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01.
arXiv (CS.CL) 2026-06-11

Evolving Agents in the Dark: Retrospective Harness Optimization via Self-Preference

AI agents rely on a harness of skills, tools, and workflows to solve complex problems. Continually improving this harness is essential for adapting to new tasks. However, existing optimization methods typically require ground-truth validation sets, yet such labeled data is difficult to acquire in practical deployment settings. To address this problem, we introduce Retrospective Harness Optimization (RHO), a self-supervised method that optimizes the agent harness using only past trajectories. Specifically, RHO selects a diverse coreset of challenging tasks from past trajectories and re-solves them in parallel. The agent analyzes these rollouts using self-validation and self-consistency, then generates candidate harness updates and selects the most effective one by its own pairwise self-preference. We evaluate RHO across three diverse domains, spanning software engineering, technical work, and knowledge work. Notably, a single optimization round improves the pass rate on SWE-Bench Pro from 59% to 78% without any external grading. Furthermore, our analysis demonstrates that RHO effectively targets prior failure modes. As a result, the optimized harness alters the agent's behavior patterns and sustains higher accuracy during long-horizon sessions.

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

Information Leakage Detection through Approximate Bayes-optimal Prediction

arXiv:2401.14283v4 Announce Type: replace-cross Abstract: In today's data-driven world, the proliferation of publicly available information raises security concerns due to the information leakage (IL) problem. IL involves unintentionally exposing sensitive information to unauthorized parties via observable system information. Conventional statistical approaches rely on estimating mutual information (MI) between observable and secret information for detecting ILs, face challenges of the curse of dimensionality, convergence, computational complexity, and MI misestimation. Though effective, emerging supervised machine learning based approaches to detect ILs are limited to binary system sensitive information and lack a comprehensive framework. To address these limitations, we establish a theoretical framework using statistical learning theory and information theory to quantify and detect IL accurately. Using automated machine learning, we demonstrate that MI can be accurately estimated by approximating the typically unknown Bayes predictor's log-loss and accuracy. Based on this, we show how MI can effectively be estimated to detect ILs. Our method performs superior to state-of-the-art baselines in an empirical study considering synthetic and real-world OpenSSL TLS server datasets.

03.
arXiv (math.PR) 2026-06-11

Hilbert space embeddings of independence tests and interaction measures of several variables

arXiv:2411.08653v2 Announce Type: replace-cross Abstract: We present a unified theoretical framework for kernel-based measures of dependence on product spaces. Building on the ideas underlying distance covariance, distance multivariance, and the Hilbert-Schmidt Independence Criterion (HSIC), we define a new family of kernels on an $n$-fold Cartesian product, termed positive definite independent of order $k$ (PDI$_{k}$ kernels). These kernels extend the concepts of positive definite and conditionally negative definite kernels to higher orders and provide the foundation for generalized independence and interaction tests, such as the generalized Lancaster interaction of order $k$ ($\Lambda_{k}^{n}$), and the Streitberg interaction ($\Sigma$). Our analysis focuses on the continuous setting, where we prove a Kernel Mean Embedding Theorem for PDI$_{k}$ kernels and establish the corresponding integrability restrictions. Based on these results, we characterize how the Kronecker products of PDI kernels behave.

04.
arXiv (CS.LG) 2026-06-18

Towards Anomaly Detection on Relational Data

arXiv:2606.18621v1 Announce Type: new Abstract: Relational databases are widely used for managing structured data in real-world systems. Detecting anomalies from such relational data is crucial for identifying fraud, risks, and abnormal behaviors, yet remains under-explored. The key challenges lie in the intrinsic complexity of relational data: multi-table attributes are high-dimensional and heterogeneous, making sparse abnormal clues easy to overwhelm by normal or irrelevant information; and anomalies may further manifest as abnormal connection patterns across different foreign-key relations, which existing tabular and graph anomaly detection methods are ill-suited to capture. To address them, we propose RelAD, a reconstruction-based framework that captures anomalies from both attribute and relational edge reconstruction. RelAD contains two core modules: conditional sparse-gated attribute reconstruction, which suppresses redundant multi-table attributes and emphasizes abnormal semantic blocks, and dual-view multi-relational edge reconstruction, which detects relation-specific abnormal connections from both intrinsic and behavioral entity profiles. The resulting attribute and relational signals are integrated through a lightweight fusion module to produce the final anomaly score. We further construct 6 benchmark datasets with systematic anomalies, on which extensive experiments show that RelAD consistently outperforms other baselines while achieving competitive efficiency.

05.
arXiv (CS.LG) 2026-06-16

ANCHOR: Error-Controlled Adaptive Numerical Correction for Neural Operator Time Marching

arXiv:2512.19643v2 Announce Type: replace Abstract: Numerical simulation of time-dependent partial differential equations (PDEs) is central to scientific and engineering applications, but high-fidelity solvers are often prohibitively expensive for long-horizon or time-critical settings. Neural operator (NO) surrogates offer fast inference across parametric and functional inputs; however, most autoregressive NO frameworks remain vulnerable to compounding errors, and ensemble-averaged metrics provide limited guarantees for individual inference trajectories. In practice, error accumulation can become unacceptable beyond the training horizon, and existing methods lack mechanisms for online monitoring or correction. To address this gap, we propose ANCHOR (Adaptive Numerical Correction for High-fidelity Operator Rollouts), an online, instance-aware hybrid inference framework for stable long-horizon prediction of nonlinear, time-dependent PDEs. ANCHOR treats a pretrained NO as the primary inference engine and adaptively couples it with a classical numerical solver using a physics-informed, residual-based error estimator. Inspired by adaptive time-stepping in numerical analysis, ANCHOR monitors an exponential moving average (EMA) of the normalized PDE residual to detect accumulating error and trigger corrective solver interventions without requiring access to ground-truth solutions. We show that the EMA-based estimator correlates strongly with the true relative L2 error, enabling data-free, instance-aware error control during inference. Evaluations on six canonical PDEs: 1D and 2D Burgers', 2D Allen-Cahn, 2D Cahn-Hilliard, 2D Navier-Stokes, and 3D heat conduction, demonstrate that ANCHOR reliably bounds long-horizon error growth, stabilizes extrapolative rollouts, and significantly improves robustness over standalone neural operators, while remaining substantially more efficient than high-fidelity numerical solvers.

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

Self-Preference Is Weak or Absent in Verifiable Instruction-Following Revision: A Four-Model Test Under Genuine Authorship

Large language models (LLMs) increasingly review and revise text, including their own. A documented self-preference bias (models favoring their own generations when acting as judges) raises the question of whether models also resist valid corrections to their own writing. We test this in a setting where "valid" is decided not by another model but by a deterministic verifier: instruction-following revision on IFEval. A model writes a draft; the official IFEval checker confirms the draft violates a constraint and that a candidate edit fixes it; the model then accepts or rejects that edit either as the genuine in-context author or as a fresh model that sees the draft neutrally. Across four mid-tier model families and 85 author-versus-fresh comparisons, we find no detectable self-preference: authors reject verified-good fixes to their own drafts at essentially the same rate as fresh models judging the same drafts (gap -5.1 pp, 95% CI [-12.9, +2.7]). A self-skepticism hint from a smaller pilot did not replicate at scale. The one robust observation is qualitative: when authors do reject a verified-good fix, 97% of their stated reasons are flaw-catching rather than preference, that is, about the character of rejections, not an elevated rate. Effects smaller than ~13 pp cannot be excluded at this sample size.

07.
arXiv (CS.CV) 2026-06-19

DiffMath: Symbol- and Graph-Aware Latent Diffusion Transformer for Handwritten Mathematical Expression Generation

Handwritten Mathematical Expression Generation (HMEG) is challenging due to the complex two-dimensional layouts and long-range structural dependencies of mathematical expressions. Existing methods typically rely on explicit spatial supervision, such as symbol-level bounding boxes, which incurs high annotation costs and limits scalability. In this work, we propose DiffMath, a symbol- and graph-aware latent diffusion framework that leverages the hierarchical structure inherent in LaTeX as a structural prior, eliminating the need for positional supervision. First, we design a Relational Abstract Syntax Tree (RelAST), a generation-oriented representation that distills MathML trees into compact triplet sequences [S, R, D], where each token directly encodes a symbol identity, spatial relation, or nesting depth. Second, we introduce MathVAE, which learns structure-preserving latent representations through symbol-aware and relation-aware perceptual regularization, ensuring that the latent space captures both character semantics and spatial topology. Third, MathDiT performs conditional denoising in this structured latent space, further guided by a global symbol-count prior via Adaptive Layer Normalization (AdaLN) to improve structural coherence. Experiments show that DiffMath produces structurally consistent handwritten expressions, achieves superior performance over existing methods, and improves the accuracy of downstream OCR models through synthetic data augmentation.

08.
arXiv (CS.AI) 2026-06-11

Harness In-Context Operator Learning with Chain of Operators

arXiv:2606.12318v1 Announce Type: cross Abstract: Neural operators approximate mappings between function spaces, but often generalize poorly to other operators and usually require fine-tuning or retraining. In-Context Operator Networks (ICON) addresses this issue by prompting the model with numerical context so that the model learns specific operators from prompts and adapt to different operators without fine-tuning. However, ICON may still fail to generalize to out-of-distribution (OOD) operator tasks. Inpired by the success of harness engineering of Large Language models (LLMs), we introduce Chain of Operators (CHOP), a framework that harness a frozen ICON to OOD operator tasks without updating its parameters. Specifically, CHOP constructs a chain of operators consisting of explicit elementary transformations and the frozen ICON. Experiments on a scalar conservation law and a mean-field control problem show that CHOP reduces relative inference error over direct ICON evaluation, while each operator in the chain remains interpretable and in closed form. A chain constructed on one PDE family further generalizes to a different family, indicating shared mechanisms across harness systems.

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

Tool-IQA: Augmenting Image Quality Assessment with Simple Tools

Vision-Language Models (VLMs) have been increasingly adopted for Image Quality Assessment (IQA). However, current methods typically employ a static one-shot scoring paradigm, despite the fact that humans assess image quality through dynamic visual inspection, e.g., selectively adjusting views to verify details and subtle artifacts. Specifically, relying solely on a single-pass observation introduces two primary limitations: first, perceiving the image only at a global scale restricts the assessment of finer local details; second, the original intensity distribution of the image may overwhelm the visibility, leading to insufficient inspection of image quality. To address these issues, we propose Tool-IQA, shifting the assessment mechanism from passive scoring to a tool-augmented workflow. In particular, we equip VLMs with simple yet effective view tools: a Magnifier to inspect local details, and a Gamma Corrector to uncover visibility and hidden artifacts. The assessment follows a structured pipeline that consists of an initial observation with rubric notes, a tool-augmented in-depth inspection, and a final quantification for calibrated quality score. Furthermore, to ensure efficient and purposeful tool callings, we introduce a batch-aware training strategy to reward tool interactions that can yield positive contributions rather than simply encouraging usage. Experiments on a variety of IQA benchmarks demonstrate that, with effective tool calling and calibrated assessment, our proposed Tool-IQA significantly outperforms existing state-of-the-art models, e.g., it achieves a PLCC of 0.854 on the challenging CLIVE dataset.

10.
arXiv (CS.CV) 2026-06-15

MirrorCheck: Efficient Adversarial Defense for Vision-Language Models

Vision-Language Models (VLMs) are increasingly susceptible to sophisticated adversarial attacks, including adaptive strategies specifically designed to bypass existing defenses. To address this vulnerability, we propose MirrorCheck, a robust and model-agnostic detection framework that operates effectively in both unimodal and multimodal settings. MirrorCheck leverages Text-to-Image (T2I) models to regenerate visual content from captions produced by the target model and assesses semantic consistency by comparing feature-space embeddings between the original and synthesized images. To enhance robustness against adaptive attacks, MirrorCheck introduces a stochastic defense strategy that randomly selects T2I generators and image encoders from a diverse model zoo. Additionally, we incorporate a novel One-Time-Use (OTU) perturbation applied to the selected encoder embeddings, regulated by a scaling factor, which decreases the effectiveness of adaptive attacks. Extensive experiments across multiple threat scenarios demonstrate that MirrorCheck consistently outperforms baseline methods, and maintains its utility even under strong adaptive adversarial conditions.

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

Active Sampling for Ultra-Low-Bit-Rate Video Compression via Conditional Controlled Diffusion

Diffusion models provide a powerful generative prior for perceptual reconstruction at ultra-low bitrates, but effective video compression requires controlling the generative process using highly compact conditioning signals. In this work, we present ActDiff-VC, a diffusion-based video compression framework for the ultra-low-bitrate regime. Our method partitions videos into variable-length segments, transmits keyframes only when needed, and summarizes temporal dynamics using a compact set of tracked point trajectories. Conditioned on these sparse signals, a conditional diffusion decoder synthesizes the remaining frames, enabling perceptually realistic reconstruction under severe rate constraints. To support this design, we introduce two mechanisms: content-adaptive keyframe selection and budget-aware sparse trajectory selection, which together enable compact yet effective conditioning for generative reconstruction. Experiments on the UVG and MCL-JCV benchmarks show that ActDiff-VC achieves up to 64.6\% bitrate reduction at matched NIQE, improves KID by up to 64.6\% and FID by up to 37.7\% at comparable bitrates against strong learned codecs, and delivers favorable perceptual rate–distortion trade-offs relative to learned and diffusion-based baselines in the ultra-low-bitrate regime.

12.
medRxiv (Medicine) 2026-06-15

Identifying the risk profile of anemia subtypes and hemodynamic obstetric complications in relation to peripartum cardiomyopathy

Background: Peripartum cardiomyopathy (PPCM) is a leading cause of maternal mortality worldwide, with worse outcomes associated with African Ancestry and delayed presentation. However, the mechanisms underlying PPCM are incompletely understood. Objective: Use a large, nationwide cohort to explore associations between PPCM and underexplored perinatal risk factors and complications of childbirth. Methods: Public hospital discharge data were obtained from eleven U.S. states between 2003-2019. Delivery hospitalizations, patient characteristics and obstetric complications were identified using ICD-9 and -10 CM codes. Only cases with unique patient identifiers enabling readmission analysis were included. The primary outcome was incident PPCM coded between 30 days antepartum and 150 days postpartum. Results: Of 7,424,916 delivering patients, 5,488 patients were diagnosed with PPCM. Patients with PPCM had higher rates of anemia, anemia of chronic disease (ACD), iron deficiency anemia (IDA), sickle cell disease (SCD), sickle cell trait (SCT), red blood cell (RBC) transfusion, and postpartum hemorrhage (PPH) (p

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

A Bifurcation Theory Framework for Gradient Descent on the Edge of Stability

Authors:

arXiv:2606.15551v1 Announce Type: new Abstract: The Edge of Stability (EoS) phenomenon, where gradient descent operates with sharpness exceeding the classical convergence threshold yet the loss decreases over long timescales, is ubiquitous in modern deep learning but remains poorly understood in realistic settings. Prior rigorous analyses have been largely confined to scalar or low-dimensional losses with specific structural forms. In this work, we develop a bifurcation theory framework for gradient descent on the edge of stability that applies directly to overparameterized neural networks. By decomposing the training dynamics into components normal and tangent to the manifold of minimizers, we show that stable EoS training arises from a flip bifurcation in the normal direction, governed by the sign of the first Lyapunov coefficient, while the tangent dynamics drift toward regions of decreasing sharpness. Under mild spectral and geometric assumptions on the loss landscape, we prove convergence to the minimizing manifold when training at the EoS threshold. As a corollary, we recover and unify prior results: we show that the product-stability condition of Gan (2026) is an instance of our framework.

14.
arXiv (math.PR) 2026-06-12

Storage and Transport Capacity Design for a Self-Reliable Two-Node Stochastic Resource System

arXiv:2606.12707v1 Announce Type: cross Abstract: We study a two-node stochastic resource system operating over a finite horizon. Each node experiences uncertain supply and demand and is equipped with finite storage. The objective is to ensure that resource levels remain within prescribed limits with high probability. To this end, we formulate a chance-constrained capacity-design problem in which resources can be exchanged through a capacity-limited transport link. We characterize the minimum storage required at each node, derive the optimal transport policy, and quantify the trade-off between storage and transport capacities. Our results show the existence of a critical transport-capacity threshold that enables full risk pooling between the nodes. Moreover, this threshold decreases with the operating horizon, implying that full-pooling performance can be achieved with progressively smaller transport capacity over longer horizons.

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

TokenPilot: Cache-Efficient Context Management for LLM Agents

As LLM agents are deployed in long-horizon sessions, context accumulation drives up inference costs. Existing approaches utilize text pruning or dynamic memory eviction to minimize token footprints; however, their unconstrained sequence mutations alter layouts, introducing prefix mismatches and cache invalidation. This reveals a critical trade-off between text sparsity and prompt cache continuity. To address this, we present TokenPilot, a dual-granularity context management framework. Globally, Ingestion-Aware Compaction acts as a framework harness to stabilize prompt prefixes and eliminate open-world environmental noise at the ingestion gate. Locally, Lifecycle-Aware Eviction monitors the ongoing residual utility of context segments, enforcing a conservative batch-turn schedule to offload content segments only when task relevance expires. Experiments on PinchBench and Claw-Eval under both isolated and continuous modes demonstrate that TokenPilot reduces costs by 61% and 56% in isolated mode, and 61% and 87% in continuous mode, while maintaining competitive performance compared to prior systems. TokenPilot has been integrated into LightMem2 at https://github.com/zjunlp/LightMem2.

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

Mind the Perspective: Let's Reason Recursively for Theory of Mind

arXiv:2606.11724v1 Announce Type: new Abstract: Theory of Mind (ToM) reasoning requires inferring agents' beliefs from partial and asymmetric observations, which remains an open challenge for LLMs. Existing prompting-based approaches improve ToM reasoning through observable-event filtering or temporal belief chains, without explicitly modeling nested beliefs. We introduce RecToM, an inference-time framework for ToM reasoning that models nested beliefs via recursive perspective construction. RecToM constructs each character perspective from the preceding character perspective along the character chain specified by the question, reducing higher-order belief questions to actual-world questions within the final constructed perspective. We further provide a KD45 analysis showing that RecToM's perspective construction induces a well-formed belief modality beyond simple event filtering. Experiments on ToM benchmarks, including Hi-ToM, Big-ToM, and FanToM, across multiple LLM backbones show that RecToM consistently outperforms recent advanced approaches, achieving state-of-the-art performance. Notably, RecToM reaches 100\% accuracy on Hi-ToM with GPT-5.4 and Qwen3.5, a benchmark requiring higher-order ToM reasoning.

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

Redact or Keep? A Fully Local AI Cascade for Educational Dialogue De-Identification

Educational dialogue is a valuable but sensitive resource for research: the same transcripts that capture authentic learning often capture personally identifiable information (PII) entangled with curricular content, where "Riemann" may refer to a real student or to a mathematical concept. Existing approaches force a tradeoff between governance and accuracy. Commercial Large Language Models (LLMs) can handle this ambiguity but require sending student data to third parties, while local named entity recognition (NER) systems preserve governance but over-redact curricular terms. We propose a fully local cascade framework that reframes de-identification from open-ended entity recognition to constrained privacy triage. A recall-first union proposer combines two lightweight encoders with deterministic rules to over-generate candidate spans; a context-aware reviewer then makes a binary Redact/Keep decision for each candidate using surrounding dialogue and speaker role. We evaluate three reviewer configurations against same-family LLM-only baselines and a commercial API on math tutoring transcripts from two large platforms. The strongest local configuration reaches 0.958 macro F1, compared with 0.767 for a same-family LLM-only baseline and 0.706 for the commercial API, while running entirely on a single laptop. On a targeted challenge set of curricular-personal name ambiguity, the same configuration degrades by only 0.03 F1 versus 0.19 to 0.25 for smaller reviewers. These results suggest that for educational de-identification, problem formulation matters more than model scale.

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

Correcting Sensor-Induced Distribution Drift with Wasserstein Adversarial Learning

arXiv:2606.18561v1 Announce Type: cross Abstract: The quality of recorded data depends on the stability of the sensor system that acquires it. Sensor motion and aging can degrade the performance and stability of downstream data-driven methods. We present a Wasserstein-GAN-inspired approach for unsupervised inference of physically interpretable transformation parameters that map a changed detector response distribution back to a nominal reference distribution. In contrast to standard generative modeling, the generator is used as a learnable calibration transformation whose trainable weights represent the sought parameters, while the critic provides a distributional distance signal via the Wasserstein objective. We validate the approach on a tracking-detector toy model with controlled layer shifts and demonstrate its application on high-granularity Geant4-simulated calorimeter data with cell-wise aging effects. The method recovers aging coefficients for individual cells with correlation to ground truth and improves agreement between calibrated and reference energy-sum distributions, while exhibiting the expected degradation at increasing channel-to-channel noise levels. These results indicate that adversarial distribution matching can serve as a data-driven component of calibration strategies in settings where direct labels for degradation parameters are unavailable.

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

Beyond Static Endpoints: Tool Programs as an Interface for Flexible Agentic Web Services

arXiv:2606.19992v1 Announce Type: cross Abstract: In the agentic web era, LLM-based agents increasingly invoke web services as tools, yet most interfaces remain static endpoints that poorly express long-horizon workflows with loops, conditionals, joins, and retries. We present ToolPro, which represents an agent's tool intent as an executable tool program that compactly encodes multi-step service interactions with explicit effect types. ToolPro combines constraint-guided program construction, effect-aware replay for exactly-once state-modifying calls, and a profile-driven policy that decides when program execution outperforms stepwise calling. We instantiate ToolPro over MCP-style services with WebAssembly sandboxing and evaluate it on diverse workflows of real-world applications. ToolPro reduces end-to-end latency by up to 53.4\% and client-side traffic by up to 96.1\%, with larger gains under higher network latency and workflow complexity.

20.
medRxiv (Medicine) 2026-06-16

Development of an automated, imaging-based preoperative screening model for early identification of malnutrition in an abdominal surgery cohort

Background: Clinical malnutrition affects one in five abdominal surgery patients and increases postoperative complications and mortality. Current screening occurs after admission, closing the window for preoperative nutritional intervention. No objective, scalable preoperative screening tool exists. Objective: To determine whether automated volumetric CT-based body composition analysis improves preoperative identification of surgical patients at risk for clinical malnutrition compared to clinical variables or single slice imaging alone. Methods: Retrospective cohort study of adults undergoing elective abdominal surgery at a quaternary academic medical center (2018 to 2021) with a preoperative CT scan within 90 days and complete nutrition assessment. Clinical malnutrition was diagnosed by a registered dietitian using ASPEN/AND criteria. Three sex stratified Elastic Net models were compared: (1) base clinical variables; (2) base plus L3 single slice skeletal muscle index and attenuation; and (3) base plus comprehensive 3D volumetric quantification of five muscle groups and two fat depots. Discrimination (AUROC), calibration (Brier score), and clinical utility (decision curve analysis) were assessed via 10-fold cross-validation. Results: Among 1,143 patients (52.4% female; mean age 60.5 years), 231 (20.2%) were diagnosed with malnutrition. Malnourished patients had significantly higher complication rates (36.4% vs. 15.4%, p

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

Cognitive Debt: AI as Intellectual Leverage and the Dynamics of Systemic Fragility

Authors:

arXiv:2606.15078v1 Announce Type: new Abstract: We develop a formal theory of cognitive debt: the stock of unverified reasoning obligations that accumulates when individuals use AI as a substitute rather than a complement for first-principles cognition. The model features two state variables per agent, cognitive capital and cognitive debt, and a multiplicative production technology in which cognitive capital functions as collateral that determines the return to AI adoption. We establish six propositions. Rational agents incur positive cognitive debt because the costs are deferred, partially external, and masked by short-run productivity gains. Tranquil periods lower subjective risk assessments, raise AI substitution intensity, and compound leverage, generating a cognitive Minsky moment in which subjective risk falls while true systemic fragility rises. Expected crisis losses are convex in aggregate leverage. Post-crisis, output-target pressure can produce a false-correction loop in which agents patch AI failures with more AI. The decentralised equilibrium over-adopts substitutive AI relative to the social optimum because of systemic risk, cognitive public goods, and arms-race externalities. In a two-type heterogeneous-agent economy, high-cognitive-capital agents adopt AI more intensively and may eventually erode their unaided cognitive capital below that of initially lower-skilled agents.

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

Small LLMs for Biomedical Claim Verification: Cost-Effective Fine-Tuning, Structural Dataset Shortcuts, and Cross-Domain Generalization

Authors:

Large Language Models such as GPT-4o and GPT-5 achieve strong zero-shot performance on biomedical claim verification, but cost and opacity limit scalable use. We fine-tune three small LLMs: Phi-3-mini (3.8B), Qwen2.5-3B, and Mistral-7B, via QLoRA on SciFact and HealthVer, providing the first study of QLoRA models against GPT-4o and fine-tuned BioLinkBERT encoders. Mistral-7B QLoRA surpasses both GPT-4o and GPT-5 (up to 12% F1 gain) at a fractional cost using just 1,008 training examples. We conduct extensive in-domain and cross-domain evaluation: models trained on SciFact tested on HealthVer and vice versa, at matched sizes to isolate dataset structure from data quantity. We identify a previously unreported structural artifact in SciFact that inflates in-domain scores, and show through bidirectional out-of-domain evaluation that training on structurally sound data enables robust cross-domain transfer. We plan to release all code and adapter checkpoints.

23.
medRxiv (Medicine) 2026-06-19

A soluble bi-specific fusion protein for the improved expansion of human CD8+ CAR-T cells

The success of Chimeric Antigen Receptor (CAR) T cell therapy is heavily dependent on the quality of the final cellular product. Current expansion protocols often rely on reagents that require removal from cell culture media, posing logistical challenges in manufacturing, and can also lead to terminal differentiation. Here, we evaluate the use of a soluble, bead-free T cell activator, T cell expansion protein (T-CEP), as a streamlined alternative for generating potent CAR-T cells. Human T cells were activated with T-CEP or known T cell activators (Dynabeads and TransAct) and transduced with either CD19 or interleukin-13 (IL-13) mutein (tetravariant-13; TV-13)-based CAR lentiviral vectors. Our results demonstrate that T-CEP supports robust CAR-T cell expansion and achieves transduction efficiencies comparable to commercial reagents for both types of CAR-T cells. Notably, T-CEP significantly favored the expansion of CD8+ T cells, yielding an enhanced CD27+ phenotype and a lower CD4:CD8 ratio compared to TransAct. Cytotoxicity assays confirmed that T-CEP-expanded CAR-T cells possess cytolytic function equivalent to commercial reagents for both CARs, while exhibiting lower levels of inflammatory cytokine secretion. In summary, T-CEP represents a competitive alternative to existing expansion agents, as it does not require its removal during CAR-T manufacturing and generates a CD8+ dominant, less-differentiated phenotype without compromising efficacy.

24.
arXiv (CS.CV) 2026-06-12

On Pitfalls of $RemOve-And-Retrain$: Data Processing Inequality Perspective

The RemOve-And-Retrain (ROAR) benchmark is widely used to evaluate feature attribution methods, yet its validity remains underexplored from an information-theoretic perspective. We show that model- and data-agnostic post-processing of attribution maps (transformations that, by the data processing inequality, cannot add information about the decision function) can often improve ROAR scores. This means that an improved ROAR ranking is not, by itself, evidence that an attribution map carries more information about the model. We trace this failure mode to a bias toward spatially blurry masks. Experiments on CIFAR-10, SVHN, and CUB-200 show a consistent association between blurriness and ROAR performance, a pattern that also appears in the ROAD variant. We provide guidelines for more cautious removal-based benchmarking, with implications for validating mechanistic understanding of neural network internals.

25.
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