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01.
medRxiv (Medicine) 2026-06-12

Sociodemographic and health correlates of reimbursement authorizations for cannabis for medical purposes in Canadian veterans: A cross-sectional study linking the Life After Services Studies 2019 and Health Administrative Databases

Background Evidence on factors associated with cannabis for medical purposes (CMP) authorizations among Veterans Affairs Canada (VAC) clients remains limited and inconsistent, particularly concerning mental health and posttraumatic stress disorder (PTSD), a leading indication for use. We investigated demographic, clinical and service characteristics associated with VAC authorizations for CMP reimbursement. Method We linked VAC administrative CMP program data with responses from the 2019 Life After Services Studies cross-sectional survey of Regular Force veterans released between 1998 and 2018. Multivariable logistic regressions examined associations between CMP reimbursement (yes/no) and demographic, clinical and well-being factors, with analyses stratified by PTSD status. Results Among 1,289 respondents (weighted n=33,131), 18.4% were authorized for CMP reimbursement. Younger age (

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

Guiding Federated Graph Recommendation with LLM-encoded knowledge

arXiv:2606.15277v1 Announce Type: cross Abstract: Graph-based recommender systems are highly effective at extracting collaborative signals from user–item interactions, and federated learning (FL) allows these models to be trained while preserving user privacy. However, aggregating graph representations across distributed, non-IID clients remains a challenge; structural embeddings learned locally often misalign, and naive averaging fails to capture meaningful cross-client relationships. Most existing federated graph methods rely exclusively on structural aggregation, neglecting the rich, global semantic context available in large language models (LLMs). In this paper, we propose a novel framework that uses LLM-encoded knowledge to guide federated graph recommendation. Specifically, clients learn structural representations from local graphs while simultaneously summarizing their typical interaction patterns into compact semantic vectors via a frozen LLM. The central server then uses these LLM-encoded semantic signals to discover related preference patterns across clients, guiding the selective aggregation of their structural representations. This enables semantically informed cross-client collaboration without exposing raw data. Extensive experiments on standard benchmarks show that guiding structural alignment with LLM-encoded knowledge consistently improves recommendation accuracy over existing federated graph baselines.

03.
arXiv (CS.AI) 2026-06-17

Constitutional On-Policy Safe Distillation

arXiv:2606.03089v2 Announce Type: replace-cross Abstract: On-policy self-distillation (OPSD) has emerged as an efficient post-training paradigm by using a teacher conditioned on privileged information to provide dense token-level supervision. Prior work has shown that OPSD can collapse in verifiable reasoning tasks, but safety alignment differs in that it is guided by high-level constitutions rather than explicit target answers, making it a natural setting to revisit dense distillation. However, our pilot study show that safety OPSD still suffers from severe collapse: constitutional conditioning contracts the teacher distribution toward short and overly conservative responses, and Reverse KL further amplifies this contraction into reduced expressiveness. We formalize this effect as geometric leakage under safety boundaries in a non-orthogonal semantic space, where safety pressure transfers into the expressiveness dimension. Based on this analysis, we propose Constitutional On-Policy Safe Distillation (COPSD), which first calibrates the teacher through a Cross-SFT cold-start and then performs constitution-conditioned on-policy distillation. Experiments on 12 benchmarks show that COPSD achieves a consistently stronger safety–helpfulness trade-off than baselines while substantially reducing the safety tax on general reasoning ability.

04.
arXiv (math.PR) 2026-06-15

A random approach to the multibonacci sequence

arXiv:2606.14294v1 Announce Type: cross Abstract: This paper presents a random approach to the multibonacci sequence. We generalise the model introduced by Benjamin, Levin, Mahlburg, and Quinn, which is based on a random tiling method using dominoes and squares that leads to the Fibonacci sequence, and which was extended to the tribonacci case in a previous work by the authors. Our approach employs tiling with linear $k$-ominoes, $k=1,\ldots,s$, combined with specific colouring, to generate a weighted multibonacci sequence. For a natural random variable~$X$ defined by this model, we establish the distribution of $X$ in terms of multibonacci numbers and compute $\mathbb{E}[X] = 2^{s+1}-3$.

05.
arXiv (CS.CV) 2026-06-12

GAE: Unleashing Physical Potential of VLM with Generalizable Action Expert

Vision-language models demonstrate strong reasoning and planning abilities, yet grounding these predictions into precise robot actions remains a central challenge. Existing Vision-Language-Action methods typically entangle reasoning and action generation, leading to limited generalization. We propose Generalizable Action Expert (GAE), a task-agnostic model that converts sparse geometric plans into dense robot actions. Our approach introduces a sparse geometric interface: the VLM predicts sparse 3D waypoints representing high-level intention, while GAE maps these waypoints together with real-time point cloud observations to continuous action trajectories. GAE is pretrained on a large-scale pointcloud-trajectory dataset comprising 150k trajectories from both simulation and real-world robots. To further improve efficiency and generalization, we introduce an Action Pre-training, Pointcloud Fine-tuning (APPF) scheme that decouples learning action dynamics from geometry grounding. After pretraining, GAE is frozen and reused across downstream tasks, requiring only lightweight fine-tuning of the VLM to produce the sparse interface. Experiments show that our method achieves strong performance and generalization across diverse visual domains, camera viewpoints, and natural language instructions.

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

CogCanvas: A Benchmark for Evaluating Multi-Subject Reference-Based Image Generation

Multi-subject reference-based image generation requires jointly preserving multiple human identities, binding per-person objects and fashion items, and respecting a specified background scene, a regime where current diffusion models remain brittle. Existing benchmarks evaluate only one axis at a time and none jointly captures multi-identity composition with human-object interaction, background grounding, and spatial plausibility. We introduce CogCanvas, a benchmark of 1,952 curated reference images spanning 100 celebrity identities, 115 distinctive objects and fashion items, and 29 real-world background scenes including landmarks, from which we construct 1,361 compositional prompts covering 2-5 person group sizes. The curation pipeline combines DINOv2-based deduplication, two-stage aesthetic filtering, and automated derivation of structured interaction and position graphs that serve as ground-truth supervision. CogCanvas supports three tasks, reference-based multi-human-object generation (primary), text-to-image compositional generation, and reference retrieval, under a unified six-axis evaluation protocol. We introduce two metrics tailored to the multi-reference setting: BG-Sim, which scores background fidelity on SAM 3-masked regions via DINOv3 feature similarity, and Attr-VQA, which uses a multimodal LLM to verify per-subject attribute binding and inter-person interactions against the structured graphs. Benchmarking five SOTA methods reveals that every model degrades substantially as group size grows from 2 to 5, with near-complete failure on object/fashion binding beyond three subjects.

07.
arXiv (CS.LG) 2026-06-19

Stochastic Linear Contextual Bandits with Bounded Noise: A Set-Membership Approach

arXiv:2606.20022v1 Announce Type: cross Abstract: This paper considers stochastic linear contextual bandits (SLCB) with bounded reward noise. Existing works typically assume sub-Gaussian reward noise and bounded expected rewards, under which the optimal regret bound scales as $\tilde{O}(\sqrt{T})$ in terms of horizon $T$. However, in many applications, realized/observed rewards are also naturally bounded, implying bounded reward noise. Bounded noise is more informative than the sub-Gaussian condition but has not been leveraged explicitly in the SLCB literature. In this paper, we propose a novel algorithm SME-OFU by utilizing an uncertainty quantification method called set-membership estimation (SME) and applying the principle of optimism in the face of uncertainty (OFU). Our algorithm enjoys an improved regret bound $O(\log T)$. Notice that this does not contradict the existing optimal bound $\tilde{O}(\sqrt{T})$ for sub-Gaussian noise because bounded noise is a stronger condition. Finally, simulations show empirical improvements of SME-OFU over a benchmark algorithm designed for sub-Gaussian noise when the reward noise is bounded.

08.
arXiv (CS.AI) 2026-06-16

SCAN: A Decision-Making Framework for Effective Task Allocation with Generative AI

arXiv:2606.15601v1 Announce Type: cross Abstract: We introduce SCAN – a human-centric decision-making framework to facilitate learners for effective task allocation with Generative Artificial Intelligence (GenAI) based on Vygotsky's Zone of Proximal Development and Metacognition. In SCAN, we systematize and formalize AI-human interaction by introducing a task-identification approach with four "sub-zones": Substitute, Complement, Aid, and Non-negotiable. After describing the four sub-zones, we demonstrate how SCAN framework can be applied for knowledge workers in the workplace and students in education to metacognitively "scan" their use of Generative AI. We then discuss how such framework can be related to cognitive load theory, cognitive offloading, sycophancy, three decision-making modes in human-AI interactions (automation, augmentation, and collaboration), future of work such as upskilling and deskilling, and how it accounts for both human-human and human-AI learning. We propose that SCAN offers a great starting point before discussing whether GenAI complements or replaces our abilities when completing a task, with a general objective of sustaining lifelong learning, and a specific goal of reaching hybrid intelligence.

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

GEMS: Geometric Constraints Enable Multi-Semantic Superposition in LLMs

作者:

Activation steering controls model behavior by modifying intermediate hidden states at inference time without retraining. Existing methods handle only single-direction injection; when multiple semantic directions are superposed without constraints, the model collapses. We show that this collapse decomposes into two independently acting sources: distributional deviation, where additive perturbations accumulate in norm across layers and drive activations outside the training distribution, and directional interference, where non-orthogonal semantic vectors mutually dampen when superposed. These two sources define the design constraints that any training-free multi-directional intervention must address. As one instantiation of these principles, we propose GEMS, a training-free method that maps each source to a corresponding geometric constraint: norm-preserving weighted superposition and targeted attention-pathway injection for distributional deviation, and real-time orthogonalization for directional interference. On GSM8K, injecting three concurrent non-mathematical directions preserves accuracy at 98% (baseline 92%), while unconstrained addition collapses to 4%; on Wikitext-2, the same injection incurs only 2.2% PPL increase. Component ablation isolates the causal role of each constraint, and layer-level probes confirm that orthogonalized signals survive the FFN pathway and reach the output distribution with semantic specificity. Qualitative steering effects transfer across architectures from 3B to 31B.

10.
arXiv (CS.LG) 2026-06-15

An Attention-based Model for Robust Forecasting with Missing Modality

arXiv:2606.13970v1 Announce Type: cross Abstract: Learning with missing modalities is a fundamental challenge in multimodal robot learning, as real-world robotic systems often operate in environments with incomplete sensor data. Attention-based models are appealing for processing multimodal data because they can handle multiple modalities with a single backbone network. However, most multimodal models assume that all modalities are available during both training and inference, limiting their applicability in robotic perception and decision-making. In this paper, we introduce a multimodal model designed to handle missing modalities during both training and inference. The model is formulated as a conditional variational autoencoder (CVAE) and incorporates a transformer-based architecture that leverages attention mechanisms to learn a unified, fixed-dimensional representation, even when some modalities are missing. We show that our proposed model can be trained with missing modalities while approximating a robust representation of all modalities. We evaluate our approach on five multimodal datasets across two robot learning tasks: human trajectory prediction and robot manipulation forecasting. Experimental results demonstrate that our model effectively learns from incomplete data and is superior to prior multimodal fusion approaches.

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

Faster Completion, Less Learning: Generative AI Reduced Study Time on Math Problems and the Knowledge They Build

arXiv:2605.21629v2 Announce Type: replace-cross Abstract: How much have students' ordinary learning processes shifted in response to generative AI, and how does that affect their durable learning outcomes? Self-report surveys show little change, while small-scale behavioral studies report widespread AI use without the scale or duration to measure learning consequences. We address both questions using a ten-year panel of $3.2$ million ALEKS learning interactions for investigating time-on-task, complemented by ALEKS PPL placement-assessment data for examining proctoring and learning outcomes, with a quasi-experimental design exploiting variation in tasks that are more susceptible to AI (text-based word problems) and less susceptible to AI (interactive graph-based problems). Learning time on AI-susceptible problems declines $2.8\%$ per quarter among college students after ChatGPT's release, cumulating to $26.9\%$ over eleven quarters; high-schoolers show $31.3\%$, middle-schoolers $9.0\%$, and Grade 5 students no detectable change. Among college students, the post-ChatGPT divergence vanishes entirely under proctoring, ruling out broad efficiency gains as the likely explanation. Logistic fixed-effects models on randomly assigned proctored retention items yield a $25\%$ cumulative decline in odds of correct response; the same estimator on non-proctored assessment produces a large opposite-signed increase – inconsistent with any platform, cohort, or curriculum explanation. These results are among the first large-scale behavioral and outcome evidence that generative AI has altered how students study and the knowledge they build – the population-level indicator of cognitive surrender, with direct implications for educational research, assessment governance, and AI policy.

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

Evaluating Pluralism in LLMs through Latent Perspectives

The growing need to represent diverse perspectives has increased interest in pluralistic LLM generation. Although difficult to operationalize, identifying perspectives expressed in text would provide clear guidance on pluralistic alignment and more clearly articulate the pluralistic gap in LLM generation. While models have been shown to reduce the diversity of training data and generate homogeneously, this has been demonstrated primarily on multiple-choice questionnaires or using high-level characteristics of free-form text. In this paper, we introduce and implement a domain-agnostic multi-layered framework for unsupervised extraction of perspectives suitable for identifying the pluralistic gap in LLM-generated text. We evaluate our framework on book reviews, a highly opinionated dataset representing diverse perspectives, and compare various prompts and models. Our results show that while some models and prompting techniques come close to covering a broad spectrum of perspectives, rarer perspectives remain disproportionately underrepresented, resulting in distributions that diverge from human text.

13.
arXiv (CS.CL) 2026-06-19

PASQA: Pitch-Accent-Focused Speech Quality Assessment Model Trained on Synthetic Speech with Accent Errors

Existing mean opinion score (MOS) prediction models typically predict utterance-level naturalness MOS and can be insensitive to localized pitch-accent errors. We propose Pitch-Accent-focused Speech Quality Assessment (PASQA), which explicitly targets pitch-accent correctness. To train our model, we construct a controlled Japanese accent-error dataset by changing accent patterns using an accent-controllable text-to-speech system, and compute a pseudo accent-quality score from the accent-error rate. PASQA builds on self-supervised representations and employs mora-conditioned fusion, ranking loss, an auxiliary accent-error localization task, and speaker-invariant training. Experiments show that conventional models fail to preserve the ordering by accent-error severity, whereas PASQA achieves high ordering accuracy on both seen and unseen speakers. Further, PASQA shows stronger agreement with human accent-correctness judgments. The code is available at https://github.com/lycorp-jp/PASQA.

14.
bioRxiv (Bioinfo) 2026-06-11

Sequence-Based Therapeutic Peptide Classification with Augmented Negative Sampling

Therapeutic peptides offer high target specificity, low toxicity, and the ability to modulate protein-protein interactions, yet experimental functional characterization remains costly and slow. Computational prediction of therapeutic function directly from sequence could accelerate peptide screening and enable generative design pipelines, but requires reliable discrimination between therapeutic and non-therapeutic peptides. Existing multi-label predictors cover few functions, rely on limited datasets, and exhibit high glspl{fpr}, limiting their practical utility. We present a lightweight CNN classifier trained on the most comprehensive therapeutic peptide database to date (54,655 peptides, 48 functional categories). A key contribution is a statistically motivated negative sampling strategy using Markov models to generate diverse synthetic decoys at multiple difficulty levels. When evaluated on this controlled decoy benchmark, the FRP is reduced from over 60% for previous models to 2.1% for our approach. Our fine-tuned five-model ensemble achieves 78.9% Micro F1 and 54.6% Macro F1 while requiring only amino acid sequences as inputs. Analysis using a sparse L1-constrained variant of our model shows that convolutional filters capture conserved functional motifs and statistically improbable non-therapeutic patterns, with downstream layers combining these signals, providing mechanistic evidence that the network learns biologically meaningful structure. In a generalization task on the TPpred-LE benchmark, our model achieves 55.3% Micro F1 and 38.6% Macro F1, comparable to TPpred-LE trained on its native dataset (57.9%/38.1%) while predicting four times more therapeutic functions with four times fewer parameters. Code and models will be made available at https://github.com/terra-quantum-public/tq-therapep-ai.

15.
arXiv (CS.LG) 2026-06-19

MassSpecGym in the Wild: Uncovering and Correcting Evaluation Pitfalls in AI-Driven Molecule Discovery

arXiv:2606.19624v1 Announce Type: new Abstract: Reliable benchmarking is critical for developing machine learning models for tandem mass spectrometry (MS/MS) based molecule discovery. Subtle issues in experimental design and model evaluation procedures can degrade the trustworthiness of such benchmarks and lead to erroneous conclusions. We conduct a thorough review of model evaluation issues in the recent MS/MS machine learning literature, using the standard MassSpecGym benchmark suite as a case study to illustrate the impact of these issues. We find evaluation issues in at least 17 of 26 papers reporting MassSpecGym benchmark results in the first year of its adoption. We isolate three classes of failures: (i) data leakage, (ii) shortcut learning, and (iii) implementation bugs and metric divergence. Through extensive experimentation and code replication, we quantify the impact of these issues and show how they corrupt the evaluation standards MassSpecGym was designed to enforce. We distill our findings into recommendations generalizable to MS/MS challenges, benchmarks, and custom evaluation setups. We also release MassSpecGym v1.5, an implementation of our recommendations in the MassSpecGym benchmarking suite which addresses the failure modes identified in this audit. MassSpecGym v1.5 is publicly available at https://github.com/pluskal-lab/MassSpecGym.

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

Graph2Idea:Retrieval-Augmented Scientific Idea Generation with Graph-Structured Contexts

arXiv:2606.09105v3 Announce Type: replace Abstract: Generating novel, feasible, and high-quality research ideas is an important yet challenging task in scientific discovery. Recent Large Language Model (LLM)-based methods often ground idea generation with retrieved literature, but the retrieved evidence is usually provided as flat text, such as titles, abstracts, or summaries. Such flat contexts may contain redundant or weakly relevant information, while making cross-paper relations among problems, methods, mechanisms, and findings difficult to identify and trace. To address this challenge, we propose Graph2Idea, a knowledge graph-guided framework for retrieval-augmented scientific idea generation.Graph2Idea first retrieves papers according to the input topic, transforms them into structured knowledge triples, and dynamically constructs a target-centered knowledge graph to make literature relations explicit. It then extracts compact graph-derived contexts that retain target-relevant relational evidence while reducing noisy textual input. Based on these contexts, a two-stage generation process first identifies promising research directions and then guides the LLM to synthesize candidate ideas from graph-grounded evidence. Experiments on a scientific idea generation benchmark show that Graph2Idea outperforms representative baselines under the automatic evaluation protocol. Compared with the strongest baseline scores, it improves Novelty from 0.45 to 0.52, Quality from 0.24 to 0.29, and Feasibility from 0.22 to 0.28. These results suggest that graph-structured evidence helps LLMs generate research ideas through more explicit, compact, and traceable recombination of prior scientific knowledge.

17.
arXiv (CS.LG) 2026-06-19

Beyond Averaging in John Ellipsoid Approximation: High-Accuracy Algorithms in the Leverage-Score Model

arXiv:2606.20082v1 Announce Type: cross Abstract: The John ellipsoid of a symmetric polytope $P=\{\mathbf{x}\in\mathbb{R}^d:\|\mathbf{A}\mathbf{x}\|_\infty\le1\}$, $\mathbf{A}\in\mathbb{R}^{n\times d}$, is computed by a long line of leverage-score algorithms, from Cohen, Cousins, Lee and Yang (COLT 2019) to its successors [WY24, CLS+25], all reaching a $(1+\varepsilon)$-approximation in $\Theta(\varepsilon^{-1}\log(n/d))$ iterations. We separate this complexity into three costs the modern line conflates (certification, identification, and accuracy) and locate the historical $\varepsilon^{-1}$ in the first alone. In the equivalent D-optimal-design form $\min_{\mathbf{p}\in\Delta_n}-\log\det(\sum_i p_i\mathbf{a}_i\mathbf{a}_i^\top)$, the leverage-score oracle is exactly the first-order oracle and the $(1+\varepsilon)$-John guarantee the Frank-Wolfe gap $g(\mathbf{p})\le\varepsilon d$; through this dictionary the costs come apart. The $\varepsilon^{-1}$ is a certification artifact: the uniform average of the iterates, the certificate used throughout the line, has gap exactly $\Theta(1/T)$, however cheap each iteration is made. Pointed instead at the last iterate the same oracle is fast: a warm-started accelerated method reaches the guarantee in $C(\mathbf{A})+O(\sqrt{\kappa}\log(1/\varepsilon))$ queries after an $\varepsilon$-independent setup $C(\mathbf{A})$, and once the optimal face is identified the facial problem is an unconstrained self-concordant minimization whose Hessian the oracle recovers exactly, so damped Newton needs only $O(\log\log(1/\varepsilon))$ steps, for a total of $C(\mathbf{A})+O(d^2\log\log(1/\varepsilon))$ queries. The accuracy dependence is thus doubly logarithmic after an $\varepsilon$-independent, condition-dependent setup; the open problem is the remaining identification cost (a condition-free bound on reaching the optimal face) and lower bounds. Accuracy is not the obstruction.

18.
arXiv (CS.CL) 2026-06-17

findsylls: A Language-Agnostic Toolkit for Syllable-Level Speech Tokenization and Embedding

Syllable-level units offer compact and linguistically meaningful representations for spoken language modeling and unsupervised word discovery, but research on syllabification remains fragmented across disparate implementations, datasets, and evaluation protocols. We introduce findsylls, a modular, language-agnostic toolkit that unifies classical syllable detectors and end-to-end syllabifiers under a common interface for syllable segmentation, embedding extraction, and multi-granular evaluation. The toolkit implements and standardizes widely used methods (e.g., Sylber, VG-HuBERT) and allows their components to be recombined, enabling controlled comparisons of representations, algorithms, and token rates. We demonstrate findsylls on English and Spanish corpora and on new hand-annotated data from Kono, an underdocumented Central Mande language, illustrating how a single framework can support reproducible syllable-level experiments across both high-resource and under-resourced settings.

19.
arXiv (CS.AI) 2026-06-17

Membership Inference Attacks against Large Audio Language Models

arXiv:2603.28378v2 Announce Type: replace-cross Abstract: We present the first systematic Membership Inference Attack (MIA) evaluation of LALMs. Using Multi-modal Blind Baselines based on textual, spectral and prosodic features, we demonstrate that common audio datasets exhibit near-perfect train/test separability (AUC ~ 1.0) even without model inference, thus MIA may primarily detect distribution shift. We therefore introduce a blind-baseline protocol to control for this confound. Under this protocol, we identify that the distribution-matched datasets enable reliable MIA evaluation without distribution-shift artifacts. We benchmark multiple MIA methods and conduct modality disentanglement experiments on these datasets. The results reveal that LALM memorization is cross-modal, arising only from binding a speaker's vocal identity with its text. These findings establish a principled standard for auditing LALMs beyond spurious correlations. Our codebase is available at https://github.com/snooow1029/ALM_MIA.

20.
arXiv (CS.CV) 2026-06-15

MCR-VQGAN: A Scalable and Cost-Effective Tau PET Synthesis Approach for Alzheimer's Disease Imaging

Tau positron emission tomography (PET) is a critical diagnostic modality for Alzheimer's disease (AD), but its widespread clinical adoption is hindered by radiation exposure, limited availability, high clinical workload, and substantial financial costs. To address these limitations, we propose the Multi-scale CBAM Residual Vector Quantized Generative Adversarial Network (MCR-VQGAN) to synthesize high-fidelity tau PET images from structural T1-weighted MRI. MCR-VQGAN advances the standard VQGAN architecture through three enhancements: multi-scale convolutions, ResNet blocks, and Convolutional Block Attention Modules (CBAM), which collectively improve the capture of local and global features. Using 222 paired T1-weighted MRI and tau PET scans from the ADNI database, we trained and compared MCR-VQGAN against cGAN, WGAN-GP, CycleGAN, and baseline VQGAN. MCR-VQGAN achieved superior image synthesis performance across all metrics (MSE = 0.0056 +/- 0.0061, PSNR = 30.65 +/- 4.47 dB, SSIM = 0.9263 +/- 0.0469). A CNN-based AD classifier trained on real tau PET achieved comparable accuracy on real (63.64%) and synthetic (65.91%) images, indicating that diagnostically relevant features are preserved. Regional SUVR-equivalent analysis across Braak-defined ROIs further indicated strong agreement between real and synthetic tau PET (Pearson r = 0.78-0.88; ICC = 0.71-0.84), with the strongest agreement in Braak V/VI (ICC = 0.838). Together, these results suggest that MCR-VQGAN offers a promising and scalable surrogate for conventional tau PET imaging, potentially improving the accessibility of tau biomarkers for AD research and clinical workflows.

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

The ASE-LSE Disagreement Landscape: An End-to-End Characterisation of Extremes and Structural Drivers

arXiv:2605.22346v3 Announce Type: replace-cross Abstract: Two of the most widely used methods for analysing graph data, Adjacency Spectral Embedding and Laplacian Spectral Embedding, often produce different results when applied to the same graph. Yet the structural reasons behind this disagreement remain incompletely understood. This paper provides an end-to-end account of ASE-LSE latent subspace disagreement. We first prove that the two methods produce identical latent subspaces for every embedding dimension whenever the Laplacian is a scalar multiple of the adjacency matrix, and show that this scalar relationship holds if and only if the graph is either regular or bipartite biregular. This anchor result identifies a sufficient condition for perfect agreement that pins down the floor of the disagreement spectrum and supplies the baseline for the perturbation analysis. We then prove that no maximal-disagreement graph or family of graphs exists: the disagreement is always strictly below its theoretical ceiling, and we exhibit a witness family demonstrating that no finite maximum is attainable, so the disagreement landscape has no maximiser. With both endpoints established, we derive a Regularity Departure Bound whose two terms isolate degree heterogeneity and eigengap as the primary structural factors influencing disagreement in the middle regime. Empirical validation across thousands of simulated graphs confirms the mechanisms predicted by the bound: heterogeneity pushes disagreement up, eigengap suppresses it, and their joint ratio emerges as a unified predictor of ASE-LSE disagreement, suggesting when the two embeddings can be treated as interchangeable and when they cannot.

22.
Nature (Science) 2026-06-10

A first-in-class pulsatile FXR agonist for bile-acid-related liver diseases

作者:

Nuclear receptors are central regulators of metabolism1, yet therapeutic strategies that enforce continuous receptor activation frequently lead to reduced efficacy and unacceptable toxicity. Here we report a first-principles drug design strategy that aligns pharmacokinetics with physiological signalling cycles. We developed linafexor, a potent non-bile-acid agonist of the farnesoid X receptor (FXR)2; it is engineered for rapid systemic clearance, which enables pulsatile receptor activation that mirrors endogenous bile acid dynamics3–5. Linafexor has robust efficacy across multiple preclinical models of metabolic dysfunction-associated steatohepatitis6, liver fibrosis7, primary biliary cholangitis and primary sclerosing cholangitis8,9. Transcriptomic analyses reveal that, unlike long-acting FXR agonists10,11, linafexor preserves cyclic FXR signalling, avoids receptor downregulation and prevents broad transcriptional dysregulation. Direct manipulation of delivery patterns demonstrates that sustained FXR activation—independent of compound identity—induces severe toxicity, establishing activation duration as a determinant of therapeutic index. In phase 1 clinical studies (ClinicalTrials.gov; NCT05082779), linafexor administered once daily produces transient FXR pathway engagement, marked by (1) induction of FGF1912–14, a key endocrine mediator of bile acid feedback regulation; and (2) suppression of C415, an intermediate reflecting hepatic bile acid synthesis, with no treatment-related adverse events. Together, these findings identify pulsatile FXR activation as a mechanistically grounded and clinically translatable strategy, and establish linafexor as a first-in-class therapeutic for bile acid–related liver diseases. Linafexor is a rapidly cleared FXR agonist designed to mimic natural bile acid signalling, achieving transient receptor activation with strong efficacy and reduced toxicity in preclinical and early clinical studies.

23.
arXiv (CS.CV) 2026-06-15

Temporal Backtracking Search for Test-time Generative Video Reasoning

While test-time scaling has revolutionized reasoning in large language models, generative video reasoning remains bottlenecked by a single-shot paradigm. We demonstrate that searching over denoising steps cannot rescue logically flawed rollouts because spatial trajectories commit early in the diffusion process. Root-level Best-of-N (BoN) sampling is similarly inefficient: reasoning errors cluster early in the temporal axis, and resampling blindly discards verified upstream progress. To unlock effective test-time scaling for video models, we introduce Temporal Backtracking Search (TBS), which shifts the search space to the temporal axis. TBS transforms video generation into an iterative generate-verify-restart loop via three core mechanisms: (1) variable-K conditioning to resume generation from arbitrary clean prefixes; (2) temporal process verification to localize failures and extract valid restart anchors; and (3) prefix-based search to reallocate compute toward extending correct trajectories rather than root resampling. Across algorithmic, navigation, and robotics domains, TBS Pareto-dominates matched-budget BoN. In a strict out-of-distribution setting where one-shot generation collapses (0.7% for BoN), TBS achieves 22.7%, with every solved episode stemming from a restarted branch. Ultimately, TBS reveals that the local reasoning competence of video models far exceeds what single-shot rollouts indicate, providing a scalable test-time framework to unlock it.

24.
bioRxiv (Bioinfo) 2026-06-15

SMLMFlow: Improving Structural Resolution in Single Molecule Localization Microscopy with Flow Matching

While Single Molecule Localization Microscopy (SMLM) aims to generate precise coordinates of molecular targets in cells, the resulting point clouds are inherently blurred by additive noise sources across the experimental, imaging, and processing workflow. This blurring often limits SMLM's ability to accurately quantify complex assembled structures required to address biological issues, despite reported localization precision down to a couple of nanometers. Here, we present SMLMFlow, a machine learning framework for improving structural resolution in SMLM datasets that combines a graph neural network and a hierarchical transformer with flow matching. We show that SMLMFlow improves structural resolution and downstream quantification across different structures, including filaments and protein nano-clusters, and generalizes to new unseen photophysics models.

25.
arXiv (quant-ph) 2026-06-16

Excited-State Quantum Chemistry on Qumode-Based Processors via Variational Quantum Deflation

arXiv:2604.13457v3 Announce Type: replace Abstract: Variational quantum algorithms on bosonic quantum processors are an emerging paradigm for quantum chemistry calculations, exploiting the natural alignment between molecular structure and harmonic oscillator-based hardware. We introduce the qumode-based variational quantum deflation framework (QumVQD) for finding both electronic and vibrational excited state energies on qumode-based architectures. We validate the approach through electronic structure calculations on H$_{2}$ and linear H$_{4}$, where we introduce Hamming-weight filtering of the Fock basis to enforce particle number conservation and eliminate spurious eigenstates by reducing the required Hilbert space, which reduces the required number of qumodes in turn. We achieve agreement with full configuration interaction (FCI) using the STO-3G basis set within the chemical accuracy threshold at most points along the potential energy surfaces. Extending to the vibrational structure, we combine QumVQD with an existing Hamiltonian fragmentation approach based on Cartan subalgebra, allowing us to compute the vibrational eigenenergies of CO$_{2}$ and H$_{2}$S to spectroscopic accuracy with per-fragment circuits that scale as $O(N)$ in single-qumode gates and $O(N^2)$ in beam-splitter gates for $N$ qumodes. For the case of CO$_{2}$, we get total gate counts more than an order of magnitude smaller than those reported for qubit-based vibrational algorithms at this system size. These results demonstrate that bosonic quantum devices are a viable platform for excited-state quantum chemistry, particularly for vibrational problems where qubit-based methods incur substantial boson-to-qubit mapping overhead.