搜索结果：Therapeutic advances in musculoskeletal disease

Effective public health decisions require early reliable inference of infectious disease properties. In this paper we assess the ability to infer infectious disease attributes from population-level stochastic epidemic trajectories. In particular, we construct stochastic Kermack-McKendrick model trajectories, sample them with and without observational error, and evaluate inversions for the population mean infectiousness as a function of time since infection, the infection duration distribution, and its complementary cumulative distribution, the infection survival distribution. Based on an integro-differential equation formulation we employ a natural regression approach to fit the corresponding integral kernels and show that these disease attributes are recoverable from both multi-trajectory inversions and regularized single trajectory inversions. Moreover, we demonstrate that the infection duration distribution (or alternatively the infection survival distribution) and population mean infectiousness kernel recovered can be used to solve for the individual infectiousness profile, the infectiousness of an individual over the duration of their infection, assuming that individual infect

The use of nanoparticles for targeted drug delivery, especially in diseased arteries, is a novel procedure. We are incorporating nanoparticles into blood vessels using a catheter, which could potentially deliver drugs precisely to affected areas, reducing side effects and increasing treatment efficiency. Considering non-Newtonian fluid modeling because blood is a complex fluid with non-linear behavior. In this paper, we are using mathematical modeling to understand blood flow dynamics, temperature, and concentration dispersion, which can provide valuable insights into the behavior of therapeutic nanoparticles in the bloodstream. The perturbation method is used to solve the complex mathematical model with permeable flow boundary conditions. We are investigating flow field characteristics including wall shear stress, pressure, and impedance to understand how nanoparticles disperse and interact with different physiological aspects. In conclusion, the proposed study focuses on the use of nanotechnology and mathematical modeling to understand the effects of therapeutic nanoparticles in diseased arteries, which is an important and valuable contribution to the medical field.

The human foot serves as the critical interface between the body and environment during locomotion. Existing musculoskeletal models typically oversimplify foot-ground contact mechanics, limiting their ability to accurately simulate human gait dynamics. We developed a novel contact-rich and deformable model of the human foot integrated within a complete musculoskeletal system that captures the complex biomechanical interactions during walking. To overcome the control challenges inherent in modeling multi-point contacts and deformable material, we developed a two-stage policy training strategy to learn natural walking patterns for this interface-enhanced model. Comparative analysis between our approach and conventional rigid musculoskeletal models demonstrated improvements in kinematic, kinetic, and gait stability metrics. Validation against human subject data confirmed that our simulation closely reproduced real-world biomechanical measurements. This work advances contact-rich interface modeling for human musculoskeletal systems and establishes a robust framework that can be extended to humanoid robotics applications requiring precise foot-ground interaction control.

Due to the aging of the world population and westernization of lifestyles, the prevalence of neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD) is rapidly rising and is expected to put a strong socioeconomic burden on health systems worldwide. Due to the limited success of clinical trials of therapies against neurodegenerative diseases, research has extended its scope to a systems medicine point of view, with a particular focus on the gastrointestinal-brain axis as a potential main actor in disease development and progression. Microbiome as well as metabolome studies along the gastrointestinal-brain axis have already revealed important insights into disease pathomechanisms. Both the microbiome and metabolome can be easily manipulated by dietary and lifestyle interventions, and might thus offer novel, readily available therapeutic options to prevent the onset as well as the progression of PD and AD. This review summarizes our current knowledge on the association between microbiota, metabolites, and neurodegeneration in light of the gastrointestinal-brain axis. In this context, we also illustrate state-of-the art methods of microbiome and metabol

Coronary Artery Disease (CAD) remains a leading cause of morbidity and mortality worldwide. Early detection is critical to recover patient outcomes and decrease healthcare costs. In recent years, machine learning (ML) advancements have shown significant potential in enhancing the accuracy of CAD diagnosis. This study investigates the application of ML algorithms to improve the detection of CAD by analyzing patient data, including clinical features, imaging, and biomarker profiles. Bi-directional Long Short-Term Memory (Bi-LSTM), Gated Recurrent Units (GRU), and a hybrid of Bi-LSTM+GRU were trained on large datasets to predict the presence of CAD. Results demonstrated that these ML models outperformed traditional diagnostic methods in sensitivity and specificity, offering a robust tool for clinicians to make more informed decisions. The experimental results show that the hybrid model achieved an accuracy of 97.07%. By integrating advanced data preprocessing techniques and feature selection, this study ensures optimal learning and model performance, setting a benchmark for the application of ML in CAD diagnosis. The integration of ML into CAD detection presents a promising avenue for

Artificial intelligence (AI) has shown promise in detecting and characterizing musculoskeletal diseases from radiographs. However, most existing models remain task-specific, annotation-dependent, and limited in generalizability across diseases and anatomical regions. Although a generalizable foundation model trained on large-scale musculoskeletal radiographs is clinically needed, publicly available datasets remain limited in size and lack sufficient diversity to enable training across a wide range of musculoskeletal conditions and anatomical sites. Here, we present SKELEX, a large-scale foundation model for musculoskeletal radiographs, trained using self-supervised learning on 1.2 million diverse, condition-rich images. The model was evaluated on 12 downstream diagnostic tasks and generally outperformed baselines in fracture detection, osteoarthritis grading, and bone tumor classification. Furthermore, SKELEX demonstrated zero-shot abnormality localization, producing error maps that identified pathologic regions without task-specific training. Building on this capability, we developed an interpretable, region-guided model for predicting bone tumors, which maintained robust performa

Accurate measures of musculoskeletal forces are critical for clinicians, biomechanists, and engineers, yet direct measurement is highly invasive and current estimation methods remain limited in accuracy. Here, we demonstrate the application of ultra-wideband radar to non-invasively estimate musculoskeletal forces by measuring changes in the electromagnetic properties of contracting muscles, in muscles with different structural properties, during various static and dynamic conditions, and in the presence of fatigue. First, we show that ultra-wideband radar scans of muscle can reliably track isometric force in a unipennate knee extensor (vastus lateralis) and a bipennate ankle dorsiflexor (tibialis anterior). Next, we integrate radar signals within machine-learning and linear models to estimate musculoskeletal forces during fatiguing isometric, and dynamic knee extension contractions, with exceptional accuracy (test R2>0.984; errors<3.3%). Finally, we identify frequency-dependent effects of musculoskeletal forces on ultra-wideband radar signals, that are independent of physiological and structural features known to influence muscle force. Together, these findings establish ultr

We seek to identify genes involved in Parkinson's Disease (PD) by combining information across different experiment types. Each experiment, taken individually, may contain too little information to distinguish some important genes from incidental ones. However, when experiments are combined using the proposed statistical framework, additional power emerges. The fundamental building block of the family of statistical models that we propose is a hierarchical three-group mixture of distributions. Each gene is modeled probabilistically as belonging to either a null group that is unassociated with PD, a deleterious group, or a beneficial group. This three-group formalism has two key features. By apportioning prior probability of group assignments with a Dirichlet distribution, the resultant posterior group probabilities automatically account for the multiplicity inherent in analyzing many genes simultaneously. By building models for experimental outcomes conditionally on the group labels, any number of data modalities may be combined in a single coherent probability model, allowing information sharing across experiment types. These two features result in parsimonious inference with few

Musculoskeletal disorders (MSDs) are a leading cause of disability worldwide, requiring advanced diagnostic and therapeutic tools for personalised assessment and treatment. Effective management of MSDs involves the interaction of heterogeneous data sources, making the Digital Twin (DT) paradigm a valuable option. This paper introduces the Musculoskeletal Digital Twin (MS-DT), a novel framework that integrates multiscale biomechanical data with computational modelling to create a detailed, patient-specific representation of the musculoskeletal system. By combining motion capture, ultrasound imaging, electromyography, and medical imaging, the MS-DT enables the analysis of spinal kinematics, posture, and muscle function. An interactive visualisation platform provides clinicians and researchers with an intuitive interface for exploring biomechanical parameters and tracking patient-specific changes. Results demonstrate the effectiveness of MS-DT in extracting precise kinematic and dynamic tissue features, offering a comprehensive tool for monitoring spine biomechanics and rehabilitation. This framework provides high-fidelity modelling and real-time visualization to improve patient-speci

Disease Intelligence (DI) is based on the acquisition and aggregation of fragmented knowledge of diseases at multiple sources all over the world to provide valuable information to doctors, researchers and information seeking community. Some diseases have their own characteristics changed rapidly at different places of the world and are reported on documents as unrelated and heterogeneous information which may be going unnoticed and may not be quickly available. This research presents an Ontology based theoretical framework in the context of medical intelligence and country/region. Ontology is designed for storing information about rapidly spreading and changing diseases with incorporating existing disease taxonomies to genetic information of both humans and infectious organisms. It further maps disease symptoms to diseases and drug effects to disease symptoms. The machine understandable disease ontology represented as a website thus allows the drug effects to be evaluated on disease symptoms and exposes genetic involvements in the human diseases. Infectious agents which have no known place in an existing classification but have data on genetics would still be identified as organism

Most of the existing disease prediction methods in the field of medical image processing fall into two classes, namely image-to-category predictions and image-to-parameter predictions. Few works have focused on image-to-image predictions. Different from multi-horizon predictions in other fields, ophthalmologists prefer to show more confidence in single-horizon predictions due to the low tolerance of predictive risk. We propose a single-horizon disease evolution network (SHENet) to predictively generate post-therapeutic SD-OCT images by inputting pre-therapeutic SD-OCT images with neovascular age-related macular degeneration (nAMD). In SHENet, a feature encoder converts the input SD-OCT images to deep features, then a graph evolution module predicts the process of disease evolution in high-dimensional latent space and outputs the predicted deep features, and lastly, feature decoder recovers the predicted deep features to SD-OCT images. We further propose an evolution reinforcement module to ensure the effectiveness of disease evolution learning and obtain realistic SD-OCT images by adversarial training. SHENet is validated on 383 SD-OCT cubes of 22 nAMD patients based on three well-

INTRODUCTION: Alzheimer's disease (AD) is genetically complex, complicating robust classification from genomic data. METHODS: We developed a transformer-based ensemble model (TrUE-Net) using Monte Carlo Dropout for uncertainty estimation in AD classification from whole-genome sequencing (WGS). We combined a transformer that preserves single-nucleotide polymorphism (SNP) sequence structure with a concurrent random forest using flattened genotypes. An uncertainty threshold separated samples into an uncertain (high-variance) group and a more certain (low-variance) group. RESULTS: We analyzed 1050 individuals, holding out half for testing. Overall accuracy and area under the receiver operating characteristic (ROC) curve (AUC) were 0.6514 and 0.6636, respectively. Excluding the uncertain group improved accuracy from 0.6263 to 0.7287 (10.24% increase) and F1 from 0.5843 to 0.8205 (23.62% increase). DISCUSSION: Monte Carlo Dropout-driven uncertainty helps identify ambiguous cases that may require further clinical evaluation, thus improving reliability in AD genomic classification.

Identifying objective neuroimaging biomarkers to forecast Alzheimer's disease (AD) progression is crucial for timely intervention. However, this task remains challenging due to the complex dysfunctions in the spatio-temporal characteristics of underlying brain networks, which are often overlooked by existing methods. To address these limitations, we develop an interpretable spatio-temporal graph neural network framework to predict future AD progression, leveraging dual Stochastic Differential Equations (SDEs) to model the irregularly-sampled longitudinal functional magnetic resonance imaging (fMRI) data. We validate our approach on two independent cohorts, including the Open Access Series of Imaging Studies (OASIS-3) and the Alzheimer's Disease Neuroimaging Initiative (ADNI). Our framework effectively learns sparse regional and connective importance probabilities, enabling the identification of key brain circuit abnormalities associated with disease progression. Notably, we detect the parahippocampal cortex, prefrontal cortex, and parietal lobule as salient regions, with significant disruptions in the ventral attention, dorsal attention, and default mode networks. These abnormaliti

Parkinson's disease (PD) is the second most common neurodegenerative disorder worldwide, yet there is no disease-modifying therapy up to this date. The biological complexity underlying PD hampers the investigation of the principal contributors to its pathogenesis. In this context, mechanistic models grounded in molecular-level knowledge provide virtual labs to uncover the primary events triggering PD onset and progression and suggest promising therapeutic targets. Multiple modeling efforts in PD research have focused on the pathological role of $α$-synuclein ($α$syn), a presynaptic protein that emerges from the intricate molecular network as a crucial driver of neurodegeneration. Here, we collect the advances in mathematical modeling of $α$syn homeostasis, focusing on aggregation and degradation pathways, and discussing potential modeling improvements and possible implications in PD therapeutic strategy design.

Plant diseases pose a significant threat to agricultural productivity and global food security, accounting for 70-80% of crop losses worldwide. Traditional detection methods rely heavily on expert visual inspection, which is time-consuming, labour-intensive, and often impractical for large-scale farming operations. In this paper, we present PlantDiseaseNet-RT50, a novel fine-tuned deep learning architecture based on ResNet50 for automated plant disease detection. Our model features strategically unfrozen layers, a custom classification head with regularization mechanisms, and dynamic learning rate scheduling through cosine decay. Using a comprehensive dataset of distinct plant disease categories across multiple crop species, PlantDiseaseNet-RT50 achieves exceptional performance with approximately 98% accuracy, precision, and recall. Our architectural modifications and optimization protocol demonstrate how targeted fine-tuning can transform a standard pretrained model into a specialized agricultural diagnostic tool. We provide a detailed account of our methodology, including the systematic unfreezing of terminal layers, implementation of batch normalization and dropout regularizatio

Identifying conditions that a certain drug takes therapeutic effect on a target disease is crucial for clinical decision-making support. However, most existing biomedical information extraction methods have focused on identifying only relations between drugs and diseases, while largely overlooking the context-specific conditions where such relations can apply. To address this problem, we introduce the task of applicability condition extraction for therapeutic drug-disease relations from biomedical research literature. We create the first dataset that has manually annotated triples of drugs, diseases, and applicability conditions on biomedical paper abstracts with 1,119 drug-disease pairs. Using this dataset, we systematically evaluate the performance of a range of existing methods. In addition, we propose a new method that enhances LoRA to consider relations between drugs and diseases. Our method consistently outperforms strong baselines across different evaluation settings.

The ability to predict the future trajectory of a patient is a key step toward the development of therapeutics for complex diseases such as Alzheimer's disease (AD). However, most machine learning approaches developed for prediction of disease progression are either single-task or single-modality models, which can not be directly adopted to our setting involving multi-task learning with high dimensional images. Moreover, most of those approaches are trained on a single dataset (i.e. cohort), which can not be generalized to other cohorts. We propose a novel multimodal multi-task deep learning model to predict AD progression by analyzing longitudinal clinical and neuroimaging data from multiple cohorts. Our proposed model integrates high dimensional MRI features from a 3D convolutional neural network with other data modalities, including clinical and demographic information, to predict the future trajectory of patients. Our model employs an adversarial loss to alleviate the study-specific imaging bias, in particular the inter-study domain shifts. In addition, a Sharpness-Aware Minimization (SAM) optimization technique is applied to further improve model generalization. The proposed m

Ultrasound Tomography (UT) is a radiation-free, high-resolution modality, but remains limited for musculoskeletal imaging due to the high computational cost and instability of full-waveform inversion in strongly scattering media. We propose a generative neural physics framework that couples generative networks with physics-informed neural simulation for fast, high-fidelity 3D UT. By learning a compact surrogate of ultrasonic wave propagation from a limited set of cross-modality images, our method merges the accuracy of wave modeling with the efficiency and stability of deep learning. This enables accurate quantitative imaging of in vivo musculoskeletal tissues, producing spatial maps of acoustic properties beyond reflection-mode images. On synthetic and in vivo data of breasts, arms, and legs, we reconstruct 3D maps of tissue parameters in under ten minutes, with sensitivity to acoustic variations in musculoskeletal tissues and resolution comparable to MRI. By overcoming computational bottlenecks in strongly scattering regimes, this approach demonstrates the feasibility of quantitative UT for musculoskeletal imaging and advances its development toward future routine clinical use.

Estimating brain age (BA) from T1-weighted magnetic resonance images (MRIs) provides a powerful framework for quantifying anatomical brain aging. Whereas global BA (GBA) summarizes overall brain health, local BA (LBA) provides cortically specific patterns of aging at the subject level. Although previous studies have examined anatomical contributors to GBA, to our knowledge, no framework has been established to estimate LBA using cortical morphology. To address this gap, we introduce a graph neural network (GNN) that uses morphometric features$\unicode{x2013}$cortical thickness, surface area, curvature, gray/white matter intensity ratio (GWR), sulcal depth$\unicode{x2013}$to estimate LBA across the cortical surface at high spatial resolution (mean inter-vertex distance = 1.37 mm). Trained on cortical surface meshes extracted from the MRIs of cognitively normal (CN) adults (N = 14,423), our model achieves lower mean absolute error (MAE) than the existing state-of-the-art while identifying more biologically plausible patterns of aging in Alzheimer's disease (AD) on the ADNI dataset. Association cortices emerge as primary sites of morphometric aging in CNs, whereas mild cognitive impai