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01.
medRxiv (Medicine) 2026-06-22

Longitudinal multi-omics characterization of the malignant evolution in multirelapsing glioblastoma

Authors:
Lackman↗M. H↗Wardell↗Darrigues↗De Loose↗Lyle↗G. A↗Xue↗Learned↗Cheney↗Vaske↗O. M↗…

Linking glioblastoma (GBM) evolution to clinical progression is challenged by multiple factors, including tumor location for repeated sample collection, and short patient survival. In a single individual, we collected and analysed samples from 11 operations distributed across 31 months of multi-relapsing and multifocal GBM, including terminal leptomeningeal progression. All samples shared genomic ancestry of the retinoblastoma protein 1 (RB1) and neurofibromin 1 (NF1) mutations while advanced progression and extracranial metastases featured mutations of tuberous sclerosis complex 2 (TSC2), PBRM1, CD22 and Fanconi anemia supplementation group I (FANCI), correlated with clinical resistance to immunotherapies and DNA-damaging agents. Single-cell analytics revealed distinct yet reversible shifts in response to the precision medicine arsenal. GBM parenchymal dissemination and extracranial progression were associated with strengthening of neuron-like cell phenotypes. Our multidimensional study describes GBM evolution over a rarely reported time scale, and provides a valuable resource linking genetic, molecular, cellular and clinical progressions.

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02.
arXiv (CS.LG) 2026-06-12

Robustness Verification of Recurrent Neural Networks with Abstraction Refinement

Authors:
Li-Jen Lin↗Chih-Duo Hong↗

arXiv:2606.12490v1 Announce Type: new Abstract: Certified local robustness verification for recurrent neural networks (RNNs) is challenging because approximation errors introduced by nonlinear relaxations can propagate through recurrent connections and accumulate over time. As a result, scalable linear bound propagation methods often become overly conservative and fail to certify inputs that are in fact robust, especially when many pre-activation intervals cross zero. We propose an abstraction-refinement framework for RNN verification that partitions such intervals to remove the dominant relaxation error: on each refined branch, ReLU becomes exact, and smooth activations such as tanh and sigmoid admit substantially tighter linear envelopes. To control the combinatorial cost of splitting in long sequences, we introduce a SHAP-guided timestep selection strategy that ranks hidden states by their contribution to the verification objective and refines only the most critical timesteps in temporal order. Experiments on CIFAR10 and MNIST stroke benchmarks demonstrate consistent improvements in verification success and robustness-margin tightness over abstraction-only baselines, while exposing clear runtime trade-offs between ReLU and tanh models.

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03.
PLOS Computational Biology 2026-06-22

Integrative modelling of innate immune response dynamics during virus infection

Authors:
Ramya Boddepalli↗

by Ramya Boddepalli, Harsh Chhajera, Rahul Roya Positive-sense RNA viruses that constitute a large class of human pathogens employ various strategies to suppress and evade host immune defenses. Understanding the dynamic interaction between the viral life cycle and immune signaling is crucial to designing effective antiviral strategies. Although significant progress has been made, quantitative models that can accurately capture the intricate interactions and the intertwined dynamics during viral infection of cells remain missing. In this study, we develop a comprehensive mathematical model that integrates the intracellular viral life cycle with key cellular innate immune pathways, including RIG-I-mediated detection and JAK-STAT signaling. The model provides mechanistic insights into long-standing observations, capturing both virus-specific dynamics and innate immune response, and the key components driving their coupled dynamics. For example, a comparison of viruses shows how the Japanese Encephalitis virus undergoes a dramatic reduction in viral load in cells, due to its rapid replication that robustly activates the RIG-I pathway, in contrast to the poor immune control of Hepatitis C virus. More importantly, our model demonstrates how virus-host interactions exhibit a sharp transition boundary behavior, where minor differences in immune strength or viral suppression capacity can determine whether infections resolve or persist. We propose that ISG mRNA translation and viral replication predominantly dictate these bimodal infection outcomes. Additionally, the model not only recapitulates IFN desensitization but also identifies the molecular players involved. We demonstrate how our model’s ability to capture IFN dynamics allows us to predict optimal timing and dosing strategies for interferon-based prophylactic therapies. Together, our approach reveals fundamental features that govern the delicate balance between the establishment of infection and immune control in RNA virus infections.

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04.
bioRxiv (Bioinfo) 2026-06-17

MetaHarmonizer: robust biomedical metadata harmonization and a contamination control for inflated LLM performance on public benchmarks

Authors:
Li↗Dahl↗Gravel-Pucillo↗K. D↗Long↗Waters↗de Bruijin↗Davis↗Oh↗

Public biomedical repositories hold substantial reuse potential, but inconsistent metadata routinely blocks integration across studies. Recent LLM-based harmonization approaches address scale but suffer from non-determinism, hallucinated ontology terms, and, in their highest-accuracy configurations, dependence on proprietary APIs or labeled fine-tuning data. A more fundamental concern is that LLM accuracies on widely-used public benchmarks may substantially inflate transferable capability: under a contamination-controlled evaluation protocol we developed, the apparent LLM-only advantage on the GDC schema-mapping benchmark is inverted, and three out of five LLMs recover 80 -100% of GDC identifiers from zero-schema context, suggesting direct memorization. Building on this insight, we present MetaHarmonizer, an automated metadata harmonization system designed to be robust by construction: SchemaMapper aligns attribute names across schemas, and OntologyMapper standardizes values to controlled vocabularies. Both modules implement a multi-stage cascade that escalates to more resource-intensive methods only when earlier stages fall short, with all candidates grounded in pre-defined controlled vocabularies to preclude hallucinated outputs and LLMs used only as bounded preprocessing components rather than inference-time dependencies. On the GDC schema-matching benchmark, SchemaMapper with the deployment-optimized LLM-generated alias dictionary achieved 71.6% Top-1 accuracy and the higher Recall@GT than Magneto bipartite variants, recovering significantly more ground-truth mappings; with the best performing alias dictionary, it reached the highest Top-1/Top-5/Recall@GT, and also matched the best Magneto reranker (fine-tuned LLM-reranker) on MRR; and it also outperforms LLM-only performance under contamination-controlled conditions. On four EFO benchmarks, OntologyMapper achieved 77.9 - 95.5% Top-1 accuracy, outperforming text2term by up to 16.4 pp and direct LLM inference (against the smaller corpus) by 19.2 pp because memorization is not a viable shortcut for this task. Across both modules, calibrated confidence scores separate correct from incorrect predictions (AUC 0.73 - 0.94), enabling principled human-in-the-loop triage. Inference is fully local, deterministic, and computationally efficient - seconds on schema mapping and under a minute for ontology mapping of up to ~7,000 terms against the pre-indexed 33,230-term corpus. Released as a Python package with a domain-agnostic architecture, MetaHarmonizer provides a scalable foundation for improving the FAIRness of biomedical data and enabling cross-study integration, alongside an evaluation methodology applicable to any LLM-augmented bioinformatics benchmark built on public benchmarks.

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05.
medRxiv (Medicine) 2026-06-15

CDH13 is associated with cellular viability after exposure to ionizing radiation using genome-wide screening

Authors:
Schmidt↗H.-L↗Ohlei↗Herwest↗Salewsky↗Bertram↗Demuth↗

Background: It is well known that genetic variants contribute to cellular sensitivity to chemotherapeutic agents and ionizing radiation (IR). The aim of this study was to identify single nucleotide polymorphisms (SNPs) and genes associated with the spectrum of normal cellular sensitivity of lymphoblastoid cell lines (LCLs) towards ionizing radiation and mitomycin C (MMC). Methods: In a first step, we determined the viability of LCLs established from male participants of the Berlin Aging Study II (BASE-II) aged >=62 years following treatments with increasing doses of IR (n=137 cell lines) or MMC (n=140 cell lines) using the alamarBlue assay. Results from intra-experimental triplicates and three independent experiments for each cell line and treatment were used to calculate the area under the curves (AUCs) representing the specific sensitivity to IR and MMC of each LCL. The data from these experiments were subsequently used as outcomes in genome-wide association studies (GWASs). In addition, we calculated polygenic risk scores (PGS) from UK Biobank GWAS results for four cancer-related phenotypes and assessed the extent to which the variance in the IR and MMC sensitivity is explained by these PGS. Results: The GWAS analyses revealed one variant, rs74728080, located in CDH13 on chromosome 16, to show genome-wide significant (p < 5 x 10-8, beta = 2.81) association with cellular viability after treatment with IR. In the GWAS on MMC sensitivity the most interesting signal was elicited by SNP rs113978558 in an intron of the PLD5 gene on chromosome 1 (p = 9.232 x 10-8; beta = 1.44). Several other SNPs with statistically suggestive (i.e., p < 1 x 10-5) evidence of association with IR or MMC sensitivity were identified. PGSs calculations from GWAS of four cancer-related traits in UKB explained ~5% and ~3% of phenotypic variance in IR- and MMC-induced cell viability, respectively. Conclusion: The genome-wide significant association of rs74728080 with IR sensitivity and the location of this variant in CDH13 is interesting and functionally highly plausible given its known involvement in oxidative-stress response and function as tumor suppressor. Taken together, our novel data suggest that CDH13 may be genuinely involved in regulating cellular IR sensitivity.

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

Stochastic Adaptive Gradient Descent Without Descent

Authors:
Jean-Fran\c{c}ois Aujol↗J\'er\'emie Bigot↗Camille Castera↗

arXiv:2509.14969v2 Announce Type: replace Abstract: We introduce a new adaptive step-size strategy for convex optimization with stochastic gradient that exploits the local geometry of the objective function only by means of a first-order stochastic oracle and without any hyper-parameter tuning. The method comes from a theoretically-grounded adaptation of the Adaptive Gradient Descent Without Descent method to the stochastic setting. We prove the convergence of stochastic gradient descent with our step-size under various assumptions, and we show that it empirically competes against tuned baselines.

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07.
arXiv (CS.AI) 2026-06-24

ARIA: Adaptive Region-Based Importance Allocation for Conditional Diffusion Distillation

Authors:
Loay Mualem↗Vinh Tong↗Samir Darouich↗Mathias Niepert↗

arXiv:2606.23898v1 Announce Type: cross Abstract: Distilling conditional diffusion models aims to transfer the behavior of a large teacher to a smaller student while preserving alignment across conditioning inputs. Unlike recognition tasks, knowledge distillation in conditional diffusion often struggles to transfer knowledge beyond the training distribution, since the predicted noise strongly depends on the conditioning signal. As a result, effective distillation requires exploring a large conditioning space. In practical settings, this creates a major bottleneck. Paired image-condition data may be limited, and generating synthetic images for every available condition is often computationally infeasible, while the pool of conditions, such as text prompts, can be extremely large. Recent work addresses this issue by switching conditions during training, exposing the student to a broader conditioning space without changing the distillation objective. Yet this raises a complementary question: once a large conditioning corpus is available, how should the training effort be allocated? In this work, we introduce ARIA, a framework that adaptively allocates training effort across coarse regions of the conditioning space. By maintaining online estimates of teacher-student discrepancy at the region level, ARIA focuses updates where misalignment persists while preserving the original distillation objective. Empirically, ARIA improves over RC across most architectures and settings, with the clearest gains observed in unseen and underrepresented regimes. We also provide a theoretical analysis showing that the proposed tracking mechanism follows the evolving discrepancy during training under bounded variance and drift assumptions.

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08.
arXiv (quant-ph) 2026-06-24

From Spectral Singularities to Multipartite Entanglement Scaling at Higher-Order Exceptional Points

Authors:
Chunlai Yang↗Shuheng Liu↗Xinyao Huang↗Kaiye Shi↗Qiongyi He↗

arXiv:2606.24205v1 Announce Type: new Abstract: Exceptional points (EPs) are non-Hermitian spectral singularities exhibiting fractional-power responses, yet their implications for multipartite entanglement of interacting quantum many-body systems remain largely unexplored. Here we develop a general framework that links higher-order non-Hermitian degeneracies to the scaling behavior of genuine multipartite entanglement in interacting identical-qubit systems. Permutation symmetry of the identical qubits decomposes the exponentially large Hilbert space into independent irreducible-representation sectors, thereby constraining the maximal EP order of $N$ qubits to $N+1$ rather than $2^N$. Near an $n$th-order EP, genuine multipartite entanglement inherits the spectral response and generically exhibits a fractional-power scaling under weak perturbations. Explicit examples show that conventional two-body interactions support third- and fourth-order EPs with the corresponding entanglement responses, whereas higher-order EPs with genuine multipartite-entangled coalesced states require additional independent interaction channels, such as three-body interactions. Our results establish a fundamental connection among non-Hermitian degeneracies, multipartite entanglement, and symmetry, extending higher-order EP physics from spectral singularities to genuine many-body quantum correlations.

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

From Simulation to Real-World: An In-Field 6D Pose Dataset and Baseline for Robotic Strawberry Harvesting

Authors:
Woojung Son↗Won Suk Lee↗Zijing Huang↗Daeun Choi↗Catia Silva↗Yu She↗Yan Gu↗

Robotic strawberry harvesting requires precise 6D pose estimation; however, collecting 6D pose ground truth in real agricultural fields is inherently challenging. Existing 6D pose estimation methods have therefore relied solely on synthetic data that lacks scene-level realism, leaving their performance under real agricultural field conditions unquantified. In this work, we present, to the best of our knowledge, the first real-world 6D pose ground truth dataset of strawberries collected in actual agricultural fields (12,040 images). We also introduce a synthetic dataset rendered in NVIDIA Isaac Sim, featuring scene-level realism and domain randomization. Nevertheless, our experiments reveal that a significant sim-to-real gap persists, underscoring the necessity of real agricultural field data for reliable evaluation. We further quantify the sim-to-real gap through baseline 6D pose estimation results across backbone encoders, serving as a reference for future work. The real-world dataset will be made available upon acceptance.

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10.
arXiv (CS.CV) 2026-06-24

BioMedVR: Confusion-Aware Mixture-of-Prompt Experts for Biomedical Visual Reprogramming

Authors:
Jiaxiang Liu↗Tianxiang Hu↗Juwei Guan↗Yujie Wu↗Yusong Wang↗Yao Mu↗Zuozhu Liu↗Mingkun Xu↗

Recent advances in vision-language models (VLMs) such as CLIP have demonstrated strong generalization across natural-image domains. However, adapting these models to biomedical imaging is non-trivial: full-model fine-tuning is computationally expensive, while medical data are often scarce and exhibit subtle, fine-grained inter-class differences, making parameter-efficient adaptation particularly critical. Visual Reprogramming (VR) offers a parameter-efficient alternative by injecting learnable perturbations into the input space, but existing VR approaches for VLMs mainly focus on positive class prompts and overlook confusing negatives, leading to miscalibrated predictions in fine-grained medical scenarios. We present BioMedVR, the first VR-based framework for biomedical imaging, enabling few-shot adaptation of pretrained VLMs through compact learnable VR modules. To mitigate class confusion, we introduce a Confusion Minimization Mechanism that leverages LLM-generated confusion-aware attributes together with a Confusion-Suppression Loss to explicitly reduce false-positive alignment. Moreover, the designed Mixture-of-Prompt Experts combines a positive expert for main-class discrimination and a negative expert for confusion suppression, balanced via adaptive gating. Extensive experiments on 18 datasets, including 11 biomedical datasets and 7 natural image benchmarks, demonstrate that BioMedVR achieves superior accuracy and generalization, effectively bridging VR and VLMs in biomedical domains.

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11.
arXiv (CS.AI) 2026-06-15

LEPO: Latent Reasoning Policy Optimization for Large Language Models

Authors:
Yuyan Zhou↗Jiarui Yu↗Hande Dong↗Zhezheng Hao↗Hong Wang↗Jianqing Zhang↗Qiang Lin↗

arXiv:2604.17892v4 Announce Type: replace-cross Abstract: Recently, latent reasoning has been introduced into large language models (LLMs) to leverage rich information within a continuous space. However, without stochastic sampling, these methods inevitably collapse to deterministic inference, failing to discover diverse reasoning paths. To bridge the gap, we inject controllable stochasticity into latent reasoning via Gumbel-Softmax, restoring LLMs' exploratory capacity and enhancing their compatibility with Reinforcement Learning (RL). Building on this, we propose \underline{L}atent R\underline{e}asoning \underline{P}olicy \underline{O}ptimization~(LEPO), a novel framework that applies RL directly to continuous latent representations. Specifically, in rollout stage, LEPO maintains stochasticity to enable diverse trajectory sampling, while in optimization stage, LEPO constructs a unified gradient estimation for both latent representations and discrete tokens. Extensive experiments show that LEPO significantly outperforms existing RL methods for discrete and latent reasoning.

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12.
arXiv (CS.AI) 2026-06-16

Where Did It Go Wrong? Process-Level Evaluation of Web Agents with Semantic State Tracking

Authors:
Jiwan Chung↗JiHyuk Byun↗Vibhav Vineet↗Seon Joo Kim↗

arXiv:2606.15673v1 Announce Type: new Abstract: Web agents act through long interaction sequences, yet existing benchmarks evaluate only terminal success, discarding all process information and offering little guidance on improvement. In this work, we conduct a process-level analysis of web agents. We introduce WebStep, a benchmark of 1,800 task instances with controlled difficulty and automatic semantic state tracking. Each website exposes a deterministic semantic MDP alongside the GUI: the agent operates on the interface, while the environment records high-level states and transitions in the background, enabling fine-grained analysis without manual annotation. Based on the semantic trajectory, we first show that process metrics reveal differences invisible to outcome evaluation: three agents whose success rates cluster within 31-33% diverge in exploration reach versus execution accuracy. Then, decomposing by skill characterizes the nature of these differences, exposing opposite per-skill rankings hidden within the same website: e.g., on Housing, OpenAI CUA outperforms Qwen3.5 by 23.7% on commit actions yet underperforms it by 15.6% on filtering, pinpointing a concrete skill to improve even within a domain. Bifurcation analysis further localizes the decisive error that loses the task and shows that this error is agent-specific rather than shared. Finally, these differences widen as tasks grow harder: success rate is similar on easy tasks but separates sharply as exploration becomes more demanding. Our process-level analysis opens a new avenue in web agent evaluation, providing fine-grained and actionable insight into where and how each agent should be improved.

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

Counterfactual Optimization of Baseball Pitch Sequences and Estimation of Its Impact on Season-Level Statistics

Authors:
Ryota Takamido↗Hiroki Nakamoto↗

arXiv:2606.17345v1 Announce Type: cross Abstract: Although pitch sequencing is a central topic in baseball analytics, previous studies have primarily focused on optimizing the final pitch within a single plate appearance, leaving the role of preceding setup pitches and their impact on long-term season-level performance insufficiently examined. To address these issues, this study conducted counterfactual analyses using MLB Statcast data. A Transformer-based machine-learning model was trained to predict whether a target pitch would result in an in-play outcome or swing-out. Counterfactual pitch sequences were then generated by replacing either the final pitch or the preceding setup pitch with alternative pitch types and locations while keeping the surrounding contextual information fixed. Optimal counterfactual selections were defined as those that minimized the predicted in-play probability, and their expected effects on pitchers' seasonal statistics were estimated using regression models linking model outputs to season statistics. The results suggest that the optimization of both final and setup pitches may substantially influence season-level performance, including improvements of more than 1.0 in K/9. The analyses also provided several practical insights, including velocity-band-specific effective locations, the importance of pitch commands, and the expansion of pitch-selection options through middle-velocity pitches. These findings quantitatively support the strategic importance of pitch sequencing in baseball.

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14.
medRxiv (Medicine) 2026-06-18

Personalizing Suicide Risk Assessment: Machine Learning Extraction of Cross-Modal Interactions Between Psychosocial and Demographic Factors in Veterans

Authors:
Levis↗M. E↗Shiner↗Dimambro↗Rozema↗Ayandeh↗Diallo↗A. B↗Zhou↗Li↗Wu↗Gui↗…

Background: Veterans face an elevated risk of suicide compared to the general population, motivating national efforts to develop predictive models that can guide proactive care. Current models used by the U.S. Department of Veterans Affairs (VA) rely primarily on structured electronic health record (EHR) data, though clinical notes contain rich contextual information that can be quantified using natural language processing (NLP) to derive psychosocial variables that may improve risk detection. Machine learning methods, particularly classification and regression trees (CART), can also uncover interactions between clinical and psychosocial variables, enabling identification of patient characteristics that modify suicide risk factors. However, integrating structured and unstructured data presents challenges because NLP features often greatly outnumber traditional clinical variables, potentially biasing interaction discovery. In prior work, we addressed this imbalance by introducing a weighted CART framework that balances structured variables with NLP-derived psychosocial features from semantic lexicons (SEANCE). While effective, semantic approaches summarize language into predefined constructs and may overlook important lexical variation present in clinical narratives. Methods: In this study, we extend that framework by replacing semantic features with a high-dimensional bag-of-words (BoW) representation of clinical notes and by evaluating models across cohorts defined by structured suicide risk stratification (low, medium, high) and varying temporal lookback windows. Using a cohort of 27,241 veterans, we analyzed clinical documentation collected up to 30, 90, or 270 days prior to death (or a matched index date for controls), enabling temporally flexible risk modeling. XGBoost models were trained to balance structured and unstructured features and identify cross-modal interactions between textual and clinical variables. Results: When incorporated into generalized linear models, these interactions improved predictive performance, particularly among low- and medium-risk patients, and substantially reduced the performance gap between interpretable and more complex models. Notably, the BoW representation outperformed our prior semantic index-based approach. Discussion and Conclusions: Together, these findings demonstrate the utility of interpretable NLP methods for uncovering clinically meaningful interactions between psychosocial and demographic factors in suicide risk and establish a strong benchmark for future deep learning approaches aimed at capturing richer contextual and temporal information from clinical narratives.

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

Stochastic Schrödinger Diffusion Models for Pure-State Ensemble Generation

Authors:
Jian Xu↗Wei Chen↗Shigui Li↗Chao Li↗Jingyuan Zheng↗Delu Zeng↗John Paisley↗Qibin Zhao↗

arXiv:2605.03573v3 Announce Type: replace-cross Abstract: Quantum machine learning increasingly relies on pure-state representations, motivating generative models that sample directly in quantum representation space rather than perturbing classical inputs and re-encoding. We introduce Stochastic Schrödinger Diffusion Models (SSDMs), a score-based generative framework that defines diffusion, scores, and reverse-time sampling intrinsically on the complex projective manifold $\mathbb{CP}^{d-1}$ under the Fubini–Study metric. SSDMs combine a Riemannian Ornstein–Uhlenbeck forward diffusion with a stochastic Schrödinger realization, and learn reverse-time dynamics driven by the Riemannian score. Our central technical contribution is a local-time learning objective that exploits the local Euclidean OU limit of intrinsic manifold diffusions in Fubini-Study normal coordinates to obtain an analytic teacher score, bypassing the intractable transition densities that limit existing Riemannian score-based models. Across synthetic, physics-inspired (TFIM, XXZ), and quantum feature-state benchmarks up to $14$ qubits, SSDMs match target pure-state ensembles by orders of magnitude on MMD and observable statistics over both ambient Euclidean and matched Riemannian score-based baselines, and improve representation-level diagnostics for downstream quantum kernel methods.

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

Conditional Score-Based Modeling of Effective Langevin Dynamics

Authors:
Ludovico T. Giorgini↗

arXiv:2604.23952v2 Announce Type: replace-cross Abstract: Stochastic reduced-order models are widely used to represent the effective dynamics of complex systems, but estimating their drift and diffusion coefficients from data remains challenging. Standard approaches often rely on short-time trajectory increments, state-space partitioning, or repeated simulation of candidate models, which become unreliable or computationally expensive for high-dimensional systems, coarse temporal sampling, or unevenly sampled data. We introduce a data-driven calibration method based on a novel relationship between the coefficients of a stochastic reduced model and the conditional score of the finite-time transition density, defined as the gradient of the logarithm of the transition density with respect to the initial state. The resulting identity expresses derivatives of lagged correlation functions as stationary expectations over observed lagged pairs involving this conditional score and the unknown model coefficients. This formulation allows the drift and diffusion structure to be constrained directly from finite-lag statistics, without differentiating trajectories, partitioning state space, or repeatedly integrating candidate reduced models during calibration, yielding a least-squares fitting problem over stationary lagged pairs. We validate the approach on three systems of increasing complexity: an analytically tractable Cox–Ingersoll–Ross diffusion, a two-dimensional nonequilibrium diffusion with affine multiplicative noise, and a periodic soft-spin stochastic Landau–Lifshitz chain. Across these tests, the inferred models preserve the invariant statistics while reproducing finite-lag dynamical correlations. The framework provides a scalable route for learning stochastic reduced-order models from data that reproduce prescribed statistical and dynamical properties.

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17.
medRxiv (Medicine) 2026-06-15

Non-invasive intracranial pressure waveform reconstruction with deep learning

Authors:
Goyal↗Zaveri↗Harris↗C. W↗Stevens↗R. D↗

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

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18.
bioRxiv (Bioinfo) 2026-06-22

Reference-guided immune recovery matching prioritizes traditional Chinese medicine ingredients

Authors:
Hu↗Xiao↗Chen↗C. Y.-C↗

Therapeutic prioritization from single-cell transcriptomes requires a target that is closer to treatment response than disease-signature reversal. In immune diseases, post-treatment recovery may follow patient- and cell-type-specific trajectories rather than a simple return along the pretreatment disease axis. We developed ImmuneNavi, a healthy-reference-anchored recovery-matching workflow for ranking traditional Chinese medicine ingredients from paired PBMC data. The workflow maps heterogeneous PBMC cohorts to a common healthy immune coordinate system, constructs patient-cell-type disease and recovery states, and processes ITCM treated-control profiles into a fixed ingredient perturbation bank. Patient and ingredient states are represented in matched gene, pathway and transcription-factor views, allowing the model to combine local transcriptional direction with more stable program-level features. A matcher trained on one paired treatment cohort preserved recovery-aligned ingredient rankings in independent PBMC cohorts without redefining the feature space, candidate set or preprocessing procedure. This provides a reusable transcriptomic pipeline for moving from paired immune-state measurements to prioritized natural-product candidates for experimental follow-up.

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19.
arXiv (CS.LG) 2026-06-12

Robust State-Conditional Feature-Weighted Jump Models for Temporal Clustering

Authors:
Federico P. Cortese↗Alessio Farcomeni↗

arXiv:2606.13146v1 Announce Type: cross Abstract: We propose a robust feature-weighted jump model for time-dependent clustering. A penalty is used to encourage smoothness of transitions over time, while robustness is achieved through the use of a Tukey's biweight loss function. An additional parameter controls the variability of feature weights across states, allowing the model to assign state-specific relevance to each feature. We illustrate in simulation how the method accurately recovers the true cluster sequence and reliably identifies relevant features, outperforming competing approaches, particularly in the presence of outliers. We conclude with two empirical applications, one on the number of conflict-related homicides in Kosovo in the period 1998-2000, and another on macroeconomic performance of twelve European countries in the period 1949-2024.

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20.
arXiv (CS.AI) 2026-06-17

Unlocking LLM Code Correction with Iterative Feedback Loops

Authors:
Le Zhang↗Suresh Kothari↗

arXiv:2606.17514v1 Announce Type: cross Abstract: Large Language Models have shown remarkable capabilities in code generation. However, most existing evaluations focus only on single-attempt accuracy and overlook the iterative refinement process that is central to real-world programming. This study presents a systematic investigation of LLMs' ability to rectify their own code through execution feedback. Using real-world programming problems across four models and two major programming languages, this study evaluates performance using iterative refinement framework where LLMs receive compiler error messages and testcase feedback after each attempt. This study introduces metrics to evaluate code failures, analyze rectification patterns, and compare the effectiveness of reasoning and non-reasoning models, offering actionable insights into both the understanding and practical application of feedback loops in LLM-driven code generation systems. Results show that reasoning models consistently improve over iterations, substantially outperforming non-reasoning models in leveraging feedback, while syntactic and runtime errors are far more tractable than logical or algorithmic failures.

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21.
arXiv (CS.LG) 2026-06-18

Self-Driving Datasets: From 20 Million Papers to Nuanced Biomedical Knowledge at Scale

Authors:
Haydn Jones↗Yimeng Zeng↗Alden Rose↗Li S. Yifei↗Yining Huang↗Kaiwen Wu↗Jiaming Liang↗Maggie Ziyu Huan↗Yoseph Barash↗Cesar de la Fuente-Nunez↗Osbert Bastani↗Zachary Ives↗…

arXiv:2605.07022v3 Announce Type: replace Abstract: Manually curated biomedical repositories – spanning bioactivity, genomics, and chemistry – are expensive to maintain, lag behind primary literature, and discard experimental context, obscuring nuances needed to assess data correctness and coverage. We show that PubMed itself can be autonomously and cost-effectively turned into structured datasets that are larger, more nuanced, and more accurate than the curated databases they replace. We present three coupled contributions: (1) an LLM-based entity-tagging pipeline, grounded in nine biomedical ontologies, that tags 4.5B entities across 19 categories in a 22.5M-paper, 2.5T-token PubMed corpus; (2) hybrid sparse-dense retrieval supporting entity-filtered semantic queries over the tagged corpus; and (3) Starling, a multi-agent deep research system that, given only a natural-language task description, designs precision- and recall-targeted retrieval filters, induces an extraction schema, and emits structured records with nuance-rich fields and supporting passages. Across six tasks – blood-brain barrier permeability, oral bioavailability, acute toxicity (LD50), gene-disease associations, protein subcellular localization, and chemical reactions – Starling produces ~6.3M records (91K-3M per task); several are, to our knowledge, the largest public datasets for their property. Frontier-model rejection of our extractions is 0.6-7.7% across tasks, far below error rates we measure on widely used curated counterparts (e.g., 16.5% on BBB_Martins, 7.3% on Bioavailability_Ma). Beyond scale and accuracy, the supporting passages carry nuance tabular databases discard – e.g., oral bioavailability may depend on fed vs. fasted state. Together, the corpus, retrieval, and agent establish a foundation for AI-driven therapeutic design. Code and datasets: https://github.com/starling-labs/starling.

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22.
arXiv (quant-ph) 2026-06-19

A Quantum Encoding of Traveling Salesperson Tours via Route Generation, Cost Phases, and a Reversible Valid-Permutation Oracle

Authors:
Alexander Johannes Stasik↗Franz Georg Fuchs↗

arXiv:2603.21283v3 Announce Type: replace Abstract: For a traveling salesperson problem (TSP) of n cities, we present a compact quantum encoding based on a time-register representation of tours. A candidate route is represented as a sequence of n-1 city labels over discrete time steps, with one fixed start city and the remaining cities encoded in binary registers. We describe three ingredients of the construction: uniform route generation over the route register, a reversible validity oracle, and a phase oracle that encodes the total tour cost. The validity oracle checks both that the non-start city labels form a permutation and, for incomplete graphs, that every directed edge used by the route exists. The cost oracle then accumulates the start-edge, intermediate-transition, and return-edge costs into a tour-dependent phase for valid routes. This yields a coherent superposition of candidate routes with feasibility and tour-length information embedded directly in the quantum state. The complete construction uses O(n log n) qubits, while a naive implementation has worst-case elementary-gate complexity O(n^3 log n). The encoding is compatible with amplitude amplification or spectral filtering techniques such as the quantum singular value transform (QSVT) or Grover's algorithm. However, due to the exponentially small fraction of valid tours, the overall complexity remains exponential even when combined with amplitude amplification.

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

Slots, Transitions, Loops: Learning Composable World Models for ARC

Authors:
Gege Gao↗Bernhard Sch\"olkopf↗Andreas Geiger↗

ARC tests in-context rule induction: given a few input-output demonstrations, a model must infer the hidden rule and apply it to a new query. While many approaches express ARC rules through language, code, or symbolic programs, ARC itself is visual-symbolic: rules appear as grid transitions over objects, colors, shapes, and spatial relations. We introduce Loop-OWM, an object-centric world-modeling architecture that learns these rules as composable transitions over structured states. It combines color-prototype slots, demonstration-conditioned task summaries, and a looped transition model with dense propagation and slot-conditioned correction. On both ARC-1 and ARC-2, Loop-OWM outperforms non-looped and looped baselines with comparable or fewer parameters. These results suggest that ARC rules can be learned not only as language descriptions or searched programs, but also as transitions over visual-symbolic world states.

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24.
arXiv (CS.LG) 2026-06-15

Dynamic Free-Rider Detection in Federated Learning via Simulated Attack Patterns

Authors:
Motoki Nakamura↗

arXiv:2604.04611v2 Announce Type: replace Abstract: Federated learning (FL) enables multiple clients to collaboratively train a global model by aggregating local updates without sharing private data. However, FL often faces the challenge of free-riders, clients who submit fake model parameters without performing actual training to obtain the global model without contributing. Chen et al. proposed a free-rider detection method based on the weight evolving frequency (WEF) of model parameters. This detection approach is a leading candidate for practical free-rider detection methods, as it requires neither a proxy dataset nor pre-training. Nevertheless, it struggles to detect ``dynamic'' free-riders who behave honestly in early rounds and later switch to free-riding, particularly under global-model-mimicking attacks such as the delta weight attack and our newly proposed adaptive WEF-camouflage attack. In this paper, we propose a novel detection method S2-WEF that simulates the WEF patterns of potential global-model-based attacks on the server side using previously broadcasted global models, and identifies clients whose submitted WEF patterns resemble the simulated ones. To handle a variety of free-rider attack strategies, S2-WEF further combines this simulation-based similarity score with a deviation score computed from mutual comparisons among submitted WEFs, and separates benign and free-rider clients by two-dimensional clustering and per-score classification. This method enables dynamic detection of clients that transition into free-riders during training without proxy datasets or pre-training. We conduct extensive experiments across three datasets and five attack types, demonstrating that S2-WEF achieves higher robustness than existing approaches.

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25.
arXiv (math.PR) 2026-06-16

Collapsibility in Multiparametric Models of Random Simplicial Complexes

Authors:
Jon V. Kogan↗

arXiv:2606.15276v1 Announce Type: cross Abstract: We study collapsibility in the multiparametric models of random simplicial complexes, namely the lower and upper models. In the upper model, we improve upon a result of Farber and Nowik, and assert that the homology is a.a.s concentrated in a single dimension by proving that the complex collapses to that \di. In the lower model, we prove that the complex a.a.s collapses to the \di\ with maximal non-trivial cohomology. We then compare this threshold to the ones derived previously for the special cases of the clique complex (by Kahle) and the Linial-Meshulam model.

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