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01.
arXiv (quant-ph) 2026-06-19

Purity and bound energy in ancilla-assisted work extraction

arXiv:2606.19945v1 Announce Type: new Abstract: We investigate ancilla-assisted work extraction in quantum batteries from the perspective of bound energy and purity. We show that the bound energy of the reduced system provides a tight upper bound to the daemonic gain and that this bound is saturated for globally pure system–ancilla states. Motivated by this relation, we introduce a purity-based gain that qualitatively predicts the daemonic gain without requiring explicit optimization over measurements. We further introduce a protocol to analyze the role of dissipation and intrinsic interactions on daemonic gain. Under a collective environment, dissipation can dynamically generate and stabilize finite daemonic gain through environment-induced correlations. In interacting systems, level crossings and spectral restructuring strongly modify the attainable gain through their influence on the accessible bound energy. Our results demonstrate that daemonic gain is governed not only by correlations, but also by the spectral structure of the underlying Hamiltonian and information loss captured by bound energy and purity.

02.
arXiv (CS.CL) 2026-06-12

The Illusion of Multi-Agent Advantage

Prevailing wisdom posits that Multi-Agent Systems (MAS) are superior to Single-Agent Systems (SAS), citing advantages like context protection, parallel processing and distributed decision-making. However, empirical support for this claim relies primarily on comparisons with SAS baselines using benchmarks that prioritize isolated reasoning tasks, which do not adequately assess these advantages. Focusing on automatically generated MAS that are designed for enhanced generalizability over manually-designed counterparts, we perform a rigorous, systematic evaluation against SAS, specifically Chain-of-Thought with Self-Consistency (CoT-SC). Across traditional reasoning datasets and tasks with interactive multi-step workflows (e.g., BrowseComp-Plus), we demonstrate that automatic MAS consistently underperform CoT-SC despite being up to 10x more expensive. To isolate these failures from limitations inherent to task structure, we introduce a diagnostic synthetic dataset tailored for MAS featuring explicit task decomposition, context separation and parallelization potential. We show that expert-architected MAS consistently outperforms automatically generated architectures in both raw performance and cost-efficiency on this dataset, demonstrating that existing evaluation frameworks mask critical architectural gaps and inefficiencies of complex MAS by failing to account for the marginal utility of increased computational cost. Critically, systematic deconstruction of the generated MAS architectures reveals that current automated design paradigms produce architectural bloat that prioritizes superficial complexity which does not translate into functional utility, exposing a fundamental misalignment with multi-agent principles.

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

Towards a Bridge Layer Between Bibliographic and Formalized Mathematical Knowledge

作者:

arXiv:2606.11430v1 Announce Type: cross Abstract: Mathematical knowledge is split between bibliographic databases (e.g., MathSciNet, zbMATH Open) and formal proof libraries (e.g., Lean mathlib), preventing unified access between published results and their formalizations. We propose a relational bridge-database that aligns publication metadata with formal artifacts, providing an interoperability layer between mathematical literature and machine-verifiable proofs. We introduce a paper-level formalization score that measures how much of a publication is covered in formal systems. As a feasibility study, we show how such scores can be estimated via cross-document alignment between informal texts and Lean formalizations, enabling large-scale analysis of formalization coverage. This framework is a first step toward integrating bibliographic and formal mathematical ecosystems into scalable, machine-actionable knowledge graphs linking publications to formal proof objects.

04.
arXiv (CS.AI) 2026-06-17

Model Validation of Agentic AI Systems: A POMDP-Based Framework for Belief-State, Forecast, and Policy Validation

arXiv:2606.17383v1 Announce Type: cross Abstract: Agentic artificial intelligence systems introduce a new class of model risk. Unlike traditional predictive models, autonomous agents continuously acquire information, form beliefs regarding latent states of the environment, generate forecasts, select actions, and adapt their behavior over time. Existing validation methodologies focus primarily on predictive accuracy and therefore provide limited insight into the quality of the underlying decision process. This paper proposes a model validation framework for agentic AI based on Partially Observable Markov Decision Processes (POMDPs). The framework decomposes autonomous decision making into information, beliefs, forecasts, actions, and utility, allowing each component to be validated independently. Large language models (LLMs) are formalized as approximate Bayesian filtering operators, and a model-risk taxonomy is developed encompassing state-space, filtering, forecast, policy, utility-specification, and parameter risks. The model risk validation methodology is demonstrated through a portfolio-management case study in which an agent infers latent market regimes from market and macroeconomic information, generates belief-conditioned forecasts, and constructs portfolios using a Black–Litterman framework. Empirical validation combines performance analysis, belief calibration diagnostics, coverage tests, ablation studies, and parameter-sensitivity analysis. The results indicate that latent-state inference contributes independently to decision quality and that the principal conclusions remain robust across a broad range of parameter values. The principal contribution of the paper is a practical framework for extending established model risk management concepts to autonomous AI systems and providing a rigorous foundation for their validation, governance, and monitoring.

05.
arXiv (CS.AI) 2026-06-15

Sensitivity Shaping for Latent Modeling

arXiv:2606.14585v1 Announce Type: cross Abstract: Generative dynamics models enable planning in challenging robotic systems, but safe deployment requires reliably detecting policy-induced out-of-distribution (OOD) transitions. Existing methods typically treat the learned dynamics as fixed and attach post hoc support surrogates. We show that these surrogates can fail when the dynamics are locally insensitive to critical action choices: unsupported control actions may produce latent predictions that resemble demonstrated transitions, suppressing OOD signals despite large true predictive errors. To address this, we introduce support-conditioned control-sensitivity regularization, which promotes sensitive local response to control input changes in learned dynamics in high-support training regions. This preserves control-induced variation while limiting unstable extrapolation due to weak empirical support. Experiments in vision-based obstacle avoidance, manipulation, and real-robot navigation show improved OOD detection and safer closed-loop planning.

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

Feature Attribution in Directed Acyclic Graphs Using Edge Intervention

arXiv:2606.15273v1 Announce Type: new Abstract: Shapley value-based feature attribution methods face challenges in scenarios involving complex feature interactions and causal relationships, even when a causal structure is provided. Existing methods typically adopt a node-centric view, attributing importance solely to individual features. Consequently, they often fail to simultaneously capture the externality and exogenous influence of features, leading to unreasonable interpretations. To overcome these limitations, we propose a novel feature attribution method called DAG-SHAP, which is based on edge intervention. DAG-SHAP treats each feature edge as an individual attribution object, ensuring that both externality and exogenous contributions of features are appropriately captured. Additionally, we introduce an approximation method for efficiently computing DAG-SHAP. Extensive experiments on both real and synthetic datasets validate the effectiveness of DAG-SHAP. Our code is available at https://github.com/ZJU-DIVER/DAG-SHAP.

07.
arXiv (CS.LG) 2026-06-16

Test-Time Compute Scaling for ASR with Depth-Conditioned Looped Transformers

arXiv:2606.04678v2 Announce Type: replace Abstract: End-to-end ASR systems typically use fixed-depth acoustic encoders at inference, making it difficult to trade additional test-time computation for improved recognition without training a larger model. A natural approach is to reuse a shared Transformer block recurrently, but we find that naive looping does not fully exploit additional recurrent compute. We introduce LARM, a depth-conditioned looped Transformer that turns recurrent encoder depth into a controllable test-time compute axis. LARM combines sparse CTC checkpoints, supervision-clock embeddings, FiLM depth conditioning, and delayed soft-posterior feedback. These components structure the loop into recognition checkpoints separated by latent refinement phases and allow shared weights to specialize across recurrent steps. On LibriSpeech, LARM improves WER as the number of inference loops increases and achieves performance competitive with deeper unshared-parameter baselines. Our results show that test-time compute scaling can extend beyond autoregressive language-model reasoning to continuous non-autoregressive speech recognition.

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

Overcoming the Impedance Mismatch: A Theoretical Roadmap for Fusing Foundation Models and Knowledge Graphs

arXiv:2606.15656v1 Announce Type: new Abstract: Modern artificial intelligence remains fundamentally divided between the continuous, probabilistic spaces of Foundation Models and the discrete, deterministic structures of Knowledge Graphs. While Retrieval-Augmented Generation (RAG) attempts to connect them by serializing graph data into text, we argue this lexical bridging is merely a superficial patch. In this paper, we formalize the underlying structural and geometric friction as the Impedance Mismatch. By categorizing current neuro-symbolic integration strategies into a three-tiered hierarchy, we demonstrate that neither surface-level prompt injection nor continuous representation alignment can preserve the strict logical motifs required for reliable multi-hop reasoning. We define the specific mathematical limits, such as the Lexical Bottleneck and Topological Collapse, that show current architectures will eventually hallucinate or conflate semantic nodes. To achieve true semantic fusion, we propose a rigorous theoretical roadmap. We advocate for natively internalizing discrete symbolic structures through Structured Residual Streams, utilizing Vector Symbolic Architectures for latent sub-graph injection, and performing model updates via Orthogonal Subspace Editing. This actionable framework paves the way for models that seamlessly fuse the precision of symbolic logic with the expressivity of parametric memory.

09.
arXiv (CS.CV) 2026-06-16

NeRD: Neuro-Symbolic Rule Distillation for Efficient Ontology-Grounded Chain-of-Thought in Medical Image Diagnosis

Interpretability is essential for trustworthy medical image diagnosis. However, existing concept-driven interpretable methods have key limitations: Concept Bottleneck Models (CBMs) require scoring all predefined concepts at inference time and for manual intervention, imposing a substantial burden on clinicians, while rationale-based generative approaches often select concepts by class discriminability, which can drift from diagnostic ontologies. To address these issues, we propose Neuro-Symbolic Rule Distillation (NeRD), a framework that produces efficient, ontology-grounded reasoning chains that are sufficient yet non-redundant, without manually crafting diagnostic rules. Experiments on two skin datasets demonstrate strong diagnostic performance and interpretability, and blinded expert evaluation confirms the clinical plausibility of NeRD rationales. Our method further enables a first expert-in-the-loop study for Multimodal Chain-of-Thought-based diagnosis, achieving efficient and effective concept-level intervention.

10.
arXiv (CS.CV) 2026-06-18

Simple Domain Generalization Methods are Strong Baselines for Open Domain Generalization

In real-world applications, a machine learning model is required to handle an open-set recognition (OSR), where unknown classes appear during the inference, in addition to a domain shift, where the data distribution differs between the training and inference phases. Domain generalization (DG) aims to handle the domain shift situation where the target domain of the inference phase is inaccessible during the model training. Open domain generalization (ODG) considers DG and OSR. Domain-augmented meta-learning (DAML) is a method targeting ODG; however, it has a complicated learning process. By contrast, although various DG methods have been proposed, they have not been evaluated in ODG situations. In this study, we comprehensively evaluate the existing DG methods in ODG and show that the two simple DG methods, CORrelation ALignment (CORAL) and maximum mean discrepancy (MMD), are competitive with DAML in several cases. In addition, we propose simple extensions of CORAL and MMD by introducing the techniques used in DAML, such as ensemble learning and Dirichlet mixup data augmentation. The experimental evaluation demonstrates that the extended CORAL and MMD can perform comparably to DAML with lower computational costs. This suggests that the simple DG methods and their simple extensions are strong baselines for ODG.

11.
arXiv (quant-ph) 2026-06-19

QPU-scale randomized benchmarking via Bell-pair injection

arXiv:2606.20123v1 Announce Type: new Abstract: Mirror randomized benchmarking (MRB) is an established technique that provides a global error metric at the scale of a whole QPU. To expand upon this we introduce Mirror Quantum Awesomeness (MQA), a hybrid protocol that adds a structured entangling layer to MRB circuits. This enables per-edge correlation dynamics to be tracked via mutual information while preserving the MRB infidelity estimate. The resulting analysis of the injected entangled pairs locates a critical circuit depth, beyond which rudimentary error mitigation techniques can be expected to fail. A topological variant, Topological MQA, supplies a second critical depth via a decoder based on the surface-code decoding problem. Both are validated in simulation and demonstrated on the 156-qubit \texttt{ibm\_fez} and \texttt{ibm\_kingston} processors, where MQA closely agrees with MRB on the entanglement infidelity and the critical depth for \texttt{ibm\_fez} is found to be $\sim 50$.

12.
arXiv (CS.AI) 2026-06-16

Gaming-Resistant Insurance Contracts for Autonomous AI Agents: Strategy-Proof Toll Mechanism Design

arXiv:2606.16326v1 Announce Type: cross Abstract: Paper A defines a time-consistent actuarial runtime that prices each side-effect-bearing action against a contractually fixed safe default and gates execution against a reserve budget. It treats the operator as passive. This paper makes the operator strategic. We characterise a five-attack space for autonomous AI-agent insurance contracts and prove when the actuarial runtime is gaming-resistant. Two attack surfaces – post-toll safe-default selection and within-boundary action splitting – are closed by Paper A's minimal-authority and no-splitting clauses. The remaining three require new contract clauses. First, common-control aggregation prevents cross-boundary re-routing from reducing toll below the boundary potential applied to total exposure. Second, interface failures such as invalid JSON are contract-relevant events, not safety wins: treating them as zero-toll safe defaults can reward unreliable models, while escalation fees reverse the incentive. We validate this interface-compliance theorem on committed cross-model traces from the companion empirical paper. Third, a model-identity menu with a componentwise-minimum penalty schedule makes truthful reporting of the deployed model weakly dominant. We then compose these clauses with Paper A's runtime guarantees to obtain joint incentive compatibility over the five-attack space. Finally, a two-parameter premium family discharges operator individual rationality and weak budget balance at the truthful equilibrium. The result is an incentive-compatibility layer for actuarial control of autonomous-agent side effects.

13.
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).

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

SkillJect: Effectively Automating Skill-Based Prompt Injection for Skill-Enabled Agents

arXiv:2602.14211v3 Announce Type: replace-cross Abstract: Agent skills extend LLM agents with task-specific instructions, executable scripts, and auxiliary resources, improving reusability but creating a new supply-chain attack surface. A malicious or compromised skill can be repeatedly loaded as trusted guidance and steer downstream tool use. Existing skill-based prompt-injection attacks are often manual and brittle, because explicit malicious instructions are rejected or ignored when they are not aligned with the original workflow. We propose SkillJect, the first automated framework for generating poisoned skills against skill-enabled agent systems. SkillJect uses two coordinated channels. In the artifact channel, it hides the payload inside an auxiliary helper script. In the instruction channel, it rewrites SKILL.md with a front-loaded inducement strategy, placing injected content at the beginning and framing the helper script as a mandatory prerequisite or initialization step. The rewritten instruction explicitly references the helper-script path and provides an executable example command, making the helper appear to be a legitimate setup step before normal skill operations. SkillJect further adopts a closed-loop multi-agent process to improve attack effectiveness. An Attack Agent generates poisoned skills, a Victim Agent executes downstream tasks with the poisoned skill, and an Evaluate Agent inspects execution traces to determine whether the hidden payload was executed. The Attack Agent then uses this feedback to diagnose failure causes and rewrite SKILL.md, while keeping the payload fixed. Experiments across skill-enabled platforms, backend LLMs, and attack categories show that SkillJect substantially outperforms naive direct injection and prior manual skill-injection attacks, highlighting poisoned skills as a persistent threat in reusable skill ecosystems.

15.
arXiv (CS.CV) 2026-06-12

Distributional Loss for Robust Classification

This paper proposes a novel loss concept for supervised classification tasks. Rather than enforcing a direct mapping from each input sample to a single assigned label, we define an optimization objective over all classifier outputs as a bimodal Gaussian distribution. This softer target formulation implicitly captures class ambiguity, mitigates overfitting, and encourages the learning of more robust decision boundaries, all without requiring additional label information. Experimental results demonstrate consistent improvements in robustness, with particularly pronounced gains in low-data regimes, while requiring only minimal modifications to standard training pipelines.

16.
arXiv (quant-ph) 2026-06-12

Influence-solvability: a systematic theory of $(1+1)D$ solvability and its application to brickwork circuits

arXiv:2606.12538v1 Announce Type: cross Abstract: `Solvable' circuits, such as dual unitaries and its generalisations, have arisen as paradigmatic examples of tractable chaotic non-equilibrium dynamics, both in classical and quantum systems. However, while increasingly more complicated sufficient conditions have been proposed, a systematic theory classifying and understanding general features of solvable circuits is missing. We develop such a theory by introducing influence-solvable circuits, a class of $(1+1)D$ circuits whose influence matrix, which represents the `bath' generated by its own evolution, is given by a uniform MPS with finite bond-dimension $\chi$. This property allows for efficient computation of subsystem dynamics and essentially contains all known examples of solvable circuits. We derive a set of necessary and sufficient local conditions by using a version of the fundamental theorem of MPS for open boundary conditions. Next we apply our theory to brickwork circuits with $\chi=1$ influence-solvability and perform a systematic classification of classical brickwork circuits with local dimension up to $d=3$ and quantum brickwork circuits with $d=2$. Our search reveals new solvable circuits that are not captured by known solvability conditions.

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

FLiP: Towards understanding and interpreting multimodal multilingual sentence embeddings

This paper presents factorized linear projection (FLiP) models for understanding pretrained sentence embedding spaces. We train FLiP models to recover the lexical content from multilingual (LaBSE), multimodal (SONAR) and API-based (Gemini) sentence embedding spaces in several high- and mid-resource languages. We show that FLiP can recall more than 75% of lexical content from the embeddings, significantly outperforming existing non-factorized baselines. Using this as a diagnostic tool, we uncover the modality and language biases across the selected sentence encoders and provide practitioners with intrinsic insights about the encoders without relying on conventional downstream evaluation tasks. Our implementation is public https://github.com/BUTSpeechFIT/FLiP.

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

Beyond Domains: Reusing Web Skills via Transferable Interaction Patterns

Large language model (LLM) web agents are usually deployed as tool callers: each turn, the model reads a fresh page observation and emits one structured tool action. When every action is a low-level primitive, horizons grow quickly and so do policy-facing LLM completions, dominating latency and cost on benchmarks such as Mind2Web and WebArena. Recent systems therefore wrap repeated interaction fragments as web skills: callable tools built from successful trajectories or induced programs, so one call can replace several primitives. However, prior skill libraries are still triggered mainly by instruction similarity or coarse site metadata, which yields low skill reuse on held-out sites and leaves much of the potential step and token reduction on the table. We present SkillMigrator, an agent that learns reusable web skills and transfers them across sites by matching layout structure rather than specific element references. Each induced skill is stored as a transferable interaction pattern (TIP): the skill paired with a structural sketch of the snapshot at induction time. At test time, SkillMigrator retrieves TIPs by layout similarity and grounds their references on the live page. The rest of the stack is standard: accessibility-snapshot observations with stable references, and fixed tool calling over primitives plus skill invocations. Compared with the state-of-the-art approaches, SkillMigrator reduces the average LLM-action count on successful trajectories by 8-10% across both WebArena and Mind2Web at matched success rate.

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

OncoReg: Medical Image Registration for Oncological Challenges

In modern cancer research, the vast volume of medical data generated is often underutilised due to challenges related to patient privacy. The OncoReg Challenge addresses this issue by enabling researchers to develop and validate image registration methods through a two-phase framework that ensures patient privacy while fostering the development of more generalisable AI models. Phase one involves working with a publicly available dataset, while phase two focuses on training models on a private dataset within secure hospital networks. OncoReg builds upon the foundation established by the Learn2Reg Challenge by incorporating the registration of interventional cone-beam computed tomography with standard planning fan-beam CT images in radiotherapy. Accurate image registration is crucial in oncology, particularly for dynamic treatment adjustments in image-guided radiotherapy, where precise alignment is necessary to minimise radiation exposure to healthy tissues while effectively targeting tumours. This work details the methodology and data behind the OncoReg Challenge and provides a comprehensive analysis of the competition entries and results. Findings reveal that feature extraction plays a pivotal role in this registration task. A new method emerging from this challenge demonstrated its versatility, while established approaches continue to perform comparably to newer techniques. Both deep learning and classical approaches still play significant roles in image registration, with the combination of methods, particularly in feature extraction, proving most effective.

20.
arXiv (quant-ph) 2026-06-11

Mathematical Basis for Analyzing Superconducting Phase Transitions Using Catastrophe Theory

arXiv:2606.11810v1 Announce Type: cross Abstract: We establish a rigorous mathematical bridge from quantum many-body path integrals to the cusp catastrophe model by Lyapunov-Schmidt reduction, which provides a theoretical foundation for analyzing superconducting phase transition using the catastrophe theory. First, it is proved that, near the critical point the infinite-dimensional effective action is diffeomorphic to a finite-dimensional catastrophe. Secondly, starting from Ginzburg-Landau free energy functional, the Euler-Lagrange partial differential equation can be reduced to the cusp catastrophe model. Thirdly, the fermionic imaginary-time path integral to the cusp catastrophe is derived through the Hubbard-Stratonovich transformation, Matsubara frequency expansion, and Grassmann algebra. Furthermore, we connect this framework with the adsorption potential theory we proposed, elucidating the catastrophic topological nature of the electron pairing mechanism in high-temperature superconductivity. The precise microscopic derivation of the adsorption potential from first-principles electronic structure calculations would strengthen the predictive power of the theory.

21.
arXiv (CS.CL) 2026-06-17

LLM Features Can Hurt GNNs: Concatenation Interference on Homophilous Graph Benchmarks

Adding LLM-generated node features to graph neural networks (GNNs) is widely reported to improve accuracy on standard benchmarks. We document a contrasting observation: when LLM features are introduced through pure input concatenation (rather than joint training, distillation, or prompt-conditioning), they can systematically degrade accuracy on the same homophilous benchmarks where end-to-end LLM pipelines succeed. With an MLP backbone on the Planetoid public split and bag-of-words original features, concatenating SBERT-encoded GPT-4o-mini TAPE features reduces PubMed test accuracy by -17.0 +/- 0.3 pp and Cora by -4.3 +/- 0.6 pp (CiteSeer -0.6 +/- 0.8 pp, within seed noise). The drop attenuates as we relax each condition (GCN / GCNII / GAT backbones, random splits, smaller encoders) and reverses on medium-homophily WikiCS (+4.4 pp) and ogbn-arxiv (+11.7 pp). To predict when concatenation helps versus hurts, we report a simple measure of LLM-alone discriminability, Delta_sig. Across 9 datasets Delta_sig correlates with the concatenation cost more strongly than homophily at point estimate (r^2 = 0.38 vs. 0.06; N=9, bootstrap CIs overlap). The bootstrap-best change-point is tau = 13.8 pp, and the rule "Delta_sig

22.
medRxiv (Medicine) 2026-06-23

Multidimensional motivation in aging: a person-centred framework spanning goal-directed behaviour, social reward and pleasure

Motivational changes are determinants of healthy aging, social engagement, and functional independence, and may signal early neurodegenerative risk. Existing assessment approaches in aging typically treat motivation as a unitary construct. Here, we introduce MotDem, an age-appropriate measure of motivation co-designed with people living with dementia, carers, and clinicians. Across a broad adult lifespan sample (18-80 years), MotDem revealed a robust three-domain motivational architecture encompassing goal-directed behaviour, social reward, and pleasure, with a fourth satiety factor retained as exploratory. This structure was replicated in an independent older cohort (45-80 years) from a different national context. MotDem showed strong convergence with established measures of apathy and anhedonia, alongside more modest associations with depressive symptomatology. Together, these findings show that motivational aging is multifaceted and poorly captured by traditional unitary assessment. MotDem provides a multidimensional framework for measuring distinct motivational drivers of heterogeneous aging trajectories, with implications for resilience, wellbeing, and neurodegenerative risk.

23.
medRxiv (Medicine) 2026-06-15

Anti-Platelet Factor 4 Antibody Clonal Heterogeneity and MGUS Status in HIT

Background Monoclonal gammopathy of thrombotic significance (MGTS) is a recently described chronic prothrombotic condition characterized by monoclonal anti-PF4 antibodies that are detected above the polyclonal antibody background in patient sera (i.e. present as monoclonal gammopathy of undetermined significance, MGUS). Due to conflicting data in the published literature on antibody clonality in heparin-induced thrombocytopenia (HIT), we evaluated clonality and abundance of anti-PF4 antibodies in HIT, including investigating whether an MGUS, if present in HIT, represents the causative anti-PF4 antibody. Methods Blood samples from 15 patients with HIT were subject to Platelet Factor 4-dependent antigen-based and functional tests. The unmanipulated serum antibody repertoire and isolated anti-PF4 antibodies were subjected to mass spectrometric evaluation. Results Two of the 15 HIT patients had an IgG MGUS. Notably, anti-PF4 antibodies were not synonymous with the MGUS antibody in either of the two patients. Eight of the 15 patients demonstrated monoclonal anti-PF4 antibodies, however, none of the anti-PF4 antibodies were detectable as an MGUS upon evaluation of the entire serum antibody repertoire, reflecting their low abundance. In the seven patients with multiple anti-PF4 antibodies, non-monoclonality was confirmed by analysis of deglycosylated antibody heavy chains. Conclusions Anti-PF4 HIT antibodies are monoclonal in approximately 50% of HIT patients, however, antibody abundance is low such that they are not detectable over the polyclonal IgG background (i.e. are MGUS-negative), differentiating HIT from MGTS. This observation helps explain the transient nature of HIT relative to the persistent prothrombotic state seen in MGTS.

24.
medRxiv (Medicine) 2026-06-22

Paired plasma and EV-enriched plasma proteomics reveal nonredundant sepsis-associated host-response signatures in critical illness

Background: Plasma proteomics may identify host-response signatures in sepsis, but it is unclear whether extracellular vesicle (EV)-enriched plasma provides distinct or redundant information compared with plasma. We compared paired plasma and EV-enriched plasma proteomes in critically ill patients with sepsis and critically ill non-sepsis controls (CINS). Methods: In this prospective observational study, paired plasma and EV-enriched plasma samples were analyzed from 56 critically ill adults, including 40 patients with sepsis and 16 CINS patients. Protein abundance was quantified using liquid chromatography-tandem mass spectrometry. Analyses compared proteomic depth, protein overlap, global concordance between compartments, and differential protein abundance between CINS and sepsis. Exploratory Gene Ontology enrichment was performed as a supplementary analysis. Results: EV-enriched plasma expanded proteomic detection, identifying 2,476 filtered proteins compared with 506 in plasma. Only 386 proteins were detected in both compartments, while 2,090 were unique to EV-enriched plasma and 120 were unique to plasma. Among shared proteins, plasma and EV-enriched plasma showed modest global concordance across critically ill patients (Spearman coeff = 0.322, p = 9.19 x 10^-11), with similar findings in sepsis alone. Differential abundance analysis identified 11 sepsis-associated proteins in plasma and 22 in EV-enriched plasma. Only SAA1, SAA2, and IGFBP6 were significant in both compartments. Exploratory pathway analysis supported acute-phase and inflammatory enrichment in plasma sepsis-associated proteins, while EV-enriched signals were directionally plausible but did not meet prespecified FDR thresholds. Conclusion: Plasma and EV-enriched plasma proteomics capture related but nonredundant sepsis-associated host-response information in critically ill patients.

25.
arXiv (CS.CL) 2026-06-19

A Layered Security Framework Against Prompt Injection in RAG-Based Chatbots

Prompt injection is ranked as the most critical vulnerability in large language model (LLM) deployments by the OWASP Top 10 for LLM Applications, yet existing defenses operate at isolated pipeline stages and remain incomplete. Input filters cannot inspect retrieved documents, while output monitors cannot prevent malicious payloads from reaching the model. Consequently, retrieval-augmented generation (RAG) chatbots remain vulnerable to indirect injection, where a poisoned knowledge-base document compromises every user whose query retrieves it. We present a three-layer framework that intercepts both direct and indirect prompt injection throughout the inference pipeline. Layer 1 screens user input using a rule-based pattern library and a fine-tuned semantic anomaly classifier. Layer 2 enforces a provenance-based instruction hierarchy during context assembly, preventing retrieved content from overriding operator policy. Layer 3 audits model output using a policy rule engine and semantic drift detector before delivery. A continuous audit loop aggregates structured logs and supports retraining to adapt the classifier to emerging attack patterns. The framework is model-agnostic and deploys as middleware without modifying the underlying LLM. Evaluation on 5,080 samples across GPT-4o, Llama 3, and Mistral 7B shows that the framework reduces Attack Success Rate (ASR) from 71.4\% to 11.3\%, outperforming the best single-layer baseline by 27.3 percentage points and a published guardrail system by 23.8 percentage points, while maintaining a 4.8\% false positive rate and a median latency overhead of 61.2 ms. Ablation studies confirm that all three layers provide complementary protection and that their combined effect exceeds the sum of individual contributions.