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01.
arXiv (CS.AI) 2026-06-19

Efficient and Sound Probabilistic Verification for AI Agents

arXiv:2606.20510v1 Announce Type: cross Abstract: Securing AI agents that operate in complex digital environments has become a critical need, and runtime monitoring approaches that formulate and enforce policies expressed in a formal language like Datalog offer a promising solution. However, existing approaches are restricted to deterministic policies. In many practical applications of AI agents, there is a need to enforce security policies in the face of ambiguity, leading to probabilistic predicates or state transitions (for example, a declassifier or Personally Identifiable Information (PII) detector that has some failure probability on each invocation). Furthermore, in many such applications, one cannot easily make the independence assumptions necessary to invoke prior work on probabilistic inference in Datalog. We address this by introducing a sound and efficient framework for such verification based on distributionally robust optimization, computing sound upper bounds on the probability of policy violation regardless of possible correlations between predicates. On standard benchmarks for terminal and tool calling agents, we demonstrate that our approach outperforms prior art and improves the security-utility trade-off while ensuring rigorous bounds on the probability of policy violation.

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

Fisher-Geometric Sharpness and the Implicit Bias of SGD toward Flat Minima

arXiv:2606.20469v1 Announce Type: new Abstract: A widely held intuition in deep learning is that stochastic gradient descent (SGD) implicitly favors flat minima and that flat minima generalize better, but standard Euclidean measures of flatness such as the trace or maximum eigenvalue of the loss Hessian are not invariant under reparametrizations that preserve the network function, which undermines the theoretical foundations of this narrative. In this study we resolve this issue by grounding flatness in the Riemannian geometry of the statistical manifold induced by the Fisher Information Matrix (FIM). We define Riemannian sharpness mathematically and prove that it is invariant under smooth, function-preserving reparametrizations, which directly addresses the critique of Dinh et al. in the paper ``Sharp minima can generalize for deep nets''.We note that this invariance is a property of the true FIM; the diagonal empirical estimator used in practice (and in all experiments below) inherits invariance only approximately, and exact invariance under arbitrary reparametrizations would require structured estimators such as K-FAC. We formalize the gradient noise of mini-batch SGD as having a covariance structure proportional to the FIM, derive the stationary distribution of the resulting stochastic differential equation, and then show that the probability mass is exponentially concentrated at Riemannian-flat minima. A PAC-Bayes generalization bound controlled explicitly by SR formally links this geometric bias to test performance. Our experiments on MNIST and CIFAR-10 confirm that SR reliably tracks generalization in ways that Euclidean sharpness does not, and that its scaling with $\eta/B$ matches the theoretical predictions. Together these results provide a rigorous, reparametrization-invariant account of why flat minima generalize.

03.
arXiv (CS.AI) 2026-06-12

Deployment-Centered Evaluation: Predicting Query-Level Rejection Risk in a Clinical LLM System

arXiv:2606.12702v1 Announce Type: new Abstract: Large language models (LLMs) are increasingly integrated into clinical systems, making it essential to evaluate the real-world utility of these systems. However, static benchmarks tend to measure correctness rather than user acceptance, aggregate performance across queries, and require densely annotated datasets – leading to major blind spots for evaluating clinical systems. In this work, we perform a deployment-centered evaluation of an LLM system embedded within electronic health records at an academic medical center, where user feedback is sparse but closely reflects the deployment conditions. Specifically, we train a pre-response classifier that estimates the risk that a future interaction will result in the user rejecting the LLM response, based on query content and deployment-specific context available before generation. We conduct a prospective analysis of our model over 4.5 months of user feedback, finding that our prediction model achieves an AUROC of 0.719. Further, we estimate the benefit of such predictions in two downstream use cases (guardrail triggering and abstention). Our key conceptual insight is that making use of deployment-specific context (i.e., the provider type, department name, language model used for response), as opposed to only query content, improves the ability to predict whether the user will reject the system output. Altogether, our empirical case study demonstrates the feasibility of predicting user rejection using deployment-specific context, opening the door to targeted guardrails.

04.
bioRxiv (Bioinfo) 2026-06-21

Machine learning evaluation of gene expression-based ALS subtypes across brain and blood tissues

The clinical and molecular heterogeneity observed in amyotrophic lateral sclerosis (ALS) presents a challenge for diagnosis, prognosis, and treatment. RNA sequencing of post-mortem brain samples from ALS patients has identified several subtypes with distinct molecular signatures. We sought to evaluate these subtypes across diverse tissues and datasets and assess the feasibility of supervised machine learning models for sample classification. Unsupervised clustering and pathway analysis were performed to confirm the presence of ALS subtypes in motor cortex samples. Three machine learning strategies were then used to create models based on post-mortem motor cortex expression data of 112 people with ALS from the London Neurodegenerative Diseases Brain Bank. These models were subsequently improved through feature selection and evaluated in independent cohorts from motor cortex (n = 257, NYGC ALS Consortium) and blood (n = 96, Macquarie University Neurodegenerative Disease Biobank) samples. Multi-class linear discriminant analysis (LDA) models were then used for subtype classification. Clustering of ALS post-mortem motor cortex samples confirmed the presence of three subtypes: neuroinflammation (ALS-Neu), extracellular matrix organisation and muscle contraction (ALS-OxA), and synaptic and neuropeptide signalling (ALS-SNs). Among all machine learning strategies, random forests produced the most accurate and stable models for binary classification (~93% accuracy across the three subtypes). After feature selection, random forest models were able to classify samples from an independent post-mortem motor cortex cohort in their respective subtypes (AUC of ~0.98 across the three subtypes). When these models were evaluated in blood using LDA, we found consistent clustering patterns, with samples aligning in the same subtype regions of the post-mortem motor cortex samples, with ALS-SNs being the subtype in which samples were classified with the highest confidence (LDA class probability ~86%). Moreover, classification for this subtype improved when blood samples were collected closer to death. Our findings support the presence of three gene expression-based ALS subtypes in motor cortex samples and the utility of machine learning strategies for subtype classification. We also observed that the subtypes identified in the brain partially match those in the blood, with samples from the late stages of the disease more likely to be correctly predicted into the ALS-SNs cluster. This suggests a longitudinal effect in subtype identification that requires further investigation.

05.
PLOS Computational Biology 2026-06-05

StPedf: Cell trajectory inference of spatial transcriptomics via spatial proximity embedding and spatial density-adaptive fusion

Authors:

by Yuan Zhang, Ziyan Sun, Zhixin Shi, Mengdi Nan, Yuhan Fu, Qing Ren, Jie Gao Spatial transcriptomics is transforming our multidimensional understanding of cellular spatial organization and its functional mechanisms in processes such as development and disease by systematically resolving the spatial heterogeneity of gene expression within tissues. To delve deeper into the dynamic processes underlying spatial expression patterns, spatial trajectory inference integrates genetic and spatial information to reconstruct the spatial developmental trajectories of cells within tissues. This approach reveals the patterns of differentiation and dynamic changes as cellular states evolve continuously along spatial axes. However, existing methods often struggle to uniformly model the complex, nonlinear interactions between high-dimensional gene expression and spatial coordinates. Here, we introduce StPedf, whose core lies in employing a neural network with a masking mechanism to capture complex nonlinear interactions between high-dimensional genes and spatial positions. It further leverages spatial proximity information as a guiding cue, dynamically and adaptively adjusting the embedding of gene and spatial information and the weighting of spatial proximity information based on spatial density. This enables trajectory inference guided by spatial information. This enables optimal transport to derive intercellular transition matrices, reconstruct cellular differentiation trajectories, and construct pseudo-spatiotemporal maps. StPedf demonstrates superior performance over existing methods on five structurally distinct simulated datasets. Using StPedf, we successfully mapped distinct lineages in the spatial trajectories of telencephalon regeneration in the Ambystoma mexicanum, multiple malignant lineages expanding within primary tumors, and developmental spatial trajectories and pseudo-spatiotemporal maps in human dorsolateral prefrontal cortex (DLPFC). StPedf significantly enhances the accuracy and interpretability of spatial trajectory inference, providing critical technical support for revealing the dynamic patterns of cellular fate transitions within tissue microenvironments.

06.
arXiv (CS.CL) 2026-06-11

Redesign Mixture-of-Experts Routers with Manifold Power Iteration

Router is the cornerstone component to the Mixture-of-Experts models. Serving as expert proxies, the rows of the router matrix compute their similarity to the MoE inputs to determine which subset of experts is activated. Ideally, each router row is designed to encode the expert matrix into this representative vector, such that its dot-product with token can better reflect token-expert affinity. However, there exists no design principles to enforce this condensation. In this paper, we propose to align each router row with the principal singular direction of the associated expert, as this direction provides the most expressive mathematical description of a matrix. Based on this principle, we propose a router redesign with Manifold Power Iteration (MPI). Specifically, it introduces a "Power-then-Retract" paradigm, where a power iteration step is performed on the router weights, followed by a retraction to impose a norm constraint to ensure both efficiency and stability. Theoretically, we show that MPI drives router rows to converge toward the principal singular directions of associated experts. Empirically, we pretrain MoE model across scales from 1B to 11B parameters to confirm that this alignment facilitates more effective MoE models.

07.
arXiv (CS.CV) 2026-06-16

Where Does Texture Evidence Live in SAM? Features, Proposal Masks, and Texture Segmentation

Texture segmentation stresses foundation segmentation because meaningful regions are defined by material or repeated appearance rather than object identity. Segment Anything Models (SAMs) often fail by default on such texture-defined partitions, but this failure is ambiguous: the texture evidence may be absent, missing from the proposal bank, or present but selected or assembled incorrectly by an object-centric readout. We ask what texture-relevant evidence is already preserved in frozen SAM before adaptation. We study two frozen evidence spaces: multiscale features, probed with a minimal clustering readout, and the automatic proposal bank, treated as evidence for a supervised consolidation readout. SAM is frozen throughout; we do not fine-tune the backbone or retrain the proposal generator. Across RWTD, STLD, an ADE20K-selected refined-crop complement, and a ControlNet-stitched PTD bridge archive, frozen SAM is not a texture segmenter by default, but its failures are not simple texture blindness. Coarse frozen features preserve texture organization, and proposal banks often contain texture-aligned masks or fragments. Natural scenes more often require assembly and commitment over fragments, while cleaner synthetic cases more often reduce to selecting an already coherent proposal. Default mask failure should therefore be decomposed into representation evidence, proposal-bank support, readout mismatch, and commitment failure.

08.
arXiv (CS.CV) 2026-06-15

QualiaNet: An Experience-Before-Inference Network

Authors:

Human 3D vision involves two distinct stages: an Experience Module, where stereo depth is extracted relative to fixation, and an Inference Module, where this experience is interpreted to estimate 3D scene properties. Paradoxically, although stereo vision does not provide us with absolute distance information, it nonetheless affects our inferences about distance. We propose the Inference Module exploits a natural scene statistic: near scenes produce vivid disparity gradients, while far scenes appear comparatively flat. QualiaNet implements this two-stage architecture computationally: disparity maps simulating human stereo experience are passed to a CNN trained to estimate distance. The network can recover distance from disparity gradients alone, validating this approach.

09.
arXiv (CS.LG) 2026-06-11

Annealed Entropic Allocation for Ranking and Selection

arXiv:2606.11347v1 Announce Type: cross Abstract: We propose Annealed Entropic Allocation, an annealed weighted soft-min framework for sequential budget allocation in ranking and selection. The central idea is to replace the non-smooth maximin large-deviation rate objective with a weighted log-sum-exp surrogate that aggregates challenger-specific pairwise scores through soft-min weights, mitigating hard switching when several challengers are nearly active. To improve finite-budget discrimination, we incorporate the saddlepoint approximation – a sub-exponential correction derived from refined pairwise tail asymptotics. Because these corrections are sub-exponential and the smoothing parameter is annealed to zero, the surrogate preserves the same first-order large-deviation target as the classical maximin formulation. We show that the surrogate converges uniformly to the hard minimum, that the soft-min weights concentrate on the active challengers, and that, under fixed weights, the induced target allocation map is continuous on the simplex interior. Numerical experiments on Gaussian and exponential instances demonstrate competitive performance, especially when multiple challengers are nearly tied.

10.
medRxiv (Medicine) 2026-06-17

Determinants of non-utilization of insecticide-treated nets among children under five in Rwanda: analyses of the 2024 Rwanda malaria indicator survey

Background Insecticide-treated nets (ITNs) are effective for preventing malaria among children under five years, who bear a disproportionate burden of malaria. This study assessed the prevalence and determinants of ITN non-utilization among children under five in Rwanda using data from the 2024 Rwanda Malaria Indicator Survey (RMIS).Methodology This cross-sectional study utilized nationally representative data from the 2024 RMIS. Analyses were restricted to children under five residing in households that owned at least one ITN. The outcome was non-utilization of ITN, defined as not sleeping under an ITN the night preceding the survey. Survey-weighted descriptive statistics were used to estimate the prevalence of ITN non-utilization. Factors associated with non-utilization were identified using a survey-weighted Poisson regression model. Adjusted prevalence ratios (aPRs), 95% confidence intervals and p-values were reported.Results A total of 1,979 children were included in the study. The weighted prevalence of ITN non-utilization among children under five years was 20.11% (95% CI: 17.81 - 22.63). After adjusting for other factors, children aged 2 - 3 years were associated with an 83% higher prevalence of ITN non-utilization compared with those aged [&le;]1 year (aPR = 1.83, 95% CI: 1.423 - 2.352, p < 0.001). Compared with households that owned only one ITN, children in households with three or more ITNs were associated with a 76% lower prevalence of ITN non-utilization (aPR = 0.24, 95% CI: 0.171 - 0.332, p < 0.001). Children living in households with 5 - 7 members were associated with an 87% higher prevalence of ITN non-utilization compared with those in households with 1 - 4 members (aPR = 1.87, 95% CI: 1.476 - 2.358, p < 0.001).Conclusion The findings suggest that ITN utilization among children is influenced not only by household access to nets but also by household composition and dynamics that shape the allocation and use of available preventive resources.

11.
medRxiv (Medicine) 2026-06-17

Characterizing the genetic basis of Cardio-Renal-Metabolic multimorbidity using multivariate genomic modelling

Cardio-renal-metabolic multimorbidity (CRMM) encompasses interrelated conditions affecting the heart, kidneys, and metabolic systems. Although the genetics of individual components are well studied, their shared architecture remains unclear. Here, we performed the largest multi-ancestry multivariate GWAS of CRMM across seven biobanks, including individuals of European (EUR; neff = 353,130), African (AFR; neff = 75,436), and East Asian (EAS; neff = 164,373) ancestry. We identified 287 lead loci in EUR, 30 in AFR, and 202 in EAS. Cross-ancestry analyses revealed ancestry-specific signals and 24 shared loci mapping to FTO and TCF7L2. Drug-repurposing highlighted candidates used for type 2 diabetes and hypertension. Mendelian randomization supported causal links with diverse diseases, while polygenic risk scores showed improved prediction across ancestries. Collectively, these findings advance understanding of CRMM genetics and inform precision medicine.

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

CausalMoE: A Billion-Scale Multimodal Foundation Model for Granger Causal Discovery with Pattern-Routed Heterogeneous Experts

arXiv:2606.13024v1 Announce Type: cross Abstract: Granger Causal Discovery (GCD) is fundamental for analyzing temporal dependencies in complex systems. However, existing neural GCD methods predominantly rely on a "one-size-fits-all" paradigm, struggling to capture distribution shifts and dynamic regime changes inherent in real-world time series. This often leads to entangled representations and spurious causal graphs. In this paper, we propose CausalMoE, a billion-scale multimodal Granger causal foundation model that explicitly models patch-level heterogeneity. CausalMoE introduces a Pattern-Routed Mixture of Heterogeneous Experts, which dynamically identifies latent temporal patterns and routes patches to specialized domain experts, effectively decoupling regime-specific mechanisms from shared dynamics. To ensure interpretable graph recovery, we design a Causality-Aware Self-Attention mechanism operating across variables, yielding sparse Granger causal graphs via proximal optimization. Furthermore, CausalMoE is the first to integrate LLMs and VLMs to align numerical signals with textual and visual priors, regularizing causal estimation in complex scenarios. Extensive experiments demonstrate that CausalMoE establishes a new state-of-the-art on fully supervised benchmarks, while effectively generalizing to few-shot settings where traditional methods fail.

13.
arXiv (CS.LG) 2026-06-11

PianoKontext: Expressive Performance Rendering from Deadpan Context

arXiv:2606.12282v1 Announce Type: cross Abstract: Expressive performance rendering (EPR) aims to generate realistic performances constrained on sequences of notes. However, flow matching audio editing models manipulate only synchronized music samples of the same duration, limiting their understanding of expressive timing. We introduce PianoKontext, a flow matching rendering model for classical piano music that generates variable-length performances in the latent space of a pretrained Music2Latent model. We synthesize MIDI scores into deadpan audio and employ Dynamic Time Warping (DTW) in the latent space to construct paired data for training. The aligned embeddings are concatenated in DiT blocks, allowing for a simple and effective learning of the dependencies between the score and performances. Audio samples are available at our demo page: https://realfolkcode.github.io/pianokontext_demo/.

14.
arXiv (CS.LG) 2026-06-12

Earth Science Foundation Models: From Perception to Reasoning and Discovery

arXiv:2605.12542v2 Announce Type: replace-cross Abstract: Large foundation models (FMs) are transforming Earth science by integrating heterogeneous multimodal data, such as multi-platform imagery, gridded reanalysis data, diverse geophysical and geochemical observations, and domain-specific text, to support tasks ranging from basic perception to advanced scientific discovery. This paper provides a unified review of Earth science foundation models (Earth FMs) through two complementary dimensions: depth, which traces the evolution of model capabilities from perception to multimodal reasoning and agentic scientific workflows, and breadth, which summarizes their expanding applications across the atmosphere, hydrosphere, lithosphere, biosphere, anthroposphere, and cryosphere, as well as coupled Earth system processes. Using this framework, we review representative multimodal Earth foundation models and compile more than 200 datasets and benchmarks spanning diverse Earth science tasks and modalities. We further discuss key challenges in multimodal data heterogeneity, scientific reliability and continual updating, scalability and sustainability, and the transition from foundation models to agentic and embodied Earth intelligence, and outline future directions toward more integrated, trustworthy, and actionable AI Earth scientists. Overall, this paper offers a structured roadmap for understanding the development of Earth foundation models from both capability depth and application breadth.

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

Compositionality Emerges in a Narrow Depth-Connectivity Regime: Architecture Constraints and Solution Manifolds

arXiv:2606.19941v1 Announce Type: new Abstract: Compositionality is believed to be the foundation for generalization, enabling models to reuse meaningful primitives in novel combinations. Yet, models trained with standard gradient-based optimization rarely, and often only weakly, exhibit compositional internal structure, and it remains unclear how or why such compositionality forms. In this work, we show that compositionality emerges in a narrow connectivity-depth sweet spot. Along the connectivity axis, compositionality only appears in some specifically sparse networks, heavily depends on which connections remain rather than on weights' sparsity alone. Along the depth axis, compositionality emerges within a narrow, target-dependent regime, peaking at specific depths, while both shallower and deeper networks fail. When either the depth or connectivity condition is violated, gradient descent silently converges to fractured solutions rather than compositional ones. To discover and exploit this emergence, we introduce (i) similarity-based pruning (SP) to recover compositional connectivity and (ii) a heuristic depth predictor to estimate where compositionality is most likely to appear. Finally, we support these empirical findings with a theoretical framework based on compositional sparsity, volume-ratio arguments, and feature-interference bounds, explaining why compositional solutions are reachable only in a narrow depth-connectivity regime.

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

When the Chain of Thought Knows Better: Failure Modes in Multi-Turn Reasoning Models

Failures in multi-turn reasoning models are largely invisible to terminal-score evaluation. A model can lock onto an unsafe stance early in a long dialogue, yet its final-turn refusal rate may appear indistinguishable from a robustly aligned baseline. To expose these hidden temporal dynamics, we propose a trace-level diagnostic - the CoT-Output 2x2 safety matrix. This framework labels every turn along two independent axes (internal reasoning and visible output), yielding four operationally defined failure cells: robust alignment, alignment faking, overt jailbreak, and a distinct failure mode we term context-injection failure (where the CoT maintains safe reasoning, but the visible output produces harm, highlighting a multi-turn manifestation of reasoning unfaithfulness). We evaluate three distilled reasoning targets against a fixed attacker across five oversight conditions, collecting 6750 turn-level observations on the Information-Hazard scenario. Our analysis reveals two reproducible vulnerabilities: an oversight paradox where explicit monitoring cues paradoxically increase alignment-faking rates rather than suppress them, and a context-injection failure where models lock onto unsafe external outputs despite safe internal states. We release the full dataset of multi-turn dialogues and CoT traces to support follow-up trace-diagnostic research.

17.
arXiv (CS.AI) 2026-06-16

LLM Jaggedness Unlocks Scientific Creativity

arXiv:2605.10574v3 Announce Type: replace Abstract: As artificial intelligence advances, models are not improving uniformly. Instead, progress unfolds in a jagged fashion, with capabilities growing unevenly across tasks, domains, and model scales. In this work, we examine this dynamic jaggedness through the lens of scientific idea generation. We introduce SciAidanBench, a benchmark of open-ended scientific questions designed to measure the scientific creativity of large language models (LLMs). Given a scientific question, models are asked to generate as many unique and coherent ideas as possible, with the total number of valid responses serving as a proxy for creative potential. Evaluating 19 base models across 8 providers (30 total variants including reasoning versions), we find that jaggedness manifests both across models and within models. First, in a cross-task comparison between general and scientific creativity, improvements in general creativity do not translate uniformly to scientific creativity, revealing divergent capability profiles across models. Second, at the prompt level, stronger models do not improve uniformly; instead, they exhibit high variability, with bursts of creativity on some questions and limited performance on others. Third, at the domain level, individual models display uneven strengths across scientific subfields, reflecting fragmented internal capability profiles. Finally, we show that this jaggedness can be harnessed. We explore mechanisms of inference-time compute, knowledge pooling, and brainstorming to combine models effectively and construct meta-model ensembles that outperform any single model. Our results position jaggedness not as a limitation, but as a resource, a structural feature of AI progress that, when understood and leveraged, can amplify LLM-driven scientific creativity.

18.
arXiv (math.PR) 2026-06-11

Unbiased Derivative Estimation for Stationary Mean of Parameterized Markov chains

arXiv:2606.11487v1 Announce Type: cross Abstract: We propose a new approach to unbiased estimation of the gradients of the stationary means associated with parametrized families of Markov chains. Our estimators are particularly efficient when the Markov chains have slow mixing rate. Our approach does not require a specific parametrization except for an oracle to evaluate the transition density and its gradient at a given data point without any additional knowledge about the density function itself. It makes our estimator suitable for parametrizations associated with neural networks. The estimator can potentially achieve large improvement in terms of efficiency. Numerical experiments confirm the good performance predicted by the theory.

19.
arXiv (CS.CL) 2026-06-17

Variable-Width Transformers

Scaling model size, specifically depth and width, has driven significant progress in transformer-based language models. However, most architectures maintain a constant width across all layers, allocating a fixed parameter and computation budget evenly despite different layers potentially playing distinct computational roles. In this work, we empirically investigate nonuniform capacity allocation across network depth by proposing a $\times$-shaped >

20.
medRxiv (Medicine) 2026-06-15

Evaluation of AI-Generated Synthetic Data for Clinical Research in Secondary Cardiovascular Prevention among Dyslipidemia Patients

Background: Access to high-quality clinical data is essential for advancing medical research and developing effective medical statistical and Artificial Intelligence models. However, privacy regulations and logistical barriers often hinder timely access to real-world data. Synthetic data offer a promising solution, preserving the statistical characteristics of original datasets while protecting patient privacy. Objectives: This study investigates the use of synthetic data for secondary cardiovascular prevention in patients with dyslipidemia, using two real-world datasets from Centro Cardiologico Monzino. Methods: Given the high dimensionality and limited sample size of the datasets, we employed a custom generative framework based on Large Language Models (LLMs). Pre-trained LLMs were fine-tuned on original clinical records to synthesize tabular data replicating source-data distributions. Fine-tuning was performed within the Centro Cardiologico Monzino's secure infrastructure to ensure data sovereignty. We evaluate clinical utility and privacy using fidelity and privacy metrics, identifying the optimal generative model and benchmarking against traditional anonymization methods. Results: Synthetic data achieved a superior trade-off than classically anonymized datasets. Real and synthetic datasets showed strong agreement, with significant distributional differences limited to few variables. Models trained on synthetic data replicated key associations from the original dataset, including therapy modification and creatine phosphokinase as predictors of SAMS, and pharmacological intensity as the main driver of LDL-C reduction. Conclusions: Results support the feasibility of using synthetic data as a proxy for real-world datasets in exploratory analyses and model development. Despite slight attenuation of some effect sizes, preserved clinical relationships reinforce the validity of synthetic data in medical research.

21.
arXiv (CS.LG) 2026-06-16

Machine Learning and the Random Walk Puzzle: Forecasting the CAD/USD Exchange Rate with Expanding Window Evaluation and SHAP Interpretability

arXiv:2606.15058v1 Announce Type: new Abstract: This study examines whether machine learning (ML) models can outperform the naive random walk benchmark in forecasting the monthly USD/CAD exchange rate. Using daily data from the Bank of Canada spanning January 2017 to May 2026, resampled into 113 monthly observations, five ML models are evaluated: linear regression, random forest, gradient boosting, XGBoost, and AdaBoost. These models are benchmarked against the naive random walk model and exponential smoothing with Holt-Winters seasonality (ETS). All models are evaluated using an expanding-window framework to maintain strict out-of-sample integrity, and forecast-accuracy differences are assessed using the Diebold-Mariano (DM) test. Structural break detection identifies four significant breakpoints in the series, corresponding to the escalation of the US-China trade war in 2018, the COVID-19 economic recovery in 2020, the peak of the Bank of Canada rate-hiking cycle in 2022, and the start of the Bank of Canada rate-cutting cycle in 2024. SHAP, or Shapley Additive Explanations, analysis is applied to interpret the drivers of the best-performing ML model. The results show that the naive random walk model remains a formidable benchmark. Linear regression is the only model that statistically outperforms the naive random walk model, with a DM statistic of 3.0585 and a p value of 0.0071, whereas the ML ensemble models show only marginal differences. Random Forest with an expanding-window framework achieves the lowest MAPE of 1.17 percent among all models except the random walk. SHAP analysis confirms that short-term lags, particularly lag1 and lag2, and recent rolling means dominate predictions, consistent with the near-random-walk behavior of exchange rates.

22.
arXiv (CS.AI) 2026-06-17

Lean4Agent: Formal Modeling and Verification for Agent Workflow and Trajectory

arXiv:2606.06523v2 Announce Type: replace Abstract: Equipping Large Language Models (LLMs) to execute reliable multi-step workflows has become a central challenge in artificial intelligence. Despite recent advances in LLMs' agentic capabilities, most agent systems still lack formal methods for specifying, verifying, and debugging their workflow and execution trajectories. This challenge mirrors a long-standing problem in mathematics, where the ambiguity of natural languages (NLs) motivates the development of formal languages (FLs). Inspired by this paradigm, we propose **Lean4Agent**, to the best of our knowledge, the first framework that uses Lean4, a dependent-type FL to model and verify agent behavior. **Lean4Agent** launches **FormalAgentLib**, an extensible Lean4 library for formally modeling and verifying agent workflows' semantic consistency under explicit assumptions, and enabling localization of execution-time failures revealed by trajectories. Building on **FormalAgentLib**, we further develop **LeanEvolve**, which applies results in **FormalAgentLib** to revise workflows to enhance its capability. Extensive experiments on a hard problem subset of SWE-Bench-Verified and a subset of ELAIP-Bench across 5 leading LLMs indicate that the verification-passing workflows outperform the failing ones by an average of **11.94%**, and **LeanEvolve** further improves SWE performance by **7.47%** on average. Furthermore, **Lean4Agent** establishes a foundation for a new field of using expressive dependent-type FL to formally model and verify agent behavior.

23.
arXiv (CS.CV) 2026-06-11

FOCUS on Contamination: Hydrology-Informed Noise-Aware Learning for Geospatial PFAS Mapping

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants with significant public health impacts, yet large-scale monitoring remains severely limited due to the high cost and logistical challenges of field sampling. The lack of samples leads to difficulty simulating their spread with physical models and limited scientific understanding of PFAS transport in surface waters. Yet, rich geospatial and satellite-derived data describing land cover, hydrology, and industrial activity are widely available. We introduce FOCUS, a geospatial deep learning framework for PFAS contamination mapping that integrates sparse PFAS observations with large-scale environmental context, including priors derived from hydrological connectivity, land cover, source proximity, and sampling distance. These priors are integrated into a principled, noise-aware loss, yielding a robust training objective under sparse labels. Across extensive ablations, robustness analyses, and real-world validation, FOCUS consistently outperforms baselines including sparse segmentation, Kriging, and pollutant transport simulations, while preserving spatial coherence and scalability over large regions. Our results demonstrate how AI can support environmental science by providing screening-level risk maps that prioritize follow-up sampling and help connect potential sources to surface-water contamination patterns in the absence of complete physical models.

24.
medRxiv (Medicine) 2026-06-17

Characterisation of disease progression in hantavirus haemorrhagic fever with renal syndrome

Hantaviruses can cause haemorrhagic fever with renal syndrome (HFRS). This is a clinically variable disease in which severe outcomes are hypothesized to arise from dysregulated host responses. To characterise this, longitudinal, label-free plasma proteomics was used to compare disease progression in a unique well-defined cohort of patients infected with either Dobrava virus (DOBV) or Puumala virus (PUUV) hantaviruses. Patients were stratified by clinical severity. The average viral load in the first available sample from hospitalized patients was higher in those who went on to have severe infection, and higher in patients infected with DOBV. There was marked separation of infected patients from controls across early, mid and late disease, including after viral RNA clearance, suggesting a sustained systemic host-response signature. Proteomic signatures were consistent with a strong acute-phase response in both mild and severe disease. There was evidence of activation of the adaptive humoral response at later stages. Hierarchical clustering identified severity-associated pathways linked to endothelial dysfunction, thrombocytopenia, vascular leakage and renal injury. These findings define a durable plasma proteomic signature of hantavirus disease and support a model in which severe HFRS is driven by persistent inflammatory, complement and platelet/coagulation pathway activation rather than viral burden alone.

25.
arXiv (CS.CL) 2026-06-15

Automatic identification of diagnosis from hospital discharge letters via weakly supervised Natural Language Processing

Identifying patient diagnoses from hospital discharge letters is essential for large-scale cohort selection and epidemiological research, but traditional supervised approaches require extensive manual annotation, which is often impractical for large textual datasets. We present a weakly supervised Natural Language Processing (NLP) pipeline for classifying Italian discharge letters without document-level manual annotation. The method extracts diagnosis-related sentences, generates semantic embeddings using a transformer model further pre-trained on Italian medical documents, and applies a two-level clustering procedure to derive weak labels that are then used to train a document-level classifier. The approach was evaluated in a case study on bronchiolitis using 33,176 discharge letters of children admitted to 44 emergency rooms or hospitals in the Veneto Region, Italy, between 2017 and 2020. The best weakly supervised model achieved an AUROC of 77.68% ($\pm4.30\%$), an AUPRC of 73.13% ($\pm4.93\%$), and an F1-score of 78.14% ($\pm4.89\%$) against manually annotated data. Performance surpassed unsupervised baselines and approached fully supervised models, while reducing the need for manual annotation by more than 1,500 hours for a dataset of this size. Similar model rankings were observed in a secondary validation on a smaller bronchitis dataset (3,188 discharge letters, 2020-2025), where the best weakly supervised model achieved an AUPRC of 76.72% ($\pm 5.02\%$). These results suggest the potential of weakly supervised NLP methods for scalable disease identification from clinical discharge letters.