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01.
medRxiv (Medicine) 2026-06-22

Modelling the decadal expansion of West Nile virus in Italy: the role of climatic, anthropogenic, and macroecological drivers

Authors:
Marcolin↗Bella↗Del Manso↗Dorigatti↗Pezzotti↗Poletti↗Riccardo↗Di Marco↗

Abstract BACKGROUND West Nile virus (WNV) is a growing health burden in Italy. Anticipating human infection risk is hampered by the pathogen's complex ecology, highlighting the need for comprehensive early-warning tools. AIM We aimed to model municipal-level WNV risk in Italy and characterize its decadal expansion in Italy, providing a comprehensive ecological understanding of viral emergence. METHODS We applied a machine learning framework to annual human WNV case data from 2014 to 2024. The model integrated a suite of environmental, socio-economic, and macroecological predictors to generate risk projections. We evaluated the model's performance through multiple validation settings. We also performed an anticipation test for the 2025 epidemic season, using 2024 environmental data to assess the model's predictive accuracy against observed 2025 human cases. RESULTS Our model achieved robust performance (True Skill Statistic > 0.4) and captured WNV progressive expansion from 184 predicted positive municipalities in 2014 to 2,012 in 2024 (an 11-fold increase in 11 years). Seasonal minimum temperature was the primary risk driver, followed by monitoring year and population density, indicating active spatial spread. Environmental suitability consistently preceded clinical detection. Municipalities with cases in 2023-2024 exhibited significantly higher predicted suitability during 2018-2022 than those without cases (average risk 0.58 vs 0.20). Our model successfully identified emerging risk hotspots along the Adriatic coast and southern Italy before the official human spillover of 2025. CONCLUSION Embedding macroecological drivers into WNV risk modelling provides an improved understanding of drivers of rapid WNV expansion. Our model enables proactive risk mapping, surveillance efforts, and targeted public health measures.

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02.
arXiv (CS.AI) 2026-06-24

Fix Initial Programs and Iteratively Refine Repair Instructions Toward Non-Elimination Multi-Turn Program Correction

Authors:
Yuto Tanaka↗Issei Sato↗

arXiv:2604.23989v2 Announce Type: replace-cross Abstract: Recent work on large language models (LLMs) has emphasized the importance of scaling inference compute. From this perspective, the state-of-the-art method Scattered Forest Search (SFS) has been proposed, employing Monte Carlo Tree Search with carefully crafted initial seeds and textual optimization for multi-turn program correction. However, its complexity makes it unclear what factors contribute to improvements in inference performance. To address this problem, we analyze SFS and propose a simpler method, \textsc{Iterative Refinement of Repair Instructions} (IRRI), which fixes initial programs and iteratively refines repair instructions. Because of the simplicity of IRRI, we theoretically establish the non-elimination of IRRI using Oracle-Guided Inductive Synthesis (OGIS). Experiments on several program generation benchmarks suggest that IRRI achieves inference performance comparable to state-of-the-art methods. These results indicate that, even without complex search structures, refining initial programs with high-quality repair instructions alone can effectively improve inference performance.

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

DiffMath: Symbol- and Graph-Aware Latent Diffusion Transformer for Handwritten Mathematical Expression Generation

Authors:
Wei Pan↗Xuhan Zheng↗Yilin Shi↗Huiguo He↗Hiuyi Cheng↗Dezhi Peng↗Minghui Liao↗Lianwen Jin↗

Handwritten Mathematical Expression Generation (HMEG) is challenging due to the complex two-dimensional layouts and long-range structural dependencies of mathematical expressions. Existing methods typically rely on explicit spatial supervision, such as symbol-level bounding boxes, which incurs high annotation costs and limits scalability. In this work, we propose DiffMath, a symbol- and graph-aware latent diffusion framework that leverages the hierarchical structure inherent in LaTeX as a structural prior, eliminating the need for positional supervision. First, we design a Relational Abstract Syntax Tree (RelAST), a generation-oriented representation that distills MathML trees into compact triplet sequences [S, R, D], where each token directly encodes a symbol identity, spatial relation, or nesting depth. Second, we introduce MathVAE, which learns structure-preserving latent representations through symbol-aware and relation-aware perceptual regularization, ensuring that the latent space captures both character semantics and spatial topology. Third, MathDiT performs conditional denoising in this structured latent space, further guided by a global symbol-count prior via Adaptive Layer Normalization (AdaLN) to improve structural coherence. Experiments show that DiffMath produces structurally consistent handwritten expressions, achieves superior performance over existing methods, and improves the accuracy of downstream OCR models through synthetic data augmentation.

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04.
arXiv (CS.CL) 2026-06-16

A large-scale pipeline for LLM-assisted corpus annotation: variation and change in the English consider construction

Authors:
Cameron Morin↗Matti Marttinen Larsson↗

As natural language corpora expand at an unprecedented rate, manual annotation remains a significant methodological bottleneck in corpus linguistic work. We address this challenge by presenting a scalable pipeline for automating grammatical annotation in voluminous corpora using large language models (LLMs). Unlike previous supervised and iterative approaches, our method employs a four-phase workflow: prompt engineering, pre-hoc evaluation, automated batch processing, and post-hoc validation. We demonstrate the pipeline's accessibility and effectiveness through a diachronic case study of variation in the English evaluative consider construction (consider X as/to be/{\O} Y). We annotate 143,933 'consider' concordance lines from the Corpus of Historical American English (COHA) via the OpenAI API in under 60 hours, achieving 98%+ accuracy on two sophisticated annotation procedures. A Bayesian multinomial GAM fitted to 44,527 true positives of the evaluative construction reveals previously undocumented genre-specific trajectories of change, enabling us to advance new hypotheses about the relationship between register formality and competing pressures of morphosyntactic reduction and enhancement. Our results suggest that LLMs can perform a range of data preparation tasks at scale with minimal human intervention, unlocking substantive research questions previously beyond practical reach, though implementation requires attention to costs, licensing, and other ethical considerations.

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05.
arXiv (CS.LG) 2026-06-19

Alzheimer's Disease Diagnosis using a Multimodal Approach with 3D MRI and PET

Authors:
Loukas Ilias↗Anthi-Maria Vozinaki↗Christos Ntanos↗Dimitris Askounis↗

arXiv:2606.20037v1 Announce Type: new Abstract: Alzheimer's disease (AD) is an irreversible neurodegenerative disorder and a leading cause of death worldwide. Early diagnosis plays an important part especially at the Mild Cognitive Impairment stage, where timely intervention can help slow its progression before it advances to AD. Neuroimaging data, like Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) scans, can help detect brain changes early by providing structural and functional brain changes related to the disease. Yet, many multimodal models still fuse MRI and PET with static concatenation and apply identical computation to all subjects, which limits robustness to patient/site heterogeneity and can waste computation. To address these limitations, we present the first study of combining 3D convolutional feature extractors with three fusion strategies - concatenation, Gated Multimodal Unit (GMU), and gated self-attention - and a sparsely gated Mixture-of-Experts (MoE) classifier that performs input-adaptive routing, activating only the most informative experts per case. Finally, we utilize Grad-CAM to visualize disease-related regions, ensuring model interpretability. Experiments are performed across three binary classification tasks (NC vs. MCI, MCI vs. AD, and NC vs. AD). Results show that GMU achieves accuracies of 80.46 % (NC vs. MCI) and 95.47 % (NC vs. AD), while gated self-attention attains 82.08 % on MCI vs. AD. Ablations show that removing the MoE consistently degrades accuracy across all tasks. These findings underscore the value of input-adaptive, multimodal modeling for AD diagnosis by leveraging the complementary nature of MRI and PET.

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

Active Inference with a Self-Prior in the Mirror-Mark Task

Authors:
Dongmin Kim↗Hoshinori Kanazawa↗Yasuo Kuniyoshi↗

arXiv:2604.09673v2 Announce Type: replace-cross Abstract: The mirror self-recognition test evaluates whether a subject touches a mark on its own body that is visible only in a mirror, and is widely used as an indicator of self-awareness. In this study, we present a computational model in which this behavior emerges spontaneously through a single mechanism, the self-prior, without any external reward. The self-prior, implemented with a Transformer, learns the density of familiar multisensory experiences; when a novel mark appears, the discrepancy from this learned distribution drives mark-directed behavior through active inference. A simulated infant, relying solely on vision and proprioception without tactile input, discovered a sticker placed on its own face in the mirror and removed it in approximately 70% of cases without any explicit instruction. Expected free energy decreased significantly after sticker removal, confirming that the self-prior operates as an internal criterion for distinguishing self from non-self. Cross-modal sampling further demonstrated that the self-prior captures visual–proprioceptive associations, functioning as a probabilistic body schema. These results provide a concise computational account of the key behavior observed in the mirror test and suggest that the free energy principle can serve as a unifying hypothesis for investigating the developmental origins of self-awareness. Code is available at: https://github.com/kim135797531/self-prior-mirror

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

Querying Counterfactuals on Tissue Graphs with Supervised Disentanglement

Authors:
Abdul Moeed↗Stefan Schrod↗Martin Rohbeck↗Marc Jan Bonder↗Pavlo Lutsik↗Oliver Stegle↗Daniel Dimitrov↗

arXiv:2606.08493v2 Announce Type: replace-cross Abstract: Tissue graph counterfactuals ask how a cell's expression would change under altered spatial neighbor contexts. Such queries are central to predicting cell behavior in tissues, but lack a unified definition, with existing methods targeting specific intervention types or treating cells as i.i.d. In this work, we first formalize tissue graph counterfactuals as a class of spatial interventions that either rewire connections between cells (edge perturbation) or modify the expression of their neighbors (node perturbation). We then introduce Cellina (https://cellina.readthedocs.io) - a framework that uses supervised disentanglement to decompose a cell's intrinsic state from its spatial context, using the latter as a conditioning input for counterfactual predictions. Across benchmarks spanning over 2.5 million spatially-resolved cells in colorectal cancer and mouse brain, Cellina outperforms spatially-informed and non-spatial competitors in in-silico graph perturbations, disentanglement, and scalability. Additionally, we show that Cellina reveals biologically distinct cancer subdomains in an unsupervised manner and enables targeted neighbor perturbation simulations.

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08.
arXiv (CS.AI) 2026-06-18

RippleBench: Capturing Ripple Effects Using Existing Knowledge Repositories

Authors:
Roy Rinberg↗Usha Bhalla↗Igor Shilov↗Flavio P. Calmon↗Rohit Gandikota↗

arXiv:2512.04144v2 Announce Type: replace Abstract: Targeted interventions on language models, such as unlearning or model editing, aim to modify specific information, but their effects often propagate to related, unintended areas (e.g., removing virology content may degrade performance on allergies); these side-effects are commonly referred to as the ripple effect. We introduce RippleBench-Maker, an automatic pipeline that retrieves semantic neighbors of any source concept from a knowledge repository and generates multiple-choice questions at varying semantic distances. We instantiate this framework using WikiRAG, an open-source RAG system over English Wikipedia, to construct RippleBench-WMDP-Bio (584 seed topics, 352,961 questions), and evaluate eight unlearning methods on Llama3-8B-Instruct. All eight exhibit accuracy drops that are largest near the unlearned target and decay with semantic distance, each with a distinct propagation profile. We replicate these findings across Mistral-7B, Zephyr-7B, and Yi-34B; cross-model delta curves are nearly identical, suggesting ripple effects are a property of the unlearning method rather than the base model. We validate all major pipeline stages using a four-experiment Mechanical Turk study (5,200+ responses, 61 workers). We release all code, data, and infrastructure.

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09.
arXiv (CS.CL) 2026-06-16

Vocabulary Dropout for Curriculum Diversity in LLM Co-Evolution

Authors:
Jacob Dineen↗Aswin RRV↗Zhikun Xu↗Ben Zhou↗

Co-evolutionary self-play, where one language model generates problems and another solves them, promises autonomous curriculum learning without human supervision. In practice, the proposer quickly converges to a narrow distribution of problems that satisfy the reward function. This diversity collapse renders the curriculum uninformative for the solver, stalling the co-evolutionary loop. We introduce vocabulary dropout, a random mask applied to the proposer's output logits during both policy training and curriculum generation, as a lightweight mechanism to sustain diversity. The mask is hard and non-stationary, preventing the proposer from locking into fixed token sequences. Training Qwen3-4B and Qwen3-8B on mathematical reasoning via R-Zero, we find that vocabulary dropout sustains proposer diversity across lexical, semantic, and functional metrics throughout training. It also yields solver improvements averaging +4.4 points at 8B, with the largest gains on competition-level benchmarks. Our findings suggest that explicit action-space constraints, analogous to the structural role that game rules play in classical self-play, can help sustain productive co-evolution in language. Vocabulary dropout is one simple instantiation of this principle.

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10.
Nature (Science) 2026-06-24

The mutational landscape of STING-induced immunity

Authors:
Bing Zhang↗

Stimulator of interferon genes (STING) is an evolutionary conserved immune signalling protein with key roles in host defence, cancer, senescence and inflammation1–3. Downstream of STING, type I interferon, inflammatory cytokine signalling and non-canonical autophagy are governed by a multilayered mechanism integrating ligand-induced structural transitions, protein–protein interactions and coordinated intracellular trafficking4–13. Despite its central role in immunity and relevance as therapeutic target14, the sequence elements that govern STING (in)activation in cells remain incompletely understood. Here we developed a massively parallel assay to systematically chart the sequence-function landscape of STING. Profiling thousands of single amino-acid variants, we identified structural and functional determinants that shape the immunostimulatory capacity of STING and its ability to translate ligand recognition into distinct signalling outputs. Cryogenic-electron microscopy structures of select STING hyperactive variants revealed new regulatory principles dictating conformational transition from inactive to signalling-competent states of STING. Mutational effects are widespread across the functional landscape and can sensitize STING towards the natural ligand 2′3′-cGAMP15–18 or decouple interferon induction from non-canonical autophagy, demonstrating a diversity of possible responses that can be accessed through single point substitutions. Finally, our data showed the clinical and evolutionary relevance of naturally occurring STING protein variants. Collectively, these findings define molecular principles that tune STING activity and chart the landscape of its functional potential across immune contexts. A massively parallel assay systematically charts the sequence-function landscape of the STING signalling protein, and the findings define molecular principles that tune STING activity and show its functional potential across immune contexts.

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11.
arXiv (quant-ph) 2026-06-24

Faster algorithm for achieving minimal-size quantum decision diagrams

Authors:
Juul Sanders↗Sebastiaan Brand↗Arend-Jan Quist↗Tim Coopmans↗

arXiv:2606.24789v1 Announce Type: new Abstract: The decision diagram (DD) data structure enables fast linear-algebra calculations by bringing vectors into a normal form and subsequently merging equivalent ones, yielding a minimally-sized DD modulo the equivalence relation. A fruitful application area is quantum-circuit simulation, where the vectors represent quantum states. The Local Invertible Map Decision Diagram (LIMDD) type, merges LIM-equivalent (typically Pauli-gate equivalent) vectors, can efficiently simulate Clifford circuits as well as some high-T-count circuits, and has theoretically been proven exponentially faster for simulation than other well-developed data structures, including other common DD variants. However, these exponential advantages have not fully materialized yet in existing implementations, for which the normal-form procedure, which is a highly complex algorithm, is either absent or only partially implemented. We here present a novel normal-form algorithm for Pauli-LIMDDs, achieving a worst-case speedup from $O(n^3)$ to $O(n^2)$ for an $n$-qubit DD node with a single child node while keeping the $O(n^3)$ run time in case of two distinct children nodes. We implement the algorithm as part of QolDDer, our Pauli-LIMDD simulator for quantum circuits, written from scratch in C/C++. The implementation realizes the theoretically-proven advantages of Pauli-LIMDDs on Clifford circuits, is significantly faster than the existing LIMDD simulators on such circuits, and on a public quantum-circuit data set often outperforms them by an order of magnitude. In the future, we envision that our work will enable further application and development of LIMDD variants, not only for quantum design tasks, but also for analysis of linear-algebra-based systems in general.

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12.
arXiv (quant-ph) 2026-06-24

Ground-State Energy Solutions of the Lithium Atom: Zeroth-, First-, and Second-Order Perturbation Theory and the Variational Method

Authors:
Afraa Mahboubi↗B\"u\c{s}ra G\"ok\c{c}e Zolmaz↗Devrim Karayer↗Handenur \c{S}ay↗O\u{g}uzhan Kaya↗Abdulkadir Senol↗

arXiv:2606.24238v1 Announce Type: new Abstract: In this work, the ground-state energy of the lithium atom is systematically investigated using both time-independent perturbation theory and the variational method to provide a comprehensive pedagogical analysis of many-body atomic systems. The unperturbed Hamiltonian is initially constructed by neglecting electron-electron interactions, treating the system as three independent hydrogen-like electrons to yield a zeroth-order energy baseline of -275.51 eV. The antisymmetric fermionic nature of the exact wave function is rigorously enforced through the Slater determinant formalism. First-order perturbation theory is applied to evaluate static inter-electronic repulsion using exact Coulomb and exchange integrals, refining the energy state to -192.01 eV. To account for dynamical electronic correlation, second-order perturbation theory is computed numerically for virtual single-electron s-orbital transitions, leading to a total perturbative energy of -196.36 eV. A brief discussion of two-electron excitations is also included to encapsulate further physical realism within the framework. Furthermore, a non-orthogonal two-parameter variational approach is employed to model the shell-specific shielding effect. By optimizing the effective nuclear charges, the variational method establishes a superior upper bound energy of -201.187 eV. The results of both methods are comprehensively contrasted against each other and the reference baseline to provide critical insights into the nature of electron correlation and screening in multi-electron atoms.

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

Phase Transitions in Attention: A Bayesian Theory of Copy Head Emergence

Authors:
Itay Lavie↗Kirsten Fischer↗Andrey Lekov↗Frederic Van Maele↗Zohar Ringel↗Moritz Helias↗

arXiv:2606.12058v1 Announce Type: cross Abstract: Attention is the key mechanism underlying in-context learning in transformers, and attention patterns have been observed empirically to emerge abruptly during training. We present a Bayesian theory of feature learning in attention; we then focus on how the copy subcircuit in the first layer of an induction head is learned by analyzing a single-layer softmax attention network trained on a copy task. We derive a closed-form posterior over the attention matrix and reduce it to a low-dimensional order parameter space. This reduction reveals a phase transition in the amount of training data, which we verify using both Bayesian sampling and standard training with Adam. We contrast our results with linear attention and find that softmax attention exhibits a first-order phase transition while in linear attention an initial second-order phase transition is followed by a smooth, continuous evolution toward the structured attention pattern (crossover). Our work provides a first-principles theoretical account of the abrupt emergence of the copy subcircuit, reminiscent of the one observed in training large language models.

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14.
arXiv (CS.LG) 2026-06-25

Asymptotic Learning Curves for Diffusion Models with Random Features Score and Manifold Data

Authors:
Anand Jerry George↗Nicolas Macris↗

arXiv:2603.22962v3 Announce Type: replace Abstract: We study the theoretical behavior of denoising score matching–the learning task associated to diffusion models–when the data distribution is supported on a low-dimensional manifold and the score is parameterized using a random feature neural network. We derive asymptotically exact expressions for the test, train, and score errors in the high-dimensional limit. Our analysis reveals that, for linear manifolds the sample complexity required to learn the score function scales linearly with the intrinsic dimension of the manifold, rather than with the ambient dimension. Perhaps surprisingly, the benefits of low-dimensional structure starts to diminish once we have a non-linear manifold. These results indicate that diffusion models can benefit from structured data; however, the dependence on the specific type of structure is subtle and intricate.

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15.
Nature Medicine 2026-06-15

Adaptive deep brain stimulation for dynamic gait control in Parkinson’s disease: a randomized feasibility trial

Authors:
Kenneth H. Louie↗

A randomized crossover study of five patients with Parkinson’s disease (PD) demonstrates that gait-synchronized adaptive deep brain stimulation is feasible and safe, and reduces falls compared with continuous stimulation. Gait dysfunction in PD is a major source of disability and is often insufficiently treated by continuous deep brain stimulation (cDBS). Although adaptive DBS (aDBS) has shown efficacy for other motor symptoms using β-based, state-driven neural signals, gait is a dynamic, cyclical behavior that may require temporally precise modulation. Here we evaluated a behavior-contingent aDBS approach that synchronizes stimulation to gait phase. We reported a single-center, blinded, randomized, crossover study evaluating the feasibility of identifying patient-specific biomarkers to drive aDBS. The primary outcome was feasibility of successful identification of gait-phase biomarkers to implement aDBS. Five participants with PD undergoing pallidal DBS and subdural electrode paddle implantation were enrolled. We successfully identified personalized gait-phase biomarkers from cortical or pallidal field potentials in all five patients and embedded them into a bidirectional neurostimulator. During acute in-clinic testing, aDBS improved step variability and step symmetry versus cDBS. Three participants subsequently completed a double-blinded, multi-day crossover phase. In this setting, aDBS maintained general motor symptom control, reduced falls and yielded patient-specific gait improvements. No adverse events occurred and aDBS was well tolerated. These findings establish the feasibility of biomarker-driven, movement-synchronized neuromodulation and support the development of a larger randomized trial to determine clinical efficacy. ClinicalTrial.gov registration: NCT04675398 . A randomized crossover study shows that gait-phase-synchronized adaptive deep brain stimulation is feasible and safe, and reduces falls compared to continuous stimulation in Parkinson’s disease.

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

PermaVid: Consistent Video Generation Across Edits via Disentangled Context Memory

Authors:
Shuai Yang↗Bingjie Gao↗Ziwei Liu↗Jiaqi Wang↗Dahua Lin↗Tong Wu↗

Consistent video generation under editing operations requires persistence: when edits modify scene appearance or layout, subsequent generations should remain coherent across time and viewpoints. However, existing memory designs struggle to maintain long-term consistency after such modifications, as stored contexts may become outdated or invalid. To address this, we propose PermaVid, a novel framework built upon a multi-modal context memory that disentangles spatial context into semantic appearance and geometric structure, together with an edit-aware memory update and retrieval strategy that keeps memory evolution aligned with subsequent observations. Specifically, we develop two complementary memory banks: an RGB context memory that captures appearance-aware observations while implicitly encoding geometry, and a depth context memory that preserves geometry-only structure disentangled from semantics. Building on this design, we introduce a memory-guided video generation model that performs multi-modal feature fusion under reference conditions drawn from mixed-modality memory contexts. Experiments demonstrate that our method maintains strong long-term semantic and structural consistency after edits, significantly outperforming state-of-the-art methods.

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

L-Proto: Language-Aware Episodic Prototypical Training for Multilingual Speaker Verification

Authors:
Hyung-Seok Oh↗Deok-Hyeon Cho↗Seung-Bin Kim↗Seong-Whan Lee↗

arXiv:2606.17416v1 Announce Type: cross Abstract: Multilingual speaker verification remains challenging because language-dependent acoustic variability causes speaker identity to become entangled with linguistic characteristics, degrading generalization across languages. In multilingual training, embeddings often encode language cues with speaker identity, causing speakers to form language-specific clusters. We propose L-Proto, a language-aware episodic prototypical training strategy that constructs language-consistent episodes. By sampling speakers from a single language per episode, L-Proto reduces language-driven variation during training and encourages embeddings to focus more directly on speaker identity. Experiments on the TidyVoice Challenge benchmark demonstrate consistent performance improvements over conventional fine-tuning and random episodic sampling across multiple backbone architectures.

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18.
arXiv (quant-ph) 2026-06-16

Boson Sampling as a Probe of Chaotic and Integrable Quantum Dynamics in a Photonic Chip

Authors:
Yuancheng Zhan↗Khen Cohen↗Norman T. W. Koo↗Kian Hwee Lim↗Hui Zhang↗Lingxiao Wan↗Sanghoon Chae↗Ai Qun Liu↗Victor M Bastidas↗Yaron Oz↗Leong-Chuan Kwek↗

arXiv:2605.25398v2 Announce Type: replace Abstract: Quantum chaos plays a key role in understanding complex quantum dynamics, while integrated photonics offers unique advantages for quantum applications, including high-speed operation, scalability, and programmable unitary transformations. However, integrated photonic approaches to probing quantum chaos remain largely unexplored, owing to the absence of a clear connection between programmable photonic dynamics and established chaos diagnostics. In this work, we establish Fock-state boson sampling as a practical probe of quantum chaos by exploiting the sensitivity of multiphoton interference to the random-matrix properties of underlying single-particle unitary dynamics. More importantly, we design and fabricate a programmable quantum photonic chip to experimentally implement this framework, achieving the first integrated-photonic demonstration of quantum-chaos probes based on boson sampling. Experimental results show that the three complementary probes proposed in this work, namely the distance to Porter–Thomas statistics, Shannon entropy, and Out-of-Time-Ordered-Correlator-equivalent observables, exhibit close agreement with theoretical predictions and consistently distinguish chaotic and integrable dynamics. Our work provides a scalable route for investigating complex quantum dynamics on programmable photonic platforms while leveraging the intrinsic advantages of boson sampling through multiphoton interference and complex output statistics.

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

Uncertainty-Aware Reward Modeling for Stable RLHF

Authors:
Licheng Pan↗Haocheng Yang↗Haoxuan Li↗Yichen Sun↗Yunsheng Lu↗Shijian Wang↗Lei Shen↗Yuan Lu↗Zhixuan Chu↗Hao Wang↗

arXiv:2606.19818v1 Announce Type: cross Abstract: Reinforcement learning from human feedback (RLHF) aligns large language models by training reward models on preference data and optimizing policies to maximize predicted rewards. However, this pipeline faces two fundamental challenges: (1) reward models cannot signal when their predictions are unreliable, since they usually act as deterministic point estimators; and (2) modern group-based policy optimization can amplify unreliable reward signals, as exemplified by GRPO's uniform treatment of rewards during advantage computation. As policies explore increasingly diverse responses, these two limitations create a critical vulnerability: unreliable reward estimates may be granted disproportionate influence, triggering severe reward hacking. We propose Uncertainty-Aware Reward Modeling (UARM), which equips reward models with calibrated uncertainty via quantile-based conformal prediction and reweights GRPO advantages through heteroscedastic variance decomposition. Experiments across HelpSteer, UltraFeedback, and PKU-SafeRLHF demonstrate that UARM significantly improves reward model calibration, reduces reward hacking, and enhances downstream alignment quality compared to standard GRPO and uncertainty-agnostic baselines.

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20.
bioRxiv (Bioinfo) 2026-06-16

Super Learner Ensemble Modeling of CPTAC Proteomic Data for Survival Prediction in Head and Neck Squamous Cell Carcinoma

Authors:
Park↗Lee↗Oh↗E. J↗Tham↗Ahn↗

Survival analysis in head and neck squamous cell carcinoma (HNSCC) is traditionally performed using Cox proportional hazards models, alongside some exploration into black-box machine learning methods. The Super Learner (SL) algorithm addresses this model selection dilemma by combining diverse candidate algorithms into a weighted ensemble to perform comparably to the best candidate method. This study evaluates the performance of SL in HNSCC. Proteomic features as well as clinical covariates from 96 CPTAC HNSCC samples were modeled with three candidate algorithms (Cox LASSO, Cox Ridge, and Random Survival Forest) as well as the ensemble SL method. Models were optimized via Uno's time-dependent Concordance Index (C-index) and tested at 1- and 3-year time horizons using 2000 bootstrap resamples. The Cox Ridge regression model achieved the highest predictive accuracy among the four total methods. However, the SL demonstrated stable performance over both time horizons (1-year C-index: 0.985; 3-year C-index: 0.960). Variable importance analysis of the Cox Ridge model successfully identified malignant proteins (ATR, MAML1, MIEN1) alongside novel potential prognostic indicators (ZNF800, KERA). This analysis emphasizes the statistical necessity for larger cohorts for ensemble learning, while providing a benchmark of proteomic indicators in HNSCC.

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21.
arXiv (CS.AI) 2026-06-25

AI Coaching for Accelerating Human Skill Development with Reinforcement Learning

Authors:
Wei Wang↗Enlin Gu↗Antonio Loquercio↗Haimin Hu↗Rahul Mangharam↗

arXiv:2606.25337v1 Announce Type: cross Abstract: AI copilots can substantially boost human performance through shared control, but excessive assistance can induce over-reliance and skill atrophy. This paper studies how an embodied AI agent can act as a coach that accelerates human motor-skill development. We argue that effective coaching requires strategic scaffolding and stepping back that are aligned with the learner's capability, allowing productive failures that drive learning. We formalize the interactive AI coaching process as a non-cooperative dynamic game in which the learner optimizes task performance while the coach targets the learner's independent competence. Building on this formalism, we develop a reinforcement learning framework combining adaptive shared control with probabilistic models of the coach's causal influence on skill evolution, enabling tractable training of coaching policies. A comprehensive user study (N=33) on first-person-view drone racing shows significant gains in human learning outcomes over state-of-the-art AI coaching baselines.

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22.
medRxiv (Medicine) 2026-06-16

The biological clock of multimorbidity: temporal dynamics of disease co-occurrence in primary care

Authors:
Sanchez-Valle↗Zambrana↗Navarro-Martinez↗Costa↗F. X↗Rocha↗L. M↗Cirillo↗Violan↗Valencia↗

Multimorbidity is the dominant clinical reality of primary care, yet the temporal dynamics governing when and how persistent comorbidity associations emerge remain poorly characterised. Most large-scale comorbidity studies adopt a single observation window after an index diagnosis, implicitly assuming that associations detectable at one year are equally detectable at five. Using 11 years of electronic health records from 5,821,197 individuals in Catalan primary care, we applied a matched cohort design across nine complementary follow-up windows, five cumulative (0-1 to 0-5 years) and four conditional (1-2 to 4-5 years), to 1,315 index diseases, identifying 144,030 significant directed comorbidity associations in the five-year network. We found that 60.1% of these associations required at least three years of follow-up and were undetectable in shorter-window analyses, demonstrating that observation window length is a primary determinant of which comorbidities can be observed. To organise this temporal heterogeneity, we introduce the biological clock of multimorbidity: a two-dimensional framework that positions ICD-10 disease categories according to their rates of cumulative signal attenuation and the persistence of conditional risk. This framework identifies four reproducible temporal patterns (episodic, chronic stable, chronic progressive, and transient-persistent) that are robust under bootstrap resampling, leave-one-disease-out sensitivity analysis, and alternative clustering approaches. The biological clock is systematically modulated by sex, with Blood/Immune and Musculoskeletal disorders showing the largest sex differences in temporal dynamics. Network analysis identified 19 disease "initiators" that generate broad downstream comorbidity burdens and 21 "sinks" representing convergent endpoints of multiple disease trajectories. Comparison with hospital-based Danish data from 6,909,676 individuals showed that shared associations were 2.7-fold enriched over chance expectation (hypergeometric test, p

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23.
arXiv (CS.AI) 2026-06-24

DeepBD: A Grounded Agentic Workflow for Variant Prioritization and Diagnosis of Genetic Birth Defects

Authors:
Shiyu Li↗Ziqi Yan↗Zhihao Wu↗Jielong Lu↗Weiran Liao↗Jiajun Yu↗Genjie Li↗Zeyu Chu↗Jiajun Bu↗Haishuai Wang↗

arXiv:2606.24779v1 Announce Type: cross Abstract: Birth defects are a major cause of fetal loss, neonatal morbidity and long-term disability. In the subset with suspected genetic etiologies, exome and genome sequencing have moved many cases from variant detection to post-sequencing interpretation: clinicians must rank patient-specific candidate variants under incomplete fetal or infant phenotypes and heterogeneous evidence from population genetics, variant-effect prediction, gene-disease validity, phenotype ontologies, cellular and pathway context, protein structure and clinical literature. We present DeepBD, a grounded agentic workflow for variant prioritization and diagnostic interpretation of genetic birth defects. DeepBD organizes the workflow into LLM-assisted case structuring, a pretrained evidence engine, specialist evidence modules and a grounded diagnostic review layer. The evidence engine learns patient-specific variant scores from structured rule evidence, sequence and variant-effect representations and phenotype-conditioned biological context, whereas specialist modules and the agentic layer provide tool-based refinement, candidate-pool review and diagnosis-oriented synthesis from ranked candidates. Developed using an in-house fetal and infant cohort comprising 18,622 cases, DeepBD achieved Recall@1/3/5/10 of 0.658/0.882/0.912/0.929 on an internal held-out solved-case benchmark, outperforming standalone Exomiser, DeepRare and prompted LLM reranking baselines evaluated on Exomiser-derived top-20 candidate variants. Ablation and overlap analyses show that rule evidence, mechanistic context, and specialist refinement provide complementary signals. These findings support a grounded agentic workflow that separates evidence integration, tool-based refinement, and LLM-assisted diagnostic review for retrospective variant prioritization in genetic birth defects.

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

DOG-DPO:Dynamic Optimization in Geometry for Safety Alignment

Authors:
Yi Nian↗Tiankai Yang↗Yudi Zhang↗Qi Pan↗Zelong Xu↗Shenzhe Zhu↗Qingqing Luan↗Yue Huang↗Xiangliang Zhang↗Yue Zhao↗

arXiv:2606.07678v2 Announce Type: replace-cross Abstract: Safety alignment for large language models relies on preference data, but current pipelines often train on large, redundant datasets. Existing data selection methods typically score each preference pair independently, collapsing directional preference information into scalar quality or diversity scores. This sample-centric view is especially limiting in multi-dataset settings, where shared safety directions coexist with dataset-specific residual risks. We propose DOG-DPO, a training-free data selection framework that treats preference pairs as structured geometric signals. DOG-DPO first represents each preference pair as a direction in model representation space. It then decomposes multi-dataset preference geometry into a global anchor subspace and dataset-specific residual subspaces. Finally, it selects subsets by maximizing diversity-based coverage, encouraging broad, non-redundant coverage of alignment directions before DPO training. Across six safety benchmarks and two model backbones, DOG-DPO achieves a strong utility-robustness trade-off using only 11% of the preference pairs. It recovers most of the safety gains of full-data training while remaining entirely teacher-free, training-free, and substantially faster than representative selection baselines.

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25.
PLOS Computational Biology 2026-06-23

CARGO: A cytometry analysis framework via Regularized graph optimal-transport

Authors:
Abida Sanjana Shemonti↗

by Abida Sanjana Shemonti, Grzegorz B. Gmyrek, Katrien L. A. Quintelier, Sofie Van Gassen, Yvan Saeys, Marcella Willemsen, Joachim G. J. V. Aerts, Eva V. E. Madsen, J. Paul Robinson, Alex Pothen, Bartek Rajwa Conventional data visualization techniques in single-cell analysis (such as two-dimensional dot plots, SPADE, PCA, t-SNE, or UMAP) often fall short in enabling an intuitive understanding of high-parameter flow cytometry data. These methods tend to oversimplify complex biological relationships, lack biologically meaningful interpretations, and offer no principled framework for downstream quantitative analysis. To address these limitations, we present a graph-based (network-based) visualization framework grounded in optimal transport theory. In this framework, cell populations are defined by their marker-expression profiles, and inter-population similarity is quantified using an efficiently computable optimal transport formulation known as the Sinkhorn distance. Our approach produces biologically consistent two-dimensional graph layouts using a phenotype-aware Hamming distance. Structural differences between sample graphs are characterized through a customized graph-edit distance that captures changes in population size, marker expression, and relationships between populations. We demonstrate our methods on two flow cytometry datasets: one from a clinical trial of dendritic cell-based immunotherapy in malignant peritoneal mesothelioma, involving 14 patients sampled at three time points with 14-color panels, and another from FlowCAP-II, which involved 43 acute myeloid leukemia patient samples analyzed with 7-color panels. Our framework produces robust, quantitative visual summaries of cell populations and supports statistical analysis based on graph edit distances, thereby offering new insights into disease progression and treatment response. Ultimately, our method bridges the gap between flow cytometry data visualization and biological interpretation.

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