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

Knowing When to Ask: Self-Gated Clarification for Hierarchical Language Agents

arXiv:2606.11349v1 Announce Type: new Abstract: In hierarchical reasoning, failures often originate at intermediate decision points where the agent commits to a wrong branch without recognizing that it lacks critical information. Rather than treating clarification as an external uncertainty trigger, we propose ACTION-RATING, a formulation that places it inside the agent's action space on a shared ordinal scale with navigation, so that asking competes directly with acting at every decision point and help-seeking becomes observable at intermediate states. Two structurally distinct information-seeking modes emerge from the agent's own ratings: mandatory (no viable branch) and opportunistic (residual uncertainty despite a leading candidate). On Harmonized Tariff Schedule classification (30,000-node taxonomy, three benchmarks, 9~LLMs across 4 families), we observe a regime shift from mandatory to opportunistic clarification, with Information-Seeking Effectiveness (ISE), a local diagnostic defined as the fraction of help interactions followed by a correct next navigation step (not a final-task metric), rising from 50% to 74%. Three diagnostic contrasts fail to reproduce this structure. A separability test shows that the information-seeking pattern (mode split, ISE ranking) persists when answer quality is degraded (-18.8% accuracy), supporting an empirical separation between where an agent seeks help and the quality of the help it receives. Under the controlled answer channel, accuracy gains reach +16.2% at 10-digit; we read this as an upper bound on what better localization could unlock, not a deployment estimate.

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

Discrete optimal transport is a strong audio adversarial attack

arXiv:2509.14959v3 Announce Type: replace-cross Abstract: In this paper, we investigate discrete optimal transport (DOT) as a black-box attack against modern automatic speaker verification (ASV) and anti-spoofing countermeasure (CM) systems. Our attack operates as a post-processing distribution-alignment step. Frame-level WavLM embeddings of generated speech (or another person speech) are aligned to an unpaired bona fide speech pool using entropic optimal transport and a top-k barycentric projection, followed by neural vocoding. Unlike gradient-based attacks, the proposed method requires no access to model parameters, gradients, or training data. Experiments on ASVspoof2019 and ASVspoof5 demonstrate that DOT attack substantially increases CM EER and substantially degrades ASV performance across multiple spoofing attacks. The attack transfers across datasets and remains effective after CM fine-tuning. Analysis using speaker similarity, Fréchet Audio Distance, and visualization of embedding distributions suggests that DOT succeeds by shifting source speech toward bona fide regions of the representation space rather than by maximizing speaker similarity. These results indicate that optimal-transport-based distribution alignment represents a previously underexplored attack vector for contemporary ASV and anti-spoofing systems.

04.
arXiv (quant-ph) 2026-06-16

Long-range nonstabilizerness of topologically encoded states from mutual information

arXiv:2605.22424v2 Announce Type: replace Abstract: We study long-range nonstabilizerness (LRN), namely the obstruction to remove nonstabilizerness with shallow-depth local quantum circuits. In one-dimensional settings, the mutual information between disconnected spatial regions has proven to be a powerful tool to diagnose LRN. In this work, we focus on encoded states of two-dimensional topologically-ordered systems, and explore the ability of the mutual information to serve as a diagnostic of LRN. Focusing on the concrete setting of lattice models defined on a torus, we show that information about LRN can be gained from the analysis of the mutual information between non-overlapping regions containing non-contractible loops, and of the change of such mutual information under modular real-space transformations. We exemplify this idea in the toric code and the non-abelian string-net model with doubled Fibonacci topological order. In the former case, we show that the mutual information provides a full classification, certifying LRN for all encoded non-stabilizer states. In the latter case, instead, our approach does not lead to a full classification, as it detects LRN for all states except from a finite subset with special transformation properties under the modular group. Finally, we discuss how our results on LRN constrain the logical gates that can be implemented fault-tolerantly on the torus.

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

Deep Learning-Driven Inverse Design of Doherty Power Amplifiers Using Pixelated Combiners and Dual-State Impedance Synthesis

arXiv:2606.18395v1 Announce Type: cross Abstract: The output combiner of a Doherty power amplifier (PA) integrates load modulation, impedance matching, and phase compensation within a single network, making its design and synthesis highly challenging. In this paper, we propose a three-port Doherty combiner design methodology that combines deep convolutional neural networks (CNNs), pixelated layout representations, and genetic algorithms (GA) with dual-state impedance synthesis to address both peak and back-off power conditions. As a proof of concept, two GaN HEMT Doherty PA prototypes incorporating three-port pixelated combiners are designed and fabricated. Both prototypes achieve a measured saturated output power exceeding 44.2 dBm with peak drain efficiency above 71.2% within 2.6-2.8 GHz. Furthermore, a drain efficiency as high as 64% is measured at the 6-dB back-off level. After applying digital predistortion, each prototype achieves an adjacent channel leakage ratio (ACLR) better than -51.3 dBc.

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

Slots, Transitions, Loops: Learning Composable World Models for ARC

ARC tests in-context rule induction: given a few input-output demonstrations, a model must infer the hidden rule and apply it to a new query. While many approaches express ARC rules through language, code, or symbolic programs, ARC itself is visual-symbolic: rules appear as grid transitions over objects, colors, shapes, and spatial relations. We introduce Loop-OWM, an object-centric world-modeling architecture that learns these rules as composable transitions over structured states. It combines color-prototype slots, demonstration-conditioned task summaries, and a looped transition model with dense propagation and slot-conditioned correction. On both ARC-1 and ARC-2, Loop-OWM outperforms non-looped and looped baselines with comparable or fewer parameters. These results suggest that ARC rules can be learned not only as language descriptions or searched programs, but also as transitions over visual-symbolic world states.

08.
arXiv (CS.AI) 2026-06-12

PolicyGuard: Towards Test-time and Step-level Adversary Defense for Reinforcement Learning Agent

arXiv:2606.12896v1 Announce Type: cross Abstract: While real-world applications of reinforcement learning (RL) are becoming increasingly popular, the security of RL systems deserve more attention and exploration. In particular, recent work has revealed that RL agents are vulnerable to backdoor attacks, where a victim agent behaves normally under standard conditions but executes malicious actions when a specific trigger is activated. Existing backdoor defenses for RL either require access to the agent's internal parameters, operate only at the model or trajectory level, or are limited to specific attack types. To ensure the security of RL agents, we propose \texttt{PolicyGuard}, a test-time step-level backdoor defense which leverages Gaussian Process (GP) posterior variance and adapts pseudo trajectories to enable uncertainty computation for individual time step. Besides, we also provide theoretical foundations to explain the efficacy of GP posterior variance. Extensive experiments across seven RL games demonstrate that PolicyGuard achieves state-of-the-art detection performance in most cases, with average AUROC of 0.856 for perturbation-based attacks and 0.859 for adversary-agent attacks.

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

MimicIK: Real-Time Generative Inverse Kinematics from Teleoperation with FK Consistency

arXiv:2606.15148v1 Announce Type: cross Abstract: Inverse kinematics (IK) remains a critical bottleneck for real-time robot manipulation. Classical numerical solvers achieve high geometric precision but often suffer from discontinuous branch switching and unstable behavior near kinematic singularities during closed-loop deployment. Meanwhile, learned IK approaches frequently struggle to balance spatial accuracy, motion smoothness, and real-time efficiency, particularly when trained on noisy human teleoperation data. We present MimicIK, a real-time generative inverse kinematics framework that learns smooth and robust joint-space motion priors from teleoperation demonstrations through conditional flow matching. Given the current joint configuration and a target end-effector pose, MimicIK predicts continuous delta-joint commands using an efficient two-step iterative refinement process based on a Minimal Iterative Policy (MIP) backbone. To enforce physical consistency, we further introduce an FK consistency loss, a differentiable forward-kinematics regularization that penalizes task-space deviations from the target pose during training. We evaluate MimicIK on a real-world 6-DOF robot dataset containing 8,848 teleoperation demonstrations. MimicIK achieves a mean position error of 4.65 mm, a 10 mm success rate of 92.01\%, and a trajectory spike rate of only 7.99\%. Compared with a UNet diffusion baseline, our method improves both spatial accuracy and motion smoothness while reducing inference latency from 21.66 ms to 6.74 ms. Furthermore, unlike deterministic MLP baselines that catastrophically diverge under out-of-distribution deployment, MimicIK remains stable near singular configurations and enables robust 20 Hz real-time control on deployment hardware.

10.
arXiv (CS.AI) 2026-06-19

cAPM: Continual AI-Assisted Pace-Mapping with Active Learning

arXiv:2606.19373v1 Announce Type: cross Abstract: Ventricular tachycardia is a life-threatening rhythm disorder and a major cause of sudden cardiac death. Pace-mapping is a clinical procedure for identifying the intervention target during catheter ablation of VT. It requires clinicians to pace different sites in the ventricles and rapidly interpret the resulting electrocardiograms to determine where to pace next or whether a target site has been identified. Active learning AI models have been proposed to guide clinicians to the next pacing site, showing promise in reducing the number of pacing sites and improving the efficiency of pace-mapping. Existing methods require retraining each target without the ability to transfer knowledge across multiple VTs within the same patient or across patients. We introduce cAPM for continuous AI-assisted pace-mapping to capture and transfer knowledge accumulated from past pace-mapping data to reduce the number of pace-mapping data needed for future target VTs. This is made possible by a task-agnostic surrogate neural network that learns the mapping from pacing sites to 12-lead ECG morphology, an active-learning strategy that refines this surrogate model by selecting the most informative pacing site for each target, and a continual learning strategy to do so sequentially while retaining knowledge from prior targets. Evaluated on an in-silico testbed consisting of sequentially-presented localization tasks across different physiological conditions and ventricular geometries, cAPM with and without replay of past data samples achieved an 81% probability of localizing within clinical tolerance (5 mm accuracy) using 4.5 pace-mapping sites, compared to the state-of-the-art active-learning method achieving 38% probability using 13.7 pacing sites. These results provide a strong basis for preparing cAPM towards in-vivo preclinical and clinical studies where it can be used to guide pace-mapping.

11.
arXiv (CS.LG) 2026-06-19

Quantum-classical physics-informed Kolmogorov-Arnold networks for PDEs

arXiv:2606.20326v1 Announce Type: new Abstract: We develop QCPIKAN, the first quantum-classical physics-informed Kolmogorov-Arnold network designed to solve partial differential equations (PDEs). Built upon Chebyshev-polynomial KAN layers and parameterized quantum circuits, this hybrid framework embeds physical constraints into the training loss to enforce physical consistency. Our theoretical investigations grounded in approximation theory prove that this design accelerates high-frequency error convergence to an exponential rate and effectively mitigates numerical dispersion. We validate the framework across three typical seepage scenarios in porous media, including single-phase flow, component transport and two-phase flow. Compared with existing quantum-classical physics-informed neural networks, QCPIKAN achieves superior performance in global prediction accuracy, local error control, dynamic evolution tracking and displacement front localization. This work provides a robust and efficient alternative for solving complex PDEs.

12.
arXiv (quant-ph) 2026-06-15

Dynamically frozen long-distance entanglement via non-Hermitian PT-symmetric systems

arXiv:2606.14177v1 Announce Type: new Abstract: In distributed quantum networks, interacting spin systems can mediate the generation of highly entangled links between distant nodes. We investigate the role of effective parity-time (PT)-symmetric non-Hermitian spin-1/2 bulks weakly coupled to two quantum links, obtained due to the environmental interactions affecting both the bulk and the links. Focusing on effective non-Hermitian nearest-neighbor (NN) Su-Schrieffer-Heeger (SSH) models, we analyze how non-Hermiticity influences the dynamical formation of long-distance entanglement (LDE). For a paradigmatic model consisting of a quantum XX bulk subjected to imaginary staggered magnetic fields, we analytically determine the exceptional points arising from the resulting bulk-mediated interactions between the links. Combining analytical and numerical methods, we demonstrate that an initially fully separable state can dynamically evolve into highly entangled link states near these exceptional points in the broken regime. Further, after optimizing over time and system parameters, near-unit time-averaged entanglement between the links emerges under weak imaginary magnetic fields and bulk-link couplings, which cannot be attained in the corresponding Hermitian systems. Moreover, the non-Hermitian dynamics exhibit a freezing of high entanglement in the vicinity of exceptional points, a feature absent in Hermitian counterparts. We also identify regimes of long-range interaction strengths that yield a higher time-averaged entanglement than the corresponding NN models. Furthermore, we establish that LDE persists in the stationary regime, highlighting the promise of engineered non-Hermitian dynamics for realizing robust and frozen entangled links in quantum networks.

13.
arXiv (CS.CL) 2026-06-18

MORTAR: Multi-turn Metamorphic Testing for LLM-based Dialogue Systems

With the widespread application of LLM-based dialogue systems in daily life, quality assurance has become more important than ever. Recent research has successfully introduced methods to identify unexpected behaviour in single-turn testing scenarios. However, multi-turn interaction is the common real-world usage of dialogue systems, yet testing methods for such interactions remain underexplored. This is largely due to the oracle problem in multi-turn testing, which continues to pose a significant challenge for dialogue system developers and researchers. In this paper, we propose MORTAR, a metamorphic multi-turn dialogue testing approach, which mitigates the test oracle problem in testing LLM-based dialogue systems. MORTAR formalises the multi-turn testing for dialogue systems, and automates the generation of question-answer dialogue test cases with multiple dialogue-level perturbations and metamorphic relations (MRs). The automated MR matching mechanism allows MORTAR more flexibility and efficiency in metamorphic testing. The proposed approach is fully automated without reliance on LLM judges. In testing six popular LLM-based dialogue systems, MORTAR reaches significantly better effectiveness with over 150\% more bugs revealed per test case when compared to the single-turn metamorphic testing baseline. Regarding the quality of bugs, MORTAR reveals higher-quality bugs in terms of diversity, precision and uniqueness. MORTAR is expected to inspire more multi-turn testing approaches, and assist developers in evaluating the dialogue system performance more comprehensively with constrained test resources and budget.

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

One Step Closer to Ground Truth: A Multi-Scale Residual-Aware Representation Learning Pipeline for Predicting Time Series Data

arXiv:2606.10678v2 Announce Type: replace Abstract: Transformer-based models have emerged as leading paradigms in time-series forecasting in recent years, employing self-attention mechanisms to capture long-range dependencies. Despite their success, these single-stage forecasting architectures exhibit persistent systematic residual biases arising from structural discrepancies, unmodeled stochastic components, or inadequate multi-scale temporal representations. This limitation persists when residuals are treated as irreducible noise, precluding adaptive correction of structured error patterns. To address this limitation, we introduce a two-stage, model-agnostic framework that explicitly decouples forecasting and residual learning into distinct stages of representation learning. A base transformer first generates the initial predictions. Subsequently, a dedicated meta-corrector dynamically models structured error patterns across multivariate channels, preserves cross-variable dependencies, and iteratively refines the residual bias of the base transformer. By formalizing this pipeline as a hypothesis space expansion, our framework addresses approximation limitations inherent in single-stage architectures, removes reliance on restrictive assumptions, and enables end-to-end learning of complex error dynamics. Evaluated on eight popular benchmark datasets using established protocols, our approach achieves state-of-the-art performance, with significant improvements in standard metrics (MSE, MAE). The results demonstrate the framework's ability to mitigate systematic biases and enhance robustness to complex temporal dynamics, advancing the practical applicability of transformer-based forecasting models.

15.
arXiv (CS.CL) 2026-06-17

When Tables Go Crazy: Evaluating Multimodal Models on French Financial Documents

Vision-language models (VLMs) perform well on many document understanding tasks, yet their reliability in specialized, non-English domains remains underexplored. This gap is especially critical in finance, where documents mix dense regulatory text, numerical tables, and visual charts, and where extraction errors can have real-world consequences. We introduce Scribe Finance, the first multimodal benchmark for evaluating French financial document understanding. The dataset contains 1,204 expert-validated questions spanning text extraction, table comprehension, chart interpretation, and multi-turn conversational reasoning, drawn from real investment prospectuses, KIDs, and PRIIPs. We evaluate six open-weight VLMs (8B-124B parameters) using an LLM-as-judge protocol. While models achieve strong performance on text and table tasks (85-90% accuracy), they struggle with chart interpretation (34-62%). Most notably, multi-turn dialogue reveals a sharp failure mode: early mistakes propagate across turns, driving accuracy down to roughly 50% regardless of model size. These results show that current VLMs are effective for well-defined extraction tasks but remain brittle in interactive, multi-step financial analysis. Scribe Finance offers a challenging benchmark to measure and drive progress in this high-stakes setting.

16.
arXiv (CS.LG) 2026-06-19

GB-LSR: A Fast Local Spectral Image Representation with a Single Global Bandwidth for Continuous Reconstruction and Super-Resolution

arXiv:2606.19617v1 Announce Type: cross Abstract: We present GB-LSR (Global-Bandwidth Local Spectral Representation), a fixed-grid local spectral representation for continuous image reconstruction. The image domain is partitioned into non-overlapping square patches, each carrying coefficients for a truncated Fourier basis predicted from shared convolutional-encoder features. A single trainable scalar bandwidth is shared globally across all patches and images, and reconstruction at any continuous coordinate is a fixed-size basis contraction whose cost is independent of image size. We study three bandwidth-handling variants: a trainable global scalar (main), a fixed global scalar, and a per-patch bandwidth field. On a standardized native-reconstruction benchmark across Kodak, Set14, and Urban100, the main variant outperforms matched-budget amortized LIIF / LTE / WIRE re-implementations by 2.8-3.6 dB PSNR and 0.11-0.15 LPIPS, while running at roughly one-quarter of the slowest baseline's inference cost. The single global scalar suffices empirically: per-patch adaptive-bandwidth alternatives do not improve over it on either a closed-form locality diagnostic or an end-to-end ablation. In a separate arbitrary-scale super-resolution (ASR) extension, GB-LSR achieves competitive PSNR-Y under a canonical-style SR protocol and runs 1.44x faster than LIIF-RDN and 3.25x faster than LTE-SwinIR at x4; within the same extension, a variant trained and evaluated without 4-corner local-ensemble averaging gives a 1.77x speedup with 35% lower peak memory and negligible PSNR change, while additionally widening the RDN encoder from 64 to 96 channels gives a small positive PSNR shift with a 1.58x speedup and 31% lower peak memory. Native-reconstruction claims are scoped to the matched-budget amortized protocol, and ASR claims are scoped to a separate canonical-style SR protocol.

17.
arXiv (CS.LG) 2026-06-15

SpikF-GO: Spiking Fourier Graph Operators for Multivariate Time Series Forecasting

arXiv:2606.13901v1 Announce Type: new Abstract: Spiking Neural Networks (SNNs) have emerged as an energy-efficient alternative to conventional neural networks, demonstrating strong performance in computer vision and robotics. More recently, SNNs have been applied to time series forecasting (TSF), with methods exploring spiking temporal backbones, spike-compatible positional encodings, Fourier-domain processing, and redesigned neuron dynamics. However, existing SNN forecasting approaches process variables independently, lacking explicit mechanisms for modeling inter-variable dependencies. This is a critical limitation in multivariate settings, where cross-variable correlations carry substantial predictive information. We propose Spiking Fourier Graph Operators (SpikF-GO), which addresses this gap by combining a hypervariate graph formulation in which every scalar observation becomes a graph node with spike-driven spectral processing. SpikF-GO introduces a Hard Concrete frequency gate for learnable sparse frequency selection and a Complex LIF gate that applies independent spiking neurons to real and imaginary Fourier components, preserving binary, event-driven computation throughout the spectral domain. We further present a variant incorporating Central Pattern Generator-based positional encodings for stronger long-range temporal modeling. Evaluated on eight benchmarks under a unified experimental protocol, SpikF-GO achieves the best average rank among all SNN methods and outperforms its ANN counterpart, FourierGNN, at reduced energy cost. SpikF-GO maintains competitive accuracy even at substantially smaller embedding dimensions, thereby achieving significant energy reductions. To our knowledge, this is among the first works to bring graph-based multivariate modeling into the spiking domain for TSF and the first to provide a unified comparison across SNN forecasting architectures under a common experimental protocol.

18.
arXiv (math.PR) 2026-06-17

Convergence Analysis of the Random Bisection Method

arXiv:2603.20483v2 Announce Type: replace-cross Abstract: We propose a generalized version of the bisection method where the cutting point between the two subintervals is chosen at random following an arbitrary distribution. We compute expected convergence rates with respect to any arbitrary a priori distribution for the position of the root in the initial interval and proved that it depends only on the the expectation $\mathbb{E}[c(1-c)]$ of the cut $c$. We also provide a generalization of the method for $K$ random cuts and study its convergence properties. Most probabilistic derivations are kept fairly simple for the ease of understanding of a larger audience. Our theoretical results are then validated numerically using statistical simulation.

19.
arXiv (math.PR) 2026-06-18

On two overlooked stick-breaking constructions of the normalized inverse Gaussian process

arXiv:2606.19306v1 Announce Type: new Abstract: We shed light on two alternative stick-breaking constructions of the normalized inverse Gaussian (NIG) random discrete distribution which appear to have been overlooked so far in the Bayesian nonparametric setting. The first is derived from a result in Aldous and Pitman (1998) for the conditional Brownian excursion partition, mixing over the local time at zero up to time one. The second arises as a particular case of a result in James (2013) for priors obtained by a random spatial and temporal change of the normalized generalized Gamma subordinator. Both constructions are in terms of straightforward transformations of standard random variables and can be easily generalized to provide the stick-breaking construction of any element, respectively, in a) the family of mixed Poisson-Kingman models driven by the $1/2$ stable Lévy measure and b) the family of Poisson-Gamma processes driven by the Inverse Gaussian subordinator.

20.
arXiv (CS.LG) 2026-06-12

Quantizing Time-Series Models As Dynamical Systems: Trajectory-Based Quantization Sensitivity Score

arXiv:2606.13300v1 Announce Type: new Abstract: We introduce the Trajectory-based Quantization Sensitivity Score (TQS), a metric that reframes post-training quantization (PTQ) through the lens of dynamical-systems stability. By modeling the network's rollout as a discrete-time dynamical system, TQS characterizes how quantization-induced errors propagate and amplify over the rollout horizon. Unlike conventional PTQ methods, where sensitivity analysis is often coupled to the quantization procedure, TQS enables a priori sensitivity estimation decoupled from quantizer selection and bit-width assignment. This separation allows for quantization budget planning even for black-box or compiled networks with fused operators. Building on this, we present TQS-PTQ, a flexible mixed-precision framework that requires no calibration data or costly second-order approximations. Our experiments show that a dynamical-systems perspective provides a robust, high-performing pathway for low-precision deployment in resource-constrained settings.

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

N(CO)$^2$: Neural Combinatorial Optimization with Chance Constraints to Solve Stochastic Orienteering

arXiv:2606.18514v1 Announce Type: cross Abstract: Neural combinatorial optimization (NCO) offers a promising alternative to traditional heuristic-based methods for solving complex graph optimization problems by proposing to learn heuristics through data. This class of problems frequently arises in automation, as it can be used to model a variety of applications. While NCO has been extensively studied for deterministic combinatorial optimization problems, there are only a few works that aim to solve stochastic combinatorial optimization problems. In this work, we present N(CO)$^2$: Neural Combinatorial Optimization with Chance cOnstraints to solve the Stochastic Orienteering Problem (SOP) without the use of hand-crafted heuristics. By integrating a reinforcement learning (RL) framework, the model optimizes path selection under uncertainty, effectively balancing exploration and exploitation. Empirical results demonstrate that our method generalizes well across diverse SOP instances, achieving competitive performance compared to the state-of-the-art mixed-integer linear program (MILP) for the task. The proposed approach reduces human effort in heuristic design while enabling adaptive and efficient decision-making in uncertain environments.

22.
Nature Medicine 2026-06-15

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

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

23.
medRxiv (Medicine) 2026-06-22

Efficacy and safety of semaglutide for obesity and hyperphagia in adults with Prader-Willi syndrome

Context: Prader-Willi syndrome is a genetic neurodevelopmental disorder characterized by hyperphagia and early-onset obesity from hypothalamic dysfunction with endocrinopathies and learning disability. Management is challenging with strict control of the food environment needed. While newer glucagon-like peptide-1 receptor agonists, such as semaglutide, have efficacy in non-PWS obesity, there have been limited case reports in PWS. Objective/Design/Setting: Retrospective records review of 12 adults with PWS and overweight/obesity treated with semaglutide at a UK academic hospital centre specialist clinic. Patients: mean +/- SD age 28.3 +/- 10.1 years, 83% female, BMI 46.6 +/- 8.2kg/m2, 75% type 2 diabetes mellitus. Intervention: Median follow-up 17.2 months (range 8.7-36.1) with median semaglutide dose 2.4mg once weekly (1.0-2.4). Results: Although there was no significant weight loss on semaglutide, there was stabilisation of the weight gain prior to treatment over previous 12.4 months (7.6-23.0) (post -3.1 +/- 9.9% vs. pre +5.7 +/- 5.6%: d -0.72, P=0.037). There was a significant decrease in hyperphagia on semaglutide from hyperphagia questionnaire for clinical trials (n=11, -7.3 +/- 6.1 (max 36), d -1.19, P=0.003), having been stable before treatment. HbA1c improved in those with elevated baseline levels (n=6, -4.2 +/- 4.9%, d -0.74, P=0.13). Mild gastrointestinal side effects were seen in 25% but did not lead to discontinuation. Conclusions: In adults with PWS, semaglutide produced weight maintenance, reduced hyperphagia, and improved glycaemic control, with good tolerability. Larger placebo-controlled trials are needed to confirm these findings in adults and adolescents with PWS, especially in those without T2DM, where efficacy may be greater.

24.
arXiv (CS.CV) 2026-06-17

Beware of Aliases – Signal Preservation is Crucial for Robust Image Restoration

Image restoration networks are usually comprised of an encoder and a decoder, responsible for aggregating image content from noisy, distorted data and to restore clean, undistorted images, respectively. Data aggregation as well as high-resolution image generation both usually come at the risk of involving aliases, i.e.~standard architectures put their ability to reconstruct the model input in jeopardy to reach high PSNR values on validation data. The price to be paid is low model robustness. In this work, we show that simply providing alias-free paths in state-of-the-art reconstruction transformers supports improved model robustness at low costs on the restoration performance. We do so by proposing BOA-Restormer, a transformer-based image restoration model that executes downsampling and upsampling operations partly in the frequency domain to ensure alias-free paths along the entire model while potentially preserving all relevant high-frequency information.

25.
Nature (Science) 2026-06-08

Targeting Cancer-Specific Mutations with RNA-Triggered Chromatin Shredding

作者:

Genetic mutations that drive cancer often occur in tumor suppressor proteins, including the p53 transcription factor which is altered in ~40-50% of cases1,2. However, current therapies fail to target most such mutations because the mutant proteins typically lack defined drug-binding pockets, and restoring the endogenous function has proven challenging. Here, we programmed CRISPR-Cas12a2, an RNA-guided nuclease with trans-nucleolytic cleavage activities3,4, to selectively kill cancer cells by targeting cancer-specific transcripts. This approach limits cell growth by inducing trans shredding of chromatin, triggering DNA damage responses and cell death. Unlike existing methods, RNA-guided Cas12a2 senses cellular RNA signatures, enabling precise targeting of undruggable mutations. Transcript-activated chromatin shredding provides a new approach to precision disease treatments for undruggable targets.