Academic Intelligence · Curated Daily

探索全球前沿学术脉络

AcademicHub 汇聚顶级期刊与预印本平台的实时文献。定制您的专属科研雷达,利用大语言模型自动生成交叉领域文献分析简报。

01.
arXiv (quant-ph) 2026-06-16

Sub-Poissonian Statistics and Quantum Non-Gaussianity from High-Harmonic Generation

arXiv:2602.10882v4 Announce Type: replace Abstract: Quantum technologies are powered by platforms to generate complex non-classical states of matter or light to realize applications. We investigate the non-classical properties of high-harmonic generation in semiconductors, an emerging photonic platform. Measuring the click statistics of three double-digit orders, we evaluate witness operators to certify the non-classicality of the generated states. We show that higher-order harmonics driven by a coherent laser are squeezed and entangled. The properties of the emission are well retrieved with an entangled Gaussian state model, obtained by numerical state optimization to multiple observables. Additionally, we perform inter-order heralded measurements to engineer the quantum state of the emission. The heralded states have distinct properties, showing sub-Poissonian photon statistics. Further, we witness the generation of a quantum non-Gaussian state, a resource highly relevant for quantum information. With this, we establish high-harmonic generation as a platform for generating quantum optical resources.

02.
arXiv (CS.AI) 2026-06-19

CADBench: A Multimodal Benchmark for AI-Assisted CAD Program Generation

arXiv:2605.10873v2 Announce Type: replace-cross Abstract: Recovering editable CAD programs from images or 3D observations is central to AI-assisted design, but progress is difficult to measure because existing evaluations are fragmented across datasets, modalities, and metrics. We introduce CADBench, a unified benchmark for multimodal CAD program generation. CADBench contains 18,000 evaluation samples spanning six benchmark families derived from DeepCAD, Fusion 360, ABC, MCB, and Objaverse; five input modalities including clean meshes, noisy meshes, single-view renders, photorealistic renders, and multi-view renders; and six metrics covering geometric fidelity, executability, and program compactness. STEP-based families are stratified by B-rep face count and all families are diversity-sampled to support controlled analysis across complexity and object variation. We benchmark eleven CAD-specialized and general-purpose vision-language systems, generating more than 1.4 million CAD programs. Under idealized inputs, specialized mesh-to-CAD models substantially outperform code-generating VLMs, which remain far from reliable CAD program reconstruction. CADBench further reveals three recurring failure modes: reconstruction quality degrades with geometric complexity, CAD-specialized models can be brittle under modality shift, and model rankings change across metrics. Together, these results position CADBench as a diagnostic testbed for measuring progress in editable 3D reconstruction and multimodal CAD understanding. The benchmark is publicly available at https://github.com/anniedoris/CADBench.

03.
arXiv (CS.CL) 2026-06-15

SciDef: Datasets and Tools for Automated Definition Extraction from Scientific Literature with LLMs

Scientific concepts are often defined inconsistently across papers, making it difficult to compare findings, reuse terminology, and build reliable downstream resources. We present SciDef, a resource suite for scientific definition extraction. The suite contains DefExtra, a benchmark of 268 human-validated author-stated definitions from 75 academic papers; DefSim, 60 human-labeled definition-pair similarity judgments; and an open LLM-based pipeline for PDF preprocessing, chunking, definition extraction, prompt optimization, and evaluation. We validate the resources by benchmarking 16 language models across prompting strategies and chunking schemes. The strongest set-level configuration achieves a score of 0.397, while the highest-coverage configuration matches at least one prediction to 86.4% of gold definitions but over-generates candidate definitions. We further show that an NLI-based matching metric agrees strongly with human DefSim judgments. These results position SciDef as a reusable benchmark and tooling layer for definition-centric literature analysis, while highlighting relevance-aware filtering as the key bottleneck for fully automatic definition extraction. Code & datasets are available at https://github.com/Media-Bias-Group/SciDef.

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

ReFree: Towards Realistic Co-Speech Video Generation via Reward-Free RL and Multilevel Speech Guidance

Speech-driven talking character animation seeks to generate life-like portrait videos that convey natural conversation behavior, aligning facial motion with spoken audio. Although recent advances in video generation have substantially improved realism in video-based animation, achieving both accurate lip articulation and expressive behavior remains challenging. Existing approaches typically trade off precise phoneme-to-lip synchronization against dynamic facial expressions and head motion, yielding animations that are either accurate yet rigid, or expressive but poorly synchronized. We address this challenge by proposing ReFree-S2V, a flow-matching speech-to-portrait animation framework that builds upon a pretrained video generation model to achieve fine-grained speech articulation and high-level expressive cues in speech-driven portrait animation. This model introduces a multi-level speech representation capturing phonetic and prosodic information at both local and global granularities. These representations are selectively injected into transformer blocks via learnable level selectors, enabling both accurate lip synchronization and natural expressive motion. To achieve natural head movements, we further introduce a novel reward-free reinforcement learning scheme into flow-matching training to discourage perceptually implausible motion without relying on handcrafted synchronization metrics or reward models, or the high cost of human preference annotation. Extensive experiments demonstrate that ReFree-S2V achieves state-of-the-art performance, significantly outperforming existing methods in both quantitative lip-sync accuracy and qualitative human evaluations of naturalness and expressivity.

05.
arXiv (CS.LG) 2026-06-19

Insulin4RL: Real-Time Insulin Management in the Intensive Care Unit for Offline Reinforcement Learning

arXiv:2606.19481v1 Announce Type: new Abstract: Offline reinforcement learning (ORL) offers the potential to improve the quality of clinical decision-making using historical electronic health record (EHR) data. Current training and evaluative practices in this field rely heavily on EHR datasets that have been temporally discretised into fixed, regular time intervals. Discretisation creates fictional representations of complex clinical scenarios and compromises the generalisability of retrospective model evaluations. In this paper, we introduce Insulin4RL, a healthcare ORL dataset featuring naturally irregular inputs and actions from real clinical trajectories. Derived from MIMIC-IV, Insulin4RL comprises over 375,000 labelled decisions across 12,209 patients requiring insulin infusion titration in the Intensive Care Unit. The dataset can thus be used for research into ORL model performance under realistic clinical sampling assumptions. We provide a description of the dataset's structure and characteristics, baseline performance metrics using model-free offline reinforcement learning, and a standardised evaluation protocol using fitted Q-evaluation. We conclude with suggested areas for future research that could be addressed using this resource.

06.
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.

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

Variable-Length Tokenization via Learnable Global Merging for Diffusion Transformers

arXiv:2606.20076v1 Announce Type: cross Abstract: Latent Diffusion Models (LDMs) have become dominant in visual synthesis, but their quality-compute trade-off is largely constrained by the tokenizer's fixed compression ratio. Variable-length tokenizers (VLTs) promise adaptive compression by varying token counts, allowing diffusion models to flexibly balance quality and compute. However, conventional VLTs modulate length by truncating ordered token sequences, which makes token semantics depend on token position and breaks representational alignment across lengths. This leads to a cross-length shift in the latent distribution that hinders a single variable-length diffusion model from operating effectively. To address this, we propose a novel variable-length tokenizer that modulates length by merging tokens. We show that encouraging similar tokens to merge enables direct cross-length representation alignment when the diffusion transformer operates according to the merging pattern. Since conventional merging methods are data-dependent, making the merging pattern inaccessible during generation, we introduce learnable global merging, which is data-independent, to ensure compatibility with diffusion transformers. On ImageNet 256$\times$256 generation, our merging-based variable-length tokenizer integrated with a diffusion transformer achieves a superior gFID-compute trade-off compared to prior VLT methods. Code is available at [this https URL](https://github.com/movinghoon/lgm)

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

Evolutionary Bilevel Reward Shaping for Generalization in Reinforcement Learning

arXiv:2606.16236v1 Announce Type: new Abstract: Reinforcement learning (RL) often suffers from performance degradation when deployed in environments that differ from those encountered during training. Existing techniques such as domain randomization (DR) mitigate this, but require access to diverse training environments and full trajectory observability, assumptions that fail in privacy-preserving or restricted scenarios where only scalar performance metrics are available. We propose Generalization via Evolutionary Reward Shaping (GERS), a bilevel optimization approach to improve generalization on unseen test environments using only scalar feedback from validation environments. At the lower level, an RL agent guided via a reward function shaped by the upper level learns a policy on a limited set of training environments with accessible trajectory data; at the upper level, CMA-ES optimizes the reward shaping parameters to maximize the cumulative unshaped reward on separate validation environments for which trajectory access is unavailable. Results on continuous control tasks indicate that GERS outperforms the standard RL baseline on unseen test environments. GERS performance is comparable to DR, despite DR treating the combined set of training and validation environments of GERS as a single training set that requires trajectory access, whereas GERS cannot access validation trajectories. These results confirm that GERS effectively enhances generalization under restricted data access constraints.

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

Predicting gestational age at birth in the context of preterm birth from multi-modal fetal MRI

arXiv:2606.20172v1 Announce Type: new Abstract: Preterm birth is associated with significant mortality and a risk for lifelong morbidity. The complex multifactorial aetiology hampers accurate prediction and thus optimal care. A pipeline consisting of bespoke machine learning methods for data imputation, feature selection, and regression models to predict gestational age (GA) at birth was developed and evaluated from comprehensive multi-modal morphological and functional fetal MRI data from 333 control cases and 93 preterm birth cases. The GA at birth predictions were classified into term and preterm categories and their accuracy, sensitivity, and specificity were reported. An ablation study was performed to further validate the design of the pipeline. Performance was evaluated using stratified 10-fold cross-validation. The pipeline achieves an R2 score of 0.13 and a mean absolute error of 2.74 weeks. It also achieves a 0.77 accuracy, 0.59 sensitivity, and 0.82 specificity across folds. The predominant features selected by the pipeline include cervical length and statistics derived from placental T2* values. The confluence of fast, motion-robust and multi-modal fetal MRI techniques and machine learning prediction allowed the prediction of the gestation at birth. This information is essential for any pregnancy. To the best of our knowledge, preterm birth had only been addressed as a classification problem in the literature. Therefore, this work provides a proof of concept. Future work will increase the cohort size to allow for finer stratification within the preterm birth cohort. Our code is available at https://github.com/dfajardorojas/ml-for-preterm-birth-.

10.
arXiv (CS.LG) 2026-06-12

BrainPro: Towards Large-scale Brain State-aware EEG Representation Learning

arXiv:2509.22050v2 Announce Type: replace Abstract: Electroencephalography (EEG) reflects underlying brain states, whose activities are distributed across brain regions and manifest as spatial patterns on the scalp. Learning these spatially structured, state-related patterns requires consistent spatial representations across datasets. However, existing EEG foundation models are typically based on self-attention, which does not preserve location-specific information and struggles to align signals recorded with different channel configurations. Moreover, brain states contain both shared and state-specific regional activity, suggesting that learning neurophysiologically plausible, state-aware representations can complement the shared representations targeted by current models and improve downstream decoding. To address these limitations, we propose BrainPro, a large EEG model that combines a retrieval-based spatial learning mechanism for cross-layout spatial alignment with a brain state-decoupling module that learns both shared and state-specific representations through parallel encoders and region-aware reconstruction. Pre-trained on a large EEG corpus, BrainPro achieves state-of-the-art performance across nine public BCI datasets spanning emotion, motor, speech, stress, mental disease, and attention tasks. Analyses of spatial filters, channel-drop robustness, and encoder contributions further validate the effectiveness of its spatial alignment and state-aware pathways. These results show that BrainPro achieves improved interpretability of learned spatial patterns and produces representations that benefit diverse EEG decoding tasks.

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

TurboGS: Accelerating 3D Gaussian Splatting via Error-Guided Sparse Pixel Sampling and Optimization

Consumer-level applications require fast optimization of 3D Gaussian Splatting (3DGS) with high-fidelity novel view rendering. However, existing 3DGS acceleration approaches still incur substantial computation on redundant pixels while sacrificing fine details. In this paper, we present TurboGS, an error-guided training framework that accelerates 3DGS by concentrating optimization on perceptually informative pixels. TurboGS is built upon four core components: (1) a tile-wise sparse pixel sampling, which, driven by multi-view reconstruction errors during training, prioritizes challenging regions and skips well-reconstructed ones to avoid redundant gradient computation; (2) a tile-wise structure-aware loss with sparse Normalized Cross-Correlation, which provides sparse yet effective supervision to preserve fine details and stabilize training; (3) an error-driven Gaussian density control strategy, which dynamically allocates model capacity and removes redundant primitives; and (4) a tailored hybrid optimizer that couples Hessian-informed updates with Adam moment damping to stabilize and improve convergence under sparse supervision. Experiments on standard benchmarks demonstrate that TurboGS can deliver on par or superior rendering quality within 100 seconds on a single RTX 5090 GPU card (up to 10x training speedup over vanilla 3DGS).

12.
PLOS Computational Biology 2026-06-01

A statistical framework for comparing epidemic forests

by Cyril Geismar, Peter J. White, Anne Cori, Thibaut Jombart Inferring who infected whom in an outbreak is essential for characterising transmission dynamics and guiding public health interventions. However, this task is challenging due to limited surveillance data and the complexity of immunological and social interactions. Instead of a single definitive transmission tree, epidemiologists often consider multiple plausible trees forming epidemic forests. Various inference methods and assumptions can yield different epidemic forests, yet no formal test exists to assess whether these differences are statistically significant. We propose such a framework using a chi-square test and permutational multivariate analysis of variance (PERMANOVA). We assessed each method’s ability to distinguish simulated epidemic forests generated under different offspring distributions. While both methods achieved perfect specificity for forests with 100+ trees, PERMANOVA consistently outperformed the chi-square test in sensitivity across all epidemic and forest sizes. Implemented in the R package mixtree, we provide the first statistical framework to robustly compare epidemic forests.

13.
arXiv (CS.CV) 2026-06-19

GenTrack: A New Generation of Multi-Object Tracking

This paper introduces a novel multi-object tracking (MOT) method, dubbed GenTrack, whose main contributions include: first-a hybrid tracking approach employing both stochastic and deterministic manners to robustly handle unknown and time-varying numbers of targets, particularly in maintaining target identity (ID) consistency and managing nonlinear dynamics, second-leveraging particle swarm optimization (PSO) with some proposed fitness measures to guide stochastic particles toward their target distribution modes, enabling effective tracking even with weak and noisy object detectors, third-integration of social interactions among targets to enhance PSO-guided particles as well as improve continuous updates of both strong (matched) and weak (unmatched) tracks, thereby reducing ID switches and track loss, especially during occlusions, fourth-a GenTrack-based redefined visual MOT baseline incorporating a comprehensive state and observation model based on space consistency, appearance, detection confidence, track penalties, and social scores for systematic and efficient target updates, and five-the first ever publicly available source-code reference implementation with minimal dependencies, featuring three variants, including GenTrack Simple, Strengthen, and Super, facilitating flexible reimplementation. Experimental results have shown that GenTrack provides superior performance on standard benchmarks and real-world scenarios compared to state-of-the-art trackers, with integrated implementations of baselines for fair comparison. Potential directions for future work are also discussed. The source-code reference implementations of both the proposed method and compared-trackers are provided on GitHub: https://github.com/SDU-VelKoTek/GenTrack

14.
arXiv (CS.CL) 2026-06-12

Does AI Reviewer See the Full Picture? Attacking and Defending Multimodal Peer Review

The integration of Large Language Models (LLMs) and Multimodal LLMs (MLLMs) into scientific peer-review workflows introduces novel and significant risks for adversarial manipulation, especially given the multimodal nature of scientific papers where figures, not just text, convey core evidence. This creates a significant gap: current robustness studies on AI peer-review are overwhelmingly text-only. Moreover, the problem is distinct from standard jailbreaking, as a peer-review attack seeks to induce a domain-specific, targeted failure (e.g., "inflate this score") rather than a general safety policy violation, for which no practical defenses exist. To address this, we introduce PaperGuard, the first comprehensive benchmark designed to systematically evaluate and defend AI-generated peer-review against these domain-specific, cross-modal attacks. Our framework is built on three pillars: (1) a new multimodal peer-review dataset spanning multiple scientific domains; (2) a unified suite of attacks, including black-box prompt injections and white-box perturbations, specifically designed to target both text (GCG) and figures (PGD); and (3) a practical defense, motivated by the long-context challenge of academic papers, that uses chunk-based embedding search to efficiently localize and mitigate harmful instructions. Our extensive experiments, conducted across state-of-the-art models, confirm that AI reviewers are pervasively vulnerable. PaperGuard establishes the foundational benchmark, protocols, and actionable defense necessary to pioneer trustworthy, attack-resilient AI-assisted scholarly reviewing.

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

DPC-VQA: Decoupling Quality Perception and Residual Calibration for Video Quality Assessment

Recent multimodal large language models (MLLMs) have shown promising performance on video quality assessment (VQA) tasks. However, adapting them to new scenarios remains expensive due to large-scale retraining and costly mean opinion score (MOS) annotations. In this paper, we argue that a pretrained MLLM already provides a useful perceptual prior for VQA, and that the main challenge is to efficiently calibrate this prior to the target MOS space. Based on this insight, we propose DPC-VQA, a decoupling perception and calibration framework for video quality assessment. Specifically, DPC-VQA uses a frozen MLLM to provide a base quality estimate and perceptual prior, and employs a lightweight calibration branch to predict a residual correction for target-scenario adaptation. This design avoids costly end-to-end retraining while maintaining reliable performance with lower training and data costs. Extensive experiments on both user-generated content (UGC) and AI-generated content (AIGC) benchmarks show that DPC-VQA achieves competitive performance against representative baselines, while using less than 2% of the trainable parameters of conventional MLLM-based VQA methods and remaining effective with only 20% of MOS labels. The code will be released upon publication.

16.
arXiv (quant-ph) 2026-06-11

Holographic Complexity, Extremality, and Cosmic Censorship

arXiv:2604.20170v2 Announce Type: replace-cross Abstract: We propose a holographic complexity origin for the third law of black-hole mechanics and weak cosmic censorship. In both complexity equals action and complexity equals volume prescriptions, the relative complexity between subextremal and extremal AdS black holes diverges logarithmically. For overcharged RN-AdS, explicit calculations in both prescriptions show that the near-singularity action terms are power-law divergent or finite, while the maximal-volume contribution is finite. Thus, the extremal-to-naked relative complexity also diverges, obstructing finite-time transitions.

17.
medRxiv (Medicine) 2026-06-11

Dissecting the functional landscape of rare diseases through genomic variation in a heterogeneous cohort of 11,000 patients

Rare diseases (RDs) remain a major diagnostic challenge. Genetic and phenotypic heterogeneity, incomplete knowledge of disease mechanisms, and limitations in variant clinical interpretation leave many patients without a molecular diagnosis. Meanwhile, the growing volume of genomic data generated in clinical practice offers an opportunity to develop data-driven methodologies for exploring disease mechanisms and improving the reanalysis of unsolved cases. We aggregated real-world genomic data from 11,084 unrelated patients with suspected RD. Patients were clinically classified into 122 diseases. We built a multi-disease genomic variant frequency database (FJD-DB), which enabled the development of variant and gene-disease association scores by means of case-control subcohort comparisons across 32 disease groups. Functional enrichment analyses were then used to highlight disease-associated protein domains, pathways, biological processes, and phenotypes. Finally, the resulting knowledge was integrated into a data-driven framework for the guided reanalysis of unsolved RD patients applied to Inherited Retinal Dystrophies (IRD) patients as first use case. FJD-DB contained more than 45 million unique variants, including ~185,000 potentially pathogenic variants. Disease-specific analyses identified disease-associated pathogenic variants and highlighted both established and candidate disease genes. We detected 179 significantly enriched protein domains across 23 diseases, 124 Human Phenotype Ontology terms across 13 diseases, 79 Reactome pathways across 10 diseases, and 72 Gene Ontology biological processes across 8 diseases, revealing highly disease-specific functional signatures. Integration of disease-specific variant, gene, and functional association signals enabled the development of a data-driven framework for guided reanalysis of unsolved RD cases. Applied to more than 1,100 unsolved IRD cases, the framework generated clinically relevant findings in 26 patients, including four molecular diagnoses, seven candidate diagnoses, and 15 cases upgraded from non-informative findings to variants of uncertain significance. Aggregated real-world genomic data can be leveraged to identify disease-associated molecular signals generating novel biological hypotheses. A unified analytical framework provides a scalable strategy for knowledge discovery and guided reanalysis, facilitating the identification of overlooked and potentially novel genetic causes of RDs.

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

Offline Preference-Based Trajectory Evaluation

arXiv:2606.17541v1 Announce Type: cross Abstract: Offline evaluation of agentic systems often collapses trajectories to terminal success, discarding information about partial progress and inducing widespread ties, creating substantial statistical inefficiency by reducing effective sample size and weakening the ability to distinguish systems. We propose preference-based trajectory evaluation, which compares trajectories directly through temporal preferences over progress and time-to-return profiles. We find that, across diverse agentic and interactive benchmarks, standard success-based metrics produce tied comparisons on roughly 75% of instances, whereas trajectory-aware preferences reduce ties to roughly 35%, improving discriminative power, ranking stability, and data efficiency. Our results suggest that benchmark saturation, often attributed to poor data collection or problem difficulty, may also be explained by the choice of evaluation measure.

19.
arXiv (quant-ph) 2026-06-16

The Optimal Rate Function in Covariant Quantum State Tomography

arXiv:2606.16948v1 Announce Type: new Abstract: The problem of quantum tomography is to estimate an unknown quantum state $\rho$ from a measurement of $n$ copies of $\rho$. One can ask which tomography protocol, i.e.\ which choice of multi-copy measurement, gives the best possible estimate of $\rho$. To do so, we characterize tomography protocols by their rate function, which governs the exponential rate at which a protocol assigns probability to a particular estimate $\sigma$ of the true state $\rho$. This rate function is a quantum mechanical generalization of the classical relative entropy between the true state and its estimate, and depends on the choice of protocol. It is bounded by the quantum relative entropy, and we show that this bound is sharp: for any $\rho$ and $\sigma$ we construct a family of protocols whose rate functions converge to the quantum relative entropy $D(\sigma\|\rho)$. We consider the family of covariant tomography protocols; these are the basis independent state estimation schemes that assume no prior information about $\rho$ and $\sigma$. Keyl described a specific tomography protocol based on Schur sampling, and conjectured that among all covariant tomography protocols it has the largest possible rate function for all $\sigma$ and $\rho$. We prove this conjecture. The resulting rate function is an annealed version of quantum relative entropy, due to the cost of learning the eigenbasis in covariant quantum state tomography.

20.
bioRxiv (Bioinfo) 2026-06-11

Machine Learning-Guided Discovery of Bacterial-Selective Membrane-Active Compounds Reveals Mechanistic Bias in Antibiotic Training Datasets

The rise of antibiotic resistance necessitates the discovery of antibacterial compounds with novel mechanisms of action (MoAs). Recent machine learning approaches have shown promise in antibacterial compound discovery, but often identify derivatives of known antibiotic classes rather than mechanistically novel compounds. Previous approaches applied Tanimoto similarity filters at the end of screening pipelines, but this method has substantial drawbacks: Tanimoto similarity can be misleading in chemical space, and post-hoc filtering does not influence what activity models learn to prioritize. Here, we present a machine learning pipeline that addresses chemical novelty upfront by employing an XGBoost-based MoA classifier to explicitly prioritize compounds predicted to have mechanisms distinct from known antibiotic classes, combined with graph neural networks for antibacterial activity and toxicity prediction. Applied to the Zinc20 database, our approach successfully identified non-toxic antibacterial compounds structurally distinct from known antibiotics. Notably, the majority of these hits exhibited membrane-targeting activity with selectivity for bacterial cells over mammalian cells, suggesting potential for next-generation membrane-active antibiotics. However, we did not identify compounds with novel protein targets. Systematic analysis revealed that this limitation stems from mechanistic bias in training data rather than model architecture. Specifically, our activity model learned to preferentially score compounds similar to specific groups in the training data, thus overrepresenting certain MoA classes including membrane-active compounds. Even substantial model architecture and training data enhancements did not overcome this constraint. Our findings demonstrate that the primary bottleneck for discovering mechanistically novel antibiotics is the scarcity of diverse, mechanistically-annotated training data. This work provides both a methodological framework for mechanism-aware screening and critical insights into data requirements for genuinely novel antibiotic discovery.

21.
arXiv (CS.CL) 2026-06-15

Is ChatGPT Fair for Recommendation? Evaluating Fairness in Large Language Model Recommendation

The remarkable achievements of Large Language Models (LLMs) have led to the emergence of a novel recommendation paradigm – Recommendation via LLM (RecLLM). Nevertheless, it is important to note that LLMs may contain social prejudices, and therefore, the fairness of recommendations made by RecLLM requires further investigation. To avoid the potential risks of RecLLM, it is imperative to evaluate the fairness of RecLLM with respect to various sensitive attributes on the user side. Due to the differences between the RecLLM paradigm and the traditional recommendation paradigm, it is problematic to directly use the fairness benchmark of traditional recommendation. To address the dilemma, we propose a novel benchmark called Fairness of Recommendation via LLM (FaiRLLM). This benchmark comprises carefully crafted metrics and a dataset that accounts for eight sensitive attributes1 in two recommendation scenarios: music and movies. By utilizing our FaiRLLM benchmark, we conducted an evaluation of ChatGPT and discovered that it still exhibits unfairness to some sensitive attributes when generating recommendations. Our code and dataset can be found at https://github.com/jizhi-zhang/FaiRLLM.

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

Learning Upper Lower Value Envelopes to Shape Online RL: A Principled Approach

arXiv:2510.19528v2 Announce Type: replace-cross Abstract: We investigate the fundamental problem of leveraging offline data to accelerate online reinforcement learning - a direction with strong potential but limited theoretical grounding. Our study centers on how to learn and apply value envelopes within this context. To this end, we introduce a principled two-stage framework: the first stage uses offline data to derive upper and lower bounds on value functions, while the second incorporates these learned bounds into online algorithms. Our method extends prior work by decoupling the upper and lower bounds, enabling more flexible and tighter approximations. In contrast to approaches that rely on fixed shaping functions, our envelopes are data-driven and explicitly modeled as random variables, with a filtration argument ensuring independence across phases. The analysis establishes high-probability regret bounds determined by two interpretable quantities, thereby providing a formal bridge between offline pre-training and online fine-tuning. Empirical results on tabular MDPs demonstrate substantial regret reductions compared with both UCBVI and prior methods while remaining competitive with related approaches.

23.
arXiv (CS.CL) 2026-06-16

JE-IRT: A Geometric Lens on LLM Abilities through Joint Embedding Item Response Theory

Standard LLM evaluation practices compress diverse abilities into single scores, obscuring their inherently multidimensional nature. We present JE-IRT, a geometric item-response framework that embeds both LLMs and questions in a shared space. For question embeddings, the direction encodes semantics and the norm encodes difficulty, while correctness on each question is determined by the geometric interaction between the model and question embeddings. This geometry replaces a global ranking of LLMs with topical specialization and enables smooth variation across related questions. Building on this framework, our experimental results reveal that out-of-distribution behavior can be explained through directional alignment, and that larger norms consistently indicate harder questions. Moreover, JE-IRT naturally supports generalization: once the space is learned, new LLMs are added by fitting a single embedding. The learned space further reveals an LLM-internal taxonomy that only partially aligns with human-defined subject categories. We also show that simple linear probes of the embedding space recover cross-subject ability directions, such as an arithmetic axis that highlights quantitatively demanding questions in seemingly distant subjects like virology and global facts. JE-IRT thus establishes a unified and interpretable geometric lens that connects LLM abilities with the structure of questions, offering a distinctive perspective on model evaluation and generalization.

24.
medRxiv (Medicine) 2026-06-18

A Brain-Aging Transcriptomic Signature Reclassifies WHO Glioma Grade and Predicts Survival Independently of IDH Status: A Multi-Cohort Study

Background Despite WHO grade and IDH status, significant survival differences remain in diffuse gliomas. We hypothesized that a brain-aging transcriptomic signature, reflecting neuroinflammation, myeloid infiltration, and synaptic loss, would independently predict survival and allow for molecular reclassification. Methods A neurodegeneration score was derived via PCA of brain MRI volumes from 1,057 OASIS-3 subjects and projected onto 888 TCGA-LGG/GBM (discovery) and 693 CGGA gliomas (validation). A 14-gene signature of glial/myeloid (GFAP, AQP4, TYROBP, TREM2, C1QA, CD68, ITGAM) and neuronal (SYP, DLG4, GRIN1, GRIA1, SNAP25, SYN1, RBFOX3) genes were computed. Elastic-net Cox regression identified a 3-gene panel (C1QA, CD68, GRIA1). Kaplan-Meier, multivariate Cox, decision curve, and single-cell RNA-seq analyses were performed. Results High brain-aging scores predicted poorer overall survival (p < 0.0001) and remained an independent prognostic factor after adjusting for WHO grade and IDH status (z = 4.72, p < 0.001); chronological age was non-significant (p = 0.231). In IDH-mutant gliomas, significance was confirmed in both cohorts (TCGA p = 0.027; CGGA p < 0.0001). Bidirectional reclassification showed high-risk Grade 2 tumors with Grade 3-like survival (p = 0.00089), and indolent Grade 3 tumors resembling Grade 2 by Ki-67. Single-cell RNA-seq confirmed macrophage localization of signature genes; DCA demonstrated net benefit over grade alone at 5-30% probability thresholds. Conclusions A brain-aging transcriptomic signature independently predicts glioma survival beyond WHO grade and IDH status, validated in an independent Chinese cohort, with clinical utility for identifying high-risk Grade 2 and sparing over-treatment of indolent Grade 3 tumors.

25.
Nature Medicine 2026-06-10

Dual-target gene therapy in Parkinson’s disease: a multicenter phase 1 trial

作者:

Restoring striatal dopamine synthesis is a promising gene therapy strategy for Parkinson’s disease. Previous adeno-associated virus-mediated aromatic L-amino acid decarboxylase (AADC) monotherapies remain dependent on exogenous levodopa, whereas multigene delivery is constrained by strict adeno-associated virus packaging limits. A ‘dual approach’ targeting the two rate-limiting enzymes, tyrosine hydroxylase (TH) and AADC, offers the potential for autonomous dopamine synthesis. We report the 12-month primary safety and tolerability outcomes of a multicenter, open-label, dose-escalation, phase 1 trial evaluating BBM-P002, a new adeno-associated virus vector—AAVT42—codelivering constitutively active TH and AADC. Ten participants with moderate-to-advanced Parkinson’s disease were enrolled and received bilateral intraputaminal infusions across doses of 4.0 × 1011 vg (Cohort 1; n = 1), 6.0 × 1011 vg (Cohort 2; n = 2), 1.0 × 1012 vg (Cohort 3; n = 2) and 1.2 × 1012 vg (Cohort 4; n = 5). The trial achieved its primary outcome, as BBM-P002 demonstrated a favorable safety and tolerability profile within 12 months post-treatment. No dose-limiting toxicities or drug-related serious adverse events occurred. A total of 23 adverse events were reported, all judged unrelated to BBM-P002 and primarily mild and transient. Systemic toxicity and clinically meaningful immunogenicity were absent. In conclusion, intraputaminal delivery of BBM-P002 was safe and well tolerated in this phase 1 trial, supporting continued clinical development. ClinicalTrials.gov registration: NCT05822739 . Phase 1 results reveal that BBM-P002, a dual-target gene therapy co-delivering TH and DDC, is safe and well tolerated in Parkinson’s disease, with 12-month motor improvements signaling therapeutic potential.