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Applications · Health

Miao Jing, Mengting Jia, Junling Lin, Zhongxia Shen, Huan Gao, Mingkun Xu, Shangyang Li

Recent advances in vision-language models (VLMs) have achieved remarkable performance on standard medical benchmarks, yet their true clinical reasoning ability remains unclear. Existing datasets predominantly emphasize classification accuracy, creating an evaluation illusion in which models appear proficient while still failing at high-stakes diagnostic reasoning. We introduce Neural-MedBench, a compact yet reasoning-intensive benchmark specifically designed to probe the limits of multimodal clinical reasoning in neurology. Neural-MedBench integrates multi-sequence MRI scans, structured electronic health records, and clinical notes, and encompasses three core task families: differential diagnosis, lesion recognition, and rationale generation. To ensure reliable evaluation, we develop a hybrid scoring pipeline that combines LLM-based graders, clinician validation, and semantic similarity metrics. Through systematic evaluation of state-of-the-art VLMs, including GPT-4o, Claude-4, and MedGemma, we observe a sharp performance drop compared to conventional datasets. Error analysis shows that reasoning failures, rather than perceptual errors, dominate model shortcomings. Our findings highlight the necessity of a Two-Axis Evaluation Framework: breadth-oriented large datasets for statistical generalization, and depth-oriented, compact benchmarks such as Neural-MedBench for reasoning fidelity. We release Neural-MedBench at https://neuromedbench.github.io/ as an open and extensible diagnostic testbed, which guides the expansion of future benchmarks and enables rigorous yet cost-effective assessment of clinically trustworthy AI.

Deep Learning · Everything Else

Jingqi Ye, Haonan He, Minglei Li, Fujun Han, Tao Chen, Peng Ye

Parameter-Efficient Fine-Tuning (PEFT) techniques, such as Low-Rank Adaptation (LoRA) and its variants, have emerged as critical tools for adapting large pretrained models under limited computational resources. However, a notable performance gap persists between these LoRA methods and Full Fine-Tuning (FFT). In this paper, we investigate a key yet overlooked cause of this gap: the relationship between LoRA's low-rank adaptation subspace and true effective update directions of FFT gradients, which we define as the **gradient intrinsic dimensionality**. To systematically quantify this dimension, we first propose a novel entropy-based estimator, uncovering substantial discrepancies (up to more than 100x) between the rank of LoRA and the gradient intrinsic dimensionality. Motivated by this finding, we introduce **RaLoRA**, which adaptively aligns the ranks of LoRA adapters with layer-specific gradient intrinsic dimensions, without increasing the number of overall parameters. We further extend this approach into **RaLoRA-Pro**, integrating intra-layer rank alignment and inter-layer parameter reallocation guided by loss sensitivity, enabling finer-grained capacity relocation under comparable parameters. Extensive experiments demonstrate the effectiveness of our methods. Specifically, compared to vanilla LoRA, our methods achieve more than +5\% improvement on GLUE, +0.57 on MT-Bench, +5.23\% on GSM8K, +5.69\% on HumanEval, and +1.58\% on image classification, confirming consistent and substantial performance gains across diverse tasks and modalities.

Applications · Language, Speech and Dialog

Zongsheng Wang, Kaili Sun, Bowen Wu, qun yu, Ying Li, Xu Chen, Baoxun Wang

Maintaining role-awareness in Role-Playing Conversational Agents (RPCAs) is a significant challenging, largely because the creative nature of role-playing makes it difficult to design verifiable reward signals for reinforcement learning (RL). To address this, we propose VeriRole, a new framework designed to enhance the role-awareness of agents through a structured, verifiable reasoning process. The core of our framework is a 'hint' mechanism, designed to first extract deterministic cues from the context, before the main response generation.Building on these hints, we introduce a Verifiable Role-Awareness Reward (VRAR) to provide a verifiable signal for role-awareness. Experimental results demonstrate the effectiveness of our approach. Our Qwen2.5-32B model, optimized with VeriRole, achieves an 18.9% and 4.55% increase in average scores on the RAIDEN and CharacterEval benchmarks, respectively. These results confirm that VeriRole can effectively quantify and improve role-awareness, leading to superior persona consistency and robustness. To ensure reproducibility, all prompts are detailed in the Appendix, and the associated training data has been made publicly available.

Applications · Genetics, Cell Biology, Health, etc

KUN WU, Zhiguo Jiang, Xinyu Zhu, Jun Shi, Yushan Zheng

Fusing histopathology images and genomics data with deep learning has significantly advanced precision oncology. However, genomics data is often missing due to its high acquisition cost and complexity in real-world clinical scenarios. Existing solutions aim to reconstruct genomics data from histopathology images. Nevertheless, these methods typically relied only on individual case and overlooked the potential relationships among cases. Additionally, they failed to take advantage of the authentic genomics data of diagnostically related cases that are accessible from training for inference. In this work, we propose a novel Multi-modal Structural Representation Learning (MSRL) framework for data-efficient precision oncology. We pre-train a histopathology-genomics multi-modal representation graph adopting Graph Structure Learning (GSL) to construct inter-case relevance based on the data inherently. During the fine-tuning stage, we dynamically capture structural relevance between the training cases and the acquired authentic cases for precise prediction. MSRL leverages prior inter-case associations and authentic genomics data from diagnosed cases based on the graph, which contributes to effective inference based on the single histopathology image modality. We evaluated MSRL on public TCGA datasets with 7,263 cases across various tasks, including survival prediction, cancer grading, and gene mutation prediction. The results demonstrate that MSRL significantly outperforms existing missing-genomics generation approaches with improvements of 1.44% to 3.12% in C-Index on survival prediction tasks and achieves comparable performance to multi-modal fusion methods. The code and data are available at https://github.com/WkEEn/MSRL.

Computer Vision · Vision Models & Multimodal

Fujun Han, Jingqi Ye, Chenglong Zhang, Peng Ye

Various vision intrusion detection models have achieved great success in many scenarios, e.g., autonomous driving, intelligent monitoring, and security, etc. However, their reliance on pre-defined classes limits their applicability in open-world intrusion detection scenarios. To remedy these, we introduce the Open-Vocabulary Intrusion Detection (OVID) project for the first time. Specifically, we first develop a novel dataset, Cityintrusion-OpenV for OVID, with more diverse intrusion categories and corresponding text prompts. Then, we design a multi-modal, multi-task, and end-to-end open-vocabulary intrusion detection framework named OVIDNet. It achieves open-world intrusion detection via aligning visual features with language embeddings. Further, two simple yet effective strategies are proposed to improve the generalization and performance of this specific task: (1) A Multi-Distributed Noise Mixing strategy is introduced to enhance the location information of unknown and unseen categories. (2) A Dynamic Memory-Gated module is designed to capture the contextual information under complex scenarios. Finally, comprehensive experiments and comparisons are conducted on multiple dominant datasets, e.g., COCO, Cityscape, Foggy-Cityscape, and Cityintrusion-OpenV. Besides, we also evaluate the universal applicability of our model in real scenarios. The results show that our method can outperform other classic and promising methods, and reach strong performance even under task-specific transfer and zero-shot settings, demonstrating its high practicality.

Applications · Genetics, Cell Biology, Health, etc

Yuxin Zhang, Yiyao Li, Ping Ho, Simon See, Zhenqin Wu, Kevin Tsia

Cell Painting combines multiplexed fluorescent staining, high‑content imaging, and quantitative analysis to generate high-dimensional phenotypic readouts to support diverse downstream tasks such as mechanism-of-action (MoA) inference, toxicity prediction, and construction of drug–disease atlases. However, existing workflows are slow, costly and difficult to interpret. Approaches for drug screening modeling predominantly focus on molecular representation learning, while neglecting actual experimental context (e.g., cell line, dosing schedule, etc.), limiting generalization and MoA resolution. We introduce CP-Agent, an agentic multimodal large language model (MLLM) capable of generating mechanism-relevant, human-interpretable rationales for cell morphological changes under drug perturbations. At its core, CP-Agent leverages a context-aware alignment module, CP-CLIP, that jointly embeds high-content images and experimental metadata to enable robust treatment and MoA discrimination (achieving a maximum F1-score of 0.896). By integrating CP-CLIP outputs with agentic tool usage and reasoning, CP‑Agent compiles rationales into a structured report to guide experimental design and hypothesis refinement. These capabilities highlight CP-Agent’s potential to accelerate drug discovery by enabling more interpretable, scalable, and context-aware phenotypic screening---streamlining iterative cycles of hypothesis generation in drug discovery.

Applications · Genetics, Cell Biology, Health, etc

ZAIXI ZHANG, Zhenghong Zhou, Ruofan Jin, Le Cong, Mengdi Wang

DNA, encoding genetic instructions for almost all living organisms, fuels groundbreaking advances in genomics and synthetic biology. Recently, DNA Language Models have achieved success in designing synthetic functional DNA sequences, even whole genomes of novel bacteriophage, verified with wet lab experiments. Such remarkable generative power also brings severe biosafety concerns about whether DNA language models can design human viruses. With the goal of exposing vulnerabilities and informing the development of robust safeguarding techniques, we perform a systematic biosafety evaluation of DNA language models through the lens of jailbreak attacks. Specifically, we introduce JailbreakDNABench, a benchmark centered on high-priority human viruses, together with an end-to-end jailbreak framework, GeneBreaker. GeneBreaker integrates three key components: (1) an LLM agent equipped with customized bioinformatics tools to design high-homology yet non-pathogenic jailbreak prompts, (2) beam search guided by PathoLM and log-probability heuristics to steer sequence generation toward pathogen-like outputs, and (3) a BLAST- and function-annotation–based evaluation pipeline to identify successful jailbreaks. On JailbreakDNABench, GeneBreaker successfully jailbreaks the latest Evo series models across 6 viral categories consistently (up to 60\% Attack Success Rate for Evo2-40B). Further case studies on SARS-CoV-2 spike protein and HIV-1 envelope protein demonstrate the sequence and structural fidelity of jailbreak output, while evolutionary modeling of SARS-CoV-2 underscores biosecurity risks. Our findings also reveal that scaling DNA language models amplifies dual-use risks, motivating enhanced safety alignment and tracing mechanisms.

Applications · Genetics, Cell Biology, Health, etc

Tianmeng Hu, Yongzheng Cui, Biao Luo, Ke Li

The inverse design of RNA three-dimensional (3D) structures is crucial for engineering functional RNAs in synthetic biology and therapeutics. While recent deep learning approaches have advanced this field, they are typically optimized and evaluated using native sequence recovery, which is a limited surrogate for structural fidelity, since different sequences can fold into similar 3D structures and high recovery does not necessarily indicate correct folding. To address this limitation, we propose RIDER, an RNA Inverse DEsign framework with Reinforcement learning that directly optimizes for 3D structural similarity. First, we develop and pre-train a GNN-based generative diffusion model conditioned on the target 3D structure, achieving a $9\\%$ improvement in native sequence recovery over state-of-the-art methods. Then, we fine-tune the model with an improved policy gradient algorithm using four task-specific reward functions based on 3D self-consistency metrics. Experimental results show that RIDER improves structural similarity by over $100\\%$ across all metrics and discovers designs that are distinct from native sequences.

Applications · Chemistry and Drug Discovery

Michael Sun, Weize Yuan, Gang Liu, Wojciech Matusik, Marinka Zitnik

Protein structure is central to biological function, and enabling multimodal protein models requires joint reasoning over sequence, structure, and function. A key barrier is the lack of principled protein structure tokenizers (PSTs): existing approaches fix token size or rely on continuous vector codebooks, limiting interpretability, multi-scale control, and transfer across architectures. We introduce GeoBPE, a geometry-grounded PST that transforms continuous, noisy, multi-scale backbone conformations into discrete ``sentences'' of geometry while enforcing global constraints. Analogous to byte-pair encoding, GeoBPE generates a hierarchical vocabulary of geometric primitives by iteratively (i) clustering Geo-Pair occurrences with k-medoids to yield a resolution-controllable vocabulary; (ii) quantizing each Geo-Pair to its closest medoid prototype; and (iii) reducing drift through differentiable inverse kinematics that optimizes boundary glue angles under an $\mathrm{SE}(3)$ end-frame loss. GeoBPE offers compression ($>$10× reduction in bits-per-residue at similar distortion rate), data efficiency ($>$10× less training data), and generalization (maintains test/train distortion ratio of $1.0-1.1$). It is architecture-agnostic: (a) its hierarchical vocabulary provides a strong inductive bias for coarsening residue-level embeddings from large PLMs into motif- and protein-level representations, consistently outperforming leading PSTs across $12$ tasks and $24$ test splits; (b) paired with a transformer, GeoBPE supports unconditional backbone generation via language modeling; and (c) tokens align with CATH functional families and support expert-interpretable case studies, offering functional meaning absent in prior PSTs.

Yuhao Huang, Shih-Hsin Wang, Andrea Bertozzi, Bao Wang

Mean flow (MeanFlow) enables efficient, high-fidelity image generation, yet its single-function evaluation (1-NFE) generation often cannot yield compelling results. We address this issue by introducing RMFlow, an efficient multimodal generative model that integrates a coarse 1-NFE MeanFlow transport with a subsequent tailored noise-injection refinement step. RMFlow approximates the average velocity of the flow path using a neural network trained with a new loss function that balances minimizing the Wasserstein distance between probability paths and maximizing sample likelihood. RMFlow achieves near state-of-the-art results on text-to-image, context-to-molecule, and time-series generation using only 1-NFE, at a computational cost comparable to the baseline MeanFlows.

Deep Learning · Everything Else

Renfei Dang, Zhening Li, Shujian Huang, Jiajun Chen

Reasoning models often exhibit overthinking, characterized by redundant reasoning steps. We identify \emph{internal bias} elicited by the input question as a key trigger of such behavior. Upon encountering a problem, the model immediately forms a preliminary guess about the answer, which we term an internal bias since it may not be explicitly generated, and it arises without systematic reasoning. When this guess conflicts with its subsequent reasoning, the model tends to engage in excessive reflection, resulting in wasted computation. We validate the association between internal bias and overthinking across multiple models and diverse reasoning tasks. To demonstrate the causal relationship more rigorously, we conduct two counterfactual interventions, showing that removing the input question after the model reduces the redundant reasoning across various complex reasoning tasks, and manually injecting bias affects overthinking accordingly. Further interpretability experiments suggest that excessive attention to the input question serves as a key mechanism through which internal bias influences subsequent reasoning trajectories. Finally, we evaluated several methods aimed at mitigating overthinking, yet the influence of internal bias persisted under all conditions.

Optimization · Large Scale, Parallel and Distributed

Jaehoon Yang, Yushin Kim, Seokwon Moon, Yeonhong Park, Jae W. Lee

Distributed inference of large-scale Mixture-of-Experts (MoE) models faces a critical challenge: expert load imbalance. Numerous system-level approaches have been proposed for load balancing, but they either fail to achieve a satisfactory level of balance or introduce new bottlenecks due to the overhead of the load balancing mechanism itself. To this end, we propose Libra, a system that achieves near-optimal load balancing with minimal overhead. Libra adopts sophisticated mechanisms that accurately predict future expert activations and, based on these predictions, systematically perform load balancing. At the same time, it effectively hides the associated overhead by reconstructing the execution flow so that these costs are overlapped with MoE computation. Evaluations with two large-scale state-of-the-art MoE models on 8 H200 GPUs demonstrate that Libra improves throughput by up to 19.2\%. The code is available at https://github.com/SNU-ARC/Libra.

Computer Vision · Vision Models & Multimodal

Yujia Cai, Boxuan Li, Chenghao Xu, Jiexi Yan

Query-based image retrieval (QBIR) requires retrieving relevant images given diverse and often stylistically heterogeneous queries, such as sketches, artworks, or low-resolution previews. While large-scale vision--language representation models (VLRMs) like CLIP offer strong zero-shot retrieval performance, they struggle with distribution shifts caused by unseen query styles. In this paper, we propose the Hypernetwork-driven Style-adaptive Retrieval (Hystar), a lightweight framework that dynamically adapts model weights to each query’s style. Hystar employs a hypernetwork to generate singular-value perturbations ($\Delta S$) for attention layers, enabling flexible per-input adaptation, while static singular-value offsets on MLP layers ensure cross-style stability. To better handle semantic confusions across styles, we design StyleNCE as part of Hystar, an optimal-transport-weighted contrastive loss that emphasizes hard cross-style negatives. Extensive experiments on multi-style retrieval and cross-style classification benchmarks demonstrate that Hystar consistently outperforms strong baselines, achieving state-of-the-art performance while being parameter-efficient and stable across styles.

Deep Learning · Everything Else

Minglei Li, Peng Ye, Jingqi Ye, Haonan He, Tao Chen

As large pre-trained models rapidly scale, Parameter-Efficient Fine-Tuning (PEFT) through methods like Low-Rank Adaptation (LoRA) becomes increasingly crucial. While LoRA has emerged as a cornerstone of PEFT, excelling at preserving performance with minimal additional parameters, exploring parameter-sharing mechanisms of LoRA remains critical to pushing efficiency boundaries. However, existing naive LoRA sharing methods often degrade performance due to sacrificed representational diversity and weakened model expressiveness. To overcome this issue, we conduct an in-depth analysis of pre-trained models using gradient-based proxy entropy, and uncover two critical, previously overlooked properties: Local Similarity and Layer-wise Information Heterogeneity. Building on these insights, we propose E²LoRA, a novel dual-adaptive sharing framework. It enables adaptive sharing interval partitioning, guided by inter-layer proxy entropy similarity, and adaptive rank allocation, informed by layer-wise absolute proxy entropy. This unique design leverages inherently informative properties of pre-trained models to significantly reduce parameter redundancy while maintaining or enhancing expressiveness. Comprehensive evaluations across diverse tasks, modalities, and models consistently demonstrate that E²LoRA achieves an excellent balance of efficiency and effectiveness, consistently matching or surpassing baselines with approximately 50% fewer trainable parameters.

Theory · Learning Theory

Seyed Mohammad Hadi Hosseini, Amir Najafi, Mahdieh Baghshah

Bandit algorithms have recently emerged as a powerful tool for evaluating machine learning models, including generative image models and large language models, by efficiently identifying top-performing candidates without exhaustive comparisons. These methods typically rely on a reward model---often distributed with public weights on platforms such as Hugging Face---to provide feedback to the bandit. While online evaluation is expensive and requires repeated trials, offline evaluation with logged data has become an attractive alternative. However, the adversarial robustness of offline bandit evaluation remains largely unexplored, particularly when an attacker perturbs the reward model (rather than the training data) prior to bandit training. In this work, we fill this gap by investigating, both theoretically and empirically, the vulnerability of offline bandit training to adversarial manipulations of the reward model. We introduce a novel threat model in which an attacker exploits offline data in high-dimensional settings to hijack the bandit's behavior. Starting with linear reward functions and extending to nonlinear models such as ReLU neural networks, we study attacks on two Hugging Face evaluators used for generative model assessment: one measuring aesthetic quality and the other assessing compositional alignment. Our results show that even small, imperceptible perturbations to the reward model’s weights can drastically alter the bandit's behavior. From a theoretical perspective, we prove a striking high-dimensional effect: as input dimensionality increases, the perturbation norm required for a successful attack decreases, making modern applications such as image evaluation especially vulnerable. Extensive experiments confirm that naive random perturbations are ineffective, whereas carefully targeted perturbations achieve near-perfect attack success rates. To address computational challenges, we design efficient heuristics that preserve almost 100\% success while dramatically reducing attack cost. In parallel, we propose a practical defense mechanism that partially mitigates such attacks, paving the way for safer offline bandit evaluation. Finally, we validate our findings on the UCB bandit and provide theoretical evidence that adversaries can delay optimal arm selection proportionally to the input dimension. Code is available at the anonymous repository: [https://anonymous.4open.science/r/offline-bandit](https://anonymous.4open.science/r/offline-bandit).

Deep Learning · Everything Else

Peijie Yu, Wei Liu, Yifan Yang, Jinjian Li, Zelong Zhang, Xiao Feng, feng zhang

Fulfilling user needs through Large Language Model multi-turn, multi-step tool-use is rarely a straightforward process. Real user interactions are inherently $\textbf{wild}$, being intricate, messy, and flexible. We identify three key challenges from user behaviour: $\textit{compositional tasks}$ that demand efficient orchestration of tool-call topologies, $\textit{implicit intent}$ spread across dialogue turns that require contextual inference, and $\textit{instruction transition}$, which mixes task queries, clarifications, and casual conversation, forcing LLMs to adjust their policies on the fly. Existing benchmarks overlook these behaviors, making the apparent progress of LLMs on tool-use spurious. To address this, we introduce $\textbf{\textit{WildToolBench}}$, an LLM tool-use benchmark grounded in real-world user behavior patterns. Comprehensive evaluations of 57 LLMs reveal that no model achieves an accuracy of more than 15\%, indicating a substantial gap in the robustness of LLMs' agentic ability. Controlled experiments and in-depth analyses further indicate that the real challenge for LLM tool-use lies not in artificially complex tasks, but in the wild nature of user behavior, emphasizing the need to reconsider the interactions among $\textit{LLMs}$, $\textit{users}$, and $\textit{tools}$.

Deep Learning · Theory

Bhavya Vasudeva, Puneesh Deora, Yize Zhao, Vatsal Sharan, Christos Thrampoulidis

The growing adoption of spectrum-aware matrix-valued optimizers such as Muon and Shampoo in deep learning motivates a systematic study of their generalization properties and, in particular, when they might outperform competitive algorithms. We approach this question by introducing appropriate simplifying abstractions as follows: First, we use imbalanced data as a testbed. Second, we study the canonical form of such optimizers, which is Spectral Gradient Descent (SpecGD)—each update step is $\mathbf{U}\mathbf{V}^T$ where $\mathbf{U}\mathbf{\Sigma}\mathbf{ V}^T$ is the truncated SVD of the gradient. Third, within this framework we identify a canonical setting for which we precisely quantify when SpecGD outperforms vanilla Euclidean GD. For a Gaussian mixture data model and both linear and bilinear models, we show that unlike GD, which prioritizes learning dominant principal components of the data first, SpecGD learns all principal components of the data at equal rates. We demonstrate how this translates to a growing gap in class balanced loss favoring SpecGD early in training and further show that the gap remains consistent even when the GD counterpart uses adaptive step-sizes via normalization. By extending the analysis to deep linear models, we show that depth amplifies these effects. We empirically verify our theoretical findings on a variety of imbalanced datasets. Our experiments compare practical variants of spectral methods, like Muon and Shampoo, against their Euclidean counterparts and Adam. The results validate our findings that these spectral optimizers achieve superior generalization by promoting a more balanced learning of the data's underlying components.

Deep Learning · Theory

Jingzhe Shi, Qinwei (Martin) Ma, Hongyi Liu, Hang Zhao, Jenq-Neng Hwang, Lei Li

Long Context Language Models have drawn great attention in the past few years. There has been work discussing the impact of long context on Language Model performance: some find that long irrelevant context could harm performance, while some experimentally summarize loss reduction by relevant long context as Scaling Laws. This calls for a more thorough understanding of how long context impacts Language Modeling. In this work, we (1) propose to use `Intrinsic Entropy' for explaining the impact of context length on language modeling; and (2) conduct experiments on natural language and synthetic data, validating our proposed theoretical assumptions and deductions. Our theoretical framework can provide practical insights such as establishing that training dataset size dictates an optimal context length and bounds context length scaling for certain cases. We hope our work may inspire new long context Language Models, as well as future work studying the physics of Language Models.

Deep Learning · Robustness

Jonathan Wenger, Beau Coker, Juraj Marusic, John Cunningham

Modern deep learning models generalize remarkably well in-distribution, despite being overparametrized and trained with little to no explicit regularization. Instead, current theory credits implicit regularization imposed by the choice of architecture, hyperparameters, and optimization procedure. However, deep neural networks can be surprisingly non-robust, resulting in overconfident predictions and poor out-of-distribution generalization. Bayesian deep learning addresses this via model averaging, but typically requires significant computational resources as well as carefully elicited priors to avoid overriding the benefits of implicit regularization. Instead, in this work, we propose to regularize variational neural networks solely by relying on the implicit bias of (stochastic) gradient descent. We theoretically characterize this inductive bias in overparametrized linear models as generalized variational inference and demonstrate the importance of the choice of parametrization. Empirically, our approach demonstrates strong in- and out-of-distribution performance without additional hyperparameter tuning and with minimal computational overhead.

Deep Learning · Robustness

Murong Ma, Ruofan Liu, Yun Lin, Zhiyong Huang, Jin Song Dong

Practical classification requires both high predictive accuracy and reliable confidence for human-AI collaboration. Given that a high-quality dataset is expensive and sometimes impossible, learning with noisy labels (LNL) is of great importance. The state-of-the-art works propose many denoising approaches by categorically correcting the label noise, i.e., change a label from one class to another. While effective in improving accuracy, they are less effective for learning reliable confidence. This happens especially when the number of classes grows, giving rise to more ambiguous samples. In addition, traditional approaches usually curate the training dataset (e.g., reweighting samples or correcting data labels) by intrinsically learning normalities from the noisy dataset. The curation performance can suffer when the noisy ratio is high enough to form a polluting normality. In this work, we propose a training-time data-curation framework, TrainRef, to uniformly address predictive accuracy and confidence calibration by (1) an extrinsic small set of reference samples $D_{{ref}}$ to avoid normality pollution and (2) curate labels into a class distribution instead of a categorical class to handle sample ambiguity. Our insights lie in that the extrinsic information allows us to select more precise clean samples even when $|D_{{ref}}|$ equals to the number of classes (i.e., one sample per class). Technically, we design (1) a reference augmentation technique to select clean samples from the dataset based on $D_{{ref}}$; and (2) a model-dataset co-evolving technique for a near-perfect embedding space, which is used to vote on the class-distribution for the label of a noisy sample. Extensive experiments on CIFAR-100, Animal10N, and WebVision demonstrate that TrainRef outperform the state-of-the-art denoising techniques (DISC, L2B, and DivideMix) and model calibration techniques (label smoothing, Mixup, and temperature scaling). Furthermore, our user study shows that the model confidence trained by TrainRef well aligns with human intuition. More demonstration, proof, and experimental details are available at https://sites.google.com/view/train-ref.