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

Guidelines for the Annotation and Visualization of Legal Argumentation Structures in Chinese Judicial Decisions

This Guideline presents a systematic and operationalizable annotation framework for representing legal argumentation structures in judicial decisions. Grounded in theories of legal reasoning and argumentation, the framework aims to reveal the logical organization of judicial reasoning and provide a reliable foundation for computational analysis. At the element level, the Guideline distinguishes between the non-propositional layer and the propositional layer. The non-propositional layer consists of two elements: Issue and Non-argumentative Component. At the propositional level, the Guideline defines four proposition types: General Normative Judgment, Particular Normative Judgment, General Factual Judgment, and Particular Factual Judgment. At the relational level, five relation types are defined to represent argumentative structures: Support, Attack, Joint, Match, and Identity. These relations capture positive and negative argumentative connections, conjunctive reasoning structures, correspondences between legal norms and case facts, and identity or semantic equivalence between propositions. The Guideline further specifies formal representation rules and visualization conventions for both basic and nested structures, enabling consistent visualization of complex argumentation patterns. In addition, it establishes a standardized annotation workflow and consistency control mechanisms to ensure the reproducibility and reliability of annotated data. By providing a clear conceptual model, formal representation rules, and practical annotation procedures, this Guideline supports large-scale analysis of judicial reasoning and future research in legal argument mining, computational modeling of legal reasoning, and AI-assisted legal analysis.

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

Graph Regularized Non-negative Reduced Biquaternion Matrix Factorization for Color Image Recognition

Non-negative reduced biquaternion matrix factorization (NRBMF) uses the product of reduced biquaternion (RB) matrices to incorporate the non-negativity constraints of color image pixels into the factorization process. However, NRBMF mainly focuses on reconstruction accuracy and does not explicitly exploit the local geometric structure of image data, which may limit the discriminative ability of the obtained low-dimensional coefficient representations. To address this issue, we propose a graph regularized non-negative reduced biquaternion matrix factorization (GNRBMF) model for color image recognition. The proposed model incorporates a graph Laplacian regularizer into the reduced biquaternion coefficient matrix, encouraging nearby samples in the original space to have similar coefficient representations. Meanwhile, GNRBMF retains the non-negativity property of NRBMF in the reduced biquaternion algebra. To solve the optimization problem, a component-wise alternating projected gradient algorithm is derived, and its convergence properties are analyzed. Experimental results on three color image datasets show that the proposed GNRBMF model achieves competitive or superior recognition performance compared with several methods in most tested settings.

03.
arXiv (CS.CV) 2026-06-11

MLT-Dedup: Efficient Large-Scale Online Video Deduplication via Multi-Level Representations and Spatial-Temporal Matching

The explosive growth of user-generated video content on online platforms is accompanied by the emergence of numerous near-duplicate videos–videos that are identical or highly similar but differ by partial edits. These duplicates degrade user experience and increase storage and bandwidth costs, making large-scale video deduplication a critical task. Existing video deduplication frameworks face a fundamental challenge in retrieving sufficient high-quality candidates under a limited index budget, as well as trade-offs between efficiency and precision. To address these issues, we propose MLT-Dedup, an efficient large-scale online video deduplication framework with Multi-Level representations and spatial-Temporal matching. Our approach employs a Multi-Level Video Encoder (ML-VE) to extract both fine-grained frame-level and sparse clip-level embeddings: sparse embeddings support efficient candidate retrieval, while fine-grained embeddings are loaded for precise pairwise matching. During matching, we introduce DiF-SiM, a Differential Feature-enhanced Similarity Module capable of locating duplicated temporal segments and providing reliable similarity evidence to support policy-driven deduplication decisions. Extensive experiments on a real-world large-scale platform demonstrate that MLT-Dedup reduces online repetition rates by 91% at 90% precision. Furthermore, our sparse retrieval design achieves a 5x increase in indexing capacity, enabling broader candidate coverage in real-world deployment.

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

Learning ground state observables from quantum computing experiments

arXiv:2606.15983v1 Announce Type: new Abstract: Recent theoretical progress has established conditions under which machine learning models can efficiently predict ground-state properties of gapped local Hamiltonians when trained on quantum-generated data. Previous experimental demonstrations in this paradigm, however, have largely been limited to small systems or highly structured states, due to the difficulty of preparing many-body ground states on quantum processors. In this work, we demonstrate learning from experimental quantum data generated from approximate ground states of the two-dimensional Heisenberg XXZ model with system sizes up to 115 qubits. We construct a dataset of single-site expectation values, two-point correlations, and 12-body loop correlations across the antiferromagnetic phase. We then train neural networks on this data and show that they can accurately predict spatially resolved observables for previously unseen Hamiltonian parameters, both within the training distribution and in an out-of-distribution regime approaching the phase boundary. Our results demonstrate the practical realization of learning from quantum data for an interacting two-dimensional many-body system at scale, motivating a path toward regimes where quantum processors could provide training data beyond the reach of classical approximation methods.

05.
Nature Medicine 2026-06-08

Effects of SGLT2 inhibition on incident heart failure in carriers of cardiomyopathy-associated genetic variants

Although the beneficial effects of sodium–glucose cotransporter 2 (SGLT2) inhibition in heart failure (HF) have been well established, it is unknown whether SGLT2 inhibition confers benefit in carriers of rare variants in cardiomyopathy-associated genes. Here we evaluated whole-exome sequencing data from the randomized DECLARE-TIMI 58 trial, in which adults with type 2 diabetes and increased cardiovascular risk were randomized to dapagliflozin or placebo treatment. Pathogenic or likely pathogenic variants (P/LP) in high-confidence cardiomyopathy genes were identified, and treatment effects on hospitalization for HF (HHF) were compared between carriers of such variants and noncarriers. Among 12,685 patients for whom sequence data were obtained, 121 carried a cardiomyopathy variant (76 dilated cardiomyopathy, 25 hypertrophic cardiomyopathy and 25 arrhythmogenic cardiomyopathy). Over a median follow-up of 4.2 years, dapagliflozin lowered the risk of HHF more strongly in carriers (hazard ratio 0.18, 95% confidence interval 0.04–0.86) than in noncarriers (hazard ratio 0.70, 95% confidence interval 0.57–0.86; P interaction 0.03). Absolute risk reduction was 13.0% in carriers and 1.0% in noncarriers (P interaction 0.03). Most carriers (82%) had no prior HF, and in carriers without prior HF, treatment with dapagliflozin reduced the absolute risk of HHF by 12.8%, compared with a reduction of 0.6% in noncarriers (P interaction 0.01). The findings from this cohort of older and high-risk patients raise the possibility that SGLT2 inhibitor treatment should be started early to prevent HF in individuals who carry P/LP cardiomyopathy variants. These results need to be confirmed in a prospective, dedicated trial of preventive HF treatments in carriers of P/LP cardiomyopathy-associated variants. In a whole-exome sequencing analysis, the beneficial effects of the SGLT2 inhibitor dapagliflozin in reducing the risk of future heart failure hospitalization in individuals with type 2 diabetes were markedly greater in individuals who carried a cardiomyopathy-associated genetic variant compared with noncarriers, suggesting a personalized preventative therapy based on genetic information.

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

A Definition of Good Explanations and the Challenges Explaining LLM Outputs

arXiv:2606.14838v1 Announce Type: new Abstract: How to define a good explanation is a long-standing philosophical debate which has found recent renewed interest in the context of AI outputs. Explainability is crucial for AI adoption in many contexts, but in order to produce good explanations of AI systems, we must first have an understanding of what good explanations are. In this paper we propose a definition inspired by the notion of counterfactual explanations, however we argue that one must also take into account the interlocutor's prior beliefs in each fact that could be offered in an explanation. We explore the ramifications of this definition for AI explainability and, in particular, why LLM outputs are difficult to produce good explanations for.

07.
arXiv (CS.AI) 2026-06-12

Graph Reduction in Multirelational Networks: A Spreading-Oriented Reduction Benchmark

arXiv:2606.12581v1 Announce Type: cross Abstract: Real-world networks are inherently incomplete, noisy, and dynamically evolving, making it difficult to capture all actors and their relationships. Their scale often renders direct analysis computationally demanding. While influence maximisation (IM) has been widely studied, the role of graph reduction as a preprocessing step, and its impact on IM accuracy, remains underexplored. In this work, we introduce the Spreading-Oriented Reduction Benchmark (SORB), an open-source, standardised framework for systematically evaluating IM models across diverse task settings. SORB provides an extensible pipeline operating on a representative collection of real-world networks, including single- and multilayer structures, and accounts for graph reduction directly into the evaluation process. This design shifts the focus from analysing IM algorithms in isolation to quantifying how graph reduction alters predictive performance. Using SORB, we study the effects of sparsification and coarsening across multiple IM scenarios. Our results show that the impact of reduction is strongly dependent on both the network type (single-layer vs. multirelational) and the downstream task ($Gain@k$ vs. $\mathrm{AUC}_{\mathrm{cutoff}}$): sparsification preserves seed set quality on single-layer networks, whereas flattened multilayer networks exhibit systematic ranking degradation regardless of reduction strategy. These findings highlight the importance of reduction-aware, multi-task evaluation when studying spreading processes in complex networks.

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

JoyAI-VL-Interaction: Real-Time Vision-Language Interaction Intelligence

Many moments in the real world do not wait for a user to ask. A fire starts on a security monitor, an expression flickers across a video call, or a product a viewer wants flashes by in a livestream. Yet today's large models remain mostly turn-based by design: they answer only when addressed, and even video-call apps that appear interactive still operate as question-answer systems, reacting only when polled or prompted. We argue for a different paradigm: a model that is present in the world like a person. It continuously watches what is happening now, decides on its own whether to speak or stay silent, interacts in real time, and delegates to a background model when the problem is hard. To advance interaction models and their adoption across domains, we make two fully open-sourced contributions. First, we release JoyAI-VL-Interaction, an 8B-scale, vision-first VL-interaction model. The model makes the response decision internally, choosing each second to stay silent, respond, or delegate to a background model, and it excels at vision-triggered responsiveness and time awareness. We pair it with a transferable training recipe, from which capabilities we never trained for emerge, such as guiding a shopper through changing app screens or improvising a lecture from a slide deck. Second, we release a complete, deployable system built around that model. The system streams any ongoing video into the model, making it genuinely present in the world. All other components are pluggable, including ASR/TTS modules, memory, visualization UI, and a background brain that can connect to any API or agent. Across six real-world scenarios, human raters prefer JoyAI-VL-Interaction over the in-app video-call assistants of Doubao and Gemini by a wide margin. To our knowledge, this is the first open, vision-driven interaction model released together with its training recipe, data, and complete deployable system.

09.
arXiv (CS.CL) 2026-06-19

Reliability without Validity: A Systematic, Large-Scale Evaluation of LLM-as-a-Judge Models Across Agreement, Consistency, and Bias

LLM-as-a-Judge has become the dominant evaluation paradigm for language models, but judge validation in practice relies on exact-match agreement, a metric that does not correct for chance and systematically overstates discriminative ability. We present the largest systematic evaluation of LLM-as-a-Judge to date: 21 judges from nine providers across MT-Bench, JudgeBench, and RewardBench, evaluated under three protocols (agreement, consistency, bias audit) over 118 runs and approximately 541,000 individual judgments. Four findings emerge, consistent across the full cohort, including the April 2026 frontier: kappa deflation between exact match and Cohen's kappa is universal (33–41 pp on MT-Bench), judge rankings shift by up to 14 positions across benchmarks, high test–retest reliability (>0.95) coexists with severe position bias (>0.10) in two production-deployed judges (instantiating a consistency–bias paradox), and verbosity bias is small (

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

Human Universal Grasping

arXiv:2606.17054v1 Announce Type: cross Abstract: Humans can grasp objects effortlessly, whereas multi-fingered robots are far from this level of generality. We argue that the most natural source of robot grasping data is from humans, who pick up thousands of objects every day. We present HUG, a flow-matching model that generates diverse human grasps for any user-specified object in a single RGB-D image captured from a stereo camera. Using smart glasses, we first collect 1M-HUGs, an egocentric dataset of human grasps spanning 1M frames (27.8 hrs) and 6,707 object instances across 41 buildings. Next, to model the distribution of natural human grasps, our novel flow-matching model fuses RGB and depth observations to output a grasp parameterized by wrist translation, wrist rotation, and MANO hand pose. Predicted grasps can be retargeted to various robot hands, enabling zero-shot grasping in everyday scenes. To standardize evaluation, we build a new simulated benchmark, HUG-Bench, of 90 unseen objects from five geometric categories and various sizes, with metric-scale 3D meshes. We evaluate HUG in the real world on the 30-object test set of HUG-Bench across multiple stereo cameras, robot embodiments, and household environments. HUG outperforms the state-of-the-art grasping baselines by +23% and +34% on our challenging object set. Code, data, benchmark, checkpoints, and an interactive demo are released on our website: https://grasping.io/

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

CoreMem: Riemannian Retrieval and Fisher-Guided Distillation for Long-Term Memory in Dialogue Agents

Personalized dialogue agents require continuous long-term memory to maintain coherent interactions across multiple sessions. However, deploying these capabilities on consumer-grade hardware (e.g., 8 GB VRAM edge devices) introduces severe memory and compute bottlenecks. Existing systems typically rely on isotropic cosine similarity for retrieval and heuristic rules for context compression. These approaches lack a unified theoretical foundation, frequently suffering from the hubness problem in high-dimensional retrieval and syntactic fragmentation during compression. To overcome these limitations, we propose CoreMem, a resource-efficient edge-cloud memory architecture fundamentally unified by information geometry. First, Riemannian retrieval replaces cosine matching with a locally adaptive Fisher-Rao metric, effectively penalizing hub memories via Mahalanobis distance with O(Ndr) Woodbury acceleration for real-time search. Second, Fisher-guided discrete token distillation (FDTD) introduces a hierarchical sentence-to-token compression mechanism. It derives sensitivity scores from Fisher information traces, providing a principled compression-KL tradeoff augmented with explicit structural syntax protection. Evaluated on the LOCOMO and LongMemEval-S benchmarks, CoreMem achieves strong accuracy improvements, yielding substantial gains in Open-domain (+4.51 pp) and Temporal (+4.17 pp) reasoning. Extensive profiling confirms that CoreMem operates seamlessly within a strict 8 GB VRAM budget, successfully bridging the gap between resource-constrained edge devices and the demand for theoretically grounded, lifelong memory agents.

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

LivePI: More Realistic Benchmarking of Agents Against Indirect Prompt Injection

arXiv:2605.17986v3 Announce Type: replace-cross Abstract: AI agents such as OpenClaw are increasingly deployed in local workflows with access to external tools. This creates indirect prompt-injection (IPI) risk: an agent may execute harmful instructions embedded in untrusted inputs such as email, downloaded files, webpages, repositories, or group-chat messages. Existing evaluations are often small, purely simulated, or focused on a narrow set of channels. We introduce LivePI (Live Prompt Injection), a structured benchmark for IPI risk in a production-like but test-controlled environment. LivePI covers seven input surfaces, twelve attack/rendering families, and five malicious goals, including protected-information exfiltration, unauthorized security-control changes, unsafe code retrieval or execution, inbox-summary exfiltration, and cryptocurrency transfer. We run LivePI on a real virtual machine with live but test-controlled email, chat, web, local-file, repository, and wallet interfaces. Across GPT-5.3-Codex, Claude Opus 4.6, Gemini 3.1 Pro, Kimi K2.5, and GLM-5, total attack success rates range from 10.7% to 29.6%. Group-chat injection is uniformly successful across the evaluated backbones in our deployment, and repository-link attacks produce high-severity failures despite a small denominator. We also evaluate a two-layer defense consisting of prompt-level filtering and pre-execution tool-call authorization. In the GPT-5.3-Codex setting, the defense intercepts all tested malicious-goal completions in LivePI before execution while preserving benign utility on PinchBench-derived workloads.

13.
medRxiv (Medicine) 2026-06-10

Longitudinal brain structural changes during clozapine treatment: associations with neuroreceptor architecture and clinical response

In treatment-resistant schizophrenia, clozapine treatment has been associated with longitudinal reductions in subcortical volumes, ventricular enlargement, and widespread cortical thinning. However, it is unknown how these structural changes relate to clozapines pharmacological profile and clinical efficacy. We combined five longitudinal datasets with MRI acquired before and on average 5 months after clozapine initiation in 143 individuals to quantify brain structural changes and their association with normative maps relating to neuroreceptor architecture and physiological systems, and improvement in symptom severity. Clozapine treatment was associated with grey matter volume reductions across multiple subcortical regions (including the amygdala, hippocampus, thalamus, caudate, putamen and nucleus accumbens), increases in pallidal volume, ventricular enlargement, and widespread cortical thinning. Cortical regions showing the greatest magnitude of thinning corresponded to areas with higher normative densities of serotonergic 5-HT1A, 5-HT2A and 5-HT4 receptors. Changes in subcortical volume or cortical thickness during clozapine treatment were not associated with changes in total or positive symptom severity. In addition, baseline subcortical volume, cortical thickness, or gyrification prior to starting clozapine did not predict subsequent symptom improvement. Cortical thinning may partly reflect clozapines activity at serotonergic receptors, which have been implicated in cortical network stabilisation and neuroplasticity, however structural remodelling during clozapine treatment may reflect a process independent from its clinical efficacy in improving core symptoms of psychosis.

14.
bioRxiv (Bioinfo) 2026-06-13

Testing the reliability of AI-generated protein structures

Authors:

Although AlphaFold2 and its competitors have demonstrated remarkable abilities to predict protein structure, more work is needed to explore the limitations of these methods. Here we investigated the reliability of AlphaFold2 and ColabFold by creating a set of realistic but false protein sequences, using ColabFold to predict their structure, and then asking how often the program produces a high-scoring structure for a sequence that does not represent a protein. We determined that AlphaFold2 has a very small but non-zero false positive rate, estimated here at approximately 1 in 435 if one uses a threshold pLDDT score of 70 to define positive predictions. We also discovered, serendipitously, that some high-scoring sequences in the human genome were not false positives, but instead were previously unknown and un-annotated pseudogenes. These latter findings indicate that some well-established human annotations of protein-coding genes may have incorrectly extended the 5-prime untranslated regions too far. They also suggest that the false positive rate of AlphaFold2 is low enough that almost any high-scoring structure, even in a noncoding region, is worthy of further investigation.

15.
medRxiv (Medicine) 2026-06-22

Impact of Antidiabetic Medications on IgG and Plasma Protein N-Glycosylation in Type 2 Diabetes Patients

Introduction. Diabetes is a growing global health challenge, necessitating effective management strategies. Glycosylation, a highly regulated post-translational protein modification, has emerged as a pivotal factor in diabetes pathophysiology. However, the modulation of protein glycosylation by antidiabetic treatment is still largely unknown. This study explored the longitudinal effects of four distinct antidiabetic therapies - metformin, insulin, sodium-glucose cotransporter-2 (SGLT2) inhibitors, and glucagon-like peptide-1 receptor agonists (GLP-1RA) - on plasma protein and immunoglobulin G (IgG) glycosylation in patients with type 2 diabetes (T2D). Research Design and Methods. Plasma protein and IgG N-glycans were enzymatically released, purified and chromatographically profiled in a cohort of 124 patients, examined at four time points, to assess therapy-induced glycan alterations. Linear mixed models adjusting for covariates and multiple testing (FDR

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

Compiler-First State Space Duality and Portable $O(1)$ Autoregressive Caching for Inference

arXiv:2603.09555v2 Announce Type: replace-cross Abstract: High-throughput Mamba-2 inference is usually tied to fused CUDA and Triton kernels, limiting portability across accelerator backends. We show that the state space duality (SSD) recurrence has a compiler-friendly structure: diagonal per-head dynamics, fixed-size chunking, einsum-dominated compute, and static control flow. Expressing this structure in standard JAX primitives gives a single-source inference path with no custom kernels, a registered JAX PyTree cache, and a compiled on-device autoregressive loop. On a single Google Cloud TPU v6e, batch-1 prefill reaches approximately 140 TFLOPS, or 15% model FLOP utilisation (MFU), the roofline ceiling for this regime, and cached decode reaches up to 64% hardware bandwidth utilisation (HBU). At a 4096-token context, cached decode is 27x–36x faster than full-prefix recomputation across five Mamba-2 checkpoints from 130M to 2.7B parameters. The same source runs unmodified on NVIDIA L40S, where cached decode remains sequence-length independent across all model scales. WikiText-103 validation perplexity matches the Triton reference mamba_ssm v2.2.2 within +/-0.0005 points, and hidden states agree to float32 rounding tolerance. Code is available at https://github.com/CosmoNaught/mamba2-jax.

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

Scalable anomaly detection via a univariate Christoffel function

arXiv:2606.12483v1 Announce Type: new Abstract: Anomaly detection plays a critical role in identifying unusual patterns across domains such as fraud detection, network intrusion, and system fault diagnosis. Recently, Christoffel function-based methods, rooted in polynomial optimization, have emerged as promising alternatives to deep learning due to their strong mathematical foundations and computational frugality. However, their practical applicability is hindered by the need to invert a matrix whose size grows exponentially with the data dimension, rendering the method intractable even for moderate-dimensional datasets. This paper addresses the dimensionality limitations of Christoffel function-based anomaly detection while preserving its key theoretical properties, i.e., the on-off support dichotomy behavior and the accurate support shape capture. We introduce UCF, a univariate Christoffel function which is based on the squared distance between the query point and the support points. Extensive experiments on the ADBench benchmark demonstrate that UCF consistently outperforms 14 state-of-the-art baselines in terms of Average Precision. By resolving the scalability bottleneck of the Christoffel Function, this work expands the toolkit of anomaly detection methods with a robust, theoretically grounded, and universally applicable approach.

18.
arXiv (CS.CL) 2026-06-15

Graph-based Target Back-Propagation for Context Adaptation in Multi-LLM Agentic Systems

Context adaptation automates prompt engineering in LLM-based systems by iteratively revising tunable prompts from task feedback, without modifying model weights. Extending this paradigm to multi-LLM agentic systems is crucial: existing methods suffer from inaccurate credit assignment and lack convergence guarantees. We propose Graph-based Target Back-Propagation (GTBP), a context adaptation framework for agentic workflows modeled as directed acyclic graphs. GTBP propagates local target outputs backward through the workflow graph and uses target–output discrepancies to guide a stage-wise prompt update mechanism. Theoretically, we show that GTBP's stage-wise prompt updates become stable over iterations, and that a sufficiently capable LLM optimizer can decrease the overall objective. Empirically, GTBP consistently outperforms strong baselines across three benchmarks while maintaining comparable computational cost.

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

Optimism Stabilizes Thompson Sampling for Adaptive Inference

arXiv:2602.06014v2 Announce Type: replace-cross Abstract: Thompson sampling (TS) is widely used for stochastic multi-armed bandits, yet its inferential properties under adaptive data collection are subtle. Classical asymptotic theory for sample means can fail because arm-specific sample sizes are random and coupled with the rewards through the action-selection rule. We study adaptive inference for Thompson sampling with Gaussian randomized indices in $K$-armed stochastic bandits with independent sub-Gaussian reward noises, and identify optimism as a key mechanism for restoring stability, meaning that each arm's pull count concentrates around a deterministic scale. This stability yields asymptotically valid Wald inference despite adaptive sampling. First, we prove that variance-inflated TS is stable for any $K \ge 2$, including the challenging regime where multiple arms are optimal, with asymptotically uniform allocation over optimal arms and sharp logarithmic pull-count asymptotics for suboptimal arms. This resolves the $K$-armed extension question raised by \citet{halder2025stable}, using new winner-map and Lyapunov-drift techniques to control allocation among multiple optimal arms. Second, we analyze an alternative optimistic modification that keeps the Gaussian index variance unchanged but adds an explicit mean bonus to the index center, and establish a similar stability conclusion. In summary, suitably implemented optimism stabilizes Thompson sampling and enables asymptotically valid Wald inference in multi-armed bandits, while incurring only a mild additional regret cost.

20.
medRxiv (Medicine) 2026-06-12

Immunologically Optimized Zmp1 Peptides Reveal a Translational Serological Biomarker Platform for Tuberculosis Diagnosis Across Disease Manifestations

Tuberculosis (TB) diagnosis remains challenging, particularly for extrapulmonary TB (EPTB), where invasive sampling, low bacillary burden, and suboptimal sensitivity of nucleic acid-based tests in peripheral specimens hinder timely detection. Here, we report an immunology-driven strategy for biomarker discovery and development of a peptide-based serological assay targeting Mycobacterium tuberculosis zinc metalloprotease-1 (Zmp1). Leveraging fundamental principles of adaptive immunity that antigenic regions containing overlapping B-cell and CD4 T-helper cell epitopes would preferentially generate high antibody titers through linked recognition and cognate T-cell help, we used an immunoinformatics pipeline to identify two nested immunodominant peptide regions within Zmp1 (Mtb-Zp-NT and Mtb-Zp-CT) enriched for overlapping B- and T-cell epitopes. The diagnostic potential of these peptides was evaluated through ELISA-based serological assays. A blinded pilot study (N=137) demonstrated a clear discrimination between active TB and TB-recovered individuals. The assay was subsequently validated in an expanded cohort (N=875) by screening 6,086 individuals, which identified 457 TB-positive cases. The cohort included pulmonary TB (PTB), EPTB, TB-recovered individuals, household contacts, non-specific infections, and healthy controls. Receiver operating characteristic analyses, supported by DeLong and bootstrap comparisons, revealed superior diagnostic performance of the peptide-based assays relative to full-length Zmp1. Mtb-Zp-CT exhibited the highest accuracy (AUC=0.93; specificity >90%), while Mtb-Zp-NT also demonstrated strong discriminatory power (AUC{approx}0.89). These findings establish that the immunologically optimized Zmp1 peptides are highly promising serological biomarkers for TB and EPTB. More broadly, they demonstrate how mechanistically informed epitope selection can accelerate translation of pathogen-specific immune signatures into sensitive, minimally invasive, and potentially point-of-care diagnostic platforms for resource-limited settings.

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

Hierarchical Modeling of ICD Codes in EHR Foundation Models

arXiv:2606.15447v1 Announce Type: new Abstract: Electronic health record foundation models typically treat ICD diagnosis codes as flat tokens, overlooking the clinically meaningful hierarchical structure that captures disease families, subcategories, and fine-grained diagnostic detail. As a result, existing EHR representation learning methods do not explicitly exploit the hierarchical structure already present in the coding system. In this work, we study ICD-10-CM hierarchy as a general inductive bias for clinical representation learning. We investigate two complementary mechanisms for incorporating hierarchy: first, by augmenting diagnosis sequences in a BERT-style transformer with tokens corresponding to different levels of the ICD hierarchy, and second, by injecting hierarchy into graph-based code representations through hierarchy-aware edges combined with diagnosis co-occurrence structure. Across these settings, we evaluate whether explicit hierarchy improves downstream prediction, which levels of the hierarchy are most useful, whether hierarchy encoding improves transfer across datasets, and how hierarchy reshapes embedding similarity structure. We conduct experiments on two large-scale real-world clinical datasets: MIMIC-IV, used for pretraining and in-domain evaluation, and eICU, used to assess cross-dataset transfer via frozen encoder probing. Our findings show that explicitly encoding ICD hierarchy improves over flat code representations in both in-domain and cross-dataset settings, while revealing that the most useful level of hierarchy depends on both the task and the modeling approach. More broadly, we focus on hierarchy-aware EHR representation learning and show that the benefits of encoding hierarchy are generalizable across modeling settings and hierarchy levels.

22.
arXiv (CS.LG) 2026-06-12

Dense Supervision, Sparse Updates: On the Sparsity and Geometry of On-Policy Distillation

arXiv:2606.13657v1 Announce Type: new Abstract: On-policy distillation (\textsc{OPD}) has recently become a prominent post-training recipe as it combines two desirable ingredients: on-policy student trajectories and dense teacher supervision, yet how this hybrid changes a model's parameters remains unclear. Across several language and vision-language model pairs and use cases, our analysis yields two main findings. On sparsity, \textsc{OPD}-style updates are small and coordinate-sparse. They are distributed across layers and are usually FFN-heavy. This sparse structure is operationally useful: training only the discovered subnetwork recovers nearly the same performance as full \textsc{OPD}. However, the sparsity-inducing SGD optimizer underperforms AdamW in our optimizer ablation, likely because dense teacher supervision preserves heterogeneous coordinate-wise gradient scales where AdamW's adaptive scaling remains useful. On geometry, the updates are numerically full-rank but spectrally concentrated; they lie mostly away from the principal singular subspaces of the source weights and fall disproportionately on coordinates where the source weights are close to zero. These findings suggest that dense teacher supervision does not turn \textsc{OPD} into ordinary dense parameter rewriting; instead, \textsc{OPD} retains important geometric signatures of on-policy post-training.

23.
arXiv (CS.AI) 2026-06-18

Robust Regularized Policy Iteration under Transition Uncertainty

arXiv:2603.09344v3 Announce Type: replace Abstract: Offline reinforcement learning (RL) enables data-efficient and safe policy learning without online exploration, but its performance often degrades under distribution shift. The learned policy may visit out-of-distribution state-action pairs where value estimates and learned dynamics are unreliable. To address policy-induced extrapolation and transition uncertainty in a unified framework, we formulate offline RL as robust policy optimization, treating the transition kernel as a decision variable within an uncertainty set and optimizing the policy against the worst-case dynamics. We propose Robust Regularized Policy Iteration (RRPI), which replaces the intractable max-min bilevel objective with a tractable KL-regularized surrogate and derives an efficient policy iteration procedure based on a robust regularized Bellman operator. We provide theoretical guarantees by showing that the proposed operator is a $\gamma$-contraction and that iteratively updating the surrogate yields monotonic improvement of the original robust objective with convergence. Experiments on D4RL benchmarks demonstrate that RRPI achieves strong average performance, outperforming recent baselines including percentile-based methods on the majority of environments while remaining competitive on the rest. Moreover, RRPI exhibits robust performance by aligning lower $Q$-values with high epistemic uncertainty, which prevents the policy from executing unreliable out-of-distribution actions.

24.
arXiv (quant-ph) 2026-06-12

Entanglement Detection by Approximate Entanglement Witnesses

arXiv:2402.14755v2 Announce Type: replace Abstract: The problem of determining whether a given quantum state is separable is known to be computationally difficult. We develop an approach to this problem based on approximations of convex polytopes in high dimensions. By showing that a convex polytope constructed from a finite number of hyperplanes approximates the Euclidean ball arbitrarily well in high dimensions, we find evidence that a finite set of approximate entanglement witnesses is potentially sufficient to determine the entanglement of a state with high probability.

25.
medRxiv (Medicine) 2026-06-15

VarEx: A Large Language Model Pipeline for Automated Extraction of Exposures, Outcomes, and Covariates from Epidemiologic Studies

Objective: Observational studies are essential for investigating risk factors for Alzheimer's disease and related dementias (ADRD), but inconsistent reporting and selection of covariates can contribute to residual confounding, omitted-variable bias, and reduced reproducibility. We developed and evaluated VAREX (Variable Extraction), a large language model (LLM)-based information extraction framework designed to automatically identify exposures, outcomes, and covariates from epidemiologic studies and populate structured evidence repositories. Materials and Methods: VAREX combines retrieval-augmented generation, biomedical language-model embeddings, semantic chunking, cross-encoder reranking, and prompt-engineered LLM workflows to extract epidemiologic variables from full-text biomedical articles. The framework was evaluated using a reference-standard corpus of observational studies examining blood pressure variability (BPV) and Alzheimer's disease-related dementias (ADRD), together with external validation datasets involving other exposure-outcome relationships. Extracted variables were compared with independently curated human reference standards using semantic matching and one-to-one assignment procedures. Covariates were additionally classified into ten epidemiologically relevant semantic categories. Results: In the primary BPV[->]ADRD corpus (10 studies), VAREX achieved a precision of 0.91, recall of 0.84, and F1-score of 0.87 for variable extraction. Covariate classification accuracy was 0.90, yielding a strict extraction-and-classification F1-score of 0.78. External validation datasets demonstrated comparable performance across diverse epidemiologic domains, with extraction F1-scores ranging from 0.73 to 0.85. Category-level performance was strongest for health behaviors (F1=0.96), sociodemographic variables (F1=0.90), and medication exposures (F1=0.89). Compared with published estimates of manual systematic-review effort, VAREX reduced processing time from approximately 61 minutes to 9 minutes per article, representing an 85.7% reduction in review time. Discussion: These findings demonstrate that LLM-based information extraction can accurately identify and classify epidemiologic variables across heterogeneous observational-study designs. Automated extraction enables scalable construction of structured repositories of exposures, outcomes, and covariates while substantially reducing the labor required for evidence synthesis and systematic reviews. Conclusion: VAREX provides an effective framework for automated extraction and classification of epidemiologic variables from the biomedical literature. By supporting large-scale evidence synthesis and structured knowledge resource development, VAREX may facilitate more rigorous observational research, improved confounder identification, and enhanced reproducibility in epidemiology.