Medical image retrieval is a valuable field for supporting clinical decision-making, yet current methods primarily support 2D images and require fully annotated queries, limiting clinical flexibility. To address this, we propose RadiomicsRetrieval, a 3D content-based retrieval framework bridging handcrafted radiomics descriptors with deep learning-based embeddings at the tumor level. Unlike existing 2D approaches, RadiomicsRetrieval fully exploits volumetric data to leverage richer spatial context in medical images. We employ a promptable segmentation model (e.g., SAM) to derive tumor-specific image embeddings, which are aligned with radiomics features extracted from the same tumor via contrastive learning. These representations are further enriched by anatomical positional embedding (APE). As a result, RadiomicsRetrieval enables flexible querying based on shape, location, or partial feature sets. Extensive experiments on both lung CT and brain MRI public datasets demonstrate that radiomics features significantly enhance retrieval specificity, while APE provides global anatomical context essential for location-based searches. Notably, our framework requires only minimal user prompts (e.g., a single point), minimizing segmentation overhead and supporting diverse clinical scenarios. The capability to query using either image embeddings or selected radiomics attributes highlights its adaptability, potentially benefiting diagnosis, treatment planning, and research on large-scale medical imaging repositories. Our code is available at https://github.com/nainye/RadiomicsRetrieval.
Providing effective treatment and making informed clinical decisions are essential goals of modern medicine and clinical care. We are interested in simulating disease dynamics for clinical decision-making, leveraging recent advances in large generative models. To this end, we introduce the Medical World Model (MeWM), the first world model in medicine that visually predicts future disease states based on clinical decisions. MeWM comprises (i) vision-language models to serve as policy models, and (ii) tumor generative models as dynamics models. The policy model generates action plans, such as clinical treatments, while the dynamics model simulates tumor progression or regression under given treatment conditions. Building on this, we propose the inverse dynamics model that applies survival analysis to the simulated post-treatment tumor, enabling the evaluation of treatment efficacy and the selection of the optimal clinical action plan. As a result, the proposed MeWM simulates disease dynamics by synthesizing post-treatment tumors, with state-of-the-art specificity in Turing tests evaluated by radiologists. Simultaneously, its inverse dynamics model outperforms medical-specialized GPTs in optimizing individualized treatment protocols across all metrics. Notably, MeWM improves clinical decision-making for interventional physicians, boosting F1-score in selecting the optimal TACE protocol by 13%, paving the way for future integration of medical world models as the second readers.
In recent years, quantum machine learning has emerged as a promising intersection between quantum physics and artificial intelligence, particularly in domains requiring advanced pattern recognition such as healthcare. This study investigates the effectiveness of Quantum Support Vector Machines (QSVM), which leverage quantum mechanical phenomena like superposition and entanglement to construct high-dimensional Hilbert spaces for data classification. Focusing on lung cancer diagnosis, a concrete and critical healthcare application, we analyze how different quantum feature maps influence classification performance. Using a real-world dataset of 309 patient records with significant class imbalance (39 non-cancer vs. 270 cancer cases), we constructed six balanced subsets for robust evaluation. QSVM models were implemented using Qiskit and executed on the qasm simulator, employing three distinct quantum feature maps: ZFeatureMap, ZZFeatureMap, and PauliFeatureMap. Performance was assessed using accuracy, precision, recall, specificity, and F1-score. Results show that the PauliFeatureMap consistently outperformed the others, achieving perfect classification in three subsets and strong performance overall. These findings demonstrate how quantum computational principles can be harnessed to enhance diagnostic capabilities, reinforcing the importance of physics-based modeling in emerging AI applications within healthcare.
Surgical risk identification is critical for patient safety and reducing preventable medical errors. While multimodal large language models (MLLMs) show promise for automated operating room (OR) risk detection, they often exhibit visual-semantic knowledge conflicts (VS-KC), failing to identify visual safety violations despite understanding textual rules. To address this, we introduce a dataset comprising over 34,000 synthetic images generated by diffusion models, depicting operating room scenes containing entities that violate established safety rules. These images were created to alleviate data scarcity and examine MLLMs vulnerabilities. In addition, the dataset includes 214 human-annotated images that serve as a gold-standard reference for validation. This comprehensive dataset, spanning diverse perspectives, stages, and configurations, is designed to expose and study VS-KC. Fine-tuning on OR-VSKC significantly improves MLLMs' detection of trained conflict entities and generalizes well to new viewpoints for these entities, but performance on untrained entity types remains poor, highlighting learning specificity and the need for comprehensive training. The main contributions of this work include: (1) a data generation methodology tailored for rule-violation scenarios; (2) the release of the OR-VSKC dataset and its associated benchmark as open-source resources; and (3) an empirical analysis of violation-sensitive knowledge consistency in representative MLLMs. The dataset and appendix are available at https://github.com/zgg2577/VS-KC.
The Context-Content Uncertainty Principle (CCUP) proposes that inference under uncertainty is governed by an entropy asymmetry between context and content: high-entropy contexts must be interpreted through alignment with low-entropy, structured content. In this paper, we develop a layered computational framework that derives operational principles from this foundational asymmetry. At the base level, CCUP formalizes inference as directional entropy minimization, establishing a variational gradient that favors content-first structuring. Building upon this, we identify four hierarchical layers of operational principles: (\textbf{L1}) \emph{Core Inference Constraints}, including structure-before-specificity, asymmetric inference flow, cycle-consistent bootstrapping, and conditional compression, all shown to be mutually reducible; (\textbf{L2}) \emph{Resource Allocation Principles}, such as precision-weighted attention, asymmetric learning rates, and attractor-based memory encoding; (\textbf{L3}) \emph{Temporal Bootstrapping Dynamics}, which organize learning over time via structure-guided curricula; and (\textbf{L4}) \emph{Spatial Hierarchical Composition}, which integrates these mechanisms into self-organizing cycles of memory, inference, and planning. We present formal equivalence theorems, a dependency lattice among principles, and computational simulations demonstrating the efficiency gains of CCUP-aligned inference. This work provides a unified theoretical foundation for understanding how brains and machines minimize uncertainty through recursive structure-specificity alignment. The brain is not just an inference machine. It is a cycle-consistent entropy gradient resolver, aligning structure and specificity via path-dependent, content-seeded simulation.
3D characters play a crucial role in our daily entertainment. To improve the efficiency of 3D character modeling, recent image-based methods use two separate models to achieve pose standardization and 3D reconstruction of the A-pose character. However, these methods are prone to generating distorted and degraded images in the pose standardization stage due to self-occlusion and viewpoints, which further affects the geometric quality of the subsequent reconstruction process. To tackle these problems, we propose PoseMaster, an end-to-end controllable 3D character generation framework. Specifically, we unify pose transformation and 3D character generation into a flow-based 3D native generation framework. To achieve accurate arbitrary-pose control, we propose to leverage the 3D body bones existing in the skeleton of an animatable character as the pose condition. Furthermore, considering the specificity of multi-condition control, we randomly empty the pose condition and the image condition during training to improve the effectiveness and generalizability of pose control. Finally, we create a high-quality pose-control dataset derived from realistic character animation data to make the model learning the implicit relationships between skeleton and skinning weights. Extensive experiments show that PoseMaster outperforms current state-of-the-art techniques in both qualitative and quantitative evaluations for A-pose character generation while demonstrating its powerful ability to achieve precise control for arbitrary poses.
Objective: Computational phenotyping is a central informatics activity with resulting cohorts supporting a wide variety of applications. However, it is time-intensive because of manual data review, limited automation, and difficulties in adapting algorithms across sources. Since LLMs have demonstrated promising capabilities for text classification, comprehension, and generation, we posit they will perform well at repetitive manual review tasks traditionally performed by human experts. To support next-generation computational phenotyping methods, we developed SHREC, a framework for comprehensive integration of LLMs into end-to-end phenotyping pipelines. Materials and Methods: We applied and tested the ability of three lightweight LLMs (Gemma2 27 billion, Mistral Small 24 billion, and Phi-4 14 billion) to classify concepts and phenotype patients using previously developed phenotypes for ARF respiratory support therapies. Results: All models performed well on concept classification, with the best model (Mistral) achieving an AUROC of 0.896 across all relevant concepts. For phenotyping, models demonstrated near-perfect specificity for all phenotypes, and the top-performing model (Mistral) reached an average AUROC of 0.853 for single-therapy phenotypes, despite lower performance on multi-therapy phenotypes. Discussion: There are several advantages of LLMs that support their application to computational phenotyping, such as their ability to adapt to new tasks with prompt engineering alone and their ability to incorporate raw EHR data. Future steps to advance next-generation phenotyping methods include determining optimal strategies for integrating biomedical data, exploring how LLMs reason, and advancing generative model methods. Conclusion: Current lightweight LLMs can feasibly assist researchers with resource-intensive phenotyping tasks such as manual data review.
Background. Chronic pain afflicts 20 % of the global population. A strictly biomedical mind-set leaves many sufferers chasing somatic cures and has fuelled the opioid crisis. The biopsychosocial model recognises pain subjective, multifactorial nature, yet uptake of psychosocial care remains low. We hypothesised that patients own pain narratives would predict their readiness to engage in psychotherapy. Methods. In a cross-sectional pilot, 24 chronic-pain patients recorded narrated pain stories on Painstory.science. Open questions probed perceived pain source, interference and influencing factors. Narratives were cleaned, embedded with a pretrained large-language model and entered into machine-learning classifiers that output ready/not ready probabilities. Results. The perception-domain model achieved 95.7 % accuracy (specificity = 0.80, sensitivity = 1.00, AUC = 0.90). The factors-influencing-pain model yielded 83.3 % accuracy (specificity = 0.60, sensitivity = 0.90, AUC = 0.75). Sentence count correlated with readiness for perception narratives (r = 0.54, p < .01) and factor narratives (r = 0.24, p < .05). Conclusion. Brief spoken pain narratives carry reliable signals of willingness to start psychosocial treatment. NLP-based screening could help clinicians match chronic-pain patients to appropriate interventions sooner, supporting a patient-centred biopsychosocial pathway.
Understanding and modeling enzyme-substrate interactions is crucial for catalytic mechanism research, enzyme engineering, and metabolic engineering. Although a large number of predictive methods have emerged, they do not incorporate prior knowledge of enzyme catalysis to rationally modulate general protein-molecule features that are misaligned with catalytic patterns. To address this issue, we introduce a two-stage progressive framework, OmniESI, for enzyme-substrate interaction prediction through conditional deep learning. By decomposing the modeling of enzyme-substrate interactions into a two-stage progressive process, OmniESI incorporates two conditional networks that respectively emphasize enzymatic reaction specificity and crucial catalysis-related interactions, facilitating a gradual feature modulation in the latent space from general protein-molecule domain to catalysis-aware domain. On top of this unified architecture, OmniESI can adapt to a variety of downstream tasks, including enzyme kinetic parameter prediction, enzyme-substrate pairing prediction, enzyme mutational effect prediction, and enzymatic active site annotation. Under the multi-perspective performance evaluation of in-distribution and out-of-distribution settings, OmniESI consistently delivered superior performance than state-of-the-art specialized methods across seven benchmarks. More importantly, the proposed conditional networks were shown to internalize the fundamental patterns of catalytic efficiency while significantly improving prediction performance, with only negligible parameter increases (0.16%), as demonstrated by ablation studies on key components. Overall, OmniESI represents a unified predictive approach for enzyme-substrate interactions, providing an effective tool for catalytic mechanism cracking and enzyme engineering with strong generalization and broad applicability.
Retinal fundus images provide valuable insights into the human eye's interior structure and crucial features, such as blood vessels, optic disk, macula, and fovea. However, accurate segmentation of retinal blood vessels can be challenging due to imbalanced data distribution and varying vessel thickness. In this paper, we propose BLCB-CNN, a novel pipeline based on deep learning and bi-level class balancing scheme to achieve vessel segmentation in retinal fundus images. The BLCB-CNN scheme uses a Convolutional Neural Network (CNN) architecture and an empirical approach to balance the distribution of pixels across vessel and non-vessel classes and within thin and thick vessels. Level-I is used for vessel/non-vessel balancing and Level-II is used for thick/thin vessel balancing. Additionally, pre-processing of the input retinal fundus image is performed by Global Contrast Normalization (GCN), Contrast Limited Adaptive Histogram Equalization (CLAHE), and gamma corrections to increase intensity uniformity as well as to enhance the contrast between vessels and background pixels. The resulting balanced dataset is used for classification-based segmentation of the retinal vascular tree. We evaluate the proposed scheme on standard retinal fundus images and achieve superior performance measures, including an area under the ROC curve of 98.23%, Accuracy of 96.22%, Sensitivity of 81.57%, and Specificity of 97.65%. We also demonstrate the method's efficacy through external cross-validation on STARE images, confirming its generalization ability.
The overexpression of the human epidermal growth factor receptor 2 (HER2) in breast cells is a key driver of HER2-positive breast cancer, a highly aggressive subtype requiring precise diagnosis and targeted therapy. Immunohistochemistry (IHC) is the standard technique for HER2 assessment but is costly, labor-intensive, and highly dependent on antibody selection. In contrast, hematoxylin and eosin (H&E) staining, a routine histopathological procedure, offers broader accessibility but lacks HER2 specificity. This study proposes an advanced deep learning-based image translation framework to generate highfidelity IHC images from H&E-stained tissue samples, enabling cost-effective and scalable HER2 assessment. By modifying the loss function of pyramid pix2pix, we mitigate mode collapse, a fundamental limitation in generative adversarial networks (GANs), and introduce a novel variance-based penalty that enforces structural diversity in generated images. Our model particularly excels in translating HER2-positive (IHC 3+) images, which have remained challenging for existing methods due to their complex morphological variations. Extensive evaluations on the BCI histopathological dataset demonstrate that our model surpasses state-of-the-art methods in terms of peak signal-tonoise ratio (PSNR), structural similarity index (SSIM), and Frechet Inception Distance (FID), particularly in accurately translating HER2-positive (IHC 3+) images. Beyond medical imaging, our model exhibits superior performance in general image-to-image translation tasks, showcasing its potential across multiple domains. This work marks a significant step toward AI-driven precision oncology, offering a reliable and efficient alternative to traditional HER2 diagnostics.
Aimed to develop and validate a CT radiomics-based explainable machine learning model for diagnosing malignancy and benignity specifically in endometrial cancer (EC) patients. A total of 83 EC patients from two centers, including 46 with malignant and 37 with benign conditions, were included, with data split into a training set (n=59) and a testing set (n=24). The regions of interest (ROIs) were manually segmented from pre-surgical CT scans, and 1132 radiomic features were extracted from the pre-surgical CT scans using Pyradiomics. Six explainable machine learning modeling algorithms were implemented respectively, for determining the optimal radiomics pipeline. The diagnostic performance of the radiomic model was evaluated by using sensitivity, specificity, accuracy, precision, F1 score, confusion matrices, and ROC curves. To enhance clinical understanding and usability, we separately implemented SHAP analysis and feature mapping visualization, and evaluated the calibration curve and decision curve. By comparing six modeling strategies, the Random Forest model emerged as the optimal choice for diagnosing EC, with a training AUC of 1.00 and a testing AUC of 0.96. SHAP identified the most important radiomic features, revealing that all selected features were significantly associated with EC (P < 0.05). Radiomics feature maps also provide a feasible assessment tool for clinical applications. DCA indicated a higher net benefit for our model compared to the "All" and "None" strategies, suggesting its clinical utility in identifying high-risk cases and reducing unnecessary interventions. In conclusion, the CT radiomics-based explainable machine learning model achieved high diagnostic performance, which could be used as an intelligent auxiliary tool for the diagnosis of endometrial cancer.
Positron emission tomography (PET) is widely used to assess metabolic activity, but its application is limited by the availability of radiotracers. 18F-labeled fluorodeoxyglucose (18F-FDG) is the most commonly used tracer but shows limited effectiveness for certain tumors. In contrast, 6-18F-fluoro-3,4-dihydroxy-L-phenylalanine (18F-DOPA) offers higher specificity for neuroendocrine tumors and neurological disorders. However, the complexity of its synthesis process and constraints on transportation time have limited its clinical application. Among different forms of raw data acquired by the scanner, sinogram is a commonly used representation in PET imaging. Therefore, modeling in projection domain enables more direct utilization of the original information, potentially reducing the accumulation errors during the image reconstruction process. Inspired by these factors, this study proposes a prior-guided joint diffusion model (PJDM) for transforming 18F-FDG PET sinograms into 18F-DOPA PET sinograms. During inference, an initial synthetic 18F-DOPA PET sinogram is first generated using a higher-order hybrid sampler. This sinogram is then degraded and serves as an additional condition to guide the iterative refinement process. Experimental results demonstrated that PJDM effectively improved both sinogram quality and the final synthetic outcomes. The code is available at: https://github.com/yqx7150/PJDM.
Elucidating the biomechanical behavior of the myocardium is crucial for understanding cardiac physiology, but cannot be directly inferred from clinical imaging and typically requires finite element (FE) simulations. However, conventional FE methods are computationally expensive and often fail to reproduce observed cardiac motions. We propose IMC-PINN-FE, a physics-informed neural network (PINN) framework that integrates imaged motion consistency (IMC) with FE modeling for patient-specific left ventricular (LV) biomechanics. Cardiac motion is first estimated from MRI or echocardiography using either a pre-trained attention-based network or an unsupervised cyclic-regularized network, followed by extraction of motion modes. IMC-PINN-FE then rapidly estimates myocardial stiffness and active tension by fitting clinical pressure measurements, accelerating computation from hours to seconds compared to traditional inverse FE. Based on these parameters, it performs FE modeling across the cardiac cycle at 75x speedup. Through motion constraints, it matches imaged displacements more accurately, improving average Dice from 0.849 to 0.927, while preserving realistic pressure-volume behavior. IMC-PINN-FE advances previous PINN-FE models by introducing back-computation of material properties and better motion fidelity. Using motion from a single subject to reconstruct shape modes also avoids the need for large datasets and improves patient specificity. IMC-PINN-FE offers a robust and efficient approach for rapid, personalized, and image-consistent cardiac biomechanical modeling.
The function and dynamics of the cortex are fundamentally shaped by the specific wiring configurations of its constituent axonal fibers, also known as the connectome. However, many dynamical properties of macroscale cortical activity are well captured by instead describing the activity as propagating waves across the cortical surface, constrained only by the surface's two-dimensional geometry. It thus remains an open question why the local geometry of the cortex can successfully capture macroscale cortical dynamics, despite neglecting the specificity of Fast-conducting, Non-local Projections (FNPs) which are known to mediate the rapid and non-local propagation of activity between remote neural populations. Here we address this question by developing a novel mathematical model of macroscale cortical activity in which cortical populations interact both by a continuous sheet and by an additional set of FNPs wired independently of the sheet's geometry. By simulating the model across a range of connectome topologies, external inputs, and timescales, we demonstrate that the addition of FNPs strongly shape the model dynamics of rapid, stimulus-evoked responses on fine millisecond timescales ($\lessapprox 30~\text{ms}$), but contribute relatively little to slower, spontaneous fluctuations over longer timescales ($> 30~\text{ms}$), which increasingly resemble geometrically constrained dynamics without FNPs. Our results suggest that the discrepant views regarding the relative contributions of local (geometric) and non-local (connectomic) cortico-cortical interactions are context-dependent: While FNPs specified by the connectome are needed to capture rapid communication between specific distant populations (as per the rapid processing of sensory inputs), they play a relatively minor role in shaping slower spontaneous fluctuations (as per resting-state functional magnetic resonance imaging).
Detecting harmful content is a crucial task in the landscape of NLP applications for Social Good, with hate speech being one of its most dangerous forms. But what do we mean by hate speech, how can we define it, and how does prompting different definitions of hate speech affect model performance? The contribution of this work is twofold. At the theoretical level, we address the ambiguity surrounding hate speech by collecting and analyzing existing definitions from the literature. We organize these definitions into a taxonomy of 14 Conceptual Elements-building blocks that capture different aspects of hate speech definitions, such as references to the target of hate (individual or groups) or of the potential consequences of it. At the experimental level, we employ the collection of definitions in a systematic zero-shot evaluation of three LLMs, on three hate speech datasets representing different types of data (synthetic, human-in-the-loop, and real-world). We find that choosing different definitions, i.e., definitions with a different degree of specificity in terms of encoded elements, impacts model performance, but this effect is not consistent across all architectures.
URL+HTML feature fusion shows promise for robust malicious URL detection, since attacker artifacts persist in DOM structures. However, prior work suffers from four critical shortcomings: (1) incomplete URL modeling, failing to jointly capture lexical patterns and semantic context; (2) HTML graph sparsity, where threat-indicative nodes (e.g., obfuscated scripts) are isolated amid benign content, causing signal dilution during graph aggregation; (3) unidirectional analysis, ignoring URL-HTML feature bidirectional interaction; and (4) opaque decisions, lacking attribution to malicious DOM components. To address these challenges, we present WebGuard++, a detection framework with 4 novel components: 1) Cross-scale URL Encoder: Hierarchically learns local-to-global and coarse to fine URL features based on Transformer network with dynamic convolution. 2) Subgraph-aware HTML Encoder: Decomposes DOM graphs into interpretable substructures, amplifying sparse threat signals via Hierarchical feature fusion. 3) Bidirectional Coupling Module: Aligns URL and HTML embeddings through cross-modal contrastive learning, optimizing inter-modal consistency and intra-modal specificity. 4) Voting Module: Localizes malicious regions through consensus voting on malicious subgraph predictions. Experiments show WebGuard++ achieves significant improvements over state-of-the-art baselines, achieving 1.1x-7.9x higher TPR at fixed FPR of 0.001 and 0.0001 across both datasets.
Evaluations of LLMs' ethical risks and value inclinations often rely on short-form surveys and psychometric tests, yet real-world use involves long-form, open-ended responses -- leaving value-related risks and preferences in practical settings largely underexplored. In this work, we ask: Do value preferences inferred from short-form tests align with those expressed in long-form outputs? To address this question, we compare value preferences elicited from short-form reactions and long-form responses, varying the number of arguments in the latter to capture users' differing verbosity preferences. Analyzing five LLMs (llama3-8b, gemma2-9b, mistral-7b, qwen2-7b, and olmo-7b), we find (1) a weak correlation between value preferences inferred from short-form and long-form responses across varying argument counts, and (2) similarly weak correlation between preferences derived from any two distinct long-form generation settings. (3) Alignment yields only modest gains in the consistency of value expression. Further, we examine how long-form generation attributes relate to value preferences, finding that argument specificity negatively correlates with preference strength, while representation across scenarios shows a positive correlation. Our findings underscore the need for more robust methods to ensure consistent value expression across diverse applications.
Label-free imaging has gained broad interest because of its potential to omit elaborate staining procedures which is especially relevant for in vivo use. Label-free multiphoton microscopy (MPM), for instance, exploits two-photon excitation of natural autofluorescence (AF) from native, metabolic proteins, making it ideal for in vivo endomicroscopy. Deep learning (DL) models have been widely used in other optical imaging technologies to predict specific target annotations and thereby digitally augment the specificity of these label-free images. However, this computational specificity has only rarely been implemented for MPM. In this work, we used a data set of label-free MPM images from a series of different immune cell types (5,075 individual cells for binary classification in mixed samples and 3,424 cells for a multi-class classification task) and trained a convolutional neural network (CNN) to classify cell types based on this label-free AF as input. A low-complexity squeezeNet architecture was able to achieve reliable immune cell classification results (0.89 ROC-AUC, 0.95 PR-AUC, for binary classification in mixed samples; 0.689 F1 score, 0.697 precision, 0.748 recall, and 0.683 MCC for six-class classification in isolated samples). Perturbation tests confirmed that the model is not confused by extracellular environment and that both input AF channels (NADH and FAD) are about equally important to the classification. In the future, such predictive DL models could directly detect specific immune cells in unstained images and thus, computationally improve the specificity of label-free MPM which would have great potential for in vivo endomicroscopy.
Language model outputs are not always reliable, thus prompting research into how to adapt model responses based on uncertainty. Common approaches include: \emph{abstention}, where models refrain from generating responses when uncertain; and \emph{linguistic calibration}, where models hedge their statements using uncertainty quantifiers. However, abstention can withhold valuable information, while linguistically calibrated responses are often challenging to leverage in downstream tasks. We propose a unified view, Conformal Linguistic Calibration (CLC), which reinterprets linguistic calibration as \emph{answer set prediction}. First we present a framework connecting abstention and linguistic calibration through the lens of linguistic pragmatics. We then describe an implementation of CLC that allows for controlling the level of imprecision in model responses. Results demonstrate our method produces calibrated outputs with conformal guarantees on factual accuracy. Further, our approach enables fine-tuning models to perform uncertainty-aware adaptive claim rewriting, offering a controllable balance between factuality and specificity.