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01.
medRxiv (Medicine) 2026-06-11

Vascular Phenotyping in Parkinson's Disease: Diabetes Mellitus Operationalizes a Microvascular Metabolic Syndrome Cluster Across PPMI Diagnostic Cohorts

Background: Diabetes mellitus elevates Parkinson's disease (PD) risk, via hypothesized cerebrovascular mediation. Whether the diabetes/prediabetes vascular-risk phenotype concentrates in cardiometabolic risk or macrovascular events across prodromal and clinically diagnosed PD remains unresolved. Objectives: To quantify the vascular-risk burden associated with diabetes/prediabetes across the PPMI diagnostic cohorts to test whether this association differs by cohort. Methods: Cross-sectional analysis of 413 PPMI participants (76 healthy controls, 145 prodromal PD, 192 clinically diagnosed PD) examined diabetes/prediabetes (n = 73) and seven vascular risk factors. The Vascular Burden Score (0 to 7) was a priori partitioned into microvascular and macrovascular sub-scores. Modified Poisson regression estimated adjusted prevalence ratios (aPR), adjusted for age, sex, and body mass index. A cohort-by-diabetes interaction tested cross-cohort consistency. Sensitivity analyses incorporated nigral diffusion tensor imaging (PD-risk biomarker) and FreeSurfer white matter hypointensity volume (cerebrovascular marker). Results: Diabetes/prediabetes elevated Vascular Burden Score ({beta} = 0.53, 95% CI 0.29 to 0.77, p < 0.001) versus non-diabetic participants, with a non-significant cohort-by-diabetes interaction (F = 0.29, p = 0.747). Three microvascular factors survived false discovery rate correction: obesity (aPR 2.28), hypertension (aPR 1.60), and hyperlipidemia (aPR 1.45). Macrovascular events showed no diabetic amplification ({beta} = -0.06, p = 0.25). In the imaging-phenotyped subset, Vascular Burden Score components contributed classifier variance distinct from nigral microstructure. Conclusions: Diabetes/prediabetes operationalize a microvascular cluster stable across prodromal and idiopathic PD. Cardiometabolic phenotyping may complement established PD-risk biomarkers (dopamine transporter SPECT, nigral diffusion), pending longitudinal validation linking vascular phenotype to dopaminergic markers.

02.
arXiv (quant-ph) 2026-06-12

Quantum Otto engine powered by an anisotropic Heisenberg XYZ model under independent local magnetic fields

arXiv:2606.12877v1 Announce Type: new Abstract: We study a quantum Otto heat engine whose working substance is an anisotropic two-qubit Heisenberg XYZ model. Independent local magnetic fields are used to control each spin individually. The influence of the longitudinal coupling, anisotropy, transverse coupling, and local fields on the net work output and efficiency is systematically examined. Reducing the longitudinal coupling is found to markedly improve both the maximum work and the peak efficiency. The engine performance reaches an optimum at a particular value of the anisotropy parameter. A local work analysis clarifies how work is produced during the cycle. Because of the asymmetric local fields and the intrinsic spin-spin interaction, the two qubits play markedly different thermodynamic roles; the interaction term itself contributes crucially to the total work. We further analyze the variation of quantum entanglement, quantified by concurrence, along the cycle. The results indicate that a pronounced change in entanglement between the hot and cold isomagnetic strokes is closely correlated with the efficiency enhancement. This work offers new insight into the operating principles and control of quantum Otto heat engines.

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

Can LLM Coding Agents Reason About Time Series?

Large language models (LLMs) are increasingly being used for automated decision-making systems in finance, healthcare, or environmental monitoring. Time series data are ubiquitous in these fields, yet hard to process automatically. Can time series be analyzed by LLM agents? We examine three approaches: providing the agent with raw numerical data, using the LLM as a coding agent, or a combination of both. In the coding agent setup, the model iteratively queries the data using Python code. Using two time series understanding benchmarks, we show that agents with code access can outperform models processing raw data by up to 10%. However, even the best performing agent still answers about 22-34% of the questions incorrectly. To get insights into models' strategies and reasoning gaps, we analyze the model outputs with a strong LLM judge. Our analysis reveals that coding agents can select appropriate statistical tests, but often miss important nuances. Meanwhile, models with access to raw data can reach the right conclusions using back-of-the-envelope calculations.

04.
arXiv (CS.LG) 2026-06-15

Curvature-Informed Potential Energy Surface for Protein-Ligand Binding Affinity Prediction

arXiv:2606.14217v1 Announce Type: new Abstract: Accurate prediction of protein-ligand binding affinity is essential for structure-based drug discovery. Recent geometric deep learning methods have achieved promising performance by representing protein-ligand complexes as three-dimensional graphs. However, most existing approaches mainly rely on static interaction geometry from a single bound conformation, while neglecting molecular flexibility and binding-induced conformational changes. To address this limitation, we propose a curvature-informed potential energy surface (CPES) graph neural network for protein-ligand binding affinity prediction, which incorporates physics-informed curvature representations to model conformational flexibility. CPES first derives curvature spectral descriptors from the Hessian of the potential energy surface evaluated at equilibrium configurations, whose eigenvalues define the local principal curvatures of the potential energy surface. It then uses spectral cross-attention to compare the unbound ligand and protein with the bound complex, thereby capturing binding-induced changes in conformational dynamics. In parallel, hierarchical protein-ligand interaction representations are learned from static structural features through geometry-aware message passing, soft clustering, and bidirectional cross-attention. Finally, CPES fuses the curvature-informed dynamic representations with static interaction representations for affinity regression. Extensive evaluations on multiple benchmark datasets demonstrate that CPES achieves improved predictive performance and offers physical interpretability.

05.
medRxiv (Medicine) 2026-06-20

EpiLink: a simulation-based compatibility model for genomic transmission clustering in infectious disease surveillance

Identifying recently linked infections from pathogen genome sequences is central to infectious disease surveillance, yet many clustering approaches rely on fixed genetic distance thresholds whose relationship to transmission is often unclear. This limitation is especially important in rapidly growing outbreaks and superspreading events, where many cases may be sampled close together in time and share little genetic variation, making true transmission links difficult to distinguish from other closely related infections. Supervised models can improve discrimination, but they require labelled transmission data that are rarely available during outbreak response. We developed EpiLink, a threshold-free method that estimates whether two cases are compatible with recent transmission. Here, compatibility means how well the observed genetic distance and sampling-time difference between two cases fit what would be expected if they were linked by defined recent transmission scenarios. EpiLink simulates plausible recent transmission histories while accounting for uncertainty in infection timing, testing delay, and mutation accumulation, then assigns higher scores to pairs whose observed differences are typical of those simulations. EpiLink was evaluated using both synthetic and empirical SARS-CoV-2 outbreak data from the 2020 Boston epidemic. Two EpiLink variants were compared to a logistic regression model trained on labelled transmission data. One EpiLink variant assumed deterministic mutation accumulation, with genetic differences proportional to elapsed evolutionary time; the other accounted for stochasticity by sampling mutation counts from a Poisson distribution. The logistic regression model performed better at distinguishing linked from unlinked pairs, but EpiLink achieved comparable clustering accuracy. In the Boston data, EpiLink recovered clusters enriched for documented conference and skilled nursing facility outbreaks. EpiLink thus provides an interpretable, simulation-based approach for identifying recent transmission clusters when fixed thresholds are difficult to justify and labelled transmission data are unavailable.

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

Moments in Rough Bergomi and Boundary Attainment in Rough Heston

arXiv:2606.07482v2 Announce Type: replace Abstract: We address two open questions in the rough volatility literature. First, we prove finite positive moments for the rough Bergomi price process, and for a wider class of Gaussian Volterra Bergomi models, in the whole subcritical range under negative correlation. More precisely, if \(\rho\in[-1,0)\), then \(\E[S_T^p]

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

A Dynamical Systems Perspective on the Analysis of Neural Networks

arXiv:2507.05164v2 Announce Type: replace-cross Abstract: In this chapter, we utilize dynamical systems to analyze several aspects of machine learning algorithms. As an expository contribution we demonstrate how to re-formulate a wide variety of challenges from deep neural networks, (stochastic) gradient descent, and related topics into dynamical statements. We also tackle three concrete challenges. First, we consider the process of information propagation through a neural network, i.e., we study the input-output map for different architectures. We explain the universal embedding property for augmented neural ODEs representing arbitrary functions of given regularity, the classification of multilayer perceptrons and neural ODEs in terms of suitable function classes, and the memory-dependence in neural delay equations. Second, we consider the training aspect of neural networks dynamically. We describe a dynamical systems perspective on gradient descent and study stability for overdetermined problems. We then extend this analysis to the overparameterized setting and describe the edge of stability phenomenon, also in the context of possible explanations for implicit bias. For stochastic gradient descent, we present stability results for the overparameterized setting via Lyapunov exponents of interpolation solutions. Third, we explain several results regarding mean-field limits of neural networks. We describe a result that extends existing techniques to heterogeneous neural networks involving graph limits via digraph measures. This shows how large classes of neural networks naturally fall within the framework of Kuramoto-type models on graphs and their large-graph limits. Finally, we point out that similar strategies to use dynamics to study explainable and reliable AI can also be applied to settings such as generative models or fundamental issues in gradient training methods, such as backpropagation or vanishing/exploding gradients.

08.
arXiv (CS.LG) 2026-06-19

A Hybrid GNN-FEM Framework for Phase-Field Fracture Simulation. Physics-Preserving Hybridization for Generalizable Surrogate Modeling

arXiv:2606.19378v1 Announce Type: new Abstract: Scientific machine learning (SciML) has emerged as a promising approach for accelerating simulations of complex physical systems, yet achieving physically consistent and generalizable predictions for nonlinear, history-dependent problems remains a central challenge. In this study, we propose a hybrid GNN–FEM framework for efficient and generalizable phase-field fracture modeling. While phase-field approaches provide a robust variational framework for simulating complex crack evolution, their high computational cost limits practical applications because they require solving coupled, nonlinear, and history-dependent systems within an incremental finite element procedure. To address this challenge, a graph neural network surrogate is integrated into the conventional staggered scheme, replacing the phase-field update at each load increment while retaining the FEM-based displacement solver to enforce mechanical equilibrium and boundary conditions. By preserving the incremental solution structure, the framework remains consistent with history-dependent fracture evolution without requiring the surrogate to approximate the full solution trajectory. This selective surrogate strategy emphasizes the identification of a physically meaningful and incrementally structured learning target, rather than relying on brute-force data generation to learn the full fracture process. The proposed framework achieves strong generalization across varying geometries, loading conditions, material properties, and discretizations through dimensionless feature design, a graph-based formulation on mesh-based domains, and a physics-informed loss derived from the governing phase-field equation. Numerical experiments demonstrate that the hybrid approach reduces computational cost while maintaining accuracy compared with conventional FEM, and exhibits robust predictive performance across diverse problem settings.

09.
arXiv (CS.LG) 2026-06-15

Direct Fisher Score Estimation for Likelihood Maximization

arXiv:2506.06542v2 Announce Type: replace-cross Abstract: We study the problem of likelihood maximization when the likelihood function is intractable but model simulations are readily available. We propose a sequential, gradient-based optimization method that directly models the Fisher score based on a local score matching technique which uses simulations from a localized region around each parameter iterate. By employing a linear parameterization to the surrogate score model, our technique admits a closed-form, least-squares solution. This approach yields a fast, flexible, and efficient approximation to the Fisher score, effectively smoothing the likelihood objective and mitigating the challenges posed by complex likelihood landscapes. We provide theoretical guarantees for our score estimator, including bounds on the bias introduced by the smoothing. Empirical results on a range of synthetic and real-world problems demonstrate the superior performance of our method compared to existing benchmarks.

10.
arXiv (CS.CL) 2026-06-11

Quantifying Subliminal Behavioral Transfer Ratios in Language Model Distillation

Distillation of a language model intended to transfer benign behavior to a student model may also transfer undesirable characteristics, if they are present in the teacher model, a phenomenon known as subliminal learning. While qualitative evidence supports the existence of this effect, its magnitude has not been systematically characterized. This study quantifies subliminal behavioral transfer ratios by steering two teacher models (Llama-2-7B-Chat and Qwen2.5-7B-Instruct) at varying steering strengths and distilling student models using only benign data. Evaluation on 100 JailbreakBench prompts with GPT-4.1, serving as the evaluator, indicates that transfer is robust but exhibits distinct scaling behaviors. Llama-2 demonstrates a sharp threshold ($\tau = {0.25,0.32} \ beyond \ \alpha = -0.15$), whereas Qwen2.5 displays continuous and higher levels of transfer ($\tau$ up to $0.61$).

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

UMA-Split: unimodal aggregation for both English and Mandarin non-autoregressive speech recognition

This paper proposes a unimodal aggregation (UMA) based nonautoregressive model for both English and Mandarin speech recognition. The original UMA explicitly segments and aggregates acoustic frames (with unimodal weights that first monotonically increase and then decrease) of the same text token to learn better representations than regular connectionist temporal classification (CTC). However, it only works well in Mandarin. It struggles with other languages, such as English, for which a single syllable may be tokenized into multiple fine-grained tokens, or a token spans fewer than 3 acoustic frames and fails to form unimodal weights. To address this problem, we propose allowing each UMA-aggregated frame map to multiple tokens, via a simple split module that generates two tokens from each aggregated frame before computing the CTC loss.

12.
arXiv (CS.AI) 2026-06-11

Physics-informed generative AI for semiconductor manufacturing: Enforcing hard physical constraints in generative models by construction

arXiv:2606.11247v1 Announce Type: cross Abstract: Generative models are increasingly used to propose designs, data, and control actions for physical systems, yet many such systems are governed by hard physical constraints rather than by perceptual plausibility. Semiconductor manufacturing provides a demanding test case: generated masks, layouts, synthetic defect data, and process recipes must obey lithography, transport, reaction, and device-physics constraints, because physically invalid samples are not merely low quality but unusable. This Perspective argues that semiconductor manufacturing exposes a broader computational-science challenge, namely that generative AI for constrained physical domains must be physics-informed by construction, not corrected only through post-hoc filtering. We survey the emerging architectural toolkit, including physics-informed diffusion, PDE-constrained variational models, neural-operator priors, and conservation-law-respecting generative networks, and show how it connects to differentiable lithography, TCAD, process simulation, and autonomous experimentation. We identify four integration patterns between generative models and physics-based simulators, and we propose a research agenda centered on physics-fidelity benchmarks, differentiable simulator infrastructure, and multimodal foundation models for physical design and manufacturing. The central claim is analytical rather than rhetorical: where physical validity is the binding criterion of success, architectures that enforce it by construction should be expected to outperform those that filter for it after the fact, and the fab is the setting where this distinction is sharpest.

13.
arXiv (CS.CV) 2026-06-17

DiffAttn: Diffusion-Based Drivers' Visual Attention Prediction with LLM-Enhanced Semantic Reasoning

Drivers' visual attention provides critical cues for anticipating latent hazards and directly shapes decision-making and control maneuvers, where its absence can compromise traffic safety. To emulate drivers' perception patterns and advance visual attention prediction for intelligent vehicles, we propose DiffAttn, a diffusion-based framework that formulates this task as a conditional diffusion-denoising process, enabling more accurate modeling of drivers' attention. To capture both local and global scene features, we adopt Swin Transformer as encoder and design a decoder that combines a Feature Fusion Pyramid for cross-layer interaction with dense, multi-scale conditional diffusion to jointly enhance denoising learning and model fine-grained local and global scene contexts. Additionally, a large language model (LLM) layer is incorporated to enhance top-down semantic reasoning and improve sensitivity to safety-critical cues. Extensive experiments on four public datasets demonstrate that DiffAttn achieves state-of-the-art (SoTA) performance, surpassing most video-based, top-down-feature-driven, and LLM-enhanced baselines. Our framework further supports interpretable driver-centric scene understanding and has the potential to improve in-cabin human-machine interaction, risk perception, and drivers' state measurement in intelligent vehicles.

14.
arXiv (CS.AI) 2026-06-19

Playful Agentic Robot Learning

arXiv:2606.19419v1 Announce Type: cross Abstract: Current agentic robot systems can write executable Code-as-Policy programs, observe feedback, and revise behavior across multiple attempts, but they remain largely task-driven: reusable skills are acquired only after explicit instructions. We study Playful Agentic Robot Learning, where an embodied coding agent uses self-directed play as a continual skill-learning stage before downstream tasks arrive. We introduce RATs, Robotics Agent Teams designed for play-time skill acquisition. During play, RATs proposes novel yet learnable exploratory tasks, plans and executes robot-code policies, verifies intermediate progress, diagnoses failures, retries with dense, step-level feedback, and distills successful executions into a persistent code skill library. At test time, the agent reuses relevant skills from this frozen library to help solve new tasks. Experiments in LIBERO-PRO and MolmoSpaces show that play-learned skills improve held-out downstream tasks over no-play and random-play baselines, with 20.6 and 17.0 percentage-point gains over CaP-Agent0 on LIBERO-PRO and MolmoSpaces, respectively. Moreover, the learned skills can be plugged into other inference-time Code-as-Policy agents by simply retrieving them into the context, improving RoboSuite and real-world transfer by 8.9 and 8.8 points, respectively, without finetuning the underlying model.

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

Active Learning with Low-Rank Structure for Data Selection

arXiv:2606.16045v1 Announce Type: new Abstract: In the data selection problem, the objective is to choose a small, representative subset of data that can be used to efficiently train a machine learning model. Sener and Savarese [ICLR 2018] showed that, given an embedding representation of the data and suitable geometric assumptions, heuristics based on $k$-center clustering can be used to perform data selection. This perspective was further explored by Axiotis et. al. [ICML 2024], who proposed a data selection approach based on $k$-means clustering and sensitivity sampling. However, these methods rely on the assumption that the dataset exhibits intrinsic geometric structure that can be effectively captured by clustering, whereas many modern datasets instead possess global algebraic structure that is better exploited by low-rank approximation or principal component analysis. In this paper, we introduce a new data selection framework based on low-rank approximation and residual-based sampling, formulated through the lens of row subset selection and loss-preserving coreset construction. Given an embedding representation of the data satisfying mild regularity conditions, which can be interpreted as algebraic or angular notions of Lipschitz continuity, we show that it is possible to select a weighted subset of $\tilde{O}\left(k + \frac{1}{\varepsilon^2}\right)$ data points whose average loss approximates the average loss over the full dataset within a $(1+\varepsilon)$ relative error, up to an additive $\varepsilon \Phi_k$ term, where $\Phi_k$ denotes the optimal rank-$k$ approximation cost of the embedding matrix. We complement these theoretical guarantees with empirical evaluations, demonstrating that on a range of real-world datasets, our data selection approach achieves improved performance over prior strategies based on uniform sampling or clustering-based sensitivity sampling.

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

Dealing with Annotator Disagreement in Hate Speech Classification

Hate speech detection is a crucial task, especially on social media where harmful content can spread quickly. Collecting social media content (tweets etc.) to train machine learning models is easy, but detecting and categorizing hate speech can be difficult due to the inherently subjective nature. This subjectivity leads to frequent disagreement among annotators, particularly for subtle or borderline content. Traditional approaches either discard non-consensus samples or force a ''gold standard'' through expert adjudication, ignoring valuable information about uncertainty and diverse human perspectives. We examine the largely overlooked problem of annotator disagreement in hate speech classification and evaluate a range of aggregation methods, including majority voting, ordinal strategies (minimum, maximum, and mean), and analyze their impact across binary, 4-class, and 6-class classification tasks. In addition, we leverage annotators' perceived hate speech strength scores to explore regression-based and hybrid modeling approaches. Among others, we show that filtering non-consensus samples results in over-optimistic results and that the perceived strength provides a complementary signal that enhance classification performance. Finally, we establish new state-of-the-art results for hate speech detection in Turkish tweets, and demonstrate that annotator disagreement, when properly modeled, is a valuable resource for building more robust and reliable systems.

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

A Unified Theory of Sinusoidal Activation Families for Implicit Neural Representations

Implicit Neural Representations (INRs) model continuous signals with compact neural networks and have become a standard tool in vision, graphics, and signal processing. A central challenge is accurately capturing fine detail without heavy hand-crafted encodings or brittle training heuristics. Across the literature, periodic activations have emerged as a compelling remedy: from SIREN, which uses a single sinusoid with a fixed global frequency, to more recent architectures employing multiple sinusoids and, in some cases, trainable frequencies and phases. We study this family of sinusoidal activations and develop a principled theoretical and practical framework for trainable sinusoidal activations in INRs. Concretely, we instantiate this framework with Sinusoidal Trainable Activation Functions (STAF), a Fourier-like activation whose amplitudes, frequencies, and phases are learned. Our analysis (i) establishes a Kronecker-equivalence construction that expresses trainable sinusoidal activations with standard sine networks and quantifies expressive growth, (ii) characterizes how the Neural Tangent Kernel (NTK) spectrum changes under trainable sinusoidal parameterization, and (iii) provides an initialization that yields standard normal post-activations without asymptotic central limit theorem (CLT) arguments. Empirically, on images, audio, shapes, inverse problems (super-resolution, denoising) and NeRF, STAF is competitive and often stronger on distortion-oriented reconstruction metrics such as PSNR/SSIM across the evaluated INR tasks, with favorable parameter efficiency under layer-wise sharing. While periodic activations can alleviate practical manifestations of spectral bias, our results indicate they do not eliminate it; instead, trainable sinusoids can improve the observed capacity-optimization trade-off in the evaluated settings.

18.
arXiv (quant-ph) 2026-06-12

A Quantum Algorithm for Random Number Generation

arXiv:2606.13034v1 Announce Type: new Abstract: We present a quantum algorithm for random number generation that achieves a provable quadratic speedup over classical Markov chain mixing, building on the Diaconis-Shahshahani Fourier analysis of the top-to-random card shuffle. The algorithm integrates three quantum primitives into a unified mixing circuit: the Quantum Fourier Transform (QFT), which diagonalizes the Markov transition operator; controlled phase rotations, which encode the shuffle eigenvalue spectrum; and the Grover diffusion operator, which acts as a quantum analogue of the Aldous-Diaconis strong uniform stopping time by reflecting amplitudes about their mean at each iteration. For an n-qubit register, the mixing time is O(\sqrt{n \log n}) iterations. Extending to m qudits of local dimension d reduces this to O(\sqrt{\log_d N}) iterations, where N = d^m, compared to the classical O(n \log n) bound. The qudit formulation further reduces QFT circuit depth from O(\log^2 N) to O(\log_d^2 N) gates per layer by encoding the same N-state space using m = \log_d N subsystems instead of \log_2 N qubits. We validate both variants on IBM superconducting hardware.

19.
arXiv (quant-ph) 2026-06-16

Experimental realization of the complete seven-phase Anderson-localization landscape

arXiv:2606.14825v1 Announce Type: cross Abstract: Anderson localization has evolved far beyond the conventional dichotomy between extended and localized states. Modern localization theory predicts a complete transport hierarchy comprising extended, critical, and localized phases together with all coexistence phases among them, forming a seven-phase Anderson-localization landscape. Despite its fundamental importance, this hierarchy has never been experimentally realized within a single system. Here we realize the complete seven-phase Anderson-localization landscape in a one-dimensional Floquet photonic lattice. By engineering quasiperiodic hopping profiles containing inhomogeneously distributed hopping zeros, we generate critical states and enable their coexistence with extended and localized sectors. The resulting transport regimes are directly resolved through their distinct spatiotemporal dynamics, including ballistic expansion, confined critical oscillations, and persistent localization. We observe all seven phases, including the elusive triply coexisting extended-critical-localized phase, and experimentally track the phase transitions connecting them. Our results establish the first complete experimental map of the Anderson-localization landscape and provide a unified platform for investigating mobility edges, multifractality, and programmable coherent transport.

20.
PLOS Medicine 2026-05-27

Sequential chemo-immunotherapy followed by standard versus reduced thoracic radiotherapy for older and/or frail stage III non-small-cell lung cancer: A randomized open-label cohort trial

Authors:

by Wei-Xiang Qi, Shuyan Li, Mengdi Wang, Huan Li, Feifei Xu, Lei Yao, Biao Yu, Linlin Chen, Gang Cai, Cheng Xu, Xianwen Sun, Zhiyao Bao, Jiayi Chen, Yi Xiang, Shengguang Zhao Background The appropriateness of concurrent chemoradiotherapy (cCRT) for older or clinically vulnerable stage III unresectable non-small-cell lung cancer (NSCLC) patients remains contentious. Furthermore, the survival implications of de-escalating thoracic radiotherapy (RT) intensity in this population have not been conclusively elucidated. Methods and findings We conducted a phase II randomized, open-label, two-cohort (non-comparative) trial at a tertiary hospital in China (NCT05557552). Between September 30, 2022 and April 30, 2024, we enrolled 56 older and/or frail patients with stage III NSCLC who were ineligible for cCRT. The primary endpoint was the 1-year progression-free survival (PFS) rate estimated using the Kaplan–Meier method. Secondary endpoints included objective response rate (ORR), overall survival (OS), and safety. In the intention-to-treat (ITT) set, which included all 56 randomized patients who received at least one dose of study treatment, the 1-year PFS was 84.3% (95% confidence interval [CI] [70.3%, 98.3%]) in the standard RT group and 70.7% (95% CI [54.3%, 87.1%]) in the reduced RT group. In the per-protocol set (53 patients), the 1-year PFS was 82.9% (95% CI [68.9%, 98.8%]) in the standard RT group and 73.4% (95% CI [58.3%, 92.4%]), with a median follow-up of 24 months. Among 56 patients in the safety analysis set, 71.4% of patients experienced grade 3/4 adverse events (AEs) in the standard RT group and 53.6% in the reduced RT group. One patient (3.6%) in the reduced RT and three patients (10.7%) in the standardized RT experienced grade 5 AEs. The main limitations are the non-comparative design, small sample size, and lack of power to establish non-inferiority or superiority. Conclusion The current study suggested that reduced RT combined with sequential chemo-immunotherapy might be feasible for older/frail patients intolerant to cCRT, showing numerically similar survival outcomes. These exploratory findings warrant confirmation in larger, adequately powered randomized trials. Trial registration The trial had been registered on ClinicalTrials.gov on Sep 30, 2022.ClinicalTrials.gov NCT05557552

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

Learn from Your Mistakes: Tree-like Self-Play for Secure Code LLMs

arXiv:2606.03489v2 Announce Type: replace-cross Abstract: While Large Language Models (LLMs) excel in code generation, they remain prone to replicating subtle yet critical vulnerabilities endemic to their training data. Current alignment techniques, such as Supervised Fine-Tuning (SFT) and Reinforcement Learning (RL), typically apply coarse-grained optimization at the sequence level. This approach often fails to address the localized nature of security flaws, where a single incorrect token choice can compromise an entire program. To bridge this gap, we introduce Tree-like Self-Play (TSP), a framework that reframes secure code generation as a fine-grained sequential decision process. Unlike standard methods that blindly maximize likelihood, TSP constructs a decision tree where the model explores branching trajectories–generating both secure "golden paths" and vulnerable variants. By treating code generation as a self-play game, the model learns to strictly discriminate against its own localized errors. This provides a dense, on-policy learning signal that forces self-correction precisely at the critical decision nodes where vulnerabilities typically emerge. Our experiments demonstrate that TSP fundamentally enhances model reliability. In Python security benchmarks, TSP boosts CodeLlama-7B's pass rate (SPR@1) to 75.8%, significantly outperforming SFT (57.0%) and unstructured self-play baselines. Crucially, TSP induces robust out-of-distribution generalization: the model not only reduces vulnerabilities in unseen categories (CWEs) by 24.5% but also successfully transfers security principles learned from C/C++ to diverse languages, including Python, Go, and JavaScript. This suggests that TSP does not merely memorize patches, but internalizes abstract, language-agnostic security logic.

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

Dual-Network PINNs for Optimal Control: A Reproducible Benchmark on the Mass-Spring-Damper System

arXiv:2606.15271v1 Announce Type: cross Abstract: This work presents a transparent and reproducible benchmark study of a direct dual-network Physics-Informed Neural Network (PINN) formulation for the optimal control of a mass-spring-damper system. The classical linear-quadratic optimal control problem is solved by two independent classical methods – Pontryagin's Minimum Principle with single shooting, and direct transcription through trapezoidal collocation – and recast as a constrained optimization problem solved by two feedforward neural networks: a state network whose boundary conditions are enforced exactly through a composite cubic-and-mask ansatz, and an unconstrained control network. The composite loss combines the physics residual at the collocation points with a trapezoidal approximation of the cost functional, weighted by a single scalar hyperparameter. On the benchmark considered, the PINN reproduces the classical optimal cost to four significant digits, satisfies the terminal state constraints exactly by construction, and produces pointwise state and control errors that fall within the spread of the two classical references. Training is approximately two orders of magnitude slower than classical shooting on this benchmark, which is honestly reported. The contribution is methodological clarity rather than methodological novelty: the formulation and the accompanying Google Colab implementation are intended to lower the barrier to entry for practitioners exploring PINN-based optimal control without prior exposure to adjoint methods or two-point boundary value problems.

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

A Unified Framework for Structured Flow Modeling: From Representation to Verification and Model Discovery

Authors:

arXiv:2605.18250v3 Announce Type: replace-cross Abstract: Many dynamical systems can be described in terms of structured flows combining source/sink behavior, cyclic dynamics, and topology-constrained transport. These features arise across a wide range of physical, engineered, and data-driven systems. The objective of this work is to establish a unified perspective on such systems, to identify modeling approaches that balance expressivity, interpretability, computational complexity, and data requirements, and to investigate how highly expressive models can be used to uncover the dominant mechanisms underlying observed dynamics. Starting from the Helmholtz-Hodge decomposition of continuous vector fields, we review the recently proposed Graph Vector Field (GVF) framework and its discrete representation on simplicial complexes. We then introduce a hierarchy of alternative approaches, including parametric conditional models, linear graph dynamical systems, and reduced Hodge representations. Finally, we propose a verification and validation methodology based on benchmark datasets from well-understood physical systems and on systematic model-reduction and ablation studies. The resulting family of structured-flow models within a common framework, ranging from low-dimensional parametric representations to full GVF formulations, supports a diagnostic methodology in which gradient, curl, harmonic, and topological contributions are systematically assessed through ablation studies. This process enables the identification of dominant mechanisms underlying the observed dynamics and guides the construction of simplified models tailored to the available data and operational constraints. By separating structural verification, behavioral verification, and domain-specific validation, the proposed approach provides a foundation for scalable and interpretable analysis of complex dynamical systems across multiple application domains.

24.
Nature Medicine 2026-06-17

Why large-scale randomized trials of live-attenuated shingles vaccination for dementia prevention are urgently needed

In my view, we have never had as robust a body of evidence from observational data on an intervention for dementia as we do for live-attenuated shingles vaccination. Both a recent US National Institutes of Health expert workshop and an international expert consensus on Alzheimer’s disease drug repurposing identified large-scale randomized trials of shingles vaccination for dementia prevention as the crucial next step for the field.

25.
medRxiv (Medicine) 2026-06-18

Antimicrobial-resistant E. coli in human, animal and environmental reservoirs in rural Bangladeshi households with young children

In low-income countries, ESBL-producing Escherichia coli (ESBL-EC) is frequently detected in humans, animals and household environments, indicating widespread exposure to antimicrobial resistance (AMR). Established risk factors such as antibiotic use do not explain the high community carriage of AMR in all settings; identifying the dominant exposure pathways can inform interventions against AMR. We aimed to investigate (i) animal-human-environment sharing of AMR by assessing associations between the abundance of ESBL-EC in the household environment, domestic animal feces and young children's stool and (ii) household factors associated with ESBL-EC abundance in these reservoirs. We enrolled 112 households from the CRADLE trial in rural Bangladesh. We enumerated ESBL-EC in drinking water, food, child hand rinses, outdoor soil, indoor floor swabs, chicken and cow feces, and stool from children aged 6 months. We recorded indicators of sanitation, animal ownership/management, human and animal antibiotic use, and child exposure behaviors using structured questionnaires and spot checks. The highest prevalence of ESBL-EC was in child stool (95.6%) and animal feces (82.3-96.9%), followed by soil (48.2%) and floors (36.6%); < 10% of food, child hands and drinking water harbored ESBL-EC. The abundance of ESBL-EC in child stool was not associated with its abundance in any sampled matrix; the abundance in chicken but not cow feces showed positive correlations with soil, floors, child hands, and drinking water (correlation coefficients: 0.19-0.39, p-values < 0.05). Higher-quality latrines (improved, pour-flush, with slab) were associated with lower ESBL-EC abundance across matrices; unsafe animal management (animals roaming or spending the night inside the home) was associated with higher abundance. Child antibiotic use and exposure behaviors (soil ingestion, time spent on floor) were not associated with ESBL-EC abundance in child stool. We observed high AMR colonization among young children and domestic animals in rural Bangladesh not explained by traditional fecal-oral exposure pathways. Future studies should explore additional pathways and assess whether sanitation and animal management improvements can reduce AMR.