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

GeoCFNet: Geometry-Aware Confidence Field Network for Robot-Assisted Endoscopic Submucosal Dissection

Advanced surgical robotics has made robot-assisted endoscopic submucosal dissection (ESD) a promising approach for the en-bloc resection of large lesions, with the potential to reduce recurrence and improve long-term outcomes. However, the technical complexity and risk of complications in ESD demand stable and precise visual guidance to maintain an accurate dissection corridor and a safe tissue margin. Dense confidence fields provide an effective representation for this purpose by describing both the preferred dissection region and its spatial transition to surrounding tissue. However, reliable confidence field estimation remains challenging in dynamic endoscopic scenes due to smoke, specular highlights, tissue deformation, weak texture, and the thin geometric structure of the target region. To address these challenges, we formulate dissection guidance as a geometry-aware confidence field estimation problem and propose GeoCFNet, a geometry-aware confidence field network built on a pretrained DINOv3 backbone. GeoCFNet integrates a Token-Differentiated Fusion module to aggregate class-token context with dense patch representations, a SegFormer decoder for confidence regression, and Geometry-Aware Spatial Regularization (GASR) to preserve spatial coherence and local geometric transitions. Experimental results show that GeoCFNet achieves RMSE 0.0480, PSNR 27.1995, SSIM 0.3397, and CC 0.2466, indicating accurate and geometrically stable confidence field estimation for robot-assisted ESD guidance.

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

AI for Maritime Security: Comparative Evaluation of CNN and Vision Transformer Architectures for Maritime Object Detection

This study aims to enhance maritime security by using advanced Artificial Intelligence (AI) and Computer Vision (CV) techniques. For this purpose, it was designed and assessed intelligent object detection systems that can detect the presence of ships on the sea surface under different real-time environments. To achieve this goal, a maritime image dataset with 6,468 images was used, covering different weather conditions like cloudy, foggy, rainy, and sunny environments. Six deep learning architectures were evaluated, including a base Convolutional Neural Network (CNN) model, four transfer learning models (Xception, VGG16, MobileNetV2, and EfficientNetV2L), and a Vision Transformer (ViT) model. The models were compared using multiple performance indicators, including accuracy, Type I and Type II errors, model size, and video processing time. The results show that model performance varies depending on computational constraints and deployment conditions. While lightweight architectures are suitable for resource-limited devices, the ViT achieved the best overall performance, reaching 100% accuracy with the lowest error rates and the fastest video processing time. The findings highlight the potential of AI-driven computer vision systems for maritime surveillance, border protection, and autonomous navigation.

04.
arXiv (CS.AI) 2026-06-19

Emergent Alignment

arXiv:2606.19527v1 Announce Type: new Abstract: Can Large Language Models (LLMs) discern when their own outputs are misaligned with human ethics? And can they self-correct? We endow an LLM with a conscience step that reviews its own reasoning and outputs, and we extend the training loss with an alignment component using Direct Preference Optimization (DPO) to steer the model away from non-ethical outputs. The result is an online technique to align models in a wide range of applications: training, fine-tuning, adversarial prompting, and zero-shot learning. It does not require a weaker or stronger judge, relying instead on a frozen copy of itself. In previous work, the Emergent Misalignment scenario showed a range of emergent unethical behaviors from fine-tuning the model to hack code. Instead, we empirically show how to achieve Emergent Alignment: a single high-level introspective question steers training toward an ethical model under the same code hacking scenario.

05.
arXiv (math.PR) 2026-06-11

Percolation phase transition on planar spin systems

arXiv:2105.13314v2 Announce Type: replace Abstract: In this article we study the continuity and sharpness of the phase transition for percolation models defined on top of planar spin systems. The two examples that we treat in detail concern the Glauber dynamics for the Ising model and a Dynamic Bootstrap process. For both of these models we prove that their phase transition is continuous and sharp, providing also quantitative estimates on the two point connectivity. The techniques that we develop in this work can be applied to a variety of different percolation models based on spin-flip dynamics. We also discuss some of the problems that can be tackled in a similar fashion.

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

MemBoost: A Memory-Boosted Framework for Cost-Aware LLM Inference

Large Language Models (LLMs) deliver strong performance but incur high inference cost in real-world services, especially under workloads with repeated or near-duplicate queries across users and sessions. In this work, we propose MemBoost, a memory-boosted LLM serving framework that enables a lightweight model to reuse previously generated answers and retrieve relevant supporting information for cheap inference, while selectively escalating difficult or uncertain queries to a stronger model. Unlike standard retrieval-augmented generation, which primarily grounds a single response, MemBoost is designed for interactive settings by supporting answer reuse, continual memory growth, and cost-aware routing. Experiments across multiple models under simulated workloads show that MemBoost substantially reduces expensive large-model invocations and overall inference cost, while maintaining high answer quality comparable to the strong model baseline.

07.
arXiv (CS.CL) 2026-06-12

LAUKIN: A Multi-jurisdictional Common Law Contract Dataset

Multinational companies increasingly require cross-jurisdictional contract review, yet existing legal NLP datasets are largely restricted to a single jurisdiction. We introduce LAUKIN (Legal equivalence dataset of Australia, UK, and INdia), a dataset of clause pairs (AU-UK, UK-IN, IN-AU) labelled for boolean legal equivalence. We develop a novel multi-stage retrieval and reranking pipeline to construct the initial clause pair mapping, with a subset of clause pairs subsequently annotated by legal experts as Equivalent or Not Equivalent. The dataset comprises 14,727 clause pairs from 204 contracts across 8 agreement types, of which 3,000 are manually labelled: 900 train, 600 dev, and 1,500 test. We evaluate 12 models across 4 techniques, achieving a best macro-F1 of 65.11%, establishing LAUKIN as a challenging benchmark. Results reveal that, despite shared legal heritage, drafting conventions diverge significantly across jurisdictions, making cross-jurisdictional equivalence classification non-trivial. LAUKIN also includes 11,727 unlabelled training pairs to support future semi-supervised learning research in legal NLP.

08.
arXiv (CS.CL) 2026-06-15

Detecting undisclosed LLM-generated content in parliamentary texts

In this paper, we evaluate the extent of undisclosed LLM-generated content in texts from the parliaments of the United Kingdom and Sweden. In many areas, such as in journalism or in academic writing, there are often requirements to clearly disclose whether AI tools, such as LLMs, have been used. In the case of parliamentary texts, the guidelines on disclosure of AI use are more vague. However, in order to maintain transparency and retain public trust, it is generally recommended that parliamentarians should state whether or not they have used AI when writing texts, such as parliamentary motions. Here, we train an interpretable (glass-box) text classifier using pre-LLM parliamentary texts and LLM-generated versions of such texts. We then apply the classifier to a test set containing recent parliamentary texts, finding a steady increase in undisclosed LLM use, in both parliaments, from 2022 onwards.

09.
arXiv (CS.CL) 2026-06-12

Why Sampling Is Not Choosing: Intentionality, Agency, and Moral Responsibility in Large Language Models

Recent advances in large language models (LLMs) have prompted claims that such systems exhibit agency or qualify as moral agents. This paper argues that these attributions are misguided. We maintain that moral responsibility requires commitment-bearing agency grounded in intrinsic intentionality and self-attributed action, and that such agency constitutes the form of free will relevant to responsibility. Although LLMs generate coherent and normatively evaluable outputs, their operation is fully characterized by probabilistic input-output mappings learned from data. Their apparent intentionality is derived rather than intrinsic, and their outputs are neither owned as commitments nor guided by reasons. Variability introduced by stochastic sampling does not amount to choice or authorship. We address objections from the intentional stance, functionalism, compatibilism, and the presence of moral reasoning in model outputs, arguing that none suffice to establish genuine agency.

10.
arXiv (CS.AI) 2026-06-18

Towards an Agent-First Web: Redesigning the Web for AI Agents

arXiv:2606.19116v1 Announce Type: new Abstract: The World Wide Web was built on an assumption held for three decades: the primary consumer of web content is a human being. This permeates every layer; its access model presumes human visitors, its economics rest on human attention, and its content targets human perception. The rapid emergence of AI agents as intermediaries between humans and web content invalidates this assumption. Yet the web resists agents through blanket blocking, CAPTCHA-based exclusion, and economic models that treat agent access as extraction rather than legitimate interaction. This paper proposes a principled redesign across three layers. At the access layer, agents acting for humans should inherit equivalent access rights, governed by rate limiting and agent identification metadata in HTTP requests, analogous to browser headers, alongside a dual-layer architecture serving human-readable and agent-optimized content from the same domain. At the economic layer, we propose an intent-based tier framework grounded in the agent-as-human-proxy principle: an agent's economic obligation mirrors that of the human it represents. A token-based subscription model meters content in tokens rather than pageviews, alongside a commissioned content economy anchoring AI content production in human intentionality. At the content layer, we identify epistemic recursion, the self-referential loop in which AI-generated content is consumed by agents to produce further content, progressively detaching web knowledge from human ground truth. We propose the Agent Text Markup Language (ATML), a four-level human supervision tier model, and a cryptographic provenance chain to counter this threat. Together these constitute ten design principles for an agent-first internet, one in which agents are first-class citizens whose integration requires renegotiating the web's foundational social contract across access, economics, and content.

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

The Third Challenge on Image Denoising at NTIRE 2026: Methods and Results

This paper reports on the NTIRE 2026 Challenge on Image Denoising, specifically focusing on the high-noise regime ($\sigma = 50$). The competition investigates advanced neural architectures designed to restore high-fidelity details from images corrupted by additive white Gaussian noise (AWGN). Unlike constrained benchmarks, this track emphasizes peak quantitative performance, measured by Peak Signal-to-Noise Ratio (PSNR), without limitations on parameter count or computational overhead. By synthesizing contributions from 20 finalist teams out of 116 registrants, this report benchmarks the latest technical innovations and provides a comprehensive snapshot of the current state-of-the-art in unconstrained image restoration.

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

Fast When, Careful Who: Dual-Process Multiparty Turn-Taking with Diffusion Augmentation

Reliable turn-taking is essential for spoken dialogue systems. However, most existing methods are designed for two-speaker interaction and struggle with realistic multiparty audio containing overlap and rapid speaker changes. We study multiparty turn-taking on the VoxConverse dataset and propose an audio-only two-stage pipeline that separates when to trigger a turn boundary from whether the floor is actually transferring. A fast trigger scans the audio and proposes candidate end-of-turn times, while a lightweight verifier runs only at those times to decide \textsc{Hold} or \textsc{Shift} and support next-speaker prediction. We report results in the full multiparty setting and a controlled dyadic top-2 projection for comparability. We also investigate diffusion-based, label-preserving background-audio mixing as a data augmentation strategy. Results show improved shift detection over a baseline, with further improvements from diffusion augmentation.

13.
arXiv (quant-ph) 2026-06-16

Watching a Superconducting Coplanar Waveguide Heat Up with a Single Color Center

arXiv:2606.15398v1 Announce Type: new Abstract: Single color centers in diamond offer a local probe of their cryogenic environment, providing a direct way to quantify heating in spin-control hardware. Here, we establish a single spectrally stable tin-vacancy (SnV) center as an on-chip thermometer for a diamond membrane and use it to characterize microwave- and radio-frequency-induced heating in a superconducting coplanar waveguide patterned on the same chip. We first calibrate the temperature dependence of the optical C-transition frequency and linewidth from $20\,\mathrm{K}$ down to the few-kelvin regime. At lower temperatures, where the optical response becomes weakly temperature dependent, we use the spin-lattice relaxation time $T_1$ as a complementary thermometer and tune its sensitivity with the transverse magnetic-field component. Applying this local thermometer to a niobium coplanar waveguide, we observe magnetic-field-dependent superconducting breakdown under GHz drive, accompanied by abrupt heating of the diamond. In contrast, at $20\,\mathrm{MHz}$ and $400\,\mathrm{mT}$, relevant for nuclear-spin control, we detect no measurable heating up to the breakdown threshold of $9.4\,\mathrm{dBm}$, corresponding to $B_\mathrm{ac}\sim1.2\,\mathrm{mT}$. These results define a safe operating window for superconducting microwave and RF control structures in diamond-based quantum nodes.

14.
arXiv (CS.CV) 2026-06-12

Learning Visually Interpretable Oscillator Networks for Soft Continuum Robots from Video

Learning soft continuum robot (SCR) dynamics from video offers flexibility but existing methods lack interpretability or rely on prior assumptions. Model-based approaches require prior knowledge and manual design. We bridge this gap by introducing: (1) The Attention Broadcast Decoder (ABCD), a plug-and-play module for autoencoder-based latent dynamics learning that generates pixel-accurate attention maps localizing each latent dimension's contribution while filtering static backgrounds, enabling visual interpretability via spatially grounded latents and on-image overlays. (2) Visual Oscillator Networks (VONs), a 2D latent oscillator network coupled to ABCD attention maps for on-image visualization of learned masses, coupling stiffness, and forces, thereby enabling mechanical interpretability. We validate our approach on single- and double-segment SCRs, demonstrating that ABCD-based models significantly improve multi-step prediction accuracy with 5.8x error reduction for Koopman operators and 3.5x for oscillator networks on a two-segment robot. VONs autonomously discover a chain structure of oscillators. This fully data-driven approach yields compact, mechanically interpretable models with potential relevance for future control applications.

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

FlowRL: A Taxonomy and Modular Framework for Reinforcement Learning with Diffusion Policies

arXiv:2603.27450v2 Announce Type: replace Abstract: Thanks to their remarkable flexibility, diffusion models and flow models have emerged as promising candidates for policy representation. However, efficient reinforcement learning (RL) upon these policies remains a challenge due to the lack of explicit log-probabilities for vanilla policy gradient estimators. While numerous attempts have been proposed to address this, the field lacks a unified perspective to reconcile these seemingly disparate methods, thus hampering ongoing development. In this paper, we bridge this gap by introducing a comprehensive taxonomy for RL algorithms with diffusion/flow policies. To support reproducibility and agile prototyping, we introduce a modular, JAX-based open-source codebase that leverages JIT-compilation for high-throughput training. Finally, we provide systematic and standardized benchmarks across Gym-Locomotion, DeepMind Control Suite, and IsaacLab, offering a rigorous side-by-side comparison of diffusion-based methods and guidance for practitioners to choose proper algorithms based on the application. Our work establishes a clear foundation for understanding and algorithm design, a high-efficiency toolkit for future research in the field, and an algorithmic guideline for practitioners in generative models and robotics. Our code is available at https://github.com/typoverflow/flow-rl.

16.
arXiv (quant-ph) 2026-06-17

Breaking the bicycle frame: Coset-based quantum LDPC codes

arXiv:2606.17268v1 Announce Type: new Abstract: Generalizing the construction of two-block group algebra (2BGA) codes, we introduce a family of two-block quantum LDPC codes constructed using the action of a group on the cosets of its subgroup. This replaces the regular group actions of the earlier two-block constructions and significantly expands the search space, yielding new quantum LDPC codes outside the 2BGA family. Through a computer search, we identify several new quantum LDPC codes, including weight-6 codes with parameters $[[48,8,6]]$, $[[96,8,10]]$, and $[[224,12,16]]$, as well as weight-8 codes with parameters $[[84,16,8]]$, $[[112,16,10]]$, $[[128,16,12]]$, and $[[168,16,15]]$. Furthermore, we introduce a maximally packed syndrome extraction schedule of depth $w+2$, including initialization and measurement steps, for any code with a maximum stabilizer weight of $w$ from our family. Under a standard circuit-level noise model, our codes, when decoded using BP-OSD, perform competitively with BB codes, achieving thresholds of $\approx0.65\%$ for the weight-6 family and $\approx0.35\%$ for the weight-8 family. Finally, we introduce a group-theoretic framework to generate sequences of graph-based covers of 2BGA codes, recovering and extending recent results on code constructions of this type.

17.
medRxiv (Medicine) 2026-06-16

Care Delivery Gap framework: a proof-of-concept patient-reported measure of guideline-referenced care-process omissions in sickle cell disease

Abstract Background:Sickle cell disease (SCD) is concentrated in sub-Saharan Africa, where delivery of guideline-referenced care remains challenging. Current evaluation approaches rely largely on access indicators and clinical outcomes, which do not directly measure care delivery. We developed the Care Delivery Gap (CDG) framework, a patient-reported approach for identifying care-process omissions, and conducted a proof-of-concept study to assess feasibility and explore variation across income strata. Methods: We conducted a cross-sectional framework-development study involving a proof-of-concept sample of 52 individuals with SCD or caregivers recruited through clinics and moderated SCD communities across Africa, North America, and Europe between June 2025 and March 2026. The CDG framework assessed patient-reported omissions in specialist involvement, follow-up continuity, cardiovascular screening, and biochemical surveillance. Analyses were descriptive. Results: Substantial multi-domain care-process omissions were identified despite high reported healthcare engagement. Across geographic income strata, cardiovascular screening was reported by 4/35 (11%) LMIC versus 16/17 (94%) HIC participants, and regular follow-up within the preceding 12 months by 14/35 (40%) versus 16/17 (94%), respectively. High CDG scores, representing 1 omissions across three or four domains, occurred in 20/35 (57%) LMIC compared with 1/17 (6%) HIC participants. Similar disparities were observed across specialist review and vitamin B12 surveillance domains. Conclusion: A structured patient-reported framework identified multi-domain omissions in guideline-referenced SCD care, including among individuals reporting healthcare access. The divergence between access indicators and reported care delivery suggests that service contact alone may not reflect care quality. The framework provides a feasible foundation for future process-level quality measurement in high-burden settings.

18.
arXiv (CS.LG) 2026-06-11

Reinforcement Learning with Action-Triggered Observations

arXiv:2510.02149v2 Announce Type: replace Abstract: We introduce Action-Triggered Sporadically Traceable Markov Decision Processes (ATST-MDPs), a reinforcement learning framework for partial observability in which full state observations occur stochastically at each step, with probability determined by the chosen action. We derive Bellman equations tailored to this setting and establish the existence of an optimal policy. Exploiting the fact that sporadic observations reveal the full state, we provide an equivalent formulation in which agents commit to action-sequences between consecutive observations. Under the linear MDP assumption, we show that the value function over such action-sequences admits a linear representation in a finite-dimensional feature map, enabling standard regression-based methods. As an application, we derive ATST-LSVI-UCB, an optimistic algorithm achieving regret $\widetilde{O}(\sqrt{Kd^3(1-\gamma)^{-3}})$ for episodic learning with geometrically distributed horizons, where $K$ is the number of episodes, $d$ the feature dimension, and $\gamma$ the discount factor (episode continuation probability), matching the known rate for linear MDPs with full observability.

19.
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.

20.
bioRxiv (Bioinfo) 2026-06-11

OCOO-T : A SIMPLE AND SCALABLE VIRTUAL CELL MODEL FOR TRANSCRIPTIONAL PERTURBATION RESPONSE PREDICTION

Predicting single-cell transcriptional responses to genetic, chemical and cytokine perturbations is a fundamental challenge in computational biology and AI Virtual Cell (AIVC) modeling, with direct implications for drug discovery and the elucidation of gene regulatory networks. Existing approaches often rely on auxiliary cell-state encoders, hierarchical variational autoencoders, dedicated Transformer encoder-decoder modules, or gene-interaction priors to compress high-dimensional expression profiles into latent representations. While effective, these designs increase architectural complexity and may limit scalability and generalizability. This paper introduces OCOO-T, a minimalist flow-matching-based AIVC model for transcriptional perturbation response prediction. OCOO-T utilizes a vanilla Transformer stack that operates directly on continuous gene expression profiles and formulates perturbation response prediction as a continuous-time denoising process. Perturbation embeddings, dosage information, and cell-line/cell-type specificity are integrated through adaptive layer normalization and in-context tokens. Comprehensive evaluations on Tahoe100M, Replogle, and PBMC benchmarks demonstrate that OCOO-T achieves state-of-the-art performance across diverse perturbations and cell types while effectively scaling to long transcriptional profiles through patching and depatching of cellular contexts. By leveraging the simplicity of Transformer-based denoising for single-cell omics, OCOO-T provides an effective and scalable framework for in-silico cellular simulation.

21.
arXiv (CS.AI) 2026-06-19

ZeSTA: Zero-Shot TTS Augmentation with Domain-Conditioned Training for Data-Efficient Personalized Speech Synthesis

arXiv:2603.04219v2 Announce Type: replace-cross Abstract: We investigate the use of zero-shot text-to-speech (ZS-TTS) as a data augmentation source for low-resource personalized speech synthesis. While synthetic augmentation can provide linguistically rich and phonetically diverse speech, naively mixing large amounts of synthetic speech with limited real recordings often leads to speaker similarity degradation during fine-tuning. To address this issue, we propose ZeSTA, a simple domain-conditioned training framework that distinguishes real and synthetic speech via a lightweight domain embedding, combined with real-data oversampling to stabilize adaptation under extremely limited target data, without modifying the base architecture. Experiments on LibriTTS and an in-house dataset with two ZS-TTS sources demonstrate that our approach improves speaker similarity over naive synthetic augmentation while preserving intelligibility and perceptual quality. Audio samples are available on our web page.

22.
arXiv (CS.LG) 2026-06-19

Do Vision-Language Models Understand 3D Scenes or Just Catalogue Objects?

arXiv:2605.20448v2 Announce Type: replace-cross Abstract: Vision-language models reliably name objects in a scene, but do they represent the 3D layout those objects inhabit? We introduce a 3,034-sample human-curated benchmark targeting three components of spatial understanding: depth-ordered occlusion (probed via three independent counterfactual operationalisations), optical-geometry inference over visible reflections, and volumetric rearrangement planning. Six frontier and open-weight VLMs, scored by trained annotators on 18,204 responses with no LLM-as-judge, reveal a sharp dissociation: models that plan rearrangements over visible layouts at 53–97% accuracy and rarely violate collision constraints fall to 6–45% on occlusion and below 7% on reflections. An embodied-reasoning model reproduces the same profile. White-box analysis on Qwen3-VL-8B-Thinking localises the failure to the visual-token merger: spatial information recoverable throughout the vision encoder becomes inaccessible after token compression and only stabilises again when clean post-merger activations are patched into the language decoder.

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

Mahalanobis-Guided Latent OOD Detection for Hybrid ES-DRL Control in Time-Varying Systems

arXiv:2606.11474v1 Announce Type: new Abstract: In this paper, we study Mahalanobis-guided latent out-of-distribution (OOD) detection for test-time RL controller switching in nonlinear time-varying systems. RL controllers can quickly control high-dimensional systems within the training distribution, but their performance can degrade when time-varying dynamics produce unseen observations. We consider a combined ES–DRL controller, where RL provides fast in-distribution actions and bounded extremum seeking (ES) provides robust model-independent control under OOD operation. The key challenge is deciding when to switch. We train a variational autoencoder (VAE) on in-distribution beam-profile observations and use Mahalanobis distance in the VAE latent space to detect OOD beam profiles at test time. This OOD decision sets a binary switch that selects either the RL controller or the ES controller. We evaluate the approach in safety-critical particle accelerator control. In this setting, spatial magnet motion creates OOD beam profiles that were not seen during RL training. Visualization of the VAE latent space shows that the proposed method identifies this OOD scenario and provides an interpretable signal for switching between RL and ES in the combined controller.

24.
medRxiv (Medicine) 2026-06-15

The clinical utility of functional testing in fibroblasts to diagnose primary mitochondrial disease

Genome sequencing of the heterogeneous primary mitochondrial disorders (PMD) frequently reveals variants of uncertain significance that require functional tests for diagnosis, and does not identify variants in all patients. We analyzed mitochondrial enzyme assays, blue native polyacrylamide gel electrophoresis (BN-PAGE) with in-gel activity staining, complex I assembly blot, and select protein abundances in fibroblasts of a case series of 204 PMD patients divided into functional classes, in comparison to 51 controls and 53 differential diagnostic conditions. Overall, sensitivity and specificity for respiratory chain enzyme assays were 46% and 93% respectively, for BN-PAGE 40% and 98%, for complex I assembly assay 49% and 99%. The overall sensitivity of all tests was 76%, specificity 93%, with positive predictive value 96% and negative predictive value 67%. Categories with high sensitivity were isolated complex deficiencies, nuclear DNA-encoded mitochondrial protein synthesis defects, co-factor defects, and mitochondrial amino-acyl-tRNA synthetase conditions when aided by protein abundance. Mitochondrial DNA mutations and maintenance disorders showed poor sensitivities. Secondary dysfunctions were rare. A complete battery of functional tests showed strong diagnostic clinical utility in fibroblasts.

25.
arXiv (CS.LG) 2026-06-19

Calibrating Generative Models to Feature Distributions with MMD Finetuning

arXiv:2606.19496v1 Announce Type: new Abstract: Generative models can produce individually plausible samples while deviating substantially from a target set in the distribution of key features. For example, a model pretrained on broad drug-like chemical space may generate molecules whose molecular features differ from those of a therapeutic class of interest, such as known antibiotics. Correcting such distributional miscalibration is challenging: direct finetuning on the target set can overfit and does not control which features are matched. To fill this gap, we introduce kernel Calibrating Generative Models (kCGM). kCGM minimizes a maximum mean discrepancy (MMD) between generated and target feature distributions using an unbiased score-function estimator, with KL regularization to remain close to the pretrained model. On a target set of 174 antibiotics, direct finetuning sacrifices chemical validity for feature-distribution matching, whereas kCGM improves target feature matching while increasing validity. We further demonstrate kCGM in protein and DNA generation tasks, showing it can adapt autoregressive, continuous-space diffusion, and discrete diffusion models using only feature-level supervision. Code is available at https://github.com/smithhenryd/cgm.