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01.
arXiv (quant-ph) 2026-06-17

When Renormalisation Remembers: UV/IR Mixing as an Entanglement Bridge

作者:

arXiv:2606.17147v1 Announce Type: cross Abstract: Renormalisation is traditionally understood to be a Wilsonian memoryless process in which ultraviolet (UV) degrees of freedom gradually decouple, leaving an autonomous infrared (IR) description. However this need not be the case: in UV/IR mixed theories correlations between widely separated scales can persist. In this work I recast UV/IR mixing as a Hilbert-space phenomenon, realised as correlations across renormalisation scales. This formulation is implemented using the Born-Reciprocal Tensor Network (BRTN), a new configuration of tensor network that is globally symmetric under phase-space reciprocity. On this network I prepare the vacuum and reproduce the expected radiative corrections. The resulting renormalisation geometry exhibits memory, with a bridge linking reciprocal representations of IR physics, whose cross-bridge entanglement provides a precise criterion for the viability of an effective description. I analyse when this criterion is met, and show that there is a large-volume limit, with the fundamental scale held fixed, in which the obstruction to a local description scales away: Wilsonian behaviour is restored and renormalisation forgets. The BRTN therefore provides a concrete and calculable platform for UV/IR mixing.

02.
arXiv (CS.AI) 2026-06-11

A New Perspective on Precision and Recall for Generative Models

arXiv:2511.02414v3 Announce Type: replace Abstract: With the recent success of generative models in image and text, the question of their evaluation has recently gained a lot of attention. While most methods from the state of the art rely on scalar metrics, the introduction of Precision and Recall (PR) for generative model has opened up a new avenue of research. The associated PR curve allows for a richer analysis, but their estimation poses several challenges. In this paper, we present a new framework for estimating entire PR curves based on a binary classification standpoint. We conduct a thorough statistical analysis of the proposed estimates. As a byproduct, we obtain a minimax upper bound on the PR estimation risk. We also show that our framework extends several landmark PR metrics of the literature which by design are restrained to the extreme values of the curve. Finally, we study the different behaviors of the curves obtained experimentally in various settings.

03.
arXiv (CS.CL) 2026-06-18

SenFlow: Inter-Sentence Flow Modeling for AI-Generated Text Detection in Hybrid Documents

Sentence-level AI-generated text detection (S-AGTD) for hybrid documents, where humans and LLMs co-author one text, faces two gaps: existing methods classify each sentence in isolation, discarding inter-sentence dependencies, and existing benchmarks omit the newest generation of generators. We construct MOSAIC, a benchmark of 16,000 hybrid documents over PubMed and XSum, generated by DeepSeek-V3.2 and Kimi K2 under stringent quality controls including a perplexity-consistency filter absent from prior benchmarks. We recast S-AGTD as structured prediction over the document sentence sequence and instantiate it as SenFlow, integrating graph-based inter-sentence propagation with linear-chain CRF decoding in a single document-level pass over a sentence graph. SenFlow reaches state-of-the-art performance on MOSAIC, with a +4.15 pp average Macro-F1 margin on cross-domain transfer, the hardest of three protocols of increasing difficulty. We further find that even after the perplexity filter equalizes overt cues, AI insertions retain a generator-dependent sentence-length gap that sentence-level detectors still exploit. Code and data: https://github.com/luojingkun22/SenFlow

04.
arXiv (math.PR) 2026-06-16

BBP Phase Transition for a Doubly Sparse Deformed Model

arXiv:2603.04832v3 Announce Type: replace Abstract: We prove the equivalent of the Baik, Ben Arous, Péché (2004) phenomenon for a novel, doubly sparse model where both the Wigner noise matrix and signal vector(s) are sparse. Specifically, we consider a deformed sub-Gaussian sparse Wigner ensemble with a fixed number of sub-Gaussian spike vectors of the same-order sparsity added. We show that spike vectors with signals greater than one are correlated with the top eigenvectors of the deformed ensemble and that each spike vector of signal greater than one induces an outlier eigenvalue. Notably, our results hold in the supercritical sparsity regime for the Wigner matrix ($q \gg \frac{\log n}{n}$) and for any sparse spike vector with an unbounded number of entries ($np\to \infty$). No further relationship between the sparsities of the noise matrix ($q$) and spike vectors ($p$) is necessary. This generalizes the work of Benaych-Georges and Nadakuditi (2010) and Péché (2005).

05.
arXiv (CS.AI) 2026-06-11

The Art of Interrogation: Consistency Amplifies Factuality in Spatial Reasoning

arXiv:2606.11918v1 Announce Type: new Abstract: Current Large Reasoning Models (LRMs) exhibit remarkable general capabilities but significantly underperform in spatial reasoning tasks. Existing approaches treat this gap as a knowledge deficit, relying on supervised fine-tuning (SFT) to ingest labeled spatial data from external vision sources or synthetic engines. In contrast, we argue that for many tasks, spatial reasoning capabilities are already present in pre-trained LRMs but require alignment through logical coherence under geometric 2D and 3D constraints. In this work, we propose a self-supervised reinforcement learning (RL) framework that targets the internal reasoning process without requiring ground-truth annotations. By formalizing the notion of consistency verifiers – reward functions that check for geometric and semantic consistency under transformations – we demonstrate that models can improve their spatial reasoning abilities. We use both image transformations, like flipping, and textual transformations, like swapping the order of objects in the question, and propose a new optimal transport-based RL strategy, OT-GRPO, which is a minimal-matching variant of group relative policy optimization tailored to pairwise verifiers. We show that this label-free consistency training approaches the accuracy of models trained with ground-truth supervision and achieves similar generalization across diverse tasks and data domains.

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

HyperTool: Beyond Step-Wise Tool Calls for Tool-Augmented Agents

Tool-augmented LLM agents commonly rely on step-wise atomic tool calls, where each invocation, observation, and value transfer is exposed in the main reasoning trace. This creates an execution-granularity mismatch: locally deterministic tool workflows are unfolded into repeated model-visible decisions, consuming context and forcing the model to manage low-level dataflow in the trace. We introduce HyperTool, a unified executable MCP-style tool interface that changes the model-visible unit of tool execution. A model invokes HyperTool with a code block that can call existing tools through their original schemas, manipulate returned values, and pass intermediate results locally, folding deterministic tool subroutines into a single outer call. To train models to use this interface, we synthesize HyperTool-format trajectories from cross-tool compositional tasks and verify them in real MCP environments. On MCP-Universe, HyperTool improves average accuracy from 15.69\% to 35.29\% on Qwen3-32B and from 9.93\% to 33.33\% on Qwen3-8B, and surpass GPT-OSS and Kimi-k2.5 on average accuracy, showing that our HyperTool can substantially improve multi-step tool use.

07.
arXiv (CS.CV) 2026-06-15

MooMIns – Monocular 3D Reconstruction and Object Pose Estimation from Multiple Instances

Simultaneous 3D reconstruction and 6D object pose estimation from a single monocular image is an inherently ill-posed problem. In industrial settings, however, multiple instances of an object are often randomly arranged in bins, implicitly providing several views of the same object within a single image. We show that this implicit multi-view geometry can be exploited to simultaneously reconstruct the object in 3D and estimate the 6D pose of each visible object instance. We present MooMIns, a new Gaussian-splatting-based approach that inverts the original Gaussian splatting formulation: instead of rendering a single scene from multiple cameras, we render multiple object instances from a single camera. Our method is initialized with SAM3 instance segmentation masks and a modified Structure from Motion (SfM) pipeline. In contrast to learned monocular depth estimation, we perform true geometry-based reconstruction from image evidence, avoiding hallucinations caused by training data priors. We evaluate MooMIns on synthetic and real bin-picking scenarios, and demonstrate accurate reconstruction of previously unseen objects as well as reliable pose estimation of individual instance

08.
arXiv (CS.LG) 2026-06-16

The Complexity of Min-Max Optimization for Quadratic Polynomials

arXiv:2606.17000v1 Announce Type: cross Abstract: We prove that computing approximate stationary points of min-max optimization over the hypercube is PPAD-hard for quadratic polynomials. This holds even when the polynomials are multilinear, each variable appears in at most three monomials, and the approximation factor is inverse polynomial. As a direct consequence, we obtain the first PPAD-hardness results for two-team zero-sum polymatrix games.

09.
arXiv (CS.AI) 2026-06-17

Belief-Space Control for Personalized Cancer Treatment via Active Inference

arXiv:2606.10376v2 Announce Type: replace Abstract: Cancer treatment is at the core a sequential decision-making problem with partial observability, latent patient heterogeneity, and explicit constraints on the budget for medical measurements. Unlike standard Reinforcement Learning (RL) approaches that control state trajectories, cancer treatments permanently modify patients' transition dynamics, changing how states evolve over time. We model cancer treatment as a belief-space planning problem using active inference, deriving an expected free-energy objective that unifies goal-directed control and information acquisition under measurement budgets without. We implement this framework using real clinical cancer data from the AACR Project GENIE Biopharma Collaborative dataset. Results on clinical data demonstrate a simultaneous patient categorization and high treatment efficacy, under real measurement and treatment constraints.

10.
arXiv (CS.LG) 2026-06-16

STAR-NT: Spatiotemporal Acceleration of Real-Time Neural Transparency Rendering

arXiv:2606.16747v1 Announce Type: cross Abstract: Neural order-independent transparency delivers high-quality rendering of overlapping transparent surfaces, but its geometry passes and network input generation remain costly, particularly on mobile and legacy hardware. We present a spatiotemporal acceleration framework that exploits spatial and temporal coherence to reduce this overhead while preserving visual quality. Spatially, we use adaptive quadtree-based screen-space subdivision to scale geometry pass resolution according to local color variance. Temporally, selected frames reuse the previous transparency result through depth-based reprojection instead of full rendering. Together, these optimizations reduce rendering cost and integrate efficiently into existing real-time rendering pipelines.

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

Acceleration of an algebraic multigrid pressure solver using graph neural networks

arXiv:2606.19251v1 Announce Type: cross Abstract: Solving the pressure-Poisson equation remains the primary computational bottleneck in incompressible unstructured flow solvers primarily due to the inherent sensitivity of traditional linear solvers to mesh irregularities. This work introduces a data-driven algebraic multigrid (AMG) smoother that uses a modified graph convolutional isomorphism network (GCIN). The graph neural network predicts optimal polynomial coefficients to construct a sparse pseudo-inverse operator across diverse grid topologies. The coefficients are optimized to reduce the residual after each V-cycle iteration. By directly capturing the algebraic structure of the system from the sparse coefficient matrix, the proposed method maintains the solver's linearity while adapting to local anisotropies in unstructured grids. Our framework demonstrates significant performance gains by reducing the number of V-cycles required for a given tolerance and delivering wall-clock speedups from 4% to 37% across diverse benchmarks. Notably, the model exhibits robust generalization by maintaining efficiency on meshes up to 128 times larger than those seen in training, and by accelerating the solver's convergence on unseen industry-relevant problems such as the AirfRANS dataset.

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

Towards Fast GNN Surrogates for CO2 Migration in Complex Geological Formations

arXiv:2606.17180v1 Announce Type: new Abstract: This chapter discusses how a data-driven machine learning approach can reproduce key aspects of the physical behavior of multiphase flows in complex geological formations. We propose an end-to-end graph neural surrogate tailored to CO$_2$ plume migration forecasting in geological storage. The method is evaluated on the SPE11A benchmark, a well-known industry test case designed to assess CO$_2$ storage scenarios and characterized by sharp gas-water interfaces, strong advective transport, and rapid convective mixing with fingering development. The benchmark is reformulated as a graph in which nodes represent computational cells and edges encode transmissibility-based interactions enriched with geometric attributes. Directional transport arising from grid geometry, permeability contrasts, and geological heterogeneity is captured through an anisotropic message-passing mechanism, where interaction weights are computed via geometry-conditioned edge embeddings, biasing message aggregation toward physically relevant transport directions. Temporal evolution is modeled in latent space using an autoregressive residual formulation trained with multi-step supervision. The proposed model produces competitive forecasts of gas saturation and liquid-phase density, which are key indicators for CO$_2$ storage monitoring, with cumulative errors that remain moderate over extended forecasting horizons.

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

DySink: Dynamic Frame Sinks for Autoregressive Long Video Generation

Autoregressive long video generation often adopts bounded-memory streaming for efficiency, typically combining local windows for short-term continuity with static early-frame sinks as long-range anchors. However, this fixed allocation keeps early frames cached even when the current visual state has substantially diverged from them, while discarding potentially more relevant intermediate history. As a result, the retained long-range context may become less adaptive and bias generation toward outdated cues; in severe cases, RoPE-induced phase re-alignment can homogenize inter-head attention and cause sink collapse, where content regresses toward sink frames. We propose DySink, a retrieval-based framework that maintains a compact memory bank and selects visually relevant historical frames as dynamic frame sinks. DySink couples adaptive retrieval with a sink anomaly gate, which detects excessive inter-head consensus over retrieved context and suppresses collapse-prone context. Experiments on minute-long videos show that DySink consistently improves dynamic degree over strong baselines while also achieving higher temporal quality. The code and model weights will be released at https://github.com/yebo0216best/DySink.

14.
arXiv (CS.CV) 2026-06-15

CausalMotion: Structured Physical Reasoning as Keyframe and Trajectory Guidance for Training-Free Video Generation

Recent advances in diffusion-based video generation have significantly improved visual quality and short-term temporal coherence. However, existing methods still struggle to produce videos with physically consistent and causally plausible dynamics, especially in scenarios involving long-horizon interactions. This limitation arises from the fact that video diffusion models primarily learn physical consistency implicitly, while vision-language models can directly model physical laws. Based on this idea, in this work, we propose CausalMotion, a training-free framework that injects explicit physical reasoning into video generation through structured intermediate representations. Our key idea is to decouple reasoning from generation by leveraging a vision-language model to decompose a text prompt into a sequence of causally consistent keyframes and object-centric motion trajectories. These representations are then aligned and integrated as soft constraints to guide a pretrained video diffusion model during inference. This design enables explicit modeling of object dynamics and causal transitions without requiring additional training or supervision. Extensive experiments show that our method consistently improves physical plausibility and temporal coherence, particularly in dynamics-intensive scenarios, while maintaining high perceptual video quality.

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

Phishing Email Detection Using Large Language Models

arXiv:2512.10104v2 Announce Type: cross Abstract: Email phishing is one of the most prevalent and globally consequential vectors of cyber intrusion. As systems increasingly deploy Large Language Models (LLMs) applications, these systems face evolving phishing email threats that exploit their fundamental architectures. Current LLMs require substantial hardening before deployment in email security systems, particularly against coordinated multi-vector attacks that exploit architectural vulnerabilities. This paper proposes LLMPEA, an LLM-based framework to detect phishing email attacks across multiple attack vectors, including prompt injection, text refinement, and multilingual attacks. We evaluate three frontier LLMs (e.g., GPT-4o, Claude Sonnet 4, and Grok-3) and comprehensive prompting design to assess their feasibility, robustness, and limitations against phishing email attacks. Our empirical analysis reveals that LLMs can detect the phishing email over 90% accuracy while we also highlight that LLM-based phishing email detection systems could be exploited by adversarial attack, prompt injection, and multilingual attacks. Our findings provide critical insights for LLM-based phishing detection in real-world settings where attackers exploit multiple vulnerabilities in combination.

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

An Evaluation of Data Leakage Risks in Tool-Using LLM Agents in Realistic Scenarios

arXiv:2606.17114v1 Announce Type: cross Abstract: AI agents are increasingly being adopted in enterprise and personal settings with access to emails, databases, documents, and other tools where they can read, update, and disseminate sensitive information. Much of prior research on data leakage risks in agents has focused on adversarial data exfiltration through prompt injections and jailbreaks. However, sensitive information may also be exposed during non-adversarial use, creating leakage risks even when users issue benign requests. We report a joint evaluation by the Singapore AI Safety Institute and the Korea AI Safety Institute examining agent data leakage in 12 realistic, non-adversarial tasks spanning customer support, DevOps, web automation, and enterprise and personal productivity. The evaluation covers five risk types: lack of data awareness, audience awareness, policy compliance, data minimization, and access-boundary awareness. Both institutes tested a common set of scenarios mirroring real-world deployments using independent testing environments and task-specific LLM-judge rubrics. Across the three tested agents, none achieved fully correct and fully safe execution across all scenarios. Successful task completion often coincided with data-handling failures such as accessing unnecessary information or disclosing information to inappropriate recipients, indicating that capability and data-handling safety should be evaluated separately. Qualitative review also revealed claim-action mismatches, simulation-aware behavior, user-simulator role reversal, and interpretation gaps in automated judging. Overall, the results indicate that operational data leakage is a first-order agent-safety concern distinct from adversarial exfiltration and provide a methodology for future evaluations of agent data-handling safety.

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

Sample from What You See: Visuomotor Policy Learning via Diffusion Bridge with Observation-Embedded Stochastic Differential Equation

arXiv:2512.07212v3 Announce Type: replace Abstract: Imitation learning with diffusion models has advanced robotic control by capturing the multi-modal action distributions. However, existing methods typically treat observations only as high-level conditions to the denoising network, rather than integrating them into the stochastic dynamics of the diffusion process itself. As a result, the sampling is forced to begin from random noise, weakening the coupling between perception and control and often yielding suboptimal performance. We propose BridgePolicy, a generative visuomotor policy that directly integrates observations into the stochastic dynamics via a diffusion-bridge formulation. By constructing an observation-informed trajectory, BridgePolicy enables sampling to start from a rich and informative prior rather than random noise, substantially improving precision and reliability in control. A key difficulty is that diffusion bridge normally connects distributions of matched dimensionality, while robotic observations are heterogeneous and not naturally aligned with actions. To overcome this, we introduce a semantic aligner to unify the visual and state inputs and align the observations with action representations, making diffusion bridge applicable to heterogeneous robot data. Extensive experiments across 52 simulation tasks on three benchmarks and 5 real-world tasks demonstrate that BridgePolicy consistently outperforms state-of-the-art generative policies. Our code is available at https://jianghcsr.github.io/BridgePolicy_page/.

18.
arXiv (CS.LG) 2026-06-12

DynamicPTQ: Mitigating Activation Quantization Collapse via Residual-Stream Dynamics

arXiv:2606.12487v1 Announce Type: new Abstract: Post-training quantization (PTQ) is essential for efficient large language model inference, but reliably quantizing activations remains challenging when weights, activations, and KV caches are all quantized to 4-bit precision. A key difficulty lies in massive activations, whose extreme values dominate the activation range and amplify quantization errors. State-of-the-art methods mainly mitigate massive activations through transformation-based smoothing, such as orthogonal rotations and affine scaling, but overlook the cross-layer dynamics of the residual stream. In this paper, we show that massive activations emerge and disappear in a phase-wise pattern across network depth, triggering large residual changes. These changes cause newly injected layer-wise updates to dominate the 4-bit quantization scale and weaken historical residual information. To characterize this behavior, we introduce Jump Ratio and Historical Feature SNR. This suggests that static transformation-based smoothing cannot fully resolve dynamic quantization instability caused by cross-layer residual changes. Based on this analysis, we propose DynamicPTQ, a Dynamic Post-Training Quantization policy for phase-aware mixed-precision activation quantization. DynamicPTQ identifies quantization-sensitive layers from residual-stream dynamics and assigns 8-bit activation precision only to these layers, while keeping weights, KV caches, and other activations in 4-bit precision. It can be directly integrated with strong PTQ baselines such as QuaRot, SpinQuant, and FlatQuant. Experiments on LLaMA-2 and LLaMA-3 show that DynamicPTQ consistently improves perplexity and zero-shot QA performance under W4A4KV4 quantization, while achieving 1.05 to 1.07 times throughput improvement with modest memory overhead. These results demonstrate a practical path toward robust low-bit LLM inference.

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

MeshLoom: Feed-Forward Non-Rigid Registration of Mesh Sequences

We present MeshLoom, a feed-forward registration network that directly reconstructs vertex deformations across mesh sequences. Our approach advances non-rigid registration beyond existing models, which are typically constrained by costly per-instance optimization, narrow object categories, pairwise-only inputs, or merely intermediate outputs. The network is simple and efficient, registering multiple meshes within seconds. At its core lies a topology-aware encoder–decoder design. Specifically, we first introduce a topology-aware point representation that encodes the anchor (reference) mesh's topology into its per-vertex features. This representation strengthens the network's understanding of the anchor-mesh geometry and disambiguates points that are Euclidean-close yet geodesically distant. We then propose a multi-modal encoder that fuses this anchor-mesh representation with complementary cues from each frame, such as shape latents and image features. These multi-source signals are compressed into a compact global motion embedding that captures dense inter-frame correspondence. A lightweight decoder then queries this global embedding with the anchor-mesh point representation, retrieving per-vertex deformations at target timestamps. Through extensive experiments across diverse motions and object categories, we show that MeshLoom achieves state-of-the-art results on non-rigid registration. In addition, we find that our global embedding-then-query paradigm naturally enables the network to generate deformations at intermediate timestamps, which extends MeshLoom to motion interpolation and mesh morphing. Project page: https://meshloom.github.io/ .

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

On the Stability of the Jacobian Matrix in Deep Neural Networks

arXiv:2506.08764v3 Announce Type: replace Abstract: Deep neural networks are known to suffer from exploding or vanishing gradients as depth increases, a phenomenon closely tied to the spectral behavior of the input-output Jacobian. Prior work has identified critical initialization schemes that ensure Jacobian stability, but these analyses are typically restricted to fully connected networks with i.i.d. weights. In this work, we go significantly beyond these limitations: we establish a general stability theorem for deep neural networks that accommodates sparsity (such as that introduced by pruning) and non-i.i.d., weakly correlated weights (e.g. induced by training). Our results rely on recent advances in random matrix theory, and provide rigorous guarantees for spectral stability in a much broader class of network models. This extends the theoretical foundation for initialization schemes in modern neural networks with structured and dependent randomness.

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

Communication-Efficient Verifiable Attention for LLM Inference

arXiv:2606.16352v1 Announce Type: cross Abstract: Computation integrity of remote large language model (LLM) serving can be questionable. For conventional deep neural networks (DNNs), the existing TEE-shielded DNN partitioning (TSDP) approach uses Trusted Execution Environment (TEE) to compute non-linear components and verify the integrity of linear components offloaded to an untrusted GPU. However, directly applying TSDP to Transformer-based LLMs incurs significant TEE computation and TEE-GPU communication overhead. This paper presents Communication-efficient TEE-GPU Attention (\textsc{VeriAttn}) for accelerating verifiable LLM inference. \textsc{VeriAttn} offloads both linear and non-linear computations of attention to the GPU, while TEE performs verification. Moreover, for prefill, \textsc{VeriAttn} uses a two-level pipeline to overlap data movement, TEE pre-/post-processing, and GPU computation. For decoding, when the key-value cache exceeds available GPU memory, \textsc{VeriAttn} partitions attention across TEE and GPU to reduce repeated key-value transfers. Evaluation on an Intel TDX platform shows that \textsc{VeriAttn} achieves 2.60-3.38$\times$ and 3.86-5.42$\times$ acceleration over TSDP for 6k-token prompts and 10k-token outputs during prefill and decoding, respectively.

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

Characterizing Narrative Content in Web-scale LLM Pretraining Data

The narrative composition of web-scale LLM pretraining corpora remains largely unexplored even though narrative is a fundamental mode of human communication. We present the first fine-grained study of narrative features in Dolma, a 3-trillion-token open pretraining corpus. Drawing on narrative theory, we design a framework spanning three core narrative elements (agency, setting, and events) operationalized as 11 interpretable dimensions. After sampling and annotating a diverse set of 400 passages, we finetune and validate NarraBERT, a RoBERTa-based model for fine-grained narrative prediction. We apply NarraBERT to 3M passages, resulting in a new dataset, NarraDolma. We find (i) narrative structure is measurable at scale across extremely heterogeneous data, (ii) we uncover a continuous, multidimensional narrative structure underlying web text, and (iii) narrative qualities are unequally distributed across pretraining sources and topics in ways that current curation practices neither measure nor account for. Our framework, dataset, and analyses provide a foundation for understanding how narrative qualities are distributed in LLM pretraining data and for studying how data composition affects narrative reasoning tasks. We publicly release NarraDolma and NarraBERT.

23.
medRxiv (Medicine) 2026-06-22

Level of Physical Activity and ApoE Status - Effects on Alzheimer's Disease and on Mortality

Background: Alzheimer's disease and related dementias (ADRD) affect over 7.2 million Americans aged 65 and older, with the APOE-4 allele representing the strongest known genetic risk factor. Physical activity (PA) has been associated with reduced dementia risk, but its interaction with APOE genotype remains poorly characterized in large, genomically informed cohorts. Methods: We conducted a retrospective cohort analysis using linked genomic, survey, and longitudinal electronic health record data from the VA Million Veteran Program (MVP). Veterans aged

24.
medRxiv (Medicine) 2026-06-15

Active commuting, anxiety symptoms and mental wellbeing: a dose-response study

Climate change draws attention to the planetary health perspective in sport and exercise sciences, that is, to physical activity that supports both human wellbeing and environmental sustainability. Active commuting is a sustainable form of physical activity with well-established somatic health benefits. However, more knowledge is needed on its relationship with mental health. We examined dose-response associations between active commuting, anxiety symptoms, and mental wellbeing among Finnish adults, and whether green commuting environment moderates these relationships. We used data from the cross-sectional Environment and Health Survey collected in June-September 2023 in the ten largest cities in Finland. Employed participants with data on anxiety symptoms (Generalized Anxiety Disorder-7, GAD-7), mental wellbeing (World Health Organization-Five Well-Being Index, WHO-5), commuting profile over a year (mode, frequency, distance, and perceived greenness along the commute route), and sociodemographic and lifestyle factors were included (n=1,672; mean age 45.3 years; 53.8% women). Active commuting was defined as travelling the entire commute by walking or cycling (including e-biking) that was converted into approximated annual km/week and MET-h/week. We used linear and logistic regression with restricted cubic splines to evaluate dose-response associations, adjusted for key covariates. The role of perceived greenness was tested using an active commuting x commute greenness interaction term. We found no dose-response relationships between active commuting and anxiety symptoms or mental wellbeing in any of the models. No effect modification by commute greenness was observed. More research on how active commuting may support planetary health from a mental health perspective is needed.

25.
bioRxiv (Bioinfo) 2026-06-12

From Proteome Mining to Structural Validation: Phosphopyruvate Hydratase as a Structurally Tractable Drug Target in Kinetoplastid Parasites

Chagas disease, caused by Trypanosoma cruzi, demands novel therapeutic strategies that overcome the toxicity and limited efficacy of current treatments. To address this need, herein we report an integrative, target-centric strategy that combines parasite proteome mining, structural modeling, and experimental validation. Functional enrichment and druggability analyses identified phosphopyruvate hydratase (PPH) as a promising candidate due to its essential metabolic role and limited similarity to human homologs. Notably, proteome mining revealed the presence and conservation of PPH across kinetoplastid parasites, including Leishmania donovani, supporting its evaluation beyond T. cruzi. For the selected PPH sequences, AlphaFold-derived three-dimensional models underwent extensive molecular dynamics refinement, yielding stable conformational ensembles suitable for structure-based studies. Using this validated model, virtual screening of the Latin American Natural Products Database - LANaPDB - identified aptosimon as a top-ranked compound candidate. Molecular dynamics simulations further showed ligand-dependent binding behavior, suggesting alternative binding modes distinct from the canonical substrate configuration. In vitro assays demonstrated consistent antiparasitic activity against intracellular T. cruzi amastigotes (IC50 = 3.52 ug/mL) and Leishmania donovani promastigotes (IC50 = 13.06 ug/mL), supporting the biological relevance of the aptosimon-related lignan chemotype, hinokinin, across two kinetoplastid parasite models. Together, these results support PPH as a structurally tractable and biologically relevant candidate target, while identifying an aptosimon-related lignan chemotype, represented experimentally by hinokinin, as a cross-species antiparasitic scaffold that warrants further biochemical target-validation studies.