Radiation therapy is crucial in cancer treatment. Experienced experts typically iteratively generate high-quality dose distribution maps, forming the basis for excellent radiation therapy plans. Therefore, automated prediction of dose distribution maps is significant in expediting the treatment process and providing a better starting point for developing radiation therapy plans. With the remarkable results of diffusion models in predicting high-frequency regions of dose distribution maps, dose prediction methods based on diffusion models have been extensively studied. However, existing methods mainly utilize CNNs or Transformers as denoising networks. CNNs lack the capture of global receptive fields, resulting in suboptimal prediction performance. Transformers excel in global modeling but face quadratic complexity with image size, resulting in significant computational overhead. To tackle these challenges, we introduce a novel diffusion model, MD-Dose, based on the Mamba architecture for predicting radiation therapy dose distribution in thoracic cancer patients. In the forward process, MD-Dose adds Gaussian noise to dose distribution maps to obtain pure noise images. In the backward process, MD-Dose utilizes a noise predictor based on the Mamba to predict the noise, ultimately outputting the dose distribution maps. Furthermore, We develop a Mamba encoder to extract structural information and integrate it into the noise predictor for localizing dose regions in the planning target volume (PTV) and organs at risk (OARs). Through extensive experiments on a dataset of 300 thoracic tumor patients, we showcase the superiority of MD-Dose in various metrics and time consumption.
Detection of malignant lesions on mammography images is extremely important for early breast cancer diagnosis. In clinical practice, images are acquired from two different angles, and radiologists can fully utilize information from both views, simultaneously locating the same lesion. However, for automatic detection approaches such information fusion remains a challenge. In this paper, we propose a new model called MAMM-Net, which allows the processing of both mammography views simultaneously by sharing information not only on an object level, as seen in existing works, but also on a feature level. MAMM-Net's key component is the Fusion Layer, based on deformable attention and designed to increase detection precision while keeping high recall. Our experiments show superior performance on the public DDSM dataset compared to the previous state-of-the-art model, while introducing new helpful features such as lesion annotation on pixel-level and classification of lesions malignancy.
The interactions between tumor cells and the tumor microenvironment (TME) dictate therapeutic efficacy of radiation and many systemic therapies in breast cancer. However, to date, there is not a widely available method to reproducibly measure tumor and immune phenotypes for each patient's tumor. Given this unmet clinical need, we applied multiple instance learning (MIL) algorithms to assess activity of ten biologically relevant pathways from the hematoxylin and eosin (H&E) slide of primary breast tumors. We employed different feature extraction approaches and state-of-the-art model architectures. Using binary classification, our models attained area under the receiver operating characteristic (AUROC) scores above 0.70 for nearly all gene expression pathways and on some cases, exceeded 0.80. Attention maps suggest that our trained models recognize biologically relevant spatial patterns of cell sub-populations from H&E. These efforts represent a first step towards developing computational H&E biomarkers that reflect facets of the TME and hold promise for augmenting precision oncology.
Despite their general capabilities, LLMs still struggle on biomedical NER tasks, which are difficult due to the presence of specialized terminology and lack of training data. In this work we set out to improve LLM performance on biomedical NER in limited data settings via a new knowledge augmentation approach which incorporates definitions of relevant concepts on-the-fly. During this process, to provide a test bed for knowledge augmentation, we perform a comprehensive exploration of prompting strategies. Our experiments show that definition augmentation is useful for both open source and closed LLMs. For example, it leads to a relative improvement of 15\% (on average) in GPT-4 performance (F1) across all (six) of our test datasets. We conduct extensive ablations and analyses to demonstrate that our performance improvements stem from adding relevant definitional knowledge. We find that careful prompting strategies also improve LLM performance, allowing them to outperform fine-tuned language models in few-shot settings. To facilitate future research in this direction, we release our code at //github.com/allenai/beacon.
As cyber-attacks become increasingly sophisticated and stealthy, it becomes more imperative and challenging to detect intrusion from normal behaviors. Through fine-grained causality analysis, provenance-based intrusion detection systems (PIDS) demonstrated a promising capacity to distinguish benign and malicious behaviors, attracting widespread attention from both industry and academia. Among diverse approaches, rule-based PIDS stands out due to its lightweight overhead, real-time capabilities, and explainability. However, existing rule-based systems suffer low detection accuracy, especially the high false alarms, due to the lack of fine-grained rules and environment-specific configurations. In this paper, we propose CAPTAIN, a rule-based PIDS capable of automatically adapting to diverse environments. Specifically, we propose three adaptive parameters to adjust the detection configuration with respect to nodes, edges, and alarm generation thresholds. We build a differentiable tag propagation framework and utilize the gradient descent algorithm to optimize these adaptive parameters based on the training data. We evaluate our system based on data from DARPA Engagement and simulated environments. The evaluation results demonstrate that CAPTAIN offers better detection accuracy, less detection latency, lower runtime overhead, and more interpretable detection alarms and knowledge compared to the SOTA PIDS.
Despite extensive safety assessments of drugs prior to their introduction to the market, certain adverse drug reactions (ADRs) remain undetected. The primary objective of pharmacovigilance is to identify these ADRs (i.e., signals). In addition to traditional spontaneous reporting systems (SRSs), electronic health (EHC) data is being used for signal detection as well. Unlike SRS, EHC data is longitudinal and thus requires assumptions about the patient's drug exposure history and its impact on ADR occurrences over time, which many current methods do implicitly. We propose an exposure model framework that explicitly models the longitudinal relationship between the drug and the ADR. By considering multiple such models simultaneously, we can detect signals that might be missed by other approaches. The parameters of these models are estimated using maximum likelihood, and the Bayesian Information Criterion (BIC) is employed to select the most suitable model. Since BIC is connected to the posterior distribution, it servers the dual purpose of identifying the best-fitting model and determining the presence of a signal by evaluating the posterior probability of the null model. We evaluate the effectiveness of this framework through a simulation study, for which we develop an EHC data simulator. Additionally, we conduct a case study applying our approach to four drug-ADR pairs using an EHC dataset comprising over 1.2 million insured individuals. Both the method and the EHC data simulator code are publicly accessible as part of the R package //github.com/bips-hb/expard.
Breast cancer is the most common malignant tumor among women and the second cause of cancer-related death. Early diagnosis in clinical practice is crucial for timely treatment and prognosis. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has revealed great usability in the preoperative diagnosis and assessing therapy effects thanks to its capability to reflect the morphology and dynamic characteristics of breast lesions. However, most existing computer-assisted diagnosis algorithms only consider conventional radiomic features when classifying benign and malignant lesions in DCE-MRI. In this study, we propose to fully leverage the dynamic characteristics from the kinetic curves as well as the radiomic features to boost the classification accuracy of benign and malignant breast lesions. The proposed method is a fully automated solution by directly analyzing the 3D features from the DCE-MRI. The proposed method is evaluated on an in-house dataset including 200 DCE-MRI scans with 298 breast tumors (172 benign and 126 malignant tumors), achieving favorable classification accuracy with an area under curve (AUC) of 0.94. By simultaneously considering the dynamic and radiomic features, it is beneficial to effectively distinguish between benign and malignant breast lesions.
In clinical practice, one often needs to identify whether a patient is at high risk of adverse outcomes after some key medical event. For example, quantifying the risk of adverse outcomes after an acute cardiovascular event helps healthcare providers identify those patients at the highest risk of poor outcomes; i.e., patients who benefit from invasive therapies that can lower their risk. Assessing the risk of adverse outcomes, however, is challenging due to the complexity, variability, and heterogeneity of longitudinal medical data, especially for individuals suffering from chronic diseases like heart failure. In this paper, we introduce Event-Based Contrastive Learning (EBCL) - a method for learning embeddings of heterogeneous patient data that preserves temporal information before and after key index events. We demonstrate that EBCL can be used to construct models that yield improved performance on important downstream tasks relative to other pretraining methods. We develop and test the method using a cohort of heart failure patients obtained from a large hospital network and the publicly available MIMIC-IV dataset consisting of patients in an intensive care unit at a large tertiary care center. On both cohorts, EBCL pretraining yields models that are performant with respect to a number of downstream tasks, including mortality, hospital readmission, and length of stay. In addition, unsupervised EBCL embeddings effectively cluster heart failure patients into subgroups with distinct outcomes, thereby providing information that helps identify new heart failure phenotypes. The contrastive framework around the index event can be adapted to a wide array of time-series datasets and provides information that can be used to guide personalized care.
The quest for accurate prediction of drug molecule properties poses a fundamental challenge in the realm of Artificial Intelligence Drug Discovery (AIDD). An effective representation of drug molecules emerges as a pivotal component in this pursuit. Contemporary leading-edge research predominantly resorts to self-supervised learning (SSL) techniques to extract meaningful structural representations from large-scale, unlabeled molecular data, subsequently fine-tuning these representations for an array of downstream tasks. However, an inherent shortcoming of these studies lies in their singular reliance on one modality of molecular information, such as molecule image or SMILES representations, thus neglecting the potential complementarity of various molecular modalities. In response to this limitation, we propose MolIG, a novel MultiModaL molecular pre-training framework for predicting molecular properties based on Image and Graph structures. MolIG model innovatively leverages the coherence and correlation between molecule graph and molecule image to execute self-supervised tasks, effectively amalgamating the strengths of both molecular representation forms. This holistic approach allows for the capture of pivotal molecular structural characteristics and high-level semantic information. Upon completion of pre-training, Graph Neural Network (GNN) Encoder is used for the prediction of downstream tasks. In comparison to advanced baseline models, MolIG exhibits enhanced performance in downstream tasks pertaining to molecular property prediction within benchmark groups such as MoleculeNet Benchmark Group and ADMET Benchmark Group.
Medical image segmentation is a fundamental and critical step in many image-guided clinical approaches. Recent success of deep learning-based segmentation methods usually relies on a large amount of labeled data, which is particularly difficult and costly to obtain especially in the medical imaging domain where only experts can provide reliable and accurate annotations. Semi-supervised learning has emerged as an appealing strategy and been widely applied to medical image segmentation tasks to train deep models with limited annotations. In this paper, we present a comprehensive review of recently proposed semi-supervised learning methods for medical image segmentation and summarized both the technical novelties and empirical results. Furthermore, we analyze and discuss the limitations and several unsolved problems of existing approaches. We hope this review could inspire the research community to explore solutions for this challenge and further promote the developments in medical image segmentation field.
Defensive deception is a promising approach for cyberdefense. Although defensive deception is increasingly popular in the research community, there has not been a systematic investigation of its key components, the underlying principles, and its tradeoffs in various problem settings. This survey paper focuses on defensive deception research centered on game theory and machine learning, since these are prominent families of artificial intelligence approaches that are widely employed in defensive deception. This paper brings forth insights, lessons, and limitations from prior work. It closes with an outline of some research directions to tackle major gaps in current defensive deception research.