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Elucidating genetic backgrounds of myasthenia gravis in Japanese by genome-wide association studies and multi-omics analyses of thymoma

Nat Commun. 2026 Mar 12. doi: 10.1038/s41467-026-70376-5. Online ahead of print.

ABSTRACT

Myasthenia gravis (MG) is an autoimmune disorder characterized by impaired neuromuscular transmission and motor symptoms. Its genetic background remains unclear, particularly beyond specific subtypes reported in European populations. Here, we perform a genome-wide association study (GWAS) of 1,434 MG cases covering all disease subtypes and 42,913 controls of Japanese, which newly identify the TERT locus (odds ratio [OR] = 1.31, P = 1.7×10-10). Subtype-stratified GWASs show stronger signals for generalized MG (gMG; OR = 1.38, P = 1.6×10-12), anti AChR antibody-positive gMG (g-AChR-Ab(+)MG; OR= 1.49, P = 2.1×10-15), and thymoma-associated gMG (g-TAMG; OR = 1.92, P = 1.1×10-15). Fine-mapping of the major histocompatibility complex region reveal distinct associations of HLA-DRB1 with late onset gMG (g-LOMG) and HLA-A with early onset gMG (g-EOMG). The MG risk TERT lead variant rs2736099 is associated with poor treatment response, especially in g-AChR-Ab(+)MG and g-EOMG (P < 0.0042). The biobank-based phenome-wide association study identify pleiotropic effects on lung cancer, hematological traits, and telomere length. Single cell transcriptomics and immunohistochemistry identified immature lymphocyte-specific TERT expression in thymoma specimens. Full-length transcriptomics reveal allele-specific decreasing effect of rs2736099-A on TERT expression. Our study unveils genetics of MG distinctly across disease subtypes, and involvement of TERT in its pathogenesis.

PMID:41820352 | DOI:10.1038/s41467-026-70376-5

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MAPK14/SLC7A11/GPX4 axis dysregulation drives podocyte ferroptosis via mediating glycerophospholipid metabolism

Cell Death Discovery, Published online: 11 March 2026; doi:10.1038/s41420-026-02990-7

MAPK14/SLC7A11/GPX4 axis dysregulation drives podocyte ferroptosis via mediating glycerophospholipid metabolism
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A Robust Incomplete Multimodal Low-Rank Adaptation Approach for Emotion Recognition

arXiv:2507.11202v1 Announce Type: cross Abstract: Multimodal Emotion Recognition (MER) often encounters incomplete multimodality in practical applications due to sensor failures or privacy protection requirements. While existing methods attempt to address various incomplete multimodal scenarios by balancing the training of each modality combination through additional gradients, these approaches face a critical limitation: training gradients from different modality combinations conflict with each other, ultimately degrading the performance of the final prediction model. In this paper, we propose a unimodal decoupled dynamic low-rank adaptation method based on modality combinations, named MCULoRA, which is a novel framework for the parameter-efficient training of incomplete multimodal learning models. MCULoRA consists of two key modules, modality combination aware low-rank adaptation (MCLA) and dynamic parameter fine-tuning (DPFT). The MCLA module effectively decouples the shared information from the distinct characteristics of individual modality combinations. The DPFT module adjusts the training ratio of modality combinations based on the separability of each modality's representation space, optimizing the learning efficiency across different modality combinations. Our extensive experimental evaluation in multiple benchmark datasets demonstrates that MCULoRA substantially outperforms previous incomplete multimodal learning approaches in downstream task accuracy.
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Stabilizing Reinforcement Learning for Diffusion Language Models

arXiv:2603.06743v1 Announce Type: cross Abstract: Group Relative Policy Optimization (GRPO) is highly effective for post-training autoregressive (AR) language models, yet its direct application to diffusion large language models (dLLMs) often triggers reward collapse. We identify two sources of incompatibility. First, GRPO relies on importance ratios defined by sequence probabilities, which are intractable in dLLMs and must be estimated (e.g., via ELBO-based or mean-field likelihood proxies), yielding inherently noisy ratios. Second, standard GRPO's formulation is not designed for estimated ratios: its conditional clipping can be anomalously bypassed by model-agnostic estimation noise, producing gradient spikes, while its fixed group-size normalization amplifies gradient-magnitude fluctuations under high-variance ratio estimates. We show these effects form a self-reinforcing instability loop that drives policy drift and further increases ratio variance. To break this loop, we propose StableDRL, a reformulation of GRPO tailored for dLLMs that uses (i) unconditional clipping to suppress outlier-induced spikes and (ii) self-normalization to constrain updates within the convex hull of per-sample gradients. We further extend StableDRL to block-wise diffusion models via a staircase attention mechanism.
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Not All Candidates are Created Equal: A Heterogeneity-Aware Approach to Pre-ranking in Recommender Systems

arXiv:2603.03770v1 Announce Type: cross Abstract: Most large-scale recommender systems follow a multi-stage cascade of retrieval, pre-ranking, ranking, and re-ranking. A key challenge at the pre-ranking stage arises from the heterogeneity of training instances sampled from coarse-grained retrieval results, fine-grained ranking signals, and exposure feedback. Our analysis reveals that prevailing pre-ranking methods, which indiscriminately mix heterogeneous samples, suffer from gradient conflicts: hard samples dominate training while easy ones remain underutilized, leading to suboptimal performance. We further show that the common practice of uniformly scaling model complexity across all samples is inefficient, as it overspends computation on easy cases and slows training without proportional gains. To address these limitations, this paper presents Heterogeneity-Aware Adaptive Pre-ranking (HAP), a unified framework that mitigates gradient conflicts through conflict-sensitive sampling coupled with tailored loss design, while adaptively allocating computational budgets across candidates. Specifically, HAP disentangles easy and hard samples, directing each subset along dedicated optimization paths. Building on this separation, it first applies lightweight models to all candidates for efficient coverage, and further engages stronger models on the hard ones, maintaining accuracy while reducing cost. This approach not only improves pre-ranking effectiveness but also provides a practical perspective on scaling strategies in industrial recommender systems. HAP has been deployed in the Toutiao production system for 9 months, yielding up to 0.4% improvement in user app usage duration and 0.05% in active days, without additional computational cost. We also release a large-scale industrial hybrid-sample dataset to enable the systematic study of source-driven candidate heterogeneity in pre-ranking.
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Relational In-Context Learning via Synthetic Pre-training with Structural Prior

arXiv:2603.03805v1 Announce Type: cross Abstract: Relational Databases (RDBs) are the backbone of modern business, yet they lack foundation models comparable to those in text or vision. A key obstacle is that high-quality RDBs are private, scarce and structurally heterogeneous, making internet-scale pre-training infeasible. To overcome this data scarcity, We introduce $\textbf{RDB-PFN}$, the first relational foundation model trained purely via $\textbf{synthetic data}$. Inspired by Prior-Data Fitted Networks (PFNs) where synthetic data generated from Structural Causal Models (SCMs) enables reasoning on single tables, we design a $\textbf{Relational Prior Generator}$ to create an infinite stream of diverse RDBs from scratch. Pre-training on $\textbf{over 2 million}$ synthetic single-table and relational tasks, RDB-PFN learns to adapt to any new database instantly via genuine $\textbf{in-context learning}$. Experiments verify RDB-PFN achieves strong few-shot performance on 19 real-world relational prediction tasks, outperforming graph-based and single-table foundation-model baselines (given the same DFS-linearized inputs), while using a lightweight architecture and fast inference. The code is available at https://github.com/MuLabPKU/RDBPFN
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Boosting Meta-Learning for Few-Shot Text Classification via Label-guided Distance Scaling

arXiv:2603.02267v1 Announce Type: cross Abstract: Few-shot text classification aims to recognize unseen classes with limited labeled text samples. Existing approaches focus on boosting meta-learners by developing complex algorithms in the training stage. However, the labeled samples are randomly selected during the testing stage, so they may not provide effective supervision signals, leading to misclassification. To address this issue, we propose a \textbf{L}abel-guided \textbf{D}istance \textbf{S}caling (LDS) strategy. The core of our method is exploiting label semantics as supervision signals in both the training and testing stages. Specifically, in the training stage, we design a label-guided loss to inject label semantic information, pulling closer the sample representations and corresponding label representations. In the testing stage, we propose a Label-guided Scaler which scales sample representations with label semantics to provide additional supervision signals. Thus, even if labeled sample representations are far from class centers, our Label-guided Scaler pulls them closer to their class centers, thereby mitigating the misclassification. We combine two common meta-learners to verify the effectiveness of the method. Extensive experimental results demonstrate that our approach significantly outperforms state-of-the-art models. All datasets and codes are available at https://anonymous.4open.science/r/Label-guided-Text-Classification.
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Adaptive Social Learning via Mode Policy Optimization for Language Agents

arXiv:2505.02156v5 Announce Type: replace-cross Abstract: Effective social intelligence simulation requires language agents to dynamically adjust reasoning depth, a capability notably absent in current studies. Existing methods either lack explicit reasoning or employ lengthy Chain-of-Thought reasoning uniformly across all scenarios, resulting in excessive token usage and inflexible social behaviors in tasks such as negotiation or collaboration. To address this, we propose an $\textbf{A}$daptive $\textbf{S}$ocial $\textbf{L}$earning ($\textbf{ASL}$) framework in this paper, aiming to improve the adaptive reasoning ability of language agents in dynamic social interactions. To this end, we first identify the hierarchical reasoning modes under such context, ranging from intuitive response to deep deliberation based on the cognitive control theory. We then develop the $\textbf{A}$daptive $\textbf{M}$ode $\textbf{P}$olicy $\textbf{O}$ptimization ($\textbf{AMPO}$) algorithm to learn the context-aware mode adaptation and reasoning. Our framework advances existing research in three key aspects: (1) Multi-granular reasoning mode design, (2) Context-aware mode switching in rich social interaction, and (3) Token-efficient reasoning with depth adaptation. Extensive experiments on the benchmark social intelligence environment verify that ASL achieves 15.6% higher task performance than GPT-4o. Notably, our AMPO outperforms GRPO by 7.0% with 32.8% shorter thinking chains, demonstrating the advantages of our AMPO and the learned adaptive reasoning ability over GRPO's solution.
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Mitigating the Safety-utility Trade-off in LLM Alignment via Adaptive Safe Context Learning

arXiv:2602.13562v1 Announce Type: cross Abstract: While reasoning models have achieved remarkable success in complex reasoning tasks, their increasing power necessitates stringent safety measures. For safety alignment, the core challenge lies in the inherent trade-off between safety and utility. However, prevailing alignment strategies typically construct CoT training data with explicit safety rules via context distillation. This approach inadvertently limits reasoning capabilities by creating a rigid association between rule memorization and refusal. To mitigate the safety-utility trade-off, we propose the Adaptive Safe Context Learning (ASCL) framework to improve the reasoning given proper context. ASCL formulates safety alignment as a multi-turn tool-use process, empowering the model to autonomously decide when to consult safety rules and how to generate the ongoing reasoning. Furthermore, to counteract the preference for rule consultation during RL, we introduce Inverse Frequency Policy Optimization (IFPO) to rebalance advantage estimates. By decoupling rule retrieval and subsequent reasoning, our method achieves higher overall performance compared to baselines.
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