Karolinska Institutet
Artificial Intelligence (AI) research in breast cancer Magnetic Resonance Imaging (MRI) faces challenges due to limited expert-labeled segmentations. To address this, we present a multicenter dataset of 1506 pre-treatment T1-weighted dynamic contrast-enhanced MRI cases, including expert annotations of primary tumors and non-mass-enhanced regions. The dataset integrates imaging data from four collections in The Cancer Imaging Archive (TCIA), where only 163 cases with expert segmentations were initially available. To facilitate the annotation process, a deep learning model was trained to produce preliminary segmentations for the remaining cases. These were subsequently corrected and verified by 16 breast cancer experts (averaging 9 years of experience), creating a fully annotated dataset. Additionally, the dataset includes 49 harmonized clinical and demographic variables, as well as pre-trained weights for a baseline nnU-Net model trained on the annotated data. This resource addresses a critical gap in publicly available breast cancer datasets, enabling the development, validation, and benchmarking of advanced deep learning models, thus driving progress in breast cancer diagnostics, treatment response prediction, and personalized care.
A study assessed the reliability of Large Language Models' self-reported confidence by comparing it against actual accuracy across various reasoning tasks. It revealed that LLMs exhibit significant overconfidence and are highly susceptible to prompt phrasing, indicating an absence of a stable, internally coherent understanding of their own certainty.
Many Mendelian randomization (MR) papers have been conducted only in people of European ancestry, limiting transportability of results to the global population. Expanding MR to diverse ancestry groups is essential to ensure equitable biomedical insights, yet presents analytical and conceptual challenges. This review examines the practical challenges of MR analyses beyond the European only context, including use of data from multi-ancestry, mismatched ancestry, and admixed populations. We explain how apparent heterogeneity in MR estimates between populations can arise from differences in genetic variant frequencies and correlation patterns, as well as from differences in the distribution of phenotypic variables, complicating the detection of true differences in the causal pathway. We summarize published strategies for selecting genetic instruments and performing analyses when working with limited ancestry-specific data, discussing the assumptions needed in each case for incorporating external data from different ancestry populations. We conclude that differences in MR estimates by ancestry group should be interpreted cautiously, with consideration of how the identified differences may arise due to social and cultural factors. Corroborating evidence of a biological mechanism altering the causal pathway is needed to support a conclusion of differing causal pathways between ancestry groups.
Learning complex robot behavior through interactions with the environment necessitates principled exploration. Effective strategies should prioritize exploring regions of the state-action space that maximize rewards, with optimistic exploration emerging as a promising direction aligned with this idea and enabling sample-efficient reinforcement learning. However, existing methods overlook a crucial aspect: the need for optimism to be informed by a belief connecting the reward and state. To address this, we propose a practical, theoretically grounded approach to optimistic exploration based on Thompson sampling. Our model structure is the first that allows for reasoning about joint uncertainty over transitions and rewards. We apply our method on a set of MuJoCo and VMAS continuous control tasks. Our experiments demonstrate that optimistic exploration significantly accelerates learning in environments with sparse rewards, action penalties, and difficult-to-explore regions. Furthermore, we provide insights into when optimism is beneficial and emphasize the critical role of model uncertainty in guiding exploration.
Parkinson's disease (PD) is a neurodegenerative disorder associated with the accumulation of misfolded alpha-synuclein aggregates, forming Lewy bodies and neuritic shape used for pathology diagnostics. Automatic analysis of immunohistochemistry histopathological images with Deep Learning provides a promising tool for better understanding the spatial organization of these aggregates. In this study, we develop an automated image processing pipeline to segment and classify these aggregates in whole-slide images (WSIs) of midbrain tissue from PD and incidental Lewy Body Disease (iLBD) cases based on weakly supervised segmentation, robust to immunohistochemical labelling variability, with a ResNet50 classifier. Our approach allows to differentiate between major aggregate morphologies, including Lewy bodies and neurites with a balanced accuracy of 80%80\%. This framework paves the way for large-scale characterization of the spatial distribution and heterogeneity of alpha-synuclein aggregates in brightfield immunohistochemical tissue, and for investigating their poorly understood relationships with surrounding cells such as microglia and astrocytes.
Modern generative AI models such as diffusion and flow matching can sample from rich data distributions, but many downstream tasks -- such as experimental design or creative content generation -- require a higher level of control than unconstrained sampling. The challenge is to efficiently identify outputs that are both probable under the model and satisfy task-specific constraints. We address this by introducing surrogate latent spaces: non-parametric, low-dimensional Euclidean embeddings that can be extracted from any generative model without additional training. The axes in the Euclidean space can be defined via examples, providing a simple and interpretable approach to define custom latent spaces that both express intended features and are convenient to use in downstream tasks. The representation is Euclidean and has controllable dimensionality, permitting direct application of standard optimisation algorithms to traverse the outputs of generative models. Our approach is architecture-agnostic, incurs almost no additional computational cost, and generalises across modalities, including images, audio, videos, and structured objects like proteins.
Researchers from Uppsala University and the University of Oxford introduce Forward-only Diffusion (FoD), a generative model leveraging a single, analytically tractable stochastic differential equation to directly learn data generation. FoD achieves state-of-the-art performance in various image restoration tasks and generates high-quality samples efficiently in as few as 10 steps.
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Synthetic molecular motors are an appealing means to control motion at the nanoscale, but understanding their behaviour as single-molecule actuators and integrating them into larger, functional systems remain technical challenges. Translating molecular actuation into coordinated device-level behaviour requires precise placement and orientation of the motors: DNA origami provides a powerful platform for positioning molecules with nanometre precision. Here, we demonstrate integration of a light-driven, rotary molecular motor into a DNA-based nanoscale actuator through site-specific, four-point conjugation. The motor is labelled with four distinct oligonucleotides, two on each side, using DNA-templated chemistry. This modular approach enables stable, oriented incorporation of the motor into a DNA assembly through DNA hybridization. Upon photoactivation with UV light, the motor transduces photon energy into rotary motion. By coupling the motor to a fluorescently labelled DNA rotor arm we amplify its movement and enable real-time observation using total internal reflection fluorescence microscopy. A subset of assembled devices exhibits light-induced conformational transitions and directional motion consistent with the expected photochemical mechanism. These results establish a programmable framework for integration of light-driven molecular motors into synthetic nanomachines and tools for the study of their behaviour.
Though diffusion models have been successfully applied to various image restoration (IR) tasks, their performance is sensitive to the choice of training datasets. Typically, diffusion models trained in specific datasets fail to recover images that have out-of-distribution degradations. To address this problem, this work leverages a capable vision-language model and a synthetic degradation pipeline to learn image restoration in the wild (wild IR). More specifically, all low-quality images are simulated with a synthetic degradation pipeline that contains multiple common degradations such as blur, resize, noise, and JPEG compression. Then we introduce robust training for a degradation-aware CLIP model to extract enriched image content features to assist high-quality image restoration. Our base diffusion model is the image restoration SDE (IR-SDE). Built upon it, we further present a posterior sampling strategy for fast noise-free image generation. We evaluate our model on both synthetic and real-world degradation datasets. Moreover, experiments on the unified image restoration task illustrate that the proposed posterior sampling improves image generation quality for various degradations.
Accurate monitoring of eating behavior is crucial for managing obesity and eating disorders such as bulimia nervosa. At the same time, existing methods rely on multiple and/or specialized sensors, greatly harming adherence and ultimately, the quality and continuity of data. This paper introduces a novel approach for estimating the weight of a bite, from a commercial smartwatch. Our publicly-available dataset contains smartwatch inertial data from ten participants, with manually annotated start and end times of each bite along with their corresponding weights from a smart scale, under semi-controlled conditions. The proposed method combines extracted behavioral features such as the time required to load the utensil with food, with statistical features of inertial signals, that serve as input to a Support Vector Regression model to estimate bite weights. Under a leave-one-subject-out cross-validation scheme, our approach achieves a mean absolute error (MAE) of 3.99 grams per bite. To contextualize this performance, we introduce the improvement metric, that measures the relative MAE difference compared to a baseline model. Our method demonstrates a 17.41% improvement, while the adapted state-of-the art method shows a -28.89% performance against that same baseline. The results presented in this work establish the feasibility of extracting meaningful bite weight estimates from commercial smartwatch inertial sensors alone, laying the groundwork for future accessible, non-invasive dietary monitoring systems.
Rare earth elements (REEs) are critical to a wide range of clean and high-tech applications, yet global trade dependencies expose countries to vulnerabilities across production networks. Here, we construct a multi-tiered input-output trade network spanning 168 REE-related product codes from 2007-2023 using a novel AI-augmented statistical framework. We identify significant differences between dependencies in upstream and intermediate (input) products, revealing that exposure and supplier concentration are systematically higher in input products, while systemic trade risk is lower, suggesting localized vulnerabilities. By computing network-based dependency indicators across countries and over time, we classify economies into five distinct clusters that capture structural differences in rare-earth reliance. China dominates the low-risk, high-influence cluster, while the EU and US remain vulnerable at intermediate tiers. Regression analyses show that high exposure across all products predicts future export strength, consistent with import substitution. However, high systemic trade risk in input products like magnets, advanced ceramics or phosphors, significantly impedes the development of comparative advantage. These results demonstrate that the structure of strategic dependencies is tier-specific, with critical implications for industrial resilience and policy design. Effective mitigation strategies must move beyond raw material access and directly address country-specific chokepoints in midstream processing and critical input production.
In recent years, the machine learning research community has benefited tremendously from the availability of openly accessible benchmark datasets. Clinical data are usually not openly available due to their highly confidential nature. This has hampered the development of reproducible and generalisable machine learning applications in health care. Here we introduce the Health Gym - a growing collection of highly realistic synthetic medical datasets that can be freely accessed to prototype, evaluate, and compare machine learning algorithms, with a specific focus on reinforcement learning. The three synthetic datasets described in this paper present patient cohorts with acute hypotension and sepsis in the intensive care unit, and people with human immunodeficiency virus (HIV) receiving antiretroviral therapy in ambulatory care. The datasets were created using a novel generative adversarial network (GAN). The distributions of variables, and correlations between variables and trends over time in the synthetic datasets mirror those in the real datasets. Furthermore, the risk of sensitive information disclosure associated with the public distribution of the synthetic datasets is estimated to be very low.
The integration of Artificial Intelligence (AI) into clinical workflows requires robust collaborative platforms that are able to bridge the gap between technical innovation and practical healthcare applications. This paper introduces MAIA (Medical Artificial Intelligence Assistant), an open-source platform designed to facilitate interdisciplinary collaboration among clinicians, researchers, and AI developers. Built on Kubernetes, MAIA offers a modular, scalable environment with integrated tools for data management, model development, annotation, deployment, and clinical feedback. Key features include project isolation, CI/CD automation, integration with high-computing infrastructures and in clinical workflows. MAIA supports real-world use cases in medical imaging AI, with deployments in both academic and clinical environments. By promoting collaborations and interoperability, MAIA aims to accelerate the translation of AI research into impactful clinical solutions while promoting reproducibility, transparency, and user-centered design. We showcase the use of MAIA with different projects, both at KTH Royal Institute of Technology and Karolinska University Hospital.
AI-based models for histopathology whole slide image (WSI) analysis are increasingly common, but unsharp or blurred areas within WSI can significantly reduce prediction performance. In this study, we investigated the effect of image blur on deep learning models and introduced a mixture of experts (MoE) strategy that combines predictions from multiple expert models trained on data with varying blur levels. Using H&E-stained WSIs from 2,093 breast cancer patients, we benchmarked performance on grade classification and IHC biomarker prediction with both CNN- (CNN_CLAM and MoE-CNN_CLAM) and Vision Transformer-based (UNI_CLAM and MoE-UNI_CLAM) models. Our results show that baseline models' performance consistently decreased with increasing blur, but expert models trained on blurred tiles and especially our proposed MoE approach substantially improved performance, and outperformed baseline models in a range of simulated scenarios. MoE-CNN_CLAM outperformed the baseline CNN_CLAM under moderate (AUC: 0.868 vs. 0.702) and mixed blur conditions (AUC: 0.890 vs. 0.875). MoE-UNI_CLAM outperformed the baseline UNI_CLAM model in both moderate (AUC: 0.950 vs. 0.928) and mixed blur conditions (AUC: 0.944 vs. 0.931). This MoE method has the potential to enhance the reliability of AI-based pathology models under variable image quality, supporting broader application in both research and clinical settings.
Recently, it has become common for applied works to combine commonly used survival analysis modeling methods, such as the multivariable Cox model and propensity score weighting, with the intention of forming a doubly robust estimator of an exposure effect hazard ratio that is unbiased in large samples when either the Cox model or the propensity score model is correctly specified. This combination does not, in general, produce a doubly robust estimator, even after regression standardization, when there is truly a causal effect. We demonstrate via simulation this lack of double robustness for the semiparametric Cox model, the Weibull proportional hazards model, and a simple proportional hazards flexible parametric model, with both the latter models fit via maximum likelihood. We provide a novel proof that the combination of propensity score weighting and a proportional hazards survival model, fit either via full or partial likelihood, is consistent under the null of no causal effect of the exposure on the outcome under particular censoring mechanisms if either the propensity score or the outcome model is correctly specified and contains all confounders. Given our results suggesting that double robustness only exists under the null, we outline two simple alternative estimators that are doubly robust for the survival difference at a given time point (in the above sense), provided the censoring mechanism can be correctly modeled, and one doubly robust method of estimation for the full survival curve. We provide R code to use these estimators for estimation and inference in the supporting information.
BrainLesion Suite is a versatile toolkit for building modular brain lesion image analysis pipelines in Python. Following Pythonic principles, BrainLesion Suite is designed to provide a 'brainless' development experience, minimizing cognitive effort and streamlining the creation of complex workflows for clinical and scientific practice. At its core is an adaptable preprocessing module that performs co-registration, atlas registration, and optional skull-stripping and defacing on arbitrary multi-modal input images. BrainLesion Suite leverages algorithms from the BraTS challenge to synthesize missing modalities, inpaint lesions, and generate pathology-specific tumor segmentations. BrainLesion Suite also enables quantifying segmentation model performance, with tools such as panoptica to compute lesion-wise metrics. Although BrainLesion Suite was originally developed for image analysis pipelines of brain lesions such as glioma, metastasis, and multiple sclerosis, it can be adapted for other biomedical image analysis applications. The individual BrainLesion Suite packages and tutorials are accessible on GitHub.
This research demonstrates that semantic knowledge, alongside social learning, functions as a critical cognitive mechanism guiding human innovation and driving cumulative cultural evolution. Through both agent-based simulations and large-scale human experiments, the study found that populations with semantic knowledge developed larger cultural repertoires and explored innovation spaces more efficiently, especially when synergistically combined with social learning.
Recent advances in machine learning and AI, including Generative AI and LLMs, are disrupting technological innovation, product development, and society as a whole. AI's contribution to technology can come from multiple approaches that require access to large training data sets and clear performance evaluation criteria, ranging from pattern recognition and classification to generative models. Yet, AI has contributed less to fundamental science in part because large data sets of high-quality data for scientific practice and model discovery are more difficult to access. Generative AI, in general, and Large Language Models in particular, may represent an opportunity to augment and accelerate the scientific discovery of fundamental deep science with quantitative models. Here we explore and investigate aspects of an AI-driven, automated, closed-loop approach to scientific discovery, including self-driven hypothesis generation and open-ended autonomous exploration of the hypothesis space. Integrating AI-driven automation into the practice of science would mitigate current problems, including the replication of findings, systematic production of data, and ultimately democratisation of the scientific process. Realising these possibilities requires a vision for augmented AI coupled with a diversity of AI approaches able to deal with fundamental aspects of causality analysis and model discovery while enabling unbiased search across the space of putative explanations. These advances hold the promise to unleash AI's potential for searching and discovering the fundamental structure of our world beyond what human scientists have been able to achieve. Such a vision would push the boundaries of new fundamental science rather than automatize current workflows and instead open doors for technological innovation to tackle some of the greatest challenges facing humanity today.
Diffusion models have achieved remarkable progress in generative modelling, particularly in enhancing image quality to conform to human preferences. Recently, these models have also been applied to low-level computer vision for photo-realistic image restoration (IR) in tasks such as image denoising, deblurring, dehazing, etc. In this review paper, we introduce key constructions in diffusion models and survey contemporary techniques that make use of diffusion models in solving general IR tasks. Furthermore, we point out the main challenges and limitations of existing diffusion-based IR frameworks and provide potential directions for future work.
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