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01.
arXiv (CS.CL) 2026-06-17

ReproRepo: Scaling Reproducibility Audits with GitHub Repository Issues

Reproducing research results from papers and released code is central to scientific progress. Existing works have introduced benchmarks to evaluate whether LLM agents can assist with reproducibility, but they are difficult to scale due to their reliance on substantial manual effort for data curation and evaluation. We introduce ReproRepo, a scalable framework for reproducibility evaluation that leverages human-raised GitHub issues as naturally occurring supervision on realistic reproduction blockers. We instantiate ReproRepo on 1,149 recent machine learning papers from major conferences and evaluate four frontier model-agent configurations. Our results show that LLM agents, even without executing code, can identify many real-world reproducibility problems from paper-repository pairs: the best agent in our study, namely Codex with GPT-5.5, surfaces at least one semantically related human-reported blocker for ~90% of papers in the study. Further analysis shows that agents are particularly effective for surfacing visible failures and identifying the right semantic region, but may still be insufficient in exact localization. ReproRepo can serve as a reusable, scalable framework for future evaluations of LLM agents on real-world reproducibility auditing. Our code is released at https://github.com/LithiumDA/ReproRepo.

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

An Empirical Analysis of Optimization Dynamics and Sparsity Boundaries in Large-Scale Pedestrian Attribute Recognition

Pedestrian Attribute Recognition (PAR) is critical for video surveillance, enabling forensic search and re-identification systems. Extreme class imbalance remains a fundamental obstacle when merging PETA and PA-100K into a 109,000-image composite corpus, where minority attributes have positive sample fractions below 1%. This causes standard BCE optimization to suppress rare traits, a phenomenon we term the majority negative class cheating trap. We present a systematic ablation of Multi-Label Focal Loss hyperparameters (alpha and gamma) on a ResNet-18 backbone. A calibrated configuration (alpha=0.50, gamma=2.0) achieves a Macro F1-score of 62.32%, matching BCE baseline while preserving superior hard-example mining and convergence dynamics. Our approach uses pure loss-function engineering with zero computational overhead for edge deployment. We identify the Sparsity Wall, a hard boundary where positive sample fractions below 0.1% make global loss reweighting ineffective, requiring instance-level intervention.

03.
arXiv (CS.CL) 2026-06-19

Manifold Bandits: Bayesian Curriculum Learning over the Latent Geometry of Large Language Models

Reinforcement learning (RL) is a central approach for improving reasoning capabilities in large language models (LLMs), where training efficiency depends critically on how problems are sampled during optimization. Existing adaptive curriculum learning methods typically prioritize prompts of intermediate difficulty, treating problem selection as a standard bandit problem with independent arms and overlooking the structured, heterogeneous nature of the task space. In this work, we frame problem sampling as a manifold-structured bandit problem with endogenous non-stationarity: problems are related through the model's latent representation space, and sampling decisions can steer how learning signals evolve across that space. To operationalize this perspective, we introduce Bayesian Manifold Curriculum (BMC), a structure-aware framework that organizes problems into a hierarchical task tree and applies Bayesian learning to guide sampling. Empirically, we find that different sampling strategies induce non-trivial tradeoffs between productivity (learning signal), diversity (coverage of the task manifold), and utility (evaluation relevance). These results show that prioritizing difficulty alone is insufficient for strong downstream performance, highlighting the importance of incorporating structure and type-awareness into problem sampling.

04.
bioRxiv (Bioinfo) 2026-06-15

Multiple Fault Analysis and Drug Therapy on Signaling Pathways Using Dynamic Bayesian Network-based Model

Cell growth is an intricate biological phenomenon that is closely regulated by the interplay between various growth factors and transcription factors. Signaling pathways are the main mediators in this event, which provide the driving force for mitosis or sometimes meiosis. However, when malfunctions occur within the biological network, they can cause uncontrolled cell division, regardless of external stimuli. By employing Dynamic Bayesian Networks (DBNs), these malfunctions can be explicitly simulated, offering insights into their effects on cellular behavior and growth regulation. To a significant extent, the resultant outcomes can be mitigated through the use of reduced drug combinations. This study delves into the intricacies of signaling pathway behavior under the influence of concurrent malfunctions. Initially, we replicate the effects of these dysfunctions within DBNs. Subsequently, drug therapy is applied to alleviate their impact. Our methodology introduces a parameter known as efficiency_score, enabling the identification of optimized drug combinations without prior knowledge of specific dysfunctions. Particularly relevant in the context of realistic cancer conditions, these tailored drug inhibition points demonstrate enhanced efficacy compared to conventional treatments. Leveraging GPU acceleration throughout the modeling process accelerates the analysis of multiple faults within the biological networks, rendering our approach notably faster and more efficient.

05.
arXiv (CS.AI) 2026-06-16

FineVLA: Fine-Grained Instruction Alignment for Steerable Vision-Language-Action Policies

arXiv:2605.27284v2 Announce Type: replace-cross Abstract: Vision-Language-Action (VLA) models are increasingly expected to not only complete robot tasks, but also follow human instructions about how those tasks should be executed. However, existing robot datasets usually pair trajectories with coarse goal-level language, leaving execution-critical details such as active arm, approach direction, and contact region unspecified. This limits steerable policy learning and robotic video understanding. We introduce FineVLA, an open framework for action-aligned fine-grained VLA supervision. The framework includes: (1) a data construction tool that unifies 972,247 trajectories across 85K tasks from 10 open-source robot datasets and builds FineVLA-Data, a human-verified dataset of 47,159 fine-grained trajectories; (2) a held-out benchmark with 500 videos, 11,631 atomic facts, and 1,030 VQA questions; (3) a robotics-specialized VLM annotator for scalable fine-grained annotation; and (4) a steerable VLA policy trained with controlled mixtures of fine-grained and raw goal-level instructions. Our experiments yield three findings. First, fine-grained supervision does not sacrifice goal-level success: FG-only improves over Raw-only by +1.4 to +8.1 success-rate points across settings. Second, fine-grained and raw instructions are complementary, following a consistent inverted-U trend peaking at FG:Raw = 1:2 to 1:1. The best mixed setting reaches 86.8%/82.5% in RoboTwin simulation and 62.7/100 in real-world dual-arm manipulation (vs. 49.9 Raw-only). Third, fine-grained supervision improves steerable control: the largest real-world gains appear on pose (+23), color (+18), and approach direction (+18)–factors where goal-level instructions provide no guidance. Overall, fine-grained language should augment goal-level instructions: specifying how to execute alongside what to achieve. Project page: https://finevla.xlang.ai/

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

Vibrato Expression Control for Singing Voice Conversion with Improving Independent Control

arXiv:2606.17126v1 Announce Type: cross Abstract: Singing style is a crucial aspect of a natural and expressive singing voice. Singers utilize singing styles to convey the feeling or emotion of the songs. Several works have been proposed to control singing style for making the more expressive singing voice. Recently, VibE-SVC successfully controls vibrato by predicting high-frequency F0 contour. In this paper, we introduce a singing voice conversion framework, called VibE-SVC2, to improve singing style conversion performance and controllability. The model offers control over two types of singing styles: a pitch style and a timbre style. For the pitch style, to resolve the pitch-energy entanglement issue that is unresolved in our previous work, we introduce a novel Energy Style Converter to address remaining style information in the energy contour. In addition, we propose a Zero-shot Pitch Style Converter, which mimics the pitch style of reference audio. To expand the controllability of the model, we propose vibrato rate scaling that is an independent control of vibrato extent, which is unavailable in VibE-SVC. For the timbre style, we extend the model to handle a variety of phonation styles. However, addressing specific styles such as vocal fry poses a challenge, as conventional F0 extraction often fails due to their inherent subharmonic characteristics, which degrades the conversion quality. To address this, we propose a novel Subharmonic Correction algorithm to refine the F0 contour for more natural timbre conversion. Through comprehensive objective and subjective evaluations, we demonstrate that VibE-SVC2 provides fine-grained, independent control over two types of singing styles, outperforming existing methods.

07.
Nature (Science) 2026-06-08

Fifty years since a simple equation described the chaos of biology

An exploration of chaos theory in population dynamics showed that unpredictable systems can often be modelled using surprisingly simple mathematics. An exploration of chaos theory in population dynamics showed that unpredictable systems can often be modelled using surprisingly simple mathematics.

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

The Price of Anarchy in Disaggregated Inference

arXiv:2606.17081v1 Announce Type: cross Abstract: Disaggregated inference architectures physically separate prefill and decode phases onto distinct GPU pools, creating competing "agents" that share a fixed hardware budget. We provide, to our knowledge, the first formal game-theoretic analysis of this architecture, using NVIDIA Dynamo as a concrete case study. We model disaggregated serving as three coupled games: a two-player resource game between prefill and decode pools, a selfish caching game over the hierarchical KV cache, and a congestion game with positive externalities for request routing. We empirically validate the latter two; the P/D resource game is treated analytically (Section 9.2). We characterize how GPU saturation induces regime transitions that shift the game's payoff structure: below saturation, selfish behavior has bounded Price of Anarchy (PoA); at saturation, superlinear latency and cache externalities drive our empirical estimator PoA-hat (defined in Section 6.4) upward. Based on this analysis, we design an adaptive controller that detects saturation transitions in real time and adjusts routing parameters accordingly, shifting from cache-affinity exploitation to load-balanced congestion avoidance. We instantiate our framework on a 3-node NVIDIA B200 cluster running Dynamo with two models, Nemotron-4-340B (TP=8, full-node workers with cross-InfiniBand KV transfers) and Llama-3.1-70B (TP=4), and find the same three-regime PoA-hat structure with the same first post-knee grid point (C=128) on both models. Adaptive routing shifts each model to a better operating point. Our strongest result is on the 70B 1P/5D topology, where PoA-hat drops 3.1x (66.4 to 21.5) in the saturated phase at a 13% throughput cost. On the 70B 1P/2D, PoA-hat drops 2.2x and TTFT P99 drops 7.6x (see Section 8.5).

09.
Nature (Science) 2026-06-17

A distant brown dwarf coplanar to a warm Jupiter and a hot super-Earth

In transiting planetary systems, in which planetary sizes are accurately determined from transit observations, the presence of transit-timing variations1 (TTVs), especially when combined with radial velocity (RV) data, provides powerful constraints on masses and orbital eccentricities. Together, these measurements offer crucial insights into system architecture, formation mechanisms and dynamical evolution. We present long-term RV and transit/TTV monitoring of the relatively young star (age approximately 1 Gyr) TOI-201, revealing an exceptional multi-planet system composed of a hot super-Earth (SE) size planet transiting every 5.8 days, a warm Jupiter (WJ) on a 53-day orbit and an eccentric (e = 0.62) low-mass brown dwarf (BD) on an approximately 8-year orbit, with an estimated mass MBD of about 16 Jupiter masses. The BD is the longest-period transiting substellar object ever characterized by means of RVs and the only one known to be coplanar with inner planets. The architecture of this system suggests that the SE was formed isolated and in the innermost region of the gaseous disk. On the other hand, the orbital configuration of the outer companions suggests a nearly in situ formation of both objects, with the WJ forming in a dense inner disk. Alternatively, the BD might have formed farther out and migrated inward, while increasing its eccentricity owing to interactions with the disk. Analysis of long-term radial velocity data and transit time variations, induced by a super-Earth, a warm Jupiter and a brown dwarf in a coplanar orbit around the relatively young star TOI201.

10.
arXiv (quant-ph) 2026-06-11

Robust Mixed-State Cluster States and Spurious Topological Entanglement Negativity

arXiv:2504.16165v2 Announce Type: replace Abstract: We investigate 1D and 2D cluster states under local decoherence to assess the robustness of their mixed-state subsystem symmetry-protected topological (SSPT) order. By exactly computing fidelity correlators via dimensional reduction of effective statistical mechanics models, we pinpoint the critical error rate for strong-to-weak spontaneous breaking of strong subsystem symmetry. Without resorting to the replica trick, we demonstrate that mixed-state SSPT order remains remarkably robust up to the maximal decoherence rate when noise respects strong subsystem symmetry. Furthermore, we propose that the mixed-state SSPT order can be detected by a constant correction to the area-law scaling of entanglement negativity, termed spurious topological entanglement negativity. This also highlights that topological entanglement negativity, a widely used diagnostic for mixed-state topological order, is generally not invariant under finite-depth quantum channels.

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

Harnessing cortical geometry, wiring, and function as inductive biases for recurrent neural networks

arXiv:2606.14975v1 Announce Type: cross Abstract: How the wiring and functional organization of cortex shape recurrent computation remains a central question in both neuroscience and machine learning. Here, we leverage data released through the Machine Intelligence from Cortical Networks (MICrONS) program–a functional connectomics resource spanning multiple areas of mouse visual cortex, in which dense calcium imaging is co-registered with high-resolution electron microscopy reconstruction from the same animal–to build biologically grounded recurrent neural networks. Using neuronal spatial coordinates, anatomical connectivity, and function-derived relationships from nearly 12,000 coregistered excitatory neurons, we initialize recurrent weights and impose communication-aware spatial constraints during learning. Across three cognitive decision-making tasks, networks constrained by cortical structure and function consistently outperform baseline and partially constrained models. Functional weight initialization provides the largest gain, while real spatial embedding yields robust additional improvements across conditions. These biologically grounded networks also develop low-entropy, modular, and small-world organization, and retain strong performance even when recurrence is restricted to positive weights. Together, our results show that the machinery of cortex–its geometry, wiring, and functional structure–can be harnessed as a powerful inductive basis for building recurrent networks that learn more effectively while converging toward key organizational principles of biological computation.

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

Strategic Decision Support for AI Agents

arXiv:2606.12587v1 Announce Type: new Abstract: Traditionally, decision support studies how humans use machine learning models to make better decisions. In modern agentic systems, this division of roles is increasingly reversed: AI agents act on behalf of users, while humans and tools becomes support mechanisms around them. This role reversal brings reliability concerns to the forefront, since agentic errors can be consequential and agent behavior must remain aligned with human goals and constraints. Departing from the classical view of decision support, we revisit its two basic principles, the cost–value tradeoff of seeking support and the role of uncertainty quantification, in a setting where AI agents are the central actors. We propose a framework for strategic decision support for AI agents through an optimization problem that minimizes support usage subject to controlling a counterfactual missed-support error: the probability that the agent acts alone on instances where support would have materially improved its output. At the population level, we show that the optimal policy is a threshold rule on the value of support. Building on this structure, we develop an online algorithm that adaptively thresholds such a score and uses randomized exploration to control missed-support error without distributional assumptions. We further introduce a calibration-on-the-fly method that reduces unnecessary support calls online. We instantiate this framework across diverse scenarios, including information gathering, human–AI collaboration, and tool use, showing how each can be modeled through the same strategic decision-support lens. Experiments across these settings show that our method reliably controls the target error while substantially reducing support usage in practice.

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

SAM3 Self-Distillation for Fine-Grained GOOSE 2D Semantic Segmentation

作者:

We describe our 4th-place entry to the ICRA 2026 GOOSE 2D Fine-Grained Semantic Segmentation Challenge, which reached a composite mean Intersection-over-Union (mIoU) of 69.73% on the official 1,815-image test set. Our model adapts the image encoder of a recent visual foundation model, Segment Anything Model 3 (SAM3), with a lightweight decoder. Beyond this, we contribute two techniques and one empirical finding: (i) a self-distillation scheme that re-uses SAM3 itself, prompted with ground-truth boxes, as a teacher on the classes where it outperforms our own model; (ii) an image-level multi-scale test-time augmentation scheme that restores multi-scale inference for a fixed-input-size model by rescaling the image rather than the model input; and (iii) the finding that an aggressive photometric distortion from a winning 2025 GOOSE 2D entry, transplanted onto our pipeline, is its single largest source of improvement.

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

Towards Distributed Inference of LLMs on a P2P Network

arXiv:2606.17059v1 Announce Type: cross Abstract: Prefix caching can reduce LLM inference latency by reusing KV caches across requests with shared prompts, but cluster-scale reuse is challenging because caches are partitioned across nodes. We propose a decentralized, prefix-cache-aware routing scheme for peer-to-peer LLM serving. Each node maintains a local radix tree of its own cached prefixes and asynchronously refreshed estimates of peer caches using periodic anti-entropy. Requests are routed to the node with the longest estimated prefix match, without centralized coordination or KV-cache transfer. Stale metadata only causes cache misses, not incorrect outputs, making weak consistency sufficient for correctness. Evaluation on simulated MMLU workloads show that decentralized routing improves latency under low communication delay and skewed prefix distributions, while high network latency and affinity-induced hotspots limit its benefits.

15.
medRxiv (Medicine) 2026-06-24

The role of Mediterranean diet adherence, smoking and their interactions in epigenetic age acceleration: A cross-sectional analysis of the Airwave cohort.

Background: Epigenetic clocks are markers of biological aging that may vary in their sensitivity to environmental stressors and lifestyle modifiers. To evaluate the utility of these biomarkers as sensors of the human exposome, we investigated how they respond to two powerful and opposing exposures: smoking, a source of oxidative stress, and the antioxidant-rich Mediterranean diet. Objectives: We assessed the sensitivity of eleven epigenetic clocks to diet and smoking and evaluated whether Mediterranean diet adherence modifies associations between smoking and epigenetic aging. Methods: We analysed 928 participants (mean age 41 years, 59% male) from the Airwave Health Monitoring Study. Linear regression models assessed associations between Mediterranean Diet Score (MDS) and epigenetic age acceleration (EAA), alongside smoking status and blood cotinine. Interaction terms between smoking status and MDS were included to detect dietary attenuation of smoking-related EAA. Models were adjusted for demographic, socioeconomic, lifestyle, and psychological covariates. Results: Higher MDS was associated with lower EAA for GrimAge ({beta} = -0.07 SD; 95% CI: -0.13, -0.01) and Bernabeu ({beta} = -0.08 SD; 95% CI: -0.14, -0.02) after false discovery rate correction. Smoking was strongly associated with increased EAA, particularly for GrimAge, Bernabeu, and DunedinPACE. Among current smokers, effect sizes were greater in those with lower dietary adherence (e.g. GrimAge: 1.79 SD, 95% CI: 1.54, 2.04) compared with those with higher adherence (1.35 SD, 95% CI: 1.01, 1.68; P_interaction < 0.001). Similar attenuation patterns were observed for Bernabeu. Higher intake of fruits, vegetables, and whole grains contributed most to the attenuation of smoking-related EAA. Conclusions: Our findings indicate that certain epigenetic clocks effectively capture the tension between harmful and protective exposures within the exposome. Rather than suggesting that diet neutralises the risks of tobacco, these results demonstrate that specific clocks are sensitive enough to monitor how lifestyle factors modify molecular responses to environmental toxins. This highlights the value of second-generation clocks in quantifying biological resilience.

16.
arXiv (CS.CV) 2026-06-17

Enhancing Pathological VLMs with Cross-scale Reasoning

Pathological images are inherently multi-scale, requiring pathologists to integrate evidence from global tissue architecture at low magnification to cellular morphology at higher magnification for accurate diagnosis. While existing pathological datasets for vision-language model (VLM) include various scales, they often lack an explicit cross-scale reasoning objective. This limitation prevents VLMs from capturing essential cross-scale representations and learning evidence-based reasoning. To bridge this gap, we introduce the first cross-scale training and evaluation paradigm that formulates pathology interpretation as multi-magnification reasoning. However, creating such a task reveals a critical challenge: multi-image visual question answering (VQA) is prone to text-only shortcuts, which allow models to guess answers using magnification-dependent artifacts rather than visual evidence. To address this, we propose a leakage-aware curation pipeline that combines adversarial text-only screening with constraint-guided question design. Using this pipeline, we construct Scale-VQA, a high-quality benchmark with 4,685 multiple-choice questions grounded in 2,537 pathology images across multiple magnification levels. Finally, we present ScaleReasoner-R1, a model trained via reinforcement learning to optimize performance on the cross-scale VQA task. ScaleReasoner-R1 achieves state-of-the-art performance on our cross-scale reasoning benchmark and generalizes to SOTA performance on established single-scale benchmarks. Findings suggest that even the limited cross-scale supervision can significantly improve pathological understanding. The code and demos will be open-sourced.

17.
arXiv (math.PR) 2026-06-12

Pathwise integration beyond Young via Faber–Schauder energy spaces

作者:

arXiv:2606.13331v1 Announce Type: cross Abstract: We develop a pathwise integration theory based on Faber–Schauder energy spaces. The approach replaces the classical Hölder–Young and finite-variation Young conditions by dyadic summability conditions expressed in terms of Faber–Schauder coefficients. On the normalized interval $[0,1]$, these conditions define Banach spaces $\mathcal{E}^p$, which we call Faber–Schauder energy spaces. For $p,q>1$ satisfying $1/p+1/q\ge1$, we prove that every pair $f\in\mathcal{E}^p$ and $g\in\mathcal {E}^q$ admits a continuous pathwise integral $I_{f,g}$, constructed from dyadic left Riemann sums. We call $I_{f,g}$ the Faber–Schauder integral, and show that it depends boundedly and bilinearly on $(f,g)$ in the corresponding energy norms. The integral satisfies additivity, integration by parts, and a dyadic Young–Loève estimate. It is also the uniform limit of classical Riemann–Stieltjes integrals of finite Faber–Schauder approximations. The Faber–Schauder integral agrees with the classical Young integral whenever the latter is available, but also applies to deterministic and Gaussian examples for which neither the Hölder–Young condition nor the finite-variation Young condition can be verified. In this sense, it provides a Faber–Schauder coefficient-based extension of Young's framework.

18.
arXiv (quant-ph) 2026-06-16

Decoherence-free algebras in quantum dynamics

arXiv:2403.12926v2 Announce Type: replace Abstract: In this Article we analyze the algebraic properties of the asymptotic dynamics of finite-dimensional open quantum systems in the Heisenberg picture. In particular, a natural product (Choi-Effros product) can be defined in the asymptotic regime. Motivated by this structure, we introduce a new space called the Choi-Effros decoherence-free algebra. Interestingly, this space is both a C*-algebra with respect to the composition product, and a B*-algebra with respect to the Choi-Effros product. Moreover, such space admits a direct-sum decomposition revealing a clear relationship with the attractor subspace of the dynamics. In particular, the equality between the attractor subspace and the Choi-Effros decoherence-free algebra is a necessary and sufficient condition for a faithful dynamics. Finally, we show how all the findings do not rely on complete positivity but on the much weaker Schwarz property.

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

Evaluating Uplift Modeling under Structural Biases: Insights into Metric Stability and Model Robustness

arXiv:2603.20775v2 Announce Type: replace Abstract: In personalized marketing, uplift models estimate the incremental effect of an intervention by modeling how customer behavior would change under alternative treatments using counterfactual analysis. However, real-world marketing data often exhibit various biases, such as selection bias, spillover effects, measurement error, and unobserved confounding. These biases can adversely affect both the accuracy of uplift estimation and the validity of evaluation metrics. Despite the importance of bias-aware assessment, there remains a lack of systematic studies evaluating how different models and metrics perform under such biased conditions. To bridge this gap, we design a systematic benchmarking framework. Unlike standard predictive tasks, real-world uplift datasets inherently lack counterfactual ground truth. This limitation renders the direct validation of evaluation metrics infeasible and prevents the precise quantification of biases. Therefore, a semi-synthetic approach serves as a critical enabler for systematic benchmarking. This approach effectively bridges the gap by retaining real-world feature dependencies while providing the ground truth needed to isolate structural biases. Our investigations reveal that (i) uplift targeting and prediction can manifest as distinct objectives, where proficiency in one does not ensure efficacy in the other; (ii) while many models exhibit inconsistent performance under diverse biases, TARNet shows notable robustness, providing insights for subsequent model design; (iii) the stability of evaluation metrics is linked to their mathematical alignment with the ATE, suggesting that ATE-approximating metrics yield more consistent model rankings under structural data imperfections. These findings suggest the need for more robust uplift models and evaluation metrics under real-world data imperfections.

20.
arXiv (CS.CV) 2026-06-18

Confidence is Not Reliability: Rethinking MC Dropout in Brain Tumour Segmentation

Glioma segmentation in multiparametric MRI is a critical component of treatment planning. A segmentation model that fails silently on treatment-critical sub-regions represents a patient safety risk that overlap-based metrics such as Dice scores cannot expose. We ask whether voxel-level uncertainty estimation via Monte Carlo (MC) Dropout can reliably identify segmentation errors in clinically critical sub-regions, and whether calibration failure modes are detectable from standard reporting metrics alone. In an empirical two-model case study on 126 BraTS21 patients, we evaluate a high-performance pretrained SegResNet and a locally trained UNet with residual units (UNet-Res). MC dropout preserved segmentation accuracy ($|\Delta Dice|$ $

22.
Nature Medicine 2026-06-10

Dual-target gene therapy in Parkinson’s disease: a multicenter phase 1 trial

作者:

Restoring striatal dopamine synthesis is a promising gene therapy strategy for Parkinson’s disease. Previous adeno-associated virus-mediated aromatic L-amino acid decarboxylase (AADC) monotherapies remain dependent on exogenous levodopa, whereas multigene delivery is constrained by strict adeno-associated virus packaging limits. A ‘dual approach’ targeting the two rate-limiting enzymes, tyrosine hydroxylase (TH) and AADC, offers the potential for autonomous dopamine synthesis. We report the 12-month primary safety and tolerability outcomes of a multicenter, open-label, dose-escalation, phase 1 trial evaluating BBM-P002, a new adeno-associated virus vector—AAVT42—codelivering constitutively active TH and AADC. Ten participants with moderate-to-advanced Parkinson’s disease were enrolled and received bilateral intraputaminal infusions across doses of 4.0 × 1011 vg (Cohort 1; n = 1), 6.0 × 1011 vg (Cohort 2; n = 2), 1.0 × 1012 vg (Cohort 3; n = 2) and 1.2 × 1012 vg (Cohort 4; n = 5). The trial achieved its primary outcome, as BBM-P002 demonstrated a favorable safety and tolerability profile within 12 months post-treatment. No dose-limiting toxicities or drug-related serious adverse events occurred. A total of 23 adverse events were reported, all judged unrelated to BBM-P002 and primarily mild and transient. Systemic toxicity and clinically meaningful immunogenicity were absent. In conclusion, intraputaminal delivery of BBM-P002 was safe and well tolerated in this phase 1 trial, supporting continued clinical development. ClinicalTrials.gov registration: NCT05822739 . Phase 1 results reveal that BBM-P002, a dual-target gene therapy co-delivering TH and DDC, is safe and well tolerated in Parkinson’s disease, with 12-month motor improvements signaling therapeutic potential.

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

OdysSim: Building Foundation Models for Human Behavior Simulation

Large language models are increasingly deployed as human simulators for interactive evaluation and social simulation. Yet helpfulness-driven post-training pulls them toward a homogeneous, overly agreeable assistant register, creating a behavioral Sim2Real gap. We present OdysSim, the largest open systematic investigation of behavioral foundation models, i.e., models trained to simulate human behavior at scale. We propose SOUL, a taxonomy of five capability axes (CONV, SS, COG, ROLE, EVAL) that unifies 62 datasets and 23 benchmark tasks under one framework. Specifically, we curate the OdysSim corpus (21.4M interactions, 10B tokens, retrofitted with back-generated social contexts), construct the SOUL-Index benchmark, and develop an end-to-end training recipe combining midtraining, task-specific RL, and expert distillation. The resulting open 8B OSim model ranks first or tied-first on 8 of 23 tasks, outperforming any individual frontier model by this count, with the strongest gains on conversational and social tasks. Its outputs are also more human-like in length, formatting, and word choice, and it transfers zero-shot to out-of-distribution user simulation on $\tau$-bench, nearly matching real users on reaction alignment (93.2 vs. 93.5). We further show that LLM-as-judge RL induces reward-hacking patterns, and that our detectors can mitigate them during post-training. Together, our findings suggest that behavioral foundation models require rethinking the LLM training paradigm. We release all artifacts to support future research.

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

Half a Link can Be Enough to Predict a Whole Link: Understanding Generalization in Knowledge Graph Foundation Models

arXiv:2606.18001v1 Announce Type: new Abstract: Knowledge graph (KG) foundation models (KGFMs) are zero-shot generalizers: trained once, they can predict links on unseen graphs without retraining. However, understanding when and how they can robustly generalize across KGs is still an open question. In this paper, we shed some light on their generalization mechanisms highlighting how their performance on unseen KGs is not uniform when it comes to partially seen links, which we call half-links. In fact, we show that to predict a test triple $(h,r,t)$ it might suffice in practice to have observed the half-link $(h,r)$ or $(r,t)$ in the inference graph. This yields a taxonomy of four scenarios when combinations of these half-links are observed or not. In a rigorous stratified analysis over these scenarios, we reveal that SoTA KGFMs use seen half links for predictions, while unseen half-links pose different challenges. As such, our finer-grained taxonomy can be a diagnostic protocol for robust KGFM generalization and highlights where novel KGFMs can improve.

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

Sycophancy as Material Failure under Pushback Loading: A Multi-Axis Characterization Across Three Loading Cases and up to Seventeen Material Charges

Sycophancy in LLMs is documented across 70+ papers, but expert agreement on construct boundaries remains low (ICC=.184; Ye et al., 2026). The construct fragments because behavioral classification depends on which surface form is privileged. We adopt a materials-science framing: conversation as test specimen under load, LLM-model as material charge, pushback as progressive load, stance-flip as material failure. We characterize this failure across three loading cases (debate n=1000; false-presuppositions n=3400; ethical-setting n=3400; 10-17 material charges per case; 7800 specimens total) using 14 turn-level axis-measurements spanning velocity, damage accumulation, frame-drift, brittleness, and direction stability, plus three speaker-resolved axes from an independent pipeline. The measurements are Hooke-coupled ($\sigma = E \cdot \varepsilon$ analog) and reproduce across loading cases with effects up to $|r_{rb}| = 0.35$ on debate; the sign structure adds a second pattern: the ethical-setting case inverts the velocity and accumulation blocks. Variance composition partitions into two profiles: debate is charge-dominated (brittle-fracture-like: the material grade decides), false-presuppositions and ethical-setting are topic-dominated (creep-like: the load decides); the ratios (2.03 vs 0.13/0.17) are estimator-dependent, for debate even in direction. Cross-judge reliability (GPT-4o vs Haiku 4.5) shows debate scoring is judge-robust (Cohen's $\kappa = 0.88$) while false-presupposition scoring is judge-sensitive ($\kappa = 0.36$) – a caveat single-judge benchmarks must report. This is the methodological move Ye et al.'s diagnosis calls for: a multi-axis characterization that does not depend on which surface form of the construct one privileges.