Cao Xiao

Zifeng Wang, Brandon Theodorou, Tianfan Fu et al.

Clinical trials are conducted to test the effectiveness and safety of potential drugs in humans for regulatory approval. Machine learning (ML) has recently emerged as a new tool to assist in clinical trials. Despite this progress, there have been few efforts to document and benchmark ML4Trial algorithms available to the ML research community. Additionally, the accessibility to clinical trial-related datasets is limited, and there is a lack of well-defined clinical tasks to facilitate the development of new algorithms. To fill this gap, we have developed PyTrial that provides benchmarks and open-source implementations of a series of ML algorithms for clinical trial design and operations. In this paper, we thoroughly investigate 34 ML algorithms for clinical trials across 6 different tasks, including patient outcome prediction, trial site selection, trial outcome prediction, patient-trial matching, trial similarity search, and synthetic data generation. We have also collected and prepared 23 ML-ready datasets as well as their working examples in Jupyter Notebooks for quick implementation and testing. PyTrial defines each task through a simple four-step process: data loading, model specification, model training, and model evaluation, all achievable with just a few lines of code. Furthermore, our modular API architecture empowers practitioners to expand the framework to incorporate new algorithms and tasks effortlessly. The code is available at https://github.com/RyanWangZf/PyTrial.

Brandon Theodorou, Cao Xiao, Jimeng Sun

Synthetic electronic health records (EHRs) that are both realistic and preserve privacy can serve as an alternative to real EHRs for machine learning (ML) modeling and statistical analysis. However, generating high-fidelity and granular electronic health record (EHR) data in its original, highly-dimensional form poses challenges for existing methods due to the complexities inherent in high-dimensional data. In this paper, we propose Hierarchical Autoregressive Language mOdel (HALO) for generating longitudinal high-dimensional EHR, which preserve the statistical properties of real EHR and can be used to train accurate ML models without privacy concerns. Our HALO method, designed as a hierarchical autoregressive model, generates a probability density function of medical codes, clinical visits, and patient records, allowing for the generation of realistic EHR data in its original, unaggregated form without the need for variable selection or aggregation. Additionally, our model also produces high-quality continuous variables in a longitudinal and probabilistic manner. We conducted extensive experiments and demonstrate that HALO can generate high-fidelity EHR data with high-dimensional disease code probabilities (d > 10,000), disease co-occurrence probabilities within visits (d > 1,000,000), and conditional probabilities across consecutive visits (d > 5,000,000) and achieve above 0.9 R2 correlation in comparison to real EHR data. This performance then enables downstream ML models trained on its synthetic data to achieve comparable accuracy to models trained on real data (0.938 AUROC with HALO data vs. 0.943 with real data). Finally, using a combination of real and synthetic data enhances the accuracy of ML models beyond that achieved by using only real EHR data.

Zhen Lin, Shubhendu Trivedi, Cao Xiao et al.

Many real-world multi-label prediction problems involve set-valued predictions that must satisfy specific requirements dictated by downstream usage. We focus on a typical scenario where such requirements, separately encoding $\textit{value}$ and $\textit{cost}$, compete with each other. For instance, a hospital might expect a smart diagnosis system to capture as many severe, often co-morbid, diseases as possible (the value), while maintaining strict control over incorrect predictions (the cost). We present a general pipeline, dubbed as FavMac, to maximize the value while controlling the cost in such scenarios. FavMac can be combined with almost any multi-label classifier, affording distribution-free theoretical guarantees on cost control. Moreover, unlike prior works, it can handle real-world large-scale applications via a carefully designed online update mechanism, which is of independent interest. Our methodological and theoretical contributions are supported by experiments on several healthcare tasks and synthetic datasets - FavMac furnishes higher value compared with several variants and baselines while maintaining strict cost control. Our code is available at https://github.com/zlin7/FavMac

Pengcheng Jiang, Cao Xiao, Tianfan Fu et al.

Molecular representation learning is vital for various downstream applications, including the analysis and prediction of molecular properties and side effects. While Graph Neural Networks (GNNs) have been a popular framework for modeling molecular data, they often struggle to capture the full complexity of molecular representations. In this paper, we introduce a novel method called GODE, which accounts for the dual-level structure inherent in molecules. Molecules possess an intrinsic graph structure and simultaneously function as nodes within a broader molecular knowledge graph. GODE integrates individual molecular graph representations with multi-domain biochemical data from knowledge graphs. By pre-training two GNNs on different graph structures and employing contrastive learning, GODE effectively fuses molecular structures with their corresponding knowledge graph substructures. This fusion yields a more robust and informative representation, enhancing molecular property predictions by leveraging both chemical and biological information. When fine-tuned across 11 chemical property tasks, our model significantly outperforms existing benchmarks, achieving an average ROC-AUC improvement of 12.7% for classification tasks and an average RMSE/MAE improvement of 34.4% for regression tasks. Notably, GODE surpasses the current leading model in property prediction, with advancements of 2.2% in classification and 7.2% in regression tasks.

Rakshith S Srinivasa, Cheng Qian, Brandon Theodorou et al.

The ongoing pandemic has highlighted the importance of reliable and efficient clinical trials in healthcare. Trial sites, where the trials are conducted, are chosen mainly based on feasibility in terms of medical expertise and access to a large group of patients. More recently, the issue of diversity and inclusion in clinical trials is gaining importance. Different patient groups may experience the effects of a medical drug/ treatment differently and hence need to be included in the clinical trials. These groups could be based on ethnicity, co-morbidities, age, or economic factors. Thus, designing a method for trial site selection that accounts for both feasibility and diversity is a crucial and urgent goal. In this paper, we formulate this problem as a ranking problem with fairness constraints. Using principles of fairness in machine learning, we learn a model that maps a clinical trial description to a ranked list of potential trial sites. Unlike existing fairness frameworks, the group membership of each trial site is non-binary: each trial site may have access to patients from multiple groups. We propose fairness criteria based on demographic parity to address such a multi-group membership scenario. We test our method on 480 real-world clinical trials and show that our model results in a list of potential trial sites that provides access to a diverse set of patients while also ensuing a high number of enrolled patients.

Zifeng Wang, Cao Xiao, Jimeng Sun

Clinical trials are essential to drug development but time-consuming, costly, and prone to failure. Accurate trial outcome prediction based on historical trial data promises better trial investment decisions and more trial success. Existing trial outcome prediction models were not designed to model the relations among similar trials, capture the progression of features and designs of similar trials, or address the skewness of trial data which causes inferior performance for less common trials. To fill the gap and provide accurate trial outcome prediction, we propose Sequential Predictive mOdeling of clinical Trial outcome (SPOT) that first identifies trial topics to cluster the multi-sourced trial data into relevant trial topics. It then generates trial embeddings and organizes them by topic and time to create clinical trial sequences. With the consideration of each trial sequence as a task, it uses a meta-learning strategy to achieve a point where the model can rapidly adapt to new tasks with minimal updates. In particular, the topic discovery module enables a deeper understanding of the underlying structure of the data, while sequential learning captures the evolution of trial designs and outcomes. This results in predictions that are not only more accurate but also more interpretable, taking into account the temporal patterns and unique characteristics of each trial topic. We demonstrate that SPOT wins over the prior methods by a significant margin on trial outcome benchmark data: with a 21.5\% lift on phase I, an 8.9\% lift on phase II, and a 5.5\% lift on phase III trials in the metric of the area under precision-recall curve (PR-AUC).

Brandon Theodorou, Cao Xiao, Jimeng Sun

Clinical trials are critical for drug development but often suffer from expensive and inefficient patient recruitment. In recent years, machine learning models have been proposed for speeding up patient recruitment via automatically matching patients with clinical trials based on longitudinal patient electronic health records (EHR) data and eligibility criteria of clinical trials. However, they either depend on trial-specific expert rules that cannot expand to other trials or perform matching at a very general level with a black-box model where the lack of interpretability makes the model results difficult to be adopted. To provide accurate and interpretable patient trial matching, we introduce a personalized dynamic tree-based memory network model named TREEMENT. It utilizes hierarchical clinical ontologies to expand the personalized patient representation learned from sequential EHR data, and then uses an attentional beam-search query learned from eligibility criteria embedding to offer a granular level of alignment for improved performance and interpretability. We evaluated TREEMENT against existing models on real-world datasets and demonstrated that TREEMENT outperforms the best baseline by 7% in terms of error reduction in criteria-level matching and achieves state-of-the-art results in its trial-level matching ability. Furthermore, we also show TREEMENT can offer good interpretability to make the model results easier for adoption.

Zhenbang Wu, Cao Xiao, Lucas M Glass et al.

Given a deep learning model trained on data from a source site, how to deploy the model to a target hospital automatically? How to accommodate heterogeneous medical coding systems across different hospitals? Standard approaches rely on existing medical code mapping tools, which have significant practical limitations. To tackle this problem, we propose AutoMap to automatically map the medical codes across different EHR systems in a coarse-to-fine manner: (1) Ontology-level Alignment: We leverage the ontology structure to learn a coarse alignment between the source and target medical coding systems; (2) Code-level Refinement: We refine the alignment at a fine-grained code level for the downstream tasks using a teacher-student framework. We evaluate AutoMap using several deep learning models with two real-world EHR datasets: eICU and MIMIC-III. Results show that AutoMap achieves relative improvements up to 3.9% (AUC-ROC) and 8.7% (AUC-PR) for mortality prediction, and up to 4.7% (AUC-ROC) and 3.7% (F1) for length-of-stay estimation. Further, we show that AutoMap can provide accurate mapping across coding systems. Lastly, we demonstrate that AutoMap can adapt to the two challenging scenarios: (1) mapping between completely different coding systems and (2) between completely different hospitals.

Zhepeng Wang, Runxue Bao, Yawen Wu et al.

Pretrained large language models (LLMs) have revolutionized natural language processing (NLP) tasks such as summarization, question answering, and translation. However, LLMs pose significant security risks due to their tendency to memorize training data, leading to potential privacy breaches and copyright infringement. Accurate measurement of this memorization is essential to evaluate and mitigate these potential risks. However, previous attempts to characterize memorization are constrained by either using prefixes only or by prepending a constant soft prompt to the prefixes, which cannot react to changes in input. To address this challenge, we propose a novel method for estimating LLM memorization using dynamic, prefix-dependent soft prompts. Our approach involves training a transformer-based generator to produce soft prompts that adapt to changes in input, thereby enabling more accurate extraction of memorized data. Our method not only addresses the limitations of previous methods but also demonstrates superior performance in diverse experimental settings compared to state-of-the-art techniques. In particular, our method can achieve the maximum relative improvement of 112.75% and 32.26% over the vanilla baseline in terms of discoverable memorization rate for the text generation task and code generation task respectively.

Junyu Luo, Cao Xiao, Fenglong Ma

The prevalent use of large language models (LLMs) in various domains has drawn attention to the issue of "hallucination," which refers to instances where LLMs generate factually inaccurate or ungrounded information. Existing techniques for hallucination detection in language assistants rely on intricate fuzzy, specific free-language-based chain of thought (CoT) techniques or parameter-based methods that suffer from interpretability issues. Additionally, the methods that identify hallucinations post-generation could not prevent their occurrence and suffer from inconsistent performance due to the influence of the instruction format and model style. In this paper, we introduce a novel pre-detection self-evaluation technique, referred to as SELF-FAMILIARITY, which focuses on evaluating the model's familiarity with the concepts present in the input instruction and withholding the generation of response in case of unfamiliar concepts. This approach emulates the human ability to refrain from responding to unfamiliar topics, thus reducing hallucinations. We validate SELF-FAMILIARITY across four different large language models, demonstrating consistently superior performance compared to existing techniques. Our findings propose a significant shift towards preemptive strategies for hallucination mitigation in LLM assistants, promising improvements in reliability, applicability, and interpretability.

Yue Zhao, Zhi Qiao, Cao Xiao et al.

Despite the explosion of interest in healthcare AI research, the reproducibility and benchmarking of those research works are often limited due to the lack of standard benchmark datasets and diverse evaluation metrics. To address this reproducibility challenge, we develop PyHealth, an open-source Python toolbox for developing various predictive models on healthcare data. PyHealth consists of data preprocessing module, predictive modeling module, and evaluation module. The target users of PyHealth are both computer science researchers and healthcare data scientists. With PyHealth, they can conduct complex machine learning pipelines on healthcare datasets with fewer than ten lines of code. The data preprocessing module enables the transformation of complex healthcare datasets such as longitudinal electronic health records, medical images, continuous signals (e.g., electrocardiogram), and clinical notes into machine learning friendly formats. The predictive modeling module provides more than 30 machine learning models, including established ensemble trees and deep neural network-based approaches, via a unified but extendable API designed for both researchers and practitioners. The evaluation module provides various evaluation strategies (e.g., cross-validation and train-validation-test split) and predictive model metrics. With robustness and scalability in mind, best practices such as unit testing, continuous integration, code coverage, and interactive examples are introduced in the library's development. PyHealth can be installed through the Python Package Index (PyPI) or https://github.com/yzhao062/PyHealth .

Tianfan Fu, Cao Xiao, Xinhao Li et al.

Molecule optimization is a fundamental task for accelerating drug discovery, with the goal of generating new valid molecules that maximize multiple drug properties while maintaining similarity to the input molecule. Existing generative models and reinforcement learning approaches made initial success, but still face difficulties in simultaneously optimizing multiple drug properties. To address such challenges, we propose the MultI-constraint MOlecule SAmpling (MIMOSA) approach, a sampling framework to use input molecule as an initial guess and sample molecules from the target distribution. MIMOSA first pretrains two property agnostic graph neural networks (GNNs) for molecule topology and substructure-type prediction, where a substructure can be either atom or single ring. For each iteration, MIMOSA uses the GNNs' prediction and employs three basic substructure operations (add, replace, delete) to generate new molecules and associated weights. The weights can encode multiple constraints including similarity and drug property constraints, upon which we select promising molecules for next iteration. MIMOSA enables flexible encoding of multiple property- and similarity-constraints and can efficiently generate new molecules that satisfy various property constraints and achieved up to 49.6% relative improvement over the best baseline in terms of success rate. The code repository (including readme file, data preprocessing and model construction, evaluation) is available https://github.com/futianfan/MIMOSA.

Yue Zhao, Xiyang Hu, Cheng Cheng et al.

Outlier detection (OD) is a key machine learning (ML) task for identifying abnormal objects from general samples with numerous high-stake applications including fraud detection and intrusion detection. Due to the lack of ground truth labels, practitioners often have to build a large number of unsupervised, heterogeneous models (i.e., different algorithms with varying hyperparameters) for further combination and analysis, rather than relying on a single model. How to accelerate the training and scoring on new-coming samples by outlyingness (referred as prediction throughout the paper) with a large number of unsupervised, heterogeneous OD models? In this study, we propose a modular acceleration system, called SUOD, to address it. The proposed system focuses on three complementary acceleration aspects (data reduction for high-dimensional data, approximation for costly models, and taskload imbalance optimization for distributed environment), while maintaining performance accuracy. Extensive experiments on more than 20 benchmark datasets demonstrate SUOD's effectiveness in heterogeneous OD acceleration, along with a real-world deployment case on fraudulent claim analysis at IQVIA, a leading healthcare firm. We open-source SUOD for reproducibility and accessibility.

Rahul Duggal, Scott Freitas, Cao Xiao et al.

In recent years, significant attention has been devoted towards integrating deep learning technologies in the healthcare domain. However, to safely and practically deploy deep learning models for home health monitoring, two significant challenges must be addressed: the models should be (1) robust against noise; and (2) compact and energy-efficient. We propose REST, a new method that simultaneously tackles both issues via 1) adversarial training and controlling the Lipschitz constant of the neural network through spectral regularization while 2) enabling neural network compression through sparsity regularization. We demonstrate that REST produces highly-robust and efficient models that substantially outperform the original full-sized models in the presence of noise. For the sleep staging task over single-channel electroencephalogram (EEG), the REST model achieves a macro-F1 score of 0.67 vs. 0.39 achieved by a state-of-the-art model in the presence of Gaussian noise while obtaining 19x parameter reduction and 15x MFLOPS reduction on two large, real-world EEG datasets. By deploying these models to an Android application on a smartphone, we quantitatively observe that REST allows models to achieve up to 17x energy reduction and 9x faster inference. We open-source the code repository with this paper: https://github.com/duggalrahul/REST.

Xiyao Wang, Jiuhai Chen, Zhaoyang Wang et al.

Large vision-language models (LVLMs) have achieved impressive results in visual question-answering and reasoning tasks through vision instruction tuning on specific datasets. However, there remains significant room for improvement in aligning visual and language modalities. Existing methods often depend on external models or data, leading to uncontrollable and unstable alignment results. In this paper, we propose SIMA, a self-improvement framework that enhances visual and language modality alignment without external dependencies. SIMA leverages existing vision instruction tuning datasets to self-generate responses, incorporating an in-context self-critic mechanism that constructs preference pairs for tuning. Crucially, our approach allows LVLMs to act as critics by designing effective critic prompts, eliminating the need for additional fine-tuning with external instruction data. We introduce three novel visual metrics within the self-critic process to guide judgment, significantly improving the accuracy of self-critic. Through extensive experiments across 14 hallucination and comprehensive benchmarks, we demonstrate that SIMA significantly improves LVLM's performance and outperforms previous approaches, achieving superior modality alignment.

Pengcheng Jiang, Cao Xiao, Zifeng Wang et al.

The advent of large language models (LLMs) has significantly advanced natural language processing tasks like text summarization. However, their large size and computational demands, coupled with privacy concerns in data transmission, limit their use in resource-constrained and privacy-centric settings. To overcome this, we introduce TriSum, a framework for distilling LLMs' text summarization abilities into a compact, local model. Initially, LLMs extract a set of aspect-triple rationales and summaries, which are refined using a dual-scoring method for quality. Next, a smaller local model is trained with these tasks, employing a curriculum learning strategy that evolves from simple to complex tasks. Our method enhances local model performance on various benchmarks (CNN/DailyMail, XSum, and ClinicalTrial), outperforming baselines by 4.5%, 8.5%, and 7.4%, respectively. It also improves interpretability by providing insights into the summarization rationale.

Lang Cao, Zifeng Wang, Cao Xiao et al.

Machine learning shows promise in predicting the outcome of legal cases, but most research has concentrated on civil law cases rather than case law systems. We identified two unique challenges in making legal case outcome predictions with case law. First, it is crucial to identify relevant precedent cases that serve as fundamental evidence for judges during decision-making. Second, it is necessary to consider the evolution of legal principles over time, as early cases may adhere to different legal contexts. In this paper, we proposed a new framework named PILOT (PredictIng Legal case OuTcome) for case outcome prediction. It comprises two modules for relevant case retrieval and temporal pattern handling, respectively. To benchmark the performance of existing legal case outcome prediction models, we curated a dataset from a large-scale case law database. We demonstrate the importance of accurately identifying precedent cases and mitigating the temporal shift when making predictions for case law, as our method shows a significant improvement over the prior methods that focus on civil law case outcome predictions.

Jiaqi Wang, Junyu Luo, Muchao Ye et al.

The development of electronic health records (EHR) systems has enabled the collection of a vast amount of digitized patient data. However, utilizing EHR data for predictive modeling presents several challenges due to its unique characteristics. With the advancements in machine learning techniques, deep learning has demonstrated its superiority in various applications, including healthcare. This survey systematically reviews recent advances in deep learning-based predictive models using EHR data. Specifically, we begin by introducing the background of EHR data and providing a mathematical definition of the predictive modeling task. We then categorize and summarize predictive deep models from multiple perspectives. Furthermore, we present benchmarks and toolkits relevant to predictive modeling in healthcare. Finally, we conclude this survey by discussing open challenges and suggesting promising directions for future research.

Aishik Konwer, Zhijian Yang, Erhan Bas et al.

Foundational models such as the Segment Anything Model (SAM) are gaining traction in medical imaging segmentation, supporting multiple downstream tasks. However, such models are supervised in nature, still relying on large annotated datasets or prompts supplied by experts. Conventional techniques such as active learning to alleviate such limitations are limited in scope and still necessitate continuous human involvement and complex domain knowledge for label refinement or establishing reward ground truth. To address these challenges, we propose an enhanced Segment Anything Model (SAM) framework that utilizes annotation-efficient prompts generated in a fully unsupervised fashion, while still capturing essential semantic, location, and shape information through contrastive language-image pretraining and visual question answering. We adopt the direct preference optimization technique to design an optimal policy that enables the model to generate high-fidelity segmentations with simple ratings or rankings provided by a virtual annotator simulating the human annotation process. State-of-the-art performance of our framework in tasks such as lung segmentation, breast tumor segmentation, and organ segmentation across various modalities, including X-ray, ultrasound, and abdominal CT, justifies its effectiveness in low-annotation data scenarios.

Aofei Chang, Le Huang, Parminder Bhatia et al.

Large Vision Language Models (LVLMs) are becoming increasingly important in the medical domain, yet Medical LVLMs (Med-LVLMs) frequently generate hallucinations due to limited expertise and the complexity of medical applications. Existing benchmarks fail to effectively evaluate hallucinations based on their underlying causes and lack assessments of mitigation strategies. To address this gap, we introduce MedHEval, a novel benchmark that systematically evaluates hallucinations and mitigation strategies in Med-LVLMs by categorizing them into three underlying causes: visual misinterpretation, knowledge deficiency, and context misalignment. We construct a diverse set of close- and open-ended medical VQA datasets with comprehensive evaluation metrics to assess these hallucination types. We conduct extensive experiments across 11 popular (Med)-LVLMs and evaluate 7 state-of-the-art hallucination mitigation techniques. Results reveal that Med-LVLMs struggle with hallucinations arising from different causes while existing mitigation methods show limited effectiveness, especially for knowledge- and context-based errors. These findings underscore the need for improved alignment training and specialized mitigation strategies to enhance Med-LVLMs' reliability. MedHEval establishes a standardized framework for evaluating and mitigating medical hallucinations, guiding the development of more trustworthy Med-LVLMs.

Shuyang Yu, Runxue Bao, Parminder Bhatia et al.

Large language models (LLMs) can learn vast amounts of knowledge from diverse domains during pre-training. However, long-tail knowledge from specialized domains is often scarce and underrepresented, rarely appearing in the models' memorization. Prior work has shown that in-context learning (ICL) with retriever augmentation can help LLMs better capture long-tail knowledge, reducing their reliance on pre-trained data. Despite these advances, we observe that LLM predictions for long-tail questions remain uncertain to variations in retrieved samples. To take advantage of the uncertainty in ICL for guiding LLM predictions toward correct answers on long-tail samples, we propose a reinforcement learning-based dynamic uncertainty ranking method for ICL that accounts for the varying impact of each retrieved sample on LLM predictions. Our approach prioritizes more informative and stable samples while demoting misleading ones, updating rankings based on the feedback from the LLM w.r.t. each retrieved sample. To enhance training efficiency and reduce query costs, we introduce a learnable dynamic ranking threshold, adjusted when the model encounters negative prediction shifts. Experimental results on various question-answering datasets from different domains show that our method outperforms the best baseline by $2.76\%$, with a notable $5.96\%$ boost in accuracy on long-tail questions that elude zero-shot inference.

Yuxin Chang, Alex Boyd, Cao Xiao et al.

Marked temporal point processes (MTPPs) model sequences of events occurring at irregular time intervals, with wide-ranging applications in fields such as healthcare, finance and social networks. We propose the state-space point process (S2P2) model, a novel and performant model that leverages techniques derived for modern deep state-space models (SSMs) to overcome limitations of existing MTPP models, while simultaneously imbuing strong inductive biases for continuous-time event sequences that other discrete sequence models (i.e., RNNs, transformers) do not capture. Inspired by the classical linear Hawkes processes, we propose an architecture that interleaves stochastic jump differential equations with nonlinearities to create a highly expressive intensity-based MTPP model, without the need for restrictive parametric assumptions for the intensity. Our approach enables efficient training and inference with a parallel scan, bringing linear complexity and sublinear scaling while retaining expressivity to MTPPs. Empirically, S2P2 achieves state-of-the-art predictive likelihoods across eight real-world datasets, delivering an average improvement of 33% over the best existing approaches.

Aofei Chang, Le Huang, Alex James Boyd et al.

Medical Large Vision-Language Models (Med-LVLMs) often exhibit suboptimal attention distribution on visual inputs, leading to hallucinated or inaccurate outputs. Existing mitigation methods primarily rely on inference-time interventions, which are limited in attention adaptation or require additional supervision. To address this, we propose A$^3$Tune, a novel fine-tuning framework for Automatic Attention Alignment Tuning. A$^3$Tune leverages zero-shot weak labels from SAM, refines them into prompt-aware labels using BioMedCLIP, and then selectively modifies visually-critical attention heads to improve alignment while minimizing interference. Additionally, we introduce a A$^3$MoE module, enabling adaptive parameter selection for attention tuning across diverse prompts and images. Extensive experiments on medical VQA and report generation benchmarks show that A$^3$Tune outperforms state-of-the-art baselines, achieving enhanced attention distributions and performance in Med-LVLMs.

Haoyan Yang, Runxue Bao, Cao Xiao et al.

LLM-as-a-Judge has emerged as a promising tool for automatically evaluating generated outputs, but its reliability is often undermined by potential biases in judgment. Existing efforts to mitigate these biases face key limitations: in-context learning-based methods fail to address rooted biases due to the evaluator's limited capacity for self-reflection, whereas fine-tuning is not applicable to all evaluator types, especially closed-source models. To address this challenge, we introduce the Reasoning-based Bias Detector (RBD), which is a plug-in module that identifies biased evaluations and generates structured reasoning to guide evaluator self-correction. Rather than modifying the evaluator itself, RBD operates externally and engages in an iterative process of bias detection and feedback-driven revision. To support its development, we design a complete pipeline consisting of biased dataset construction, supervision collection, distilled reasoning-based fine-tuning of RBD, and integration with LLM evaluators. We fine-tune four sizes of RBD models, ranging from 1.5B to 14B, and observe consistent performance improvements across all scales. Experimental results on 4 bias types--verbosity, position, bandwagon, and sentiment--evaluated using 8 LLM evaluators demonstrate RBD's strong effectiveness. For example, the RBD-8B model improves evaluation accuracy by an average of 18.5% and consistency by 10.9%, and surpasses prompting-based baselines and fine-tuned judges by 12.8% and 17.2%, respectively. These results highlight RBD's effectiveness and scalability. Additional experiments further demonstrate its strong generalization across biases and domains, as well as its efficiency.

Chenliang Li, Adel Elmahdy, Alex Boyd et al.

Reinforcement learning (RL) algorithms such as PPO and GRPO are widely used to train large language models (LLMs) for multi-turn agentic tasks. However, in off-policy training pipelines, these methods often exhibit unstable optimization dynamics and are prone to performance collapse. Through empirical analysis, we identify two fundamental sources of instability in this setting: (1)~a granularity mismatch between token-level policy optimization and turn-structured interactions, and (2) high-variance and unreliable gradient updates induced by off-policy importance sampling and inaccurate advantage estimation. To address these challenges, we propose SORL, \underline{S}tabilizing \underline{O}ff-Policy \underline{R}einforcement \underline{L}earning for Long-Horizon Agent Training. SORL introduces principled mechanisms that align policy optimization with the structure of multi-turn interactions and adaptively suppress unreliable off-policy updates, yielding more conservative and robust learning dynamics. Within this framework, we instantiate two stabilized algorithms: SO-PPO and SO-GRPO. Both algorithms are designed to mitigate gradient variance and prevent optimization collapse without requiring careful early stopping or heuristic tuning. We evaluate SO-PPO and SO-GRPO on a range of multi-turn search benchmarks, including general question answering, multi-hop question answering, and medical multiple-choice QA tasks. Experimental results show that both methods consistently prevent training instabilities and performance collapses observed in standard PPO and GRPO, maintain lower clipping ratios and more stable optimization trajectories, and achieve superior or comparable task performance. These results demonstrate that the proposed algorithm provides a practical, scalable, and general framework for stabilizing reinforcement learning in multi-turn LLM agent training.

Sicheng Zhou, Lei Wu, Cao Xiao et al.

Self-supervised learning (SSL) has transformed vision encoder training in general domains but remains underutilized in medical imaging due to limited data and domain specific biases. We present MammoDINO, a novel SSL framework for mammography, pretrained on 1.4 million mammographic images. To capture clinically meaningful features, we introduce a breast tissue aware data augmentation sampler for both image-level and patch-level supervision and a cross-slice contrastive learning objective that leverages 3D digital breast tomosynthesis (DBT) structure into 2D pretraining. MammoDINO achieves state-of-the-art performance on multiple breast cancer screening tasks and generalizes well across five benchmark datasets. It offers a scalable, annotation-free foundation for multipurpose computer-aided diagnosis (CAD) tools for mammogram, helping reduce radiologists' workload and improve diagnostic efficiency in breast cancer screening.

Jintai Chen, Yaojun Hu, Mingchen Cai et al.

Clinical trials are pivotal for developing new medical treatments but typically carry risks such as patient mortality and enrollment failure that waste immense efforts spanning over a decade. Applying artificial intelligence (AI) to predict key events in clinical trials holds great potential for providing insights to guide trial designs. However, complex data collection and question definition requiring medical expertise have hindered the involvement of AI thus far. This paper tackles these challenges by presenting a comprehensive suite of 23 meticulously curated AI-ready datasets covering multi-modal input features and 8 crucial prediction challenges in clinical trial design, encompassing prediction of trial duration, patient dropout rate, serious adverse event, mortality rate, trial approval outcome, trial failure reason, drug dose finding, design of eligibility criteria. Furthermore, we provide basic validation methods for each task to ensure the datasets' usability and reliability. We anticipate that the availability of such open-access datasets will catalyze the development of advanced AI approaches for clinical trial design, ultimately advancing clinical trial research and accelerating medical solution development.

Yuan Zhong, Xiaochen Wang, Jiaqi Wang et al.

Synthesizing electronic health records (EHR) data has become a preferred strategy to address data scarcity, improve data quality, and model fairness in healthcare. However, existing approaches for EHR data generation predominantly rely on state-of-the-art generative techniques like generative adversarial networks, variational autoencoders, and language models. These methods typically replicate input visits, resulting in inadequate modeling of temporal dependencies between visits and overlooking the generation of time information, a crucial element in EHR data. Moreover, their ability to learn visit representations is limited due to simple linear mapping functions, thus compromising generation quality. To address these limitations, we propose a novel EHR data generation model called EHRPD. It is a diffusion-based model designed to predict the next visit based on the current one while also incorporating time interval estimation. To enhance generation quality and diversity, we introduce a novel time-aware visit embedding module and a pioneering predictive denoising diffusion probabilistic model (PDDPM). Additionally, we devise a predictive U-Net (PU-Net) to optimize P-DDPM.We conduct experiments on two public datasets and evaluate EHRPD from fidelity, privacy, and utility perspectives. The experimental results demonstrate the efficacy and utility of the proposed EHRPD in addressing the aforementioned limitations and advancing EHR data generation.

Mintong Kang, Zhen Lin, Jimeng Sun et al.

Conformal prediction has shown impressive capacity in constructing statistically rigorous prediction sets for machine learning models with exchangeable data samples. The siloed datasets, coupled with the escalating privacy concerns related to local data sharing, have inspired recent innovations extending conformal prediction into federated environments with distributed data samples. However, this framework for distributed uncertainty quantification is susceptible to Byzantine failures. A minor subset of malicious clients can significantly compromise the practicality of coverage guarantees. To address this vulnerability, we introduce a novel framework Rob-FCP, which executes robust federated conformal prediction, effectively countering malicious clients capable of reporting arbitrary statistics with the conformal calibration process. We theoretically provide the conformal coverage bound of Rob-FCP in the Byzantine setting and show that the coverage of Rob-FCP is asymptotically close to the desired coverage level. We also propose a malicious client number estimator to tackle a more challenging setting where the number of malicious clients is unknown to the defender and theoretically shows its effectiveness. We empirically demonstrate the robustness of Rob-FCP against diverse proportions of malicious clients under a variety of Byzantine attacks on five standard benchmark and real-world healthcare datasets.

Brandon Theodorou, Shrusti Jain, Cao Xiao et al.

Generative models can produce synthetic patient records for analytical tasks when real data is unavailable or limited. However, current methods struggle with adhering to domain-specific knowledge and removing invalid data. We present ConSequence, an effective approach to integrating domain knowledge into sequential generative neural network outputs. Our rule-based formulation includes temporal aggregation and antecedent evaluation modules, ensured by an efficient matrix multiplication formulation, to satisfy hard and soft logical constraints across time steps. Existing constraint methods often fail to guarantee constraint satisfaction, lack the ability to handle temporal constraints, and hinder the learning and computational efficiency of the model. In contrast, our approach efficiently handles all types of constraints with guaranteed logical coherence. We demonstrate ConSequence's effectiveness in generating electronic health records, outperforming competitors in achieving complete temporal and spatial constraint satisfaction without compromising runtime performance or generative quality. Specifically, ConSequence successfully prevents all rule violations while improving the model quality in reducing its test perplexity by 5% and incurring less than a 13% slowdown in generation speed compared to an unconstrained model.

Brandon Theodorou, Lucas Glass, Cao Xiao et al.

Despite many efforts to address the disparities, the underrepresentation of gender, racial, and ethnic minorities in clinical trials remains a problem and undermines the efficacy of treatments on minorities. This paper focuses on the trial site selection task and proposes FRAMM, a deep reinforcement learning framework for fair trial site selection. We focus on addressing two real-world challenges that affect fair trial sites selection: the data modalities are often not complete for many potential trial sites, and the site selection needs to simultaneously optimize for both enrollment and diversity since the problem is necessarily a trade-off between the two with the only possible way to increase diversity post-selection being through limiting enrollment via caps. To address the missing data challenge, FRAMM has a modality encoder with a masked cross-attention mechanism for handling missing data, bypassing data imputation and the need for complete data in training. To handle the need for making efficient trade-offs, FRAMM uses deep reinforcement learning with a specifically designed reward function that simultaneously optimizes for both enrollment and fairness. We evaluate FRAMM using 4,392 real-world clinical trials ranging from 2016 to 2021 and show that FRAMM outperforms the leading baseline in enrollment-only settings while also achieving large gains in diversity. Specifically, it is able to produce a 9% improvement in diversity with similar enrollment levels over the leading baselines. That improved diversity is further manifested in achieving up to a 14% increase in Hispanic enrollment, 27% increase in Black enrollment, and 60% increase in Asian enrollment compared to selecting sites with an enrollment-only model.

Pengcheng Jiang, Cao Xiao, Adam Cross et al.

Clinical predictive models often rely on patients' electronic health records (EHR), but integrating medical knowledge to enhance predictions and decision-making is challenging. This is because personalized predictions require personalized knowledge graphs (KGs), which are difficult to generate from patient EHR data. To address this, we propose \textsc{GraphCare}, an open-world framework that uses external KGs to improve EHR-based predictions. Our method extracts knowledge from large language models (LLMs) and external biomedical KGs to build patient-specific KGs, which are then used to train our proposed Bi-attention AugmenTed (BAT) graph neural network (GNN) for healthcare predictions. On two public datasets, MIMIC-III and MIMIC-IV, \textsc{GraphCare} surpasses baselines in four vital healthcare prediction tasks: mortality, readmission, length of stay (LOS), and drug recommendation. On MIMIC-III, it boosts AUROC by 17.6\% and 6.6\% for mortality and readmission, and F1-score by 7.9\% and 10.8\% for LOS and drug recommendation, respectively. Notably, \textsc{GraphCare} demonstrates a substantial edge in scenarios with limited data availability. Our findings highlight the potential of using external KGs in healthcare prediction tasks and demonstrate the promise of \textsc{GraphCare} in generating personalized KGs for promoting personalized medicine.

Zifeng Wang, Chufan Gao, Cao Xiao et al.

Tabular data prediction has been employed in medical applications such as patient health risk prediction. However, existing methods usually revolve around the algorithm design while overlooking the significance of data engineering. Medical tabular datasets frequently exhibit significant heterogeneity across different sources, with limited sample sizes per source. As such, previous predictors are often trained on manually curated small datasets that struggle to generalize across different tabular datasets during inference. This paper proposes to scale medical tabular data predictors (MediTab) to various tabular inputs with varying features. The method uses a data engine that leverages large language models (LLMs) to consolidate tabular samples to overcome the barrier across tables with distinct schema. It also aligns out-domain data with the target task using a "learn, annotate, and refinement" pipeline. The expanded training data then enables the pre-trained MediTab to infer for arbitrary tabular input in the domain without fine-tuning, resulting in significant improvements over supervised baselines: it reaches an average ranking of 1.57 and 1.00 on 7 patient outcome prediction datasets and 3 trial outcome prediction datasets, respectively. In addition, MediTab exhibits impressive zero-shot performances: it outperforms supervised XGBoost models by 8.9% and 17.2% on average in two prediction tasks, respectively.

Zifeng Wang, Cao Xiao, Jimeng Sun

Clinical trials are critical for drug development. Constructing the appropriate eligibility criteria (i.e., the inclusion/exclusion criteria for patient recruitment) is essential for the trial's success. Proper design of clinical trial protocols should consider similar precedent trials and their eligibility criteria to ensure sufficient patient coverage. In this paper, we present a method named AutoTrial to aid the design of clinical eligibility criteria using language models. It allows (1) controllable generation under instructions via a hybrid of discrete and neural prompting, (2) scalable knowledge incorporation via in-context learning, and (3) explicit reasoning chains to provide rationales for understanding the outputs. Experiments on over 70K clinical trials verify that AutoTrial generates high-quality criteria texts that are fluent and coherent and with high accuracy in capturing the relevant clinical concepts to the target trial. It is noteworthy that our method, with a much smaller parameter size, gains around 60% winning rate against the GPT-3.5 baselines via human evaluations.

Muchao Ye, Junyu Luo, Guanjie Zheng et al.

Deep neural networks (DNNs) have been broadly adopted in health risk prediction to provide healthcare diagnoses and treatments. To evaluate their robustness, existing research conducts adversarial attacks in the white/gray-box setting where model parameters are accessible. However, a more realistic black-box adversarial attack is ignored even though most real-world models are trained with private data and released as black-box services on the cloud. To fill this gap, we propose the first black-box adversarial attack method against health risk prediction models named MedAttacker to investigate their vulnerability. MedAttacker addresses the challenges brought by EHR data via two steps: hierarchical position selection which selects the attacked positions in a reinforcement learning (RL) framework and substitute selection which identifies substitute with a score-based principle. Particularly, by considering the temporal context inside EHRs, it initializes its RL position selection policy by using the contribution score of each visit and the saliency score of each code, which can be well integrated with the deterministic substitute selection process decided by the score changes. In experiments, MedAttacker consistently achieves the highest average success rate and even outperforms a recent white-box EHR adversarial attack technique in certain cases when attacking three advanced health risk prediction models in the black-box setting across multiple real-world datasets. In addition, based on the experiment results we include a discussion on defending EHR adversarial attacks.

Tianfan Fu, Wenhao Gao, Cao Xiao et al.

The structural design of functional molecules, also called molecular optimization, is an essential chemical science and engineering task with important applications, such as drug discovery. Deep generative models and combinatorial optimization methods achieve initial success but still struggle with directly modeling discrete chemical structures and often heavily rely on brute-force enumeration. The challenge comes from the discrete and non-differentiable nature of molecule structures. To address this, we propose differentiable scaffolding tree (DST) that utilizes a learned knowledge network to convert discrete chemical structures to locally differentiable ones. DST enables a gradient-based optimization on a chemical graph structure by back-propagating the derivatives from the target properties through a graph neural network (GNN). Our empirical studies show the gradient-based molecular optimizations are both effective and sample efficient. Furthermore, the learned graph parameters can also provide an explanation that helps domain experts understand the model output.

Chaoqi Yang, Cheng Qian, Navjot Singh et al.

Tensor decompositions are powerful tools for dimensionality reduction and feature interpretation of multidimensional data such as signals. Existing tensor decomposition objectives (e.g., Frobenius norm) are designed for fitting raw data under statistical assumptions, which may not align with downstream classification tasks. In practice, raw input tensors can contain irrelevant information while data augmentation techniques may be used to smooth out class-irrelevant noise in samples. This paper addresses the above challenges by proposing augmented tensor decomposition (ATD), which effectively incorporates data augmentations and self-supervised learning (SSL) to boost downstream classification. To address the non-convexity of the new augmented objective, we develop an iterative method that enables the optimization to follow an alternating least squares (ALS) fashion. We evaluate our proposed ATD on multiple datasets. It can achieve 0.8% - 2.5% accuracy gain over tensor-based baselines. Also, our ATD model shows comparable or better performance (e.g., up to 15% in accuracy) over self-supervised and autoencoder baselines while using less than 5% of learnable parameters of these baseline models

Chaoqi Yang, Navjot Singh, Cao Xiao et al.

Existing tensor completion formulation mostly relies on partial observations from a single tensor. However, tensors extracted from real-world data are often more complex due to: (i) Partial observation: Only a small subset (e.g., 5%) of tensor elements are available. (ii) Coarse observation: Some tensor modes only present coarse and aggregated patterns (e.g., monthly summary instead of daily reports). In this paper, we are given a subset of the tensor and some aggregated/coarse observations (along one or more modes) and seek to recover the original fine-granular tensor with low-rank factorization. We formulate a coupled tensor completion problem and propose an efficient Multi-resolution Tensor Completion model (MTC) to solve the problem. Our MTC model explores tensor mode properties and leverages the hierarchy of resolutions to recursively initialize an optimization setup, and optimizes on the coupled system using alternating least squares. MTC ensures low computational and space complexity. We evaluate our model on two COVID-19 related spatio-temporal tensors. The experiments show that MTC could provide 65.20% and 75.79% percentage of fitness (PoF) in tensor completion with only 5% fine granular observations, which is 27.96% relative improvement over the best baseline. To evaluate the learned low-rank factors, we also design a tensor prediction task for daily and cumulative disease case predictions, where MTC achieves 50% in PoF and 30% relative improvements over the best baseline.

Cheng Qian, Nikos Kargas, Cao Xiao et al.

Real-world spatio-temporal data is often incomplete or inaccurate due to various data loading delays. For example, a location-disease-time tensor of case counts can have multiple delayed updates of recent temporal slices for some locations or diseases. Recovering such missing or noisy (under-reported) elements of the input tensor can be viewed as a generalized tensor completion problem. Existing tensor completion methods usually assume that i) missing elements are randomly distributed and ii) noise for each tensor element is i.i.d. zero-mean. Both assumptions can be violated for spatio-temporal tensor data. We often observe multiple versions of the input tensor with different under-reporting noise levels. The amount of noise can be time- or location-dependent as more updates are progressively introduced to the tensor. We model such dynamic data as a multi-version tensor with an extra tensor mode capturing the data updates. We propose a low-rank tensor model to predict the updates over time. We demonstrate that our method can accurately predict the ground-truth values of many real-world tensors. We obtain up to 27.2% lower root mean-squared-error compared to the best baseline method. Finally, we extend our method to track the tensor data over time, leading to significant computational savings.

Chaoqi Yang, Cao Xiao, Lucas Glass et al.

Deep learning is revolutionizing predictive healthcare, including recommending medications to patients with complex health conditions. Existing approaches focus on predicting all medications for the current visit, which often overlaps with medications from previous visits. A more clinically relevant task is to identify medication changes. In this paper, we propose a new recurrent residual network, named MICRON, for medication change prediction. MICRON takes the changes in patient health records as input and learns to update a hidden medication vector and the medication set recurrently with a reconstruction design. The medication vector is like the memory cell that encodes longitudinal information of medications. Unlike traditional methods that require the entire patient history for prediction, MICRON has a residual-based inference that allows for sequential updating based only on new patient features (e.g., new diagnoses in the recent visit) more efficiently. We evaluated MICRON on real inpatient and outpatient datasets. MICRON achieves 3.5% and 7.8% relative improvements over the best baseline in F1 score, respectively. MICRON also requires fewer parameters, which significantly reduces the training time to 38.3s per epoch with 1.5x speed-up.

Chaoqi Yang, Cao Xiao, Fenglong Ma et al.

Medication recommendation is an essential task of AI for healthcare. Existing works focused on recommending drug combinations for patients with complex health conditions solely based on their electronic health records. Thus, they have the following limitations: (1) some important data such as drug molecule structures have not been utilized in the recommendation process. (2) drug-drug interactions (DDI) are modeled implicitly, which can lead to sub-optimal results. To address these limitations, we propose a DDI-controllable drug recommendation model named SafeDrug to leverage drugs' molecule structures and model DDIs explicitly. SafeDrug is equipped with a global message passing neural network (MPNN) module and a local bipartite learning module to fully encode the connectivity and functionality of drug molecules. SafeDrug also has a controllable loss function to control DDI levels in the recommended drug combinations effectively. On a benchmark dataset, our SafeDrug is relatively shown to reduce DDI by 19.43% and improves 2.88% on Jaccard similarity between recommended and actually prescribed drug combinations over previous approaches. Moreover, SafeDrug also requires much fewer parameters than previous deep learning-based approaches, leading to faster training by about 14% and around 2x speed-up in inference.

Kexin Huang, Cao Xiao, Lucas M. Glass et al.

Thanks to the increasing availability of genomics and other biomedical data, many machine learning approaches have been proposed for a wide range of therapeutic discovery and development tasks. In this survey, we review the literature on machine learning applications for genomics through the lens of therapeutic development. We investigate the interplay among genomics, compounds, proteins, electronic health records (EHR), cellular images, and clinical texts. We identify twenty-two machine learning in genomics applications across the entire therapeutics pipeline, from discovering novel targets, personalized medicine, developing gene-editing tools all the way to clinical trials and post-market studies. We also pinpoint seven important challenges in this field with opportunities for expansion and impact. This survey overviews recent research at the intersection of machine learning, genomics, and therapeutic development.

Zhen Lin, Cao Xiao, Lucas Glass et al.

Despite deep learning (DL) success in classification problems, DL classifiers do not provide a sound mechanism to decide when to refrain from predicting. Recent works tried to control the overall prediction risk with classification with rejection options. However, existing works overlook the different significance of different classes. We introduce Set-classifier with Class-specific RIsk Bounds (SCRIB) to tackle this problem, assigning multiple labels to each example. Given the output of a black-box model on the validation set, SCRIB constructs a set-classifier that controls the class-specific prediction risks with a theoretical guarantee. The key idea is to reject when the set classifier returns more than one label. We validated SCRIB on several medical applications, including sleep staging on electroencephalogram (EEG) data, X-ray COVID image classification, and atrial fibrillation detection based on electrocardiogram (ECG) data. SCRIB obtained desirable class-specific risks, which are 35\%-88\% closer to the target risks than baseline methods.

Kexin Huang, Tianfan Fu, Wenhao Gao et al.

Therapeutics machine learning is an emerging field with incredible opportunities for innovatiaon and impact. However, advancement in this field requires formulation of meaningful learning tasks and careful curation of datasets. Here, we introduce Therapeutics Data Commons (TDC), the first unifying platform to systematically access and evaluate machine learning across the entire range of therapeutics. To date, TDC includes 66 AI-ready datasets spread across 22 learning tasks and spanning the discovery and development of safe and effective medicines. TDC also provides an ecosystem of tools and community resources, including 33 data functions and types of meaningful data splits, 23 strategies for systematic model evaluation, 17 molecule generation oracles, and 29 public leaderboards. All resources are integrated and accessible via an open Python library. We carry out extensive experiments on selected datasets, demonstrating that even the strongest algorithms fall short of solving key therapeutics challenges, including real dataset distributional shifts, multi-scale modeling of heterogeneous data, and robust generalization to novel data points. We envision that TDC can facilitate algorithmic and scientific advances and considerably accelerate machine-learning model development, validation and transition into biomedical and clinical implementation. TDC is an open-science initiative available at https://tdcommons.ai.

Tianfan Fu, Kexin Huang, Cao Xiao et al.

Clinical trials are crucial for drug development but are time consuming, expensive, and often burdensome on patients. More importantly, clinical trials face uncertain outcomes due to issues with efficacy, safety, or problems with patient recruitment. If we were better at predicting the results of clinical trials, we could avoid having to run trials that will inevitably fail more resources could be devoted to trials that are likely to succeed. In this paper, we propose Hierarchical INteraction Network (HINT) for more general, clinical trial outcome predictions for all diseases based on a comprehensive and diverse set of web data including molecule information of the drugs, target disease information, trial protocol and biomedical knowledge. HINT first encode these multi-modal data into latent embeddings, where an imputation module is designed to handle missing data. Next, these embeddings will be fed into the knowledge embedding module to generate knowledge embeddings that are pretrained using external knowledge on pharmaco-kinetic properties and trial risk from the web. Then the interaction graph module will connect all the embedding via domain knowledge to fully capture various trial components and their complex relations as well as their influences on trial outcomes. Finally, HINT learns a dynamic attentive graph neural network to predict trial outcome. Comprehensive experimental results show that HINT achieves strong predictive performance, obtaining 0.772, 0.607, 0.623, 0.703 on PR-AUC for Phase I, II, III, and indication outcome prediction, respectively. It also consistently outperforms the best baseline method by up to 12.4\% on PR-AUC.

Nikos Kargas, Cheng Qian, Nicholas D. Sidiropoulos et al.

Accurate prediction of the transmission of epidemic diseases such as COVID-19 is crucial for implementing effective mitigation measures. In this work, we develop a tensor method to predict the evolution of epidemic trends for many regions simultaneously. We construct a 3-way spatio-temporal tensor (location, attribute, time) of case counts and propose a nonnegative tensor factorization with latent epidemiological model regularization named STELAR. Unlike standard tensor factorization methods which cannot predict slabs ahead, STELAR enables long-term prediction by incorporating latent temporal regularization through a system of discrete-time difference equations of a widely adopted epidemiological model. We use latent instead of location/attribute-level epidemiological dynamics to capture common epidemic profile sub-types and improve collaborative learning and prediction. We conduct experiments using both county- and state-level COVID-19 data and show that our model can identify interesting latent patterns of the epidemic. Finally, we evaluate the predictive ability of our method and show superior performance compared to the baselines, achieving up to 21% lower root mean square error and 25% lower mean absolute error for county-level prediction.

Junyu Luo, Zifei Zheng, Hanzhong Ye et al.

Patients with low health literacy usually have difficulty understanding medical jargon and the complex structure of professional medical language. Although some studies are proposed to automatically translate expert language into layperson-understandable language, only a few of them focus on both accuracy and readability aspects simultaneously in the clinical domain. Thus, simplification of the clinical language is still a challenging task, but unfortunately, it is not yet fully addressed in previous work. To benchmark this task, we construct a new dataset named MedLane to support the development and evaluation of automated clinical language simplification approaches. Besides, we propose a new model called DECLARE that follows the human annotation procedure and achieves state-of-the-art performance compared with eight strong baselines. To fairly evaluate the performance, we also propose three specific evaluation metrics. Experimental results demonstrate the utility of the annotated MedLane dataset and the effectiveness of the proposed model DECLARE.

Zhi Qiao, Austin Bae, Lucas M. Glass et al.

To test the possibility of differentiating chest x-ray images of COVID-19 against other pneumonia and healthy patients using deep neural networks. We construct the X-ray imaging data from two publicly available sources, which include 5508 chest x-ray images across 2874 patients with four classes: normal, bacterial pneumonia, non-COVID-19 viral pneumonia, and COVID-19. To identify COVID-19, we propose a Focal Loss Based Neural Ensemble Network (FLANNEL), a flexible module to ensemble several convolutional neural network (CNN) models and fuse with a focal loss for accurate COVID-19 detection on class imbalance data. FLANNEL consistently outperforms baseline models on COVID-19 identification task in all metrics. Compared with the best baseline, FLANNEL shows a higher macro-F1 score with 6% relative increase on Covid-19 identification task where it achieves 0.7833(0.07) in Precision, 0.8609(0.03) in Recall, and 0.8168(0.03) F1 score.

Yanbo Xu, Cao Xiao, Jimeng Sun

Counterfactual prediction is about predicting outcome of the unobserved situation from the data. For example, given patient is on drug A, what would be the outcome if she switch to drug B. Most of existing works focus on modeling counterfactual outcome based on static data. However, many applications have time-varying confounding effects such as multiple treatments over time. How to model such time-varying effects from longitudinal observational data? How to model complex high-dimensional dependency in the data? To address these challenges, we propose Deep Recurrent Inverse TreatmEnt weighting (DeepRite) by incorporating recurrent neural networks into two-phase adjustments for the existence of time-varying confounding in modern longitudinal data. In phase I cohort reweighting we fit one network for emitting time dependent inverse probabilities of treatment, use them to generate a pseudo balanced cohort. In phase II outcome progression, we input the adjusted data to the subsequent predictive network for making counterfactual predictions. We evaluate DeepRite on both synthetic data and a real data collected from sepsis patients in the intensive care units. DeepRite is shown to recover the ground truth from synthetic data, and estimate unbiased treatment effects from real data that can be better aligned with the standard guidelines for management of sepsis thanks to its applicability to create balanced cohorts.

Chacha Chen, Junjie Liang, Fenglong Ma et al.

Successful health risk prediction demands accuracy and reliability of the model. Existing predictive models mainly depend on mining electronic health records (EHR) with advanced deep learning techniques to improve model accuracy. However, they all ignore the importance of publicly available online health data, especially socioeconomic status, environmental factors, and detailed demographic information for each location, which are all strong predictive signals and can definitely augment precision medicine. To achieve model reliability, the model needs to provide accurate prediction and uncertainty score of the prediction. However, existing uncertainty estimation approaches often failed in handling high-dimensional data, which are present in multi-sourced data. To fill the gap, we propose UNcertaInTy-based hEalth risk prediction (UNITE) model. Building upon an adaptive multimodal deep kernel and a stochastic variational inference module, UNITE provides accurate disease risk prediction and uncertainty estimation leveraging multi-sourced health data including EHR data, patient demographics, and public health data collected from the web. We evaluate UNITE on real-world disease risk prediction tasks: nonalcoholic fatty liver disease (NASH) and Alzheimer's disease (AD). UNITE achieves up to 0.841 in F1 score for AD detection, up to 0.609 in PR-AUC for NASH detection, and outperforms various state-of-the-art baselines by up to $19\%$ over the best baseline. We also show UNITE can model meaningful uncertainties and can provide evidence-based clinical support by clustering similar patients.