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01.
arXiv (CS.AI) 2026-06-18

TRIDENT: Breaking the Hybrid-Safety-Physics Coupling for Provably Safe Multi-Agent Reinforcement Learning

arXiv:2606.18308v1 Announce Type: cross Abstract: Safe coordination in networked cyber-physical systems forces learning algorithms to simultaneously handle hybrid discrete-continuous actions, hard training-time safety constraints, and physics-governed dynamics. We show that these three features form a directed cycle of biases that defeats any naive composition of off-the-shelf modules, and formalize this as a three-way coupling lemma. We then introduce TRIDENT, the first MARL framework whose three components are co-designed to cancel each leak: a Richardson-Romberg gradient correction reducing Gumbel-Softmax bias from O(tau) to O(tau^2), a Lyapunov-constrained sequential trust-region update enforcing per-iterate feasibility, and a physics-informed residual critic that decomposes value rather than reward. We prove an O~(1/sqrt(K)) convergence rate to a constrained Nash equilibrium and an O(sqrt(K)) cumulative-violation bound. On multi-UAV mobile-edge computing, autonomous intersection management, and a hybrid SMAC variant, TRIDENT cuts training-time violations by 95.5% over MADDPG and 76.3% over MACPO, while improving reward by 13.5% over the strongest unconstrained baseline.

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

Exploring Extrinsic and Intrinsic Properties for Effective Reasoning with Code Interpreter

Reasoning with a Code Interpreter (CI) has emerged as an effective paradigm for enhancing the reasoning capabilities of large language models (LLMs) through executable computation and iterative verification. Despite its growing adoption, the behavioral properties underlying effective code reasoning remain largely underexplored. In this work, we investigate code reasoning from two distinct perspectives inspired by prior studies of natural language reasoning: extrinsic properties, represented by crucial tokens, and intrinsic properties, represented by code-specific cognitive behaviors. Across multiple LLMs, we find that stronger CI reasoning models consistently exhibit a higher prevalence of crucial tokens and cognitive behaviors, particularly verification, backtracking, and backward chaining. Building on these observations, we examine how these properties can be leveraged during both inference and training. At inference time, appending code-specific crucial tokens improves performance on several reasoning capabilities, including mathematical, ordering, and optimization, while yielding limited benefits elsewhere. At training time, augmenting a state-of-the-art framework with code-specific cognitive behaviors improves supervised fine-tuning and reinforcement learning performance in two of three evaluated models. Further analysis shows that these behaviors reduce overthinking in incorrect responses and improve token efficiency, while also revealing factors that limit gains in a certain model. Our findings provide the first systematic characterization of effective reasoning with CI and demonstrate both the potential and limitations of leveraging key properties to improve CI-based reasoning.

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

Bridging the Gap: Enabling Natural Language Queries for NoSQL Databases through Text-to-NoSQL Translation

arXiv:2502.11201v3 Announce Type: replace-cross Abstract: NoSQL databases are core data infrastructure, yet natural-language access to them remains underdeveloped: correct query generation must recover how a non-relational data model represents entities, nested paths, arrays, missing fields, and dynamic keys. This paper studies Text-to-NoSQL, translating natural-language requests into executable NoSQL queries, instantiated with MongoDB aggregation pipelines over schema-less document stores. We present TEND, short for Text-to-NoSQL Dataset, an execution-verified benchmark with 1,210 MongoDB-native tasks across 11 databases. To our knowledge, TEND is the first Text-to-NoSQL benchmark whose database worlds are MongoDB-native by design: experts manually define collection boundaries, nested arrays, optional and sparse paths, polymorphic shapes, and dynamic-key conventions; these worlds are populated with real data and verified through frozen MongoDB execution, so TEND evaluates schema-less document reasoning rather than SQL-to-MQL transfer. We further introduce SAG, a Schema-as-Data Grounding solver that induces path and value grounding from stored-document evidence before bounded MQL generation, execution-grounded repair, and result-consistency selection. Evaluation uses bounded column-tolerant execution accuracy (EXC) as the headline metric, complemented by a graded result-set F1 and a mutually exclusive execution-outcome decomposition. Experiments show that LLMs with strong NL2SQL performance degrade substantially on TEND, validating Text-to-NoSQL as a distinct schema-less document reasoning problem.

05.
arXiv (CS.LG) 2026-06-18

A Streaming Sparse Cholesky Method for Derivative-Informed Gaussian Process Surrogates Within Digital Twin Applications

arXiv:2511.00366v2 Announce Type: replace-cross Abstract: Digital twins are developed to model the behavior of a specific physical asset (or twin), and they can consist of high-fidelity physics-based models or surrogates. A highly accurate surrogate is often preferred over multi-physics models as they enable forecasting the physical twin future state in real-time. To adapt to a specific physical twin, the digital twin model must be updated using in-service data from that physical twin. In this paper, we combine and extend several previous surrogate-related advancements with the goal of demonstrating an end-to-end digital twin (DT) solution for predicting performance of an aircraft structure (the physical asset). To this end, we extend Gaussian process (GP) models to include derivative data, for improved accuracy, with dynamic updating to ingest physical twin data during service. Including derivative data, however, comes at a prohibitive cost of increased covariance matrix dimension. We circumvent this issue through our modified dynamic sparse Cholesky linear system solver. Numerical experiments demonstrate that the prediction accuracy of the derivative-enhanced sparse Cholesky GP method produces improved models upon dynamic data additions. Lastly, we demonstrate the developed algorithm within a DT framework to model fatigue crack growth in an aerospace vehicle, thereby exhibiting through our assembled engineered system how digital twin technologies can be combined in practice.

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

Litespark Inference For CPUs: Ultra-Fast SIMD Framework for Ternary (1.58-bit) Language Models

Large language models (LLMs) have transformed artificial intelligence, but their computational requirements remain prohibitive for most users. Standard inference demands expensive datacenter GPUs or cloud API access, leaving over one billion personal computers underutilized for AI workloads. Ternary models offer a path forward: their weights are constrained to {-1, 0, +1}, theoretically eliminating the need for floating-point multiplication. However, existing frameworks fail to exploit this structure, treating ternary models as dense floating-point networks. We address this gap with custom SIMD kernels that replace matrix multiplication with simple addition and subtraction operations, targeting the integer dot product instructions available on modern CPUs. Our implementation, Litespark-Inference, is pip-installable and integrates directly with Hugging-Face, achieving 18.15x higher throughput, 7.15x faster time-to-first-token and 6.03x memory reduction compared to standard PyTorch inference on Apple Silicon, with comparable or higher throughput speedups up to 95.81x on Intel and AMD processors.

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

Advances in 4D Representation: Geometry, Motion, and Interaction

We present a survey on 4D generation and reconstruction, a fast-evolving subfield of computer graphics whose developments have been propelled by recent advances in neural fields, geometric and motion deep learning, as well as 3D generative artificial intelligence (GenAI). While our survey is not the first of its kind, we build our coverage of the domain from a unique and distinctive perspective of 4D representations, to model 3D geometry evolving over time while exhibiting motion and interaction. Specifically, instead of offering an exhaustive enumeration of many works, we take a more selective approach by focusing on representative works to highlight both the desirable properties and ensuing challenges of each representation under different computation, application, and data scenarios. The main take-away message we aim to convey to the readers is on how to select and then customize the appropriate 4D representations for their tasks. Organizationally, we separate the 4D representations based on three key pillars: geometry, motion, and interaction. Our discourse will not only encompass the most popular representations of today, such as neural radiance fields (NeRFs) and 3D Gaussian Splatting (3DGS), but also bring attention to relatively under-explored representations in the 4D context, such as structured models and long-range motions. Throughout our survey, we will reprise the role of large language models (LLMs) and video foundational models (VFMs) in a variety of 4D applications, while steering our discussion towards their current limitations and how they can be addressed. We also provide a dedicated coverage on what 4D datasets are currently available, as well as what is lacking, in driving the subfield forward. Project page:https://mingrui-zhao.github.io/4DRep-GMI/

08.
arXiv (CS.LG) 2026-06-15

Operator Calculus for Population-Based Optimization: A Mean-Field Convergence Theory

arXiv:2606.14289v1 Announce Type: cross Abstract: Population-based and distributional optimization methods, from evolution strategies and consensus-based optimization to covariance-matrix adaptation and stochastic gradient methods viewed as distributional dynamics, are widely used for nonconvex or black-box problems, yet their convergence analyses remain fragmented across algorithm-specific techniques. We introduce an operator calculus in which a broad class of such methods, after choosing an appropriate state space and, where necessary, augmenting the state by memory or strategy variables, is described as a composition of three elementary operators (mutation, selection, and recombination) acting on probability measures. Under explicit stability and regularity conditions, the composite operator admits a pre-generator whose continuous-time limit is a transport-reaction-jump (TRJ) PDE that preserves the operator splitting. On this foundation we establish a modular Lyapunov principle. If a state-space Lyapunov function both dissipates under the full generator and controls the relevant search-space gauges, then the state-space Lyapunov functional and the induced search errors decay exponentially. The additive generator structure allows dissipation estimates to be assembled operator by operator, providing a toolkit for certifying convergence of composite mean-field algorithms.

09.
arXiv (CS.AI) 2026-06-11

FACTR 2: Learning External Force Sensing for Commodity Robot Arms Improves Policy Learning

arXiv:2606.12406v1 Announce Type: cross Abstract: Contact-rich manipulation requires force sensitivity, but many robot arms lack dedicated force sensors due to their high cost. We present Neural External Torque Estimation (NEXT), a data-driven method that estimates external joint torques without needing any dedicated force sensors. NEXT trains in 1 minute from only 10 minutes of free-motion data, yet achieves estimates comparable to dedicated joint-torque sensors. NEXT enables force-feedback teleoperation on low-cost arms and improves policy learning through Force-Informed Re-Sampling Training (FIRST), which up-samples pre-contact and contact segments during behavior cloning. Across five long-horizon tasks, FIRST outperforms prior force-aware policies by over 17% in task progress. Together, NEXT and FIRST bring force-aware teleoperation and policy learning to off-the-shelf robots without additional sensing hardware. Video results and code are available at https://jasonjzliu.com/factr2

10.
Nature (Science) 2026-06-17

Optical metasurfaces for general vision processing on the edge

作者:

Large-scale artificial intelligence (AI) models achieve notable performance in computer vision but require substantial computational resources, limiting their deployment on edge devices1,2. Optical neural networks (ONNs) promise reduced latency and energy consumption by making use of the inherent parallelism of light3. However, present ONNs struggle to scale and are confined to simple tasks, owing to the challenges of replicating exact algebraic operations of digital models using physical (analogue) systems. This work introduces a new paradigm that directly embeds core computer vision principles, including similarity-based recognition, attention-guided perception and detail–context fusion, into a large-scale optical metasurface. By unifying optical physics with these computer vision fundamentals, we develop a photonic–electronic engine that overcomes scalability and generality barriers, enabling high-accuracy, general-purpose computer vision at the edge. The resulting system combines a 41-million-parameter optical metasurface front end with a co-designed, ultraefficient 87,000-parameter digital back end, outperforming many digital models with tens of millions of parameters across object detection, segmentation, 3D reconstruction and video understanding. We build a deployable prototype and demonstrate real-time edge visual processing in natural scenes. This work represents a path towards practical optical computing for general vision tasks in complex natural environments, enabling a new paradigm for low-energy, low-latency, real-time on-device vision intelligence. By embedding core computer vision principles into a large-scale optical metasurface, an efficient vision processing system using far fewer parameters is demonstrated to outperform many digital models and enables deployment on edge devices.

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

Semantic Robustness Certification for Vision-Language Models

Vision-language models (VLMs) are now widely used in downstream tasks. However, real-world applications often expose VLMs to distribution shifts induced by semantic variation (e.g., shape, size, and style). Robustness certification determines if a model's prediction changes when transformations are applied to its input. While most certification frameworks study geometric or pixel-level transformations over inputs, this work proposes a novel framework that enables certifying VLM robustness under semantic-level transformations. Leveraging the open-vocabulary capability of VLMs, we use text prompts as semantic proxies to construct transformations parameterized by an extent that controls the degree of semantic variation. By characterizing the VLM decision boundary in closed form, our framework quantitatively certifies extent intervals for which the predicted class remains unchanged under the semantic transformation. Our framework is the first to certify VLM robustness under semantic-level variations without requiring additional data for each variation, making it practical to apply. Experiments on both synthetic and real-world data show that our framework enables certifying robustness under diverse semantic variations across scenarios.

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

Reload-Mamba: Hierarchical Anti-Dilution State-Space Modeling for Multi-Class Semantic Segmentation

Mamba-based state space models offer linear-time long-range modeling for high-resolution dense prediction, but sequential state-space propagation can attenuate boundary-sensitive and detail-sensitive responses that are critical in multi-class semantic segmentation. We propose Reload-Mamba, a semantic segmentation framework that addresses this propagation-induced response dilution through three segmentation-specific designs: (i) a boundary-supervised local detail prior that is explicitly trained with ground-truth boundary masks to identify regions requiring response restoration; (ii) a class-uncertainty-aware Reload Gate that incorporates per-pixel class entropy from a pre-reload auxiliary head as an additional gating signal, a formulation that is informative only under multi-class dense prediction; and (iii) a hierarchical multi-level Reload mechanism that applies anti-dilution refinement at three decoder levels and fuses the restored representations top-down. Built upon a ConvNeXt-Tiny encoder with a multi-scale decoder and four-directional Mamba scanning with pixel-wise directional attention, Reload-Mamba achieves 47.9% single-scale (48.9% multi-scale) mIoU on ADE20K and 83.2% single-scale mIoU on Cityscapes. With ResNet-101 + COCO pre-training under the standard DeepLab-style protocol, Reload-Mamba reaches 87.8% mIoU on PASCAL VOC 2012 val. Controlled ablations show that each of the three segmentation-specific designs contributes beyond a direct port of the prior anti-dilution architecture proposed for binarization, cumulatively improving over the direct-port baseline by +2.2 mIoU on ADE20K.

13.
arXiv (quant-ph) 2026-06-12

Cayley's First Hyperdeterminant is an Entanglement Measure

arXiv:2504.15511v2 Announce Type: replace Abstract: Previously, it was shown that both the concurrence and $n$-tangle on $2n$-qubit pure quantum states can be expressed in terms of Cayley's first hyperdeterminant [dobes2024qubits], indicating that Cayley's first hyperdeterminant, denoted $\mathrm{hdet}$, captures some aspects of a state's $2n$-way entanglement. In this paper, we rigorously prove that on both pure and mixed states, $|\mathrm{hdet}|^{2/d}$ is identically zero on separable states, is an LU invariant, and is non-increasing on average under LOCC, thus demonstrating that $|\mathrm{hdet}|^{d/2}$ is a physically meaningful and legitimate entanglement measure. Moreover, we discuss a few key examples to illustrate the particular type of entanglement Cayley's first hyperdeterminant is detecting: genuine full $d$-level GHZ-type entanglement across all $2n$ parties. Combined, this establishes Cayley's first hyperdeterminant (or $|\mathrm{hdet}|^{2/d}$ to be precise), as a genuine, physically significant generalization of the concurrence and the $n$-tangle to $2n$-qudit states.

14.
arXiv (CS.AI) 2026-06-16

Is Code Better Than Language for Algorithmic Reasoning

arXiv:2606.15589v1 Announce Type: cross Abstract: For tool-augmented language models, comparing natural-language reasoning with code-execution pipelines is difficult because the comparison changes both the intermediate representation and the execution mechanism. We separate these factors with an intermediate intervention: the model expresses its reasoning as executable code, and the language model simulates that code in context to produce an answer. On a 40-task verifiable algorithmic benchmark, deterministic code execution outperforms natural-language reasoning by +31.6pp. We observe that the intermediate intervention is not meaningfully different from natural-language reasoning (+0.15pp). These results suggest that, in our evaluated setting, changing the intermediate representation alone does not explain the tool-use advantage, providing evidence for the performance gains requiring reliable external execution. We formalize this intuition with a simple statistical decision-theoretic model that characterizes when execution dominates end-to-end risk in our disentangled trace-generation/execution regime. We validate our theory using a reconstruction intervention that leverages a proxy language model to infer natural-language reasoning traces from code representations, recovering performance comparable to the original natural-language reasoning pipeline. All experiments are at https://github.com/TerryTong-Git/ToolProj.

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

Bright Emission from Dark Sources in Hyperbolic Media

arXiv:2606.16071v1 Announce Type: cross Abstract: Hyperbolic media enable ultra-strong light-matter interactions through their extreme field localization and small mode volumes, but low-loss realizations are fundamentally limited to the mid-infrared, owing to the long lifetimes of optical phonons in high-quality crystals. Here we show that bright emitters operating at visible or near-infrared frequencies can be used to generate radiation in this regime by inducing mid-infrared population dynamics, thereby creating a source in the hyperbolic frequency band without a corresponding dipole transition. We demonstrate that even a source with vanishing dipole and higher multipole moments - strictly non-radiating in any isotropic medium - becomes radiatively active in a hyperbolic environment. This enables visible and near-infrared control of light-matter interactions in polaritonic hyperbolic materials, establishing a new low-loss solid-state quantum optics platform.

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

Mind the Gap: Diagnosing Constraint Discovery Failures in Text-in-Image Editing

作者:

A key challenge in multimodal reasoning is determining which visual dependencies become relevant under a specific task, rather than merely recognizing visible content. We study this through edit-induced constraint discovery in text-in-image editing, a controlled diagnostic setting where a local text change can activate secondary consistency constraints: given a valid editing instruction and an image, can a model identify the secondary regions that must also change? Across 461 diagnostic cases, four MLLMs, and 19 constraint subtypes, models recover only 46% case-level macro recall under unguided prompting versus 94% when constraints are explicitly provided, suggesting that a substantial portion of the failure arises when models must decide which unstated dependencies to surface. Oracle-field decomposition shows that case-specific causal explanations are the most effective partial guidance (0.782 recall), above region names (0.610) or type labels (0.646), suggesting that edit-specific causal cues account for much of the oracle gain. A downstream experiment further shows that higher self-discovery recall does not necessarily improve task performance: unverified self-discovery introduces false positives that offset recall gains, motivating precision-aware constraint elicitation.

17.
arXiv (CS.CV) 2026-06-11

MentisOculi: Revealing the Limits of Reasoning with Mental Imagery

Frontier models are transitioning from multimodal large language models (MLLMs) that merely ingest visual information to unified multimodal models (UMMs) capable of native interleaved generation. This shift has sparked interest in using intermediate visualizations as a reasoning aid, akin to human mental imagery. Central to this idea is the ability to form, maintain, and manipulate visual representations in a goal-oriented manner. To evaluate and probe this capability, we develop MentisOculi, a procedural, stratified suite of multi-step reasoning problems amenable to visual solution, tuned to challenge frontier models. Evaluating visual strategies ranging from latent tokens to explicit generated imagery, we find they generally fail to improve performance. Analysis of UMMs specifically exposes a critical limitation: While they possess the textual reasoning capacity to solve a task and can sometimes generate correct visuals, they suffer from compounding generation errors and fail to leverage even ground-truth visualizations. Our findings suggest that despite their inherent appeal, visual thoughts do not yet benefit model reasoning. MentisOculi establishes the necessary foundation to analyze and close this gap across diverse model families.

18.
arXiv (CS.LG) 2026-06-17

ResAware: Cross-Environment Website Fingerprinting via Resource-Privileged Distillation

arXiv:2606.17462v1 Announce Type: new Abstract: While Website Fingerprinting (WF) attacks achieve high accuracy in controlled laboratory settings, they often degrade substantially in real-world environments due to spatio-temporal drift, browser heterogeneity, proxy obfuscation and etc. This limitation stems from their sole reliance on low-level traffic features that are noisy and highly sensitive to environmental perturbations. To address this problem, we propose ResAware, a cross-environment resource-aware distillation framework under a training-rich/inference-poor asymmetric setting. Specifically, ResAware trains a teacher model on resource-level features, and then distills the resulting privileged knowledge into a student model through heterogeneous knowledge distillation. At deployment time, the student model performs inference using only encrypted traffic, incurring zero additional cost. We evaluate ResAware on a large-scale dataset collected over five months from six globally distributed vantage points, comprising more than $160{,}000$ paired samples. The results show that ResAware significantly enhances the cross-environment robustness of diverse WF baselines. Under a 150-day temporal drift, for example, ResAware improves the F1-score of Var-CNN from $72.77\%$ to $81.49\%$ and the open-world $TPR@1\%FPR$ from $22.40\%$ to $27.20\%$. Our results demonstrate that resource-level supervision improves WF robustness without expanding online observation capabilities.

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

All-valid-state HOBO encoding for constrained combinatorial optimization on NISQ devices

arXiv:2606.20017v1 Announce Type: new Abstract: Continued advancements in quantum computing have stimulated growing interest in translating quantum technologies into real-world applications. Consequently, the investigation of practically motivated NP-hard problems is of significant value. This study investigates the performance of a variational quantum eigensolver (VQE) in addressing the traveling salesperson problem (TSP) through noiseless simulations representative of noisy intermediate-scale quantum (NISQ) devices using higher-order binary optimization (HOBO) encodings. We construct a HOBO Hamiltonian with an efficient binary representation and propose an all-valid-state HOBO (AVS-HOBO) scheme based on cyclic mapping that eliminates one penalty term and reuses states that would otherwise be invalid. Using TSP instances of up to 20 cities, we compare the original HOBO and AVS-HOBO encodings from multiple perspectives, including the energy convergence behavior and the approximation, tour-length, and feasibility ratios. In addition to simulations, we perform computations on real quantum hardware with different device architectures, where we not only compare the performances of different chips but also investigate the effects of different error-mitigation methods on actual quantum machines. The results indicate that AVS-HOBO encoding enhances the practical reliability of VQE on NISQ devices and improves scalability for larger TSP instances, with broader applicability to constrained quantum optimization problems.

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

Towards Scalable Customization and Deployment of Multi-Agent Systems for Enterprise Applications

Large language model (LLM)-based multi-agent systems demonstrate strong performance on complex reasoning and task execution, enabling broad enterprise applications. However, production deployment remains challenging due to domain-specific customization requirements and high latency and inference costs in agentic workflows. We propose a unified framework for customization and efficient deployment of multi-agent systems in real-world settings. The first stage, Agentic Model Customization, combines continual pretraining, supervised fine-tuning, and preference optimization to adapt a compact model to specialized domains while retaining strong agentic capabilities. The second stage, Inference Optimization, integrates speculative decoding and FP8 quantization with targeted calibration to enable cost-efficient serving with minimal quality loss. Across enterprise workloads, our framework enables rapid domain adaptation and achieves a 4.48x speedup in throughput while maintaining performance and improving robustness on long-tail scenarios.

21.
arXiv (CS.CV) 2026-06-11

MedVeriSeg: Teaching LISA-Like Medical Segmentation Models to Verify Query Validity Without Extra Training

Despite recent progress in text-prompt-based medical image segmentation, existing LISA-like MLLM-based methods typically generate masks regardless of whether the target specified in the query is present, leading to hallucinated segmentation. In this work, we propose MedVeriSeg, a training-free query verification framework that enables LISA-like medical segmentation models to reject false segmentation queries. MedVeriSeg first quantifies the response quality between the [SEG] token and image features through a Similarity Response Quality Scoring Module. To further improve robustness, it employs a Lightweight Routed Multi-Agent Verification Module, which fuses quantitative score evidence with qualitative agent evidence to comprehensively verify the validity of the query. To support systematic evaluation, we construct MedVeriSeg-Bench, a benchmark designed for query verification in medical image segmentation. Experimental results demonstrate that MedVeriSeg effectively identifies false segmentation queries and reduces hallucinated segmentation, while maintaining a high acceptance rate for valid queries, thereby largely preserving the segmentation utility of LISA-like medical segmentation models.

22.
arXiv (CS.CL) 2026-06-17

From Parasocial Scripts to Dyadic Persistence in Autonomous AI-Agent Communities

While parasocial interactions (PSIs) and parasocial relationships (PSRs) have been studied in conventional media settings, we investigate whether PSI- (colloquial) relational cues also exist in online communities where both sides are autonomous AI agents. We analyze 4,434 posts and 50,338 comments from Moltbook through three theory-based textual indicators: attachment/intimacy language, reciprocity bids, and self-identification to original poster (OP). The combined results across methods based on keyword matching, few-shot large language model (LLM) annotation, and grouped-context LLM annotation reveal that PSI colloquial cues prevail and are strongly associated with OP re-engagement and a reciprocal reply structure. These results are robust across negative controls, nullification, clustered-standard-error re-estimation, and multiple-testing correction. A dyadic persistence test further affirms reciprocity bids aligned with sustained OP-involving mutual recurrence, providing empirical evidence for bridging interaction-level PSI scripts with PSR-consistent repeated dyadic patterns. We interpret the evidence as a behavioral structure in discourse by LLM-enabled agents.

23.
medRxiv (Medicine) 2026-06-17

A non-invasive liquid biopsy resolves the diagnostic blind spot in chronic kidney disease

Chronic kidney disease is a major global health burden, and its early detection is critical for delaying progression to kidney failure using recently developed targeted therapies. However, current diagnostic screening relies heavily on blood markers that are confounded by muscle mass, and on urine tests that frequently miss structural damage occurring without protein leakage. This creates a critical diagnostic blind spot that hinders timely intervention. Here we show a non-invasive liquid biopsy platform that quantifies a specific protein marker, MUC1, on urinary extracellular vesicles to accurately assess renal parenchymal integrity. By bypassing the systemic metabolic noise of traditional blood tests, our assay provides a remarkably stable, person-specific functional signature. Following extensive validation across diverse cohorts, our longitudinal analysis demonstrated that the discrepancy between this novel urine-based readout and standard blood tests unmasks hidden renal vulnerability, successfully predicting rapid functional decline. By comprehensively evaluating both tubular and glomerular integrity from a single spot urine sample, these findings establish a completely non-invasive, highly scalable prescreening tool that resolves the diagnostic blind spot, enabling broader early detection strategies and ushering in a new era of proactive risk management.

24.
bioRxiv (Bioinfo) 2026-06-14

Structural Analysis of Prostate Cancer N-Glycans Using Graph-Based Structural Metrics

The N-linked glycans are structurally complex carbohydrate modifications that regulate protein folding, immune recognition, and cellular signaling, and their expression is extensively remodeled during cancer progression, making them promising biomarkers. In this study, prostate cancer-associated N-glycans from a range of relevant peer-reviewed studies were curated and digitized to develop a versatile computational framework that quantitatively encodes their spatial complexity across diverse biological systems. We invented two indices – the Distance & Connectivity Index (DCI) and the Position & Composition Index (PCI) – to capture the spatial information in N-glycans as layered architectures, enabling calculation of residue-level path lengths, branching structure, and compositional diversity. DCI summarizes glycan structure as both a scalar and matrix representation, while PCI does the same but also captures monosaccharide diversity, linkage heterogeneity, and cross-layer branching features. These metrics were computed with GlycoAssessor, an open-source platform that extracts information for the DCI and PCI from glycans drawn via Symbol Nomenclature for Glycans (SNFG) notation. Principal Component Analysis (PCA) was applied to evaluate whether glycans from prostate cancer tissues cluster distinctly in a disease-relevant manner. Results show that the spatial information in N-glycans: (1) increased in a multi-dimensional, non-linear manner, (2) objectively segregated structural themes, (3) could function as a potential prostate cancer biomarker that is distinct from mass-to-charge ratio and relative abundance, and (4) could objectively quantify novel subtype classifications of glycans associated with disease states and progression.

25.
medRxiv (Medicine) 2026-06-10

Development of a Novel Blood-Based Assay for Brain-Derived Tau and Its Validation in Traumatic Brain Injury

Brain-derived tau (BD-tau) is an emerging blood-based biomarker for neurodegeneration, yet there are currently limited well validated BD-tau assays available for research and clinical use. To enhance access to this vital biomarker for neurological disorders including traumatic brain injury (TBI), we developed a novel blood-based immunoassay for BD-tau on the ultra-sensitive Quanterix HD-X platform using Single Molecule Array technology. Analytical validation assessed dilution linearity, specificity, precision, detection limits, and spike recovery, each recording robust metrics in agreement with international expert recommendations. The assay demonstrated robust validation metrics, achieving between-run stability of 95% when analyzing aliquots from six independent plasma and serum samples across five analytical runs. It also showed strong dilution linearity when diluted four-fold and achieved over 90% recovery when spiked with cerebrospinal fluid. Next, we evaluated the clinical utility of the assay in cohorts of individuals with traumatic brain injury (TBI), where strong performances were recorded whether using the 2-step or 3-step assay formats ({rho}= 0.94; p < 0.0001). Furthermore, plasma BD-tau distinguished samples from TBI patients based on time from injury and severity (AUC=0.93). Plasma BD-tau differentiated between favorable and unfavorable functional outcomes in the acute-severe group. Our findings underscore the significant potential of the BD-tau assay as a biomarker for TBI in the severe phase.