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01.
medRxiv (Medicine) 2026-06-18

Cost-effectiveness of a virtual fracture clinic versus traditional in-person fracture clinic care for adults with acute simple fractures: a protocol for a health economic evaluation within the RECITAL trial

ABSTRACT Introduction Traditional in-person fracture clinics are often overcrowded and inconvenient for patients. Virtual fracture clinics aim to address some of these concerns by improving the efficiency of the orthopaedic service and reducing unnecessary interventions while maintaining safety and quality of care. The RECITAL trial is a non-inferiority randomised controlled trial comparing follow-up care provided at a virtual fracture clinic for people with acute simple fractures to follow-up care provided at an in-person fracture clinic. This study describes the protocol for an economic evaluation of RECITAL where the primary aim is to investigate the cost-effectiveness of a virtual fracture clinic compared with traditional in-person fracture clinic care from a health system perspective. Methods and analysis The RECITAL trial recruited 312 participants with acute simple fractures and randomised them to receive follow-up care provided at a virtual fracture clinic or follow-up care provided at an in-person fracture clinic. We will conduct a within-trial analysis from a health system perspective (primary analysis), as well as a health service, patient and societal perspective. The economic evaluation will estimate the difference in the cost of resource inputs on an intention to treat basis used by participants in the two arms of the trial, allowing comparisons to be made between the in-person and virtual fracture clinics. Data for intervention costs and healthcare utilisation will be collected from trial records, hospital electronic medical records and district performance units. The results of the economic evaluation will be expressed in terms of incremental cost per utility weight gained at 12 weeks and will be plotted on a cost-effectiveness plane. Bootstrapping by resampling will be used to estimate 95% confidence intervals around costs and outcomes, and to calculate the confidence intervals around the incremental cost-effectiveness ratio. A cost-effectiveness acceptability curve (CEAC) will be plotted, which will provide information about the probability that an intervention is cost-effective, given the level of a decision makers willingness to pay for each additional outcome. Ethics and Dissemination The trail was approved by the SLHD Ethics Review Committee (RPAH Zone) (X23-0200 and 2023/ETH01038). The findings will be disseminated through a peer-reviewed journal and conference presentations. Trial registration number The trial was prospectively registered on the Australian New Zealand Clinical Trials Registry (ANZCTR; 12623000934640)

02.
arXiv (quant-ph) 2026-06-15

Multiple-time Quantum Imaginary Time Evolution

arXiv:2512.10875v2 Announce Type: replace Abstract: Quantum Imaginary-Time Evolution (QITE) is a powerful method for preparing ground states on quantum hardware. However, executing QITE has costly measurement budgets for general Hamiltonians. Both fidelity and computational cost are strongly dependent on the definition of suitable local domains and Hamiltonian partitions. In this work, we introduce the Multiple-Time QITE algorithm (MT-QITE). We show how using more than one imaginary time substantially improves the fidelity of the resulting ground state as well as the measurement overhead with respect to the previously published QITE algorithm, while preserving its deterministic character and its independence from ad hoc ansatze. Moreover, unlike QITE and other QITE-based algorithms, MT-QITE is parallelizable, and we show that even in Hamiltonians with non-local interactions, partitioning may entail a computational advantage.

03.
Nature (Science) 2026-06-12

An innovative technology boosts image quality for protein structures

After years of effort, two research teams have developed ‘laser phase plate’ systems that could help cryo-electron-microscopy users to generate high-quality structures for a broad range of proteins. After years of effort, two research teams have developed ‘laser phase plate’ systems that could help cryo-electron-microscopy users to generate high-quality structures for a broad range of proteins.

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

An Exploratory Study of Blood Glucose Estimation from Photoplethysmography Signals using Machine Learning

arXiv:2606.15927v1 Announce Type: new Abstract: Diabetes and extreme blood sugar levels are some of the major health problems faced by humans today across the world. While Continuous Glucose Monitoring (CGM) has emerged as an effective technology for management of diabetes as well as for monitoring blood sugar levels, this technology has traditionally been invasive (that is, requiring the piercing of the skin) and carries the risk of irritation, induration, etc. This highlights the need for accurate and non-invasive CGM methods that can be deployed at scale. With the emergence of various sensing technologies and their integration in wearables like the smart-watch, we now have the capability to continuously monitor body signals like the Photoplethysmogram (PPG) in a non-invasive manner. Having the ability to continuously monitor blood glucose through CGMs and continuously monitor PPG signals through a smart-watch offers an opportunity to get dense data on these two, opening the possibility of building machine learning and deep learning based models to estimate blood glucose level from PPG signals. In this work, we first present a paired dataset comprising continuous PPG signals from a smartwatch along with glucose values recorded using a CGM device. We also present the results of some preliminary experimental explorations performed on our dataset. These preliminary results suggest that some predictive signals may exist, though more exploration is needed with more data from a larger number of individuals. The dataset can be accessed at https://zenodo.org/records/20577959

05.
arXiv (quant-ph) 2026-06-16

Trainable Quantum Channels as Computational Primitives for Quantum Learning

arXiv:2606.15808v1 Announce Type: new Abstract: Variational quantum learning is traditionally constrained to unitary dynamics, often treating quantum channels as detrimental noise. In this work, we reformulate the quantum channels as trainable computational primitives and establish a non-unitary quantum machine learning framework grounded in open-system dynamics. We demonstrate that the outputs of channel-enhanced quantum models form a structured superposition of multiple functional components. Each component is governed by an effective observable whose spectrum can be adaptively modulated during training, a significant departure from the spectral invariance in unitary transformations. Moreover, the proposed framework generalizes conventional unitary quantum models by retaining them as a special case while introducing additional non-unitary degrees of freedom. Furthermore, we reveal that trainable quantum channels enrich the optimization geometry through ensemble-averaged gradient and additional optimization directions induced by the Kraus operators. Empirical evaluations on classification tasks using trainable amplitude-damping and phase-damping channels confirm enhanced optimization dynamics and predictive performance. Our work provides a principled approach for leveraging quantum channels as trainable resources and advances the design of high-performance quantum learning architectures.

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

Semantic-Anchored Evidential Fusion for Domain-Robust Whole-Slide Survival Analysis

arXiv:2606.19966v1 Announce Type: cross Abstract: Whole-slide images (WSIs) are widely used for computational cancer prognosis. However, most existing methods primarily focus on in-domain performance and fail to generalize across clinical centers. This limitation stems from their reliance on pixel-derived representations that are highly susceptible to domain-specific artifacts caused by staining protocols and scanner hardware. We hypothesize that high-level pathology semantics, such as tumor grade and micro-environmental architecture, provide a domain-invariant semantic representation that mirrors the robust diagnostic logic of human pathologists. Therefore, we propose a Semantic-Anchored Evidential Fusion Survival (SAEFS) framework, where SAEFS derives semantic anchors from WSIs via Visual Question Answering (VQA), employs a dual-stream WSI evidence extraction architecture, uses Dirichlet-based Subjective Logic to model uncertainty, and fuses semantic and visual evidence through a cautious conjunction rule to avoid overconfident fusion from correlated sources. Trained exclusively on one source domain and evaluated zero-shot across four unseen domains, SAEFS consistently outperforms state-of-the-art models both in prediction accuracy and reliability, improving the average C-index by 10.2%. Quantitative analyses further show that VQA-derived semantic features exhibit significantly lower cross-center divergence than pixel-derived features, highlighting their robustness for cross-center clinical applications.

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

Conditional Local Importance by Quantile Expectations

arXiv:2411.08821v4 Announce Type: replace-cross Abstract: Global variable importance measures are commonly used to interpret the results of machine learning models. Local variable importance techniques assess how variables contribute to individual observations. Current, popular methods, including LIME and SHAP, provide useful measures of feature contribution in the prediction space, while leaving opportunities for improved characterization of local structure in the model loss space. Additionally, they are not natively adapted for multi-class classification problems. We propose a new model-agnostic method for calculating local variable importance, CLIQUE, that highlights locally dependent relationships, provides improved stability over permutation-based methods, and can be directly applied to multi-class classification problems. Simulated and real-world examples show that CLIQUE emphasizes locally dependent information, captures interaction behavior beyond what can be evaluated by correlations, and assigns zero importance in regions where the response is invariant to changes in variables.

08.
arXiv (CS.CV) 2026-06-17

GeneralVLA-2: Geometry-Aware Reconstruction and Governed Memory for Robot Planning

Generalist vision-language-action systems need object-centric 3D evidence and reusable manipulation experience to plan reliable robot trajectories. GeneralVLA provides a hierarchical interface for converting language and RGB-D observations into 3D end-effector paths, but two bottlenecks remain. First, monocular SAM3D-style object reconstruction can hallucinate pose and unseen geometry, while manipulation benefits from stable object shape when calibrated multi-view observations are available. Second, the original KnowledgeBank mainly retrieves semantically similar snippets and appends new knowledge, which makes it difficult to control memory quality, conflicts, confidence, and geometric relevance. To address the first challenge, we introduce GeoFuse-MV3D, a geometry-prior-guided MV-SAM3D reconstruction branch that verifies external geometry cues with input-view masks, applies soft visual-hull support, performs axis-wise refinement, and fuses only geometry while preserving appearance. To address the second challenge, we upgrade KnowledgeBank into a governed long-term memory system with explicit quality, confidence, lifecycle, verifier, and conflict metadata, together with precision-oriented retrieval. Finally, we evaluate the reconstruction branch on GSO-30 and the memory module on Terminal-Bench 2.0 and SWE-Bench Verified; GeoFuse-MV3D improves over the MV-SAM3D baseline by reducing CD and LPIPS by 2.20% and 2.02% while increasing PSNR and SSIM by 2.36% and 1.03%, and KnowledgeBank improves over ReasoningBank by 4.53% on Terminal-Bench SR and 3.73% on SWE-Bench resolve rate, while reducing AS by 4.95% and 5.65%, respectively. Code: https://github.com/AIGeeksGroup/GeneralVLA-2. Website: https://aigeeksgroup.github.io/GeneralVLA-2.

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

PSCT-Net: Geometry-Aware Pediatric Skull CT Reconstruction via Differentiable Back-Projection and Attention-Guided Refinement

arXiv:2606.19867v1 Announce Type: cross Abstract: Computed Tomography (CT) is essential for diagnosing pediatric craniofacial abnormalities, yet poses radiation risks to developing anatomies. Reconstructing 3D CT from sparse bi-planar X-rays offers a low-dose alternative but is severely ill-posed. Existing methods employ geometry-agnostic feature lifting, naively projecting 2D features into 3D without explicit spatial modeling, causing depth ambiguity and degraded osseous boundaries. We present PSCT-Net, a geometry-aware framework with differentiable back-projection. Differentiable back-projection establishes a spatially faithful volumetric prior, alleviating depth ambiguity. An Attention-Guided Projection (AGP-3D) module then learns non-linear voxel-wise correspondences between 2D regions and 3D locations. A Bidirectional Mamba (BiM-3D) module captures long-range volumetric dependencies with linear complexity. We further curate a private institutional pediatric skull CT cohort, PedSkull-CT, comprising normal and pathological cases for internal evaluation, addressing the gap in adult-centric, trunk-focused datasets.

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

A Complexity Measure for Active Learning in Multi-group Mean Estimation

arXiv:2606.14690v1 Announce Type: new Abstract: We study a max-risk objective for active learning in a multi-group mean estimation $d$-armed bandits: a learner adaptively allocates a budget of $T$ samples across $d$ groups to minimize the worst-case uncertainty index $\max_{k\in[d]}\sigma_k^2/n_k$, where $\sigma_k$ is the standard deviation of the distribution of arm $d$, and $n_k$ is the number of times arm $d$ is sampled. We develop a local minimax framework and prove the first general lower bound for this objective, valid for any finite-variance hypothesis class. The bound separates difficulty into three orthogonal factors: a budget term, a heteroscedasticity index measuring how unevenly the uncertainty is spread across arms, and a model-dependent complexity measure, the Variance Local Curvature ($\mathrm{VLC}$), which captures how much information a local change of variance creates inside the hypothesis class. For smooth classes, the $\mathrm{VLC}$ is a reparametrization of a variance–Fisher information, with closed-form values for common families. Benchmarking against the strongest available upper bound shows near-optimality up to logarithmic factors in broad regimes, and pinpoints a systematic gap in highly heterogeneous instances. Our proof introduces two key ingredients: a loss-induced $\ell_1$ geometry on the decision space, and a representation-based instance generator that reduces hard-instance construction to an explicit random matrix calculation.

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

How Well Do Large Language Models Capture Human Personality?

arXiv:2606.18263v1 Announce Type: cross Abstract: Large language models (LLMs) are increasingly used to simulate human populations via persona prompting, often under the assumptions that richer persona descriptions improve behavioral fidelity, similarly sized attribute combinations are equally simulatable, and persona definitions generalize across tasks. In this work, we formalize these assumptions and systematically evaluate them across multiple architectures, scales, and simulation settings. We identify a fundamental limitation we term persona manifold collapse, where increasingly expressive persona specifications lead to systematic contraction of representational and behavioral diversity. Across models, increasing persona complexity consistently reduces inter-persona separation in latent space and weakens behavioral differentiation in downstream simulation tasks. These effects persist across multiple analyses as richer personas fail to preserve human subgroup disagreement, performance varies across attribute combinations of similar size, and adding descriptive detail often degrades rather than improves simulation fidelity. Surprisingly, simple Age-Gender personas consistently outperform richly specified Ideal Customer Profiles (ICPs) across industries, achieving substantially higher downstream prediction accuracy. We find that collapse is not uniform across attributes. Certain combinations remain behaviorally stable and preserve stronger alignment with human responses, forming localized regions we term alignment bridges. Together, our results provide empirical and conceptual foundations for understanding the limits of persona-conditioned simulation, highlighting the need for representation-aware persona construction rather than increasing persona expressivity alone.

12.
arXiv (CS.CL) 2026-06-17

Security and Privacy Prompts in the Wild: What Users Ask LLMs and How LLMs Respond

Large language models (LLMs) are widely used to fulfill users' information needs; users ask LLMs about the weather, pose educational questions, and consult them for legal assistance. One particularly understudied area is digital security and privacy (S&P), where users may seek LLMs' help on how to secure their online accounts or protect their computers from cyber attacks. To the best of our knowledge, no prior study has collected or analyzed the S&P questions users ask LLMs; prior research on LLM response quality relied on expert-authored S&P misconceptions or FAQs rather than user queries. Drawing from WildChat, a dataset of 3.2M user-LLM conversations collected in the wild, our study identifies 14,727 S&P prompts and categorizes them into nine categories covering a wide range of S&P topics. From the S&P prompts, we sampled 450 and performed a thematic analysis to characterize the S&P questions users ask LLMs. Separate from the thematic analysis, we curated 270 advice-seeking S&P prompts, where users ask for recommendations, guidance, or specific S&P information. We measured LLM response quality and consistency when posing the prompt to LLMs 10 times. We found that commercial LLMs outperform open-weight models (GPT 5.5 provided "good enough" responses on 98% of prompts; Llama 4 on 47%). However, among prompts that received high-quality responses on average, commercial models sometimes produce contradictory responses across runs, risking confusing or misleading users.

13.
arXiv (CS.CV) 2026-06-16

Learning Sparse Latent Predictive Foundation Model for Multimodal Neuroimaging

Brain MRIs are routinely acquired as multiple complementary sequences with unique contrast weighting, including T1-weighed imaging (T1w) anatomic and fluid-sensitive T2-weighted (T2w) contrasts. However, methods for learning unified representations across the multitude of MRI contrast mechanisms at health-system scale are lacking. In this study, we introduce Neuro-JEPA, a sparse multimodal neuroimaging foundation model that combines a latent predictive objective with a Mixture-of-Experts architecture to encode brain MRI across core T1w, T2w, and fluid-suppressed FLAIR imaging (FLAIR). We further provide a systematic methodological study of architectural, masking, objective, and sparsity design choices beneficial for robust neuroimaging multimodal representation learning. Neuro-JEPA was pretrained on 1,551,862 scans from 428,647 studies after modality-specific preprocessing with data curation across three core structural brain MRI sequences. We evaluated the learned representations across clinical and research settings, including 25 tasks from three health systems: NYU Langone, NYU Long Island, and Massachusetts General Hospital, and 22 tasks from 12 public datasets, covering unimodal, multimodal and cross-domain evaluation configurations. Across these benchmarks, existing neuroimaging foundation models showed inconsistent gains over a simple convolutional neural network (CNN) baseline, whereas Neuro-JEPA achieved stronger and more consistent performance across all evaluated settings. These results establish a scalable methodological framework for multimodal neuroimaging representation learning and highlight the need for foundation model evaluation protocols that include simple baselines, clinically heterogeneous cohorts and controlled multimodal comparisons.

14.
arXiv (CS.AI) 2026-06-17

MathVis-Fine: Aligning Visual Supervision with Necessity via Progressive Dependency-Guided Training for Multimodal Mathematical Reasoning

arXiv:2606.17888v1 Announce Type: new Abstract: Chain-of-Thought (CoT) reasoning has extended from purely linguistic domains to multimodal scenarios; however, existing approaches often treat visual inputs as homogeneous or auxiliary signals, failing to capture the intricate and sample-specific dependencies between text and images in mathematical problem-solving. This gives rise to two core issues: first, the supervisory signals for visual content are generalized and coarse-grained, lacking adaptation to the actual necessity of visual information in each sample; second, training feedback becomes inaccurate when visual rewards are uniformly applied without distinguishing the complementary relationships among inputs. These limitations hinder models from achieving precise multimodal reasoning. In this work, we propose a framework for modeling fine-grained visual dependencies in mathematical reasoning. We first construct the MathVis-Fine dataset, augmenting fine-grained visual annotations with visual dependency ratings. Building upon this dataset, we introduce a two-stage progressive visual enhancement training paradigm that balances answer correctness rewards and visual grounding rewards according to the intrinsic visual dependency level of each sample, thereby mitigating reward bias and improving supervision accuracy. Extensive experiments demonstrate that the MathVis-Fine framework effectively enhances visual perception progressively based on visual dependency, offering a more precise training framework for multimodal mathematical reasoning. We will release the dataset upon acceptance.

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

TeleMorpher: Toward Robust Simultaneous Motion-Location Editing

arXiv:2606.19676v1 Announce Type: cross Abstract: Diffusion models have achieved remarkable success in image and video generation and editing. While recent studies have extended these efforts toward motion editing, simultaneously transforming both motion and location-despite its practical importance-remains largely unexplored. To better understand robust motion-location editing, we first analyze the fundamental factors that degrade its quality. Based on this analysis, we propose TeleMorpher, one of the first one-shot frameworks to the best of our knowledge, for simultaneous motion-location editing. Our approach leverages motion priors, a target motion-centric video generated from an off-the-shelf model as motion-editing guidance, and the ground truth motion to enable more controllable and precise motion-location editing. Via this, our framework works as follows: (1) we first disentangle the protagonist and the background via pre-trained segmentation and inpainting models. (2) Then, we introduce a training-free pose warping that edits the protagonist's motion with the motion prior as the guidance. (3) The result of warped motion video is directly injected into a baseline motion editor during inference, mitigating the difference between source and target motions while preserving the appearance of the source video. (4) To enhance the reliability of quantitative evaluations, we propose two new LPIPS-based metrics that measure the background consistency before and after the motion editing and the fidelity of motion editing performance via measuring the difference between the extracted protagonist's skeletons from source and target videos. Experiments with in-the-wild videos and the TaiChi dataset demonstrate that TeleMorpher achieves superior performance across both quantitative and qualitative measurements (real-human evaluation), underscoring its effectiveness.

16.
arXiv (quant-ph) 2026-06-15

Experimental violation of a Bell-like inequality for causal order

arXiv:2506.20516v2 Announce Type: replace Abstract: Quantum mechanics is compatible with scenarios where physical processes happen in an indefinite order. In theory, this feature could be detected through violations of inequalities on the observed correlations, analogous to Bell inequalities. However, experimental demonstrations of such violations have been missing until recently due to the complexity of the required setup. Here we report an experimental violation of a Bell-like inequality involving the correlations of four parties, one of which is spacelike separated from the others. Our demonstration employs 3 km fiber spools to simulate spacelike separation, and achieves high-speed operations in photonic time-bin encoding, nanosecond synchronization, and accurate temperature stabilization. These experimental advances enable a violation by 5.7 standard deviations and open a path towards a certification of indefinite order in conditions that guarantee spacelike separation with existing state-of-the-art devices. However, the certification is not device-independent, as it relies on knowledge about the setup to exclude bidirectional signaling–a loophole inherent to implementations in classical acyclic spacetimes, which may be resolved in future quantum-spacetime tests.

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

Conformal Path Reasoning: Trustworthy Knowledge Graph Question Answering via Path-Level Calibration

Knowledge Graph Question Answering (KGQA) offers grounded, interpretable reasoning, but existing methods often fail to provide reliable coverage guarantees over retrieved answers. While Conformal Prediction (CP) offers a principled framework for producing prediction sets with statistical guarantees, prior conformal KGQA methods suffer from two critical pitfalls: violated coverage guarantees due to invalid calibration, and weak score discriminability that yields excessively large prediction sets. We propose Conformal Path Reasoning (CPR), a novel trustworthy KGQA framework built on two key innovations. First, query-level conformal calibration over path-level scores preserves exchangeability to ensure valid coverage guarantees. Second, we introduce the Residual Conformal Value Network (RCVNet), a lightweight module trained via PUCT-guided exploration to learn discriminative path-level nonconformity scores. Extensive experiments show that CPR significantly improves the Empirical Coverage Rate by 45% while reducing prediction set size by 52% on average over conformal baselines across benchmark datasets, highlighting its effectiveness for reliable conformal reasoning over knowledge graphs.

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

Library-Aware Doubles and Iterative Repair for Large Language Model-Generated Unit Tests in OpenSIL Firmware

arXiv:2606.19725v1 Announce Type: cross Abstract: Validating changes in low-level C firmware is expensive because unit tests (UTs) are fragile under strict build constraints, where missing headers, unresolved symbols, and dependency mismatches frequently prevent compilation and linking. This study introduces an automated UT authoring workflow for the Open-Source Silicon Initialization Library (openSIL) firmware codebase maintained by Advanced Micro Devices (AMD) that reduces manual effort through a large language model (LLM) guided multi-agent pipeline. The workflow combines automated generation of test scaffolds, library-aware creation or reuse of stubs, mocks, and fakes, and an iterative compile-dispatch repair loop driven by build logs and line-coverage feedback. We evaluate the approach using compilation success, repair iterations, dispatch success, and line coverage, with time, cost, and token usage as secondary measures. Across 76 functions under test, the workflow generated compilable UTs for 73 functions. In a configuration without line coverage guidance or retrieval augmentation, mean line coverage reached 73.9%. On a 48-function subset evaluated under both configurations, mean line coverage reached 98.8% with line-coverage guidance alone and reached 94.7% when combined with vector-database retrieval. Results show that automated generation-and-repair pipelines can substantially improve UT creation efficiency and coverage for constrained firmware environments while reducing manual debugging effort.

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

Artemis: Anatomy-Resolved inTervention for Eliminating Multimodal NeuroImage confounderS

arXiv:2606.18287v1 Announce Type: new Abstract: Multimodal neuroimaging, integrating functional connectivity from fMRI and structural connectivity from DTI, enables non-invasive analysis of brain networks using graph neural networks. However, demographic factors such as age and sex systematically confound the relationship between brain connectivity and clinical outcomes, causing GNNs to exploit spurious shortcuts rather than learning causally invariant representations. While recent causal GNN methods introduce causality at the graph-modeling level, their causal mechanisms remain domain-agnostic without accounting for the real-world confounders inherent in clinical neuroimaging data. Moreover, brain networks are constructed from atlas-based parcellations where each region exhibits distinct sensitivity to demographic factors, necessitating region-aware adjustment. We propose Artemis, a region-level causal framework that bridges this gap with causal intervention at each brain region independently by learning region-specific confounder representations with lightweight parameters. Our adjustment comprehensively utilized the multimodal functional and structural features for graph reasoning as a plug-in module compatible with arbitrary GNN backbones. Experiments on three benchmarks, ADNI for disease diagnosis, OASIS for dementia staging, and HCP for sex classification, demonstrate consistent improvements over representative GNN-based baselines. Multiple supporting experiments further demonstrate statistical significance and neuroscientific interpretability.

20.
medRxiv (Medicine) 2026-06-18

AlphaGenome identifies a deep intronic variant in a family with PLA2G6-associated neurodegeneration: Closing the diagnostic gap in rare genetic diseases

A molecular diagnosis remains out of reach for a substantial subset of patients with clinically recognizable Mendelian disorders, even after comprehensive next-generation sequencing. Causal variants in non-coding regions are difficult to detect and interpret using standard pipelines. Deep intronic variants that disrupt splicing are a known but underexplored source of pathogenic alleles, and systematic tools to evaluate them at scale have only recently emerged. We aimed to resolve an incomplete genetic diagnosis in two siblings with early-onset parkinsonism, prominent neuropsychiatric features, and autonomic dysfunction consistent with PLA2G6-associated neurodegeneration (PLAN), an autosomal recessive condition. Prior clinical exome sequencing, genome sequencing, Multiplex Ligation-dependent Probe Amplification (MLPA), and long-read sequencing had identified only a single heterozygous PLA2G6 missense variant, c.2132C>G (p.Pro711Arg). We used AlphaGenome to score 91 non-coding variants shared among the affected siblings and their father within 1 megabase of the PLA2G6 locus. The deep-learning model identified an intronic variant (c.2034+355G>A) that was predicted to create a cryptic splice acceptor site that could result in inclusion of a 160-bp cryptic exon. Tissue-specific predictions indicated the aberrant splicing would be detectable in blood, confirmed by junction-spanning RNA-seq reads from an unrelated carrier. This analysis completed a compound heterozygous PLAN diagnosis nearly two decades after symptom onset and demonstrates the utility of sequence-to-function models. Systematic integration of tools like AlphaGenome into rare disease workflows offers a practical, low-barrier route to closing the diagnostic gap for patients with compelling Mendelian phenotypes and incomplete genetic diagnoses.

21.
arXiv (CS.AI) 2026-06-18

DN-Hypo-Pipeline: An AI-Driven Workflow for Hypothesis Generation via Large Language Models and Scientific Explanations

arXiv:2606.08532v2 Announce Type: replace Abstract: A scientific hypothesis is the first step in research and undergoes experimental validation, yet it also reflects a deep understanding of and reasoning about scientific phenomena. We introduce DN-Hypo-Pipeline, an AI-powered workflow based on large language models, designed to support structured scientific thinking and hypothesis generation by leveraging scientific explanations as prior knowledge. This pipeline assists researchers in deriving novel hypotheses from existing literature. Given the explanandum (i.e., the conclusion) of a research paper, it identifies underlying laws, theories, and principles, and reconstructs a new, yet-to-be-verified explanation for the observed phenomenon. We evaluated DN-Hypo-Pipeline in the field of data science modeling using three highly cited papers. Statistical inference, supported by both LLM-as-judge assessment and human expert evaluation, demonstrates that our pipeline is more effective than direct generation methods. Additionally, we validated the two highest-scoring generated hypotheses by developing corresponding novel algorithms, which outperformed the baseline models presented in the original papers. Beyond application in data science, DN-Hypo-Pipeline provides a theoretical framework that not only encompasses theory-guided data science modeling methods but also reveals a more fundamental structure of the modeling process. Moreover, this approach is essentially a generalization of theory-guided modeling, offering potential for extension to other domains and across a broader range of scientific disciplines.

22.
arXiv (CS.LG) 2026-06-15

Decoupled Latent Optimization of Diffusion Models for Full Waveform Inversion

arXiv:2606.14139v1 Announce Type: new Abstract: Full waveform inversion (FWI) recovers subsurface velocity from seismic recordings by solving a severely ill-posed, nonconvex PDE-constrained optimization. Classical regularizers stabilize the inversion but fail to reproduce realistic geological structures; recent diffusion-prior methods improve realism at the cost of a fragile trade-off between data fidelity and prior consistency. We propose Decoupled Latent Optimization (DLO), which relaxes the standard latent-optimization formulation into a quadratic-penalty objective over an auxiliary physical variable and a latent variable. The data-fidelity gradient acts in physical space, the diffusion sampler contributes only through a decoded prior sample, and the standard smoothed-velocity initialization of classical FWI is preserved. On the OpenFWI benchmark, DLO outperforms classical regularizers and existing diffusion-based methods under clean, noisy, and missing-trace acquisitions. The prior, trained on 70*70 OpenFWI models, transfers directly to the Marmousi and Overthrust benchmarks, where DLO recovers intricate fault structures and remains robust to initialization smoothing and measurement noise.

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

Through-Foliage Surface-Temperature Reconstruction for Early Wildfire Detection

We present a method to reconstruct surface temperatures through forest vegetation by combining signal processing and machine learning, enabling fully automated aerial wildfire monitoring with drones for early fire detection. Synthetic aperture (SA) sensing reduces canopy occlusion but introduces thermal blur. To overcome this, we train a visual state space model to recover subtle thermal signals of partially occluded soil and fire hotspots from blurred data. To address limited real-world training data, we generate realistic surface temperature simulations using a latent diffusion model, temperature augmentation, and procedural thermal forest modeling. On simulated datasets, our method reduces RMSE by 2-2.5 versus conventional thermal and uncorrected SA imaging; in field experiments on hotspots, RMSE improved by 12.8-fold and 2.6-fold, respectively. Our approach also generalizes to other thermal signals, including human signatures, capturing morphology and extent – critical where simple thresholding fails – while conventional imaging struggles with partial occlusion.

24.
arXiv (CS.AI) 2026-06-11

Towards Responsibly Non-Compliant Machines

arXiv:2606.12147v1 Announce Type: new Abstract: We consider the problem of engineering autonomous intelligent agents that are capable to responsibly not comply with user requests. We argue that machine non-compliance comes in many different forms, and sketch the issues we should pursue on the road of accomplishing responsibly non-compliant intelligent machines. We anchor responsible non-compliance in justifications for task refusal, pathways to override the non-compliance, as well as careful tracking of security risks and liability transfers.

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

MedSynth: Realistic, Synthetic Medical Dialogue-Note Pairs

Physicians spend significant time documenting clinical encounters, a burden that contributes to professional burnout. To address this, robust automation tools for medical documentation are crucial. We introduce MedSynth – a novel dataset of synthetic medical dialogues and notes designed to advance the Dialogue-to-Note (Dial-2-Note) and Note-to-Dialogue (Note-2-Dial) tasks. Informed by an extensive analysis of disease distributions, this dataset includes over 10,000 dialogue-note pairs covering over 2000 ICD-10 codes. We demonstrate that our dataset markedly enhances the performance of models in generating medical notes from dialogues, and dialogues from medical notes. The dataset provides a valuable resource in a field where open-access, privacy-compliant, and diverse training data are scarce. Code is available at https://github.com/ahmadrezarm/MedSynth/tree/main and the dataset is available at https://huggingface.co/datasets/Ahmad0067/MedSynth.