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01.
medRxiv (Medicine) 2026-06-16

The Target48 Neurodegeneration Panel: A Novel Tool for Profiling Protein Signatures in Neurodegenerative Disorders

Authors:
Hok-A-Hin↗Y. S↗Vermunt↗de Jong↗del Campo↗Vijverberg↗Lemstra↗A. W↗Pijnenburg↗Y. A. L↗Van Harten↗A. C↗…

Introduction: Novel tools for absolute quantification of established and emerging fluid neuro-biomarkers are required to advance diagnostic studies and improve biological insights. Methods: We conducted an extensive analytical and clinical validation of the Olink Target 48 Neurodegeneration panel (T48 Neuropanel) in 352 paired CSF and plasma samples from cognitively unimpaired controls (CU), Alzheimer dementia (AD), frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB), n=44 per group. Comparisons with benchmark assays were performed. Results: Good detectability (CSF: 31 out of 42 assays; plasma: 38 out of 42 assays) and technical performance was observed. Benchmark assays showed good correlations, supporting method transformation formulas. Next to emerging biomarkers (MMP10, ITGB2), discriminative performance was excellent in AD: CSF pTau217: AUC=1; FTD: plasma NfL: AUC=0.952; and DLB: CSF DDC: AUC=0.901. Discussion: This analytical and clinical validation of the T48 Neuropanel highlights initial cut-offs and emerging biomarkers to aid clinical studies for the diagnosis, prognosis, and monitoring of neurodegenerative diseases. Highlights: The T48 Neuropanel shows robust analytical performance, with high detectability across both plasma and CSF matrices. The T48 Neuropanel validates established (i.e., pTau217, Abeta42, NfL, and GFAP) and emerging biomarkers (i.e., DDC, MMP10, ITGB2, ITGAM, NPTX2, NPTXR, SMOC1, sTREM1, and sTREM2) in CSF and plasma. CSF NfL, GFAP, ITGB2, and ITGAM and plasma GFAP were dysregulated across AD, FTD, and DLB dementias. -The multiplex design of the T48 Neuropanel enables rich biological interpretation by simultaneously quantifying established and emerging neurodegeneration biomarkers. Importantly, the inclusion of absolute quantification facilitates the establishment of cut-offs, supporting its potential for clinical translation.

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

Analyzing Visual Aircraft Representations with Sparse Autoencoders

Authors:
Deepshik Sharma↗

Vision models can achieve strong performance on classification tasks, but the internal representations supporting their predictions are often difficult to interpret. This work investigates whether sparse autoencoders can decompose intermediate representations of a vision model into interpretable features. We train a ConvNeXt classifier on the FGVC-Aircraft dataset, extract spatial activations from its final feature stage, and train a sparse autoencoder on these activations. The learned sparse features are analyzed using top-activating image patches, activation strength, and class selectivity. Qualitative visual inspection reveals that several features correspond to recognizable aircraft structures and visual patterns. We evaluate a subset of selected features using input-space and feature-space ablations, measuring how blurring image patches and suppressing sparse features affect class logits, classification margins, and prediction confidence. The results suggest that sparse autoencoders can reveal partially interpretable, class-relevant visual features associated with aircraft recognition, while also exposing limitations such as polysemanticity and coarse spatial localization.

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03.
bioRxiv (Bioinfo) 2026-06-10

Is level-1 blob reconstruction under the network multispecies coalescent easy?

Authors:
Dai↗Molloy↗

Hybridization is an important evolutionary process, commonly modeled by the network multispecies coalescent. Reconstructing evolutionary histories under this model is notoriously costly, even for level-1 networks where hybridization events are isolated from each other. The widely used methods that combine speed with statistical guarantees rely on quartet concordance factors computed for all subsets of four species, resulting in an o(n^4k) bottleneck that severely limits scalability to large numbers of species (n) and genes (k). Among quartet-based methods, NANUQ+ is notable because it decomposes the problem into two steps: first reconstructing a tree of blobs, which compresses each non-treelike part of the network, called a blob, into a single vertex, and second reconstructing the internal structure of each level-1 blob, specifically its circular order and hybrid vertex. Here, we investigate whether level-1 blob reconstruction is difficult once the tree of blobs is known. We present a fast and statistically consistent algorithm, called NetCS, based on two simple primitives: majority voting and merge sort, circumventing the bottleneck of computing all quartet concordance factors. In simulations, NetCS achieved comparable accuracy to NANUQ+ and was dramatically faster, enabling analyses of 200 taxa and 1000 genes in only a few minutes. Both methods attained near-perfect accuracy when given the true tree of blobs; however, their performance degraded in end-to-end pipelines due to errors in tree of blobs reconstruction. Strikingly, even methods that reconstruct level-1 networks directly struggled to accurately predict hybrid ancestry. Our results suggest that reconstructing level-1 blobs is unexpectedly easy once the tree of blobs is known, and that a major challenge for phylogenetic network inference lies in accurate tree of blobs reconstruction.

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04.
arXiv (CS.CV) 2026-06-11

From Correspondence to Actions: Human-Like Multi-Image Spatial Reasoning in Multi-modal Large Language Models

Authors:
Masanari Oi↗Koki Maeda↗Ryuto Koike↗Daisuke Oba↗Nakamasa Inoue↗Naoaki Okazaki↗

While multimodal large language models (MLLMs) have made substantial progress in single-image spatial reasoning, multi-image spatial reasoning, which requires integration of information from multiple viewpoints, remains challenging. Cognitive studies suggest that humans address such tasks through two mechanisms: cross-view correspondence, which identifies regions across different views that correspond to the same physical locations, and stepwise viewpoint transformation, which composes relative viewpoint changes sequentially. However, existing studies incorporate these mechanisms only partially and often implicitly, without explicit supervision for both. We propose Human-Aware Training for Cross-view correspondence and viewpoint cHange (HATCH), a training framework with two complementary objectives: (1) Patch-Level Spatial Alignment, which encourages patch representations to align across views for spatially corresponding regions, and (2) Action-then-Answer Reasoning, which requires the model to generate explicit viewpoint transition actions before predicting the final answer. Experiments on three benchmarks demonstrate that HATCH consistently outperforms baselines of comparable size by a clear margin and achieves competitive results against much larger models, while preserving single-image reasoning capabilities.

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05.
arXiv (CS.CL) 2026-06-17

Environment-Grounded Automated Prompt Optimization for LLM Game Agents

Authors:
Rean Clive Fernandes↗Lukas Fehring↗Theresa Eimer↗Marius Lindauer↗Matthias Feurer↗

LLM agents in interactive environments are highly sensitive to their prompts, yet prompt engineering remains a manual, task-specific process. We introduce an automated prompt optimization framework for LLM agents that decomposes the observation-to-action pipeline into a goal-conditioned descriptor agent and an action selection agent, and iteratively refines each module's prompt through an LLM-driven evolutionary loop guided by environment returns. We propose a behavior analyzer to attribute episode outcomes to specific prompt components, and a mutator to propose targeted revisions to the prompt, before validating them through environment rollouts. We evaluate on all five BabyAI tasks in the BALROG benchmark, comparing our pipeline against BALROG's RobustCoTAgent under both plain and guided prompt initializations. Optimization improves performance consistently across tasks and conditions, without requiring updates to the model weights. On PutNext, a multi-step coordination task where the RobustCoTAgent achieves 0% success, our framework reaches up to 72.5% success rate using the same underlying LLM with optimized prompts. These results suggest that a multi-agent framework, combined with automatic prompt optimization, enhances LLMs without the need for fine-tuning or extensive human supervision.

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

Deterministic Integrity Gates for LLM-Assisted Clinical Manuscript Preparation: An Auditable Biomedical Informatics Architecture

Authors:
Yoojin Nam↗Jinhoon Jeong↗Namkug Kim↗

arXiv:2606.09500v3 Announce Type: replace Abstract: As autonomous research agents and AI co-scientist systems push large language models (LLMs) from drafting toward end-to-end manuscript production, the bottleneck shifts from generation to verification. Fluent LLM output can hide fabricated citations, numbers that drift from source tables, and unmet reporting-guideline items; existing tools generate without verifying, and self-critique inherits the blind spots that produce confident fabrication. We describe an architecture pairing generation with verification, resting on three principles: decompose the workflow into self-contained skills, gate every stage transition with halt-on-failure, and resolve each integrity question with the cheapest sufficient mechanism, a deterministic, re-executable check where one suffices and a prose-level probe only where interpretation is unavoidable. This determinism-where-possible split, organized as an integrity-gate taxonomy, is the core contribution. It is realized as MedSci Skills, an open-source toolkit of 43 skills with a 21-detector deterministic tier, evaluated on three public-dataset pipelines (STARD, PRISMA, STROBE) and a seeded-defect ablation. Across the three pipelines every content-hash manifest verified clean and the gates surfaced real defects; on 27 identical injected defects the deterministic gates detected all 27 with no false positives on the matched clean fixtures, whereas a single-prompt LLM reviewer detected 11, its misses in code, bibliography, and style defects the prose hides. Determinism-where-possible verification yields an auditable, re-executable trail that exposes the evidence a human needs to check an LLM-assisted manuscript: feasibility and reproducibility evidence, not a claim of human-competitive quality, which a separate blinded study addresses. MedSci Skills is MIT-licensed and archived (v3.8.0).

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07.
arXiv (CS.LG) 2026-06-11

A Riemannian Approach to Low-Rank Optimal Transport

Authors:
Pratik Jawanpuria↗Bamdev Mishra↗

arXiv:2606.12120v1 Announce Type: new Abstract: Low-rank optimal transport (OT) mitigates the quadratic scaling of classical solvers, yet existing approaches rely heavily on first-order mirror-descent updates that require careful hyperparameter tuning and ignore the optimization landscape's curvature. To address these limitations, we propose a unified Riemannian geometric framework for low-rank OT, modeling balanced and unbalanced rank-$r$ positive factored couplings as novel smooth embedded submanifolds of the positive orthant. By equipping these manifolds with the Fisher-Rao product metric, we derive tractable formulations for Riemannian projectors, retractions, and Hessian-vector products. Our cost-agnostic framework seamlessly extends to linear OT, Gromov-Wasserstein (GW), fused GW, and their unbalanced counterparts. For balanced OT, our geometric ingredients are computed via efficient conjugate-gradient and iterative Bregman updates. For the unbalanced OT, our operations elegantly reduce to closed-form scalings, completely eliminating inner iterative loops. In both regimes, per-iteration complexity scales linearly with dataset size, and we provide a rank-sufficiency certificate for global optimality verification. Extensive experiments across a range of problem sizes demonstrate that our regularization-free first- and second-order solvers achieve faster convergence and superior performance over existing state-of-the-art low-rank OT solvers.

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

Controlled ion-ion interactions and cavity-enhanced emission of a coherent dinuclear Eu$^{3+}$ complex

Authors:
Evgenij Vasilenko↗Vishnu Unni Chorakkunnath↗Barbora Brachnakova↗Nicholas Lester Jobbitt↗Senthil Kumar Kuppusamy↗David Hunger↗Mario Ruben↗

arXiv:2606.11947v1 Announce Type: new Abstract: Molecular rare-earth-ion complexes offer unique opportunities for quantum technologies by combining the intrinsic coherence properties of rare-earth ions with chemically tunable molecular environments. A crucial capability is the realization of multi-qubit architectures with defined qubit couplings to enable two-qubit quantum gates. Here, we investigate the optical coherence properties and excitation-induced interactions of two Eu$^{3+}$-based molecular complexes, comparing a mononuclear reference system with a dinuclear analogue in which two Eu$^{3+}$ ions are positioned at a well-defined intramolecular distance of about 7 Angstrom. Using cryogenic ensemble spectroscopy, including spectral hole burning, free-induction decay, and photon echo measurements at temperatures down to 100 mK, we demonstrate long optical coherence times $T_{2,o}$ of up to 9 $\mu$s. As a key step toward scalable multi-qubit architectures, a control-target sequence was implemented to probe conditional ion-ion interactions, revealing a stronger interaction-induced dephasing in the dinuclear complex. Finally, we show the integration of the dinuclear complex into a fiber-based optical microcavity, and observe an 380-fold emission enhancement of the $\mathrm{}^5\mathrm{D}_0\rightarrow\mathrm{}^7\mathrm{F}_0$ transition. Together, these results position molecular rare-earth complexes as versatile and chemically tunable building blocks for scalable quantum technologies.

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09.
arXiv (math.PR) 2026-06-11

Matrix Discrepancy for Representations of Finite Groups

Authors:
Afonso S. Bandeira↗Helmut B\"olcskei↗

arXiv:2606.12181v1 Announce Type: new Abstract: Given a finite group $G$, we prove that there exist signs $\varepsilon\in\{\pm1\}^G$ such that $$\left\| \sum_{g\in G} \varepsilon_g\rho(g) \right\|\leq C\, \sqrt{|G|},$$ where $\rho$ is the left regular representation of $G$, and $C$ is a universal constant. This special case of the Matrix Spencer conjecture was posed in [BKMZ24], where it was established for simple groups.

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10.
arXiv (CS.CV) 2026-06-16

Latent Space Reinforcement Learning for Inverse Material Estimation in Food Fracture Simulation

Authors:
Adrian Ramlal↗Yuhao Chen↗John S. Zelek↗

Realistic visual simulation of food manipulation requires accurate material parameters, yet these are difficult to measure directly and vary across the heterogeneous regions of a single food item. We address the inverse problem of estimating material parameters from a target description of fracture behavior in a non-differentiable continuum damage mechanics simulator. Using orange peeling as a test case, we train a neural surrogate on 2,000 forward simulations and compare Covariance Matrix Adaptation Evolution Strategy (CMA-ES, a gradient-free evolutionary optimizer) with Proximal Policy Optimization (PPO, a reinforcement learning algorithm) across the original 9-dimensional parameter space and two learned 4-dimensional latent representations. Since different oranges have different material properties, a practical inverse system must handle arbitrary targets without retraining. We train a goal-conditioned PPO policy that learns a general inverse mapping: given any target description of peeling behavior, the policy produces a material parameter estimate in a single forward pass (8 surrogate evaluations, approximately 10ms). Operating in a normalizing flow latent space with a shared surrogate evaluator, the goal-conditioned policy achieves 0.642 actual recovery when validated through the simulator, outperforming the original parameter space by 23%. A warm-start extension that initializes CMA-ES refinement from the policy's output further improves recovery to 0.828 with 540 evaluations. These findings provide a practical framework for inverse food physics and lay groundwork for vision-driven material identification from video observations of food manipulation.

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11.
arXiv (math.PR) 2026-06-16

Atypical Decay Rates for Atypical Heights in Random Recursive Trees

Authors:
Xinxin Chen↗Heng Ma↗

arXiv:2604.20139v2 Announce Type: replace Abstract: We establish the large deviation probabilities for the height of random recursive trees, revealing polynomial upper-tail decay and stretched-exponential lower-tail decay. Remarkably, the lower tail features an atypical prefactor that grows to infinity more slowly than any $n$-fold iterated logarithm.

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

Persona-Pruner: Sculpting Lightweight Models for Role-Playing

Authors:
Jinsu Kim↗Jihoon Tack↗Noah Lee↗Jongheon Jeong↗

Language Models (LMs) have shown remarkable potential as role-playing chatbots, delivering consistent, stylized interactions when given a specification of a character or user persona. However, applying these capabilities to real-world applications (e.g., ecosystems with numerous NPCs interacting simultaneously) exposes a critical inefficiency due to the excessive computational cost. In this paper, we question the necessity of dedicating a full, generalist model to a single persona, hypothesizing that a specific character identity relies on only a fraction of the model's total capacity. We observe that naively pruning LMs often severely degrades the role-playing performance for a specific persona; it does not distinguish between redundant knowledge and essential character traits. We propose Persona-Pruner, a framework that sculpts a lightweight role-playing model by isolating persona-specific sub-networks from a single description. Our experiments consistently show that Persona-Pruner preserves role-playing performance substantially more effectively than existing state-of-the-art LLM pruning techniques, reducing the performance drop from the dense model by up to 93.8% over the strongest baseline on RoleBench in LLM-as-a-judge score, while still maintaining general LLM capabilities. Code is available at https://github.com/jsu-kim/Persona-Pruner.

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13.
arXiv (CS.LG) 2026-06-15

A Water Efficiency Dataset for African Data Centers

Authors:
Noah Shumba↗Opelo Tshekiso↗Pengfei Li↗Giulia Fanti↗Shaolei Ren↗

arXiv:2412.03716v3 Announce Type: replace Abstract: Artificial intelligence (AI) computing and data centers consume large amounts of freshwater, both directly for cooling and indirectly for electricity generation. While most attention has been paid to developed countries such as the U.S., this paper presents the first-of-its-kind dataset that combines nation-level weather and electricity generation data to estimate water usage effectiveness for data centers in 41 African countries across five different climate regions. We also use our dataset to evaluate and estimate the water consumption of inference on two large language models (i.e., Llama-3-70B and GPT-4) in 11 selected African countries. Our estimates suggest that writing a 10-page report using Llama-3-70B could consume as much as {0.66 liters} of water, while the water consumption by GPT-4 for the same task may go up to about {59 liters}. For writing a medium-length email of 120-200 words, Llama-3-70B and GPT-4 could consume about {0.13 liters} and {2.9 liters} of water, respectively. All the numbers for generative model inference tasks are based on public information available in 2024, when we initially prepared the analysis. Since then, AI inference systems have improved substantially. For example, recent disclosures suggest that energy efficiency improved by more than 30x between May 2024 and May 2025. Accordingly, our 2024 estimates should be interpreted as historical reference values rather than as representative of current performance. Interestingly, given the same AI model, 9 of the 11 selected African countries consume less water than the global average, mainly because of lower water intensities for electricity generation.

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

A New Perspective on Precision and Recall for Generative Models

Authors:
Benjamin Sykes↗Lo\"ic Simon↗Julien Rabin↗Jalal Fadili↗

arXiv:2511.02414v3 Announce Type: replace Abstract: With the recent success of generative models in image and text, the question of their evaluation has recently gained a lot of attention. While most methods from the state of the art rely on scalar metrics, the introduction of Precision and Recall (PR) for generative model has opened up a new avenue of research. The associated PR curve allows for a richer analysis, but their estimation poses several challenges. In this paper, we present a new framework for estimating entire PR curves based on a binary classification standpoint. We conduct a thorough statistical analysis of the proposed estimates. As a byproduct, we obtain a minimax upper bound on the PR estimation risk. We also show that our framework extends several landmark PR metrics of the literature which by design are restrained to the extreme values of the curve. Finally, we study the different behaviors of the curves obtained experimentally in various settings.

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

Service-Induced Congestion in Memory-Constrained LLM Serving

Authors:
Ruicheng Ao↗Jing Dong↗Gan Luo↗David Simchi-Levi↗

arXiv:2606.15555v1 Announce Type: cross Abstract: In large language model (LLM) serving, each request accumulates persistent graphics processing unit (GPU) memory during service as its key-value cache grows with every generated token. Under high concurrency, aggregate memory usage therefore increases endogenously over time: the service process itself creates future capacity pressure. When memory capacity is exceeded, systems evict active requests, discarding cached state and restarting them later, which wastes computation and reduces throughput. We develop a discrete-time dynamical model of memory-constrained LLM inference that captures admission, memory growth, and eviction under continuous batching. In the saturated-input regime, the system admits both eviction-free fixed points and limit cycles with evictions. For homogeneous workloads, we show that the eviction-free equilibrium is unstable and that, except for a Lebesgue-measure-zero exact-capture set, the system converges to a unique worst-case limit cycle that is asymptotically stable outside this exceptional set, with throughput losses as large as 50%. For heterogeneous workloads, we prove a stability criterion in the two-class common-input setting and explain how the survival-polynomial mechanism generalizes to multiple classes and heterogeneous-input lengths. Under an input-dominated scaling regime, coprime decoding lengths stabilize the eviction-free equilibrium, while non-coprime lengths create synchronized modes that drive instability. These results characterize when workload heterogeneity desynchronizes completions and helps stabilize memory-constrained serving. More broadly, we identify service-induced congestion as a structural instability mechanism and derive scheduling design principles for sustaining high throughput.

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16.
medRxiv (Medicine) 2026-06-16

Utilising Artificial Intelligence to Identify Ventricular Tachycardia Ablation Targets in Sinus Rhythm

Authors:
Wang↗Mayer↗Dennis↗Chow↗Al-Sheikhli↗Siang↗Winter↗O'Shea↗Dhanjal↗Lambiase↗Orini↗

Background and Aims: Machine learning has shown potential in predicting ablation targets for ventricular tachycardia (VT) in an animal model. This study progresses to externally validating deep learning approaches for human data. Methods: The development and external validation dataset included 21 and 13 patients, respectively, with structural VT undergoing catheter ablation. In the development datasets, electrophysiological studies were conducted using the AdvisorTM HD grid (EnsiteTM X), while both CARTO and Ensite Precision were used in the validation dataset. In each patient, VT ablation targets were defined as mapping points within 8 mm of VT isthmuses. Three advanced machine learning models were trained using cardiac mapping data acquired in both omnipolar and unipolar configurations during sinus rhythm and ventricular pacing. Discrimination was evaluated using nested leave-one-out cross-validation at patient level. Results: Overall, graph convolutional networks (GCNs), which integrate intracardiac signal waveforms with three-dimensional electroanatomical geometries, achieved the highest performance, with optimal results obtained from unipolar electrograms acquired in sinus rhythm (median AUC 0.793, sensitivity 83.6%, specificity 69.0%). This may be partly explained by the inclusion of repolarization dynamics in unipolar electrograms and the higher point density of sinus rhythm maps. Comparable performance was observed in the external dataset. Conclusion: This study demonstrates that graph convolutional networks applied to sinus rhythm EGM waveforms collected during substrate mapping can localise critical components of VT re-entry circuits. This approach has potential to provide fast and accurate ablation guidance without the need to induce and map VT, improving safety and efficacy of VT catheter ablation.

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

Focus When Necessary: Adaptive Routing and Collaborative Grounding for Training-Free Visual Grounding

Authors:
Yifan Wang↗Peiming Li↗Shiyu Li↗Zhiyuan Hu↗Xiaochen Yang↗Wenming Yang↗Yang Tang↗Zheng Wei↗

While Multimodal Large Language Models (MLLMs) excel in cross-modal reasoning, they often struggle to perceive fine-grained details in complex high-resolution images. Recent training-free methods address this through image scaling and localized cropping. However, applying these manipulations indiscriminately introduces computational redundancy for simple queries and can degrade accuracy by truncating essential global context or introducing irrelevant background noise. To this end, we propose LazyMCoT, a dynamic and training-free framework that adaptively allocates visual grounding efforts based on sample difficulty. The framework features an Adaptive Routing mechanism that evaluates predictive uncertainty using first-token statistics from a single forward pass. This efficiently bypasses confident cases while ensuring the recall of difficult samples via conformal calibration. For these challenging cases, a Collaborative Grounding module integrates the inherent cross-modal attention of the model with an external visual expert through a two-stage refinement process. This refinement process generates a precise localized display to recover small or occluded targets. Extensive experiments across diverse benchmarks demonstrate that LazyMCoT rivals training-based approaches by simultaneously improving reasoning accuracy and reducing average inference latency. Our code is availble at https://github.com/TencentBAC/LazyMCoT.

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18.
medRxiv (Medicine) 2026-06-22

AI-driven Multimodal Representation Learning for Latent Mediation Structure Discovery of Socioeconomic Disadvantage, Psychosocial Factors, and Cardiometabolic Multimorbidity

Authors:
Ma↗Cao↗

Social disadvantage is associated with multimorbidity, but the pathways linking social conditions to disease burden remain poorly understood. We developed an AI-driven multimodal mediation framework that integrates socioeconomic, psychosocial, clinical, laboratory, behavioral, and genomic data from the All of Us Research Program. Modality-specific variational autoencoders were used to derive latent representations of each data domain, and mediation analyses were subsequently performed in latent space to evaluate indirect associations between socioeconomic disadvantage, psychosocial factors, and multimorbidity. The final analytic cohort included 20,804 participants with complete multimodal data. Across 800 exposure–mediator–outcome combinations, mediation signals were concentrated within a small number of latent dimensions. The strongest indirect association linked a socioeconomic disadvantage dimension, a psychosocial vulnerability dimension, and a cardiometabolic multimorbidity dimension (NIE = 0.002517). The psychosocial dimension was characterized by poorer mental health, greater loneliness, lower social well-being, and lower health literacy, whereas the outcome dimension was associated with hypertension, diabetes, hyperlipidemia, obesity, chronic kidney disease, and heart disease. Bootstrap analyses supported the stability of the leading pathway. These findings suggest that psychosocial vulnerability may contribute to the association between socioeconomic disadvantage and cardiometabolic multimorbidity. More broadly, the proposed framework illustrates how AI-based representation learning can be used to investigate complex relationships across high-dimensional multimodal health data.

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

Neural Additive and Basis Models with Feature Selection and Interactions

Authors:
Yasutoshi Kishimoto↗Kota Yamanishi↗Takuya Matsuda↗Shinichi Shirakawa↗

arXiv:2606.19850v1 Announce Type: cross Abstract: Deep neural networks (DNNs) exhibit attractive performance in various fields but often suffer from low interpretability. The neural additive model (NAM) and its variant called the neural basis model (NBM) use neural networks (NNs) as nonlinear shape functions in generalized additive models (GAMs). Both models are highly interpretable and exhibit good performance and flexibility for NN training. NAM and NBM can provide and visualize the contribution of each feature to the prediction owing to GAM-based architectures. However, when using two-input NNs to consider feature interactions or when applying them to high-dimensional datasets, training NAM and NBM becomes intractable due to the increase in the computational resources required. This paper proposes incorporating the feature selection mechanism into NAM and NBM to resolve computational bottlenecks. We introduce the feature selection layer in both models and update the selection weights during training. Our method is simple and can reduce computational costs and model sizes compared to vanilla NAM and NBM. In addition, it enables us to use two-input NNs even in high-dimensional datasets and capture feature interactions. We demonstrate that the proposed models are computationally efficient compared to vanilla NAM and NBM, and they exhibit better or comparable performance with state-of-the-art GAMs.

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20.
medRxiv (Medicine) 2026-06-22

Paired plasma and EV-enriched plasma proteomics reveal nonredundant sepsis-associated host-response signatures in critical illness

Authors:
Rice↗S. J↗Khaleghi Ardabili↗Ruiz-Velasco↗Bonavia↗A. S↗

Background: Plasma proteomics may identify host-response signatures in sepsis, but it is unclear whether extracellular vesicle (EV)-enriched plasma provides distinct or redundant information compared with plasma. We compared paired plasma and EV-enriched plasma proteomes in critically ill patients with sepsis and critically ill non-sepsis controls (CINS). Methods: In this prospective observational study, paired plasma and EV-enriched plasma samples were analyzed from 56 critically ill adults, including 40 patients with sepsis and 16 CINS patients. Protein abundance was quantified using liquid chromatography-tandem mass spectrometry. Analyses compared proteomic depth, protein overlap, global concordance between compartments, and differential protein abundance between CINS and sepsis. Exploratory Gene Ontology enrichment was performed as a supplementary analysis. Results: EV-enriched plasma expanded proteomic detection, identifying 2,476 filtered proteins compared with 506 in plasma. Only 386 proteins were detected in both compartments, while 2,090 were unique to EV-enriched plasma and 120 were unique to plasma. Among shared proteins, plasma and EV-enriched plasma showed modest global concordance across critically ill patients (Spearman coeff = 0.322, p = 9.19 x 10^-11), with similar findings in sepsis alone. Differential abundance analysis identified 11 sepsis-associated proteins in plasma and 22 in EV-enriched plasma. Only SAA1, SAA2, and IGFBP6 were significant in both compartments. Exploratory pathway analysis supported acute-phase and inflammatory enrichment in plasma sepsis-associated proteins, while EV-enriched signals were directionally plausible but did not meet prespecified FDR thresholds. Conclusion: Plasma and EV-enriched plasma proteomics capture related but nonredundant sepsis-associated host-response information in critically ill patients.

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21.
arXiv (CS.AI) 2026-06-11

Sample-Efficient Hypergradient Estimation for Decentralized Bi-Level Reinforcement Learning

Authors:
Mikoto Kudo↗Takumi Tanabe↗Akifumi Wachi↗Youhei Akimoto↗

arXiv:2603.14867v4 Announce Type: replace-cross Abstract: Many strategic decision-making problems, such as environment design for warehouse robots, can be naturally formulated as bi-level reinforcement learning (RL), where a leader agent optimizes its objective while a follower solves a Markov decision process (MDP) conditioned on the leader's decisions. In many situations, a fundamental challenge arises when the leader cannot intervene in the follower's optimization process; it can only observe the optimization outcome. We address this decentralized setting by deriving the hypergradient of the leader's objective, i.e., the gradient of the leader's strategy that accounts for changes in the follower's optimal policy. Unlike prior hypergradient-based methods that require extensive data for repeated state visits or rely on gradient estimators whose complexity can increase substantially with the high-dimensional leader's decision space, we leverage the Boltzmann covariance trick to derive an alternative hypergradient formulation. This enables efficient hypergradient estimation solely from interaction samples, even when the leader's decision space is high-dimensional. Additionally, to our knowledge, this is the first method that enables hypergradient-based optimization for 2-player Markov games in decentralized settings. Experiments highlight the impact of hypergradient updates and demonstrate our method's effectiveness in both discrete and continuous state tasks.

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22.
medRxiv (Medicine) 2026-06-16

AI-assisted continuous-time modelling of metastatic breast cancer reveals subtype-specific spatiotemporal organ interactions

Authors:
Vaisband↗Rinnerthaler↗Gampenrieder↗S. P↗Binder↗Singer↗C. F↗Sliwa↗Roitner↗Hager↗Pichler↗Udovica↗…

Metastatic breast cancer is one of the leading causes of premature mortality among women worldwide. A major barrier to optimal care is the marked heterogeneity in both the temporal dynamics of metastatic spread and the organ-specific spatial distribution of metastases. Existing analyses do not adequately capture this complexity, as they either neglect temporal dependencies or assume independence between metastasic sites. As a result, it remains unclear how established metastases influence subsequent organ-specific dissemination. We address this question using patient-level longitudinal trajectories from a large multicentre real-world metastatic breast cancer registry, combined with an AI-assisted disease-progression modelling framework based on continuous-time Markov chains that represent combinations of metastatic sites and the non-uniform and practice-driven timing of radiologic response assessments, as encountered in routine clinical care. We present a stochastic model determined by progression rates, which are parameterised to capture baseline organ-specific transition risks, patient-level covariates, and pairwise inter-organ interaction effects. High-dimensional treatment information is incorporated using an large language model based encoding. We find that metastatic spread follows non-independent, subtype-specific spatiotemporal patterns, with subtype-specific inter-organ interaction patterns that shape progression. Visceral metastases, particularly lung and liver metastasis, are associated with an increased hazard of subsequent brain metastasis, with effects varying across hormone receptor-positive, HER2-positive, and triple-negative subtypes. Together, these findings define a clinically relevant spatiotemporal architecture of metastatic progression in breast cancer. This framework enables refined mechanism-informed risk stratification and provides a data-driven rationale for targeted and risk-adapted – rather than symptom-triggered – surveillance strategies.

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23.
arXiv (CS.AI) 2026-06-16

PISA: A Pragmatic Psych-Inspired Unified Memory System for Enhanced AI Agency

Authors:
Shian Jia↗Ziyang Huang↗Xinbo Wang↗Haofei Zhang↗Mingli Song↗

arXiv:2510.15966v2 Announce Type: replace Abstract: Memory systems are fundamental to AI agents, yet existing work often lacks adaptability to diverse tasks and overlooks the constructive and task-oriented role of AI agent memory. Drawing from Piaget's theory of cognitive development, we propose PISA, a pragmatic, psych-inspired unified memory system that addresses these limitations by treating memory as a constructive and adaptive process. To enable continuous learning and adaptability, PISA introduces a trimodal adaptation mechanism (i.e., schema updation, schema evolution, and schema creation) that preserves coherent organization while supporting flexible memory updates. Building on these schema-grounded structures, we further design a hybrid memory access architecture that seamlessly integrates symbolic reasoning with neural retrieval, significantly improving retrieval accuracy and efficiency. Our empirical evaluation, conducted on the existing LOCOMO benchmark and our newly proposed AggQA benchmark for data analysis tasks, confirms that PISA sets a new state-of-the-art by significantly enhancing adaptability and long-term knowledge retention.

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24.
arXiv (CS.LG) 2026-06-16

Stop the Sampler! Classifier-Based Adaptive Stopping for Sampling Kernels

Authors:
Kirill Korolev↗Nikita Morozov↗Stepan Pavlenko↗Esmeralda S. Whitammer↗Sergey Samsonov↗

arXiv:2606.16073v1 Announce Type: new Abstract: Sampling from complex, unnormalized probability densities is a fundamental challenge in Bayesian inference and probabilistic modeling. While Markov chain Monte Carlo (MCMC) methods provide asymptotic guarantees, they often suffer from slow mixing and high computational costs due to fixed or manually tuned trajectory lengths. In this work, we propose a novel framework that treats trajectory termination as a learnable component of the sampling dynamics. By framing MCMC within the theory of non-acyclic generative flow networks (GFlowNets), we train state-dependent neural classifiers to decide when a trajectory has reached a high-density region and should terminate. We theoretically establish the connection between optimal classifiers and the target density via detailed balance conditions and introduce a multilevel training scheme to facilitate exploration in complex geometries. Experimental results across various benchmark densities demonstrate that our approach significantly reduces average trajectory lengths while improving mode coverage and mixing compared to standard MCMC baselines.

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25.
arXiv (CS.CL) 2026-06-17

AIPatient Arena: EHR-grounded evaluation of large language models in end-to-end clinical consultation workflows

Authors:
Jiahui Niu↗Huizi Yu↗Wenkong Wang↗Guangxin Dai↗Jingxian He↗Xiang Li↗Zhiying Liang↗Xinxin Lin↗Kent CY So↗Bryan YP Yan↗Yun Kwok Wing↗Yanqiu Xing↗…

Large language models (LLMs) are increasingly considered for use in clinical consultation tasks, yet most medical evaluations remain static, single-turn, or narrowly outcome-based, limiting their ability to reflect the sequential, uncertain, and interactive nature of real-world care. Here, we propose AIPatient Arena, an EHRs-grounded evaluation framework for assessing the clinical utility of LLMs across eight dimensions of clinical competence. The framework integrates EHR data into patient-specific knowledge graphs, enabling multi-turn physician-patient interactions. We applied AIPatient Arena on a primary cohort of 437 patients and two out-of-distribution validation cohorts of 119 and 67 patients. We observe that LLMs performed well in medical interview questioning skills (QS; mean scores, 4.43-4.99/5), ethical and professional conduct (ET; 4.38-4.93/5), and clarity and transparency of clinical explanations (EX; 3.80-4.72/5). Performance was moderate in information integration (II; 3.19-4.21/5) and medication safety and justification (MS; 3.13-3.78/5), but persistent weaknesses were observed in handling of ambiguous patient responses (HR; 2.57-3.32/5), information coverage (IC; 2.08-3.02/5), and diagnostic accuracy and reasoning (Dx; 2.63-3.55/5). Process-based evaluation revealed recurrent interaction failures, including repetitive questioning, omission of past medical history, and inadequate handling of uncertainty. Richer conversational context improved diagnostic reasoning but yielded limited gains in treatment planning. These findings indicate that final-answer accuracy alone is insufficient for evaluating clinical readiness and highlight the importance of assessing how models gather, interpret, and communicate information throughout a consultation. AIPatient Arena provides an EHR-grounded framework for workflow-oriented pre-deployment evaluation of medical LLMs.

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