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

VideoSketcher: Sequential Sketch Generation Using Video Model Priors

Sketching is inherently sequential: strokes are drawn progressively to explore and refine ideas. Yet most generative approaches treat sketches as static images, ignoring the temporal process underlying creative exploration. Modeling this sequential structure remains challenging: prior methods either rely on large-scale human-drawn datasets with limited diversity, or use large language models (LLMs) to produce drawing instructions, often at the cost of visual fidelity. We present VideoSketcher, a method for generating high-quality sketching processes by adapting pretrained text-to-video diffusion models to the sparse, continuous nature of sketch formation. Our key insight is that LLMs and video diffusion models offer complementary strengths: LLMs act as semantic planners that decompose concepts into step-by-step instructions, while video diffusion models serve as powerful "renderers" that translate them into temporally coherent sketch sequences. We introduce a two-stage fine-tuning strategy that decouples temporal structure from visual appearance: stroke ordering is learned from synthetic shape compositions, while style is distilled from as few as seven hand-drawn examples. Despite minimal supervision, our method can generate diverse, high-quality sequential sketches that faithfully follow specified drawing orders. Our framework naturally extends to brush style control and autoregressive generation, supporting artistic applications.

02.
medRxiv (Medicine) 2026-06-15

Diabetes and the Life-Course: Evidence from Panel Data and Electronic Health Records

Incidence of type 2 diabetes is increasing at ages when education, work, family, and financial transitions are taking place, yet we lack robust evidence of whether earlier treatment changes life-course outcomes and over which time span this takes place. This paper uses the medical cutoff for diabetes diagnosis (HbA1c of 6.5 percent) as a natural experiment to study the effects of diabetes treatment using electronic health records (EHR) and panel data. This paper has three main findings. First, using EHR data, we find that there is a sharp increase in the probability of both diagnosis of diabetes and prescription when the HbA1c equals 6.5 percent. Second, we find that treating diabetes reduces HbA1c levels, weight, BMI, and blood pressure and increases the amount of care received, proxied by the number of HbA1c tests. Both the diagnosis and a prescription are independently able to produce positive changes in metabolic health, although a prescription is more effective in this regard. Third, we conclude that treating diabetes does not have a significant effect on life-course outcomes for a cohort of young Americans aged 24-32, although it does result in a reduction in HbA1c levels that are seen even eight years after the intervention. Taken together, these findings suggest that receiving a diagnosis and prescription are both effective treatments for diabetes, but they do not translate to significant alterations in the lives of young adults in the medium-term.

03.
arXiv (CS.AI) 2026-06-19

LLM Doesn't Know What It Doesn't Know: Detecting Epistemic Blind Spots via Cross-Model Attribution Divergence on Clinical Tabular Data

arXiv:2606.19509v1 Announce Type: new Abstract: Large language models (LLMs) are increasingly applied to structured clinical data, yet whether they can recognize the limits of their own knowledge on such tasks remains unexplored. We study this question through the lens of cross-model attribution divergence with the goal of reducing epistemic uncertainty for structured tasks, comparing Qwen 2.5 7B and XGBoost on a prediction task via attribution divergence analysis. We report four findings. First, LLM verbalized confidence is epistemically vacuous, it outputs a near-constant (0.856-0.937) regardless of whether accuracy is 49% or 75.3%, tracking prompt format rather than prediction quality. Second, the LLM exhibits an inverse difficulty effect: accuracy drops to 64.8% when XGBoost is 99% correct, but matches XGBoost (73.8% vs. 73.1%) when it is moderately uncertain. Third, few-shot examples and SHAP-derived feature evidence are orthogonal, super-additive interventions: they reduce the Attribution Disagreement Score (ADS) from 1.54 to 0.38 and improve accuracy from 49% to 75.3% without training. Fourth, a cross-model calibrator that determined LLM reliability using attribution divergence signals reduces expected calibration error from 0.254 to 0.080, replacing uninformative verbalized confidence with patient-specific reliability estimates, without accessing model internals or requiring repeated inference. We frame these findings as a cold start problem for LLMs on structured data and outline a path toward genuine epistemic self-awareness.

04.
bioRxiv (Bioinfo) 2026-06-14

FENNEC: Fine-Tuned Ensemble Neural Networks Accelerate Chemically Modified siRNA Design and Screening

Small interfering RNAs (siRNAs) are a clinically validated therapeutic modality, yet designing potent chemically modified siRNAs remains a costly and iterative process, limited by scarce public data. Computational prediction of siRNA efficacy is therefore essential for rational design and accelerated preclinical development. However, despite the critical role of chemical modifications in therapeutic performance, current state-of-the-art machine learning methods either are not designed to model the chemical diversity of therapeutic siRNAs, or exhibit poor generalization performance. Here, we present FENNEC (Fine-Tuned Ensemble of Neural Networks for siRNA Efficiency Characterization), a machine-learning framework for predicting siRNA activity across chemically diverse design spaces. To support this effort, we curated the largest patent-derived dataset to date of chemically modified siRNAs from 42 patents using OCR-based table extraction and stringent filtering. FENNEC combines temporal convolutional networks with thermodynamic descriptors, experimental covariates, and embeddings from RNA foundation models to capture both local chemical determinants and broader target-context information. Importantly, we show that language-model-derived embeddings provide meaningful higher-order representations of target transcripts, particularly in data-scarce settings. FENNEC achieved robust predictive performance across both gene-level and scaffold-level validation settings, with additional experimental validation on a novel AHSA1-targeting dataset further supporting its generalizability across chemically modified siRNAs. In benchmarking, FENNEC outperformed classical machine-learning and state-of-the-art deep learning models, demonstrating generalization to unseen chemistry. Model interpretation recovered established design principles, including position-specific effects of glycol nucleic acid, 2'-fluoro modifications, and phosphorothioate backbones. Furthermore, in silico perturbation analyses suggest that FENNEC can serve not only as a predictive model, but also as an oracle for the design and optimization of chemically modified siRNAs. Together, our work addresses a key gap in the field by enabling chemically aware deep learning for siRNA design, supported by a large and diverse collection of chemically modified siRNA measurements.

05.
arXiv (CS.CV) 2026-06-11

SheafStain: Sheaf-Theoretic Schrödinger Bridge for Spatially and Biologically Coherent Virtual Staining

Current virtual staining approaches offer the potential for time- and cost-efficient biomarker quantification in cancer diagnostics and prognostics. However, patch-wise inference for gigapixel whole slide images (WSIs) fails to maintain spatial continuity, yielding artifacts that cause catastrophic mismatches with ground-truth images. Although pathology Vision Foundation Models (VFMs) offer rich representations, their self-attention causes varying global contexts to produce inconsistent embeddings for the same physical region. We formalize and validate this ``context contamination'' as a sheaf-theoretic problem where these embeddings form a presheaf that violates the gluing axiom. To address this, we propose SheafStain, a new approach that reinterprets VFM features as sheaf-like sections for spatially and biologically coherent virtual staining. Specifically, SheafStain integrates class and patch tokens into a Schrödinger Bridge framework as sheaf-like sections. While the class token anchors biological consistency, patch tokens form a per-position spatial map. A backbone co-pretrained on Hematoxylin \& Eosin (H\&E) and Immunohistochemistry (IHC) yields non-degenerate cross-stain stalks, so a single VFM feature space supervises both input conditioning and output stain alignment. Departing from prior work that evaluates on isolated $256 \times 256$ patches and either random-crops or resizes the $1024 \times 1024$ ground truth, we translate at $256 \times 256$ and evaluate on the stitched $1024 \times 1024$ outputs across HER2, ER, PR, and Ki-67. SheafStain demonstrates promising results against six prior methods while mitigating patch-boundary stitching artifacts. Code will soon be released.

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

MapSatisfyBench: Benchmarking Satisfaction-Aware Map Agents through Behavior-Grounded Implicit Decision Factors

arXiv:2606.17453v1 Announce Type: new Abstract: Large language model agents are increasingly integrated into map services. Since map services are embedded in everyday-life scenarios rather than professional task settings, users often express their needs informally, resulting in underspecified queries with many unspoken needs, namely, implicit decision factors that are critical for user satisfaction. Although clarification is an effective way to mitigate this issue, it increases user burden in daily interaction, and a capable agent should first proactively recover such factors from available information sources. However, evaluating this ability is challenging. The first challenge is to determine which implicit decision factors are suitable for evaluation. A factor is evaluable only if it affects user acceptance and can be recovered from information available to the agent before it responds. Second, user satisfaction cannot be reliably represented by a single reference answer, requiring a benchmark that converts satisfaction-relevant factors into objective and quantifiable evaluation targets. To address these challenges, we propose a restore-identify-filter framework that reconstructs complete user needs from behavior-chain evidence, identifies implicit decision factors, and retains only those supported by pre-query evidence. Building on this methodology, we construct MapSatisfyBench from large-scale, real-world anonymized user data and annotate ground truth from five dimensions and enables full-chain evaluation of satisfaction-aware map agents. Experiments show that current agents generally perform well on explicit task completion, but remain limited in satisfying implicit decision factors and proactively acquiring the evidence needed for satisfaction-aware decisions. These findings establish MapSatisfyBench as a benchmark for shifting map-agent evaluation from task completion toward satisfaction-aware spatial decision making.

07.
arXiv (CS.LG) 2026-06-17

Conditional Attribution for Root Cause Analysis in Time-Series Anomaly Detection

arXiv:2604.17616v3 Announce Type: replace Abstract: Root cause analysis (RCA) for time-series anomaly detection is critical for the reliable operation of complex real-world systems. Existing explanation methods often rely on unrealistic feature perturbations and ignore temporal and cross-feature dependencies, leading to unreliable attributions. We propose a conditional attribution framework that explains anomalies relative to contextually similar normal system states. Instead of using marginal or randomly sampled baselines, our method retrieves representative normal instances conditioned on the anomalous observation, enabling dependency-preserving and operationally meaningful explanations. To support high-dimensional time-series data, contextual retrieval is performed in learned low-dimensional representations using both variational autoencoder latent spaces and UMAP manifold embeddings. By grounding the retrieval process in the system's learned manifold, this strategy avoids out-of-distribution artifacts and ensures attribution fidelity while maintaining computational efficiency. We further introduce confidence-aware and temporal evaluation metrics for assessing explanation reliability and responsiveness. Experiments on the SWaT and MSDS benchmarks demonstrate that the proposed approach consistently improves root-cause identification accuracy, temporal localization, and robustness across multiple anomaly detection models. These results highlight the practical utility of conditional attribution for explainable anomaly diagnosis in complex time-series systems. Code and models are available at: https://github.com/dfki-av/Conditional-Attribution-for-Root-Cause-Analysis-in-Time-Series-Anomaly-Detection.

08.
arXiv (quant-ph) 2026-06-11

Time-Frequency Grid States for Reconstruction and Correction of Channel-Induced Distortion in Entangled Photons

arXiv:2606.12216v1 Announce Type: new Abstract: Characterization of time-frequency (TF) quantum states requires reliable reconstruction of their TF distributions. However, imperfect transmission or measurement channels can distort reconstructed joint spectral intensities (JSIs), especially when the underlying perturbation mechanism is unknown. Here, we experimentally demonstrate a reconstruction and correction framework that uses a TF grid state as an intrinsic frequency-domain reference. By analyzing the displacement of the grid points, a Gaussian process regression model is employed to reconstruct a correction mapping for the nonlinear coordinate deformation without assuming a prior physical model of the distortion. The learned mapping reduces the residual coordinate deviation of the TF grid state by approximately a factor of 11 and, when applied to an independent frequency-entangled test state, improves the Gaussian-shape fidelity from 76.2\% to 90.0\%. These results establish TF grid states as practical metrological resources for diagnosing and correcting distortions in TF quantum systems, providing a pathway toward distortion-resilient quantum communication and high-dimensional quantum information processing.

09.
arXiv (CS.AI) 2026-06-19

Improving End-to-End Speech Recognition for Dysarthric Speech through In-Domain Data Augmentation

arXiv:2606.19797v1 Announce Type: cross Abstract: Dysarthric speech recognition is crucial for facilitating effective communication among individuals with dysarthria. However, accurately recognizing dysarthric speech poses significant challenges due to varying severity levels and limited data availability. In this paper, we explore data augmentation techniques for dysarthric automatic speech recognition (ASR) systems by fine-tuning the End-to-End pre-trained Wav2Vec2 model, with a specific focus on severity levels. To address the challenges of data scarcity and the need for extensive data in fine-tuning pre-trained ASR systems for dysarthric speech, we investigate four prominent data augmentation methods: Speaking-Rate Modification (SRM), Pitch Modification (PM), Formant Modification (FM), and vocal tract Length Perturbation (VTLP), tailored to different aspects of dysarthria. The study uses individually fine-tuned Wav2Vec2 models for each severity class as baseline systems. Additionally, we conducted severity-specific fine-tuning of the ASR model using augmented data. Results demonstrate distinct efficacy patterns for each augmentation technique across severity levels. The best WERs were achieved with SRM ($s$=0.8) for low (9.02\%) and medium (38.11\%) severities, and with PM ($\tau$=0.8) for high severity (55.15\%), reflecting relative improvements of 30.02\%, 16.64\%, and 15.47\%, respectively. These results confirm the effectiveness of the augmentation methods in improving dysarthric ASR performance.

10.
arXiv (quant-ph) 2026-06-19

Approximating optimal decoding of quantum LDPC codes with narrow frontiers

arXiv:2606.20513v1 Announce Type: new Abstract: We introduce the Frontier decoder, a pruned dynamic-programming decoder for sparse quantum decoding problems. Frontier processes error variables in a chosen order, merges prefixes with the same residual syndrome and logical label, and approximates logical-coset posterior masses by retaining only a narrow scored frontier. Without pruning, the recursion is exact ordered inference with exponential complexity. In the code-capacity setting, the decoder reaches thresholds close to optimal for the surface code and the color code. In the circuit-level noise model, it achieves state-of-the-art performance with a very small average retained list size: less than 100 for the gross code $[[144,12,12]]$ at a physical error rate of $0.001$. When the list size is constant, the decoder has linear complexity, suggesting the possibility of low-latency implementations.

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

Beyond Rebalancing: Benchmarking Binary Classifiers Under Class Imbalance Without Rebalancing Techniques

arXiv:2509.07605v2 Announce Type: replace-cross Abstract: Class imbalance poses a significant challenge to supervised classification, particularly in critical domains like medical diagnostics and anomaly detection where minority class instances are rare. While numerous studies have explored rebalancing techniques to address this issue, less attention has been given to evaluating the performance of binary classifiers under imbalance when no such techniques are applied. Therefore, the goal of this study is to assess the performance of binary classifiers "as-is", without performing any explicit rebalancing. Specifically, we systematically evaluate the robustness of a diverse set of binary classifiers across both real-world and synthetic datasets, under progressively reduced minority class sizes, using one-shot and few-shot scenarios as baselines. Our approach also explores varying data complexities through synthetic decision boundary generation to simulate real-world conditions. In addition to standard classifiers, we include experiments using undersampling, oversampling strategies, and one-class classification (OCC) methods to examine their behavior under severe imbalance. The results confirm that classification becomes more difficult as data complexity increases and the minority class size decreases. While traditional classifiers deteriorate under extreme imbalance, advanced models like TabPFN and boosting-based ensembles retain relatively higher performance and better generalization compared to traditional classifiers. Visual interpretability and evaluation metrics further validate these findings. Our work offers valuable guidance on model selection for imbalanced learning, providing insights into classifier robustness without dependence on explicit rebalancing techniques.

12.
arXiv (quant-ph) 2026-06-12

Non-invertible symmetries out of equilibrium: Eigenstate order and Floquet physics

arXiv:2508.14213v2 Announce Type: replace-cross Abstract: Through the study of the Rep($D_8$) non-invertible symmetry, we show how non-invertible symmetries manifest in dynamics. Results are presented for dynamics generated by Hamiltonians as well as Floquet unitaries. For both examples, the role of the non-invertible symmetry is studied through the appearance of non-invertible symmetry protected edge modes. In addition, the role of the non-invertible symmetry for the Hamiltonian is studied through eigenstate order. In particular, by considering the effect of symmetry preserving disorder, the non-invertible symmetry is shown to give rise to degeneracies in the spectra of the Hamiltonian that can only be completely lifted at orders of perturbation that scale with system size. The eigenstates of disordered Hamiltonians, whose ground state correspond to non-trivial symmetry protected topological (SPT) states, are shown to have either trivial or non-trivial SPT order that are detected as non-zero expectation value of string order-parameters. In contrast, non-trivial SPT order is absent in the eigenstates of trivial SPT Hamiltonians with disorder. The interface between two different SPT phases host edge modes whose dynamics is studied numerically and analytically. The edge mode is shown to oscillate at frequencies related to different effective chain lengths that are weighted by the temperature, becoming an exact zero mode in the limit of zero temperature. A Floquet model with the non-invertible symmetry is constructed whose edge mode is shown to exhibit period-doubled dynamics at low effective-temperatures. The zero and period-doubled edge modes differ from those in conventional SPTs by being symmetric under the invertible symmetry, while being charged under the non-invertible symmetry.

13.
arXiv (CS.CV) 2026-06-18

Efficient Image-to-Image Schrödinger Bridge for CT Field of View Extension

Computed tomography (CT) is a cornerstone imaging modality for non-invasive, high-resolution visualization of internal anatomical structures. However, when the scanned object exceeds the scanner's field of view (FOV), projection data are truncated, resulting in incomplete reconstructions and pronounced artifacts near FOV boundaries. Conventional reconstruction algorithms struggle to recover accurate anatomy from such data, limiting clinical reliability. Deep learning approaches have been explored for FOV extension, with diffusion generative models representing the latest advances in image synthesis. Yet, conventional diffusion models are computationally demanding and slow at inference due to their iterative sampling process. To address these limitations, we propose an efficient CT FOV extension framework based on the image-to-image Schrödinger Bridge (I$^2$SB) diffusion model. Unlike traditional diffusion models that synthesize images from pure Gaussian noise, I$^2$SB learns a direct stochastic mapping between paired limited-FOV and extended-FOV images. This direct correspondence yields a more interpretable and traceable generative process, enhancing anatomical consistency and structural fidelity in reconstructions. I$^2$SB achieves superior quantitative performance, with root-mean-square error (RMSE) values of 49.8 HU on simulated noisy data and 152.0 HU on real data, outperforming state-of-the-art diffusion models such as conditional denoising diffusion probabilistic models (cDDPM) and patch-based diffusion methods. Moreover, its one-step inference enables reconstruction in just 0.19 s per 2D slice, representing over a 700-fold speedup compared to cDDPM (135 s) and surpassing DiffusionGAN (0.58 s), the second fastest. This combination of accuracy and efficiency indicates that I$^2$SB has potential for real-time or clinical deployment.

14.
arXiv (CS.CV) 2026-06-19

SSD: Spatially Speculative Decoding Accelerates Autoregressive Image Generation

Autoregressive models excel in visual generation by treating images as 1D sequences of discrete tokens, mirroring language modeling. However, this flattening discards the intrinsic 2D spatial locality of visual signals, creating severe computational bottlenecks during inference. We introduce Spatially Speculative Decoding (SSD), a framework that aligns the predictive objective with the natural geometry of images. Rather than predicting only the immediate next token in a 1D sequence, our model simultaneously predicts the adjacent horizontal token and the token directly below it. By capitalizing on this 2D spatial correlation, spatially speculative decoding overcomes the memory wall in visual inference. Our approach accelerates autoregressive image generation by up to 13.3x while maintaining high fidelity on DPG-Bench and GenEval. Our results suggest that respecting the underlying geometry of vision unlocks massive computational efficiencies, paving the way for real-time, high-resolution autoregressive generative models.

15.
arXiv (CS.AI) 2026-06-16

Your Agent Has a Genome: Sequence-Level Behavioral Analysis and Runtime Governance of LLM-Powered Autonomous Agents

Authors:

arXiv:2606.15579v1 Announce Type: new Abstract: We propose Base Sequence Analysis, a framework that encodes the runtime behavior of LLM-powered autonomous agents into compact symbolic sequences using a four-letter alphabet: X (Explore), E (Execute), P (Plan), and V (Verify). Drawing an analogy to genomic sequence analysis, we apply n-gram pattern mining, Markov transition matrices, and point-biserial correlation to 347 real-world execution traces collected from a production ReAct agent system over 8 days. Our analysis reveals that (1) the trigram P-X-P is the only statistically significant high-risk pattern, lowering success rate by 10.4%; (2) P-ratio is the strongest negative predictor of success (r=-0.256, pV transition probability is only 2.1%, indicating a systemic verification deficit. Based on these findings, we design Governor, a three-layer runtime intervention system comprising a rule engine, a statistical accumulator, and a chi-square-based threshold adaptor. In a natural before/after deployment evaluation (N=101 vs. N=246), Governor achieves a +6.2% absolute increase in task success rate while simultaneously reducing average token consumption by 44%. To validate cross-system generality, we apply the XEPV encoding to 2,000 public SWE-agent trajectories on SWE-bench, confirming that exploration spirals and the E->V verification deficit replicate in an independent system. We outline six research directions including base sequence language models, cross-agent behavioral fingerprinting, and reward shaping, and release an open-source toolkit for reproducibility.

16.
arXiv (CS.AI) 2026-06-15

Regional Climate Model Emulation with Diffusion Approaches: What is the Added Value of Generative Machine Learning?

arXiv:2606.14570v1 Announce Type: cross Abstract: Emulators provide a cost-effective alternative to regional climate models (RCMs) by capturing their dynamical downscaling function. They link large-scale predictors simulated by global climate models (GCMs) to RCM-simulated high-resolution fields of the target variable, here precipitation. Machine learning methods, typically deep learning, are cheaper than running RCMs in computation time and energy. Among them, generative models are appealing because they can simulate ensembles of local high-resolution fields consistent with the predictors. This ensemble, which we call the uncertainty envelope, remains to be properly assessed for added value. Here, we make three contributions. First, we introduce ParamDiffusion, a new two-stage diffusion-based framework, and compare it with a state-of-the-art diffusion approach. Second, we expand standard validation through a comprehensive framework aligned with climate-science needs, examining specific precipitation events, including extremes. Third, within this framework, we assess the added value of diffusion approaches relative to deterministic methods. We intercompare four deep-learning models: a deterministic model designed to capture the precipitation tail; a parametric probabilistic model based on it; a recently proposed diffusion approach; and ParamDiffusion, which couples the parametric model with a diffusion model. Our results show that diffusion-based approaches reproduce climatological precipitation statistics with high skill, including distributional tails and spatially compounded extremes, while generating spatially detailed fields. However, none of the assessed models consistently accounts for the most extreme RCM-simulated events within its uncertainty envelope. Diffusion models are therefore promising for probabilistic RCM emulation, but progress is still required before they can reliably represent high-impact precipitation extremes.

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

Belief-Space Control for Personalized Cancer Treatment via Active Inference

arXiv:2606.10376v2 Announce Type: replace Abstract: Cancer treatment is at the core a sequential decision-making problem with partial observability, latent patient heterogeneity, and explicit constraints on the budget for medical measurements. Unlike standard Reinforcement Learning (RL) approaches that control state trajectories, cancer treatments permanently modify patients' transition dynamics, changing how states evolve over time. We model cancer treatment as a belief-space planning problem using active inference, deriving an expected free-energy objective that unifies goal-directed control and information acquisition under measurement budgets without. We implement this framework using real clinical cancer data from the AACR Project GENIE Biopharma Collaborative dataset. Results on clinical data demonstrate a simultaneous patient categorization and high treatment efficacy, under real measurement and treatment constraints.

18.
arXiv (quant-ph) 2026-06-15

Computational regimes in matrix-product-state-based quantum trajectory simulations

arXiv:2606.13779v1 Announce Type: new Abstract: Efficient simulation of open quantum systems is central to modeling noisy quantum hardware and many-body dynamics. In trajectory-based tensor network methods, cost is often associated with trajectory-level quantities such as entanglement growth or bond dimension. However, the total cost of a fixed-accuracy simulation also depends on statistical sampling, and the interplay between per-trajectory complexity and sampling effort remains poorly understood. Here we introduce a cost-resolved framework for matrix product state (MPS)-based quantum trajectory simulations that decomposes total cost into memory per trajectory, runtime per trajectory, and sampling effort. We show that physically equivalent stochastic unravelings of the same Lindblad dynamics do not necessarily reduce total cost, but instead redistribute cost between trajectory complexity and statistical convergence. This trade-off is quantified by two dimensionless inflation factors: a bond dimension inflation $\alpha$ and a sampling inflation $\kappa$, which together determine the preferred unraveling under hardware-dependent memory and parallelism constraints. We provide a practical protocol for extracting $(\alpha,\kappa)$ from modest pilot simulations and demonstrate it using benchmarks across multiple noise channels. The resulting decision maps show that the computationally favorable unraveling can change with noise strength, time-step resolution, system size, and available parallelism. These results establish unraveling choice as a hardware-aware simulation design problem rather than an intrinsic optimization of trajectory entanglement alone.

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

Generative Molecular Design with Steerable and Granular Synthesizability Control

arXiv:2505.08774v2 Announce Type: replace-cross Abstract: Designing molecules that are both property-optimal and readily synthesizable is a central challenge in drug discovery. Existing works that do consider synthesizability can jointly output predicted synthesis routes for generated molecules. However, there has been minimal attention in addressing the ease of synthesis and with flexibility to incorporate desired reaction constraints. On the other hand, virtual screening searches for commercially available compounds, but imposes challenges when scaling to ultra-large (billion-size and beyond) chemical spaces. Here, we propose a generative design framework that unifies synthesis-constrained molecular design and ultra-large-scale virtual screening through steerable and granular synthesizability control. Generated molecules satisfy arbitrary multi-parameter optimization objectives with predicted synthesis routes satisfying mix-and-match constraints: including or avoiding certain reactions, incorporating specific building blocks, and minimizing synthesis route length. In an end-to-end in-house campaign targeting BRD4, we designed molecules synthesizable with specific selected reactions and building blocks, synthesized all six selected compounds, and identified two micromolar binders. We further demonstrate that reaction control enables efficient navigation of ultra-large make-on-demand chemical spaces to identify property-optimal candidates. By applying our framework to Chemspace's Freedom 4.0 make-on-demand space (142 billion molecules), we generated ~320k molecules (0.00023% of the library) on a single consumer-grade GPU (with only 8 GB GPU memory) and identified a micromolar Wee1 binder amongst 60 synthesized candidates. The single unified framework thus enables generating novel synthesizable molecules and retrieving catalogue-ready candidates, offering a flexible solution to mitigating the synthesizability bottleneck.

20.
arXiv (CS.CV) 2026-06-16

Enhancing Precision Agriculture with a Hybrid Deep Learning Framework for Multi-Class Plant Disease Classification and Interpretability

This study proposes an overall deep learning architecture for multi-class classification of plant diseases from high-resolution leaf imagery, with a particular interest in investigating the behavior of ResNet-50 and a hybrid ResNet + Vision Transformer (ViT) design. A specially gathered image database with 15,200 training images and 3,800 validation images spanning 38 classes across multiple crops, including tomato, apple, grape etc. were subjected to preprocessing steps such as resizing, normalization, and data augmentation to enhance model robustness. Multiple architectures, including ResNet-50, MobileNetV2, and EfficientNet-B0, were trained and compared with the hybrid ResNet + ViT model. All models were fine-tuned using the AdamW optimizer and cross-entropy loss, with early stopping applied to prevent overfitting and ensure generalization. Furthermore, interpretability techniques such as Grad-CAM and saliency maps were implemented to indicate disease-relevant regions, while segmentation-based analysis was performed to identify the affected parts of a leaf. For every one of the considered architectures, ResNet-50 led to the highest accuracy of 98.74%, whereas the hybrid ResNet + ViT model achieved a competitive accuracy of 98.58%, showing that the hybrid architectures were effective in capturing both local and overall information. The experimental results showcase the promise of transformer-based models to achieve highly accurate, interpretable, and computationally efficient computer-based multi-class multi-disease classification systems, providing helpful assistance for cultivation management practices as well as for precision farming.

21.
medRxiv (Medicine) 2026-06-18

Digital self-efficacy as a potential intermediary between vision impairment and daily internet use among older adults: A cross-sectional analysis of HINTS 2024

Background: Older adults with vision impairment often experience barriers to using digital technology. The indirect associations between vision impairment and digital access and skills via digital self-efficacy and frustration among older adults remain largely unknown. Objective: This study aimed to 1) explore factors associated with digital access, skills, self-efficacy, and frustration among older adults with vision impairment; 2) examine associations between vision impairment and digital access, skills, self-efficacy, and frustration among older adults; and 3) examine whether digital self-efficacy and frustration may help explain associations between vision impairment and digital access and skills among older adults. Methods: This was a cross-sectional study using nationally representative data from the Health Information National Trends Survey (HINTS) 2024. Respondents aged 60 and older were included. Vision impairment was assessed using a self-reported item. Outcomes included self-reported digital access, skills, self-efficacy, and frustration. Survey-weighted multivariable logistic regression and generalized structural equation modeling were conducted, adjusting for age, sex, race/ethnicity, education, and the number of comorbidities. Results: Among 3,149 older adults (mean [SD] age, 70.7 [10.0] years; 45.6% female), 7.1% (n=223) reported vision impairment. Among older adults with vision impairment, 65.6% (95% CI, 53.5% to 75.9%) used the internet daily, and 79.5% (95% CI, 66.8% to 88.2%) used a smartphone in the past 12 months. In multivariable logistic regression analyses among older adults with vision impairment, older age was associated with lower odds of daily internet use (OR, 0.84; 95% CI, 0.79 to 0.90), smartphone use (OR, 0.85; 95% CI, 0.75 to 0.97), wearable device use (OR, 0.88; 95% CI, 0.79 to 0.97), and using the internet to send a message to a healthcare provider (OR, 0.87; 95% CI, 0.80 to 0.93). Older adults who self-identified as racial and ethnic minority groups (e.g., Black/African American, Hispanic) had lower odds of daily internet use (OR, 0.15; 95% CI, 0.05 to 0.50) and using the internet to send a message to a healthcare provider (OR, 0.17; 95% CI, 0.04 to 0.73) compared with Non-Hispanic White older adults. Vision impairment was associated with lower odds of daily internet use (OR, 0.60; 95% CI, 0.37 to 0.99) and digital self-efficacy (OR, 0.53; 95% CI, 0.32 to 0.86). Digital self-efficacy was associated with higher odds of daily internet use (OR, 2.95; 95% CI, 2.04 to 4.26). Generalized structural equation modeling identified an indirect association between vision impairment and daily internet use via digital self-efficacy (coefficient, -0.68; 95% CI, -1.24 to -0.12). Conclusions: Findings suggest that reduced digital self-efficacy may help explain the observed association between vision impairment and daily internet use among older adults. Interventions targeting digital self-efficacy, including accessible interface designs, personalized coaching, and peer support, may help bridge the digital divide among older adults with vision impairment.

22.
Nature Medicine 2026-06-08

Post-adjuvant chemotherapy in ctDNA-positive patients with resected colorectal cancer: a randomized phase 3 trial

Authors:

Tumor-informed circulating tumor DNA (ctDNA) enables detection of molecular residual disease (MRD) after curative resection of colorectal cancer (CRC), but whether early intervention improves outcomes remains uncertain. ALTAIR was a randomized, double-blind, phase 3 trial embedded in the CIRCULATE-Japan platform evaluating a post-adjuvant ctDNA surveillance strategy with treatment initiation upon molecular recurrence. Patients with resected stage 0–IV CRC who became ctDNA positive after completion of standard-of-care therapy and had no radiological evidence of disease were randomly assigned (1:1) to receive trifluridine/tipiracil (FTD/TPI) or placebo for 6 months. The primary endpoint was investigator-assessed disease-free survival (DFS). Between July 2020 and June 2023, 243 patients were randomized to FTD/TPI (n = 122) or placebo (n = 121). Median DFS was 9.30 months with FTD/TPI and 5.55 months with placebo (hazard ratio = 0.79, 95% confidence interval: 0.60–1.05, P = 0.107), and the primary endpoint was not met. FTD/TPI increased grade 3 or higher hematologic adverse events (73.0% versus 3.3%) without new safety signals. These findings indicate that post-adjuvant intervention with FTD/TPI did not significantly improve DFS in ctDNA-positive patients without radiological disease. ClinicalTrials.gov identifier: NCT04457297 . In the randomized, double-blind phase 3 ALTAIR trial, patients with resected colorectal cancer who became positive for circulating tumor DNA during post-adjuvant surveillance received trifluridine/tipiracil hydrochloride therapy, which did not significantly prolong disease-free survival compared with placebo.

23.
arXiv (quant-ph) 2026-06-11

Sharing quantum indistinguishability with multiple parties

arXiv:2512.15199v3 Announce Type: replace Abstract: Quantum indistinguishability of non-orthogonal quantum states is a valuable resource in quantum information applications such as cryptography and randomness generation. In this article, we present a sequential state-discrimination scheme that enables multiple parties to share quantum uncertainty, in terms of the max relative entropy, generated by a single party. Our scheme is based upon maximum-confidence measurements and takes advantages of weak measurements to allow a number of parties to perform state discrimination on a single quantum system. We review known sequential state discrimination and show how our scheme would work through a number of examples where ensembles may or may not contain symmetries. Our results will have a role to play in understanding the ultimate limits of sequential information extraction and guide the development of quantum resource sharing in sequential settings.

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

Geometric and Quantum Kernel Methods for Predicting Skeletal Muscle Outcomes in chronic obstructive pulmonary disease

arXiv:2601.00921v3 Announce Type: replace-cross Abstract: Chronic obstructive pulmonary disease (COPD) affects hundreds of millions of people worldwide, and skeletal-muscle dysfunction is clinically important. Quantum machine learning is increasingly explored for biomedical prediction, but its value in small biomarker cohorts requires benchmarking against strong classical baselines. We analysed a cigarette-smoke COPD cohort of 213 animals with blood and bronchoalveolar-lavage biomarkers to predict tibialis anterior muscle weight, muscle quality, and force. We developed a kernel-geometric quantum hybrid method in which synthetic symmetric positive definite (SPD) references are mapped through a reproducing kernel Hilbert space, compressed using train-only random projection, normalised, and supplied to low-dimensional quantum regression circuits. We benchmarked this approach against classical ridge/kernel models, SPD relational representations, and quantum-kernel regression (QKR). All methods were evaluated using condition-stratified repeated cross-validation. The largest numerical improvement was observed for muscle weight, where the proposed method had the numerically lowest mean root mean squared error (RMSE), approximately 1.8% below the best classical comparator; paired fold-level testing did not establish statistically significant superiority after Holm adjustment, but the endpoint is biologically meaningful. The method also had the numerically lowest mean RMSE for muscle quality. For force, biomarker-only Ridge performed best, suggesting a more linear endpoint structure.

25.
medRxiv (Medicine) 2026-06-10

A Three-Tier Operational Benchmark for Evaluating Large Language Models on Hospital Medication Safety

Objective. To introduce PsiBench, a clinically validated medication-safety benchmark for evaluating large language models (LLMs) against the standards used to certify hospital computerized provider order entry (CPOE) and electronic health record (EHR) systems, and a non-overlapping three-tier evaluation framework separating highest-stakes discrimination, the operational CDS regime, and category-correct alerting. Materials and Methods. PsiBench comprises 492 medication-safety scenarios across 11 safety categories, created by clinical pharmacology experts whose work underpins an annualized testing procedure used by more than 2,000 U.S. hospitals. The three-tier framework partitions the scenarios non-overlappingly: Discrimination (98 scenarios, 50 fatal vs 48 deception, near-balanced 51%/49%); Operational (394 scenarios, 261 serious unsafe plus 133 safe including 41 Excessive Alerts reclassified as operational negatives); and Attribution (311 alert-required scenarios). We evaluated 40 frontier LLMs from 10 providers over 3 runs per scenario at temperature 0.2 (or the provider default where temperature is not configurable), yielding 59,040 evaluations conducted April 21-23, 2026. Results. Headline binary performance on the full benchmark spans a wide range across the 40 models: F1 78.5%-92.3%, accuracy 65.4%-89.8%, sensitivity 81.4%-100.0%, specificity 6.1%-81.8%. Leading models by F1 (o4-mini 92.3%; o3 92.2%) pair high sensitivity with meaningful specificity; three models saturate sensitivity at 100% but fall below 25% specificity, indistinguishable from a naive always-alert classifier. The wide spread on a single headline metric motivates tier-specific analyses, developed in a separate clinical paper. Discussion and Conclusion. PsiBench and the three-tier framework operationalize a rigorous evaluation rubric for LLM medication safety, grounded in two decades of national hospital audit experience. The framework generalizes to any binary medication-safety classifier (rule-based, conventional ML, or LLM-driven), supporting tier-aware model selection and post-deployment surveillance.