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PubMed2026

Reference-Free Microsatellite Instability Detection from Tumor Sequencing Using Intrasample Variability Modeling.

Microsatellite instability (MSI) is a predictive biomarker in several tumor types. However, many next-generation sequencing-based callers require matched normal samples, reference panels, or pretrained models, limiting their portability across assays and sequencing centers. We developed PROMIS (PROfiling of Microsatellite InStability), a tumor-only, reference-free pipeline that uses a discrete mixture model to characterize intrasample repeat-length distributions at predefined microsatellite loci. Locus-level classifications are then aggregated into a continuous MSI score. We benchmarked PROMIS in colorectal (CRC), endometrial (UCEC), and gastric (STAD) cancers from The Cancer Genome Atlas. PROMIS achieved an overall area under the receiver operating characteristic curve (AUC) of 0.995 and cohort-specific AUCs of 1.00 in CRC and stomach adenocarcinoma and 0.999 in uterine corpus endometrial carcinoma, comparable to established tools despite not using matched normals or pretrained models. Subsampling demonstrated robust performance with substantially fewer loci. In silico dilution showed progressively reduced MSI-microsatellite-stable discrimination, with the pooled AUC declining from 0.83 at 10% tumor fraction to 0.53 at 1%. At low tumor fractions, tumor-type-specific baseline microsatellite variability increasingly influenced PROMIS scores. Finally, in prostate and CRC cell-free DNA cohorts, including Illumina TSO500 data and an 18-gene panel, PROMIS yielded MSI scores concordant with orthogonal tissue- and panel-based classifications across the evaluated Illumina-based sequencing contexts. Accordingly, the present validation should be considered limited to Illumina-based sequencing platforms. PROMIS is intended to complement existing genomic profiling workflows by enabling MSI assessment from sequencing data already generated for broader molecular analyses. Prospective clinical validation remains necessary before clinical implementation.

Journal Article↗
PubMed2002

Development of an internet-based rainfall atlas for Alabama.

In the United States, rainfall information needed for intensity-duration-frequency (IDF) curves or design storm hyetographs can be found in TP 40, HYDRO-35, and the NOAA Atlas 2. Additional rainfall data collected since the dates of those publications, and improved methods for statistical treatment of data, have motivated update studies in several regions of the United States. One of the new studies has been performed for the State of Alabama. Results of the Alabama study are embodied in an internet-based graphical user interface, which permits users to interactively point and click on a geographical location of interest, and have IDF curves and/or storm hyetographs returned on demand. Reactions to the internet-based rainfall atlas have been promising, and have led to additional work for the National Weather Service, Office of Hydrologic Development.

Alabama↗
PubMedDate not supplied

Anatomic and computed tomographic atlas of the head of the newborn bottlenose dolphin (Tursiops truncatus).

The head of a newborn dolphin (Tursiops truncatus), that died shortly after birth was imaged using computed tomography (CT). Gross cross-sectional slices of the head were compared with the CT images to identify normal structures of the cranium, brain, and respiratory and digestive pathways. Labelled transverse CT images of the dolphin head are presented sequentially as a reference for normal anatomy.

Animals↗
PubMed1993

[The crystal structure atlas data base system for chemical constituents of Chinese traditional and folk medicine].

The atlas data base system for chemical constituents of Chinese traditional and folk medicine is the first one for single crystal structure in China. It includes about 250 crystal structures of chemical ingredients of Chinese traditional and folk medicine. It has searching, plotting and computing functions. It is a useful reference base. All softwares are written in dbaseIII, FORTRAN and Assembler Languages. They can be run on PC-286,386,486 and their compatible microcomputers.

Crystallography↗
PubMed1996

Radiographic assessment of knee osteoarthritis: reproducibility and sensitivity to change.

OBJECTIVE: To determine the cross sectional and longitudinal reproducibility of various measures used for assessing radiographic knee osteoarthritis (OA) and to compare the sensitivity to change over a one year period of these measures. METHODS: We studied 55 patients referred to hospital with knee OA (clinical and radiographic ACR criteria). Anteroposterior radiographs at baseline and after 12 months were read by methods both qualitative (Kellgren and Lawrence grading scale, joint space narrowing scale) and quantitative (joint space width measurement at 3 different points). All qualitative methods used standardized atlases. The intraclass correlation coefficient and the graphical method of Bland and Altman were used to assess cross sectional and longitudinal reproducibility. Reproducibility was tested using 2 readers (interreader) and 2 readings for one of the readers (intrareader). Sensitivity to change was assessed using standardized response mean (SRM). RESULTS: All methods tested were shown to be reproducible both for cross sectional and longitudinal data. Intrareader was higher than interreader reproducibility for most radiographic features. Significant changes were observed after one year for methods measuring joint space narrowing. The sensitivity to change of the methods assessing joint space narrowing (joint space narrowing scale and joint space width measurement) was higher, with SRM varying from 0.37 to 0.57, than for the Kellgren and Lawrence grading system (SRM 0.19 and 0.23). CONCLUSION: These data suggest that methods measuring narrowing should be preferred as outcome measures in clinical trials or longitudinal epidemiologic studies; and show that in a particular subset of patients with very active disease, significant radiographic changes in knee OA can be detected after a one year period.

Aged↗
PubMed1999

Model creation and deformation for the automatic segmentation of the brain in MR images.

In this paper a method for the automatic segmentation of the brain in magnetic resonance images is presented and validated. The proposed method involves two steps 1) the creation of an initial model and 2) the deformation of this model to fit the exact contours of the brain in the images. A new method to create the initial model has been developed and compared to a more traditional approach in which initial models are created by means of brain atlases. A comprehensive validation of the complete segmentation method has been conducted on a series of three-dimensional T1-weighted magnetization-prepared rapid gradient echo image volumes acquired both from control volunteers and patients suffering from Cushing's disease. This validation study compares results obtained with the method we propose and contours drawn manually. Averages differences between manual and automatic segmentation with the model creation method we propose are 1.7% and 2.7% for the control volunteers and the Cushing's patients, respectively. These numbers are 1.8% and 5.6% when the atlas-based method is used.

Algorithms↗
PubMed1994

Leukaemia clusters in childhood: geographical analysis in Britain.

STUDY OBJECTIVE: To validate previously demonstrated spatial clustering of childhood leukaemias by showing relative proximities of selected map features to cluster locations, compared with control locations. If clusters are real, then they are likely to be close to a determining hazard. DESIGN: Cluster postcode loci and partially matched control postcodes were compared in terms of distances to railways, main roads, churches, surface water, woodland areas, and railside industrial installations. Further supporting comparisons between non-clustered cases and random postcode controls with those map features representable as single grid points were made. SETTING: England, Wales, and Scotland 1966-83. SUBJECTS: Grid referenced registrations of 9406 childhood leukaemias and non-Hodgkin's lymphomas, including 264 pairs (or more) separated by < 150 m, and grid references of random postcodes in equal numbers. MAIN RESULTS: The 264 clusters showed relative proximities (or the inverse) to several map features, of which the most powerful was an association with railways. The non-railway associations seemed to be statistically indirect. Some railside industrial installations, identified from a railway atlas, also showed relative proximities to leukaemia clusters, as well as to non-clustered cases, but did not "explain" the railway effect. These installations, with seemingly independent geographical associations, included oil refineries, petrochemical plants, oil storage and oil distribution depots, power stations, and steelworks. CONCLUSIONS: The previously shown childhood leukaemia clusters are confirmed to be non-random through their systematic associations with certain map features when compared with the control locations. The common patterns of close association of clustered and non-clustered cases imply a common aetiological component arising from a common environmental hazard--namely the use of fossil fuels, especially petroleum.

Adolescent↗
PubMed1993

An interactive, computer-based atlas of neurologic positron emission tomographic studies for use in teaching.

Recent developments in personal computer hardware and software allow the manipulation of radiologic images. We developed an interactive, computer-based atlas of clinical neurologic positron emission tomographic studies for use as an educational resource. A personal computer and multimedia software were used to assemble the clinical case studies. For each clinical case, the user had available the clinical history, positron emission tomographic and correlative anatomic images, study interpretation, discussion, and references. The clinical cases were selected for their educational value, either as a representative example of an abnormality or for their ability to illustrate a common pitfall in positron emission tomographic imaging of the brain.

Central Nervous System Diseases↗
PubMed1983

Prorenin in plasma and kidney.

Circulating prorenin is an enzymatically inactive form of renin, also present in kidney, which can be activated in vitro. Its biochemical properties and physiological behavior suggest that it may be a biosynthetic precursor of active renin. However, in contrast to typical prohormones, the normal plasma concentrations of prorenin are much higher than the active hormone. The purposes and functions of prorenin are unclear. It may have no further role after its secretion into the circulation. On the other hand, it may be a transport form of renin that can enter or exit cells more easily than the active form. It is also possible that the activity of the renin-angiotensin system may be regulated by the conversion of prorenin to renin in the kidney (which may be under beta-adrenergic control) or at other possible sites. Irreversible activation of prorenin appears to be a proteolytic process. In addition, acidification causes reversible activation, perhaps through a change in molecular conformation. Such reversible activation might occur in vivo by unknown mechanisms. Future studies are needed to define the biochemical processes by which increased physiological demand for renin is translated into the production of more active enzyme.

Adrenergic beta-Antagonists↗
PubMed1985

Mapping of different neuropeptides in the lower brainstem of the rat: with special reference to the ventral surface.

A neuropeptide map of beta-endorphin-, vasoactive intestinal peptide-, substance P-, and somatostatin-like reactive neurons and nerve fibers was made by means of immunohistochemistry. Indirect immunofluorescence was carried out in parallel to peroxidase-antiperoxidase reaction using a modified fixation technique. Special interest was directed to the superficial ventral regions of the medulla oblongata where regulative centers for respiration and circulation have been localized. The atlas presented offers a reliable tool for a precise neuromorphological localization of these neuropeptides in pharmacophysiological experiments.

Animals↗
PubMed2002

Visualization of conserved structures by fusing highly variable datasets.

INTRODUCTION: Skill, effort, and time are required to identify and visualize anatomic structures in three-dimensions from radiological data. Fundamentally, automating these processes requires a technique that uses symbolic information not in the dynamic range of the voxel data. We were developing such a technique based on mutual information for automatic multi-modality image fusion (MIAMI Fuse, University of Michigan). This system previously demonstrated facility at fusing one voxel dataset with integrated symbolic structure information to a CT dataset (different scale and resolution) from the same person. The next step of development of our technique was aimed at accommodating the variability of anatomy from patient to patient by using warping to fuse our standard dataset to arbitrary patient CT datasets. METHODS: A standard symbolic information dataset was created from the full color Visible Human Female by segmenting the liver parenchyma, portal veins, and hepatic veins and overwriting each set of voxels with a fixed color. Two arbitrarily selected patient CT scans of the abdomen were used for reference datasets. We used the warping functions in MIAMI Fuse to align the standard structure data to each patient scan. The key to successful fusion was the focused use of multiple warping control points that place themselves around the structure of interest automatically. The user assigns only a few initial control points to align the scans. Fusion 1 and 2 transformed the atlas with 27 points around the liver to CT1 and CT2 respectively. Fusion 3 transformed the atlas with 45 control points around the liver to CT1 and Fusion 4 transformed the atlas with 5 control points around the portal vein. The CT dataset is augmented with the transformed standard structure dataset, such that the warped structure masks are visualized in combination with the original patient dataset. This combined volume visualization is then rendered interactively in stereo on the ImmersaDesk in an immersive Virtual Reality (VR) environment. RESULTS: The accuracy of the fusions was determined qualitatively by comparing the transformed atlas overlaid on the appropriate CT. It was examined for where the transformed structure atlas was incorrectly overlaid (false positive) and where it was incorrectly not overlaid (false negative). According to this method, fusions 1 and 2 were correct roughly 50-75% of the time, while fusions 3 and 4 were correct roughly 75-100%. The CT dataset augmented with transformed dataset was viewed arbitrarily in user-centered perspective stereo taking advantage of features such as scaling, windowing and volumetric region of interest selection. CONCLUSIONS: This process of auto-coloring conserved structures in variable datasets is a step toward the goal of a broader, standardized automatic structure visualization method for radiological data. If successful it would permit identification, visualization or deletion of structures in radiological data by semi-automatically applying canonical structure information to the radiological data (not just processing and visualization of the data's intrinsic dynamic range). More sophisticated selection of control points and patterns of warping may allow for more accurate transforms, and thus advances in visualization, simulation, education, diagnostics, and treatment planning.

Algorithms↗
PubMed2000

Four different genes responsible for nonimmune immunoglobulin-binding activities within a single strain of Escherichia coli.

Certain Escherichia coli strains bind the Fc fragment of immunoglobulin G (IgG) at the bacterial cell surface. Previous work established that this nonimmune Ig binding depends on several large proteins with apparent molecular masses that can exceed 200 kDa. For E. coli strain ECOR-9, four distinct genes (designated eibA, eibC, eibD, and eibE) are responsible for Ig binding. Two eib genes are linked to eaa genes, which are homologous to genes for the autotransporter family of secreted proteins. With reference to the E. coli K-12 chromosome, the eibA-eaaA cluster is adjacent to trpA (min 28.3) while the eibC-eaaC cluster is adjacent to aspS (min 42. 0). Sequence adjacent to the eibA-eaaA cluster converges with that of strain K-12 precisely as observed for the Atlas family of prophages, suggesting that eibA is part of one of these. All four eib genes, when cloned into plasmid vectors, impart IgG binding to E. coli K-12 strains, and three impart IgA binding also. The IgG binding occurs at the bacterial cell surface, and its expression increases survival in serum by up to 3 orders of magnitude. The eib sequences predict a C-terminal peptide motif that is characteristic of outer membrane proteins, and the protein sequences show significant similarity near the C terminus to both the YadA virulence factor of Yersinia species and the universal surface protein A II of Moraxella catarrhalis. The sizes predicted for Eib proteins from DNA sequence are much smaller than their apparent sizes on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, possibly reflecting stable oligomerization.

Amino Acid Sequence↗
PubMed1997

A three-dimensional multimodality brain map of the nemestrina monkey.

A three-dimensional multimodality computerized map of the nemestrina monkey brain was created with serial sectioning and digital imaging techniques. An adult female Macaca nemestrina (pigtail macaque) weighing 7.2 kg was used in constructing this atlas. CT, PET, and MRI were performed on the monkey before the specimen's head was frozen and cryoplaned. Closely spaced (50 microns) images of the specimen blockface were then digitally acquired and modified to produce whole head and brain-only 3D image sets. The resulting data sets were organized into a digital volume and repositioned into a stereotaxic coordinate system defined by Horsley and Clark in 1908 [7]. Orthogonal images were obtained by digitally resampling the volume in order to produce a full set of coronal, sagittal, and horizontal images. Stereotaxic reference grids were applied to each image indicating the A/P, M/L, or Ho position within the digital volume. Specific anatomic structures were outlined from the cryosection data set and 3D surface models reconstructed. Structural labels indicating nuclei, tracts, and other neuroanatomical features were incorporated into coronally sliced cryosection images spaced at 500 microns. The CT, PET, and MRI data sets were reconstructed into a digital volume and coregistered to the cryosection volume. All images constructed from this 3D map are available for public access via the internet using an anonymous file transfer protocol (FTP) and the World Wide Web (http:@www.loni.ucla.edu). The foremost advantage of this digital map is an integrated multimodality three-dimensional representation of the Macaca nemestrina brain, which is not possible with traditional atlases.

Animals↗
PubMed2006

Acute psychotic symptoms in HIV-1 infected patients are associated with increased levels of kynurenic acid in cerebrospinal fluid.

Human immunodeficiency virus type 1 (HIV-1) infection is associated with psychiatric complications including cognitive impairment, affective disorders, and psychosis. Previous studies have revealed a disturbed kynurenine metabolism in these patients leading to increased levels of neuroactive compounds acting at glutamatergic neurotransmission. Kynurenic acid (KYNA), one of these metabolites is a glutamate-receptor antagonist, preferentially blocking the glycine site of the N-methyl-d-aspartate (NMDA) receptor. Increased levels of brain KYNA have been suggested to induce a NMDA receptor hypofunction that is associated with psychotic symptoms. In the present study, we analyze the concentration of KYNA in the cerebrospinal fluid (CSF) from HIV-1 infected patients (n=22), including HIV-1 infected patients with psychotic symptoms (n=8) and HIV-1 infected patients without psychiatric symptoms (n=14). We found that HIV-1 infected patients had significantly higher median concentration of CSF KYNA (3.02nM) compared to healthy controls (1.17nM). Furthermore, CSF KYNA levels were significantly elevated in HIV-1 infected patients with psychotic symptoms (4.54nM) compared to patients with HIV-1 without psychiatric symptoms (2.28nM). Present results indicate that increased levels of CSF KYNA may be associated with development of psychotic symptoms in HIV-1 infected patients.

Adult↗
PubMed2006

A spatially unbiased atlas template of the human cerebellum.

This article presents a new high-resolution atlas template of the human, cerebellum and brainstem, based on the anatomy of 20 young healthy individuals. The atlas is spatially unbiased, i.e., the location of each structure is equal to the expected location of that structure across individuals in MNI space, a result that is cross-validated with an independent sample of 16 individuals. At the same time, the new template preserves the anatomical detail of cerebellar structures through a nonlinear atlas generation algorithm. In comparison to current whole-brain templates, it allows for an improved voxel-by-voxel normalization for functional MRI and lesion analysis. Alignment to the template requires that the cerebellum and brainstem are isolated from the surrounding tissue, a process for which an automated algorithm has been developed. Compared to normalization to the MNI whole-brain template, the new method strongly improves the alignment of individual fissures, reducing their spatial spread by 60%, and improves the overlap of the deep cerebellar nuclei. Applied to functional MRI data, the new normalization technique leads to a 5-15% increase in peak t values and in the activated volume in the cerebellar cortex for movement vs. rest contrasts. This indicates that the new template significantly improves the overlap of functionally equivalent cerebellar regions across individuals. The template and software are freely available as an SPM-toolbox, which also allows users to relate the new template to the annotated volumetric (Schmahmann, J.D., Doyon, J., Toga, A., Petrides, M., Evans, A. (2000). MRI atlas of the human cerebellum. San Diego: Academic Press) and surface-based (Van Essen, D.C. (2002a) Surface-based atlases of cerebellar cortex in the human, macaque, and mouse. Ann. N. Y. Acad. Sci. 978:468-479.) atlas of one individual, the "colin27"-brain.

Adult↗
PubMed1996

Assessing progression of patellofemoral osteoarthritis: a comparison between two radiographic methods.

OBJECTIVE: To compare two plain radiographic methods for sensitivity to detect progression of patellofemoral osteoarthritis. METHODS: Two sets of paired skyline and lateral knee radiographs from 54 hospital referred patients (108 knees) with knee osteoarthritis were taken an average of 31 months apart (range 12-40). Films were examined separately in random order by a single observer blind to patient identity and time order. Minimum joint space was measured by metered caliper; individual features of osteoarthritis were graded 0-3 using an atlas. RESULTS: Intraobserver reproducibility assessed on 40 knees was to within +/- 0.5 mm for skyline lateral facet and +/- 0.7 mm for medial facet and lateral views. On the lateral view measured joint space decreased in 51% of knees but increased in 43%, with overall no significant mean group change with time (-0.2 mm, 95% confidence interval, 0.1 to -0.5). By contrast on the skyline view joint space decreased in at least one facet in 71% of knees, with significant decrease in mean joint space for both lateral facets (-0.4 mm, 95% CI, -0.2 to -0.6) and medial facets (-0.5 mm, 95% CI, -0.1 to -0.8). CONCLUSIONS: It is possible to detect significant joint space loss with time on the skyline view that is not apparent on the lateral view. The skyline view should be the method of choice to detect progression of patellofemoral osteoarthritis.

Adult↗
PubMed2026

MRI-based radiomics model for predicting VEGFA expression and prognosis in lower-grade glioma.

BACKGROUND: Gliomas are the most common primary tumors of the central nervous system. Their treatment remains highly challenging, with high rates of associated disability and mortality. Conventional prognostic indicators no longer adequately satisfy the clinical demands of precision medicine. Therefore, it is essential to further explore novel prognostic biomarkers to enable accurate risk stratification and to provide new reference indicators for personalized precision therapy. PURPOSES: This study aimed to investigate the prognostic significance of vascular endothelial growth factor A (VEGFA) in patients diag nosed with lower-grade gliomas (LGGs) using an MRI based radiomics model. METHODS: Data regarding VEGFA expression and clinical records of LGG patients were retrieved from The Cancer Genome Atlas (TCGA). Corresponding preoperative MRI data were obtained from The Cancer Imaging Archive (TCIA) for radiomic feature extraction. Patients were stratified into high- and low- VEGFA expression groups based on survival information from the current cohort using the survminer package. The overall survival (OS) was assessed using Kaplan-Meier analysis and Cox proportional hazards regression. Predictive models were developed using logistic regression (LR), and model performance was evaluated via receiver operating characteristic (ROC) curve analysis, with area under the curve (AUC) values reported. An optimized model incorporating the Akaike information criterion (AIC) was also constructed (AIC-LR). RESULTS: VEGFA expression was significantly associated with OS (P&#xa0;=&#xa0;0.002). Multivariate Cox regression confirmed VEGFA as an independent prognostic factor (hazard ratio [HR]&#xa0;=&#xa0;2.545, 95% confidence interval: 1.422-4.555). Furthermore, VEGFA expression correlated with immune infiltration levels, particularly of M1 and M2 macrophages and T follicular helper cells, and was associated with enrichment in Wnt signaling and B cell receptor signaling pathways. The LR and AIC-LR models demonstrated acceptable predictive performance, with AUCs of 0.728 (95% CI: 0.612-0.843) and 0.725(95% CI: 0.612-0.839) in the training cohort, and 0.704 (95% CI: 0.562-0.847) and 0.718(95% CI: 0.576-0.861) in the validation cohort, respectively. CONCLUSIONS: The MRI based radiomics model showed potential for noninvasive assessment of VEGFA expression and may provide auxiliary information for prognostic evaluation in LGG. Further validation in larger samples and independent external cohorts is required before clinical application.

Radiomics↗