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A semantic-based kernel for advanced health information systems.

This paper reports on the design and development of an infrastructure allowing one to share and exchange multimedia data in the context of a health network. A single technology exploiting a semantic model of the hospital universe provides users with information and data of diverse origins, generated by the various actors or departments of the health organization. Functions provided include act management and patient record management governed by domain semantics. The functionality has been validated through laboratory experiments against the requirements of protocol directed care and health networks. The functionality is integrated into a clinician workstation exploited in the Internet/Intranet environment thanks to a commercial browser. These results have been obtained with the support of several projects in the frame of the Health-Care Telematics Applications Programme of the European Community and of the Eurêka Programme.

Artificial Intelligence↗

Comparison of helical and cine acquisitions for 4D-CT imaging with multislice CT.

We proposed a data sufficiency condition (DSC) for four-dimensional-CT (4D-CT) imaging on a multislice CT scanner, designed a pitch factor for a helical 4D-CT, and compared the acquisition time, slice sensitivity profile (SSP), effective dose, ability to cope with an irregular breathing cycle, and gating technique (retrospective or prospective) of the helical 4D-CT and the cine 4D-CT on the General Electric (GE) LightSpeed RT (4-slice), Plus (4-slice), Ultra (8-slice) and 16 (16-slice) multislice CT scanners. To satisfy the DSC, a helical or cine 4D-CT acquisition has to collect data at each location for the duration of a breathing cycle plus the duration of data acquisition for an image reconstruction. The conditions for the comparison were 20 cm coverage in the cranial-caudal direction, a 4 s breathing cycle, and half-scan reconstruction. We found that the helical 4D-CT has the advantage of a shorter scan time that is 10% shorter than that of the cine 4D-CT, and the disadvantages of 1.8 times broadening of SSP and requires an additional breathing cycle of scanning to ensure an adequate sampling at the start and end locations. The cine 4D-CT has the advantages of maintaining the same SSP as slice collimation (e.g., 8 x 2.5 mm slice collimation generates 2.5 mm SSP in the cine 4D-CT as opposed to 4.5 mm in the helical 4D-CT) and a lower dose by 4% on the 8- and 16-slice systems, and 8% on the 4-slice system. The advantage of faster scanning in the helical 4D-CT will diminish if a repeat scan at the location of a breathing irregularity becomes necessary. The cine 4D-CT performs better than the helical 4D-CT in the repeat scan because it can scan faster and is more dose efficient.

Artifacts↗

Three-dimensional object detection under arbitrary lighting conditions.

A novel method of 3D object recognition independent of lighting conditions is presented. The recognition model is based on a vector space representation using an orthonormal basis generated by the Lambertian reflectance functions obtained with distant light sources. Changing the lighting conditions corresponds to multiplying the elementary images by a constant factor and because of that, all possible lighting views will be elements that belong to that vector space. The recognition method proposed is based on the calculation of the angle between the vector associated with a certain illuminated 3D object and that subspace. We define the angle in terms of linear correlations to get shift and illumination-invariant detection.

Algorithms↗

Classifying vertical facial deformity using supervised and unsupervised learning.

OBJECTIVES: To evaluate the potential for machine learning techniques to identify objective criteria for classifying vertical facial deformity. METHODS: 19 parameters were determined from 131 lateral skull radiographs. Classifications were induced from raw data with simple visualisation, C5.0 and Kohonen feature maps; and using a Point Distribution Model (PDM) of shape templates comprising points taken from digitised radiographs. RESULTS: The induced decision trees enable a direct comparison of clinicians' idiosyncrasies in classification. Unsupervised algorithms induce models that are potentially more objective, but their blackbox nature makes them unsuitable for clinical application. The PDM methodology gives dramatic visualisations of two modes separating horizontal and vertical facial growth. Kohonen feature maps favour one clinician and PDM the other. Clinical response suggests that while Clinician 1 places greater weight on 5 of 6 parameters, Clinician 2 relies on more parameters that capture facial shape. CONCLUSIONS: While machine learning and statistical analyses classify subjects for vertical facial height, they have limited application in their present form. The supervised learning algorithm C5.0 is effective for generating rules for individual clinicians but its inherent bias invalidates its use for objective classification of facial form for research purposes. On the other hand, promising results from unsupervised strategies (especially the PDM) suggest a potential use for objective classification and further identification and analysis of ambiguous cases. At present, such methodologies may be unsuitable for clinical application because of the invisibility of their underlying processes. Further study is required with additional patient data and a wider group of clinicians.

Algorithms↗

Dynamic and interactive generation of object handling behaviors by a small humanoid robot using a dynamic neural network model.

This study presents experiments on the learning of object handling behaviors by a small humanoid robot using a dynamic neural network model, the recurrent neural network with parametric bias (RNNPB). The first experiment showed that after the robot learned different types of ball handling behaviors using human direct teaching, the robot was able to generate adequate ball handling motor sequences situated to the relative position between the robot's hands and the ball. The same scheme was applied to a block handling learning task where it was shown that the robot can switch among learned different block handling sequences, situated to the ways of interaction by human supporters. Our analysis showed that entrainment of the internal memory structures of the RNNPB through the interactions of the objects and the human supporters are the essential mechanisms for those observed situated behaviors of the robot.

Algorithms↗

Accurate identification of alternatively spliced exons using support vector machine.

MOTIVATION: Alternative splicing is a major component of the regulatory action on mammalian transcriptomes. It is estimated that over half of all human genes have more than one splice variant. Previous studies have shown that alternatively spliced exons possess several features that distinguish them from constitutively spliced ones. Recently, we have demonstrated that such features can be used to distinguish alternative from constitutive exons. In the current study, we used advanced machine learning methods to generate robust classifier of alternative exons. RESULTS: We extracted several hundred local sequence features of constitutive as well as alternative exons. Using feature selection methods we find seven attributes that are dominant for the task of classification. Several less informative features help to slightly increase the performance of the classifier. The classifier achieves a true positive rate of 50% for a false positive rate of 0.5%. This result enables one to reliably identify alternatively spliced exons in exon databases that are believed to be dominated by constitutive exons.

Algorithms↗

A 3-d surface reconstruction approach based on postnonlinear ICA model.

Photometric stereo technique deals with the reconstruction of three-dimensional (3-D) shape of an object by using several images of the same surface taken from the same viewpoint but under illuminations from different directions. In this paper, we propose a new photometric stereo scheme based on a new reflectance model and the postnonlinear (PNL) independent components analysis (ICA) method. The proposed nonlinear reflectance model consists of diffuse components and specular components for modeling the surface reflectance of a stereo object in an image. Unlike the previous approaches, these two components are not separated and processed individually in the proposed model. An unsupervised learning adaptation algorithm is developed to estimate the reflectance model based on image intensities. In this algorithm, the PNL ICA method is used to obtain the surface normal on each point of an image. Then, the 3-D surface model is reconstructed based on the estimated surface normal on each point of image by using the enforcing integrability method. Two experiments are performed to assess the performance of the proposed approach. We test our algorithm on synthetically generated images for the reconstruction of surface of objects and on a number of real images captured from the Yale Face Database B. These testing images contain variability due to illumination and varying albedo in each point of surface of human faces. All the experimental results are compared to those of the existing photometric stereo approaches tested on the same images. The results clearly indicate the superiority of the proposed nonlinear reflectance model over the conventional Lambertian model and the other linear hybrid reflectance model.

Algorithms↗

Joint multiregion segmentation and parametric estimation of image motion by basis function representation and level set evolution.

The purpose of this study is to investigate a variational method for joint segmentation and parametric estimation of image motion by basis function representation of motion and level set evolution. The functional contains three terms. One term is of classic regularization to bias the solution toward a segmentation with smooth boundaries. A second term biases the solution toward a segmentation with boundaries which coincide with motion discontinuities, following a description of motion discontinuities by a function of the image spatio-temporal variations. The third term refers to region information and measures conformity of the parametric representation of the motion of each region of segmentation to the image spatio-temporal variations. The components of motion in each region of segmentation are represented as functions in a space generated by a set of basis functions. The coefficients of the motion components considered combinations of the basis functions are the parameters of representation. The necessary conditions for a minimum of the functional, which are derived taking into consideration the dependence of the motion parameters on segmentation, lead to an algorithm which condenses to concurrent curve evolution, implemented via level sets, and estimation of the parameters by least squares within each region of segmentation. The algorithm and its implementation are verified on synthetic and real images using a basis of cosine transforms.

Artificial Intelligence↗

Identification of statistical patterns in complex systems via symbolic time series analysis.

Identification of statistical patterns from observed time series of spatially distributed sensor data is critical for performance monitoring and decision making in human-engineered complex systems, such as electric power generation, petrochemical, and networked transportation. This paper presents an information-theoretic approach to identification of statistical patterns in such systems, where the main objective is to enhance structural integrity and operation reliability. The core concept of pattern identification is built upon the principles of Symbolic Dynamics, Automata Theory, and Information Theory. To this end, a symbolic time series analysis method has been formulated and experimentally validated on a special-purpose test apparatus that is designed for data acquisition and real-time analysis of fatigue damage in polycrystalline alloys.

Artificial Intelligence↗

A computer system to perform structure comparison using TOPS representations of protein structure.

We describe the design and implementation of a fast topology-based method for protein structure comparison. The approach uses the TOPS topological representation of protein structure, aligning two structures using a common discovered pattern and generating measure of distance derived from an insert score. Heavy use is made of a constraint-based pattern-matching algorithm for TOPS diagrams that we have designed and described elsewhere (Bioinformatics 15(4) (1999) 317). The comparison system is maintained at the European Bioinformatics Institute and is available over the Web at tops.ebi.ac.uk/tops. Users submit a structure description in Protein Data Bank (PDB) format and can compare it with structures in the entire PDB or a representative subset of protein domains, receiving the results by email.

Algorithms↗

Constraining active contour evolution via lie groups of transformation.

We present a novel approach to constraining the evolution of active contours used in image analysis. The proposed approach constrains the final curve obtained at convergence of curve evolution to be related to the initial curve from which evolution begins through an element of a desired Lie group of plane transformations. Constraining curve evolution in such a way is important in numerous tracking applications where the contour being tracked in a certain frame is known to be related to the contour in the previous frame through a geometric transformation such as translation, rotation, or affine transformation, for example. It is also of importance in segmentation applications where the region to be segmented is known up to a geometric transformation. Our approach is based on suitably modifying the Euler-Lagrange descent equations by using the correspondence between Lie groups of plane actions and their Lie algebras of infinitesimal generators, and thereby ensures that curve evolution takes place on an orbit of the chosen transformation group while remaining a descent equation of the original functional. The main advantage of our approach is that it does not necessitate any knowledge of nor any modification to the original curve functional and is extremely straightforward to implement. Our approach therefore stands in sharp contrast to other approaches where the curve functional is modified by the addition of geometric penalty terms. We illustrate our algorithm on numerous real and synthetic examples.

Algorithms↗

Generation of a large gene/protein lexicon by morphological pattern analysis.

The identification of gene/protein names in natural language text is an important problem in named entity recognition. In previous work we have processed MEDLINE documents to obtain a collection of over two million names of which we estimate that perhaps two thirds are valid gene/protein names. Our problem has been how to purify this set to obtain a high quality subset of gene/protein names. Here we describe an approach which is based on the generation of certain classes of names that are characterized by common morphological features. Within each class inductive logic programming (ILP) is applied to learn the characteristics of those names that are gene/protein names. The criteria learned in this manner are then applied to our large set of names. We generated 193 classes of names and ILP led to criteria defining a select subset of 1,240,462 names. A simple false positive filter was applied to remove 8% of this set leaving 1,145,913 names. Examination of a random sample from this gene/protein name lexicon suggests it is composed of 82% (+/-3%) complete and accurate gene/protein names, 12% names related to genes/proteins (too generic, a valid name plus additional text, part of a valid name, etc.), and 6% names unrelated to genes/proteins. The lexicon is freely available at ftp.ncbi.nlm.nih.gov/pub/tanabe/Gene.Lexicon.

Algorithms↗

Intuitive operation planning based on force feedback.

In the craniofacial surgery image-slices obtained from tomographies are used for planning and simulation of surgical interventions. Using these image-slices three-dimensional geometric models can be reconstructed, representing bones and soft tissue. However, for planning complex surgical interventions simulation methods are needed additionally to the pure visualisation. Exemplary, planning a Frontal Orbital Advancement (FOA) operation the cutting trajectories, their depth and orientation in each point, the drill hole, the position, orientation and deformation of bones, etc. are the point of interest. Especially for intraoperative execution supported by navigation systems or robots. In order to be able to plan such complex interventions with the help of computers, geometrical and haptical models must be generated from the image-slices. On the one hand these models represent the anatomical structures exactly, on the other hand they are needed for the simulation of the different activities, which have to be performed during the surgical intervention like drilling, milling, deforming, positioning, etc. Beside the geometrical and haptical models methods for interactions must be supplied to the physician for an accurate and intuitive planning of the surgical intervention. We developed such an operation planning system which is already used in clinical practise in Heidelberg.

Artificial Intelligence↗

Unsupervised learning with independent component analysis can identify patterns of glaucomatous visual field defects.

PURPOSE: We previously reported the use of clustering by unsupervised learning with machine learning classifiers to segment clusters of patterns in standard automated perimetry (SAP) for glaucoma. In this study, the process of unsupervised learning by independent component analysis decomposed SAP field patterns into axes, and the information represented by these axes was evaluated. METHODS: SAP fields were obtained with the Humphrey Visual Field Analyzer on 189 normal eyes and 156 eyes with glaucomatous optic neuropathy (GON) determined by masked review with stereoscopic optic disc photos. The variational Bayesian independent component analysis mixture model (vB-ICA-mm) partitioned the SAP fields into the most informative number of clusters. Simultaneously, it learned an optimal number of maximally independent axes for each cluster. RESULTS: The most informative number of clusters was two. vB-ICA-mm placed 68.6% of the SAP fields from eyes with GON in a cluster labeled G and 98.4% of the fields from eyes with normal optic discs in a cluster labeled N. Cluster G optimally contained six axes. Post hoc analysis of patterns generated at -1 SD and +2 SD from the cluster G mean on the six axes revealed defects similar to those identified by experts as indicative of glaucoma. SAP fields associated with an axis showed increasing severity as they were located farther in the positive direction from the cluster G mean. CONCLUSIONS: vB-ICA-mm represented the SAP fields with patterns that were meaningful for glaucoma experts. This process also captured severity in the patterns uncovered. These findings should validate vB-ICA-mm as a data mining technique for new and unfamiliar complex tests.

Artificial Intelligence↗

Hierarchical minimization with distance and angle constraints.

The incorporation of experimentally-determined constraints into structure-prediction methods based on energy minimization leads to both improved selectivity with empirical potential functions and structure determination with far fewer constraints than are required for distance-geometry calculations. Some methods will be described for using both distance and angle constraints with the hierarchical minimization algorithm. The simulation is based on a combination of Monte Carlo Simulated Annealing and Genetic Algorithm techniques which are integrated into a single framework. The selection cycle of the genetic algorithm is carried out at the same temperature as the mutations, or alternatively the crossover cycle can be considered as a type of Monte Carlo trial move, such that each temperature annealing step corresponds to a new generation. The sequence is divided up into segments, and the mutation step consists of replacing an entire segment with a choice from a pre-selected list. This list is in turn constructed from a list of smaller segments, and the number of overall conformations can thus be pruned at each level of selection. Results will be shown for test cases using a small number of flexible distance constraints used as an additional term in the potential, and for restrictions placed on backbone dihedral angles used as an additional screening criterion for constructing trial moves.

Algorithms↗

Molecular Landscape and Advanced Diagnostic Technologies for BRAF Mutations in Cancer: From Quantitative PCR and ddPCR to CRISPR-Based Platforms.

BRAF mutations are key oncogenic alterations across multiple malignancies, including melanoma, thyroid carcinoma, colorectal cancer, non-small cell lung cancer, glioma, and hairy cell leukemia. The most prevalent variant, BRAF-V600E, induces constitutive activation of the MAPK signaling pathway, promoting tumor progression and influencing therapeutic responsiveness. Accurate detection of BRAF alterations is therefore essential for molecular classification, prognostic assessment, treatment selection, and resistance surveillance. This review summarizes the molecular heterogeneity of BRAF mutations and critically evaluates current diagnostic methodologies. Conventional approaches such as allele-specific PCR and Sanger sequencing are compared with advanced quantitative platforms, including high-resolution melting analysis, droplet digital PCR, and next-generation sequencing, with emphasis on analytical sensitivity, mutation coverage, and clinical applicability. Emerging technologies such as CRISPR-based assays, rolling circle amplification systems, and nanoparticle-based biosensors and point-of-care diagnostic platforms are also discussed for their potential to enhance ultra-sensitive detection, particularly in liquid biopsy settings. These emerging tools are highlighted for their potential to enable ultra-sensitive, rapid, and decentralized mutation detection, particularly in liquid biopsy settings. Key challenges, including intratumoral heterogeneity, low allele-frequency variants, FFPE-associated artifacts, and clonal evolution under therapeutic pressure, are examined within a translational framework. In addition, we examine critical barriers to clinical implementation, including standardization, cost, and global accessibility of molecular diagnostics, and outline potential solutions through scalable technologies and decentralized testing strategies. We propose that optimal BRAF testing requires a mutation subclass-informed and clinically integrated strategy combining comprehensive baseline profiling with longitudinal molecular monitoring. Future diagnostic paradigms will likely integrate multi-omics data and artificial intelligence (AI)-assisted interpretation to refine precision oncology implementation. Looking forward, we propose that optimal BRAF testing will require integration of multi-omics profiling with AI-assisted interpretation, enabling automated variant classification, real-time clinical decision support, and improved prediction of therapeutic response and resistance.

Humans↗

Partially supervised learning using an EM-boosting algorithm.

Training data in a supervised learning problem consist of the class label and its potential predictors for a set of observations. Constructing effective classifiers from training data is the goal of supervised learning. In biomedical sciences and other scientific applications, class labels may be subject to errors. We consider a setting where there are two classes but observations with labels corresponding to one of the classes may in fact be mislabeled. The application concerns the use of protein mass-spectrometry data to discriminate between serum samples from cancer and noncancer patients. The patients in the training set are classified on the basis of tissue biopsy. Although biopsy is 100% specific in the sense that a tissue that shows itself to have malignant cells is certainly cancer, it is less than 100% sensitive. Reference gold standards that are subject to this special type of misclassification due to imperfect diagnosis certainty arise in many fields. We consider the development of a supervised learning algorithm under these conditions and refer to it as partially supervised learning. Boosting is a supervised learning algorithm geared toward high-dimensional predictor data, such as those generated in protein mass-spectrometry. We propose a modification of the boosting algorithm for partially supervised learning. The proposal is to view the true class membership of the samples that are labeled with the error-prone class label as missing data, and apply an algorithm related to the EM algorithm for minimization of a loss function. To assess the usefulness of the proposed method, we artificially mislabeled a subset of samples and applied the original and EM-modified boosting (EM-Boost) algorithms for comparison. Notable improvements in misclassification rates are observed with EM-Boost.

Algorithms↗

Pulmonary nodule detection in CT images with quantized convergence index filter.

A novel filter termed quantized convergence index filter (QCI filter) that is capable of enhancing the conspicuity of rounded lesions is proposed as part of a CAD (computer-aided diagnosis) scheme for detecting pulmonary nodules in computed tomography (CT) images. In this filter and its predecessor, the convergence index filter (CI filter), the output at a pixel represents the degree of convergence toward the pixel shown by the directions of gray-level gradients at surrounding pixels. The QCI filter and the CAD scheme were evaluated using five clinical datasets containing 50 nodules. With the support region of 9 x 9 pixels, the QCI filter showed more selective response to the nodules than the CI filter. In the CAD scheme, intermediate nodule candidates are generated based on the QCI filter output and then classified using linear discriminant analysis of eight features that are attributed to each intermediate nodule candidate. The QCI filter output level itself was used as one of the features. The scheme achieved a sensitivity of 90% with 1.67 false positives per slice. The QCI filter output level was most effective among the features in correctly classifying intermediate nodule candidates. The QCI filter is promising as a tool of preprocessing for automated pulmonary nodule detection in CT images.

Algorithms↗