In medicine, treatments often influence multiple, interdependent outcomes, such as primary endpoints, complications, adverse events, or other secondary endpoints. Hence, to make optimal treatment decisions, clinicians are interested in learning the distribution of multi-dimensional treatment outcomes. However, the vast majority of machine learning methods for predicting treatment effects focus on single-outcome settings, despite the fact that medical data often include multiple, interdependent outcomes. To address this limitation, we propose a novel diffusion-based method called DIME to learn the joint distribution of multiple outcomes of medical treatments. We addresses three challenges relevant in medical practice: (i)it is tailored to learn the joint interventional distribution of multiple medical outcomes, which enables reliable decision-making with uncertainty quantification rather than relying solely on point estimates; (ii)it explicitly captures the dependence structure between outcomes; (iii)it can handle outcomes of mixed type, including binary, categorical, and continuous variables. In DIME, we take into account the fundamental problem of causal inference through causal masking. For training, our method decomposes the joint distribution into a series of conditional distributions with a customized conditional masking to account for the dependence structure across outcomes. For inference, our method auto-regressively generates predictions. This allows our method to move beyond point estimates of causal quantities and thus learn the joint interventional distribution. To the best of our knowledge, DIME is the first neural method tailored to learn the joint, multi-outcome distribution of medical treatments. Across various experiments, we demonstrate that our method effectively learns the joint distribution and captures shared information among multiple outcomes.

Rational speakers are supposed to know what they know and what they do not know, and to generate expressions matching the strength of evidence. In contrast, it is still a challenge for current large language models to generate corresponding utterances based on the assessment of facts and confidence in an uncertain real-world environment. While it has recently become popular to estimate and calibrate confidence of LLMs with verbalized uncertainty, what is lacking is a careful examination of the linguistic knowledge of uncertainty encoded in the latent space of LLMs. In this paper, we draw on typological frameworks of epistemic expressions to evaluate LLMs' knowledge of epistemic modality, using controlled stories. Our experiments show that the performance of LLMs in generating epistemic expressions is limited and not robust, and hence the expressions of uncertainty generated by LLMs are not always reliable. To build uncertainty-aware LLMs, it is necessary to enrich semantic knowledge of epistemic modality in LLMs.

Multimodal sentiment analysis (MSA) aims to understand human sentiment through multimodal data. In real-world scenarios, practical factors often lead to uncertain modality missingness. Existing methods for handling modality missingness are based on data reconstruction or common subspace projections. However, these methods neglect the confidence in multimodal combinations and impose constraints on intra-class representation, hindering the capture of modality-specific information and resulting in suboptimal performance. To address these challenges, we propose a Confidence-Aware Self-Distillation (CASD) strategy that effectively incorporates multimodal probabilistic embeddings via a mixture of Student's $t$-distributions, enhancing its robustness by incorporating confidence and accommodating heavy-tailed properties. This strategy estimates joint distributions with uncertainty scores and reduces uncertainty in the student network by consistency distillation. Furthermore, we introduce a reparameterization representation module that facilitates CASD in robust multimodal learning by sampling embeddings from the joint distribution for the prediction module to calculate the task loss. As a result, the directional constraint from the loss minimization is alleviated by the sampled representation. Experimental results on three benchmark datasets demonstrate that our method achieves state-of-the-art performance.

Understanding the interaction between different drugs (drug-drug interaction or DDI) is critical for ensuring patient safety and optimizing therapeutic outcomes. Existing DDI datasets primarily focus on textual information, overlooking multimodal data that reflect complex drug mechanisms. In this paper, we (1) introduce MUDI, a large-scale Multimodal biomedical dataset for Understanding pharmacodynamic Drug-drug Interactions, and (2) benchmark learning methods to study it. In brief, MUDI provides a comprehensive multimodal representation of drugs by combining pharmacological text, chemical formulas, molecular structure graphs, and images across 310,532 annotated drug pairs labeled as Synergism, Antagonism, or New Effect. Crucially, to effectively evaluate machine-learning based generalization, MUDI consists of unseen drug pairs in the test set. We evaluate benchmark models using both late fusion voting and intermediate fusion strategies. All data, annotations, evaluation scripts, and baselines are released under an open research license.

Recent studies have shown that integrating multimodal data fusion techniques for imaging and genetic features is beneficial for the etiological analysis and predictive diagnosis of Alzheimer's disease (AD). However, there are several critical flaws in current deep learning methods. Firstly, there has been insufficient discussion and exploration regarding the selection and encoding of genetic information. Secondly, due to the significantly superior classification value of AD imaging features compared to genetic features, many studies in multimodal fusion emphasize the strengths of imaging features, actively mitigating the influence of weaker features, thereby diminishing the learning of the unique value of genetic features. To address this issue, this study proposes the dynamic multimodal role-swapping network (GenDMR). In GenDMR, we develop a novel approach to encode the spatial organization of single nucleotide polymorphisms (SNPs), enhancing the representation of their genomic context. Additionally, to adaptively quantify the disease risk of SNPs and brain region, we propose a multi-instance attention module to enhance model interpretability. Furthermore, we introduce a dominant modality selection module and a contrastive self-distillation module, combining them to achieve a dynamic teacher-student role exchange mechanism based on dominant and auxiliary modalities for bidirectional co-updating of different modal data. Finally, GenDMR achieves state-of-the-art performance on the ADNI public dataset and visualizes attention to different SNPs, focusing on confirming 12 potential high-risk genes related to AD, including the most classic APOE and recently highlighted significant risk genes. This demonstrates GenDMR's interpretable analytical capability in exploring AD genetic features, providing new insights and perspectives for the development of multimodal data fusion techniques.

Abstract--Deep learning approaches process data in a layer-by-layer way with intermediate (or latent) features. We aim at designing a general solution to optimize the latent manifolds to improve the performance on classification, segmentation, completion and/or reconstruction through probabilistic models. This paper proposes a variational inference model which leads to a clustered embedding. We introduce additional variables in the latent space, called nebula anchors, that guide the latent variables to form clusters during training. T o prevent the anchors from clustering among themselves, we employ the variational constraint that enforces the latent features within an anchor to form a Gaussian distribution, resulting in a generative model we refer as Nebula Variational Coding (NVC). Since each latent feature can be labeled with the closest anchor, we also propose to apply metric learning in a self-supervised way to make the separation between clusters more explicit. As a consequence, the latent variables of our variational coder form clusters which adapt to the generated semantic of the training data, e.g. the categorical labels of each sample. We demonstrate experimentally that it can be used within different architectures designed to solve different problems including text sequence, images, 3D point clouds and volumetric data, validating the advantage of our proposed method. They rely on compressing the input to its latent representations while identifying its discriminative information. On the other hand, solutions in image processing [6], [7], [8], [9] and 3D understanding [8], [10], [11], [12], [13], [14] aim at preserving the information from the input data as part of the output, formulating additional skip connection [8], [9], [10], [12] and fusion [11] between them. Although there are traditional methods that can reduce the dimensionality of the input in an unsupervised way, such as principal component analysis (PCA) [15] and independent component analysis (ICA) [16], as well as in a supervised way, e.g.

--This paper introduces an innovative error feedback framework designed to mitigate quantization noise in distributed graph filtering, where communications are constrained to quantized messages. It comes from error spectrum shaping techniques from state-space digital filters, and therefore establishes connections between quantized filtering processes over different domains. In contrast to existing error compensation methods, our framework quantitatively feeds back the quantization noise for exact compensation. We examine the framework under three key scenarios: (i) deterministic graph filtering, (ii) graph filtering over random graphs, and (iii) graph filtering with random node-asynchronous updates. Rigorous theoretical analysis demonstrates that the proposed framework significantly reduces the effect of quantization noise, and we provide closed-form solutions for the optimal error feedback coefficients. Moreover, this quantitative error feedback mechanism can be seamlessly integrated into communication-efficient decentralized optimization frameworks, enabling lower error floors. Numerical experiments validate the theoretical results, consistently showing that our method outperforms conventional quantization strategies in terms of both accuracy and robustness. Index T erms --Graph signal processing, distributed graph filtering, quantization, error feedback, stochastic linear system, decentralized optimization. HE theory of graph filtering has seen substantial progress in recent years [1]-[4], emerging as a cornerstone of modern signal processing and machine learning on networked data.

Understanding the various properties of glycans with machine learning has shown some preliminary promise. However, previous methods mainly focused on modeling the backbone structure of glycans as graphs of monosaccharides (i.e., sugar units), while they neglected the atomic structures underlying each monosaccharide, which are actually important indicators of glycan properties. We fill this blank by introducing the GlycanAA model for All-Atom-wise Glycan modeling. GlycanAA models a glycan as a heterogeneous graph with monosaccharide nodes representing its global backbone structure and atom nodes representing its local atomic-level structures. Based on such a graph, GlycanAA performs hierarchical message passing to capture from local atomic-level interactions to global monosaccharide-level interactions. To further enhance model capability, we pre-train GlycanAA on a high-quality unlabeled glycan dataset, deriving the PreGlycanAA model. We design a multi-scale mask prediction algorithm to endow the model about different levels of dependencies in a glycan. Extensive benchmark results show the superiority of GlycanAA over existing glycan encoders and verify the further improvements achieved by PreGlycanAA. We maintain all resources at https://github.com/kasawa1234/GlycanAA

Decentralized training of large language models offers the opportunity to pool computational resources across geographically distributed participants but faces significant network communication bottlenecks, particularly in pipeline-parallel settings. While pipeline parallelism partitions model layers across devices to handle large-scale models, it necessitates frequent communication of intermediate activations, creating challenges when network bandwidth is limited. Existing activation compression methods, such as AQ-SGD, mitigate quantization-induced errors through error compensation but impose prohibitive memory overhead by requiring storage of previous activations. To address these issues, we introduce TAH-Quant (Tile-wise Adaptive Hadamard Quantization), a novel activation quantization framework designed specifically for pipeline parallelism. Our approach integrates fine-grained tile-wise quantization for precise control, entropy-guided token-level adaptive bit allocation for optimal bit usage, and a Hadamard-based transform with pivot element swapping to effectively suppress quantization outliers. We further provide a theoretical analysis, proving that pipeline parallel training equipped with TAH-Quant maintains a convergence rate of $\mathcal{O}(1/\sqrt{T})$, matching that of vanilla stochastic gradient descent. Extensive experiments on diverse LLM tasks demonstrate that TAH-Quant achieves aggressive activation quantization (3-4 bits) ratio, which provides up to 4.3$\times$ end-to-end speedup without compromising training convergence, matches state-of-the-art methods, incurs no extra memory overhead, and generalizes well across different training scenarios.

It is well known that traditional drug discovery is costly, time-consuming, and with high failure rates [1]. To streamline the process of drug discovery and mitigate resource-intensive laboratory work, significant research has been dedicated to the development of computational methods. Existing literature provides some comprehensive reviews on deep learning approaches in drug discovery [2, 3, 4, 5]. In this review, we focus on the development and applications of Graph Neural Networks (GNNs) on three related areas of computational drug development, namely, Molecule Generation, Molecular Property Prediction, and Drug-Drug Interaction Prediction, which not only receive increasing attention but also show promising results. We will summarize some most recent developments in these research areas and focus on computational advances published since 2021.