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01.
arXiv (CS.CL) 2026-06-15

Does the Judge Prefer English? Evaluating Language-Switching Invariance in LLM-as-a-Judge

作者:

Large language models (LLMs) are now widely used as automatic judges for open-ended instruction-following evaluation. This practice is convenient, scalable, and often more semantically aware than reference-based metrics, but it also introduces a new reliability question: does a judge evaluate the quality of an answer, or does it also react to the language in which the comparison is presented? We propose Judge-LS, a lightweight meta-evaluation protocol that transforms LLMBar response-pair items into English, Chinese, and Chinese-English language-switched variants. A reliable judge should preserve its preference under label-preserving language transformations and should not prefer a language when two answers are translation-equivalent. We evaluate four API-accessible judges on the full 419-item LLMBar benchmark, producing 13,408 successful pairwise judgments. Across models, Chinese and language-switched presentations induce 10.7–14.4% preference flips relative to English, and all judges achieve their highest accuracy in English. However, translation-equivalent tie probes do not reveal a systematic English preference: most probes are judged as ties, and non-tie decisions more often favor Chinese. We add confidence intervals, paired significance tests, and an automatic transformation audit with a sensitivity analysis that excludes mechanically flagged high-risk variants. The experiment requires no model training, uses only API calls, and is feasible on modest local hardware.

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

YOLO-AMC: An Improved YOLO Architecture with Attention Mechanisms for Building Crack Detection

Crack detection plays an important role in infrastructure inspection and Structural Health Monitoring (SHM). However, cracks typically appear as thin, low-contrast structures and are easily affected by background noise, posing challenges for existing object detection models. This study proposes an improved YOLO-based architecture with integrated attention mechanisms, termed YOLO-AMC (YOLO with Attention Mechanisms for Crack Detection), to enhance automated crack detection performance. Based on YOLOv11, the original C2PSA module is removed, and multiple attention mechanisms, including Global Attention Mechanism (GAM), Residual Convolutional Block Attention Module (Res-CBAM), and Shuffle Attention (SA), are introduced into the multi-scale feature fusion layers of the Neck to strengthen cross-scale feature integration. Experimental results demonstrate that YOLO-AMC consistently outperforms baseline models YOLOv11n and YOLOv8n across multiple evaluation metrics. Among the evaluated attention modules, GAM achieves the best detection performance, obtaining mAP@0.5 = 0.9917 and mAP@0.5:0.95 = 0.9506 on the test dataset, which are higher than those of YOLOv11 (0.9833 / 0.9112) and YOLOv8 (0.9707 / 0.8921). Furthermore, while maintaining a computational complexity of 7.6 GFLOPs, the proposed model achieves 110.95 FPS on an NVIDIA RTX 4090 platform and approximately 5 FPS on a Raspberry Pi 5 edge device, demonstrating a favorable trade-off between accuracy and deployment efficiency. The implementation code for this study is available on GitHub at https://github.com/CY-Tsai24/YOLO-AMC.

03.
arXiv (CS.CV) 2026-06-19

How Fragile Are Training-Free AI-Generated Image Detectors? A Controlled Audit of Score Direction, Preprocessing, and Compression

Training-free detectors of AI-generated images promise generator-agnostic deployment without classifier training, yet their reported numbers are rarely compared under a single controlled protocol. We audit two representative training-free scores – an autoencoder-reconstruction score (AEROBLADE-style) and a noise-perturbation feature-similarity score (RIGID-style) – plus a naive feature-kNN control, on a common 1,500-image GenImage-derived benchmark spanning seven generators and JPEG compression at quality 70 and 50. The audit yields three cautionary findings. (i) Implementation details masquerade as method differences: replacing the LPIPS backbone (AlexNet -> VGG-16) changes overall AUROC by +0.085, and switching between resize-to-512 and native-resolution preprocessing flips per-generator conclusions by up to 0.38 AUROC. (ii) Score direction is not a property of the method but of its hyperparameters: the RIGID-style score is inverted (AUROC < 0.5) on SD1.5 and Wukong at noise level sigma=0.05, recovers to >0.5 for every generator at sigma=0.01, and collapses to 0.15 at sigma=0.3. (iii) Dataset format bias inflates robustness claims: without unified re-encoding, AUROC under JPEG-50 exceeds the clean condition for the AlexNet-backbone reconstruction score; after bias correction the residual anomaly localizes to a single generator (BigGAN). The audited scores have complementary per-generator failure sets, but naive z-score fusion does not beat the best single score, indicating that exploiting complementarity requires direction-aware combination.

04.
arXiv (CS.CL) 2026-06-12

AI SciBrief as a Gateway to Research: A Framework for Onboarding Students into New Research Areas

Students at all levels of higher education face a significant barrier in the form of information overload, which often paralyzes the initial stages of the research process and suppresses motivation. In response, this article introduces a pedagogical framework that leverages AI SciBrief, a platform powered by a Large Language Model (LLM) designed to automatically generate digests of scientific trends. We describe how this multidisciplinary tool - with initial coverage in finance, medicine, and education - can be integrated into the curriculum to overcome this "entry barrier." The framework provides concrete methodologies for utilizing these digests to facilitate topic selection for term papers, accelerate literature reviews for dissertations, and enable postgraduate students to continuously monitor emerging trends. We conclude that AI SciBrief functions as a "gateway to research" effectively reducing students' cognitive load and empowering them to transition more rapidly from information searching to knowledge creation.

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

Lifecycle-Aware Dynamic Analysis for Secure ML Model Execution

arXiv:2606.19023v1 Announce Type: cross Abstract: The growing reliance on pre-trained Machine Learning (ML) models has introduced new attack surfaces. Recent vulnerabilities demonstrate that malicious behavior can be embedded within model artifacts, often bypassing existing defenses. Current model-scanning solutions primarily rely on static, format-specific rules or known attack signatures, which limit their ability to generalize across frameworks and to detect novel exploitation paths. In contrast, we propose a solution that focuses on the effects an attack has on the host system executing the model and builds on foundational intuitions about ML model execution. In particular, we observe that ML models operate within well-defined lifecycle phases and that, within each phase, interactions with the host system are highly structured and predictable. We translate these intuitions into Moat, a dynamic lifecycle-aware approach for securing ML model execution, and instantiate this design in Re-Moat, our reference implementation. We evaluate Re-Moat across multiple ML frameworks using 77,974 real-world model artifacts from the Hugging Face Hub, 31 Proofs-of-Concept (PoCs) from CVEs, and 334 models from a state-of-the-art dataset, and compare it against state-of-the-art model-scanning solutions. Our results show that our approach detects all evaluated attack classes while maintaining a close-to-zero false-positive rate, validating our intuitions and motivating dynamic analysis for securing ML model execution.

06.
medRxiv (Medicine) 2026-06-17

MedAgent: A Retrieval-Augmented Clinical Decision Support Agent with Verifiable Evidence Grounding for Evidence-Based Medicine

Evidence-based medicine demands clinical answers that are not only fluent and medically plausible, but also anchored in traceable evidence, tailored to patient-specific clinical questions, sensitive to the hierarchy of evidence, and respectful of clinical safety boundaries. While general-purpose large language models (LLMs) exhibit strong medical language generation ability, they tend to lean on parametric memory, underuse retrieved evidence, hallucinate citations, conflate evidence levels, and draw conclusions that are not fully supported by the underlying literature. Such limitations pose particular risks in clinical decision support, where answer reliability, evidence traceability, and reasoning consistency are paramount. To address these issues, we present MedAgent, an evidence-based medical agent trained through an end-to-end pipeline that integrates supervised fine-tuning (SFT) cold start, reward modeling, and Group Relative Policy Optimization (GRPO). The agent is designed to execute a structured workflow encompassing clinical question understanding, PICO extraction, evidence retrieval, evidence stratification, citation-grounded answer generation, and quality evaluation. Specifically, a Qwen2.5-14B-Instruct backbone is first cold-started on 200 human-verified agent trajectories, equipping it with tool invocation, PICO parsing, structured response generation, and citation faithfulness. Next, a Qwen2.5-7B reward model is trained on 2{,}099 pairwise preference samples to provide semantic-level quality signals for evidence-based responses. Finally, GRPO reinforcement learning is conducted in a retrieval-augmented agent environment, where every rollout involves real evidence retrieval and is scored jointly by rule-based rewards and reward-model signals. To avoid over-reliance on training rewards, we further construct an independent evidence-based medical evaluation benchmark, MedTrustBench, which contains 200 clinical questions spanning 10 specialties and four difficulty levels. Each question is annotated with standardized PICO elements and rubric-based scoring criteria. The benchmark includes 1{,}187 rubrics across seven dimensions: question relevance, evidence hierarchy, evidence quality and timeliness, evidence-answer consistency, completeness and depth, logical rigor, and medical terminology. Under an identical RAG pipeline, retrieval tool, retrieval configuration, and evaluation protocol, MedAgentv17 attains 78.6 points, outperforming GPT-4.1 (75.3) and approaching GPT-5.4 (80.3). These results show that a 14B domain-aligned model can surpass strong general-purpose baselines on specialized evidence-based medical reasoning, while delivering practical advantages in cost, privacy, controllability, and hospital-oriented private deployment. The model and associated datasets are publicly released at https://www.modelscope.cn/profile/InfoxmedModel

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

A Survey on Agentic Security: Applications, Threats and Defenses

LLM-based agents are now used throughout cybersecurity. While these agents facilitate powerful and autonomous security applications, their autonomy opens up new attack surfaces, and the security community is actively building defenses to secure them. Yet the literature on this subject has grown quickly and unevenly. Existing surveys treat applications, threats, and defenses in isolation, leaving no unified account of how an agent's capabilities, vulnerabilities, and countermeasures interconnect. In this work we present the first holistic survey of the agentic security landscape, structuring the field around the fundamental pillars of Applications, Threats and Defenses. We provide a comprehensive taxonomy of over 260 papers, explaining how agents are used in downstream cybersecurity applications, inherent threats to agentic systems, and countermeasures designed to protect them. In addition, we provide detailed pillar-specific and cross-cutting analyses that show the security-lifecycle coverage of agentic applications, comparison between red-teaming and blue-teaming agents, and the adversarial use of red-teaming applications. On the threat side, we analyze the entry points and agent-loop stages that attacks target, their specificity to the agentic setting, and the threat models they assume. On the defense side, we analyze the prevailing defense strategies, their cost and security trade-offs, and where in the agent lifecycle they are deployed. We further map which defenses cover which attack classes and chart trends in agent architecture, backbone model usage, data modality coverage, and the growth of attack and defense research over time. Taken together, these findings indicate that agentic systems are structurally fragile by default and that securing them will require defenses that span the full agent lifecycle rather than single-layer fixes.

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

From Correspondence to Actions: Human-Like Multi-Image Spatial Reasoning in Multi-modal Large Language Models

While multimodal large language models (MLLMs) have made substantial progress in single-image spatial reasoning, multi-image spatial reasoning, which requires integration of information from multiple viewpoints, remains challenging. Cognitive studies suggest that humans address such tasks through two mechanisms: cross-view correspondence, which identifies regions across different views that correspond to the same physical locations, and stepwise viewpoint transformation, which composes relative viewpoint changes sequentially. However, existing studies incorporate these mechanisms only partially and often implicitly, without explicit supervision for both. We propose Human-Aware Training for Cross-view correspondence and viewpoint cHange (HATCH), a training framework with two complementary objectives: (1) Patch-Level Spatial Alignment, which encourages patch representations to align across views for spatially corresponding regions, and (2) Action-then-Answer Reasoning, which requires the model to generate explicit viewpoint transition actions before predicting the final answer. Experiments on three benchmarks demonstrate that HATCH consistently outperforms baselines of comparable size by a clear margin and achieves competitive results against much larger models, while preserving single-image reasoning capabilities.

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

MemRerank: Preference Memory for Personalized Product Reranking

LLM-based shopping agents increasingly rely on long purchase histories and multi-turn interactions for personalization, yet naively appending raw history to prompts is often ineffective due to noise, length, and relevance mismatch. We propose MemRerank, a preference memory framework that distills user purchase history into concise, query-independent signals for personalized product reranking. To study this problem, we build an end-to-end benchmark and evaluation framework centered on an LLM-based 1-in-5 selection task, which measures both memory quality and downstream reranking utility. We further train the memory extractor with reinforcement learning (RL), using downstream reranking performance as supervision. Experiments with two LLM-based rerankers show that MemRerank consistently outperforms no-memory, raw-history, and off-the-shelf memory baselines, yielding up to +10.61 absolute points in 1-in-5 accuracy. These results suggest that explicit preference memory is a practical and effective building block for personalization in agentic e-commerce systems.

11.
arXiv (CS.AI) 2026-06-19

ORAgentBench: Can LLM Agents Solve Challenging Operations Research Tasks End to End?

arXiv:2606.19787v1 Announce Type: new Abstract: Large language models are increasingly deployed as autonomous agents for multi-step tasks in executable environments, yet their ability to perform realistic operations research (OR) work remains unclear. Existing OR evaluations often decouple modeling from solving, rely on pre-formalized or text-only instances, and rarely test the full workflow from operational artifacts to validated decisions. In this work, we introduce ORAgentBench, an execution-grounded benchmark for evaluating autonomous agents on challenging end-to-end operations research tasks. It contains 107 human-reviewed tasks across diverse operational scenarios, each packaged in an isolated environment with a natural-language brief, multi-file data, configuration artifacts, and a required submission schema. Agents must write and run solution code, and their submissions are evaluated by hidden validators for schema validity, hard-constraint feasibility, and normalized objective quality. Experiments with fourteen frontier agent-model configurations show that current agents remain far from reliable OR practice. The best agent passes only 35.51% of all tasks and 20.59% of hard tasks, and many feasible submissions still fall below the required quality threshold. Failure analysis further shows that errors are dominated by strategic weaknesses, including missed operational rules, brittle formulations, weak feasible-solution construction, and insufficient solution improvement. OR-specific procedural skills increase hard-task feasibility, but do not reliably improve solution quality or pass rate. These results suggest that progress in OR agents requires moving beyond plausible optimization code toward dependable, high-quality operational decision-making.

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

Nothing from Something: Can a Language Model Discover 0?

AI systems based on artificial neural networks are being developed with aspirations of pushing the boundary of human mathematical knowledge. A key question for these systems is how much they can reach beyond their training data. Mathematical discovery requires a strong form of out of distribution generalization; the ability to hypothesize genuinely new - and potentially logically more powerful - mathematical structures. It has been hypothesized that language abilities support such generalizations in human cognition. In this work, we use simple arithmetic as a case study for examining how modern AI models could expand their mathematical horizons, evaluating whether these models can independently discover the concept of "zero". We show that We show that (1) language models of a GPT-2 size are unable to perform this generalization at test time regardless of language pretraining, but (2) models can improve substantially after training on tens or hundreds of examples of zero. Additionally, we find that language pretraining reduces the number of required examples by approximately $50\%$, showing that language abilities can scaffold mathematical discovery in neural models.

13.
arXiv (CS.AI) 2026-06-11

Sparse probes and murky physics: a case study of interpretability challenges in a foundation model for continuum dynamics

arXiv:2606.11657v1 Announce Type: cross Abstract: Generative AI emulators are increasingly used in scientific domains where we already have strong theory, benchmarks, and physical intuition. This raises a central evaluation and interpretability question: when a foundation-style model can reproduce known continuum dynamics, what internal mechanism supports that behavior, is the internal behaviour consistent with known physics, and how does it relate to where the emulator succeeds or fails? We investigate a cross-domain foundation model for continuum dynamics, Walrus by Polymathic, using mechanistic interpretability guided by physical principles. We apply a sparse autoencoder (SAE) to probe a selected layer, and address the practical challenge of triaging a large feature set (over 20,000) using enstrophy as a physically grounded metric. As a deliberately simple testbed, we focus on shear flow and compare feature recruitment across multiple shear-flow setups, i.e. parameter values in the numerical simulation. Across setups we find evidence of piecewise consistency, with subsets of features recurring in similar roles, but this structure is intermittent and does not map cleanly onto standard physical decompositions. In parallel, direct comparisons between numerical simulation and the emulator reveal systematic output-level discrepancies, including regimes where energy/structures become too diffuse or too localized. We connect parts of these discrepancies to changes in specific SAE feature usage. Our work highlights open questions for scientific foundation models: how to robustly prioritize mechanistically meaningful features, how to separate stable structure from analysis artifacts (including single-layer and SAE limitations), and how to use established benchmarks to decide when "different" internal representations are genuinely informative rather than merely effective.

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

The Algebra of Units: From Buckingham's Pi-grec Theorem to Latent-Variable Learning

arXiv:2606.16737v1 Announce Type: cross Abstract: Engineers often measure many quantities-speed, pressure, temperature, length-expressed in different physical units. The Buckingham Pi-grec theorem states that these variables can always be combined into a smaller set of dimensionless numbers whose values fully determine the system's behaviour. Identifying the appropriate dimensionless groups has traditionally required expert knowledge and physical insight. This paper shows that they can instead be discovered automatically from data, without prior knowledge of the governing physics. The key observation is that, after logarithmic transformation, measurements collected under different scalings of the same system lie on a low-dimensional manifold whose geometry is determined by the underlying dimensionless groups. Singular value decomposition (SVD) identifies this manifold directly from data. A subsequent search over integer-exponent combinations recovers candidate dimensionless quantities, while a repeating-variable filter retains only those constructed from the machine's characteristic scales. This procedure recovers familiar engineering groups, including the flow coefficient, head coefficient, and Mach number, while excluding equivalent but less interpretable alternatives. The method is demonstrated on a synthetic compressor dataset containing 16,000 measurements. Starting from raw dimensional variables and no physics input, it recovers the correct dimensionless groups to numerical precision and reproduces the compressor performance map with an error below 0.01%. More broadly, the work reveals a close connection between classical dimensional analysis and modern data-driven learning. Both rely on the same underlying algebraic structure, suggesting new approaches for building physical models that are simultaneously interpretable, scalable, and data-efficient.

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

OrthoReg: Orthogonal Regularization for Hybrid Symbolic-Neural Dynamical Systems

arXiv:2606.19145v1 Announce Type: cross Abstract: Dynamical systems are fundamental to modeling the natural world, yet modeling them involves a persistent trade-off: manually prescribed mechanistic models are interpretable by design but often overly simplistic and misspecified; in contrast, flexible data-driven neural methods lack physical insight. Hybrid modeling aims for the best of both worlds by combining a prescribed or symbolic, physics-based component with a flexible neural network. A critical challenge, however, is that the neural component may relearn mechanistic parts, yielding redundant and uninterpretable models, especially when the symbolic structure itself is discovered from data. Existing methods based on standard $L^2$ regularization rely on a projection argument that breaks when the symbolic component is learned through sparse discovery, allowing the neural augmentation to overlap with symbolic structure. We introduce OrthoReg (Orthogonal Regularization), which directly penalizes overlap between the symbolic and neural components, preventing symbolic structure from being absorbed by the neural residual. This yields a complementary decomposition: the symbolic part captures what the library can express, and the neural part captures what remains. On benchmark dynamical systems with partial library mismatch, OrthoReg improves symbolic recovery and out-of-distribution behavior.

16.
arXiv (quant-ph) 2026-06-17

Quantum statistical functions

作者:

arXiv:2602.05821v2 Announce Type: replace Abstract: Statistical functions such as the moment-generating, characteristic, cumulant-generating, and second characteristic functions are standard tools in classical statistics and probability theory. They provide a systematic means to analyze the statistical properties of a system and find applications in diverse fields. While these functions are ubiquitous in classical theory, a quantum counterpart has remained underdeveloped because of the noncommutativity of operators. The absence of such a framework has obscured the connections between statistical quantities and the nonclassical features of quantum mechanics. Here, we construct a framework for quantum statistical functions that addresses these limitations and unifies the languages of quantum statistics. We show that the functions reproduce standard statistical quantities such as expectation values, variance, and covariance upon differentiation. By extending the framework to include pre- and post-selection, we define conditional functions that generate conditional statistical quantities, including the weak value and the weak variance. We further show that multivariable functions, defined with specific operator orderings, correspond to the Kirkwood–Dirac, Margenau–Hill, and Wigner distributions. By generalizing Bochner's theorem within the theory of compactly supported distributions, we obtain a criterion that separates classical statistics from quantum statistics, linking the failure of positive definiteness of the multivariable function to the emergence of quasiprobability. As an application, we import the classical method of moments and generalized method of moments into quantum estimation, introducing quantum estimators that exploit the proposed functions. Our framework reproduces quantum statistical quantities and incorporates the nonclassical features of quasiprobability, providing a basis for further study of quantum statistics.

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

Functional Equivalence in Attention: A Comprehensive Study with Applications to Linear Mode Connectivity

arXiv:2606.17830v1 Announce Type: cross Abstract: Neural network parameter spaces are inherently non-injective, as distinct parameter configurations can realize identical functions through functional equivalence. While this symmetry is well understood in classical fully connected and convolutional models, it becomes substantially more intricate in modern attention-based architectures. Existing analyses of multihead attention have largely focused on the vanilla formulation, overlooking positional encodings that fundamentally reshape architectural symmetries. In this work, we provide a formal study of functional equivalence in Transformers with positional encodings. Focusing on the two most widely used variants–sinusoidal and rotary positional encodings (RoPE)–we show that sinusoidal encodings preserve the equivalence structure of vanilla attention, whereas rotary encodings significantly reduce the symmetry group, thereby enhancing expressivity. This offers a principled explanation for the growing prominence of RoPE in practice. We further examine how positional encodings affect linear mode connectivity, and through an alignment algorithm, empirically demonstrate that the presence and variability of connectivity across Transformer settings crucially depend on the positional encoding.

18.
arXiv (CS.LG) 2026-06-16

On the Energy Distribution of the Galactic Center Excess' Sources

arXiv:2507.17804v2 Announce Type: replace-cross Abstract: The Galactic Center Excess (GCE) may yet herald the discovery of annihilating dark matter. Weighing against that conclusion are analyses showing evidence for dim point sources within the spatial structure of the emission. Due to technical limitations these analyses are purely spatial with all spectral information that could disentangle the excess from astrophysical backgrounds discarded. Here, we demonstrate that a neural network simulation-based inference approach can jointly analyze the spatial and spectra data. The addition is profound: energy information drives the putative point sources to be significantly dimmer, indicating either the GCE is truly diffuse in nature or made of an exceptionally large number of sources. Quantitatively, for our best fit background model, the excess is essentially consistent with Poisson emission as predicted by dark matter. If due to point sources, our median prediction is $\mathcal{O}(10^5)$ sources, or more than 35,000 at 90\% confidence, both orders of magnitude larger than the hundreds preferred by earlier point-source analyses of the GCE, although variations allowed by background systematics could reduce the required number of sources by roughly an order of magnitude.

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

Quantum-Accelerated Self-Consistent Field: A Hybrid Algorithm

arXiv:2606.20176v1 Announce Type: new Abstract: We present the Grover adaptive search self-consistent field (GAS-SCF) algorithm. GAS-SCF leverages quantum arithmetic to construct an efficient oracle that marks target states (Fock states) which improve upon some initial classical energy estimate. Amplitude amplification then increases the probability of measuring these states. This approach offers a theoretical quadratic speed-up for the optimization problem encountered in SCF quantum chemistry and establishes a baseline against which structured optimization algorithms, such as QAOA and DQI may be compared. In this work, we classically simulate three examples as proofs of concept of the algorithm, the largest consisting of 26 qubits. We then extend our analysis to two larger systems, with O3 representing the largest case at 330 qubits. These examples are chosen to probe classically challenging SCF regimes. Achieving chemically relevant applications of GAS-SCF will require large-scale, fault-tolerant quantum hardware.

20.
Nature Medicine 2026-06-08

Post-adjuvant chemotherapy in ctDNA-positive patients with resected colorectal cancer: a randomized phase 3 trial

Tumor-informed circulating tumor DNA (ctDNA) enables detection of molecular residual disease (MRD) after curative resection of colorectal cancer (CRC), but whether early intervention improves outcomes remains uncertain. ALTAIR was a randomized, double-blind, phase 3 trial embedded in the CIRCULATE-Japan platform evaluating a post-adjuvant ctDNA surveillance strategy with treatment initiation upon molecular recurrence. Patients with resected stage 0–IV CRC who became ctDNA positive after completion of standard-of-care therapy and had no radiological evidence of disease were randomly assigned (1:1) to receive trifluridine/tipiracil (FTD/TPI) or placebo for 6 months. The primary endpoint was investigator-assessed disease-free survival (DFS). Between July 2020 and June 2023, 243 patients were randomized to FTD/TPI (n = 122) or placebo (n = 121). Median DFS was 9.30 months with FTD/TPI and 5.55 months with placebo (hazard ratio = 0.79, 95% confidence interval: 0.60–1.05, P = 0.107), and the primary endpoint was not met. FTD/TPI increased grade 3 or higher hematologic adverse events (73.0% versus 3.3%) without new safety signals. These findings indicate that post-adjuvant intervention with FTD/TPI did not significantly improve DFS in ctDNA-positive patients without radiological disease. ClinicalTrials.gov identifier: NCT04457297 . In the randomized, double-blind phase 3 ALTAIR trial, patients with resected colorectal cancer who became positive for circulating tumor DNA during post-adjuvant surveillance received trifluridine/tipiracil hydrochloride therapy, which did not significantly prolong disease-free survival compared with placebo.

21.
arXiv (CS.CL) 2026-06-12

TAB-PO: Preference Optimization with a Token-Level Adaptive Barrier for Token-Critical Structured Generation

Direct Preference Optimization (DPO) is an effective and widely adopted approach for offline alignment but is poorly matched to ontology-driven structured prediction, where preferred and rejected JSON objects often differ in only a few schema-defining tokens. In this low-edit-distance regime, sequence-level DPO spreads gradient mass across non-critical serialization tokens (gradient dilution) and can reduce likelihood on rare, under-confident preferred schema tokens (token erosion). To address these limitations, we first develop a confusion-aware preference-construction strategy that augments expert-curated ambiguity patterns with empirical structured-error modes estimated from validation-set SFT predictions, synthesizing minimally perturbed, schema-valid negatives that focus preference learning on realistic ontology-level decision errors. We then introduce Token-Adaptive Barrier Preference Optimization (TAB-PO), a post-SFT objective for token-critical structured generation. TAB-PO adds a confidence-gated token-level barrier that applies supervised anchoring to under-confident schema tokens. On the public SciERC scientific information extraction task, evaluated with Llama/Qwen models from 1.5B to 70B, TAB-PO improves ontology-critical semantic-label and relational-linking metrics over SFT by 11.59% on average, wins 100% of comparisons against the strongest token-level and sequence-level DPO variants on these metrics, and surpasses leading frontier models by 14.71%, while delivering strong gains in textual grounding.

22.
medRxiv (Medicine) 2026-06-11

Ferritin across long-term conditions in England: cross-sectional primary care study

Background Iron deficiency (ID) is a readily treatable condition once identified. Ferritin is the primary diagnostic marker, but cut-offs vary and inflammation complicates interpretation in patients with long-term conditions (LTCs). Aim To describe ferritin distribution and the prevalence of threshold-defined low ferritin in adults with and without LTCs in primary care. Design and setting Cross-sectional observational study using routinely collected electronic health records from a national primary care database in England (1st January 2015 to 31st December 2021). Method Adults with >1 ferritin test in Clinical Practice Research Datalink (CPRD) Aurum were included. LTCs were identified using validated primary-care code lists. Outcomes included ferritin distribution and threshold-defined ID prevalence using World Health Organization (WHO) (

23.
arXiv (CS.LG) 2026-06-15

PepALD: Macrocyclic Peptide Generation via Autoregressive Latent Diffusion

arXiv:2606.14510v1 Announce Type: new Abstract: Macrocyclic peptides are promising therapeutic candidates for intracellular targets, but their design requires simultaneous control over non-natural monomer chemistry, ring topology, membrane permeability, and target binding. Existing SMILES- or HELM-string generative models either operate in long atom-level sequence spaces or treat monomers as symbolic tokens with limited chemical grounding. We introduce PepALD, an Autoregressive Latent Diffusion (ALD) foundation model for de novo macrocyclic peptide generation. The model represents HELM monomers with structured chemical embeddings, generates each residue through context-conditioned diffusion in chemically informed latent space, predicts R-group-aware ring closures during autoregressive generation, and aligns the denoiser to affinity rewards using winner-protected diffusion-adapted preference optimization. In silico experiments demonstrate PepALD's generation quality and reward-optimization performance against representative peptide generation baselines.

24.
arXiv (CS.AI) 2026-06-17

Learning Cardiac Electrophysiology Digital Twins Through Agentic Discovery of Hybrid Structure

arXiv:2606.18154v1 Announce Type: new Abstract: Building personalized cardiac electrophysiology (EP) digital twins requires identifying the appropriate model structure for each patient, not merely fitting parameters. Traditional methods rely on experts to manually prescribe hybrid physics-neural architectures, which requires deep domain expertise and does not transfer across patients. Recent works have applied large language models (LLMs) to generate or act as hybrid models. However, despite their promising generalization capacity, these LLM-based methods lack the structural priors needed for stable cardiac simulations. Hence, we propose LEADS, a framework that formulates cardiac EP domain knowledge as a structured action space and utilizes an LLM agent to discover hybrid models. The agent follows an iterative reasoning-and-action loop to select, combine, and refine hybrid models, whilst gradient descent handles parameter fitting. The proposed LEADS designs every candidate model towards physically grounded, interpretable, and numerically stable, while allowing open-ended architectural discovery. We validate LEADS on synthetic data with three ground-truth reaction models and on real cardiac EP data, demonstrating that it outperforms both human-designed hybrid models and other LLM-based hybrid modeling.

25.
arXiv (CS.CL) 2026-06-12

RAGPPI: RAG Benchmark for Protein-Protein Interactions in Drug Discovery

Retrieving the biological impacts of protein-protein interactions (PPIs) is essential for target identification (Target ID) in drug development. Given the vast number of proteins involved, this process remains time-consuming and challenging. Large Language Models (LLMs) and Retrieval-Augmented Generation (RAG) frameworks have supported Target ID; however, no benchmark currently exists for identifying the biological impacts of PPIs. To bridge this gap, we introduce the RAG Benchmark for PPIs (RAGPPI), a factual question-answer benchmark of 4,420 question-answer pairs that focus on the potential biological impacts of PPIs. Through interviews with experts, we identified criteria for a benchmark dataset, such as a type of QA and source. We built a gold-standard dataset (500 QA pairs) through expert-driven data annotation. We developed an ensemble auto-evaluation LLM that incorporates expert labeling characteristics, average fact-abstract similarity (F1), and low-similarity fact counts (F2), enabling the construction of a silver-standard dataset (3,720 QA pairs). We are committed to maintaining RAGPPI as a resource to support the research community in advancing RAG systems for drug discovery QA solutions.