, and highlights the importance of integrating the data to aid compound selection in drug discovery projects.

Chemical Phenomena↗
PubMed2002

The medical communications officer. A resource for data collection, quality management and medical control.

Pinellas County EMS' Medical Communications Officers provide a wide variety of services to patients, field clinicians, managers and their medical director. The concurrent data collection processes used in the MCO program for performance measurement of resuscitation efforts, intubations, submersion incidents and aeromedical transports for trauma cases have been very effective in the integration of data from multiple computer databases and telephone follow-ups with field crews and receiving emergency department staffs. This has facilitated significant improvements in the performance of these and many other aspects of our EMS system.

Administrative Personnel↗
PubMed1992

Keyless data capture: a report of the Automatic Identification Teacher's Institute.

There is tremendous potential in auto ID technologies for increasing productivity and accuracy in the management of health information. We must make a commitment to integrate keyless data capture technologies into medical record administration and medical record technology curricula. Our profession will seize the opportunity if we can educate students and practitioners in the knowledge and skills to unleash this potential. A recent study of medical record administration, and medical record technology, programs by Elaine Patrikas revealed that, at best, some programs devote a maximum of 10 hours of instructional time to the teaching of keyless data capture technologies. HIM professionals can aggressively pursue applications that demonstrate tremendous cost savings, so that upper management will seriously consider them. Improvements in the flow of, and access to, information do directly impact patient care thus helping our profession fulfill its mission and preparing tomorrow's leaders and decision makers.

Curriculum↗
PubMed2003

Display of fused images: methods, interpretation, and diagnostic improvements.

The use of integrated visualization for medical images aims at assisting clinicians in the difficult task of mentally translating and integrating medical image data from multiple sources into a three-dimensional (3D) representation of the patient. This interpretation of the enormous amount and complexity of contemporary, multiparameter, and multimodal image data demands efficient methods for integrated presentation. This article reviews methods for fused display with the main focus on integration of functional with anatomical images. First, an overview of integrated two-dimensional (2D) and 3D medical image display techniques is presented, and topics related to the interpretation of the integrated images are discussed. Then we address the key issue for clinical acceptance, ie, whether these novel visualization techniques lead to diagnostic improvements. Methods for fused display appear to be powerful tools to assist the clinician in the retrieval of relevant information from multivariate medical image data. Evaluation of the different methods for fused display indicates that the diagnostic process improves, notably as concerns the anatomical localization (typically of functional processes), the registration procedure, enhancement of signal, and efficiency of information presentation (which increases speed of interpretation and comprehension). Consequently, fused display improves communication with referring specialists, increases confidence in the observations, and facilitates the intra- and intersubject comparison of a large part of the data from the different sources, thereby simplifying the extraction of additional, valuable information. In most diagnostic tasks the clinician is served best by providing several (interactive and flexible) 2D and 3D methods for fused display for a thorough assessment of the wealth of image information from multiple sources.

Anatomy, Cross-Sectional↗
PubMed1997

FlyBase: a Drosophila database. The FlyBase consortium.

FlyBase is a database of genetic and molecular data concerning Drosophila. FlyBase is maintained as a relational database (in Sybase) and is made available as html documents and flat files. The scope of FlyBase includes: genes, alleles (and phenotypes), aberrations, transposons, pointers to sequence data, clones, stock lists, Drosophila workers and bibliographic references. The Encyclopedia of Drosophila is a joint effort between FlyBase and the Berkeley Drosophila Genome Project which integrates FlyBase data with those from the BDGP.

Animals↗
PubMed2026

Genomic hallmarks of depot medroxyprogesterone acetate-associated meningiomas.

BACKGROUND: Population-based studies have linked progestin exposure to increased meningioma risk. However, the molecular basis of meningiomas associated with depot medroxyprogesterone acetate (DMPA)-a common injectable contraceptive-remains undefined. METHODS: We performed an integrated clinicopathologic and genomic analysis of meningiomas from 10 women with long-term DMPA exposure. Tumors underwent histopathological analysis, targeted sequencing, and DNA methylation profiling. Data were integrated with reference cohorts (Baylor and Heidelberg) and analyzed through classifier assignment, consensus clustering, copy number analysis, differential methylation testing, and dimensionality reduction. RESULTS: Depot medroxyprogesterone acetate-associated meningiomas were all newly diagnosed, World Health Organization grade 1 tumors with a predilection for the anterior and central skull base (n&#x2009;=&#x2009;6). Nine patients harbored multiple meningiomas. Four experienced regression of untreated meningiomas following DMPA cessation, while 5 demonstrated stabilization. Histopathology demonstrated relative overrepresentation of metaplastic morphology, an uncommon meningioma subtype. All DMPA-associated meningiomas mapped to benign molecular groups, and most exhibited low copy number alteration burden. Targeted sequencing revealed enrichment for TRAF7 mutations (n&#x2009;=&#x2009;5), with no NF2 mutations detected. Eight tumors shared consensus cluster identity, with cohesive grouping on principal component analysis and t-distributed stochastic neighbor embedding. No differential methylation was identified at the progesterone receptor locus. CONCLUSIONS: Depot medroxyprogesterone acetate-associated meningiomas represent a recognizable phenotype within the broader NF2-wildtype/TRAF7-enriched spectrum of benign meningiomas, characterized by chromosomal stability, a shared methylation profile, tumor multiplicity, and regression or stabilization following DMPA cessation. While derived from a small single-institution cohort, these findings provide a molecular framework for understanding progestin-associated meningioma biology, reinterpreting epidemiologic literature, and informing population-level risk stratification.

Humans↗
PubMed2005

Global Pseudomonas aeruginosa biodiversity as reflected in a Belgian river.

The biodiversity of the bacterium Pseudomonas aeruginosa in an aquatic environment (the Woluwe River, Brussels, Belgium) was analysed. Surface water was sampled bimonthly over a 1-year period (2000-2001) at seven sites evenly dispersed over the river. Total bacterial counts were performed and P. aeruginosa strains were isolated on a selective medium. A weighed out sample of 100 randomly chosen presumptive P. aeruginosa isolates was further analysed. A set of data consisting of the nucleotide sequence of the oprL gene, a DNA-based fingerprint (amplified fragment length polymorphism, AFLP), serotype, pyoverdine type and antibiogram (MICs of 21 clinically relevant antibiotics) was assembled. These data were integrated with those previously obtained for 73 P. aeruginosa clinical and environmental isolates collected across the world. The combined results were analysed and compared using biological data analysis software. Our findings indicate a positive relationship between the extent of pollution and the prevalence of P. aeruginosa. Surprisingly, the Woluwe River P. aeruginosa community was almost as diverse as the global P. aeruginosa population. Indeed, the Woluwe River harboured members of nearly all successful clonal complexes. With the exception of one multidrug-resistant (MDR) strain, belonging to a ubiquitous and clinically relevant serotype O11 clone, antibiotic resistance levels were relatively low. These findings illustrate the significance of river water as a reservoir and source of distribution of potentially pathogenic P. aeruginosa strains and could have repercussions on antinosocomial infection strategies.

Anti-Bacterial Agents↗
PubMed1983

Auditing clinical research data: objectives, applications and results.

Formal auditing of clinical research data has become a standard contemporary practice within the pharmaceutical industry. Its basic purpose is to provide documentation relevant to an assessment of the quality and integrity of data collected in the course of a clinical trial. This paper outlines the audit procedures developed within one major pharmaceutical firm. These procedures require an intensive investigation of internal and external aspects of study management, records management, data entry, data analysis and statistical report preparation. A qualitative evaluation of the results achieved by this auditing procedure are presented.

Clinical Trials as Topic↗
PubMed2002

Prediction of pharmacokinetics prior to in vivo studies. II. Generic physiologically based pharmacokinetic models of drug disposition.

Many in vitro data on physicochemical properties and specific absorption, distribution, metabolism, and elimination (ADME) processes are already available at early stages of drug discovery. These data about new drug candidates could be integrated/connected in physiologically based pharmacokinetic (PBPK) models to estimate a priori the overall plasma and tissue kinetic behaviors under in vivo conditions. The objective of the present study was to illustrate that generic PBPK models integrating such data can be developed in drug discovery prior to any in vivo studies. This approach was illustrated with three example compounds, including two lipophilic bases (diazepam, propranolol) and one neutral more hydrophilic drug (ethoxybenzamide). Distribution and liver metabolism were the processes integrated in the generic rat PBPK models of disposition. Tissue:plasma partition coefficients (P(t:p)s) used for description of distribution were estimated from established tissue composition-based equations, which need only in vitro data on drug lipophilicity and plasma protein binding as sole input parameters. Furthermore, data on intrinsic clearance (CL(int)) determined in vitro with hepatocytes were scaled to the in vivo situation to estimate hepatic metabolic clearance. These prediction approaches were both incorporated in the PBPK models to enable automated estimation of distribution and liver metabolism for each drug studied. The generic PBPK models suggested can simulate a priori concentration-time profiles of plasma and several tissues after intravenous administrations to rat. The results indicate that most of the simulated concentration-time profiles of plasma and 10 tissues are in reasonable agreement with the corresponding experimental data determined in vivo (less than a factor of two). However, some more relevant deviations were observed for specific tissues (brain and gut for diazepam; liver and gut for ethoxybenzamide; lung for propranolol) because of important ADME processes were probably neglected in the PBPK models of these drugs. In this context, generic PBPK models were also used for mechanistic evaluations of pharmacokinetics for generating research hypotheses to understand these deviations. Overall, the present generic and integrative PBPK approach of drug disposition suggested as a tool for a priori simulations and mechanistic evaluations of pharmacokinetics has the potential to improve the selection and optimization of new drug candidates.

Animals↗
PubMed1999

Integration and visualization of multimodality brain data for language mapping.

A goal of the University of Washington Brain Project is to develop software tools for processing, integrating and visualizing multimodality language data obtained at the time of neurosurgery, both for surgical planning and for the study of language organization in the brain. Data from a single patient consist of four magnetic resonance-based image volumes, showing anatomy, veins, arteries and functional activation (fMRI). The data also include the location, on the exposed cortical surface, of sites that were electrically stimulated for the presence of language. These five sources are mapped to a common MR-based neuroanatomical model, then visualized to gain a qualitative appreciation of their relationships, prior to quantitative analysis. These procedures are described and illustrated, with emphasis on the visualization of fMRI activation, which may be deep in the brain, with respect to surface-based stimulation sites.

Anatomy, Cross-Sectional↗
PubMed1997

Integrating women's healthcare--serving the whole woman.

Health systems across the country are setting up centers to serve all the health needs of women. The driver for comprehensive care programs, they say, is expert intuition, not hard data, that integrated care will result in better outcomes than traditional fragmented care has produced. They point to women's preferences for "one-stop shopping" and government initiatives that encourage integration. And they offer six keys to successfully launching a comprehensive care program--insights gained in developing their programs.

Comprehensive Health Care↗
PubMed2001

Migration of the Japanese healthcare enterprise from a financial to integrated management: strategy and architecture.

The Hospital Information System (HIS) has been positioned as the hub of the healthcare information management architecture. In Japan, the billing system assigns an "insurance disease names" to performed exams based on the diagnosis type. Departmental systems provide localized, departmental services, such as order receipt and diagnostic reporting, but do not provide patient demographic information. The system above has many problems. The departmental system's terminals and the HIS's terminals are not integrated. Duplicate data entry introduces errors and increases workloads. Order and exam data managed by the HIS can be sent to the billing system, but departmental data cannot usually be entered. Additionally, billing systems usually keep departmental data for only a short time before it is deleted. The billing system provides payment based on what is entered. The billing system is oriented towards diagnoses. Most importantly, the system is geared towards generating billing reports rather than at providing high-quality patient care. The role of the application server is that of a mediator between system components. Data and events generated by system components are sent to the application server that routes them to appropriate destinations. It also records all system events, including state changes to clinical data, access of clinical data and so on. Finally, the Resource Management System identifies all system resources available to the enterprise. The departmental systems are responsible for managing data and clinical processes at a departmental level. The client interacts with the system via the application server, which provides a general set of system-level functions. The system is implemented using current technologies CORBA and HTTP. System data is collected by the application server and assembled into XML documents for delivery to clients. Clients can access these URLs using standard HTTP clients, since each department provides an HTTP compliant web-server. We have implemented an integrated system communicating via CORBA middleware, consisting of an application server, endoscopy departmental server, pathology departmental server and wrappered legacy HIS. We have found this new approach solves the problems outlined earlier. It provides the services needed to ensure that data is never lost and is always available, that events that occur in the hospital are always captured, and that resources are managed and tracked effectively. Finally, it reduces costs, raises efficiency, increases the quality of patient care, and ultimately saves lives. Now, we are going to integrate all remaining hospital departments, and ultimately, all hospital functions.

Computer Systems↗