Implementing Trust in Non-Small Cell Lung Cancer Diagnosis with a Conformalized Uncertainty-Aware AI Framework in Whole-Slide Images

Ensuring trustworthiness is fundamental to the development of artificial intelligence (AI) that is considered societally responsible, particularly in cancer diagnostics, where a misdiagnosis can have dire consequences. Current digital pathology AI models lack systematic solutions to address trustworthiness concerns arising from model limitations and data discrepancies between model deployment and development environments. To address this issue, we developed TRUECAM, a framework designed to ensure both data and model trustworthiness in non-small cell lung cancer subtyping with whole-slide images. TRUECAM integrates 1) a spectral-normalized neural Gaussian process for identifying out-of-scope inputs and 2) an ambiguity-guided elimination of tiles to filter out highly ambiguous regions, addressing data trustworthiness, as well as 3) conformal prediction to ensure controlled error rates. We systematically evaluated the framework across multiple large-scale cancer datasets, leveraging both task-specific and foundation models, illustrate that an AI model wrapped with TRUECAM significantly outperforms models that lack such guidance, in terms of classification accuracy, robustness, interpretability, and data efficiency, while also achieving improvements in fairness. These findings highlight TRUECAM as a versatile wrapper framework for digital pathology AI models with diverse architectural designs, promoting their responsible and effective applications in real-world settings.

Catalysts of Conversation: Examining Interaction Dynamics Between Topic Initiators and Commentors in Alzheimer's Disease Online Communities

Informal caregivers (e.g.,family members or friends) of people living with Alzheimers Disease and Related Dementias (ADRD) face substantial challenges and often seek informational or emotional support through online communities. Understanding the factors that drive engagement within these platforms is crucial, as it can enhance their long-term value for caregivers by ensuring that these communities effectively meet their needs. This study investigated the user interaction dynamics within two large, popular ADRD communities, TalkingPoint and ALZConnected, focusing on topic initiator engagement, initial post content, and the linguistic patterns of comments at the thread level. Using analytical methods such as propensity score matching, topic modeling, and predictive modeling, we found that active topic initiator engagement drives higher comment volumes, and reciprocal replies from topic initiators encourage further commentor engagement at the community level. Practical caregiving topics prompt more re-engagement of topic initiators, while emotional support topics attract more comments from other commentors. Additionally, the linguistic complexity and emotional tone of a comment influence its likelihood of receiving replies from topic initiators. These findings highlight the importance of fostering active and reciprocal engagement and providing effective strategies to enhance sustainability in ADRD caregiving and broader health-related online communities.

Do You Know What You Are Talking About? Characterizing Query-Knowledge Relevance For Reliable Retrieval Augmented Generation

Language models (LMs) are known to suffer from hallucinations and misinformation. Retrieval augmented generation (RAG) that retrieves verifiable information from an external knowledge corpus to complement the parametric knowledge in LMs provides a tangible solution to these problems. However, the generation quality of RAG is highly dependent on the relevance between a user's query and the retrieved documents. Inaccurate responses may be generated when the query is outside of the scope of knowledge represented in the external knowledge corpus or if the information in the corpus is out-of-date. In this work, we establish a statistical framework that assesses how well a query can be answered by an RAG system by capturing the relevance of knowledge. We introduce an online testing procedure that employs goodness-of-fit (GoF) tests to inspect the relevance of each user query to detect out-of-knowledge queries with low knowledge relevance. Additionally, we develop an offline testing framework that examines a collection of user queries, aiming to detect significant shifts in the query distribution which indicates the knowledge corpus is no longer sufficiently capable of supporting the interests of the users. We demonstrate the capabilities of these strategies through a systematic evaluation on eight question-answering (QA) datasets, the results of which indicate that the new testing framework is an efficient solution to enhance the reliability of existing RAG systems.

Leveraging Generative AI for Clinical Evidence Summarization Needs to Achieve Trustworthiness

Evidence-based medicine aims to improve the quality of healthcare by empowering medical decisions and practices with the best available evidence. The rapid growth of medical evidence, which can be obtained from various sources, poses a challenge in collecting, appraising, and synthesizing the evidential information. Recent advancements in generative AI, exemplified by large language models, hold promise in facilitating the arduous task. However, developing accountable, fair, and inclusive models remains a complicated undertaking. In this perspective, we discuss the trustworthiness of generative AI in the context of automated summarization of medical evidence.

SAC$^3$: Reliable Hallucination Detection in Black-Box Language Models via Semantic-aware Cross-check Consistency

Hallucination detection is a critical step toward understanding the trustworthiness of modern language models (LMs). To achieve this goal, we re-examine existing detection approaches based on the self-consistency of LMs and uncover two types of hallucinations resulting from 1) question-level and 2) model-level, which cannot be effectively identified through self-consistency check alone. Building upon this discovery, we propose a novel sampling-based method, i.e., semantic-aware cross-check consistency (SAC$^3$) that expands on the principle of self-consistency checking. Our SAC$^3$ approach incorporates additional mechanisms to detect both question-level and model-level hallucinations by leveraging advances including semantically equivalent question perturbation and cross-model response consistency checking. Through extensive and systematic empirical analysis, we demonstrate that SAC$^3$ outperforms the state of the art in detecting both non-factual and factual statements across multiple question-answering and open-domain generation benchmarks.

Split Learning for Distributed Collaborative Training of Deep Learning Models in Health Informatics

Deep learning continues to rapidly evolve and is now demonstrating remarkable potential for numerous medical prediction tasks. However, realizing deep learning models that generalize across healthcare organizations is challenging. This is due, in part, to the inherent siloed nature of these organizations and patient privacy requirements. To address this problem, we illustrate how split learning can enable collaborative training of deep learning models across disparate and privately maintained health datasets, while keeping the original records and model parameters private. We introduce a new privacy-preserving distributed learning framework that offers a higher level of privacy compared to conventional federated learning. We use several biomedical imaging and electronic health record (EHR) datasets to show that deep learning models trained via split learning can achieve highly similar performance to their centralized and federated counterparts while greatly improving computational efficiency and reducing privacy risks.

Risk of re-identification for shared clinical speech recordings

Large, curated datasets are required to leverage speech-based tools in healthcare. These are costly to produce, resulting in increased interest in data sharing. As speech can potentially identify speakers (i.e., voiceprints), sharing recordings raises privacy concerns. We examine the re-identification risk for speech recordings, without reference to demographic or metadata, using a state-of-the-art speaker recognition system. We demonstrate that the risk is inversely related to the number of comparisons an adversary must consider, i.e., the search space. Risk is high for a small search space but drops as the search space grows ($precision >0.85$ for $<1*10^{6}$ comparisons, $precision <0.5$ for $>3*10^{6}$ comparisons). Next, we show that the nature of a speech recording influences re-identification risk, with non-connected speech (e.g., vowel prolongation) being harder to identify. Our findings suggest that speaker recognition systems can be used to re-identify participants in specific circumstances, but in practice, the re-identification risk appears low.

A Multifaceted Benchmarking of Synthetic Electronic Health Record Generation Models

Synthetic health data have the potential to mitigate privacy concerns when sharing data to support biomedical research and the development of innovative healthcare applications. Modern approaches for data generation based on machine learning, generative adversarial networks (GAN) methods in particular, continue to evolve and demonstrate remarkable potential. Yet there is a lack of a systematic assessment framework to benchmark methods as they emerge and determine which methods are most appropriate for which use cases. In this work, we introduce a generalizable benchmarking framework to appraise key characteristics of synthetic health data with respect to utility and privacy metrics. We apply the framework to evaluate synthetic data generation methods for electronic health records (EHRs) data from two large academic medical centers with respect to several use cases. The results illustrate that there is a utility-privacy tradeoff for sharing synthetic EHR data. The results further indicate that no method is unequivocally the best on all criteria in each use case, which makes it evident why synthetic data generation methods need to be assessed in context.

Blending Knowledge in Deep Recurrent Networks for Adverse Event Prediction at Hospital Discharge

Deep learning architectures have an extremely high-capacity for modeling complex data in a wide variety of domains. However, these architectures have been limited in their ability to support complex prediction problems using insurance claims data, such as readmission at 30 days, mainly due to data sparsity issue. Consequently, classical machine learning methods, especially those that embed domain knowledge in handcrafted features, are often on par with, and sometimes outperform, deep learning approaches. In this paper, we illustrate how the potential of deep learning can be achieved by blending domain knowledge within deep learning architectures to predict adverse events at hospital discharge, including readmissions. More specifically, we introduce a learning architecture that fuses a representation of patient data computed by a self-attention based recurrent neural network, with clinically relevant features. We conduct extensive experiments on a large claims dataset and show that the blended method outperforms the standard machine learning approaches.

Re-identification of Individuals in Genomic Datasets Using Public Face Images

DNA sequencing is becoming increasingly commonplace, both in medical and direct-to-consumer settings. To promote discovery, collected genomic data is often de-identified and shared, either in public repositories, such as OpenSNP, or with researchers through access-controlled repositories. However, recent studies have suggested that genomic data can be effectively matched to high-resolution three-dimensional face images, which raises a concern that the increasingly ubiquitous public face images can be linked to shared genomic data, thereby re-identifying individuals in the genomic data. While these investigations illustrate the possibility of such an attack, they assume that those performing the linkage have access to extremely well-curated data. Given that this is unlikely to be the case in practice, it calls into question the pragmatic nature of the attack. As such, we systematically study this re-identification risk from two perspectives: first, we investigate how successful such linkage attacks can be when real face images are used, and second, we consider how we can empower individuals to have better control over the associated re-identification risk. We observe that the true risk of re-identification is likely substantially smaller for most individuals than prior literature suggests. In addition, we demonstrate that the addition of a small amount of carefully crafted noise to images can enable a controlled trade-off between re-identification success and the quality of shared images, with risk typically significantly lowered even with noise that is imperceptible to humans.