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

TopoHR: Hierarchical Centerline Representation for Cyclic Topology Reasoning in Driving Scenes with Point-to-Instance Relations

Topology reasoning is crucial for autonomous driving. Current methods primarily focus on instance-level learning for centerline detection, followed by a sequential module for topology reasoning that relies on simplified MLP layers. Moreover, they often neglect the importance of point-to-instance (P2I) relationships in topology reasoning. To address these limitations, we present TopoHR (Topological Hierarchical Representation), a novel end-to-end framework that establishes cyclic interaction between centerline detection and topology reasoning, allowing them to iteratively enhance each other. Specifically, we introduce a hierarchical centerline representation including point queries, instance queries, and semantic representations. These multi-level features are seamlessly integrated and fused within a hierarchical centerline decoder. Furthermore, we design a hierarchical topology reasoning module that captures both fine-grained P2I relationships and global instance-to-instance (I2I) connections within a unified architecture. With these novel components, TopoHR ensures accurate and robust topology reasoning. On the OpenLane-V2 benchmark, TopoHR refreshes state-of-the-art performance with significant improvements. Notably, compared with previous best results, TopoHR achieves +3.8 in $\mathrm{DET}_{l}$, +5.4 in $\mathrm{TOP}_{ll}$ on $subset_A$ and +11.0 in $\mathrm{DET}_{l}$, +7.9 in $\mathrm{TOP}_{ll}$ on $subset_B$, validating the effectiveness of the proposed components. The code will be shared publicly at https://github.com/Yifeng-Bai/TopoHR.git.

02.
medRxiv (Medicine) 2026-06-22

Level of Physical Activity and ApoE Status - Effects on Alzheimer's Disease and on Mortality

Background: Alzheimer's disease and related dementias (ADRD) affect over 7.2 million Americans aged 65 and older, with the APOE-4 allele representing the strongest known genetic risk factor. Physical activity (PA) has been associated with reduced dementia risk, but its interaction with APOE genotype remains poorly characterized in large, genomically informed cohorts. Methods: We conducted a retrospective cohort analysis using linked genomic, survey, and longitudinal electronic health record data from the VA Million Veteran Program (MVP). Veterans aged

03.
arXiv (CS.CL) 2026-06-16

Uncertainty Is Not a Safety Net for Clinical VQA, but Can It Anticipate Model Failure?

Safe deployment of clinical vision-language models (VLMs) requires reliable uncertainty estimation (UE): a signal indicating when predictions should be trusted or escalated to a clinician. We test whether current UE methods actually deliver this signal. Benchmarking 8 methods across 12 VLMs on clinical visual question-answering (VQA), we find that UE quality is not an intrinsic property of the UE method: it tracks model accuracy, degrading precisely where the model performance is weakest, and therefore where reliability is most needed. When we stress-test models by hiding the correct option among the multiple-choice answers (NOTA perturbations), accuracy collapses while uncertainty barely changes, leaving models systematically miscalibrated. Yet, we find that uncertainty on the unperturbed input reliably anticipates which predictions will collapse under NOTA, indicating that UE in current VLMs carries diagnostic information about model fragility. Our results position UE as a diagnostic tool for identifying fragile predictions and motivate perturbation-based evaluation as a path toward safe clinical deployment.

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

Hidden Ghost Hand: Unveiling Backdoor Vulnerabilities in MLLM-Powered Mobile GUI Agents

Graphical user interface (GUI) agents powered by multimodal large language models (MLLMs) have shown greater promise for human-interaction. However, due to the high fine-tuning cost, users often rely on open-source GUI agents or APIs offered by AI providers, which introduces a critical but underexplored supply chain threat: backdoor attacks. In this work, we first unveil that MLLM-powered GUI agents naturally expose multiple interaction-level triggers, such as historical steps, environment states, and task progress. Based on this observation, we introduce AgentGhost, an effective and stealthy framework for red-teaming backdoor attacks. Specifically, we first construct composite triggers by combining goal and interaction levels, allowing GUI agents to unintentionally activate backdoors while ensuring task utility. Then, we formulate backdoor injection as a Min-Max optimization problem that uses supervised contrastive learning to maximize the feature difference across sample classes at the representation space, improving flexibility of the backdoor. Meanwhile, it adopts supervised fine-tuning to minimize the discrepancy between backdoor and clean behavior generation, enhancing effectiveness and utility. Extensive evaluations of various agent models in two established mobile benchmarks show that AgentGhost is effective and generic, with attack accuracy that reaches 99.7\% on three attack objectives, and shows stealthiness with only 1\% utility degradation. Furthermore, we tailor a defense method against AgentGhost that reduces the attack accuracy to 22.1\%. Our code is available at \texttt{anonymous}.

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

Muse Spark Safety & Preparedness Report

arXiv:2606.12429v1 Announce Type: cross Abstract: Muse Spark is the latest large language model developed by Meta. In this report, we first present evaluations for catastrophic risk domains under Meta's Advanced AI Scaling Framework, along with the evidence that informed our launch decision. We then discuss additional considerations, such as Muse Spark's broader content safety and behavioral profile, that are relevant to overall safety but fall outside the catastrophic risk domains governed by the Framework. Our preparedness results covering Chemical and Biological, Cybersecurity, and Loss of Control risks assess Muse Spark's deployment within Meta AI as presenting acceptable levels of residual risks under our Advanced AI Scaling Framework. We conducted a broad set of evaluations targeting dual-use and high-risk capabilities across these catastrophic risk domains. Those evaluations identified elevated risks prior to mitigations, with Chemical and Biological capabilities assessed as likely reaching the "high risk" category under the Advanced AI Scaling Framework before safeguards were applied. We have implemented a multi-layered set of mitigations that address the identified risks, and Muse Spark demonstrates state-of-the-art refusal across a range of benchmarks related to hazardous workflows in chemistry and biology. We therefore release Muse Spark as the underlying model of Meta AI.

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

Ling and Ring 2.6 Technical Report: Efficient and Instant Agentic Intelligence at Trillion-Parameter Scale

Efficient and scalable agentic intelligence requires models that can deliver both low-latency responses and strong reasoning capabilities while remaining practical to train, serve, and deploy. In this report, we present Ling-2.6 and Ring-2.6, a family of models designed to address this challenge at scale. Ling-2.6 is optimized for instant response generation and high capability per output token, whereas Ring-2.6 is tailored for deeper reasoning and more advanced agentic workflows. Instead of training from scratch, we upgrade the Ling-2.0 base model through architectural migration pre-training and large-scale post-training. This upgrade is guided by a unified co-design of model architecture, optimization objectives, serving systems, and agent training environments, enabling improvements in both model capability and deployment efficiency. At the architectural level, we introduce a hybrid linear attention design that integrates Lightning Attention with MLA, improving the efficiency of long-context training and decoding. To further enhance token efficiency, we optimize capability per output token through Evolutionary Chain-of-Thought, Linguistic Unit Policy Optimization, bidirectional preference alignment, and shortest-correct-response distillation. For agentic capabilities, we propose KPop, a reinforcement learning framework designed to support stable training of Ring-2.6-1T on large-scale environment-grounded data. KPop improves training efficiency through asynchronous scheduling across coding, search, tool use, and workflow execution, enabling scalable learning from complex agent-environment interactions. Together, Ling-2.6 and Ring-2.6 provide a practical pathway toward efficient, scalable, and open agentic systems. We open-source all checkpoints in the 2.6 family to support further research and development in practical agentic intelligence.

07.
arXiv (CS.CL) 2026-06-17

PACE-RAG: Patient-Aware Contextual and Evidence-Constrained RAG for Clinical Drug Recommendation

Drug recommendation requires a deep understanding of individual patient context, especially for complex conditions like Parkinson's disease. While LLMs possess broad medical knowledge, they fail to capture the subtle nuances of actual prescribing patterns. Existing RAG methods also struggle with these complexities because guideline-based retrieval remains too generic and similar-patient retrieval often replicates majority patterns without accounting for the unique clinical nuances of individual patients. To bridge this gap, we propose PACE-RAG (Patient-Aware Contextual and Evidence-Constrained RAG). Rather than directly copying frequent medications from retrieved patients, PACE-RAG personalizes recommendations by first extracting patient-specific clinical features, retrieving cases around these features, and then refining the final prescription using the patient's current symptoms, active medication history, and focus-specific prescribing tendencies. By analyzing treatment patterns tailored to specific clinical features, PACE-RAG generates patient-specific medication recommendations along with an explainable clinical summary. Evaluated on a Parkinson's cohort and the MIMIC-IV benchmark using Llama-3.1-8B and Qwen3-8B, PACE-RAG achieved state-of-the-art performance, reaching F1 scores of 80.84% and 47.22%, respectively. These results suggest that PACE-RAG is a robust and clinically grounded framework for personalized decision support. Our code is available at: https://github.com/ChaeYoungHuh/PACE-RAG.

08.
medRxiv (Medicine) 2026-06-11

Parent and physiotherapist perceptions about movement skills of young children with juvenile idiopathic arthritis

Objective: The onset of juvenile idiopathic arthritis (JIA) in the early years ([≤]5 years) may negatively impact movement skill (encompassing related concepts of gross motor skills, fundamental movement skills, and functional ability) development. Few studies have explored the perceptions and needs of parents and physiotherapists towards children's difficulty with these movement skills, essential to identify potential areas for added support. The objective of this study is to understand the perceptions of physiotherapists and parents towards movement skills of children with JIA. Methods: Seventeen parents and 24 physiotherapists completed an online questionnaire consisting of multiple choice and open-ended questions about the movement skills of young children with JIA. Demographic and multiple choice questions were quantitively analysed using descriptive statistics. Open-ended responses were analyzed using qualitative conventional content analysis. Results: About half (47%) of parents perceived their children to have movement difficulties, and 75% of physiotherapists described the movement skills of children with JIA as worse than other children of the same age. Our qualitative analysis revealed three general themes including: functional task difficulties; clinical variability in movement skills; and psychosocial components of movement skill difficulties. Conclusion: This study provides an analysis of perceptions of physiotherapists and parents towards the movement skills of young children with JIA. A significant proportion of parents and physiotherapists identify movement difficulties among children with JIA that impact daily life. Future interventions co-designed with both parents and care providers targeting movement skills are needed.

09.
medRxiv (Medicine) 2026-06-22

Characteristics and Outcomes of Gene-Elusive Dilated Cardiomyopathy

Background and Aims Genetic testing in dilated cardiomyopathy (DCM) guides risk stratification and family screening. Likely pathogenic or pathogenic (LP/P) variants are identified in approximately one-third of patients, leaving many without a genetic diagnosis. Cohort studies suggest that "gene-elusive" patients have a lower risk of adverse events. This study aims to better characterise this group and identify factors associated with adverse outcomes. Methods Consecutive and unrelated DCM patients undergoing genetic testing and returning no LP/P variants were retrospectively recruited and compared to two control cohorts of DCM patients carrying LP/P variants in LMNA and TTN for a primary composite endpoint of end-stage heart failure (ESHF) or malignant ventricular arrhythmia (MVA). Results Among patients without prior MVA, the composite endpoint occurred in 36/423 (8.5%) gene-elusive, 14/39 (35.9%) LMNA and 11/100 (11%) TTN cardiomyopathy patients (log-rank p

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

Chroma-gated, differentiable OKLCH interpolation: Continuous Oklab fallback for color-cast reduction

OKLCH – the cylindrical (lightness, chroma, hue) form of Ottosson's Oklab color space – is the interpolation space recommended by CSS Color 4 for gradients and color-mix(), and it is now broadly deployed. Its polar parameterization, however, casts color near the neutral axis in two ways: (1) an inter-hue detour between two chromatic endpoints that sweeps through an unintended hue (blue to yellow visibly passing through green), and (2) an off-line bow when one endpoint is achromatic. Existing remedies are uniformly two-valued – a threshold switch that fires only at an achromatic endpoint – so they address only (2); on chromatic pairs every one of them reduces to raw OKLCH, leaving the (1) inter-hue cast untreated. We introduce Continuous Oklab fallback (COFb), a one-parameter, differentiable chroma gate $w(C)=C^n/(C^n+\sigma^n)$ that continuously blends the OKLCH path toward the linear Oklab path as chroma falls. A single gate reduces the (1) cast that the two-valued family leaves untreated and unifies the handling of (1) and (2) without any endpoint test. We characterize a cast-hue trade-off frontier, adopt a default ($n=1$, the rational Michaelis-Menten form; $\sigma\approx0.19$ for a typical sRGB palette, from a normalization-independent cast-half criterion), and verify the gate's properties symbolically. At the default, COFb halves the inter-hue path detour (mean lateral deviation -49.5%, chroma-weighted hue excursion -35.5%). We also state the method's limits: on (2) alone the two-valued switch remains better, and like any Cartesian blend COFb does not preserve chroma. In deployment, COFb runs entirely in plain Oklab (a,b) to sRGB, so it serves as a fallback that delivers the same cast-reduced gradients where modern CSS color interpolation (color-mix(in oklch) and the like) is unavailable – older engines, image and video pipelines, or GPU shaders.

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

A Lightweight Multi-Agent Framework for Automated Concrete Barrier Design

arXiv:2606.12040v1 Announce Type: new Abstract: The design of reinforced concrete highway barriers is a safety-critical process that requires strict compliance with regulatory provisions such as the AASHTO-LRFD bridge design guidelines. Current engineering practice relies heavily on manual, iterative, and heuristic calculations to satisfy complex nonlinear material and mechanics constraints. Although Large Language Models (LLMs) demonstrate strong generative capabilities, their direct application to structural engineering remains limited by hallucination risks and insufficient physical grounding. To address these challenges, this study proposes a novel "generation-evaluation-optimization" closed-loop framework for automated concrete barrier design using the multi-agent orchestration capabilities of AutoGen. Experimental results demonstrate that the proposed agentic framework achieves over 98% design accuracy, significantly outperforming standalone general-purpose LLMs. More importantly, the study reveals that design performance is not necessarily correlated with model scale, where an 8B-parameter lightweight model could outperform unconstrained 631B-parameter flagship models. This finding highlights the potential to substantially reduce computational costs while improving the accessibility of AI-assisted engineering tools for industry applications. The source code for the proposed multi-agent design framework is available at the project GitHub repository: https://github.com/MXY820/barrier-design. Keywords: Structural Engineering; Multi-Agent Systems; Large Language Models; Concrete Barrier Design; AutoGen; Design Automation.

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

Loss-Shift Transfer via Bayes Quotients

arXiv:2606.13178v1 Announce Type: new Abstract: Transfer learning is usually studied as a consequence of distribution shift. This paper identifies an orthogonal failure mode in which the data distribution is fixed and the loss changes. This setting is called loss shift. A loss determines which information in \(X\) is Bayes-relevant, and two losses may therefore require different representations even under the same joint law \(P(X,Y)\). The idea is formalized using Bayes quotients, which allow losses to be ordered by refinement. In the Bayes-quotient formulation, strict refinement gives an immediate qualitative obstruction. A source-minimal representation for a coarser loss is insufficient for a strictly finer target loss. For finite-output log loss, this obstruction becomes an exact quantitative identity. The excess risk is the conditional information about \(Y\) discarded by the representation. Experiments in controlled, learned, synthetic-image, and real-image settings show the predicted effect, i.e., classification-equivalent representations can have different optimal log-loss performance under a fixed data distribution.

13.
arXiv (math.PR) 2026-06-18

A scaling limit theorem for controlled branching processes with a size-divisible term

arXiv:2508.17116v2 Announce Type: replace Abstract: This paper establishes general sufficient conditions for a sequence of controlled branching processes to converge weakly on the Skorokhod space. We focus on a class of control mechanisms that extend previous results by decomposing those random variables into the sum of two independent components: an immigration term, which depends on the current population size, and a size-divisible term, which can be expressed as the sum of random contributions from each individual. This extension allows us to capture a broad range of control functions including Poisson, binomial, and negative binomial distributions, commonly used in the literature. The assumptions are formulated in terms of probability generating functions of the offspring and control laws, distinguishing in this latter between the immigration and the size-divisible parts. The limit process is shown to be a continuous-state branching process with dependent immigration. The proof essentially relies on tightness arguments and the identification of a martingale problem. We also identify the special case in which the limit reduces to a classical Feller branching diffusion with immigration.

14.
arXiv (CS.CV) 2026-06-18

DreamReg: Belief-Driven World Model for 2D-3D Ultrasound Registration

Ultrasound (US) is widely used for surgical navigation, yet real-time registration between intraoperative 2D slices and preoperative 3D volumes remains challenging due to partial observability, speckle noise, and the action-dependent US acquisition. Existing methods are one-shot or short-horizon, making it hard for them to gather evidence over time or capture how surgeons adjust probe motion based on on-screen feedback. We propose DreamReg, a belief-driven world-model framework that formulates 2D-3D registration as belief updating over rigid transformations. DreamReg maintains a latent belief state that summarizes past observations and poses information, and continuously refines the transformation through learned dynamics as new slices arrive. During training, DreamReg is exposed to probe-motion trajectories that mimic clinical scanning behavior and learns to update its belief by conditioning pose refinement on the current US observation. During inference, DreamReg refines registration via internal imagination: it rolls out the learned world model to simulate candidate probe motions and their predicted observations, and integrates these imagined outcomes to converge to an accurate rigid transformation. Experiments on CAMUS and u-RegPro datasets demonstrate improved robustness and competitive registration accuracy for real-time guidance compared with state-of-the-art methods.

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

VinQA: Visual Elements Interleaved Long-form Answer Generation for Real-World Multimodal Document QA

Real-world documents combine text with tables, charts, photographs, and diagrams arranged in diverse layouts, yet existing research on multimodal large language models (MLLMs) for document QA predominantly produces text-only responses, underutilizing these visual elements. We introduce VinQA, a dataset for long-form answer generation where cited visual elements are explicitly interleaved with their supporting text and grounded in relevant document pages. To support this task, we study two encoding methods for feeding raw document page images into an MLLM, along with their visual-element citation mechanisms: (1) Page Encoding, which directly encodes full-page images with bounding boxes of visual elements and treats these boxed regions as citable units; and (2) Modality Encoding, which parses each page to extract text and crop visual elements, encodes them separately, and uses these cropped elements as citable units. In our experiments, we propose M-GroSE, a multimodal evaluation framework extending GroUSE to assess answers along four dimensions: completeness, answer relevancy, faithfulness, and unanswerability. We additionally report Visual Source F1 to directly measure visual citation accuracy. Although proprietary frontier models still achieve the best overall scores on the VinQA test split, fine-tuning open Qwen2.5-VL models on the training split substantially improves their performance and narrows this gap. Modality Encoding is initially more robust for complex documents with long text, many visual elements, and diverse citation requirements. After training on VinQA, however, Page Encoding reaches a comparable level, competing effectively even without the explicit parsing used in Modality Encoding. Finally, Visual G-Eval, an MLLM-based judge, confirms that fine-tuned models insert visual elements at semantically appropriate positions with faithful supporting text.

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

LiteOdyssey: A Lightweight Reasoning AI Agent for Interpretable Rare-Disease Diagnosis

arXiv:2606.16149v1 Announce Type: new Abstract: Most medical AI systems improve by scaling additional machinery: more fine-tuning data, more agents, and/or larger retrieval databases. In rare-disease diagnosis, however, such scaling can produce systems that are difficult to deploy, audit, and maintain. We asked whether state-of-the-art diagnostic performance could instead be achieved by extending the reasoning chain of a single AI agent: guiding it with a diagnostic policy, developed through human-AI collaboration and augmenting with freely available biomedical tools. We introduce LiteOdyssey, a lightweight rare-disease diagnostic framework that guides reasoning language model through a clinical genetics workflow. This framework was developed through Policy Iteration with Human Feedback (PIHF) and uses dynamic access to public biomedical tools. On two challenging benchmarks that provide only patient clinical features, LiteOdyssey achieved state-of-the-art performance, with an overall disease Recall@1 of 59.3% over the combined 1,243 cases of LIRICAL (n = 370) and the PhenoPacket Store (n = 873). Both benchmarks have a high proportion of ultra-rare disease (a prevalence below 1 in 1,000,000, with ultra-rare shares of approximately 45% and 52.8%, respectively). On the more difficult PhenoPacket subset, where causal diseases were not mapped to Orphanet in our rarity-mapping pipeline, LiteOdyssey achieved 60.7% Recall@1, compared with 10.7% for the same baseline model (GPT-5.4) without tools. This performance was achieved without fine-tuning, multi-agent ensembles, or a large case-retrieval database. Gains were also observed in the following: on cases never seen during development, on a private cohort of real-world rare disease patients, and on a smaller open-weights model. LiteOdyssey suggests a path toward rare-disease AI systems that are accurate, easier to deploy, and more transparent for physician review.

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

Decoupling Search from Reasoning: A Vendor-Agnostic Grounding Architecture for LLM Agents

Production LLM agents increasingly depend on real-time search, yet native search grounding bundles retrieval policy, provider choice, evidence injection, cost, latency, and generation behavior behind a single model-provider boundary. This coupling makes grounding hard to inspect, tune, reuse, or port, and can trigger Search-Induced Verbosity that breaks strict output contracts. We present Decoupled Search Grounding (DSG), a vendor-agnostic boundary that moves grounding outside the reasoning model through an MCP-compatible gateway, exposing provider routing, source-aware context rendering, configured fallback, retrieval-depth control, and exact plus semantic caching as first-class controls. Across five frontier models on SimpleQA, FreshQA, and HotpotQA, native search leads on recency-sensitive FreshQA, but DSG exposes a stronger frontier when control matters: on SimpleQA it nearly matches native accuracy (86.1% vs. 87.7%) at 91% lower search cost, preserves concise answer contracts, and reaches a 99.4% warm-cache hit rate with 68% lower latency. Deployed as a shared production grounding layer for large-scale agentic workloads with interchangeable models, DSG matches or slightly exceeds native-search accuracy on an e-commerce query-understanding (QIU) workload while cutting search cost by over 98%. Real-time grounding is best treated as an optimizable interface boundary, not a fixed model feature.

18.
arXiv (CS.CL) 2026-06-19

The Almost Intelligent Revolution: Options for Scaling Up Deliberation and Empowering People with AI

The increasing prominence of Large Language Models (LLMs) in public discourse presents both opportunities and challenges for democratic deliberation. While red teaming strategies help mitigate specific risks, broader concerns persist regarding linguistic constraints, biases, and the sycophantic tendencies of LLMs. This chapter explores how LLMs can be used to significantly scale up and democratise deliberation, particularly in fostering inclusivity and empowering traditionally marginalised groups. Drawing on concepts from Systemic-Functional Linguistics, the chapter examines how variations across language users (for example, with respect to socio-demographic groups) and across language use (for example, with respect to communicative functions) shape participation in AI-supported deliberation. The chapter presents AI-driven deliberation studies and assesses their potential to scaffold argumentation, enhance access, and reduce the influence of exclusionary linguistic norms and biases which are embedded in prestigious registers. At the same time, the chapter cautions against both overclaiming, which leads to unrealistic expectations, and underclaiming, which risks missed opportunities for AI-assisted engagement. The chapter concludes by identifying future research directions to maximise the democratic potential of AI-assisted participation while embedding ethical safeguards to counteract the reproduction of linguistic inequalities.

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

Enhancing Generative Auto-bidding with Offline Reward Evaluation and Policy Search

arXiv:2509.15927v5 Announce Type: replace-cross Abstract: Auto-bidding is a critical tool for advertisers to improve advertising performance. Recent progress has demonstrated that AI-Generated Bidding (AIGB), which learns a conditional generative planner from offline data, achieves superior performance compared to typical offline reinforcement learning (RL)-based auto-bidding methods. However, existing AIGB methods still face a performance bottleneck due to their inherent inability to explore beyond the static dataset with feedback. To address this, we propose AIGB-Pearl (Planning with \textbf{EvaluAtor via RL}), a novel method that integrates generative planning and policy optimization. The core of AIGB-Pearl lies in constructing a trajectory evaluator to assess the quality of generated scores and designing a provably sound KL-Lipschitz-constrained score-maximization scheme to ensure safe and efficient exploration beyond the offline dataset. A practical algorithm that incorporates the synchronous coupling technique is further developed to ensure the model regularity required by the proposed scheme. Extensive experiments on both simulated and real-world advertising systems demonstrate the state-of-the-art performance of our approach.

20.
medRxiv (Medicine) 2026-06-11

Dissecting the functional landscape of rare diseases through genomic variation in a heterogeneous cohort of 11,000 patients

Rare diseases (RDs) remain a major diagnostic challenge. Genetic and phenotypic heterogeneity, incomplete knowledge of disease mechanisms, and limitations in variant clinical interpretation leave many patients without a molecular diagnosis. Meanwhile, the growing volume of genomic data generated in clinical practice offers an opportunity to develop data-driven methodologies for exploring disease mechanisms and improving the reanalysis of unsolved cases. We aggregated real-world genomic data from 11,084 unrelated patients with suspected RD. Patients were clinically classified into 122 diseases. We built a multi-disease genomic variant frequency database (FJD-DB), which enabled the development of variant and gene-disease association scores by means of case-control subcohort comparisons across 32 disease groups. Functional enrichment analyses were then used to highlight disease-associated protein domains, pathways, biological processes, and phenotypes. Finally, the resulting knowledge was integrated into a data-driven framework for the guided reanalysis of unsolved RD patients applied to Inherited Retinal Dystrophies (IRD) patients as first use case. FJD-DB contained more than 45 million unique variants, including ~185,000 potentially pathogenic variants. Disease-specific analyses identified disease-associated pathogenic variants and highlighted both established and candidate disease genes. We detected 179 significantly enriched protein domains across 23 diseases, 124 Human Phenotype Ontology terms across 13 diseases, 79 Reactome pathways across 10 diseases, and 72 Gene Ontology biological processes across 8 diseases, revealing highly disease-specific functional signatures. Integration of disease-specific variant, gene, and functional association signals enabled the development of a data-driven framework for guided reanalysis of unsolved RD cases. Applied to more than 1,100 unsolved IRD cases, the framework generated clinically relevant findings in 26 patients, including four molecular diagnoses, seven candidate diagnoses, and 15 cases upgraded from non-informative findings to variants of uncertain significance. Aggregated real-world genomic data can be leveraged to identify disease-associated molecular signals generating novel biological hypotheses. A unified analytical framework provides a scalable strategy for knowledge discovery and guided reanalysis, facilitating the identification of overlooked and potentially novel genetic causes of RDs.

21.
arXiv (CS.AI) 2026-06-16

Rethinking Scaffolding in LLM Tutors: The Interactional Mismatch Between Benchmarks and Real-World Deployments

arXiv:2606.15766v1 Announce Type: new Abstract: A central pedagogical value evaluated in AI tutor benchmarks is scaffolding: guiding students through graduated steps toward a solution. Alignment and evaluation methods for embedding scaffolding behaviour into chatbots, however, rest on an implicit assumption: that students will take up the scaffolding and engage in the conversation. To examine whether this assumption holds, we introduce an evaluation pipeline around two metrics - Chatbot Scaffolding and Student Uptake - and apply them across nine datasets of 9,490 chats, spanning AI tutor benchmarks and real-world deployments of educational chatbots. Our analysis reveals that while benchmarks assume a high-scaffolding, high-student-uptake environment, students in real-world settings exhibit lower levels of uptake overall - frequently bypassing the chatbot's pedagogical framing to drive the interaction toward their own learning goals at little interpersonal cost. We argue that bypassing scaffolding is not necessarily detrimental; rather, it frequently highlights a mismatch between a chatbot's pedagogical framing and the student's learning goals. To meaningfully evaluate the effectiveness of a chatbot's assistance, future benchmarks must move beyond the assumption that students will simply take up the scaffolding, and instead evaluate how these chatbots navigate diverse learning contexts and student-driven interaction patterns.

22.
arXiv (CS.AI) 2026-06-16

SpecAlign: Efficient Specification-Grounded Alignment of Large Language Models via Synthetic Data

arXiv:2606.16276v1 Announce Type: new Abstract: As large language models (LLMs) are increasingly deployed in real-world applications, alignment is no longer governed by a single universal notion of safety or helpfulness, but instead by provider- or application-specific model specifications. These specifications are typically long, structured, and frequently updated, yet existing alignment pipelines lack a systematic mechanism to operationalize them as training signals. In this paper, we propose specification-grounded alignment, a new alignment paradigm that treats provider-authored model specifications as the primary alignment target rather than abstract principles or static benchmarks. To instantiate this paradigm, we introduce SpecAlign, a framework that synthesizes alignment data directly from specification documents. SpecAlign combines structured rule annotation, controllable specification instantiation, and multi-agent adversarial data synthesis to generate fine-grained, boundary-aware preference pairs that capture both compliant behaviors and meaningful specification violations. Experiments across multiple model specifications and backbone models demonstrate that training with SpecAlign consistently improves rule compliance while preserving general capabilities and avoiding over-conservative behavior. These results suggest that grounding alignment in explicit model specifications enables rapid, precise, and scalable adaptation of LLM behavior to evolving policy requirements.

23.
arXiv (quant-ph) 2026-06-15

An integrated ultrahigh vacuum cluster tool for diamond surface science and single nitrogen-vacancy center measurements

arXiv:2606.13961v1 Announce Type: new Abstract: We present a custom-designed ultrahigh vacuum (UHV) cluster tool developed for studying shallow nitrogen-vacancy (NV) centers in diamond, enabling in situ diamond surface preparation, characterization, and single NV center dynamics measurements within a single connected platform. The system combines a surface science chamber for controlled surface modification and analysis with a cryogenic confocal microscope chamber dedicated to NV spin and optical measurements. This integrated approach enables a direct correlation between diamond surface chemistry and the resulting NV spin and charge properties. The instrument provides a versatile platform for systematic studies of surface-induced decoherence mechanisms and charge dynamics for shallow NV centers, and establishes a pathway toward reproducible surface engineering for quantum sensing applications.

24.
bioRxiv (Bioinfo) 2026-06-10

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

作者:

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

25.
arXiv (CS.LG) 2026-06-16

Floating-Point Networks with Automatic Differentiation Can Represent Almost All Floating-Point Functions and Their Gradients

arXiv:2605.01702v2 Announce Type: replace Abstract: Theoretical studies show that for any differentiable function on a compact domain, there exists a neural network that approximates both the function values and gradients. However, such a result cannot be used in practice since it assumes real parameters and exact internal operations. In contrast, real implementations only use a finite subset of reals and machine operations with round-off errors. In this work, we investigate whether a similar result holds for neural networks under floating-point arithmetic, when the gradient with respect to the input is computed by the automatic differentiation algorithm $D^\mathtt{AD}$. We first show that given a floating-point function $\phi$ (e.g., a loss function), arbitrary function values and gradients can be represented by a floating-point network $f$ and $D^\mathtt{AD}(\phi\circ f)$, respectively. We further extend this result: given $\phi_1,\dots,\phi_n$, $D^\mathtt{AD}(\phi_i\circ f)$ can simultaneously represent arbitrary gradients while $f$ represents the target values, under mild conditions. Our results hold for practical activation functions, e.g., $\mathrm{ReLU}$, $\mathrm{ELU}$, $\mathrm{GeLU}$, $\mathrm{Swish}$, $\mathrm{Sigmoid}$, and $\mathrm{tanh}$.