The Image Biomarker Standardisation Initiative (IBSI) aims to improve reproducibility of radiomics studies by standardising the computational process of extracting image biomarkers (features) from images. We have previously established reference values for 169 commonly used features, created a standard radiomics image processing scheme, and developed reporting guidelines for radiomic studies. However, several aspects are not standardised. Here we present a complete version of a reference manual on the use of convolutional filters in radiomics and quantitative image analysis. Filters, such as wavelets or Laplacian of Gaussian filters, play an important part in emphasising specific image characteristics such as edges and blobs. Features derived from filter response maps were found to be poorly reproducible. This reference manual provides definitions for convolutional filters, parameters that should be reported, reference feature values, and tests to verify software compliance with the reference standard.

Foundation models (FMs) have shown transformative potential in radiology by performing diverse, complex tasks across imaging modalities. Here, we developed CT-FM, a large-scale 3D image-based pre-trained model designed explicitly for various radiological tasks. CT-FM was pre-trained using 148,000 computed tomography (CT) scans from the Imaging Data Commons through label-agnostic contrastive learning. We evaluated CT-FM across four categories of tasks, namely, whole-body and tumor segmentation, head CT triage, medical image retrieval, and semantic understanding, showing superior performance against state-of-the-art models. Beyond quantitative success, CT-FM demonstrated the ability to cluster regions anatomically and identify similar anatomical and structural concepts across scans. Furthermore, it remained robust across test-retest settings and indicated reasonable salient regions attached to its embeddings. This study demonstrates the value of large-scale medical imaging foundation models and by open-sourcing the model weights, code, and data, aims to support more adaptable, reliable, and interpretable AI solutions in radiology.

We present a publicly available multimodal dataset for head and neck cancer research, comprising 1123 annotated Positron Emission Tomography/Computed Tomography (PET/CT) studies from patients with histologically confirmed disease, acquired from 10 international medical centers. All studies contain co-registered PET/CT scans with varying acquisition protocols, reflecting real-world clinical diversity from a long-term, multi-institution retrospective collection. Primary gross tumor volumes (GTVp) and involved lymph nodes (GTVn) were manually segmented by experienced radiation oncologists and radiologists following established guidelines. We provide anonymized NifTi files, expert-annotated segmentation masks, comprehensive clinical metadata, and radiotherapy dose distributions for a patient subset. The metadata include TNM staging, HPV status, demographics, long-term follow-up outcomes, survival times, censoring indicators, and treatment information. To demonstrate its utility, we benchmark three key clinical tasks: automated tumor segmentation, recurrence-free survival prediction, and HPV status classification, using state-of-the-art deep learning models like UNet, SegResNet, and multimodal prognostic frameworks.

Background: Structural variants (SVs) are genomic differences $\ge$50 bp in length. They remain challenging to detect even with long sequence reads, and the sources of these difficulties are not well quantified. Results: We identified 35.4 Mb of low-complexity regions (LCRs) in GRCh38. Although these regions cover only 1.2% of the genome, they contain 69.1% of confident SVs in sample HG002. Across long-read SV callers, 77.3-91.3% of erroneous SV calls occur within LCRs, with error rates increasing with LCR length. Conclusion: SVs are enriched and difficult to call in LCRs. Special care need to be taken for calling and analyzing these variants.

Accurate blind docking has the potential to lead to new biological breakthroughs, but for this promise to be realized, docking methods must generalize well across the proteome. Existing benchmarks, however, fail to rigorously assess generalizability. Therefore, we develop DockGen, a new benchmark based on the ligand-binding domains of proteins, and we show that existing machine learning-based docking models have very weak generalization abilities. We carefully analyze the scaling laws of ML-based docking and show that, by scaling data and model size, as well as integrating synthetic data strategies, we are able to significantly increase the generalization capacity and set new state-of-the-art performance across benchmarks. Further, we propose Confidence Bootstrapping, a new training paradigm that solely relies on the interaction between diffusion and confidence models and exploits the multi-resolution generation process of diffusion models. We demonstrate that Confidence Bootstrapping significantly improves the ability of ML-based docking methods to dock to unseen protein classes, edging closer to accurate and generalizable blind docking methods.

Large language models (LLMs) integrated into agent-driven workflows hold immense promise for healthcare, yet a significant gap exists between their potential and practical implementation within clinical settings. To address this, we present a practitioner-oriented field manual for deploying generative agents that use electronic health record (EHR) data. This guide is informed by our experience deploying the "irAE-Agent", an automated system to detect immune-related adverse events from clinical notes at Mass General Brigham, and by structured interviews with 20 clinicians, engineers, and informatics leaders involved in the project. Our analysis reveals a critical misalignment in clinical AI development: less than 20% of our effort was dedicated to prompt engineering and model development, while over 80% was consumed by the sociotechnical work of implementation. We distill this effort into five "heavy lifts": data integration, model validation, ensuring economic value, managing system drift, and governance. By providing actionable solutions for each of these challenges, this field manual shifts the focus from algorithmic development to the essential infrastructure and implementation work required to bridge the "valley of death" and successfully translate generative AI from pilot projects into routine clinical care.

Self-supervised learning (SSL) has emerged as a powerful approach for learning visual representations without manual annotations. However, the robustness of standard SSL methods to domain shift -- systematic differences across data sources -- remains uncertain, posing an especially critical challenge in biomedical imaging where batch effects can obscure true biological signals. We present AdvDINO, a domain-adversarial self-supervised learning framework that integrates a gradient reversal layer into the DINOv2 architecture to promote domain-invariant feature learning. Applied to a real-world cohort of six-channel multiplex immunofluorescence (mIF) whole slide images from non-small cell lung cancer patients, AdvDINO mitigates slide-specific biases to learn more robust and biologically meaningful representations than non-adversarial baselines. Across $>5.46$ million mIF image tiles, the model uncovers phenotype clusters with distinct proteomic profiles and prognostic significance, and improves survival prediction in attention-based multiple instance learning. While demonstrated on mIF data, AdvDINO is broadly applicable to other imaging domains -- including radiology, remote sensing, and autonomous driving -- where domain shift and limited annotated data hinder model generalization and interpretability.

Nanoparticles (NPs) formed in nonthermal plasmas (NTPs) can have unique properties and applications. However, modeling their growth in these environments presents significant challenges due to the non-equilibrium nature of NTPs, making them computationally expensive to describe. In this work, we address the challenges associated with accelerating the estimation of parameters needed for these models. Specifically, we explore how different machine learning models can be tailored to improve prediction outcomes. We apply these methods to reactive classical molecular dynamics data, which capture the processes associated with colliding silane fragments in NTPs. These reactions exemplify processes where qualitative trends are clear, but their quantification is challenging, hard to generalize, and requires time-consuming simulations. Our results demonstrate that good prediction performance can be achieved when appropriate loss functions are implemented and correct invariances are imposed. While the diversity of molecules used in the training set is critical for accurate prediction, our findings indicate that only a fraction (15-25\%) of the energy and temperature sampling is required to achieve high levels of accuracy. This suggests a substantial reduction in computational effort is possible for similar systems.

Survival models are a popular tool for the analysis of time to event data with applications in medicine, engineering, economics, and many more. Advances like the Cox proportional hazard model have enabled researchers to better describe hazard rates for the occurrence of single fatal events, but are unable to accurately model competing events and transitions. Common phenomena are often better described through multiple states, for example: the progress of a disease modeled as healthy, sick and dead instead of healthy and dead, where the competing nature of death and disease has to be taken into account. Moreover, Cox models are limited by modeling assumptions, like proportionality of hazard rates and linear effects. Individual characteristics can vary significantly between observational units, like patients, resulting in idiosyncratic hazard rates and different disease trajectories. These considerations require flexible modeling assumptions. To overcome these issues, we propose the use of neural ordinary differential equations as a flexible and general method for estimating multi-state survival models by directly solving the Kolmogorov forward equations. To quantify the uncertainty in the resulting individual cause-specific hazard rates, we further introduce a variational latent variable model and show that this enables meaningful clustering with respect to multi-state outcomes as well as interpretability regarding covariate values. We show that our model exhibits state-of-the-art performance on popular survival data sets and demonstrate its efficacy in a multi-state setting

Clinical notes contain rich data, which is unexploited in predictive modeling compared to structured data. In this work, we developed a new text representation Clinical XLNet for clinical notes which also leverages the temporal information of the sequence of the notes. We evaluated our models on prolonged mechanical ventilation prediction problem and our experiments demonstrated that Clinical XLNet outperforms the best baselines consistently.

Graph Neural Networks (GNNs) traditionally employ a message-passing mechanism that resembles diffusion over undirected graphs, which often leads to homogenization of node features and reduced discriminative power in tasks such as node classification. Our key insight for addressing this limitation is to assign fuzzy edge directions -- that can vary continuously from node $i$ pointing to node $j$ to vice versa -- to the edges of a graph so that features can preferentially flow in one direction between nodes to enable long-range information transmission across the graph. We also introduce a novel complex-valued Laplacian for directed graphs with fuzzy edges where the real and imaginary parts represent information flow in opposite directions. Using this Laplacian, we propose a general framework, called Continuous Edge Direction (CoED) GNN, for learning on graphs with fuzzy edges and prove its expressivity limits using a generalization of the Weisfeiler-Leman (WL) graph isomorphism test for directed graphs with fuzzy edges. Our architecture aggregates neighbor features scaled by the learned edge directions and processes the aggregated messages from in-neighbors and out-neighbors separately alongside the self-features of the nodes. Since continuous edge directions are differentiable, they can be learned jointly with the GNN weights via gradient-based optimization. CoED GNN is particularly well-suited for graph ensemble data where the graph structure remains fixed but multiple realizations of node features are available, such as in gene regulatory networks, web connectivity graphs, and power grids. We demonstrate through extensive experiments on both synthetic and real graph ensemble datasets that learning continuous edge directions significantly improves performance both for undirected and directed graphs compared with existing methods.