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01.
arXiv (CS.LG) 2026-06-17

Learn from Your Mistakes: Self-Correcting Masked Diffusion Models

arXiv:2602.11590v3 Announce Type: replace Abstract: Masked diffusion models (MDMs) have emerged as a promising alternative to autoregressive models, enabling parallel token generation while achieving competitive performance. Despite these advantages, MDMs face a fundamental limitation: once tokens are unmasked, they remain fixed, leading to error accumulation and ultimately degrading sample quality. We address this by proposing a framework that trains a model to perform both unmasking and correction. By reusing outputs from the MDM denoising network as inputs for corrector training, we train a model to recover from potential mistakes. During generation we apply additional corrective refinement steps between unmasking ones in order to change decoded tokens and improve outputs. We name our training and sampling method Progressive Self-Correction (ProSeCo) for its unique ability to iteratively refine an entire sequence, including already generated tokens. We conduct extensive experimental validation across multiple conditional and unconditional tasks, demonstrating that \method~yields better quality-efficiency trade-offs (up to ~4x faster sampling) and enables inference-time compute scaling to further increase sample quality beyond standard MDMs (up to ~1.2x improvement on benchmarks).

02.
arXiv (CS.AI) 2026-06-19

Optimal Order of Multi-Agent and General Many-Body Systems

作者:

arXiv:2606.20485v1 Announce Type: cross Abstract: This paper develops a general framework for analyzing multi-agent systems with feedback loops between agents actions and collective observations. The framework is built on two fundamental agent-level variables: power, which measures agent influence on collective outcomes, and response functions, which determine how agents react to observations. We derive how macroscopic properties, including total power, useful power, entropy, order, fragility, and mobility, emerge from these two variables of heterogeneous agents. To study the trade off between growth and resilience, we introduce a system-level utility function parameterized by a risk-appetite coefficient and derive an optimal degree of order that balances productivity, stability, and adaptability. The analysis suggests that stronger synchronization can increase collective output but may also increase systemic fragility and reduce mobility. We further argue that order, entropy, information, and useful energy are task-dependent and system-relative concepts whose meanings depend on the objectives of the system. By measuring and designing agent power distributions and response functions, it may be possible to better understand, predict, and optimize collective behavior and identify the conditions under which collective intelligence and optimal order emerge.

03.
bioRxiv (Bioinfo) 2026-06-23

Multi-Scale Machine Learning for Antibody-Antigen Binding Affinity Prediction Using Deep Mutational Scanning and Structural Features

Predicting how mutations alter antibody-antigen binding affinity is essential for antibody engineering and vaccine design, yet current methods generalize poorly to unseen complexes. We present a multi-scale machine learning framework integrating 93 descriptors across four modalities: physicochemical, structural, ESM-2 protein language model, and solvent-accessible surface area (SASA)/{Delta}{Delta}G_fold features. Under leave-one-complex-out deep mutational scanning (LOCO-DMS) cross-validation on AbAgym (36,541 mutations, 68 experiments, 13 pathogens), gradient boosting achieved MCC = 0.206; a confidence-stratified ensemble reached MCC = 0.374 (83.5% accuracy, 25.5% coverage). No single modality exceeds the majority baseline alone; only multi-scale fusion succeeds. Boltzmann ceiling analysis shows 45.9% of mutations are near-neutral (|{Delta}{Delta}G| < k_BT), bounding theoretical maximum MCC at 0.473; our method achieves 79.1% of this limit. Five deep learning architectures benchmarked under LOCO-DMS showed self-attention matching gradient boosting (MCC = 0.200). Cross-pathogen transfer failed systematically (mean 46.7%), confirming universal binding predictors remain an open challenge.

04.
bioRxiv (Bioinfo) 2026-06-16

Orion: Towards Lab Automation with Computer-Using Agents

Laboratory discovery increasingly depends on computational workflows that connect experimental data to analysis, interpretation and follow-up hypotheses. Yet these workflows remain constrained by labor-intensive use of specialized software, visual inspection through graphical user interfaces, and integration of knowledge across multiple sources. Here, we present Orion, a computer-using AI agent for biomedical image analysis and interpretation that moves towards lab automation by automating this computational layer of laboratory work. Orion combines large language models with terminal execution, GUI control and adaptive multi-step reasoning in a shared computing environment. It can inspect visual data, operate standard scientific software, mine web resources and conduct end-to-end analysis and interpretation workflows without requiring bespoke software integrations. Across benchmarks, Orion achieved over 90% accuracy on biomedical database and literature retrieval tasks, learned to use the popular tools CellProfiler and QuPath for quantitative analysis of cellular and tissue images, respectively, and facilitated autonomous discovery in experimental imaging data. In 100 hours of autonomous exploration of a large-scale perturbation imaging dataset, Orion generated 52 research reports, of which human scientist review prioritized 22 plausible mechanistic hypotheses. These results show that computer-using AI agents can substantially expand the reach of laboratory automation, providing a scalable and auditable route from experimental imaging data to quantitative analysis, reports and biologically grounded hypotheses.

05.
arXiv (CS.LG) 2026-06-12

One Step Closer to Ground Truth: A Multi-Scale Residual-Aware Representation Learning Pipeline for Predicting Time Series Data

arXiv:2606.10678v2 Announce Type: replace Abstract: Transformer-based models have emerged as leading paradigms in time-series forecasting in recent years, employing self-attention mechanisms to capture long-range dependencies. Despite their success, these single-stage forecasting architectures exhibit persistent systematic residual biases arising from structural discrepancies, unmodeled stochastic components, or inadequate multi-scale temporal representations. This limitation persists when residuals are treated as irreducible noise, precluding adaptive correction of structured error patterns. To address this limitation, we introduce a two-stage, model-agnostic framework that explicitly decouples forecasting and residual learning into distinct stages of representation learning. A base transformer first generates the initial predictions. Subsequently, a dedicated meta-corrector dynamically models structured error patterns across multivariate channels, preserves cross-variable dependencies, and iteratively refines the residual bias of the base transformer. By formalizing this pipeline as a hypothesis space expansion, our framework addresses approximation limitations inherent in single-stage architectures, removes reliance on restrictive assumptions, and enables end-to-end learning of complex error dynamics. Evaluated on eight popular benchmark datasets using established protocols, our approach achieves state-of-the-art performance, with significant improvements in standard metrics (MSE, MAE). The results demonstrate the framework's ability to mitigate systematic biases and enhance robustness to complex temporal dynamics, advancing the practical applicability of transformer-based forecasting models.

06.
arXiv (CS.LG) 2026-06-16

An Integrable Token Mixing Layer from the Generalized Yang Baxter Equation

arXiv:2606.15085v1 Announce Type: new Abstract: The YB Mixer is a sequence token mixing layer derived from free fermion and generalized Yang Baxter structures. It applies a core principle from integrable systems where a local algebraic constraint guarantees global computational stability. By using the Ising exchange algebra the mixer creates a free fermionic structure that acts as an exactly norm preserving orthogonal map. This algebra also produces commuting transfer matrices which allow inference to be order free and adaptable to any variable budget. To ensure the model can generalize to longer sequence lengths it uses a spectral circulant generator. This generator maintains the crucial orthogonal and commuting properties of the system. The result is a highly stable and mathematically grounded architecture for sequence processing.

07.
arXiv (CS.CV) 2026-06-12

PaLMR: Towards Faithful Visual Reasoning via Multimodal Process Alignment

Reinforcement learning has recently improved the reasoning ability of Large Language Models and Multimodal LLMs, yet prevailing reward designs emphasise final-answer correctness and consequently tolerate process hallucinations–cases where models reach the right answer while misperceiving visual evidence. We address this process-level misalignment with PaLMR, a framework that aligns not only outcomes but also the reasoning process itself. PaLMR comprises two complementary components: a perception-aligned data layer that constructs process-aware reasoning data with structured pseudo-ground-truths and verifiable visual facts, and a process-aligned optimisation layer that constructs a hierarchical reward fusion scheme with a process-aware scoring function to encourage visually faithful chains-of-thought and improve training stability. Experiments on Qwen2.5-VL-7B show that our approach substantially reduces reasoning hallucinations and improves visual reasoning fidelity, achieving state-of-the-art results on HallusionBench while maintaining strong performance on MMMU, MathVista, and MathVerse. These findings indicate that PaLMR offers a principled and practical route to process-aligned multimodal reasoning, advancing the reliability and interpretability of MLLMs.

08.
bioRxiv (Bioinfo) 2026-06-19

FeatureMSEA: Metabolic Feature-based Metabolite Set Enrichment Analysis

Liquid chromatography-mass spectrometry (LC-MS) untargeted metabolomics detects thousands of metabolic features, but converting these chemical signals into metabolite set-level biological knowledge remains challenging. This is because most features lack unambiguous metabolite identities. Conventional metabolite set enrichment analysis (MSEA) generally requires identified metabolites and metabolite-level ranked inputs, leaving much of the untargeted feature space unused. Here, we present FeatureMSEA, a feature rank-based framework for metabolite set enrichment directly from metabolic features with ambiguous annotations. FeatureMSEA integrates multi-evidence feature-to-metabolite annotation, feature rank-based enrichment scoring, permutation-based inference, and iterative leading-edge-guided annotation refinement, with an optional LLM-assisted module for post-enrichment interpretation. In null comparisons of randomly split healthy samples, FeatureMSEA detected no significant metabolite sets, whereas metabolite-set spike-in simulations showed recovery of implanted signals. In a cerebrospinal fluid metabolomics study of Huntington's disease, FeatureMSEA identified dysregulated metabolite sets related to amino acid metabolism, mitochondrial energy metabolism, and neuroactive signaling. MS/MS-based annotation analysis further showed that FeatureMSEA refinement reduced annotation ambiguity and prioritized chemically consistent candidate metabolites. In summary, FeatureMSEA provides a general framework for extracting metabolite set-level biological insights from LC-MS untargeted metabolomics in which confident metabolite identification remains incomplete.

09.
bioRxiv (Bioinfo) 2026-06-16

PhenoBIC: operator-free single-cell spatial phenotyping in multiplex imaging data using deep learning of cell staining patterns

Multiplex imaging is a valuable tool for spatially examining tissue microenvironments at the single-cell level to uncover biological and clinical insights. However, most multiplex image analysis workflows currently require manual intervention for cell phenotyping, which slows progress, demands human effort, and yields operator-dependent outputs. Here, we developed PhenoBIC, a pre-trained deep learning model for image classification of the multiplexed biomarker signals in a cell (Biomarker Imprint of a Cell) to classify cell phenotypes. We show that PhenoBIC (F1-score ~0.88) outperforms manual gating (widely used) and other machine learning-based computational approaches for cell marker expression classification. We validated this across multiple biomarkers, tissue sampling strategies (whole biopsies and tissue microarrays), multiplex panels, imaging platforms, and tissue types. We have released our in-house training and validation datasets of ~1.4 million manually curated cell expression ground truth labels. We have also open-sourced PhenoBIC and enabled its community-wide deployment via the QuPath interface.

10.
arXiv (CS.AI) 2026-06-17

Ensemble RL through Classifier Models: Enhancing Risk-Return Trade-offs in Trading Strategies

作者:

arXiv:2502.17518v3 Announce Type: replace-cross Abstract: This paper presents a comprehensive study on the use of ensemble Reinforcement Learning (RL) models in financial trading strategies, leveraging classifier models to enhance performance. By combining RL algorithms such as A2C, PPO, and SAC with traditional classifiers like Support Vector Machines (SVM), Decision Trees, and Logistic Regression, we investigate how different classifier groups can be integrated to improve risk-return trade-offs. The study evaluates the effectiveness of various ensemble methods, comparing them with individual RL models across key financial metrics, including Cumulative Returns, Sharpe Ratios (SR), Calmar Ratios, and Maximum Drawdown (MDD). Our original experimental results demonstrate that ensemble methods often outperform base models in terms of risk-adjusted returns, providing better management of drawdowns and overall stability. However, both the original analysis and the additional reproduction reported in this version show that ensemble performance is sensitive to the choice of variance threshold \(\tau\), classifier group, RL-agent pair, and market universe. The reproduction evidence strengthens the conclusion that classifier-assisted ensemble selection can improve robustness, while also clarifying that the advantage is conditional rather than automatic across all datasets. This study emphasizes the value of combining RL with classifiers for adaptive decision-making, with implications for financial trading, robotics, and other dynamic environments.

11.
arXiv (CS.AI) 2026-06-16

LLM-as-Code Agentic Programming for Agent Harness

arXiv:2606.15874v1 Announce Type: new Abstract: Every major LLM agent framework gives the LLM the role of orchestrator; the model decides what to do next, when to call tools, and when to stop. We argue that token explosion, control-flow hallucination, and unreliable completion are not implementation bugs but architectural consequences of assigning the deterministic work of looping, branching, and sequencing to a probabilistic system. A better prompt or a stronger model cannot guarantee the reliability of the LLM agent. We therefore propose Agentic Programming, in which the program governs all control flow, and the LLM is itself part of it, an adaptive component we call LLM-as-Code and invoke only where a task calls for reasoning or generation. Within each call the model keeps full flexibility, but it cannot alter the program's execution path. With control in the program, the LLM's context is built from the execution history's call tree and forms a directed acyclic graph (DAG). Each call's context length is then determined by its call depth rather than by accumulation over steps. A case study of computer-use agents shows that the design is practical, not just a theoretical stance, substantially improving the stability of long visual operation sequences.

12.
arXiv (CS.AI) 2026-06-15

DIFF-ERO: A Conformance-Aware Loss for Deep Learning in Process Mining

arXiv:2606.14283v1 Announce Type: cross Abstract: Deep learning has driven many recent advances in process analytics, especially for predictive and prescriptive monitoring. However, standard objectives such as cross-entropy optimize local next-step likelihoods and only implicitly capture control-flow structure. As a result, models can achieve high token-level accuracy while permitting imprecise global behaviour. We introduce DIFF-ERO, a conformance-aware loss function for deep learning models on process data. DIFF-ERO is a differentiable formulation of entropy-based stochastic conformance that incorporates control-flow information during training. Our approach constructs batch-level stochastic transition matrices with soft edge memberships, allowing structural precision and recall signals to directly inform backpropagation. The loss is model-agnostic and can be applied whenever the final representation parametrizes stochastic transitions. We instantiate DIFF-ERO in transformer encoder-decoder pipelines for next-activity prediction and use it jointly with cross-entropy to analyse its theoretical components with respect to convergence. Across benchmarks comparing other loss functions and targets, DIFF-ERO shows improved predictive performance where structure matters most while maintaining parity elsewhere. At the same time, the learned stochastic automaton converges towards the structural ground truth, indicating that the network internalizes process model structure.

13.
arXiv (CS.AI) 2026-06-17

Surrogate Assisted Pedestrian Protection Design via a Foundation Model Orchestrated Workflow

arXiv:2606.17577v1 Announce Type: new Abstract: AI-driven engineering workflows face particular challenges in crash safety design: unlike aerodynamics, crash events involve highly nonlinear contact dynamics, material nonlinearity, and discrete state transitions that are difficult to capture with data-driven surrogate models. To the best of our knowledge, we present the first foundation model–orchestrated workflow for crash safety design that enables surrogate-assisted exploration for pedestrian protection, reducing evaluation time from hours per CAE simulation to seconds. The workflow integrates four components: (1) a surrogate trained on CAE crash simulations to predict pedestrian leg injury metrics from design parameters, achieving an average $R^2=0.87$ and providing distribution-free conformal prediction intervals; (2) multiobjective evolutionary search (NSGA-II) to discover diverse feasible parameter sets under user-specified constraints; (3) a morphing-based geometry generator that maps parameters to topology-preserving 3D shapes; and (4) a natural-language interface in which an LLM orchestrates the workflow and a vision–language model supports semantic comparison of generated designs. In an automotive front-bumper case study, the workflow produces 35 distinct safety-compliant alternatives from a single exploration, a process that would require weeks with conventional CAE iteration. These results suggest that foundation models can serve as integration layers between ML surrogates and physics-based simulation, helping bring AI capabilities to safety-critical engineering domains.

14.
arXiv (CS.LG) 2026-06-11

Triangular-Reference Schrödinger Bridges for Time Series Generation

arXiv:2605.27478v3 Announce Type: replace-cross Abstract: Schrödinger bridges for time series (SBTS) generate synthetic paths by projecting, in relative entropy, a Brownian reference onto the path laws that match the joint distribution of the data on the observation grid. The Brownian reference, however, fixes the quadratic variation of the generated paths, which is restrictive when stochastic volatility, correlated noise, or rank-deficient covariance structures must be reproduced. We introduce "Triangular-Reference Schrödinger Bridges for Time Series" (TR-SBTS), which keeps the entropy-projection backbone of SBTS but replaces the Brownian reference by a triangular, volatility-informed, intervalwise frozen reference on a state augmented with latent covariance descriptors. The construction remains a single entropy projection on the augmented state: the minimiser is the \(h\)-transform of the reference, and on each frozen interval the optimal drift has the logarithmic-gradient form \(b^\star(t,x)=A\,\nabla\log H(t,x)\), intrinsic to the active covariance directions when the frozen covariance \(A\) is degenerate. We prove stability of the frozen approximation and consistency of the associated regularised kernel estimators, describe a reference-aware Nadaraya–Watson implementation of the conditional next-increment law, and evaluate the construction on numerical experiments.

15.
arXiv (CS.AI) 2026-06-19

Rethinking Shrinkage Bias in LLM FP4 Pretraining: Geometric Origin, Systemic Impact, and UFP4 Recipe

arXiv:2606.20381v1 Announce Type: new Abstract: FP4 training promises substantial reductions in memory and computation cost for LLM pretraining, yet current FP4 hardware paths and recipes, including NVIDIA Blackwell/Rubin-class systems and AMD MI350-series GPUs, remain centered on E2M1 data elements. In this study, we identify a fundamental limitation of that choice: non-uniform formats such as E2M1 inherently suffer from Shrinkage Bias, a systematic negative rounding error caused by the geometric asymmetry of their representable bins. We show that this bias accumulates multiplicatively across layers and is amplified by the Random Hadamard Transform (RHT), providing a unified explanation for the training instability observed in existing E2M1-based FP4 recipes. In contrast, uniform grids (E1M2/INT4) bypass this grid-geometry error and better convert the improved bucket utilization from RHT into higher quantization quality. Based on this finding, we propose UFP4, a uniform 4-bit training recipe that applies RHT to all three training GEMMs while restricting stochastic rounding to dY alone. On Dense 1.5B, MoE 7.9B, and MoE 124B long-run pretraining, UFP4 consistently achieves lower BF16-relative loss degradation than strong E2M1-based baselines, supported by scaling-law analysis and ablation studies. Our results suggest that future accelerators should support E1M2/INT4-style uniform 4-bit grids as first-class training primitives alongside E2M1.

16.
arXiv (CS.LG) 2026-06-18

Decomposing Prediction Mechanisms for In-Context Recall

arXiv:2507.01414v2 Announce Type: replace Abstract: We introduce a new family of toy problems that combine features of linear-regression-style continuous in-context learning (ICL) with discrete associative recall. We pretrain transformer models on sample traces from this toy, specifically symbolically-labeled interleaved state observations from randomly drawn linear deterministic dynamical systems. We study if the transformer models can recall the state of a sequence previously seen in its context when prompted to do so with the corresponding in-context label. Taking a closer look at this task, it becomes clear that the model must perform two functions: (1) identify which system's state should be recalled and apply that system to its last seen state, and (2) continuing to apply the correct system to predict the subsequent states. Training dynamics reveal that the first capability emerges well into a model's training. Surprisingly, the second capability, of continuing the prediction of a resumed sequence, develops much earlier. Via out-of-distribution experiments, and a mechanistic analysis on model weights via edge pruning, we find that next-token prediction for this toy problem involves at least two separate mechanisms. One mechanism uses the discrete symbolic labels to do the associative recall required to predict the start of a resumption of a previously seen sequence. The second mechanism, which is largely agnostic to the discrete symbolic labels, performs a "Bayesian-style" prediction based on the previous token and the context. These two mechanisms have different learning dynamics. To confirm that this multi-mechanism (manifesting as separate phase transitions) phenomenon is not just an artifact of our toy setting, we used OLMo training checkpoints on an ICL translation task to see a similar phenomenon: a decisive gap in the emergence of first-task-token performance vs second-task-token performance.

17.
bioRxiv (Bioinfo) 2026-06-14

Systematic AI-Driven Drug Repurposing via Clinical Trial Data Mining: A Framework and Six Cross-Therapeutic Case Studies.

作者:

Drug repurposing, the application of approved or shelved compounds to new therapeutic indications, offers a cost- and time-efficient alternative to de novo drug discovery. However, the systematic identification of repurposing candidates from the rapidly expanding body of clinical trial data remains a significant challenge. Here we present a publicly accessible AI-powered tool that mines the ClinicalTrials.gov registry to identify approved drugs with under-explored therapeutic potential in high-value disease areas. The tool integrates natural language processing, mechanism-of-action pathway analysis, and trial density scoring to surface candidates where biological plausibility is high and clinical trial coverage is sparse. We demonstrate the tool's utility across six cross-therapeutic case studies spanning oncology, cardiology, neurology, rare diseases, immunology, and infectious disease. Key findings include: the identification of Zonisamide as an under-explored combination candidate for obesity alongside GLP-1 receptor agonists; mechanistic validation of SGLT2 inhibitors in heart failure with preserved ejection fraction (HFpEF); and a novel cross-domain mapping of anti-TNF biologics to early-stage neurodegeneration via shared neuroinflammatory pathways. The tool is freely accessible and designed to lower the barrier for academic and industry researchers to systematically pursue repurposing opportunities.

18.
arXiv (CS.AI) 2026-06-17

Learning Fair Pareto-Optimal Policies in Multi-Objective Reinforcement Learning

arXiv:2606.18111v1 Announce Type: cross Abstract: Fairness is an important aspect of decision-making in multi-objective reinforcement learning (MORL), where policies must ensure both optimality and equity across multiple, potentially conflicting objectives. While single-policy MORL methods can learn fair policies for fixed user preferences using welfare functions such as the generalized Gini welfare function (GGF), they fail to provide the diverse set of policies necessary for dynamic or unknown user preferences. To address this limitation, we formalize the fair optimization problem in multi-policy MORL, where the goal is to learn a set of Pareto-optimal policies that ensure fairness across all possible user preferences. Our key technical contributions are threefold: (1) We show that for concave, piecewise-linear welfare functions (e.g., GGF), fair policies remain in the convex coverage set (CCS), which is an approximated Pareto front for linear scalarization. (2) We demonstrate that non-stationary policies, augmented with accrued reward histories, and stochastic policies improve fairness by dynamically adapting to historical inequities. (3) We propose three novel algorithms, which include integrating GGF with multi-policy multi-objective Q-Learning (MOQL), state-augmented multi-policy MOQL for learning non-statoinary policies, and its novel extension for learning stochastic policies. We evaluate our algorithms across various domains and compare our methods against the state-of-the-art MORL baselines. The empirical results show that our methods learn a set of fair policies that accommodate different user preferences.

19.
arXiv (CS.CV) 2026-06-16

ActiveSAM: Image-Conditional Class Pruning for Fast and Accurate Open-Vocabulary Segmentation

Segment Anything Model 3 (SAM 3) provides a strong frozen backbone for concept-prompted segmentation, but applying it directly to open-vocabulary semantic segmentation (OVSS) is inefficient: full-resolution decoding is typically run over the entire dataset vocabulary, whereas each image contains only a small active subset of classes. We introduce ActiveSAM, a training-free, zero-shot inference framework that turns SAM 3 into an active-vocabulary segmenter. ActiveSAM first canonicalizes and expands class prompts, then estimates an image-conditioned active set from a low-resolution presence preview. Only the retained classes are decoded at full resolution, using bucketed prompt multiplexing with the frozen SAM 3 decoder. The preview stage uses only class-presence evidence and skips unnecessary segmentation-head computation, while the final stage applies margin-aware background calibration to suppress low-confidence pixels. ActiveSAM requires no target-dataset training, no weight updates, and no oracle class-presence labels. Across eight OVSS benchmarks, ActiveSAM improves the speed-accuracy tradeoff of training-free open-vocabulary semantic segmentation, outperforming the current state-of-the-art SegEarth-OV3 by approximately +1.4 mIoU on average while running up to 5.5x faster on large-vocabulary datasets. ActiveSAM also demonstrates the strongest robustness under image corruption that simulates real-world distribution shift, making it well-suited for deployment in noisy-input domains such as autonomous driving and embodied AI. Code is available at https://github.com/VILA-Lab/ActiveSAM.

20.
medRxiv (Medicine) 2026-06-15

Non-invasive intracranial pressure waveform reconstruction with deep learning

Purpose: Continuous intracranial pressure (ICP) monitoring requires invasive instrumentation, reaching only a narrow subset of critically ill patients. We tested whether deep learning models trained on routinely acquired extracranial signals can reconstruct continuous ICP waveforms at clinically relevant accuracy in an independent external cohort. Methods: In adults admitted to the ICU at a single quaternary health system, five deep learning architectures were trained on high-frequency arterial blood pressure (ABP), photoplethysmography (PPG), and electrocardiography (ECG) waveforms, using invasive (intraparenchymal) ICP as ground truth. Two fusion strategies (early and late) and three training objectives (waveform-morphology, baseline robust regression, and weighted robust regression) were evaluated. Models were externally validated on the held-out MIMIC-III Waveform Database. Performance was assessed by mean absolute error (MAE) and waveform similarity by Pearson correlation (r). Results: We analyzed data from 158 critically ill adults (~5,322 hours) across two quaternary health systems (Johns Hopkins Hospital, Baltimore; Beth Israel Deaconess Medical Center, Boston). Validation MAE ranged from 4.276 mmHg [95% CI 4.269, 4.283] (gated recurrent, late fusion) to 4.946 mmHg [95% CI 4.938, 4.956] (attention-based, early fusion), with Pearson r ranging from 0.599 [95% CI 0.599, 0.600] to 0.722 [95% CI 0.722, 0.723]. The multiscale encoder-decoder model demonstrated the most favorable MAE-correlation tradeoff. Conclusion: This is the first demonstration that continuous ICP waveform reconstruction from bedside signals generalizes across institutions at clinically relevant accuracy, establishing a foundation for non-invasive ICP monitoring and motivating validation across broader populations and ICP ranges.

21.
medRxiv (Medicine) 2026-06-18

Looked but didn't see: inattentional blindness and yes-bias confabulation in vision-language models

Previous work showed that many participants fail to notice a gorilla in a video of people playing basketball. Another study found that 83% of trained radiologists failed to report a gorilla figure inserted into a chest CT nodule-search task, even though eye-tracking revealed that most observers had foveated the figure. We ask whether a similar phenomenon exists in contemporary vision-language models (VLMs). We find that (i) VLMs are capable of spotting the gorilla in both still-frame images and videos of lung CT scans; (ii) models display inattentional blindness, which varies according to model generation and type of stimulus presented; (iii) Gemini-3.1-Pro outperforms most other flagship and open-weight VLMs at identifying the presence or absence of the gorilla. We additionally ran a segmentation experiment utilizing two different model classes: a generalist (SAM 3), which found the gorilla but produced little to no results for anatomy-based prompts; a medical specialist (BiomedParse), which produced more promising anatomy-based results but flagged "gorilla" on gorilla-free control videos on 82% of frames. The behavioral signature of inattentional blindness reproduces in VLMs, but a unique confabulation failure mode means that any "did the model see X" claim requires signal-detection analysis with a matched-control false-alarm baseline.

22.
bioRxiv (Bioinfo) 2026-06-23

FateLimit quantifies the prediction horizon of cell fate

Single-cell technologies have enabled increasingly detailed reconstruction of developmental trajectories, yet a fundamental question remains unresolved: when does future cellular identity become predictable from cells current molecular state? Existing approaches infer lineage relationships, transition probabilities or future transcriptional dynamics, but do not directly quantify the emergence of fate predictability during cellular state transitions. Here we present FateLimit, an information-theoretic framework for measuring the temporal dynamics of cell-fate predictability from single-cell omics data. FateLimit combines probabilistic fate assignment, fate entropy and mutual information to quantify how information about future cellular outcomes is encoded in present molecular states. We introduce two quantitative descriptors: the Fate Information Half-Life (FIHL), which measures the characteristic timescale of fate-information dynamics, and the Prediction Horizon (PH), defined as the earliest developmental stage at which observed fate predictability exceeds the 95th percentile of a permutation-derived null distribution. We applied FateLimit across developmental, lineage-tracing and reprogramming systems, including pancreatic endocrinogenesis, CellTag reprogramming, human hematopoiesis and zebrafish embryogenesis. Across all datasets, FateLimit identified significant fate information and reproducible prediction horizons that were robust to cell-state representation, lineage structure and biological context. Comparative analysis revealed that prediction horizons differ substantially among cellular lineages, indicating that distinct developmental programs acquire predictive information at different rates. FateLimit establishes a general framework for quantifying the predictability of future cellular identity from present molecular states. By transforming developmental trajectories into predictability landscapes, FateLimit enables systematic comparison of commitment dynamics across biological systems and establishes prediction horizons as a quantitative measure of cell-fate determination.

23.
bioRxiv (Bioinfo) 2026-06-24

Systematic benchmarking of multi-modal approaches for tumor-naive ctDNA detection and quantification

Longitudinal monitoring of circulating tumor DNA (ctDNA) has emerged as a promising framework for characterizing treatment response dynamics in cancer. Scalable tumor-naive approaches for quantifying ctDNA often involve whole-genome sequencing (WGS) or DNA methylation profiling, but their comparative performance and capacity for complementary integration remain poorly understood. Here we systematically benchmarked tumor-naive WGS- and methylation-based ctDNA quantification methods using plasma from 150 patients with colorectal, lung and breast cancer. Using paired high-depth WGS and EM-seq data, we generated 40,000 in silico samples and evaluated detection accuracy, limits of detection (LoD) and quantification (LoQ) across cancer types and sequencing depths (0.1x-30x). We further assessed single- and multimodal method combinations, identifying conditions under which integrated approaches enhance analytical performance for detection and quantification relative to single modalities. This benchmark delineates key performance trade-offs and provides a practical framework to support method development and guide future research applications in ctDNA-based biomarker studies.

24.
arXiv (CS.LG) 2026-06-12

Limits of spectral learning under noise

arXiv:2606.13067v1 Announce Type: new Abstract: Learning functional relationships from noisy data is a central problem in scientific inference. Spectral methods approximate unknown functions by expanding them in a basis and estimating the corresponding coefficients from data, but the stability of these coefficients under noise remains poorly understood. Here we study supervised regression with additive label noise using sparse spectral representations across multiple bases and dimensions. We show that noise induces a predictable drift in the learned coefficient vector whose magnitude depends on the effective number of active spectral modes. After whitening the empirical feature geometry, we derive a closed-form expression for the overlap between noisy and noiseless coefficient vectors, revealing a universal degradation curve governed by a single intrinsic noise scale. Numerical experiments across Fourier, Legendre, Bessel, and Haar bases confirm the theoretical prediction. The results demonstrate that spectral learning exhibits a fundamental noise threshold beyond which coefficient estimates become unstable, placing intrinsic limits on recovering functional structure from noisy data.

25.
arXiv (CS.CV) 2026-06-16

A Multi-Center Benchmark for Abdominal Disease Diagnosis and Report Generation from Non-Contrast CT

Multiphasic contrast-enhanced CT (CECT) is widely used for abdominal lesion characterization, yet it carries inherent risks of contrast-induced nephropathy, escalates acquisition burden, and heavily contributes to radiologist workload. To address these challenges, we introduce a novel multi-center benchmark for multi-organ abdominal disease diagnosis and automated radiology report generation, which learns to synthesize contrast-enhanced findings from single-phase non-contrast CT (NCCT). To support this, we curated a large-scale dataset of paired NCCT-CECT studies and their corresponding contrast-enhanced radiology reports from two centers, partitioned into internal sets and an external validation cohort. Under a unified evaluation protocol, we benchmarked five contemporary deep learning architectures encompassing chest-specific, abdomen-specific, and general-purpose multimodal domains. Extensive experiments demonstrate that NCCT retains diagnostic signals, achieving an average multi-organ AUC of 69.1% on the internal cohort and 63.1% on the external cohort, respectively. By releasing this dataset and standardized benchmark publicly, this study aims to catalyze future research into safer, resource-efficient, and globally accessible contrast-free abdominal imaging workflows. Code is available at: https://github.com/xmed-lab/TriALS-Report.