Visualization of multimode radiation patterns of acoustic transducers by acousto-optic diffraction.
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Acoustics↗
SEARCH · PubMed Health
Results for “multimodal modeling”
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
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Predictive camera tracking for bronchoscope simulation with CONDensation.
This paper exploits the use of temporal information to minimize the ambiguity of camera motion tracking in bronchoscope simulation. The condensation algorithm (Sequential Monte Carlo) has been used to propagate the probability distribution of the state space. For motion prediction, a second-order auto-regressive model has been used to characterize camera motion in a bounded lumen as encountered in bronchoscope examination. The method caters for multimodal probability distributions, and experimental results from both phantom and patient data demonstrate a significant improvement in tracking accuracy especially in cases where there is airway deformation and image artefacts.
Algorithms↗
High angular resolution diffusion imaging reveals intravoxel white matter fiber heterogeneity.
Magnetic resonance (MR) diffusion tensor imaging (DTI) can resolve the white matter fiber orientation within a voxel provided that the fibers are strongly aligned. However, a given voxel may contain a distribution of fiber orientations due to, for example, intravoxel fiber crossing. The present study sought to test whether a geodesic, high b-value diffusion gradient sampling scheme could resolve multiple fiber orientations within a single voxel. In regions of fiber crossing the diffusion signal exhibited multiple local maxima/minima as a function of diffusion gradient orientation, indicating the presence of multiple intravoxel fiber orientations. The multimodality of the observed diffusion signal precluded the standard tensor reconstruction, so instead the diffusion signal was modeled as arising from a discrete mixture of Gaussian diffusion processes in slow exchange, and the underlying mixture of tensors was solved for using a gradient descent scheme. The multitensor reconstruction resolved multiple intravoxel fiber populations corresponding to known fiber anatomy. Ma
Anisotropy↗
Chiral separations of polar compounds by hydrophilic interaction chromatography with evaporative light scattering detection.
The chiral separations of drug substances and underivatized amino acids were demonstrated in this study through the use of hydrophilic interaction chromatography (HILIC). The polar character of the model compounds presented challenges for their analysis by traditional modes of chromatography, but through the employment of multimodal chromatography utilizing the HILIC mechanism and cyclodextrin- or teicoplanin-derivatized stationary phases, effective resolution was achieved. The analytes lacked sufficient ultraviolet chromophores, requiring their determination by evaporative light scattering detection. HILIC was demonstrated to represent a novel technique for the facilitation of chiral chromatography by providing an environment of solubility and retention that could not be achieved through the use of the traditional methods of reversed-phase, normal-phase, or polar organic mode.
Anti-Bacterial Agents↗
Distributional expectations and the induction of category structure.
Previous research on how categories are learned from observation of exemplars has largely ignored the possible role of prior expectations concerning how exemplars will be distributed. The experiments reported here explored this issue by presenting subjects with category-learning tasks in which the distributions of exemplars defining the categories were varied. In Experiments 1 and 2 the distributional form of a category was found to affect speed of learning. Learning was faster when a category's distribution was normal than when it was multimodal. Also, subjects in the early stages of learning a multimodal category responded as if it were unimodal. These results suggested that subjects enter category-learning tasks with expectations of unimodal, possibly normal, distributions of exemplars. Experiments 3 and 4 attempted to manipulate subjects' prior expectations by varying the distribution of exemplars in the first of two consecutive category-learning tasks. Learning a multimodal category was influenced by the shape of a previously learned distribution and was facilitated when the earlier distribution was either multimodal or skewed, rather than normal. These results are interpreted as support for a dual-process model of category learning that incorporates the effects of prior expectations concerning exemplar distributions.
Adolescent↗
Surgical treatment of thymic tumors.
Thymoma is a rare neoplasm usually with an indolent growth pattern; however, local invasion and/or metastases may occur. The association with several paraneoplastic syndromes, especially myasthenia gravis, makes thymoma an interesting biologic tumor model. Surgery has been the standard of care for early stage disease with high cure rates anticipated. Multimodality therapy can result in long-term disease-free survival for patients presenting with locally advanced disease.
Disease-Free Survival↗
Replicative oncolytic adenoviruses in multimodal cancer regimens.
The use of replication-competent viruses that have a cytolytic cycle has emerged as a viable strategy (oncolytic virotherapy) to specifically kill tumor cells and the field has advanced to the point of clinical trials. A theoretical advantage of replicative oncolytic viruses is that their numbers should increase via viral replication within infected tumor cells and resulting viral progeny can then infect additional cells within the tumor mass. The life cycle of a virus involves multiple interactions between viral and cellular proteins/genes, which maximize the ability of the virus to infect and replicate within cells. Understanding such interactions has led to the design of numerous genetically engineered adenovirus (Ad) vectors that selectively kill tumor cells while sparing normal cells. These viruses have also been modified to function as therapeutic gene delivery vehicles, thus augmenting their anticancer capacity. In addition, the oncolytic mode of tumor killing differs from that of standard anticancer therapies, providing the possibility for synergistic interactions with other therapies in a multimodal antitumor approach. In this review, we describe the oncolytic Ad vectors tested in preclinical and clinical models and their use in combination with chemo-, radio-, and gene therapies.
Adenoviridae↗
Crisis treatment of a preadolescent who accidentally killed his twin.
Justification and effectiveness of a multimodal approach to treating a preadolescent who accidentally killed his twin is presented and recommended as a model for treatment of similarly disturbed children. The interaction of dynamically oriented therapy, pharmacotherapy, conflict-resolution/problem-solving-skills training, biofeedback/desensitization, and family work is detailed.
Accidents↗
Proposal for a new model of breast cancer metastatic development.
BACKGROUND: The commonly accepted theory of breast cancer metastatic development assumes continuous tumor growth from tumor seeding until documentation of clinical recurrence. In particular, Gompertzian growth kinetics is currently the theoretical cornerstone of the natural history of breast cancer, and has been widely utilized for planning treatments. MATERIALS AND METHODS: To verify agreement between findings and the implications of the continuous growth model, several published papers about the natural history of breast cancer after removal of the primary tumor were reviewed. Also, findings from animal models concerning metastasis biology were considered. RESULTS: The continuous growth model failed in important ways upon this critical reappraisal. As an alternative, the tumor dormancy hypothesis was considered to provide a more reasonable description of tumor recurrence. Moreover, primary tumor removal was revealed as a potentially perturbing factor for metastasis development. CONCLUSIONS: A new general outline of metastatic development of breast cancer incorporating tumor dormancy in specific micrometastatic phases, stochastic transitions between them, and start signals from surgery for micrometastatic growth was designed. The proposed model suggests new views concerning scheduling of current chemotherapy, new treatment approaches aimed at keeping micrometastases in a dormant state for the patient's entire life, and the careful reappraisal of the timing of surgery within the multimodal treatment of operable breast cancer.
Breast Neoplasms↗
Next-Generation Disease Profiling by Integrating Histopathology with Spatial Multi-Omics Data.
The field of pathology has experienced several transformative changes in recent years with the advent of digital pathology and spatial multi-omics. These technologies have enhanced every aspect of pathology practice, from streamlining daily workflows to generating high-fidelity multi-omics data that provide pathologists with novel tools to refine disease profiling and clinical diagnosis. Each layer of multimodal data (genomic, metabolomic, proteomic, or transcriptomic) has uncovered a distinct facet of disease pathologies, and combined with machine learning/artificial intelligence-based data analysis and pattern recognition models, has provided holistic understanding of regulatory mechanisms underpinning them. However, high-dimensional data have far exceeded the volume, scale, and complexity of immunostaining methods implemented by pathologists and, thus, have generated significant challenges related to deconvolution, interpretation, and clinical translation. Furthermore, these multimodal studies have predominantly relied on computational methods to process data and extract disease-relevant insights, thus raising questions around relevance or role of a pathologist in this new era of multi-omics. This review will provide a perspective on the evolving fields of molecular histopathology and spatial -omics, leveraging them to approach disease profiling, and redefining the role of a pathologist during this process.
Humans↗
Process-based reactive transport modeling of a permeable reactive barrier for the treatment of mine drainage.
Reactive transport modeling of a permeable reactive barrier for the treatment of mine drainage was used to integrate a comprehensive data set including pore water chemistry and solid phase data from several sampling events over a >3-year time period. The simulations consider the reduction of sulfate by the organic carbon-based treatment material and the removal of sulfate and iron by precipitation of reduced mineral phases including iron monosulfides and siderite. Additional parameters constraining the model include dissolved H2S, alkalinity and pH, as well as a suite of solid phase S-fractions identified by extractions. Influences of spatial heterogeneity necessitated the use of a 2-dimensional modeling approach. Simulating observed seasonal fluctuations and long-term changes in barrier reactivity required the use of temperature dependent rate coefficients and a multimodal Monod-type rate expression accounting for the variable reactivity of different organic carbon fractions. Simulated dissolved concentrations of SO4, Fe, H2S, alkalinity and pH, as well as solid phase accumulations of reduced sulfur phases generally compare well to observed trends over 23 months. Spatial variations, seasonal fluctuations and the time-dependent decline in reactivity were also captured. The modeling results generally confirm, and further strengthen, the existing conceptual model for the site. Overall sulfate reduction and S-accumulation rates are constrained with confidence within a factor of 1.5.
Hydrogen-Ion Concentration↗
A nonlinear mesh-warping technique for correcting brain deformation after stroke.
This article presents a warping technique for correcting brain tissue distortion on magnetic resonance imaging (MRI) scans due to stroke lesion growth and for mapping MRI scans to histological sections. Meshes are imposed upon the images for feature specification, and these features are exactly matched in the different images to be mapped, while the other voxels are matched by interpolation. This technique was tested on serial MR images and histological sections that were acquired in a nonhuman primate model of stroke. This technique was able to deliver satisfactory warping results. It is simple and robust and can be utilized in many applications for comparison of multimodality medical images and histological sections.
Algorithms↗
Combined spectral estimator for phase velocities of multimode Lamb waves in multilayer plates.
A novel combined spectral estimate (CSE) method for differentiation and estimation the phase velocities of multimode Lamb waves whose wave numbers are much close or overlap one another in multiplayer plates is presented in this paper, which based on auto-regressive (AR) model and 2-D FFT. Simulated signals in brass plate were processed by 2-D FFT and CSE. And experiments are performed by using two conventional angle probes as emitter and receiver on the same surface of three-layered aluminum/xpoxy/aluminum plates, which include symmetrical and unsymmetrical plates. The multimode Lamb waves are excited in these laminates, and the received signal is processed by 2-D FFT and CSE, respectively. The results showed that the phase velocities of multimode signals whose wave numbers are much closed cannot be differentiated by 2-D FFT, but CSE has strong spatial resolution. Compared the measured phase velocities with the theoretical values, the error is smaller than 2% on the whole. It promises to be a useful method in experimental signals processing of multimode Lamb waves.
Journal Article↗
Exploring extra-binomial variation in teratology data using continuous mixtures.
Discrete data from animal teratology experiments are known to exhibit extra-binomial variation. For example, we discuss a dominant lethal assay experiment in which male mice are exposed to various levels of radiation and are then mated to females. The response of interest is the number of resorptions out of the number of implantations. Most statistical work on analyzing such data has focused on modeling response rates as a function of dose of a suspected teratogen (radiation in this case) while accounting for the extra-binomial variability when calculating standard errors of the regression coefficients. Sometimes, however, when an unobserved genetic or exposure variable is suspected, the shape of the mixing distribution is of interest. We propose a mixture of beta-binomials (MBB) family of distributions that includes the non-parametric mixture of binomials model of Laird (1978) as a special case. The MBB family can accommodate a mixing distribution with one or more modes, and we develop a bootstrap test for multimodality. We apply the method to data from a dominant lethal teratology experiment.
Animals↗
CRISPR-Enabled functional genomics in hPSCs-derived neural models for autism spectrum disorder.
Autism Spectrum Disorder (ASD) is a genetically heterogeneous neurodevelopmental condition in which hundreds of individually rare risk variants converge on a small number of shared biological pathways, including synaptic scaffolding, chromatin remodeling, excitation-inhibition balance, and cellular energy metabolism. Translating this genetic heterogeneity into mechanistic insight requires experimental systems capable of interrogating individual gene functions in human-relevant neural contexts at scale. CRISPR-enabled functional genomics in human pluripotent stem cell (hPSC)-derived neural models, spanning neural progenitors, cortical and inhibitory neurons, astrocytes, microglia, and brain organoids, provides precisely this capability. By integrating pooled perturbation screens with multimodal readouts including single-cell and spatial transcriptomics, chromatin accessibility profiling, proximity labeling proteomics, multi-electrode array electrophysiology, and metabolic flux analysis, these platforms enable systematic, causal mapping of ASD gene function at system resolution. Early applications have already revealed convergent mechanisms: BAF complex disruption expands the ventral progenitor pool and biases its fate toward oligodendrocyte and interneuron lineages; ADNP loss impairs microglial synaptic pruning through altered endocytic trafficking; and mTOR pathway dysregulation in PTEN- and TSC2-perturbed models links genetic risk directly to metabolic and mitochondrial dysfunction. Computational frameworks including MIMOSCA and SCEPTRE enable causal network reconstruction and pseudotime inference from these datasets, moving the field from gene lists toward pathway-level models of ASD pathobiology. Translational applications leverage isogenic iPSC panels and variant-level base and prime editing to stratify ASD variants by functional impact, informing gene therapy design for haploinsufficient targets such as CHD8 and SCN2A via AAV or antisense oligonucleotide delivery. Remaining challenges, including model developmental immaturity, batch variability, and the difficulty of modeling polygenic risk, are addressed by a roadmap integrating spatial perturbomics, AI-driven causal inference, and population-scale standardized biobanks. This review synthesizes the current state of CRISPR-based functional genomics in human stem cell neural models as a coherent experimental framework for converting ASD genetic associations into mechanistic understanding and therapeutic opportunity.
Humans↗
Multiome Perturb-seq unlocks scalable discovery of integrated perturbation effects on the transcriptome and epigenome.
Single-cell CRISPR screens link genetic perturbations to transcriptional states, but high-throughput methods connecting these induced changes to their regulatory foundations are limited. Here, we introduce Multiome Perturb-seq, extending single-cell CRISPR screens to simultaneously measure perturbation-induced changes in gene expression and chromatin accessibility. We apply Multiome Perturb-seq in a CRISPRi screen of 13 chromatin remodelers in human RPE-1 cells, achieving efficient assignment of sgRNA identities to single nuclei via an improved method for capturing barcode transcripts from nuclear RNA. We organize expression and accessibility measurements into coherent programs describing the integrated effects of perturbations on cell state, finding that ARID1A and SUZ12 knockdowns induce programs enriched for developmental features. Modeling of perturbation-induced heterogeneity connects accessibility changes to changes in gene expression, highlighting the value of multimodal profiling. Overall, our method provides a scalable and simply implemented system to dissect the regulatory logic underpinning cell state. A record of this paper's transparent peer review process is included in the supplemental information.
Humans↗
Filial imprinting in domestic chicks is associated with spine pruning in the associative area, dorsocaudal neostriatum.
Juvenile emotionally modulated learning events are fundamental for the normal development of socio-emotional competence and intellectual capabilities. Filial imprinting in the domestic chick provides a suitable model to investigate the neural mechanisms underlying such juvenile learning events. The forebrain area dorsocaudal neostriatum (Ndc), a multimodal integration area and presumed equivalent to mammalian parietotemporal association cortices, has been shown to be critically involved in this learning process. We investigated whether filial imprinting is associated with changes of synaptic connectivity in the Ndc. Quantitative measurements of spine densities of a large neuron type in the Ndc revealed a massive pruning of spine synapses after filial imprinting. Compared with 7-day-old naive control chicks, imprinted chicks displayed significantly lower spine frequencies on all dendritic segments. Since the average length of the dendritic segments did not change during imprinting, these results can be interpreted as a reduction of the absolute number of spine synapses on this neuron type. In a control region, the primary sensory forebrain area ectostriatum, spine density and dendritic length remained unchanged. These results indicate that synaptic pruning may represent a mechanism of selective synaptic reorganization in higher associative forebrain areas as a fundamental feature of juvenile learning events.
Animals↗
Multidimensional family therapy for adolescent drug abuse: results of a randomized clinical trial.
Random assignment was made of 182 clinically referred marijuana- and alcohol-abusing adolescents to one of three treatments: multidimensional family therapy (MDFT), adolescent group therapy (AGT), and multifamily educational intervention (MEI). Each treatment represented a different theory base and treatment format. All treatments were based on a manual and were delivered on a once-a-week outpatient basis. The therapists were experienced community clinicians trained to model-specific competence prior to the study and then supervised throughout the clinical trial. A theory-based multimodal assessment strategy measured symptom changes and prosocial functioning at intake, termination, and 6 and 12 months following termination. Results indicate improvement among youths in all three treatments, with MDFT showing superior improvement overall. MDFT participants also demonstrated change at the 1-year follow-up period in the important prosocial factors of school/academic performance and family functioning as measured by behavioral ratings. Results support the efficacy of MDFT, a relatively short-term, multicomponent, multitarget, family-based intervention in significantly reducing adolescent drug abuse and facilitating adaptive and protective developmental processes.
Adolescent↗