Clinical trials are vital in advancing drug development and evidence-based medicine, but their success is often hindered by challenges in patient recruitment. In this work, we investigate the potential of large language models (LLMs) to assist individual patients and referral physicians in identifying suitable clinical trials from an extensive selection. Specifically, we introduce TrialGPT, a novel architecture employing LLMs to predict criterion-level eligibility with detailed explanations, which are then aggregated for ranking and excluding candidate clinical trials based on free-text patient notes. We evaluate TrialGPT on three publicly available cohorts of 184 patients and 18,238 annotated clinical trials. The experimental results demonstrate several key findings: First, TrialGPT achieves high criterion-level prediction accuracy with faithful explanations. Second, the aggregated trial-level TrialGPT scores are highly correlated with expert eligibility annotations. Third, these scores prove effective in ranking clinical trials and exclude ineligible candidates. Our error analysis suggests that current LLMs still make some mistakes due to limited medical knowledge and domain-specific context understanding. Nonetheless, we believe the explanatory capabilities of LLMs are highly valuable. Future research is warranted on how such AI assistants can be integrated into the routine trial matching workflow in real-world settings to improve its efficiency.
Scarcity of health care resources could result in the unavoidable consequence of rationing. For example, ventilators are often limited in supply, especially during public health emergencies or in resource-constrained health care settings, such as amid the pandemic of COVID-19. Currently, there is no universally accepted standard for health care resource allocation protocols, resulting in different governments prioritizing patients based on various criteria and heuristic-based protocols. In this study, we investigate the use of reinforcement learning for critical care resource allocation policy optimization to fairly and effectively ration resources. We propose a transformer-based deep Q-network to integrate the disease progression of individual patients and the interaction effects among patients during the critical care resource allocation. We aim to improve both fairness of allocation and overall patient outcomes. Our experiments demonstrate that our method significantly reduces excess deaths and achieves a more equitable distribution under different levels of ventilator shortage, when compared to existing severity-based and comorbidity-based methods in use by different governments. Our source code is included in the supplement and will be released on Github upon publication.
The pursuit of long-term autonomy mandates that robotic agents must continuously adapt to their changing environments and learn to solve new tasks. Continual learning seeks to overcome the challenge of catastrophic forgetting, where learning to solve new tasks causes a model to forget previously learnt information. Prior-based continual learning methods are appealing for robotic applications as they are space efficient and typically do not increase in computational complexity as the number of tasks grows. Despite these desirable properties, prior-based approaches typically fail on important benchmarks and consequently are limited in their potential applications compared to their memory-based counterparts. We introduce Bayesian adaptive moment regularization (BAdam), a novel prior-based method that better constrains parameter growth, leading to lower catastrophic forgetting. Our method boasts a range of desirable properties for robotic applications such as being lightweight and task label-free, converging quickly, and offering calibrated uncertainty that is important for safe real-world deployment. Results show that BAdam achieves state-of-the-art performance for prior-based methods on challenging single-headed class-incremental experiments such as Split MNIST and Split FashionMNIST, and does so without relying on task labels or discrete task boundaries.
While standard speaker diarization attempts to answer the question "who spoken when", most of relevant applications in reality are more interested in determining "who spoken what". Whether it is the conventional modularized approach or the more recent end-to-end neural diarization (EEND), an additional automatic speech recognition (ASR) model and an orchestration algorithm are required to associate the speaker labels with recognized words. In this paper, we propose Word-level End-to-End Neural Diarization (WEEND) with auxiliary network, a multi-task learning algorithm that performs end-to-end ASR and speaker diarization in the same neural architecture. That is, while speech is being recognized, speaker labels are predicted simultaneously for each recognized word. Experimental results demonstrate that WEEND outperforms the turn-based diarization baseline system on all 2-speaker short-form scenarios and has the capability to generalize to audio lengths of 5 minutes. Although 3+speaker conversations are harder, we find that with enough in-domain training data, WEEND has the potential to deliver high quality diarized text.
Due to the imbalanced nature of networked observational data, the causal effect predictions for some individuals can severely violate the positivity/overlap assumption, rendering unreliable estimations. Nevertheless, this potential risk of individual-level treatment effect estimation on networked data has been largely under-explored. To create a more trustworthy causal effect estimator, we propose the uncertainty-aware graph deep kernel learning (GraphDKL) framework with Lipschitz constraint to model the prediction uncertainty with Gaussian process and identify unreliable estimations. To the best of our knowledge, GraphDKL is the first framework to tackle the violation of positivity assumption when performing causal effect estimation with graphs. With extensive experiments, we demonstrate the superiority of our proposed method in uncertainty-aware causal effect estimation on networked data.
Fast screening of drug molecules based on the ligand binding affinity is an important step in the drug discovery pipeline. Graph neural fingerprint is a promising method for developing molecular docking surrogates with high throughput and great fidelity. In this study, we built a COVID-19 drug docking dataset of about 300,000 drug candidates on 23 coronavirus protein targets. With this dataset, we trained graph neural fingerprint docking models for high-throughput virtual COVID-19 drug screening. The graph neural fingerprint models yield high prediction accuracy on docking scores with the mean squared error lower than $0.21$ kcal/mol for most of the docking targets, showing significant improvement over conventional circular fingerprint methods. To make the neural fingerprints transferable for unknown targets, we also propose a transferable graph neural fingerprint method trained on multiple targets. With comparable accuracy to target-specific graph neural fingerprint models, the transferable model exhibits superb training and data efficiency. We highlight that the impact of this study extends beyond COVID-19 dataset, as our approach for fast virtual ligand screening can be easily adapted and integrated into a general machine learning-accelerated pipeline to battle future bio-threats.
Bipedal robots promise the ability to traverse rough terrain quickly and efficiently, and indeed, humanoid robots can now use strong ankles and careful foot placement to traverse discontinuous terrain. However, more agile underactuated bipeds have small feet and weak ankles, and must constantly adjust their planned footstep position to maintain balance. We introduce a new model-predictive footstep controller which jointly optimizes over the robot's discrete choice of stepping surface, impending footstep position sequence, ankle torque in the sagittal plane, and center of mass trajectory, to track a velocity command. The controller is formulated as a single Mixed Integer Quadratic Program (MIQP) which is solved at 50-200 Hz, depending on terrain complexity. We implement a state of the art real-time elevation mapping and convex terrain decomposition framework to inform the controller of its surroundings in the form on convex polygons representing steppable terrain. We investigate the capabilities and challenges of our approach through hardware experiments on the underactuated biped Cassie.
Automatic identification of clinical trials for which a patient is eligible is complicated by the fact that trial eligibility is stated in natural language. A potential solution to this problem is to employ text classification methods for common types of eligibility criteria. In this study, we focus on seven common exclusion criteria in cancer trials: prior malignancy, human immunodeficiency virus, hepatitis B, hepatitis C, psychiatric illness, drug/substance abuse, and autoimmune illness. Our dataset consists of 764 phase III cancer trials with these exclusions annotated at the trial level. We experiment with common transformer models as well as a new pre-trained clinical trial BERT model. Our results demonstrate the feasibility of automatically classifying common exclusion criteria. Additionally, we demonstrate the value of a pre-trained language model specifically for clinical trials, which yields the highest average performance across all criteria.
Understanding causality helps to structure interventions to achieve specific goals and enables predictions under interventions. With the growing importance of learning causal relationships, causal discovery tasks have transitioned from using traditional methods to infer potential causal structures from observational data to the field of pattern recognition involved in deep learning. The rapid accumulation of massive data promotes the emergence of causal search methods with brilliant scalability. Existing summaries of causal discovery methods mainly focus on traditional methods based on constraints, scores and FCMs, there is a lack of perfect sorting and elaboration for deep learning-based methods, also lacking some considers and exploration of causal discovery methods from the perspective of variable paradigms. Therefore, we divide the possible causal discovery tasks into three types according to the variable paradigm and give the definitions of the three tasks respectively, define and instantiate the relevant datasets for each task and the final causal model constructed at the same time, then reviews the main existing causal discovery methods for different tasks. Finally, we propose some roadmaps from different perspectives for the current research gaps in the field of causal discovery and point out future research directions.
Textual entailment is a fundamental task in natural language processing. Most approaches for solving the problem use only the textual content present in training data. A few approaches have shown that information from external knowledge sources like knowledge graphs (KGs) can add value, in addition to the textual content, by providing background knowledge that may be critical for a task. However, the proposed models do not fully exploit the information in the usually large and noisy KGs, and it is not clear how it can be effectively encoded to be useful for entailment. We present an approach that complements text-based entailment models with information from KGs by (1) using Personalized PageR- ank to generate contextual subgraphs with reduced noise and (2) encoding these subgraphs using graph convolutional networks to capture KG structure. Our technique extends the capability of text models exploiting structural and semantic information found in KGs. We evaluate our approach on multiple textual entailment datasets and show that the use of external knowledge helps improve prediction accuracy. This is particularly evident in the challenging BreakingNLI dataset, where we see an absolute improvement of 5-20% over multiple text-based entailment models.
Clinical Named Entity Recognition (CNER) aims to identify and classify clinical terms such as diseases, symptoms, treatments, exams, and body parts in electronic health records, which is a fundamental and crucial task for clinical and translational research. In recent years, deep neural networks have achieved significant success in named entity recognition and many other Natural Language Processing (NLP) tasks. Most of these algorithms are trained end to end, and can automatically learn features from large scale labeled datasets. However, these data-driven methods typically lack the capability of processing rare or unseen entities. Previous statistical methods and feature engineering practice have demonstrated that human knowledge can provide valuable information for handling rare and unseen cases. In this paper, we address the problem by incorporating dictionaries into deep neural networks for the Chinese CNER task. Two different architectures that extend the Bi-directional Long Short-Term Memory (Bi-LSTM) neural network and five different feature representation schemes are proposed to handle the task. Computational results on the CCKS-2017 Task 2 benchmark dataset show that the proposed method achieves the highly competitive performance compared with the state-of-the-art deep learning methods.