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01.
arXiv (CS.CL) 2026-06-11

Geometric Metrics and LLMs: What They Measure and When They Work

作者:
Viacheslav Yusupov↗Anna Antipina↗Ameliia Alaeva↗Danil Maksimov↗Anna Vasileva↗Tatyana Zaitseva↗Alina Ermilova↗Evgeny Burnaev↗Egor Shvetsov↗

We present a systematic stress-test of geometric metrics for LLM evaluation. Rank-based geometric properties of internal representations have shown promise as reference-free quality signals, but the conditions under which they are reliable remain unclear. We evaluate eight commonly-used metrics: intrinsic-dimensionality estimators, spectral norms, and related quantities across six tester models (0.5-8B) and eight generators on contrasting tasks, separating genuine geometric signal from text-length effects and from what standard text statistics already capture. Three findings emerge. First, some metrics (notably Schatten Norm and MOM) mainly reflect output length, and their apparent discriminative power collapses once length is controlled. Second, geometric metrics add modest but real information beyond text statistics: combined with them, a classifier reaches 78% accuracy on 6-way generator identification versus 69% for text statistics alone. Third, rather than tracking a general notion of text quality, the metrics demonstrate only moderate association between the intrinsic-dimensionality and lexical diversity (RTTR). We give use-case-specific recommendations and identify failure detection as the most promising near-term application.

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02.
arXiv (CS.CV) 2026-06-16

MolSight: Molecular Property Prediction with Images

作者:
Aaditya Baranwal↗Akshaj Gupta↗Yogesh S Rawat↗Shruti Vyas↗

Every molecule ever synthesised can be drawn as a 2D skeletal diagram, yet in modern property prediction this universally available representation has received less focus in favour of molecular graphs, 3D conformers, or billion-parameter language models, each imposing its own computational and data-engineering overhead. We present $MolSight$, the first systematic large-scale study of vision-based Molecular Property Prediction (MPP). Using 10 vision architectures, 7 pre-training strategies, and $2\,M$ molecule images, we evaluate performance across 10 downstream tasks spanning physical-property regression, drug-discovery classification, and quantum-chemistry prediction. To account for the wide variation in structural complexity across pre-training molecules, we further propose a $chemistry-informed curriculum$: five structural complexity descriptors partition the corpus into five tiers of increasing chemical difficulty, consistently outperforming non-curriculum baselines. We show that a single rendered bond-line image, processed by a vision encoder, is sufficient for competitive molecular property prediction, i.e. $chemical insight from sight alone$. The best curriculum-trained configuration achieves the top result on $5 of 10$ benchmarks and top two on $all 10$, at $$80$\times$ lower$$ FLOPs than the nearest multi-modal competitor.

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

Zero-Inflated Gaussian Distributions Enable Parameter-Space Sparsity in Estimation-of-Distribution Algorithms

作者:
Andreas Faust↗Sven Nitzsche↗Juergen Becker↗

arXiv:2606.19369v1 Announce Type: cross Abstract: Estimation-of-distribution algorithms (EDAs) are a powerful class of evolutionary methods for black-box optimization, especially when little is known about the structure of the objective. Whereas classical evolutionary algorithms rely on hand-designed mutation and crossover operators, hard to devise for unknown problem structures, and a source of bias, EDAs sidestep operator design entirely: they fit a probability distribution to the best individuals and sample the next generation from it. EDAs are well established on continuous parameter spaces, but they have not previously been generalized to sparse ones, in which most coefficients of a good solution are exactly zero. Existing sparse black-box optimizers therefore reintroduce exactly what EDAs were designed to avoid: hand-crafted sparsity operators, bi-level schemes alternating between support set and active values, zeroing thresholds, and other baked-in assumptions. We close this gap by proposing multivariate zero-inflated Gaussian (ZIG) distributions as EDA sampling laws. A latent Gaussian model with separate indicator and value dimensions represents sparsity patterns, correlations among active parameters, and the interactions between the two, so sparsity patterns and active values are optimized jointly, hierarchy-free. We show that the latent parameters of this model are identifiable from observed samples, unlike in the missing-data settings where related constructions originate, and introduce practical amortized inversion-based estimators for them. The estimators accurately recover latent correlation structures, and on the Lunar Lander benchmark the resulting ZIG-EDA converges faster and reaches higher final returns than a dense Gaussian EDA, a hand-crafted sparse evolutionary algorithm, and an ad-hoc sparse EDA, while finding controllers with only a small fraction of parameters active.

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04.
arXiv (CS.CV) 2026-06-12

InterleaveThinker: Reinforcing Agentic Interleaved Generation

作者:
Dian Zheng↗Harry Lee↗Manyuan Zhang↗Kaituo Feng↗Zoey Guo↗Ray Zhang↗Hongsheng Li↗

Recent image generators have demonstrated impressive photorealism and instruction-following capabilities in single-image generation and editing. However, constrained by their architectures, they cannot achieve interleaved generation (text-image sequence), which has crucial applications in visual narratives, guidance, and embodied manipulation. Even the latest open-source Unified Multimodal Models (UMMs) exhibit limited performance in this regard. In this paper, we introduce InterleaveThinker, the first multi-agent pipeline designed to endow any existing image generator with interleaved generation capabilities. Specifically, we employ a planner agent to organize the image-text input sequence, instructing the image generator on the required execution at each step. Subsequently, we introduce a critic agent to evaluate the generator's outputs, identify samples that deviate from the planned instructions, and refine the instructions for regeneration. To implement this pipeline, we construct the Interleave-Planner-SFT-80k and Interleave-Critic-SFT-112k to perform a format cold-start. Then we develop Interleave-Critic-RL-13k to reinforce the step-wise instruction correction capability within a generation trajectory using GRPO. Since a single interleaved generation trajectory may involve over 25 generator calls, optimizing the entire trajectory is computationally impractical. Therefore, we propose accuracy reward and step-wise reward, allowing single-step RL to effectively guide the entire generation trajectory. The results show that InterleaveThinker improves performance across various image generators. On interleaved generation benchmarks, it achieves performance comparable to Nano Banana and GPT-5. Surprisingly, it also significantly enhances the base model on reasoning-based benchmarks; for example, on 4-step FLUX.2-klein, we observe substantial gains on WISE and RISE.

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05.
Nature (Science) 2026-06-12

Daily briefing: How Venus flytraps snap shut

作者:
Flora Graham↗

Softening cells enable flytraps to shut with astonishing speed. Plus, the cutting-edge science happening at the World Cup and why scientists shouldn’t ignore the Pope’s AI message. Softening cells enable flytraps to shut with astonishing speed. Plus, the cutting-edge science happening at the World Cup and why scientists shouldn’t ignore the Pope’s AI message.

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

ChronoID: Infusing Explicit Temporal Signals into Semantic IDs for Generative Recommendation

作者:
Dongdong Nian↗Dongqi Fu↗Chenliang Xu↗Yinglong Xia↗Hong Li↗Hong Yan↗Jian Kang↗

arXiv:2606.14260v1 Announce Type: cross Abstract: Semantic IDs are crucial in generative recommendation, but with a fundamental limitation: temporal information is not well incorporated into semantic IDs. Instead, time influences recommendation only implicitly (e.g., through session construction heuristics, preference alignment, or sequence order), while existing semantic ID learning remains entirely time-agnostic. This design conflates interactions occurring under distinct temporal contexts into identical semantic representations, implicitly assuming that item semantics and user intent are temporally stationary. Such an assumption is misaligned with real-world recommendation scenarios, where evolving interaction rhythms play a central role. In this work, we investigate where and how the explicit time should be incorporated into semantic ID for generative recommendation. First, we systematically characterize the design space along three orthogonal dimensions of temporal signals and present a unified framework, ChronoID, for time-aware semantic ID learning. Then, by contributing a new time-explicit generation recommendation benchmark, ChronoID answers the questions: what is the effective way of infusing time, how to design the architecture, and where does the gain come from.

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

Simplex-Constrained Sparse Bagging: Transitioning from Uniform Priors to Sparse Posteriors in Ensemble Learning

作者:
Meher Sai Preetam↗Meher Bhaskar↗

arXiv:2606.13589v1 Announce Type: new Abstract: We present Simplex-Constrained Sparse Bagging (SCSB), a mathematically rigorous framework for post-training compression and probability calibration of bootstrap-based bagging ensembles. Standard bagging ensembles (such as Random Forests, Bagged SVMs, and Bagged Neural Networks) assign uniform voting power to all constituent estimators. However, this naive uniform prior ignores the varying local competence of base estimators and contributes to model overconfidence. We formulate ensemble pruning and calibration as a joint optimization problem over the probability simplex by minimizing the Out-Of-Bag (OOB) loss. To induce sparsity, we address the theoretical "L1-simplex paradox" – the mathematical reality that the L1 norm is constant on the simplex and fails to prune – by introducing a concave quadratic penalty. SCSB is model-agnostic and achieves up to 96% ensemble compression, yielding linear inference speedups and superior probability calibration (lowered Expected Calibration Error) while preserving or enhancing generalization accuracy.

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08.
arXiv (CS.LG) 2026-06-17

Geometrical fairness in graph neural networks

作者:
Arturo P\'erez-Peralta↗Sandra Ben\'itez-Pe\~na↗Blas Kolic↗Rosa E. Lillo↗

arXiv:2606.17684v1 Announce Type: cross Abstract: Graph-based learning methods have become increasingly prominent due to their strong performance across diverse applications. Among these, recent frameworks grounded in diffusion processes provide a unifying perspective that extends traditional graph neural network formulations while addressing limitations of standard message-passing mechanisms. Despite these advances, concerns remain regarding the fairness of such models, as they may propagate or amplify biases present in the data. In this work, we introduce a fairness-aware adaptation of graph-based diffusion by modifying the underlying Laplacian operator. Our approach incorporates multiple complementary transformations, including subspace projections, spectral adjustments, and frequency-based filtering, to mitigate bias-related components. Leveraging the intrinsic smoothing properties of graph diffusion, we provide a principled analysis of the resulting behavior and establish theoretical insights into fairness properties. We evaluate the proposed framework on both synthetic and real-world datasets, demonstrating that it achieves competitive performance while improving fairness metrics with limited additional computational cost.

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09.
arXiv (CS.CV) 2026-06-15

Boundary-Centric Clip-Budgeted Active Learning for Temporal Action Segmentation

作者:
Halil Ismail Helvaci↗Sen-ching Samson Cheung↗

Temporal action segmentation (TAS) in untrimmed videos requires dense temporal supervision. However, most of the annotation cost is spent identifying action transitions where segmentation errors concentrate and small temporal shifts can disproportionately degrade segment-level metrics. We introduce B-ACT, a clip-budgeted active learning framework that explicitly allocates supervision to these error-prone boundary regions. B-ACT operates in a hierarchical two-stage loop: (i) it ranks and queries unlabeled videos using predictive uncertainty, and (ii) within each selected video, it detects candidate transitions from the current model predictions and selects the top-$K$ boundaries via a novel boundary score. The boundary score fuses neighborhood uncertainty, class ambiguity, and temporal prediction dynamics to reveal the underlying importance of each frame. Importantly, our annotation protocol requests labels only at the boundary frames while still training on boundary-centered clips to exploit temporal context through the model's receptive field. Extensive experiments on GTEA, 50Salads, and Breakfast demonstrate that boundary-centric supervision delivers strong label efficiency and consistently surpasses representative TAS active learning baselines and prior state of the art under sparse budgets. Gains are largest on datasets where performance is highly sensitive to boundary placement, as measured by edit and overlap-based F1 metrics.

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

Turning music identification into a neural forward pass

作者:
Muhammad Taimoor Haseeb↗Ahmad Hammoudeh↗Gus Xia↗

arXiv:2606.17301v1 Announce Type: cross Abstract: Search, a foundational operation in computer science, maps a query to a matching item in a collection. It is typically implemented as a System-2 like, rule-based pipeline in which a key is computed, an index is probed, and candidates are verified. By contrast, human recognition resembles a System-1 like, associative model of identity recovery, in which even partial cues can trigger a recall without explicitly enumerating, ranking, or even accessing discrete candidates. Here, we show that music sound identification, a difficult search problem, can be performed in a single neural feed-forward pass by a generative transformer. Trained on an audio dataset, the model predicts the corresponding track identifier from a short audio excerpt. This approach surpasses state-of-the-art acoustic fingerprinting, with the largest gains for short audio segments (1 second), demonstrating the method is not only viable but advantageous. Moreover, it reduces external storage to 0.33% of the baseline footprint and improves inference latency by 2.3x (p95). Furthermore, the model can reject queries for unseen tracks, supporting open-set operation while reducing misattribution risk. Using music track identification as an example, this work reframes search, bringing it closer in spirit to human associative recognition and away from algorithmic database lookup.

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11.
arXiv (quant-ph) 2026-06-15

Quantum-Classical Hierarchical Equations of Motion

作者:
Amartya Bose↗

arXiv:2606.14363v1 Announce Type: new Abstract: We develop a quantum-classical hierarchical equations of motion (QC-HEOM) approach for simulating non-Markovian open quantum systems. The method combines the ensemble-averaged classical path reference of the quantum-classical path integral formalism with a hierarchy of auxiliary quantum influence functionals. By incorporating thermal fluctuations through an ensemble average over reference trajectories, the hierarchy is required to represent only the residual quantum memory associated with the imaginary part of the bath response function. Consequently, unlike conventional hierarchical equations of motion, QC-HEOM does not require Matsubara or Padé expansions of the thermal kernel and exhibits only weak temperature dependence of the hierarchy size. Furthermore, because thermal fluctuations are supplied through reference classical trajectories, the framework naturally extends beyond harmonic baths and enables the incorporation of anharmonic and molecular environments through externally generated trajectories. We derive the formalism and demonstrate its exactness for a harmonic bath. Applications to an asymmetric spin-boson model and the seven-site Fenna–Matthews–Olson complex illustrate the accuracy of QC-HEOM. It reproduces benchmark quasi-adiabatic path integral and hierarchical equations of motion results while requiring substantially fewer auxiliary objects, particularly at low temperatures. These results establish QC-HEOM as an efficient framework for treating residual quantum memory in quantum-classical descriptions of open-system dynamics. The separation of thermal fluctuations from residual quantum memory through the use of Wigner trajectories provides an approximate route toward hierarchical treatments of complex anharmonic environments that are inaccessible to conventional HEOM approaches.

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12.
arXiv (quant-ph) 2026-06-16

Non-Markovianity-based ultrasensitive parameter estimation

作者:
Olli Siltanen↗

arXiv:2211.05142v2 Announce Type: replace Abstract: Accurate parameter estimation is a central task in quantum metrology and sensing, where quantum resources can provide precision beyond classical limits. In realistic settings, however, system-environment interactions lead to decoherence, reducing these strategies to their classical counterparts. Noise is typically classified as Markovian or non-Markovian, with the latter often preserving quantum coherence longer and thus supporting better metrological performance. Still, the absence of noise is generally considered ideal. In this work, we uncover a striking reversal: certain non-Markovian environments not only outperform Markovian ones - including their quantum Cramér-Rao bounds - but can also surpass the entirely noiseless case. We demonstrate these findings numerically for an all-optical setup, which is experimentally feasible and can be extended to other physical platforms. In general, our results open new avenues for noise-assisted quantum metrology beyond conventional limits.

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13.
arXiv (CS.CL) 2026-06-16

Not What, But How: A Framework for Auditing LLM Responses across Positioning, Generalization, Anthropomorphism, and Maxims

作者:
Siddhesh Milind Pawar↗Sarah Masud↗Haneul Yoo↗Alice Oh↗Isabelle Augenstein↗

Large language models (LLMs) are being increasingly used to answer subjective, information-seeking questions, where users are sensitive to how responses are communicated, not just whether the answers are correct. Existing LLM evaluations for subjective cultural queries largely focus on factual correctness, ignoring how the response is framed. To this end, we introduce FRANZ, an automated FRAmework for respoNse characteriZation to conduct communicative audit of LLM responses along four dimensions: cultural positioning, use of generalizing language, anthropomorphic cues, and adherence to conversational maxims. To enable this evaluation, we contribute SQUARE - a corpus of 376k subjective questions sourced from 57 subreddits, and mapped to 7 countries and 19 question categories. We demonstrate FRANZ's applicability by scoring responses from three open-weight LLMs. We observe that LLMs show statistically significant differences in the frequency with which they employ each response characteristic. Unlike single-dimensional audits, FRANZ reveals that insider positioning and anthropomorphism are positively coupled, with the degree of coupling varying by country, providing a diagnostic lens for identifying framing divergences.

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14.
medRxiv (Medicine) 2026-06-15

Association of Genetic Liability to Psychiatric Disorders with Peripheral Metabolic Dysregulation

作者:
De la Hoz↗J. F↗Lee↗Y. H↗Tubbs↗J. D↗Meyerson↗Cudic↗Watts↗Feng↗Y.-C. A↗Chen↗…

Importance: Individuals with psychiatric disorders face elevated cardiometabolic risk which is linked to increased mortality. The extent to which this reflects shared pathogenesis or the downstream effects of illness and treatment remains poorly understood. Objective: To characterize the direct pleiotropic effects of psychiatric genetic liability on circulating metabolites and aggregate cardiometabolic risk, independent of psychiatric diagnosis and psychotropic medication use. Design: Cohort study. Setting: Mass General Brigham Biobank (MGBB). Participants: MGBB participants with metabolomic profiling, genomic data, and linked electronic health records. Exposures: Genetic liability to nine psychiatric disorders quantified using polygenic risk scores (PRS): attention deficit/hyperactivity disorder (ADHD), anorexia nervosa (ANO), anxiety disorder (ANX), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), PTSD, schizophrenia (SCZ), and substance use disorder (SUD). Main Outcomes and Measures: 249 circulating metabolites and four metabolomic risk scores (MRS) for type 2 diabetes, myocardial infarction, ischemic stroke, and vascular dementia. PRS-metabolite associations were estimated using nested models adjusting for lifetime psychiatric diagnosis and psychotropic medication use. Results: Across 25,290 participants, we identified 604 significant PRS-metabolite associations (Bonferroni p< 1.36 x 10-4), of which 89% persisted after adjustment for lifetime diagnosis and medication use, suggesting that the direct genetic effects on metabolism are largely independent of illness or treatment. PRS for MDD, PTSD, and ADHD showed the most extensive dysregulation, with a transdiagnostic pattern of elevated lipids and systemic inflammation, specifically triglycerides ({beta} = 0.04 to 0.05, all p< 4.4 x10-13) and glycoprotein acetyls ({beta} = 0.05, all p< 2.2 x10-16). Notably, PRS for SCZ and BD showed minimal metabolite dysregulation despite having the strongest association with their target diagnoses. PRS for MDD, PTSD, ADHD, and SUD were associated with increased MRS across cardiometabolic conditions ({beta} = 0.03 to 0.08, all p< 2.1 x10-4). Sensitivity analyses controlling for BMI or excluding participants without any psychiatric history (N: 21,305 and 11,150, respectively) showed a similar pattern. Conclusions and Relevance: Psychiatric genetic liability is associated with systemic metabolic dysregulation independent of illness onset or treatment, supporting a partially pleiotropic basis for psychiatric-cardiometabolic comorbidity.

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

Mean-Field Parallel Decoding for Discrete Diffusion Language Models

作者:
Tamim Zoabi↗Ameen Ali↗Liran Ringel↗Lior Wolf↗

arXiv:2606.15805v1 Announce Type: new Abstract: Discrete diffusion language models enable parallel token generation, offering a pathway to low-latency decoding. However, selecting tokens independently by marginal confidence limits effective parallelism: tokens that appear reliable in isolation can form incompatible configurations when several positions are updated at once. We introduce a training-free decoding framework that coordinates these parallel updates. At each forward pass, the method assigns a commit score to each masked position and refines these scores using pairwise interactions derived from the model's predictive distributions. A variational relaxation yields a simple fixed-point update that suppresses conflicting simultaneous commitments within a single forward pass. This mechanism allows the decoder to commit more tokens in parallel while maintaining competitive generation quality. The method is lightweight, requires no auxiliary model or retraining, and drops into existing diffusion decoding pipelines without modification. Experiments on reasoning and code-generation benchmarks show consistent improvements in the quality-latency trade-off.

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

QoS-Aware Token Scheduling and Private Data Valuation for Multi-Modal Agentic Networks

作者:
Yao Du↗Jing Liu↗Pengfei Xu↗Zehua Wang↗Victor C. M. Leung↗Cyril Leung↗Victoria Lemieux↗

arXiv:2606.15573v1 Announce Type: new Abstract: In agentic systems, human-generated data records anchor the value of AI services. Yet cloud compute pipelines centralize processing on remote servers. Data centralization reduces personal data sovereignty and may potentially degrade the quality of service (QoS). Meanwhile, user contributions are diverse in quantity and quality: decentralized records can be biased, noisy, and heterogeneously distributed. To address the data challenge, we study fair token allocation and private data valuation for decentralized and resource-constrained agentic systems. Our approach embeds multi-modal representations in a shared semantic space and releases differentially private (DP) prototypes to preserve utility while reducing semantic leakage. With the DP guarantee, we design a fair token allocation scheme that rewards effective contributions and remains robust to data heterogeneity and AI resource scarcity. Extensive simulations demonstrate improved contribution-based fairness and QoS compared to standard benchmarks. The improved resistance to image reconstruction attacks indicates enhanced privacy for multi-modal personal data.

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17.
arXiv (CS.LG) 2026-06-12

Learning-Augmented Approximation for Unrelated-Machines Makespan Scheduling

作者:
Kaito Baba↗Evripidis Bampis↗Giorgos Mitropoulos↗

arXiv:2606.13133v1 Announce Type: cross Abstract: Recently, Antoniadis et al. (ICLR 2025) proposed a framework for incorporating predictions to approximate NP-hard selection problems. Despite its simplicity, this approach tightly matches theoretical lower bounds, making its generalization highly compelling. We address an open question raised in the work of Antoniadis et al., concerning the extension of this approach to other important problems outside the class of selection problems, such as scheduling. We develop a learning-augmented algorithm for the makespan minimization problem on unrelated machines, denoted by $R\|C_{\max}$. By using predictions of heavy job assignments, we achieve a polynomial-time $(1+\varepsilon)$-approximation for accurate predictions that smoothly degrades to a worst-case 2-approximation as the error increases. We conclude our work with an empirical analysis of our method.

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18.
arXiv (quant-ph) 2026-06-12

Coupling-Grouped XY-QAOA for Joint Anomaly-Feature Selection

作者:
Pauli Taipale↗

arXiv:2606.13244v1 Announce Type: new Abstract: Selecting anomalous samples and explanatory features under fixed budgets defines a coupled constrained-optimization problem. Sequential feature-first selection ranks features before choosing samples, which can overlook features whose utility depends on which samples are selected, especially when scores are calibrated from reference data that may be limited, noisy, or drifting. We instead formulate the task as joint sample-feature selection under the same fixed counts. In the analyzed formal model, calibration-error sensitivity grows linearly with the number of samples for feature-first ordering but stays constant for joint selection. We introduce Coupling-Grouped XY-QAOA, a constraint-preserving grouped-angle variant for the resulting optimization problem. On matched sparse IBM Heron R3 benchmarks, a hardware-aware implementation reduces circuit depth by 45.9%-61.3% and two-qubit gates by 2.6%-5.2% relative to Qiskit optimization level 3 on the CZ-basis target. It enables, to our knowledge, the largest reported width-depth configurations for constraint-preserving bipartite-selection QAOA hardware executions with feasible-sector retention: 64 qubits at p=2 and 36 qubits at p=3. The 20-qubit p=5 runs retain 63% valid samples. Across 36-64 qubits, fixed-angle runs yield lower-energy feasible samples than matched random-feasible sampling. Warm starts reduce the gap to strict-feasible classical references by 57.5%-80.5%, and near-budget repair matches the sparse classical reference at 36 qubits. Benchmarks show gains in balanced fixed-budget regimes, and noiseless simulations show that problem-structured angle grouping improves over same-depth XY-QAOA and matched-parameter, type-preserving randomization controls. Overall, the results support calibrated joint selection and hardware-realizable constrained-mixer execution in the tested regimes.

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19.
bioRxiv (Bioinfo) 2026-06-14

TopoMIL: Topology Improves Multiple Instance Learning in Diagnostic Microscopic Images

作者:
Kazeminia↗Dasdelen↗M. F↗Rieck↗Marr↗

Microscopic images of cells and tissues are central to disease diagnosis. In computational pathology, multiple instance learning (MIL) has emerged as a key paradigm for analyzing numerous images within a single patient sample. While the representative distribution of cells in a sample is important for diagnosis, existing MIL frameworks largely overlook it. We introduce TopoMIL, a framework that extracts the representative topological structure of the sample and integrates it into the MIL classifier. Three topological representations are assessed, each with distinct advantages and computational costs. We evaluate TopoMIL on four histopathology and cytomorphology datasets, each presenting unique challenges. Integrating the sample's topological information into MIL enhances classification across average, max, attention-based, and transformer pooling, yielding AUCROC gains of 3.3%, 4.2%, 5.9%, and 0.5%, respectively, with moderate computational cost. Our work underscores the potential of TopoMIL as a scalable extension to existing morphology-based models in computational pathology.

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20.
medRxiv (Medicine) 2026-06-17

Low-Density Lipoprotein Cholesterol and Dementia Risk: Integrating Mendelian Randomization and Target Trial Emulation Within the Heart-Brain Axis

作者:
Mukumbi↗Liu↗Shi↗Toyli↗Hung↗G.-U↗Chen↗Q.-H↗Sha↗Chiu↗P.-Y↗Zhou↗…

Background: The heart-brain axis links cardiovascular and neurodegenerative disease through shared vascular and inflammatory mechanisms. Although low-density lipoprotein cholesterol (LDL-C) is an established causal factor in atherosclerotic cardiovascular disease (ASCVD), its relationship with dementia remains uncertain, with midlife elevations associated with increased risk but late-life associations often appearing null or inverse. To address this cholesterol paradox, we integrated mendelian randomization (MR) with an active-comparator new-user target trial emulation. Methods: We applied a triangulated causal inference framework integrating two-sample MR with observational target trial emulation. Genetic variants associated with LDL-C were used as instrumental variables to evaluate Alzheimer disease (AD), dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), and any dementia (AnyDem), with causal estimates derived using inverse-variance weighted models and sensitivity analyses for heterogeneity and pleiotropy. In parallel, an active-comparator new-user design compared statin versus ezetimibe initiation among adults aged 60 years or older using propensity score (PS) overlap weighting and Cox proportional hazards models to evaluate cardiovascular and dementia outcomes. Results: Genetically predicted LDL-C was associated with increased risk of DLB (OR 1.65, 95% CI 1.30-2.10; p

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21.
bioRxiv (Bioinfo) 2026-06-10

A Unified Spatial AI Framework for Cross-Domain Tissue-State Analysis in Trauma, Oral, and Cardiovascular Pathology

作者:
Pham↗T. D↗

Objective: To develop a cross-domain spatial AI framework for identifying conserved tissue-state organisation across trauma, oral disease, and cardiovascular tissue using spatial transcriptomic data. Methods: Four public spatial transcriptomic datasets spanning wound healing, periodontitis, oral squamous cell carcinoma, and cardiac tissue were integrated using recurrence modelling, graph-based spatial learning, fuzzy tissue-state analysis, and tensor decomposition. Cross-domain coupling, spatial fragmentation, recurrence structure, and permutation-based topological validation were evaluated. Results: Six conserved fuzzy tissue states were identified, dominated by extracellular matrix remodelling, fibroblast/stromal activation, endothelial signalling, and inflammatory pathways. Latent embedding analysis demonstrated strong overlap between trauma and oral domains, while cardiovascular tissue exhibited more compact spatial organisation. Oral inflammatory tissue showed the highest fragmentation, whereas cardiovascular tissue demonstrated greater recurrence coherence. Tensor decomposition identified conserved stromal-remodelling programmes across domains. Permutation testing confirmed significantly elevated graph modularity and reduced spatial entropy relative to null distributions. Conclusion: The proposed framework identified conserved spatial tissue-state architecture linking wound healing, oral pathology, and cardiovascular tissue despite differences in tissue origin, pathology, and acquisition technology. Significance: These findings demonstrate the potential of spatial AI for investigating conserved stromal and inflammatory microenvironmental organisation across clinically related disease systems and may support spatial biology research in trauma–oral–systemic health.

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22.
arXiv (CS.LG) 2026-06-18

Provable quantum speedups for computing persistence in topological data analysis

作者:
Casper Gyurik↗Alexander Schmidhuber↗Robbie King↗Vedran Dunjko↗Ryu Hayakawa↗

arXiv:2410.21258v2 Announce Type: replace-cross Abstract: Topological data analysis (TDA) aims to extract noise-robust features from a data set by examining the number and persistence of holes in its topology. We provide an efficient quantum algorithm for a computational problem closely related to a core task in TDA – determining whether a given hole persists across different length scales. Further, we prove the problem itself is $\mathsf{BQP}_1$-hard, implying that a classical solution is extremely unlikely; this stands in contrast to all previous quantum approaches to TDA, where the problems were also intractable for quantum computers, or where a rigorous proof of classical hardness still remains open. This result implies an {exponential} quantum speedup for this problem under standard complexity-theoretic assumptions. Our approach relies on encoding the persistence of a hole in a variant of the guided sparse Hamiltonian problem, where the guiding state is constructed from a harmonic representative of the hole.

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23.
arXiv (CS.CV) 2026-06-12

Plug-and-Play image restoration with Stochastic deNOising REgularization

作者:
Marien Renaud↗Jean Prost↗Arthur Leclaire↗Nicolas Papadakis↗

Plug-and-Play (PnP) algorithms are a class of iterative algorithms that address image inverse problems by combining a physical model and a deep neural network for regularization. Even if they produce impressive image restoration results, these algorithms rely on a non-standard use of a denoiser on images that are less and less noisy along the iterations, which contrasts with recent algorithms based on Diffusion Models (DM), where the denoiser is applied only on re-noised images. We propose a new PnP framework, called Stochastic deNOising REgularization (SNORE), which applies the denoiser only on images with noise of the adequate level. It is based on an explicit stochastic regularization, which leads to a stochastic gradient descent algorithm to solve ill-posed inverse problems. A convergence analysis of this algorithm and its annealing extension is provided. Experimentally, we prove that SNORE is competitive with respect to state-of-the-art methods on deblurring and inpainting tasks, both quantitatively and qualitatively.

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24.
arXiv (CS.LG) 2026-06-19

Representing Piecewise-Linear Functions by Functions with Minimal Arity

作者:
Christoph Koutschan↗Anton Ponomarchuk↗Josef Schicho↗

arXiv:2406.02421v2 Announce Type: replace-cross Abstract: Any continuous piecewise-linear function $F\colon \mathbb{R}^{n}\to \mathbb{R}$ can be represented as a linear combination of $\max$ functions of at most $n+1$ affine-linear functions. In our previous paper [``Representing piecewise linear functions by functions with small arity'', AAECC, 2023], we showed that this upper bound of $n+1$ arguments is tight. In the present paper, we extend this result by establishing a correspondence between the function $F$ and the minimal number of arguments that are needed in any such decomposition. We show that the tessellation of the input space $\mathbb{R}^{n}$ induced by the function $F$ has a direct connection to the number of arguments in the $\max$ functions.

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25.
bioRxiv (Bioinfo) 2026-06-11

DyMoTree decodes early cell state transitions and drivers from single-cell transcriptomes using a tree-structured neural network

作者:
Wang↗Xu↗Tu↗Qiang↗Guo↗Li↗

Inferring early cell fate from single-cell RNA-sequencing data is essential for identifying cellular origins and fate plasticity in development and disease. However, existing methods often fail to exploit tree-structured lineage trajectories, limiting the accuracy and interpretability of fate mapping. Here we present DyMoTree, a computational framework that models cell fate decisions as nonlinear mappings between progenitor and terminal cell states under explicit lineage constraints. By integrating lineage graphs with a tree-structured neural architecture, DyMoTree learns lineage-resolved cell-state transition maps from single-cell transcriptomes, enabling robust inference of early fate bias and identification of fate-specific progenitor substates and driver genes. Across simulations, lineage-tracing experiments, and in vivo systems, DyMoTree outperformed existing methods in resolving early fate biases. Applications to mouse embryogenesis, lung adenocarcinoma progression, and CAR-T immunotherapy revealed regulatory programs underlying developmental and disease-associated transitions. DyMoTree provides a general framework for modeling lineage-resolved cell-state dynamics underlying development and disease progression.

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