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PubMed2025

Generative AI Models in Time-Varying Biomedical Data: Scoping Review.

BACKGROUND: Trajectory modeling is a long-standing challenge in the application of computational methods to health care. In the age of big data, traditional statistical and machine learning methods do not achieve satisfactory results as they often fail to capture the complex underlying distributions of multimodal health data and long-term dependencies throughout medical histories. Recent advances in generative artificial intelligence (AI) have provided powerful tools to represent complex distributions and patterns with minimal underlying assumptions, with major impact in fields such as finance and environmental sciences, prompting researchers to apply these methods for disease modeling in health care. OBJECTIVE: While AI methods have proven powerful, their application in clinical practice remains limited due to their highly complex nature. The proliferation of AI algorithms also poses a significant challenge for nondevelopers to track and incorporate these advances into clinical research and application. In this paper, we introduce basic concepts in generative AI and discuss current algorithms and how they can be applied to health care for practitioners with little background in computer science. METHODS: We surveyed peer-reviewed papers on generative AI models with specific applications to time-series health data. Our search included single- and multimodal generative AI models that operated over structured and unstructured data, physiological waveforms, medical imaging, and multi-omics data. We introduce current generative AI methods, review their applications, and discuss their limitations and future directions in each data modality. RESULTS: We followed the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines and reviewed 155 articles on generative AI applications to time-series health care data across modalities. Furthermore, we offer a systematic framework for clinicians to easily identify suitable AI methods for their data and task at hand. CONCLUSIONS: We reviewed and critiqued existing applications of generative AI to time-series health data with the aim of bridging the gap between computational methods and clinical application. We also identified the shortcomings of existing approaches and highlighted recent advances in generative AI that represent promising directions for health care modeling.

Artificial Intelligence↗
PubMedDate not supplied

[Use of the computer simulation method of complementary amino acids base on a genetic code algorithm for the search for new peptide compounds belonging to tuftsin-like activity].

Methods of k-neighbours and neural networks were used for prediction of pharmacological effects of new compounds wits tuftsin-like activities. The tested compounds were constructed by the complementarity rule of genetic code algorithm. Five of seven substitutions with stereocomplement amino acids in the tuftsin sequence lead to new active compounds. Thus, the use of amino acid complementary code can be a helpful tool for the construction of a new immunomodulating peptide.

Algorithms↗
PubMed1991

[New electronic-mathematical method for measuring the condylar center of rotation].

Until today, not all methodical details and problems concerning the exact and reproducible determination of the condylar hinge axis have been solved yet. All familiar mechanical-manual and electronically supported methods as well as computer methods of some electronical recording systems have their limitations and are partly incorrect up to now. The reason for this lies mainly in the theoretical respectively mathematical approach towards these methods. With the aim of determining a point of minimal translatory movement ("steady point") during the rotatory opening movement in the TMJ condyle, a mathematical method is presented, which calculates the 3D coordinates of the condylar rotation centers automatically, i.e. without manual manipulation of the recording system. Contrary to conventional methods, this new technique is very precise and relatively less sensitive towards superimposed translatory movements.

Dental Articulators↗
PubMed2006

Interactions in native binding sites cause a large change in protein dynamics.

Cellular functions are regulated by molecules that interact with proteins and alter their activities. To enable such control, protein activity, and therefore protein conformational distributions, must be susceptible to alteration by molecular interactions at functional sites. Here we investigate whether interactions at functional sites cause a large change in the protein conformational distribution. We apply a computational method, called dynamics perturbation analysis (DPA), to identify sites at which interactions have a large allosteric potential D(x), which is the Kullback-Leibler divergence between protein conformational distributions with and without an interaction. In DPA, a protein is decorated with surface points that interact with neighboring protein atoms, and D(x) is calculated for each of the points in a coarse-grained model of protein vibrations. We use DPA to examine hundreds of protein structures from a standard small-molecule docking test set, and find that ligand-binding sites have elevated values of D(x): for 95% of proteins, the probability of randomly obtaining values as high as those in the binding site is 10(-3) or smaller. We then use DPA to develop a computational method to predict functional sites in proteins, and find that the method accurately predicts ligand-binding-site residues for proteins in the test set. The performance of this method compares favorably with that of a cleft analysis method. The results confirm that interactions at small-molecule binding sites cause a large change in the protein conformational distribution, and motivate using DPA for large-scale prediction of functional sites in proteins. They also suggest that natural selection favors proteins whose activities are capable of being regulated by molecular interactions.

Algorithms↗
PubMed2002

Modeling the structure of agitoxin in complex with the Shaker K+ channel: a computational approach based on experimental distance restraints extracted from thermodynamic mutant cycles.

Computational methods are used to determine the three-dimensional structure of the Agitoxin (AgTx2)-Shaker complex. In a first stage, a large number of models of the complex are generated using high temperature molecular dynamics, accounting for side chain flexibility with distance restraints deduced from thermodynamic analysis of double mutant cycles. Four plausible binding mode candidates are found using this procedure. In a second stage, the quality and validity of the resulting complexes is assessed by examining the stability of the binding modes during molecular dynamics simulations with explicit water molecules and by calculating the binding free energies of mutant proteins using a continuum solvent representation and comparing with experimental data. The docking protocol and the continuum solvent model are validated using the Barstar-Barnase and the lysozyme-antibody D1.2 complexes, for which there are high-resolution structures as well as double mutant data. This combination of computational methods permits the identification of two possible structural models of AgTx2 in complex with the Shaker K+ channel, additional structural analysis providing further evidence in favor of a single model. In this final complex, the toxin is bound to the extracellular entrance of the channel along the pore axis via a combination of hydrophobic, hydrogen bonding, and electrostatic interactions. The magnitude of the buried solvent accessible area corresponding to the protein-protein contact is on the order of 1000 A with roughly similar contributions from each of the four subunits. Some side chains of the toxin adopt different conformation than in the experimental solution structure, indicating the importance of an induced-fit upon the formation of the complex. In particular, the side chain of Lys-27, a residue highly conserved among scorpion toxins, points deep into the pore with its positively charge amino group positioned at the outer binding site for K+. Specific site-directed mutagenesis experiments are suggested to verify and confirm the structure of the toxin-channel complex.

Animals↗
PubMed2004

Simulation of the interaction between ScyTx and small conductance calcium-activated potassium channel by docking and MM-PBSA.

Computational methods are employed to simulate interaction of scorpion toxin ScyTx in complex with the small conductance calcium-activated potassium channel rsk2. All of available 25 structures of ScyTx in the Protein Data Bank determined by NMR were considered for improving performance of rigid protein docking of ZDOCK. Four main binding modes were found among a large number of predicted complexes by using clustering analysis, screening with expert knowledge, energy minimization, and molecular dynamics simulations. The quality and validity of the resulting complexes were further evaluated by molecular dynamics simulations with the generalized Born solvation model and by calculation of relative binding free energies with the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) in the AMBER 7 suit of programs. The complex formed by the 22nd structure of the ScyTx and rsk2 channel was identified as the most favorable complex by using a combination of computational methods, which contain further introduction of flexibility without restraining residue side chain. From the resulted spatial structure of the ScyTx and rsk2 channel, ScyTx associates the mouth of the rsk2 channel with alpha-helix rather than beta-sheet. Structural analysis first revealed that Arg(13) played a novel and vital role of blocking the pore of the rsk2 channel, whose role is remarkably different from that of highly homologous scorpion toxin P05. Between the interfaces in the ScyTx-rsk2 complex, strong electrostatic interaction and hydrogen bonds exist between Arg(13) of ScyTx and Gly-Tyr-Gly-Asp sequential residues located in the four symmetrical chains of the pore region. Simultaneously, five hydrogen bonds between Arg(6) of ScyTx and Asp(341)(C), Val(366)(C), and Pro(367)(C), and electrostatic interaction between Arg(6) of ScyTx and Asp(364)(B) and Asp(341)(C) are also found by structural analysis. In addition, His(31) located at the C-terminal of ScyTx is surrounded by Val(342)(A), Asp(364)(A), Met(365)(A), Pro(367)(B), and Asn(366)(B) within a contact distance of 4.0 A. These simulation results are in good agreement with experimental data and can effectively explain the binding phenomena between ScyTx and the potassium channel at the level of molecular spatial structure. The consistency between results of molecular modeling and experimental data strongly suggests that our spatial structure model of the ScyTx-rsk2 complex is reasonable. Therefore, molecular docking combined with molecular dynamics simulations followed by molecular mechanics Poisson-Boltzmann surface area analysis is an attractive approach for modeling scorpion toxin-potassium channel complexes a priori for further biological studies.

Animals↗
PubMed1986

Methods for computing comet core temperatures.

General analytic expressions are derived that relate the surface temperature to the temperature deep within the nucleus of a spherically symmetric layered comet in thermal equilibrium. The relation between the average surface temperature and the mean temperature at great depths depends entirely on the temperature dependence of the thermal conductivity. The core temperature is given by the inverse of the anti-derivative of the thermal conductivity, with respect to temperature, operating on the average value of the anti-derivative of the thermal conductivity evaluated at the surface temperature. Using these expressions detailed numerical models of the surface temperature of comets can be used to directly estimate the core temperature. For the special, albeit unphysical, case of an isothermal, low-conductivity comet nucleus, without sublimation, the core temperature can be determined analytically. To illustrate the dependence of core temperature on eccentricity this simple case is solved assuming that the temperatures dependence of the thermal conductivity is given by that of crystalline ice. For an eccentricity of approximately 0.5, the core temperature obtained is 3% colder than the corresponding value obtained assuming constant thermal conductivity an is 11% colder than the result of Klinger's (1981) formula. This method is also applied to a detailed numerical model with a complicated nonintegrable thermal conductivity.

Astronomy↗
PubMed2026

A systematic review of human avoidance learning: Cognition, computation, and methods.

Avoidance behaviour is fundamental for survival but can become maladaptive in clinical conditions. A large body of literature has accumulated on the dynamics of human avoidance learning. However, current theories and overviews do not provide an exhaustive account of this evidence. In this systematic review, we identify N = 116 studies on human avoidance learning. We analyse these studies with the goal of distilling robust empirical phenomena as a basis for theory-building, and examine their diagnostic value in differentiating between competing theories. We find that the evidence is difficult to reconcile with foundational two-factor and classical safety-signal accounts, and most strongly supports expectancy- and inference-based views, in which avoidance responses are selected with respect to represented consequences. At the same time, no current framework provides a complete account of the evidence: several findings point to an additional role for operant valuation, Pavlovian influences, and contextual or latent-state control over the expression of avoidance. Methodologically, we observe that the problem setting in the most common experimental paradigms is radically simpler than real-world avoidance and therefore unlikely to expose the limits of inferential or reflective mechanisms. Consequently, we argue that paradigms with greater computational demands and more realistic action affordances are required to identify the mechanisms underlying avoidance learning. Collectively, these insights provide a foundation for theoretical refinement, computational modelling, and methodological innovation, with implications for advancing interventions targeting maladaptive avoidance.

Humans↗
PubMed2005

Computational characterization of behavioral response of medaka (Oryzias latipes) treated with diazinon.

The behavior of indicator specimens in response to sub-lethal doses of toxic substances has been used to detect contamination in aquatic ecosystems. Changes in the movement behaviors of medaka (Oryzias latipes) were analyzed after being treated with diazinon at a concentration of 0.1 mg/l. The movement tracks of medaka were continuously recorded in two-dimension by a digital image processing system both before and after the treatments. Subsequently, two computational methods--two-dimensional fast Fourier transform (2D FFT) and self-organizing map (SOM), were implemented to extract information from the movement data. The differences in the shapes of the movement tracks before and after the treatments were clearly manifested through 2D FFT. The short-distance, irregular turnings in the movement tracks observed after the treatments in the time domain were characteristically transformed to circular or ellipsoidal patterns in the frequency domain. The amplitudes of 2D FFT were efficiently classified by SOM, demonstrating the effects of the different treatments. To evaluate the feasibility of information extraction by 2D FFT, SOM was similarly carried out on the parameters (speed, meander, stop duration, etc.) conventionally used for characterizing the movement tracks. 2D FFT was more efficient in information extraction from the movement data than the parameters. The 2D FFT and SOM were useful as computational methods for automatically detecting response behaviors of indicator specimens exposed to toxic chemicals in aquatic ecosystems.

Animals↗
PubMed2000

A simple method of computing hip axis length using fan-beam densitometry and anthropometric measurements.

Hip axis length (HAL), a simple measure obtained from dual X-ray absorptiometry (DXA) scans of the proximal femur, predicts hip fracture, independent of bone mineral density and age. Owing to a magnification error associated with newer fan-beam DXA, automatic calculation of HAL, which is available in pencil-beam DXA, is inaccurate. The purpose of this study was to model HAL, measured from a pencil-beam DXA, as a function of HAL from a fan-beam DXA combined with other anthropometric measures. Proximal femur scans were performed using pencil- and fan-beam DXA in 21 women (ages 24-60). Height, weight, hip circumference, subject thickness, height of the greater trochanter and anterior superior iliac spine from the scanning table, and HAL as measured by a ruler from the scan printouts were recorded. Anthropometric measurements were taken by two researchers; all but the greater trochanter were reproducible (r > or = 0.92). A simple linear model using the manual measurement of HAL from the fan-beam scan, height, weight, body mass index, and hip circumference was able to predict HAL measured using the pencil-beam DXA with a high degree of accuracy (R(2) > or = 0.96). The fan-beam-acquired values of HAL using our model are nonbiased and accurate estimates of the "gold standard" pencil-beam method. This model may provide researchers and clinicians with a simple method of calculating HAL using fan-beam DXA.

Absorptiometry, Photon↗
PubMed2001

Quantitative drug interactions prediction system (Q-DIPS): a dynamic computer-based method to assist in the choice of clinically relevant in vivo studies.

Metabolic drug interactions are a major source of clinical problems, but their investigation during drug development is often incomplete and poorly specific. In vitro studies give very accurate data on the interactions of drugs with selective cytochrome P450 (CYP) isozymes, but their interpretation in the clinical context is difficult. On the other hand, the design of in vivo studies is sometimes poor (choice of prototype substrate, doses, schedule of administration, number of volunteers), with the risk of minimising the real potential for interaction. To link in vitro and in vivo studies, several authors have suggested using extrapolation techniques, based on the comparison of in vitro inhibition data with the active in vivo concentrations of the inhibitor. However, the lack of knowledge of one or several important parameters (role of metabolites, intrahepatocyte accumulation) often limits the possibility for safe and accurate predictions. In consequence, these methods are useful to complement in vitro studies and help design clinically relevant in vivo studies, but they will not totally replace in vivo investigation in the future. We have developed a computerised application, the quantitative drug interactions prediction system (Q-DIPS), to make both qualitative deductions and quantitative predictions on the basis of a database containing updated information on CYP substrates, inhibitors and inducers, as well as pharmacokinetic parameters. We also propose a global approach to drug interactions problems--'good interactions practice--to help design rational drug interaction investigations, sequentially associating in vitro studies, in vitrolin vivo extrapolation and finally well-designed in vivo clinical studies.

Computers↗
PubMed2002

Computer-based method for the 3-D kinematic analysis of posterior cruciate ligament and postero-lateral corner lesions.

Posterior cruciate ligament (PCL) rupture, whether or not combined with postero-lateral corner (PLC) tears, are more often diagnosed today thanks to improved imaging techniques. However, due to the lack of reliable instrumentation to quantitatively evaluate the knee, much is still unknown about the function of these ligamentous structures. The aim of this paper is to present results on the effect of progressive resection of the PCL and PLC on knee laxity and 3-D knee kinematics. The results show that 3-D movement analysis is important and complements laxity measurements by helping to interpret the complex alteration of knee function.

Aged↗
PubMedDate not supplied

Computer-based methods for measurement, recording and modeling vessel responses in vitro: a pilot study with noradrenaline.

This paper reports the first results of an ongoing methodological pilot study aimed at designing techniques for the automatic measurement and digital recording of vessel responses to biologically active substances under in vitro conditions and for the mathematical modeling of the underlying processes. The techniques presented in this pilot study allowed us to determine model-based estimates of the parameters characterizing vasoconstrictor responses, i.e., the vessel sensitivity parameter, the mean time of vasoconstrictor response and the rate constant of vessel relaxation. The given parameters are not dependent on doses of biologically active substances, provided that the underlying processes satisfy the principle of superposition. Use of these techniques is shown in the classic study of vasoconstrictor responses to noradrenaline in the rat renal artery.

Animals↗
PubMed2000

Relationship between phase and energy methods for disparity computation.

The phase and energy methods for computing binocular disparity maps from stereograms are motivated differently, have different physiological relevances, and involve different computational steps. Nevertheless, we demonstrate that at the final stages where disparity values are made explicit, the simplest versions of the two methods are exactly equivalent. The equivalence also holds when the quadrature-pair construction in the energy method is replaced with a more physiologically plausible phase-averaging step. The equivalence fails, however, when the phase-difference receptive field model is replaced by the position-shift model. Additionally, intermediate results from the two methods are always quite distinct. In particular, the energy method generates a distributed disparity representation similar to that found in the visual cortex, while the phase method does not. Finally, more elaborate versions of the two methods are in general not equivalent. We also briefly compare these two methods with some other stereo models in the literature.

Animals↗
PubMed2003

Computer based method for the three-dimensional kinematic analysis of combined posterior cruciate ligament and postero-lateral complex reconstructions on cadaver knees.

The aim of this study is to evaluate the effect of combined posterior cruciate ligament (PCL) and postero-lateral corner (PLC) reconstruction on laxity and three-dimensional kinematics of cadaver knees. We performed anatomical double bundle PCL reconstruction, and functional one bundle 'over-the-bottom' PCL reconstruction combined with one type of PLC reconstruction, running from the postero-lateral tibia to an isometric point near the lateral epicondyle of the femur. Our results showed that combined reconstruction was necessary to restore rotatory laxity. PLC reconstruction, according to the technique described, invariably created a shift towards internal rotation of the kinematic curves, compared to the intact knee.

Aged↗
PubMed2005

The structures of higher boron halides B8X12(X = F, Cl, Br and I) by gas-phase electron diffraction and ab initio calculations.

The structure of B8F12 has been shown by gas electron diffraction and computational methods (up to MP2/6-31+G*) to have the same highly asymmetric form observed in crystalline phases. The structure can be regarded as derived from a central B2 group, bridged by two BF2 groups to give a central B4 core that is folded, not planar, and with a very short bond [164.3 pm calculated, 164.2(19) pm experimental] along the fold line. There are also four terminal BF2 groups. One of the other four bonds in the core is consistently 20-30 pm longer than the others. This asymmetry has been attributed to many intra-molecular B...F interactions, particularly those between core boron atoms and fluorines of the terminal BF2 groups. Calculations for the chloro analogue lead to a structure similar to that for B8F12, but with the long core bond extended so that one of the bridging BCl2 groups may now be regarded as terminal. With bromine as the halogen the structure changes again, with one bromine atom taking up a bridging position. With iodine, this process continues further, and there are three bridging iodine atoms. However, in this case this is not the lowest energy structure, and instead a loosely associated dimer of B4I6 is preferred. In all these cases, and particularly with the heavier halogens, there are huge differences between the results obtained with different computational methods.

Journal Article↗
PubMed1997

A computed tomography method for studying the degree of postoperative aeration of maxillary sinuses.

Most patients with chronic odontogenic sinusitis experience aeration problems which remain unresolved even after classic radical antrotomy has been performed. The aim of this study was to create a high-yield diagnostically feasible and accurate CT technique which would allow the evaluation of the degree of postoperative changes of maxillary sinus aeration and overcome the limited value of traditional imaging modalities. We studied the aeration sequelae in the maxillary sinus following antrotomy in thirty-five patients employing Sytec 3000 CT scan equipment with modern densoprofile software. We found a prevalence of 62.92% for minor complications following antrotomy--a reduction in the volume of the maxillary sinus up to 25%, whereas the more serious complications accounted for 5.72%. Conventional radiologic modalities demonstrated only 25% of these changes. Our results underscore the importance of the densoprofile CT technique as a valuable and accurate diagnostic tool in detecting the changes consistent with the postantrotomy syndrome.

Adult↗
PubMed2002

Glycosylation of proteins: a computer based method for the rapid exploration of conformational space of N-glycans.

Inspection of protein databases suggests that as many as 70% of proteins have potential N-glycosylation sites. Unfortunately glycoproteins often refuse to crystallize and NMR techniques do not allow an unambiguous determination of the complete conformation of the sugar part. Therefore, time-consuming complex simulation methods are often used to explore the conformational space of N-glycans. The generation of a comprehensive data base describing the conformational space of larger fragments of N-glycans taking into account the effects of branching is presented. High-temperature molecular dynamics simulations of essential N-glycan fragments are performed until conformational equilibrium has been reached. Free energy landscapes are calculated for each glycosidic linkage. All possible conformations for each N-glycan fragment are automatically assigned, ranked according to their relative population and stored in a database. These values are recalled for the generation of a complete set of all possible conformations for a given N-glycan topology. The constructed conformations are ranked according to their energy content. Since this approach allows to explore the complete conformational space of a given N-glycan within a few minutes of CPU-time on a standard PC, it is well suited to be used as a Web-Based application.

Carbohydrate Conformation↗