Generative models for sequential data often struggle with sparsely sampled and high-dimensional trajectories, typically reducing the learning of dynamics to pairwise transitions. We propose Interpolative Multi-Marginal Flow Matching (IMMFM), a framework that learns continuous stochastic dynamics jointly consistent with multiple observed time points. IMMFM employs a piecewise-quadratic interpolation path as a smooth target for flow matching and jointly optimizes drift and a data-driven diffusion coefficient, supported by a theoretical condition for stable learning. This design captures intrinsic stochasticity, handles irregular sparse sampling, and yields subject-specific trajectories. Experiments on synthetic benchmarks and real-world longitudinal neuroimaging datasets show that IMMFM outperforms existing methods in both forecasting accuracy and further downstream tasks.

The increasing volume of drug combinations in modern therapeutic regimens needs reliable methods for predicting drug-drug interactions (DDIs). While Large Language Models (LLMs) have revolutionized various domains, their potential in pharmaceutical research, particularly in DDI prediction, remains largely unexplored. This study thoroughly investigates LLMs' capabilities in predicting DDIs by uniquely processing molecular structures (SMILES), target organisms, and gene interaction data as raw text input from the latest DrugBank dataset. We evaluated 18 different LLMs, including proprietary models (GPT-4, Claude, Gemini) and open-source variants (from 1.5B to 72B parameters), first assessing their zero-shot capabilities in DDI prediction. We then fine-tuned selected models (GPT-4, Phi-3.5 2.7B, Qwen-2.5 3B, Gemma-2 9B, and Deepseek R1 distilled Qwen 1.5B) to optimize their performance. Our comprehensive evaluation framework included validation across 13 external DDI datasets, comparing against traditional approaches such as l2-regularized logistic regression. Fine-tuned LLMs demonstrated superior performance, with Phi-3.5 2.7B achieving a sensitivity of 0.978 in DDI prediction, with an accuracy of 0.919 on balanced datasets (50% positive, 50% negative cases). This result represents an improvement over both zero-shot predictions and state-of-the-art machine-learning methods used for DDI prediction. Our analysis reveals that LLMs can effectively capture complex molecular interaction patterns and cases where drug pairs target common genes, making them valuable tools for practical applications in pharmaceutical research and clinical settings.

Medical applications of machine learning (ML) have experienced a surge in popularity in recent years. The intensive care unit (ICU) is a natural habitat for ML given the abundance of available data from electronic health records. Models have been proposed to address numerous ICU prediction tasks like the early detection of complications. While authors frequently report state-of-the-art performance, it is challenging to verify claims of superiority. Datasets and code are not always published, and cohort definitions, preprocessing pipelines, and training setups are difficult to reproduce. This work introduces Yet Another ICU Benchmark (YAIB), a modular framework that allows researchers to define reproducible and comparable clinical ML experiments; we offer an end-to-end solution from cohort definition to model evaluation. The framework natively supports most open-access ICU datasets (MIMIC III/IV, eICU, HiRID, AUMCdb) and is easily adaptable to future ICU datasets. Combined with a transparent preprocessing pipeline and extensible training code for multiple ML and deep learning models, YAIB enables unified model development. Our benchmark comes with five predefined established prediction tasks (mortality, acute kidney injury, sepsis, kidney function, and length of stay) developed in collaboration with clinicians. Adding further tasks is straightforward by design. Using YAIB, we demonstrate that the choice of dataset, cohort definition, and preprocessing have a major impact on the prediction performance - often more so than model class - indicating an urgent need for YAIB as a holistic benchmarking tool. We provide our work to the clinical ML community to accelerate method development and enable real-world clinical implementations. Software Repository: this https URL.

Automated volumetric segmentation of the pancreas on cross-sectional imaging is needed for diagnosis and follow-up of pancreatic diseases. While CT-based pancreatic segmentation is more established, MRI-based segmentation methods are understudied, largely due to a lack of publicly available datasets, benchmarking research efforts, and domain-specific deep learning methods. In this retrospective study, we collected a large dataset (767 scans from 499 participants) of T1-weighted (T1W) and T2-weighted (T2W) abdominal MRI series from five centers between March 2004 and November 2022. We also collected CT scans of 1,350 patients from publicly available sources for benchmarking purposes. We developed a new pancreas segmentation method, called PanSegNet, combining the strengths of nnUNet and a Transformer network with a new linear attention module enabling volumetric computation. We tested PanSegNet's accuracy in cross-modality (a total of 2,117 scans) and cross-center settings with Dice and Hausdorff distance (HD95) evaluation metrics. We used Cohen's kappa statistics for intra and inter-rater agreement evaluation and paired t-tests for volume and Dice comparisons, respectively. For segmentation accuracy, we achieved Dice coefficients of 88.3% (std: 7.2%, at case level) with CT, 85.0% (std: 7.9%) with T1W MRI, and 86.3% (std: 6.4%) with T2W MRI. There was a high correlation for pancreas volume prediction with R^2 of 0.91, 0.84, and 0.85 for CT, T1W, and T2W, respectively. We found moderate inter-observer (0.624 and 0.638 for T1W and T2W MRI, respectively) and high intra-observer agreement scores. All MRI data is made available at this https URL. Our source code is available at this https URL.

Foundation models are increasingly used in scientific research, but evaluating AI-generated scientific work remains challenging. While expert reviews are costly, large language models (LLMs) as proxy reviewers have proven to be unreliable. To address this, we investigate two automatic evaluation metrics, specifically citation count prediction and review score prediction. We parse all papers of OpenReview and augment each submission with its citation count, reference, and research hypothesis. Our findings reveal that citation count prediction is more viable than review score prediction, and predicting scores is more difficult purely from the research hypothesis than from the full paper. Furthermore, we show that a simple prediction model based solely on title and abstract outperforms LLM-based reviewers, though it still falls short of human-level consistency.

The sustainability of the ocean ecosystem is threatened by increased levels of sound pollution, making monitoring crucial to understand its variability and impact. Passive acoustic monitoring (PAM) systems collect a large amount of underwater sound recordings, but the large volume of data makes manual analysis impossible, creating the need for automation. Although machine learning offers a potential solution, most underwater acoustic recordings are unlabeled. Self-supervised learning models have demonstrated success in learning from large-scale unlabeled data in various domains like computer vision, Natural Language Processing, and audio. However, these models require large, diverse, and balanced datasets for training in order to generalize well. To address this, a fully automated self-supervised data curation pipeline is proposed to create a diverse and balanced dataset from raw PAM data. It integrates Automatic Identification System (AIS) data with recordings from various hydrophones in the U.S. waters. Using hierarchical k-means clustering, the raw audio data is sampled and then combined with AIS samples to create a balanced and diverse dataset. The resulting curated dataset enables the development of self-supervised learning models, facilitating various tasks such as monitoring marine mammals and assessing sound pollution.

Hemodynamic quantities are valuable biomedical risk factors for cardiovascular pathology such as atherosclerosis. Non-invasive, in-vivo measurement of these quantities can only be performed using a select number of modalities that are not widely available, such as 4D flow magnetic resonance imaging (MRI). In this work, we create a surrogate model for hemodynamic flow field estimation, powered by machine learning. We train graph neural networks that include priors about the underlying symmetries and physics, limiting the amount of data required for training. This allows us to train the model using moderately-sized, in-vivo 4D flow MRI datasets, instead of large in-silico datasets obtained by computational fluid dynamics (CFD), as is the current standard. We create an efficient, equivariant neural network by combining the popular PointNet++ architecture with group-steerable layers. To incorporate the physics-informed priors, we derive an efficient discretisation scheme for the involved differential operators. We perform extensive experiments in carotid arteries and show that our model can accurately estimate low-noise hemodynamic flow fields in the carotid artery. Moreover, we show how the learned relation between geometry and hemodynamic quantities transfers to 3D vascular models obtained using a different imaging modality than the training data. This shows that physics-informed graph neural networks can be trained using 4D flow MRI data to estimate blood flow in unseen carotid artery geometries.

Ultra-high resolution 7 tesla (7T) magnetic resonance imaging (MRI) provides detailed anatomical views, offering better signal-to-noise ratio, resolution and tissue contrast than 3T MRI, though at the cost of accessibility. We present an advanced deep learning model for synthesizing 7T brain MRI from 3T brain MRI. Paired 7T and 3T T1-weighted images were acquired from 172 participants (124 cognitively unimpaired, 48 impaired) from the Swedish BioFINDER-2 study. To synthesize 7T MRI from 3T images, we trained two models: a specialized U-Net, and a U-Net integrated with a generative adversarial network (GAN U-Net). Our models outperformed two additional state-of-the-art 3T-to-7T models in image-based evaluation metrics. Four blinded MRI professionals judged our synthetic 7T images as comparable in detail to real 7T images, and superior in subjective visual quality to 7T images, apparently due to the reduction of artifacts. Importantly, automated segmentations of the amygdalae of synthetic GAN U-Net 7T images were more similar to manually segmented amygdalae (n=20), than automated segmentations from the 3T images that were used to synthesize the 7T images. Finally, synthetic 7T images showed similar performance to real 3T images in downstream prediction of cognitive status using MRI derivatives (n=3,168). In all, we show that synthetic T1-weighted brain images approaching 7T quality can be generated from 3T images, which may improve image quality and segmentation, without compromising performance in downstream tasks. Future directions, possible clinical use cases, and limitations are discussed.

Radiation therapy plays a crucial role in cancer treatment, necessitating precise delivery of radiation to tumors while sparing healthy tissues over multiple days. Computed tomography (CT) is integral for treatment planning, offering electron density data crucial for accurate dose calculations. However, accurately representing patient anatomy is challenging, especially in adaptive radiotherapy, where CT is not acquired daily. Magnetic resonance imaging (MRI) provides superior soft-tissue contrast. Still, it lacks electron density information while cone beam CT (CBCT) lacks direct electron density calibration and is mainly used for patient positioning. Adopting MRI-only or CBCT-based adaptive radiotherapy eliminates the need for CT planning but presents challenges. Synthetic CT (sCT) generation techniques aim to address these challenges by using image synthesis to bridge the gap between MRI, CBCT, and CT. The SynthRAD2023 challenge was organized to compare synthetic CT generation methods using multi-center ground truth data from 1080 patients, divided into two tasks: 1) MRI-to-CT and 2) CBCT-to-CT. The evaluation included image similarity and dose-based metrics from proton and photon plans. The challenge attracted significant participation, with 617 registrations and 22/17 valid submissions for tasks 1/2. Top-performing teams achieved high structural similarity indices (>0.87/0.90) and gamma pass rates for photon (>98.1%/99.0%) and proton (>97.3%/97.0%) plans. However, no significant correlation was found between image similarity metrics and dose accuracy, emphasizing the need for dose evaluation when assessing the clinical applicability of sCT. SynthRAD2023 facilitated the investigation and benchmarking of sCT generation techniques, providing insights for developing MRI-only and CBCT-based adaptive radiotherapy.

Physical inactivity significantly contributes to obesity and other non-communicable diseases, yet efforts to increase population-wide physical activity levels have met with limited success. The built environment plays a pivotal role in encouraging active behaviors like walking. Walkability indices, which aggregate various environmental features, provide a valuable tool for promoting healthy, walkable environments. However, a standardized, high-resolution walkability index for Europe has been lacking. This study addresses that gap by developing a standardized, high-resolution walkability index for the entire European region. Seven core components were selected to define walkability: walkable street length, intersection density, green spaces, slope, public transport access, land use mix, and 15-minute walking isochrones. These were derived from harmonized, high-resolution datasets such as Sentinel-2, NASA's elevation models, OpenStreetMap, and CORINE Land Cover. A 100 m x 100 m hierarchical grid system and advanced geospatial methods, like network buffers and distance decay, were used at scale to efficiently model real-world density and proximity effects. The resulting index was weighted by population and analyzed at different spatial levels using visual mapping, spatial clustering, and correlation analysis. Findings revealed a distinct urban-to-rural gradient, with high walkability scores concentrated in compact urban centers rich in street connectivity and land use diversity. The index highlighted cities like Barcelona, Berlin, Munich, Paris, and Warsaw as walkability leaders. This standardized, high-resolution walkability index serves as a practical tool for researchers, planners, and policymakers aiming to support active living and public health across diverse European contexts.

SlicerNNInteractive integrates nnInteractive, a state-of-the-art promptable deep learning-based framework for 3D image segmentation, into the widely used 3D Slicer platform. Our extension implements a client-server architecture that decouples computationally intensive model inference from the client-side interface. Therefore, SlicerNNInteractive eliminates heavy hardware constraints on the client-side and enables better operating system compatibility than existing plugins for nnInteractive. Running both the client and server-side on a single machine is also possible, offering flexibility across different deployment scenarios. The extension provides an intuitive user interface with all interaction types available in the original framework (point, bounding box, scribble, and lasso prompts), while including a comprehensive set of keyboard shortcuts for efficient workflow.

Recent challenges in operating power networks arise from increasing energy demands and unpredictable renewable sources like wind and solar. While reinforcement learning (RL) shows promise in managing these networks, through topological actions like bus and line switching, efficiently handling large action spaces as networks grow is crucial. This paper presents a hierarchical multi-agent reinforcement learning (MARL) framework tailored for these expansive action spaces, leveraging the power grid's inherent hierarchical nature. Experimental results indicate the MARL framework's competitive performance with single-agent RL methods. We also compare different RL algorithms for lower-level agents alongside different policies for higher-order agents.

Group equivariance has emerged as a valuable inductive bias in deep learning, enhancing generalization, data efficiency, and robustness. Classically, group equivariant methods require the groups of interest to be known beforehand, which may not be realistic for real-world data. Additionally, baking in fixed group equivariance may impose overly restrictive constraints on model architecture. This highlights the need for methods that can dynamically discover and apply symmetries as soft constraints. For neural network architectures, equivariance is commonly achieved through group transformations of a canonical weight tensor, resulting in weight sharing over a given group $G$. In this work, we propose to learn such a weight-sharing scheme by defining a collection of learnable doubly stochastic matrices that act as soft permutation matrices on canonical weight tensors, which can take regular group representations as a special case. This yields learnable kernel transformations that are jointly optimized with downstream tasks. We show that when the dataset exhibits strong symmetries, the permutation matrices will converge to regular group representations and our weight-sharing networks effectively become regular group convolutions. Additionally, the flexibility of the method enables it to effectively pick up on partial symmetries.

Large language models (LLMs) offer unprecedented opportunities to generate concise summaries of patient information and alleviate the burden of clinical documentation that overwhelms healthcare providers. We present Distillnote, a framework for LLM-based clinical note summarization, and generate over 64,000 admission note summaries through three techniques: (1) One-step, direct summarization, and a divide-and-conquer approach involving (2) Structured summarization focused on independent clinical insights, and (3) Distilled summarization that further condenses the Structured summaries. We test how useful are the summaries by using them to predict heart failure compared to a model trained on the original notes. Distilled summaries achieve 79% text compression and up to 18.2% improvement in AUPRC compared to an LLM trained on the full notes. We also evaluate the quality of the generated summaries in an LLM-as-judge evaluation as well as through blinded pairwise comparisons with clinicians. Evaluations indicate that one-step summaries are favoured by clinicians according to relevance and clinical actionability, while distilled summaries offer optimal efficiency (avg. 6.9x compression-to-performance ratio) and significantly reduce hallucinations. We release our summaries on PhysioNet to encourage future research.

Medical image segmentation is a critical task in healthcare applications, and U-Nets have demonstrated promising results. This work delves into the understudied aspect of receptive field (RF) size and its impact on the U-Net and Attention U-Net architectures. This work explores several critical elements including the relationship between RF size, characteristics of the region of interest, and model performance, as well as the balance between RF size and computational costs for U-Net and Attention U-Net methods for different datasets. This work also proposes a mathematical notation for representing the theoretical receptive field (TRF) of a given layer in a network and proposes two new metrics - effective receptive field (ERF) rate and the Object rate to quantify the fraction of significantly contributing pixels within the ERF against the TRF area and assessing the relative size of the segmentation object compared to the TRF size respectively. The results demonstrate that there exists an optimal TRF size that successfully strikes a balance between capturing a wider global context and maintaining computational efficiency, thereby optimizing model performance. Interestingly, a distinct correlation is observed between the data complexity and the required TRF size; segmentation based solely on contrast achieved peak performance even with smaller TRF sizes, whereas more complex segmentation tasks necessitated larger TRFs. Attention U-Net models consistently outperformed their U-Net counterparts, highlighting the value of attention mechanisms regardless of TRF size. These novel insights present an invaluable resource for developing more efficient U-Net-based architectures for medical imaging and pave the way for future exploration. A tool is also developed that calculates the TRF for a U-Net (and Attention U-Net) model, and also suggest an appropriate TRF size for a given model and dataset.