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 (CS.AI) 2026-06-12

Beyond Problem Solving: UOJ-Bench for Evaluating Code Generation, Hacking, and Repair in Competitive Programming

arXiv:2606.12864v1 Announce Type: cross Abstract: Despite strong performance in competitive programming, the role of Large Language Models (LLMs) in supporting human learning in the same setting remains largely unexplored. In this work, we introduce UOJ-Bench, a benchmark designed to evaluate not only the problem-solving ability of LLMs, but also their ability to identify errors in human-written code – a crucial educational activity traditionally supported by running test cases over online judge systems. UOJ-Bench consists of three distinct tasks: code generation, code hacking, and code repair, all constructed from real-world code submissions on the Universal Online Judge (UOJ) and evaluated through UOJ's native judging infrastructure. Our results show that under one-shot evaluation, even the strongest models fail to identify errors in more than 50% of a set of submissions that have been found to be incorrect by UOJ users. While test-time scaling improves success rates to above 90%, the substantial computational costs incurred from model inference limit its practicality for large-scale deployment. Despite these limitations, we find that the best-performing models under test-time scaling can uncover errors in over 5% of full-score submissions across roughly 30 problems, suggesting that frontier LLMs can already provide complementary signals beyond standard judging systems.

02.
arXiv (math.PR) 2026-06-12

On McDiarmid's Inequality under Dependence via Approximate Tensorization of Entropy

arXiv:2606.12720v1 Announce Type: new Abstract: We argue that dependent versions of McDiarmid's inequality are a useful but underutilized tool in mathematical statistics, learning theory and theoretical computer science. To make this point, we first highlight that approximate tensorization of entropy (ATE) implies McDiarmid's via the Entropy Method. Second, we derive McDiarmid's inequality for non-isotropic Gaussian random vectors $X \sim \mathcal N(\mu, \Sigma)$ through ATE with a constant of the order of the condition number of $\Sigma$. We both independently obtain this ATE through a simple application of stochastic localization and also discuss how a more general ATE for the Gibbs sampler due to Ascolani et al., 2026 generalizes McDiarmid's-like concentration to strongly log-concave and log-smooth probability measures. We then apply the resulting concentration inequalities to resolve a question on the concentration of $\operatorname{sign}(X)$ posed by Simone Bombari, investigate Erdős-Rényi graphs under dependence and prove a Dvoretzky-Kiefer-Wolfowitz-type inequality for observations from a joint measure fulfilling ATE and continuous marginal CDFs. For the class of strongly log-concave and log-smooth measures, this result improves upon a prior Dvoretzky-Kiefer-Wolfowitz-type inequality for non-i.i.d. observations due to Bobkov and Götze, 2010, by establishing the expected $1/\sqrt{n}$-rate of convergence under weak dependence instead of $n^{-1/3}$.

03.
medRxiv (Medicine) 2026-06-19

Cardiometabolic multimorbidity and care experiences in primary healthcare among Brazilian adults aged 50 and over (ELSI-Brazil)

Background: Population aging and the rising burden of non-communicable diseases have increased the prevalence of cardiometabolic multimorbidity (CM-MM) among older adults. Patient-reported experience measures (PREMs) are recognized as essential components of healthcare quality assessment, yet evidence on primary care experiences among individuals with CM-MM remains scarce. Objective: To analyze primary care experiences according to the presence of cardiometabolic multimorbidity among Brazilians aged 50 years and older. Methods: Cross-sectional study using data from the second wave of the Brazilian Longitudinal Study of Aging (ELSI-Brazil, 2019-2021; n = 9,949). CM-MM was defined as the self-reported coexistence of two or more of the following conditions: hypertension, diabetes mellitus, dyslipidemia, acute myocardial infarction, and stroke. Primary care experiences were assessed using a validated 12-item instrument organized into four domains: first-contact access, longitudinality, communication, and care coordination. Associations were estimated using Poisson regression adjusted for sociodemographic, health conditions, and healthcare utilization variables, with stratified analysis by Family Health Strategy (FHS) coverage. Results: CM-MM prevalence was 25.5%, with a progressive increase by age and an inverse gradient by education. Individuals with CM-MM reported significantly more positive experiences in longitudinality (mean index 2.53 vs. 2.34; adjusted PR = 1.22; 95%CI 1.12-1.33; p < 0.001) and, to a lesser extent, in communication (mean index 2.68 vs. 2.58; adjusted PR = 1.10; 95%CI 1.00-1.20; p = 0.041). No statistically significant differences were found in first-contact access or care coordination. After stratified by FHS coverage, the observed differences in longitudinality and communication were no longer statistically significant. Conclusions: CM-MM was associated with more positive primary care experiences in longitudinality and communication. The absence of differentiated experiences in first-contact access and coordination highlights structural gaps in primary care responsiveness to individuals with greater clinical complexity. Keywords: Multimorbidity; Cardiometabolic diseases; Primary Care; Patient-reported experience measures; Older adults; ELSI-Brazil.

04.
arXiv (CS.LG) 2026-06-16

MacrOData: New Benchmarks of Thousands of Datasets for Tabular Outlier Detection

arXiv:2602.09329v3 Announce Type: replace Abstract: Quality benchmarks are essential for fairly and accurately tracking scientific progress and enabling practitioners to make informed methodological choices. Outlier detection (OD) on tabular data underpins numerous real-world applications, yet existing OD benchmarks remain limited. The prominent OD benchmark AdBench is the de facto standard in the literature, yet comprises only 57 datasets. In addition to other shortcomings discussed in this work, its small scale severely restricts diversity and statistical power. We introduce MacrOData, a large-scale benchmark suite for tabular OD comprising three carefully curated components: OddBench, with 790 datasets containing real-world semantic anomalies; OvrBench, with 856 datasets featuring real-world statistical outliers; and SynBench, with 800 synthetically generated datasets spanning diverse data priors and outlier archetypes. Owing to its scale and diversity, MacrOData enables comprehensive and statistically robust evaluation of tabular OD methods. Our benchmarks further satisfy several key desiderata: We provide standardized train/test splits for all datasets, public/private benchmark partitions with held-out test labels for the latter reserved toward an online leaderboard, and annotate our datasets with semantic metadata. We conduct extensive experiments across all benchmarks, evaluating a broad range of OD methods comprising classical, deep, and foundation models, over diverse hyperparameter configurations. We report detailed empirical findings, practical guidelines, as well as individual performances as references for future research. All benchmarks containing 2,446 datasets combined are open-sourced, along with a publicly accessible leaderboard hosted at https://huggingface.co/MacrOData-CMU.

05.
bioRxiv (Bioinfo) 2026-06-18

fuzzyfold: a high-performance framework for stochastic RNA folding kinetics

作者:

The analysis of nucleic acid secondary structures is overwhelmingly dominated by methods that analyze the thermodynamic equilibrium distribution and which ignore all dynamic aspects of nucleic acid folding. Yet, there are numerous popular examples of nucleic acid folding that rely on kinetic models, such as RNA riboswitches or DNA strand displacement systems. Here, I am presenting fuzzyfold, a Rust-based software package for nucleic acid secondary structure analysis with an explicit focus on stochastic modeling. The framework introduces three-way and four-way shift moves with a biophysically motivated rate-model parameterization, and it is developed with an emphasis on both model flexibility and performance, e.g. allowing for the generation of single co-transcriptional trajectories for thousand-nucleotide long RNA molecules in just a few minutes. The main strength of the fuzzyfold package, however, is its focus on user and developer interfaces for long-term development. It provides easily installable command-line interfaces, e.g. for aggregating data from multiple parallel trajectories efficiently into an ensemble-level dynamic analysis. For developers, the code-base supports straight-forward substitution of thermodynamic and kinetic free-energy models, and a flexible library interface with Python bindings, enabling integration of individual components into custom computational workflows.

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

When the Past Matters: FlashBack Memory for Precipitation Nowcasting

Accurate precipitation nowcasting is crucial for disaster mitigation and socio-economic planning, yet existing methods often struggle with false alarms, missed events, and long range dependency modeling at high spatiotemporal resolution. To address these challenges, we propose FlashBack Memory (FB), a module that dynamically retrieves key historical states and integrates them via an adaptive fusion gate, enhancing the spatiotemporal representation capability of recurrent-based models. We incorporate FB into PredRNN, PredRNNpp, MIM, MotionRNN, and PredRNN-V2, and evaluate on CIKM2017, Shanghai2020, and SEVIR datasets. Experimental results demonstrate that FB significantly improves MSE, MAE, SSIM, and CSI metrics, particularly for high-intensity rainfall and long-sequence predictions, while reducing false alarms and missed events and enhancing temporal consistency and spatial localization. The proposed method provides a general and efficient memory enhancement mechanism, improving the overall performance of recurrent-based precipitation nowcasting models.

07.
arXiv (CS.CV) 2026-06-18

SP-TransientBench: A Real-Captured Single Photon Perception Benchmark

Single-photon LiDAR (SPL) based on single-photon avalanche diode (SPAD) sensing enables time-resolved photon measurements with extreme sensitivity, offering unique potential for active 3D perception in photon-starved scenarios.However, real-world single photon perception remains fundamentally challenging due to unique measurement noise and complex multi-return transient phenomena, which jointly complicate geometric reconstruction and semantic scene understanding. Despite growing interest in SPAD-based sensing, existing studies are largely limited to simulated data or small-scale controlled captures. As a result, systematic evaluation of real-world single photon perception across depth estimation, multi-view reconstruction, and 3D semantic understanding remains underexplored. To bridge this gap, we introduce SP-TransientBench (STB), a real-captured multi-task benchmark for single photon perception. SP-TransientBenc comprises 10 diverse scenes and 10,297 views captured using a solid-state single-photon LiDAR at $256\times192$ resolution. Each view provides full time-of-flight histograms with multi-return behavior,standardized metadata, and calibrated camera poses for multi-view evaluation. We further provide 13-class 3D semantic annotations for selected scenes. By providing dedicated data splits and evaluation protocols for each task, STB enables consistent and reproducible benchmarking of real-world single photon perception across multiple 3D vision problems. The dataset and code will be released upon acceptance.

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

Semantic Grading of Written Answers in Low-Resource Language Bangla Using a Fine-Tuned Lightweight Language Model

Bangla is among the world's most widely spoken languages, yet it remains underserved in educational NLP research. In many remote and rural regions, access to qualified subject teachers is limited, and written answers are consequently graded largely by hand, restricting timely and consistent feedback. Automatic assessment is challenging because semantically correct responses can vary substantially in surface form. We present a bilingual (Bangla-English) evaluation system designed for low-resource educational settings that prioritizes semantic correctness over lexical overlap. Our approach fine-tunes a lightweight language model to grade each response using the question, reference answer, and student answer, producing a numeric score and concise, context-grounded feedback suitable for classroom deployment. We also construct a synthetic bilingual dataset to enable controlled training and evaluation. Across proprietary and open-source LLMs evaluated under a unified protocol, our QLoRA-tuned Qwen3-8B confirms consistent improvement by producing the most leakage-resistant feedback (RoRa = 0.819) in synthetic evaluation and the strongest agreement with human scores (rho = 0.936, MAE = 0.725) in a dedicated human study.

09.
arXiv (CS.CL) 2026-06-12

How reliable are LLMs when it comes to playing dice?

We investigate the probabilistic reasoning capabilities of large language models through a controlled benchmarking study on discrete probability problems. We constructed two datasets, respectively a set of standard exercises and a set of counterintuitive exercises, designed to trigger heuristic reasoning, and evaluated 8 state-of-the-art models, each tested with and without Chain-of-Thought prompting. Models achieve an average accuracy of 0.96 on standard problems but only 0.59 on counterintuitive ones. We further provide empirical evidence of token bias: performance drops by over 20% when canonical formulations are replaced by disguised variants. Embedding misleading suggestions in the prompt reduces performance by up to 34%, with no model proving immune. Taken together, the reported findings suggest that current LLMs are not yet genuine probabilistic reasoners, despite their success in advanced mathematical problems.

10.
arXiv (CS.CV) 2026-06-16

Attention-Based Prototype Calibration for Multi-Rater Few-Shot Medical Image Segmentation

Few-shot medical image segmentation methods typically assume a single ground-truth annotation, overlooking systematic variability across expert raters commonly observed in clinical datasets. We propose an attention-based prototype calibration framework for few-shot multi-rater segmentation that models rater-specific deviations from a consensus representation in prototype space. A lightweight yet principled attention operator directly refines rater prototypes without modifying the backbone feature extractor, making the approach fully compatible with existing prototype-based few-shot segmentation methods. This design preserves semantic consistency while enabling personalized segmentation outputs with minimal computational overhead. Experiments on multi-rater medical imaging datasets demonstrate consistent improvements over baseline prototype approaches, highlighting the effectiveness of structured prototype calibration for modeling annotation variability. Our code is available at https://github.com/truong2710-cyber/JAPC.

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

Geometric Action Model for Robot Policy Learning

Generalist robot policies must follow user instructions while reasoning about how objects, cameras, and robot actions interact in the 3D physical world. Recent vision-language-action models (VLAs) and video world-action models (WAMs) inherit strong semantic or temporal priors from large-scale foundation models, but they still operate primarily on 2D image frames or 2D-derived latent spaces, leaving implicit the 3D geometry required for contact-rich manipulation. We propose the Geometric Action Model (GAM), a language-conditioned manipulation policy that directly repurposes a pretrained geometric foundation model (GFM) as a shared substrate for perception, temporal prediction, and action decoding. GAM splits the GFM at an intermediate layer: the shallow layers serve as an observation encoder, and a causal future predictor inserted at the split layer forecasts future latent tokens conditioned on language, proprioception, and action history. The predicted future tokens are then routed through the remaining GFM blocks for feature propagation and decoding, allowing a single backbone to produce both future geometry and actions. This design equips the GFM with language-conditioned temporal world modeling through minimal architectural modification while preserving its rich geometric priors. Across a broad suite of simulation and real-robot manipulation benchmarks, GAM is more accurate, more robust, faster, and lighter than current foundation-model-scale baselines.

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

Doc-to-Atom: Learning to Compile and Compose Memory Atoms

Long input sequences are central to document understanding and multi-step reasoning in Large Language Models, yet the quadratic cost of attention makes inference both memory-intensive and slow. Context distillation mitigates this by compressing contextual information into model parameters, and recent work such as Doc-to-LoRA amortizes context distillation into a single forward pass that generates one LoRA adapter per document. However, producing a single monolithic adapter for all queries leads to irrelevant-query interference, limited compositional recall, and poor scalability to long-document reasoning. To address these challenges, we propose Doc-to-Atom (Doc2Atom), a compositional parametric memory framework that decomposes each document into semantically typed knowledge atoms. Each atom is compiled into an independent micro-LoRA adapter and a provenance retrieval key. At inference time, a lightweight query router selects and assembles only the relevant atoms into a query-specific adapter, which is then injected into a frozen base model. The entire system is trained end-to-end through a multi-objective distillation framework. Experiments on six diverse QA benchmarks demonstrate that Doc2Atom outperforms Doc-to-LoRA baselines while reducing the memory cost of document internalization.

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

UniT: Unified Multimodal Chain-of-Thought Test-time Scaling

Unified models can handle both multimodal understanding and generation within a single architecture, yet they typically operate in a single pass without iteratively refining their outputs. Many multimodal tasks, especially those involving complex spatial compositions, multiple interacting objects, or evolving instructions, require decomposing instructions, verifying intermediate results, and making iterative corrections. While test-time scaling (TTS) has demonstrated that allocating additional inference compute for iterative reasoning substantially improves language model performance, extending this paradigm to unified multimodal models remains an open challenge. We introduce UniT, a framework for multimodal chain-of-thought test-time scaling that enables a single unified model to reason, verify, and refine across multiple rounds. UniT combines agentic data synthesis, unified model training, and flexible test-time inference to elicit cognitive behaviors including verification, subgoal decomposition, and content memory. Our key findings are: (1) unified models trained on short reasoning trajectories generalize to longer inference chains at test time; (2) sequential chain-of-thought reasoning provides a more scalable and compute-efficient TTS strategy than parallel sampling; (3) training on generation and editing trajectories improves out-of-distribution visual reasoning. These results establish multimodal test-time scaling as an effective paradigm for advancing both generation and understanding in unified models.

15.
arXiv (CS.AI) 2026-06-17

The Stanford EDGAR Filings Dataset: Reconstructing U.S. Corporate and Financial Disclosures into Layout-Faithful and Token-Efficient Pretraining Data

arXiv:2606.18192v1 Announce Type: new Abstract: As high-quality public web corpora become increasingly exhausted, clean long-context documents have become a scarce and expensive source of training data for large language models (LLMs). Existing long-context corpora are often proprietary and costly to acquire, synthetically generated, or concentrated in narrow domains such as programming. We introduce the Stanford EDGAR Filings Dataset (SEFD), an open reconstruction of SEC filings into layout-faithful MultiMarkdown for financial language modeling and evaluation. SEFD makes audited financial statements, risk disclosures, ownership reports, accounting notes, and market-moving event filings usable as long-context pretraining data and as a basis for financial reasoning, forecasting, compliance, and document understanding. The resulting corpus is token-efficient, model-ready, and has less than 0.1% overlap with Common Crawl-derived corpora. We release SEFD-v1, a 152B-token initial public snapshot, and provide corpus-level analyses of a larger 18.5M-filing archive estimated at 550B tokens. We further introduce two SEFD-derived benchmarks: EDGAR-Forecast, which evaluates filing-grounded numerical forecasting after model knowledge cutoffs, and EDGAR-OCR, which evaluates transcription of complex financial tables.

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

SceneMiner: Identity-Preserving Multi-Task Fine-Tuning for Unified BEV Scene Mining

Mining hard, safety-critical scenes from driving logs is bottlenecked by the absence of difficulty labels, and no single proxy, collision risk, trajectory ambiguity, or semantic rarity suffices to find such scenes on its own. We present SceneMiner, a unified, camera-only bird's-eye-view pipeline that emits complementary mining signals from a frozen vision-language backbone in a single forward pass, with no LiDAR or radar: a retrieval embedding for text-prompted scenario search, a multi-label scene-tag distribution, and a continuous physics-based risk score (a motion forecast is a byproduct, not a contribution). Building such a multi-head model exposes our central finding, a failure mode we term cross-task interference: adding or upgrading one head shifts a shared activation stream and degrades weight-frozen sibling heads, so freezing parameters alone is insufficient. Our contribution, identity-preserving multi-task fine-tuning, removes this interference by zero-initializing every new sub-module and freezing every parameter that feeds the shared stream. The mining heads are thereby preserved bit-identically while training only ~102k parameters. The tagging head reaches mAP 0.4614 (micro-F1 0.5557) on 20 scene tags by pooling each scene into 32 visual tokens, and the embedding head supports text-prompted retrieval, validated qualitatively. Code is available at: https://anonymous.4open.science/r/sceneminer_anonymous-64E5

17.
arXiv (CS.LG) 2026-06-16

Hierarchical Advantage Weighting for Online RL Fine-Tuning of VLAs from Sparse Episode Outcomes

arXiv:2606.17043v1 Announce Type: cross Abstract: When pretrained VLA policies are fine-tuned through online RL, each rollout episode produces only a single binary outcome (success or failure), yet the actor update requires per-transition supervision. Existing approaches commonly reduce this sparse outcome to a single scalar reward or advantage signal, which conflates distinct forms of transition-level feedback and provides limited guidance once basic task success becomes achievable. First, a single scalar signal conflates the two objectives of viability and efficiency; once basic success is achieved, the binary label provides no gradient to distinguish efficient completions from slow ones. Second, real-world rollouts mix autonomous and intervention segments; naively assigning episode outcomes across these boundaries introduces incorrect credit assignment. To address these issues, we propose Hierarchical Advantage-Weighted Behavior Cloning (HABC), which trains separate critic heads for these two objectives on different data subsets and combines their outputs with a state-adaptive balance. A state-adaptive gate $g_t$ merges their one-step advantages, prioritizing viability when success is uncertain and shifting to efficiency only when viability is high, and converts the result into per-transition weights on the actor loss. Intervention-aware credit assignment further restricts outcome labels to segments executed by the current policy, preventing supervision from leaking across intervention boundaries. In real-robot experiments on three contact-rich bimanual tasks, HABC raises success from supervised fine-tuning (SFT) baselines of 36%, 44%, and 12% to 92%, 88%, and 38%.

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

Adapting Vision-Language Models from Iconic to Inclusive for Multi-Label Recognition Without Labels

Understanding multi-label images remains a challenging task in computer vision. With the rapid progress of vision-language multimodal learning, vision-language models (VLMs) enable zero-shot recognition without labeled data. However, due to their intrinsic design, these models often prioritize the most iconic object and omit other contextual positives. This intrinsic bias conflicts with the nature of multi-label learning, thereby limiting their applicability. In this work, we propose an unsupervised framework that adapts VLMs from iconic recognition toward inclusive understanding, enabling label-free multi-label image recognition. Our approach consists of two key stages, ``cutting'' and ``sewing'': In the cutting stage, we present the multi-sampling response estimator to prevent the model from concentrating only on one single object. In the second sewing stage, the multi-object blend adaptation is introduced to adjust the labels to better conform to the multi-label distribution while preserving the intrinsic characteristics of the original model within only one epoch. Extensive experiments show that our framework significantly outperforms existing unsupervised approaches on four public datasets, even surpassing several representative weakly supervised baselines. These results demonstrate the potential of adapting pre-trained VLMs for more comprehensive visual understanding without manual annotations. Our code is publicly available at https://github.com/iCVTEAM/TailorCLIP.

20.
arXiv (CS.AI) 2026-06-11

Are LLMs Bad at Moral Reasoning?

arXiv:2606.11635v1 Announce Type: cross Abstract: For highly capable AI systems to operate safely in dynamic, open-ended environments, they must be able to identify, understand, and respond to moral reasons for action, and constrain their behaviour accordingly. A growing body of research aims to evaluate this capacity – moral competence – in today's most capable AI systems, recently reaching broadly pessimistic conclusions. One of the most ambitious such papers collects gold-standard human-authored rubrics for evaluating moral reasoning in 1,000 cases, and benchmarks frontier AI models against those rubrics, with underwhelming results. In this paper, we argue that the MoReBench dataset can be redeployed to give a much more optimistic picture of LLMs' moral reasoning (an essential part of moral competence). We show that if, instead of scoring LLMs' responses to these cases against these rubrics, we instead give the LLMs the same task given to humans – to generate scoring rubrics for the moral analysis of particular cases – the rubrics they generate are both better calibrated to the human rubrics than their open-ended responses, and, where they differ, plausibly reflect nothing more than the vast dimensionality of most moral problems, as well as highlighting some human departures from the "rubric for creating rubrics". Taking these points into consideration, the MoReBench dataset suggests that LLMs are significantly more capable at moral reasoning than was previously believed.

21.
arXiv (quant-ph) 2026-06-12

First-order and interior-point methods for entanglement detection

arXiv:2508.05854v3 Announce Type: replace Abstract: Quantum entanglement lies at the heart of quantum information science, yet its reliable detection in high-dimensional or noisy systems remains a fundamental computational challenge. Semidefinite programming (SDP) hierarchies, such as the Doherty-Parrilo-Spedalieri (DPS) and Extension (EXT) hierarchies, offer complete methods for entanglement detection, but it is well known that their practical use is limited by exponential growth in problem size if implemented naively. We make three contributions. First, we introduce a new SDP hierarchy, PST, that is sandwiched between EXT and DP – offering a tighter approximation to the set of separable states than EXT, while incurring significantly lower computational overhead than DPS. Second, we explicitly construct compact, polynomially-scalable descriptions of EXT and PST using partition mappings and operators. These descriptions in turn yield formulations that satisfy desirable properties such as the Slater condition and are well-suited to both first-order methods (FOMs) and interior-point methods (IPMs). Third, we design a suite of entanglement detection algorithms: three FOMs (Frank-Wolfe, projected gradient, and fast projected gradient) based on a least-squares formulation, and a custom primal-dual IPM based on a conic programming formulation. These methods are numerically stable and capable of producing entanglement witnesses or proximity measures, even in cases where states lie near the boundary of separability. Numerical experiments on benchmark quantum states demonstrate that our algorithms improve the ability to solve deeper levels of the SDP hierarchy.

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

Physics-Aware Auxiliary Losses Improve Out-of-Distribution Generalization of a GNN Synthesizability Filter

arXiv:2606.12651v1 Announce Type: new Abstract: Machine-learning drug-discovery pipelines increasingly rely on generative models that propose molecules far from the data used to train downstream synthesizability filters. Existing filters (SAScore, SCScore, RAscore, DeepSA) are purely statistical and degrade in exactly this out-of-distribution (OOD) regime. We ask whether cheap, closed-form physical priors, used as auxiliary supervision on a graph neural network (GNN), improve OOD generalization. We add two auxiliary losses to a GINE backbone: a topological complexity regression supervised by the Bertz index, and a strain-energy soft penalty supervised by MMFF94 force-field energy. On a 65,177-molecule corpus (HIV, Tox21, COCONUT) labeled by SAScore thresholds we reproduce a strong in-distribution baseline, then evaluate a 4-way ablation (baseline / +complexity / +strain / +both) on a single-source OOD split (train on drug-like HIV+Tox21, test on COCONUT natural products), repeated over 5 seeds with paired bootstrap confidence intervals. All three physics-aware variants give a small but statistically significant OOD improvement over the baseline (mean OOD AUC 0.9774): +complexity Delta = +0.0060 (95% CI [+0.0023, +0.0102]), +strain Delta = +0.0032 ([+0.0008, +0.0052]), +both Delta = +0.0066 ([+0.0038, +0.0093]); every interval excludes zero, and the combination is best. The variants are indistinguishable in-distribution, so the effect is visible only under OOD evaluation. We are explicit that the effects are modest, and we report a cautionary methodological finding: a single-seed version of this experiment produced a qualitatively different (non-monotone) story that did not survive multi-seed evaluation.

23.
arXiv (CS.CV) 2026-06-17

Principled RL for Flow Matching Emerges from the Chunk-level Policy Optimization

Recent Progress in post-training flow matching for text-to-image (T2I) generation with Group Relative Policy Optimization (GRPO) has demonstrated strong potential. However, it is hindered by a critical limitation: inaccurate advantage attribution. In this work, we argue that aggregating consecutive steps into a coherent 'chunk' and shifting the policy optimization paradigm from GRPO's step level to the chunk level can effectively mitigate the negative impact of this issue. Building on this insight, we propose Group Chunking Policy Optimization (GCPO), the first chunk-level reinforcement learning approach for post-training flow matching. Extensive experiments demonstrate that GCPO achieves superior performance on both standard T2I benchmarks and preference alignment, with up to 43% relative gains over GRPO, highlighting the promise of chunk-level policy optimization. The code is available on https://github.com/xingzhejun/GCPO.

24.
medRxiv (Medicine) 2026-06-16

MRMU: A New Paradigm for Mendelian Randomization by Accounting for Measured Covariates and Unmeasured Confounders

Mendelian randomization (MR) is a powerful approach for causal inference, however, its reliability is frequently compromised by unadjusted covariates and unmeasured confounders, such as unmeasured pleiotropy and sample structure. To address these challenges, we introduce MRMU, a novel paradigm for the MR framework. Unlike traditional single-variable or multivariable MR methods, MRMU selects instrumental variables only from the exposure of interest and estimates one exposure effect at a time, while jointly accounting for measured covariates and unmeasured confounders. This design improves the reliability of MR analyses. In simulations and real data, MRMU achieved better type I error control, higher statistical power, and more accurate effect estimation than existing MR methods. Applying to coronary artery disease (CAD), MRMU identified robust cardiometabolic risk factors, including LDL-C, APOB, systolic blood pressure, body mass index, and smoking initiation, with consistent evidence across multiple CAD datasets. In contrast, traits such as HDL-C, height, and educational attainment, which were found to be significant by existing MR methods, were no longer supported by MRMU. MRMU further supported blood pressure-related traits, rather than lipid traits, as the more relevant pathway linking urate to CAD. Finally, by integrating large-scale plasma proteomics data, MRMU identified candidate CAD drug targets beyond established HMGCR- and PCSK9-related pathways, highlighting its utility for therapeutic target prioritization.

25.
bioRxiv (Bioinfo) 2026-06-14

Robust integration of weakly anchored spatial multi-omics

Spatial multi-omics holds great promise for dissecting complex biological processes, though inherent technical constraints continue to limit its widespread adoption. Currently, most studies therefore measure distinct omics features on separate tissue sections, necessitating spatial diagonal integration. An emerging practical solution is to leverage hematoxylin and eosin (H&E) images as an integration anchor, given their ubiquity, low cost, and compatibility across tissue preparations. However, this anchor is frequently compromised in real-world settings by variations in H&E staining style, absence of reliable histological landmarks, and mismatches in spatial resolutions across omics modalities. To address this, we introduce SpaWeaver, a computational framework that couples a pathology foundation model with a graph Transformer and a latent feature aligner module, providing a highly robust solution for weakly anchored spatial omics data diagonal integration. Extensive experiments demonstrate that SpaWeaver exhibits superior robustness against isolated or synergistic weak-anchoring factors. The spatial multi-omics profiles generated by SpaWeaver link molecular features originally separated on two sections, unlocking diverse downstream analyses once exclusive to co-assayed spatial multi-omics data, including niche-aware cell-cell communication inference and multi-omics resolved cell state. In this study, it unveils tumor-distance-dependent fibroblast-CD4+ T-cell signaling in human colon adenocarcinoma and identifies a hypoxic glycolytic tumor state with pyknotic nuclei in human ovarian cancer. Overall, our approach bridges readily accessible single-omics measurements across weakly anchored tissue sections, enabling unified spatial multi-omics characterization and system-level tissue analysis.