Internal clustering validity indices (ICVIs) assess clustering quality without ground truth labels. Comparative studies consistently find that no single ICVI outperforms others across datasets, leaving practitioners without principled ICVI selection. We argue that inconsistent ICVI performance arises because studies evaluate them based on matching human labels rather than measuring the quality of the discovered structure in the data, using datasets without formally quantifying the structure type and quality. Structure type refers to the mathematical organisation in data that clustering aims to discover. Validity theory requires a theoretical definition of clustering quality, which depends on structure type. We demonstrate this through the first validity assessment of clustering quality measures for correlation patterns, a structure type that arises from clustering time series by correlation relationships. We formalise 23 canonical correlation patterns as the theoretical optimal clustering and use synthetic data modelling this structure with controlled perturbations to evaluate validity across content, criterion, construct, and external validity. Our findings show that Silhouette Width Criterion (SWC) and Davies-Bouldin Index (DBI) are valid for correlation patterns, whilst Calinski-Harabasz (VRC) and Pakhira-Bandyopadhyay-Maulik (PBM) indices fail. Simple Lp norm distances achieve validity, whilst correlation-specific functions fail structural, criterion, and external validity. These results differ from previous studies where VRC and PBM performed well, demonstrating that validity depends on structure type. Our structure-type-specific validation method provides both practical guidance (quality thresholds SWC>0.9, DBI<0.15) and a methodological template for establishing validity for other structure types.

Background: Text-to-image generation models are widely used across numerous domains. Among these models, Stable Diffusion (SD) - an open-source text-to-image generation model - has become the most popular, producing over 12 billion images annually. However, the widespread use of these models raises concerns regarding their social and environmental sustainability. Aims: To reduce the harm that SD models may have on society and the environment, we introduce SustainDiffusion, a search-based approach designed to enhance the social and environmental sustainability of SD models. Method: SustainDiffusion searches the optimal combination of hyperparameters and prompt structures that can reduce gender and ethnic bias in generated images while also lowering the energy consumption required for image generation. Importantly, SustainDiffusion maintains image quality comparable to that of the original SD model. Results: We conduct a comprehensive empirical evaluation of SustainDiffusion, testing it against six different baselines using 56 different prompts. Our results demonstrate that SustainDiffusion can reduce gender bias in SD3 by 68%, ethnic bias by 59%, and energy consumption (calculated as the sum of CPU and GPU energy) by 48%. Additionally, the outcomes produced by SustainDiffusion are consistent across multiple runs and can be generalised to various prompts. Conclusions: With SustainDiffusion, we demonstrate how enhancing the social and environmental sustainability of text-to-image generation models is possible without fine-tuning or changing the model's architecture.

Abstract--Deep learning has revolutionized neuroimage analysis by delivering unprecedented speed and accuracy. However, the narrow scope of many training datasets constrains model robustness and generalizability. This challenge is particularly acute in magnetic resonance imaging (MRI), where image appearance varies widely across pulse sequences and scanner hardware. A recent domain-randomization strategy addresses the generalization problem by training deep neural networks on synthetic images with randomized intensities and anatomical content. By generating diverse data from anatomical segmentation maps, the approach enables models to accurately process image types unseen during training, without retraining or fine-tuning. It has demonstrated effectiveness across modalities including MRI, computed tomography, positron emission tomography, and optical coherence tomography, as well as beyond neuroimaging in ultrasound, electron and fluorescence microscopy, and X-ray microtomography. This tutorial paper reviews the principles, implementation, and potential of the synthesis-driven training paradigm. It highlights key benefits, such as improved generalization and resistance to overfitting, while discussing trade-offs such as increased computational demands. Finally, the article explores practical considerations for adopting the technique, aiming to accelerate the development of generalizable tools that make deep learning more accessible to domain experts without extensive computational resources or machine learning knowledge. EUROIMAGING techniques, such as magnetic resonance imaging (MRI), have enabled the study of the human brain in vivo. Alongside advances in acquisition technology, research in neuroimage processing has led to software that automates systematic data analysis, minimizing human effort while improving accuracy and reproducibility [1]. In recent years, deep learning (DL) has been driving the development of a new class of algorithms with unprecedented speed and accuracy, and for a broad range of tasks, deep neural networks have largely replaced classical techniques. However, a key challenge for DL in neuroimaging is small and highly specific datasets. Many studies include only hundreds or even tens of subjects [2], due to factors such as the high cost of data acquisition, multiple modalities competing for scan time, the large size of multi-dimensional data like time-series acquisitions, the low prevalence of certain neurological disorders, and privacy concerns regarding data sharing [3]. Malte Hoffmann (mhoffmann@mgh.harvard.edu) is with the Athinoula A. Martinos Center for Biomedical Imaging and the Departments of Radiology at Harvard Medical School and Massachusetts General Hospital.

Single-cell RNA sequencing technologies have revolutionized our understanding of cellular heterogeneity, yet computational methods often struggle to balance performance with biological interpretability. Embedded topic models have been widely used for interpretable single-cell embedding learning. However, these models suffer from the potential problem of interpretation collapse, where topics semantically collapse towards each other, resulting in redundant topics and incomplete capture of biological variation. Furthermore, the rise of single-cell foundation models creates opportunities to harness external biological knowledge for guiding model embeddings. Here, we present scE2TM, an external knowledge-guided embedded topic model that provides a high-quality cell embedding and interpretation for scRNA-seq analysis. Through embedding clustering regularization method, each topic is constrained to be the center of a separately aggregated gene cluster, enabling it to capture unique biological information. Across 20 scRNA-seq datasets, scE2TM achieves superior clustering performance compared with seven state-of-the-art methods. A comprehensive interpretability benchmark further shows that scE2TM-learned topics exhibit higher diversity and stronger consistency with underlying biological pathways. Modeling interferon-stimulated PBMCs, scE2TM simulates topic perturbations that drive control cells toward stimulated-like transcriptional states, faithfully mirroring experimental interferon responses. In melanoma, scE2TM identifies malignant-specific topics and extrapolates them to unseen patient data, revealing gene programs associated with patient survival.

The Genomic Data Commons (GDC) provides access to high quality, harmonized cancer genomics data through a unified curation and analysis platform centered around patient cohorts. While GDC users can interactively create complex cohorts through the graphical Cohort Builder, users (especially new ones) may struggle to find specific cohort descriptors across hundreds of possible fields and properties. However, users may be better able to describe their desired cohort in free-text natural language. We introduce GDC Cohort Copilot, an open-source copilot tool for curating cohorts from the GDC. GDC Cohort Copilot automatically generates the GDC cohort filter corresponding to a user-input natural language description of their desired cohort, before exporting the cohort back to the GDC for further analysis. An interactive user interface allows users to further refine the generated cohort. We develop and evaluate multiple large language models (LLMs) for GDC Cohort Copilot and demonstrate that our locally-served, open-source GDC Cohort LLM achieves better results than GPT-4o prompting in generating GDC cohorts. We implement and share GDC Cohort Copilot as a containerized Gradio app on HuggingFace Spaces, available at https://huggingface.co/spaces/uc-ctds/GDC-Cohort-Copilot. GDC Cohort LLM weights are available at https://huggingface.co/uc-ctds. All source code is available at https://github.com/uc-cdis/gdc-cohort-copilot.

Flawed planning from VLM-driven embodied agents poses significant safety hazards, hindering their deployment in real-world household tasks. However, existing static, non-interactive evaluation paradigms fail to adequately assess risks within these interactive environments, since they cannot simulate dynamic risks that emerge from an agent's actions and rely on unreliable post-hoc evaluations that ignore unsafe intermediate steps. To bridge this critical gap, we propose evaluating an agent's interactive safety: its ability to perceive emergent risks and execute mitigation steps in the correct procedural order. We thus present IS-Bench, the first multi-modal benchmark designed for interactive safety, featuring 161 challenging scenarios with 388 unique safety risks instantiated in a high-fidelity simulator. Crucially, it facilitates a novel process-oriented evaluation that verifies whether risk mitigation actions are performed before/after specific risk-prone steps. Extensive experiments on leading VLMs, including the GPT-4o and Gemini-2.5 series, reveal that current agents lack interactive safety awareness, and that while safety-aware Chain-of-Thought can improve performance, it often compromises task completion. By highlighting these critical limitations, IS-Bench provides a foundation for developing safer and more reliable embodied AI systems. Code and data are released under https://github.com/AI45Lab/IS-Bench.

The rapid expansion of cross-border e-commerce (CBEC) has created significant opportunities for small- and medium-sized sellers, yet financing remains a critical challenge due to their limited credit histories. Third-party logistics (3PL)-led supply chain finance (SCF) has emerged as a promising solution, leveraging in-transit inventory as collateral. We propose an advanced credit risk management framework tailored for 3PL-led SCF, addressing the dual challenges of credit risk assessment and loan size determination. Specifically, we leverage conditional generative modeling of sales distributions through Quantile-Regression-based Generative Metamodeling (QRGMM) as the foundation for risk measures estimation. We propose a unified framework that enables flexible estimation of multiple risk measures while introducing a functional risk measure formulation that systematically captures the relationship between these risk measures and varying loan levels, supported by theoretical guarantees. To capture complex covariate interactions in e-commerce sales data, we integrate QRGMM with Deep Factorization Machines (DeepFM). Extensive experiments on synthetic and real-world data validate the efficacy of our model for credit risk assessment and loan size determination. This study explores the use of generative models in CBEC SCF risk management, illustrating their potential to strengthen credit assessment and support financing for small- and medium-sized sellers.

Contrastive learning has proven to be highly efficient and adaptable in shaping representation spaces across diverse modalities by pulling similar samples together and pushing dissimilar ones apart. However, two key limitations persist: (1) Without explicit regulation of the embedding distribution, semantically related instances can inadvertently be pushed apart unless complementary signals guide pair selection, and (2) excessive reliance on large in-batch negatives and tailored augmentations hinders generalization. To address these limitations, we propose Variational Supervised Contrastive Learning (VarCon), which reformulates supervised contrastive learning as variational inference over latent class variables and maximizes a posterior-weighted evidence lower bound (ELBO) that replaces exhaustive pair-wise comparisons for efficient class-aware matching and grants fine-grained control over intra-class dispersion in the embedding space. Trained exclusively on image data, our experiments on CIFAR-10, CIFAR-100, ImageNet-100, and ImageNet-1K show that VarCon (1) achieves state-of-the-art performance for contrastive learning frameworks, reaching 79.36% Top-1 accuracy on ImageNet-1K and 78.29% on CIFAR-100 with a ResNet-50 encoder while converging in just 200 epochs; (2) yields substantially clearer decision boundaries and semantic organization in the embedding space, as evidenced by KNN classification, hierarchical clustering results, and transfer-learning assessments; and (3) demonstrates superior performance in few-shot learning than supervised baseline and superior robustness across various augmentation strategies. Our code is available at https://github.com/ziwenwang28/VarContrast.

Modern AI systems, especially those interacting with the physical world, increasingly require real-time performance. However, the high latency of state-of-the-art generalist models, including recent vision-language action models (VLAs), poses a significant challenge. While action chunking has enabled temporal consistency in high-frequency control tasks, it does not fully address the latency problem, leading to pauses or out-of-distribution jerky movements at chunk boundaries. This paper presents a novel inference-time algorithm that enables smooth asynchronous execution of action chunking policies. Our method, real-time chunking (RTC), is applicable to any diffusion- or flow-based VLA out of the box with no re-training. It generates the next action chunk while executing the current one, "freezing" actions guaranteed to execute and "inpainting" the rest. To test RTC, we introduce a new benchmark of 12 highly dynamic tasks in the Kinetix simulator, as well as evaluate 6 challenging real-world bimanual manipulation tasks. Results demonstrate that RTC is fast, performant, and uniquely robust to inference delay, significantly improving task throughput and enabling high success rates in precise tasks $\unicode{x2013}$ such as lighting a match $\unicode{x2013}$ even in the presence of significant latency. See https://pi.website/research/real_time_chunking for videos.

Abstract--This paper introduces GEX, an innovative low-cost dexterous manipulation system that combines the GX11 tri-finger anthropomorphic hand (11 DoF) with the EX12 tri-finger exoskeleton glove (12 DoF), forming a closed-loop teleopera-tion framework through kinematic retargeting for high-fidelity control. Both components employ modular 3D-printed finger designs, achieving ultra-low manufacturing costs while maintaining full actuation capabilities. This full-actuation architecture enables precise bidirectional kinematic calculations, substantially enhancing kinematic retargeting fidelity between the exoskeleton and robotic hand. The proposed system bridges the cost-performance gap in dexterous manipulation research, providing an accessible platform for acquiring high-quality demonstration data to advance embodied AI and dexterous robotic skill transfer learning. Hand dexterity is fundamental to human cognition, enabling active manipulation, tool use, and the way we learn from our environment.