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Long-term microbiome and clinical effects of a microbiome-guided personalized diet versus low-FODMAP diet in irritable bowel syndrome: A 12-month follow-up randomized controlled trial.

Dietary therapy is central to irritable bowel syndrome (IBS) management, yet the long-term durability of the low-FODMAP diet (LFD), and of microbiome-guided personalization, remains unclear. We assessed the long-term clinical and gut-microbiome effects of a microbiome-guided personalized diet (PD) compared with a standard LFD in adults meeting Rome IV criteria for IBS. In this multicenter, open-label randomized controlled trial with blinded outcome assessment, participants who completed a 6-week dietary intervention (PD or LFD) were followed at 6 and 12 months without further dietary intervention. Outcomes included the IBS Severity Scoring System (IBS-SSS), IBS Quality of Life (IBS-QOL), and the Hospital Anxiety and Depression Scale (HADS); gut microbiota were profiled by 16S rRNA sequencing. Longitudinal changes were evaluated using linear mixed-effects models, responder analyses, PERMANOVA, and PERMDISP. Both diets reduced IBS-SSS at 6 weeks. PD maintained symptom improvement at 6 and 12 months (-82.0 and -78.3 points from baseline), whereas LFD benefits regressed by 12 months (+29.3 points; between-group p&#x2009;=&#x2009;0.001). At 12 months, IBS-SSS responder rates were higher with PD than LFD (62.5% vs 34.5%; absolute risk difference&#x2009;+28.0%, 95% CI 4.2-47.7; Fisher p&#x2009;=&#x2009;0.029), and IBS-QOL, HADS-anxiety, and HADS-depression showed more favourable trajectories with PD. PD was associated with sustained Shannon alpha-diversity gains (+0.488 at 6 weeks;&#x2009;+0.205 at 12 months; both p&#x2009;<&#x2009;0.01). A modest between-group beta-diversity difference at 6 months (R2&#x2009;=&#x2009;0.035; p&#x2009;=&#x2009;0.011) was not significant at 12 months. This hypothesis-generating follow-up suggests more durable benefit with PD; larger trials powered for long-term clinical and microbiome outcomes are warranted.

Humans↗

Deformable shape finding with models based on kernel methods.

In this paper, a new kernel-based deformable model is proposed for detecting deformable shapes. To incorporate valuable information for shape detection, such as edge orientations into the shape representation, a novel scheme based on kernel methods has been utilized. The variation model of a deformable shape is established by a set of training samples of the shape represented in a kernel feature space. The proposed deformable model consists of two parts: a set of basis vectors describing the sample subspace, including the shape representations of the training samples, and a feasibility constraint generated by the one-class support vector machine to describe the feasible region of the training samples in the sample subspace. The aim of the proposed feasibility constraint is to avoid finding some invalid shapes. By using the proposed deformable model, an efficient algorithm without initial solutions is developed for shape detection. The proposed approach was tested against real images. Experimental results show the effectiveness of the proposed deformable model and prove the feasibility of the proposed approach.

Algorithms↗

Compensating for intraoperative soft-tissue deformations using incomplete surface data and finite elements.

Image-guided liver surgery requires the ability to identify and compensate for soft tissue deformation in the organ. The predeformed state is represented as a complete three-dimensional surface of the organ, while the intraoperative data is a range scan point cloud acquired from the exposed liver surface. The first step is to rigidly align the coordinate systems of the intraoperative and preoperative data. Most traditional rigid registration methods minimize an error metric over the entire data set. In this paper, a new deformation-identifying rigid registration (DIRR) is reported that identifies and aligns minimally deformed regions of the data using a modified closest point distance cost function. Once a rigid alignment has been established, deformation is accounted for using a linearly elastic finite element model (FEM) and implemented using an incremental framework to resolve geometric nonlinearities. Boundary conditions for the incremental formulation are generated from intraoperatively acquired range scan surfaces of the exposed liver surface. A series of phantom experiments is presented to assess the fidelity of the DIRR and the combined DIRR/FEM approaches separately. The DIRR approach identified deforming regions in 90% of cases under conditions of realistic surgical exposure. With respect to the DIRR/FEM algorithm, subsurface target errors were correctly located to within 4 mm in phantom experiments.

Algorithms↗

Can Hebbian volume learning explain discontinuities in cortical maps?

It has recently been shown that orientation and retinotopic position, both of which are mapped in primary visual cortex, can show correlated jumps (Das & Gilbert, 1997). This is not consistent with maps generated by Kohonen's algorithm (Kohonen, 1982), where changes in mapped variables tend to be anticorrelated. We show that it is possible to obtain correlated jumps by introducing a Hebbian component (Hebb, 1949) into Kohonen's algorithm. This correspondents to a volume learning mechanism where synaptic facilitation depends not only on the spread of a signal from a maximally active neuron but also requires postsynaptic activity at a synapse. The maps generated by this algorithm show discontinuities across which both orientation and retinotopic position change rapidly, but these regions, which include the orientation singularities, are also aligned with the edges of ocular dominance columns, and this is not a realistic feature of cortical maps. We conclude that cortical maps are better modeled by standard, non-Hebbian volume learning, perhaps coupled with some other mechanism (e.g., that of Ernst, Pawelzik, Tsodyks, & Sejnowski, 1999) to produce receptive field shifts.

Algorithms↗

Automated global structure extraction for effective local building block processing in XCS.

Learning Classifier Systems (LCSs), such as the accuracy-based XCS, evolve distributed problem solutions represented by a population of rules. During evolution, features are specialized, propagated, and recombined to provide increasingly accurate subsolutions. Recently, it was shown that, as in conventional genetic algorithms (GAs), some problems require efficient processing of subsets of features to find problem solutions efficiently. In such problems, standard variation operators of genetic and evolutionary algorithms used in LCSs suffer from potential disruption of groups of interacting features, resulting in poor performance. This paper introduces efficient crossover operators to XCS by incorporating techniques derived from competent GAs: the extended compact GA (ECGA) and the Bayesian optimization algorithm (BOA). Instead of simple crossover operators such as uniform crossover or one-point crossover, ECGA or BOA-derived mechanisms are used to build a probabilistic model of the global population and to generate offspring classifiers locally using the model. Several offspring generation variations are introduced and evaluated. The results show that it is possible to achieve performance similar to runs with an informed crossover operator that is specifically designed to yield ideal problem-dependent exploration, exploiting provided problem structure information. Thus, we create the first competent LCSs, XCS/ECGA and XCS/BOA, that detect dependency structures online and propagate corresponding lower-level dependency structures effectively without any information about these structures given in advance.

Algorithms↗

Data, knowledge and method bases in chemical sciences. Part IV. Current status in databases.

Computer readable databases have become an integral part of chemical research right from planning data acquisition to interpretation of the information generated. The databases available today are numerical, spectral and bibliographic. Data representation by different schemes--relational, hierarchical and objects--is demonstrated. Quality index (QI) throws light on the quality of data. The objective, prospects and impact of database activity on expert systems are discussed. The number and size of corporate databases available on international networks crossed manageable number leading to databases about their contents. Subsets of corporate or small databases have been developed by groups of chemists. The features and role of knowledge-based or intelligent databases are described.

Artificial Intelligence↗

A knowledge-based, concept-oriented view generation system for clinical data.

Information overload is a well-known problem for clinicians who must review large amounts of data in patient records. Concept-oriented views, which organize patient data around clinical concepts such as diagnostic strategies and therapeutic goals, may offer a solution to the problem of information overload. However, although concept-oriented views are desirable, they are difficult to create and maintain. We have developed a general-purpose, knowledge-based approach to the generation of concept-oriented views and have developed a system to test our approach. The system creates concept-oriented views through automated identification of relevant patient data. The knowledge in the system is represented by both a semantic network and rules. The key relevant data identification function is accomplished by a rule-based traversal of the semantic network. This paper focuses on the design and implementation of the system; an evaluation of the system is reported separately.

Artificial Intelligence↗

Neural network explanation using inversion.

An important drawback of many artificial neural networks (ANN) is their lack of explanation capability [Andrews, R., Diederich, J., & Tickle, A. B. (1996). A survey and critique of techniques for extracting rules from trained artificial neural networks. Knowledge-Based Systems, 8, 373-389]. This paper starts with a survey of algorithms which attempt to explain the ANN output. We then present HYPINV, a new explanation algorithm which relies on network inversion; i.e. calculating the ANN input which produces a desired output. HYPINV is a pedagogical algorithm, that extracts rules, in the form of hyperplanes. It is able to generate rules with arbitrarily desired fidelity, maintaining a fidelity-complexity tradeoff. To our knowledge, HYPINV is the only pedagogical rule extraction method, which extracts hyperplane rules from continuous or binary attribute neural networks. Different network inversion techniques, involving gradient descent as well as an evolutionary algorithm, are presented. An information theoretic treatment of rule extraction is presented. HYPINV is applied to example synthetic problems, to a real aerospace problem, and compared with similar algorithms using benchmark problems.

Algorithms↗

A hybrid machine-learning approach for segmentation of protein localization data.

MOTIVATION: Subcellular protein localization data are critical to the quantitative understanding of cellular function and regulation. Such data are acquired via observation and quantitative analysis of fluorescently labeled proteins in living cells. Differentiation of labeled protein from cellular artifacts remains an obstacle to accurate quantification. We have developed a novel hybrid machine-learning-based method to differentiate signal from artifact in membrane protein localization data by deriving positional information via surface fitting and combining this with fluorescence-intensity-based data to generate input for a support vector machine. RESULTS: We have employed this classifier to analyze signaling protein localization in T-cell activation. Our classifier displayed increased performance over previously available techniques, exhibiting both flexibility and adaptability: training on heterogeneous data yielded a general classifier with good overall performance; training on more specific data yielded an extremely high-performance specific classifier. We also demonstrate accurate automated learning utilizing additional experimental data.

Animals↗

AClAP, Autonomous hierarchical agglomerative Cluster Analysis based protocol to partition conformational datasets.

MOTIVATION: Sampling the conformational space is a fundamental step for both ligand- and structure-based drug design. However, the rational organization of different molecular conformations still remains a challenge. In fact, for drug design applications, the sampling process provides a redundant conformation set whose thorough analysis can be intensive, or even prohibitive. We propose a statistical approach based on cluster analysis aimed at rationalizing the output of methods such as Monte Carlo, genetic, and reconstruction algorithms. Although some software already implements clustering procedures, at present, a universally accepted protocol is still missing. RESULTS: We integrated hierarchical agglomerative cluster analysis with a clusterability assessment method and a user independent cutting rule, to form a global protocol that we implemented in a MATLAB metalanguage program (AClAP). We tested it on the conformational space of a quite diverse set of drugs generated via Metropolis Monte Carlo simulation, and on the poses we obtained by reiterated docking runs performed by four widespread programs. In our tests, AClAP proved to remarkably reduce the dimensionality of the original datasets at a negligible computational cost. Moreover, when applied to the outcomes of many docking programs together, it was able to point to the crystallographic pose. AVAILABILITY: AClAP is available at the "AClAP" section of the website http://www.scfarm.unibo.it.

Algorithms↗

Analyzing array data using supervised methods.

Pharmacogenomics is the application of genomic technologies to drug discovery and development, as well as for the elucidation of the mechanisms of drug action on cells and organisms. DNA microarrays measure genome-wide gene expression patterns and are an important tool for pharmacogenomic applications, such as the identification of molecular targets for drugs, toxicological studies and molecular diagnostics. Genome-wide investigations generate vast amounts of data and there is a need for computational methods to manage and analyze this information. Recently, several supervised methods, in which other information is utilized together with gene expression data, have been used to characterize genes and samples. The choice of analysis methods will influence the results and their interpretation, therefore it is important to be familiar with each method, its scope and limitations. Here, methods with special reference to applications for pharmacogenomics are reviewed.

Artificial Intelligence↗

Integration of textual guideline documents with formal guideline knowledge bases.

Numerous approaches have been proposed to integrate the text of guideline documents with guideline-based care systems. Current approaches range from serving marked up guideline text documents to generating advisories using complex guideline knowledge bases. These approaches have integration problems mainly because they tend to rigidly link the knowledge base with text. We are developing a bridge approach that uses an information retrieval technology. The new approach facilitates a versatile decision-support system by using flexible links between the formal structures of the knowledge base and the natural language style of the guideline text.

Artificial Intelligence↗

A Bayesian approach to generating tutorial hints in a collaborative medical problem-based learning system.

OBJECTIVES: Today a great many medical schools have turned to a problem-based learning (PBL) approach to teaching. While PBL has many strengths, effective PBL requires the tutor to provide a high degree of personal attention to the students, which is difficult in the current academic environment of increasing demands on faculty time. This paper describes intelligent tutoring in a collaborative medical tutor for PBL. The main contribution of our work is the development of representational techniques and algorithms for generating tutoring hints in PBL group problem solving, as well as the implementation of these techniques in a collaborative intelligent tutoring system, COMET. The system combines concepts from computer-supported collaborative learning with those from intelligent tutoring systems. METHODS AND MATERIALS: The system uses Bayesian networks to model individual student clinical reasoning, as well as that of the group. The prototype system incorporates substantial domain knowledge in the areas of head injury, stroke and heart attack. Tutoring in PBL is particularly challenging since the tutor should provide as little guidance as possible while at the same time not allowing the students to get lost. From studies of PBL sessions at a local medical school, we have identified and implemented eight commonly used hinting strategies. In order to evaluate the appropriateness and quality of the hints generated by our system, we compared the tutoring hints generated by COMET with those of experienced human tutors. We also compared the focus of group activity chosen by COMET with that chosen by human tutors. RESULTS: On average, 74.17% of the human tutors used the same hint as COMET. The most similar human tutor agreed with COMET 83% of the time and the least similar tutor agreed 62% of the time. Our results show that COMET's hints agree with the hints of the majority of the human tutors with a high degree of statistical agreement (McNemar test, p=0.652, kappa=0.773). The focus of group activity chosen by COMET agrees with that chosen by the majority of the human tutors with a high degree of statistical agreement (McNemar test, p=0.774, kappa=0.823). CONCLUSION: Bayesian network clinical reasoning models can be combined with generic tutoring strategies to successfully emulate human tutor hints in group medical PBL.

Artificial Intelligence↗

Modeling of cyclin-dependent kinase inhibition by 1H-pyrazolo[3,4-d]pyrimidine derivatives using artificial neural network ensembles.

Artificial neural network ensembles were used for modeling the cyclin-dependent kinase inhibition of 1H-pyrazolo[3,4-d]pyrimidine derivatives. The structural characteristics of these inhibitors were encoded in relevant 3D-spatial descriptors extracted by genetic algorithm feature selection. Bayesian-regularized multilayer neural networks, trained by the back-propagation algorithm, were developed using these variables as inputs. The predictive power of the model was tested by leave-one-out cross validation. In addition, for a more rigorous measure of the predictive capacity, multiple validation sets were randomly generated as members of neural network ensembles, which makes doing averaged predictions feasible. In this way, the predictive power was analyzed accounting for the averaged test set R values and test set mean-square errors. Otherwise, Kohonen self-organizing maps were used as an additional tool for the same modeling. The location of the inhibitors in a map facilitates the analysis of the connection between compounds and serves as a useful tool for qualitative predictions.

Algorithms↗

EEG and MEG brain-computer interface for tetraplegic patients.

We characterized features of magnetoencephalographic (MEG) and electroencephalographic (EEG) signals generated in the sensorimotor cortex of three tetraplegics attempting index finger movements. Single MEG and EEG trials were classified offline into two classes using two different classifiers, a batch trained classifier and a dynamic classifier. Classification accuracies obtained with dynamic classifier were better, at 75%, 89%, and 91% in different subjects, when features were in the 0.5-3.0-Hz frequency band. Classification accuracies of EEG and MEG did not differ.

Artificial Intelligence↗

Glasses removal from facial image using recursive error compensation.

In this paper, we propose a new method of removing glasses from a human frontal facial image. We first detect the regions occluded by the glasses and generate a natural looking facial image without glasses by recursive error compensation using PCA reconstruction. The resulting image has no trace of the glasses frame or of the reflection and shade caused by the glasses. The experimental results show that the proposed method provides an effective solution to the problem of glasses occlusion and we believe that this method can also be used to enhance the performance of face recognition systems.

Algorithms↗

Min-max hyperellipsoidal clustering for anomaly detection in network security.

A novel hyperellipsoidal clustering technique is presented for an intrusion-detection system in network security. Hyperellipsoidal clusters toward maximum intracluster similarity and minimum intercluster similarity are generated from training data sets. The novelty of the technique lies in the fact that the parameters needed to construct higher order data models in general multivariate Gaussian functions are incrementally derived from the data sets using accretive processes. The technique is implemented in a feedforward neural network that uses a Gaussian radial basis function as the model generator. An evaluation based on the inclusiveness and exclusiveness of samples with respect to specific criteria is applied to accretively learn the output clusters of the neural network. One significant advantage of this is its ability to detect individual anomaly types that are hard to detect with other anomaly-detection schemes. Applying this technique, several feature subsets of the tcptrace network-connection records that give above 95% detection at false-positive rates below 5% were identified.

Algorithms↗

Sensitivity of a computer adaptive assessment for measuring functional mobility changes in children enrolled in a community fitness programme.

OBJECTIVE: To examine the relative sensitivity to detect functional mobility changes with a full-length parent questionnaire compared with a computerized adaptive testing version of the questionnaire after a 16-week group fitness programme. DESIGN: Prospective, pre- and posttest study with a 16-week group fitness intervention. SETTING: Three community-based fitness centres. SUBJECTS: Convenience sample of children (n = 28) with physical or developmental disabilities. INTERVENTIONS: A 16-week group exercise programme held twice a week in a community setting. MAIN MEASURES: A full-length (161 items) paper version of a mobility parent questionnaire based on the Pediatric Evaluation of Disability Inventory, but expanded to include expected skills of children up to 15 years old was compared with a 15-item computer adaptive testing version. Both measures were administered at pre- and posttest intervals. RESULTS: Both the full-length Pediatric Evaluation of Disability Inventory and the 15-item computer adaptive testing version detected significant changes between pre- and posttest scores, had large effect sizes, and standardized response means, with a modest decrease in the computer adaptive test as compared with the 161-item paper version. Correlations between the computer adaptive and paper formats across pre- and posttest scores ranged from r = 0.76 to 0.86. CONCLUSIONS: Both functional mobility test versions were able to detect positive functional changes at the end of the intervention period. Greater variability in score estimates was generated by the computerized adaptive testing version, which led to a relative reduction in sensitivity as defined by the standardized response mean. Extreme scores were generally more difficult for the computer adaptive format to estimate with as much accuracy as scores in the mid-range of the scale. However, the reduction in accuracy and sensitivity, which did not influence the group effect results in this study, is counterbalanced by the large reduction in testing burden.

Adolescent↗