BACKGROUND & AIMS: Histological remission (HR) is advocated and considered as a new therapeutic target in ulcerative colitis (UC). Diagnosis of histologic remission currently relies on biopsy; during this process, patients are at risk for bleeding, infection, and post-biopsy fibrosis. In addition, histologic response scoring is complex and time-consuming, and there is heterogeneity among pathologists. Endocytoscopy (EC) is a novel ultra-high magnification endoscopic technique that can provide excellent in vivo assessment of glands. Based on the EC technique, we propose a neural network model that can assess histological disease activity in UC using EC images to address the above issues. The experiment results demonstrate that the proposed method can assist patients in precise treatment and prognostic assessment. METHODS: We construct a neural network model for UC evaluation. A total of 5105 images of 154 intestinal segments from 87 patients undergoing EC treatment at a center in China between March 2022 and March 2023 are scored according to the Geboes score. Subsequently, 103 intestinal segments are used as the training set, 16 intestinal segments are used as the validation set for neural network training, and the remaining 35 intestinal segments are used as the test set to measure the model performance together with the validation set. RESULTS: By treating HR as a negative category and histologic activity as a positive category, the proposed neural network model can achieve an accuracy of 0.9, a specificity of 0.95, a sensitivity of 0.75, and an area under the curve (AUC) of 0.81. CONCLUSION: We develop a specific neural network model that can distinguish histologic remission/activity in EC images of UC, which helps to accelerate clinical histological diagnosis. keywords: ulcerative colitis; Endocytoscopy; Geboes score; neural network.
Segmentation of nodules in thyroid ultrasound imaging plays a crucial role in the detection and treatment of thyroid cancer. However, owing to the diversity of scanner vendors and imaging protocols in different hospitals, the automatic segmentation model, which has already demonstrated expert-level accuracy in the field of medical image segmentation, finds its accuracy reduced as the result of its weak generalization performance when being applied in clinically realistic environments. To address this issue, the present paper proposes ASTN, a framework for thyroid nodule segmentation achieved through a new type co-registration network. By extracting latent semantic information from the atlas and target images and utilizing in-depth features to accomplish the co-registration of nodules in thyroid ultrasound images, this framework can ensure the integrity of anatomical structure and reduce the impact on segmentation as the result of overall differences in image caused by different devices. In addition, this paper also provides an atlas selection algorithm to mitigate the difficulty of co-registration. As shown by the evaluation results collected from the datasets of different devices, thanks to the method we proposed, the model generalization has been greatly improved while maintaining a high level of segmentation accuracy.
Microsatellite instability-high (MSI-H) is a tumor agnostic biomarker for immune checkpoint inhibitor therapy. However, MSI status is not routinely tested in prostate cancer, in part due to low prevalence and assay cost. As such, prediction of MSI status from hematoxylin and eosin (H&E) stained whole-slide images (WSIs) could identify prostate cancer patients most likely to benefit from confirmatory testing and becoming eligible for immunotherapy. Prostate biopsies and surgical resections from de-identified records of consecutive prostate cancer patients referred to our institution were analyzed. Their MSI status was determined by next generation sequencing. Patients before a cutoff date were split into an algorithm development set (n=4015, MSI-H 1.8%) and a paired validation set (n=173, MSI-H 19.7%) that consisted of two serial sections from each sample, one stained and scanned internally and the other at an external site. Patients after the cutoff date formed the temporal validation set (n=1350, MSI-H 2.3%). Attention-based multiple instance learning models were trained to predict MSI-H from H&E WSIs. The MSI-H predictor achieved area under the receiver operating characteristic curve values of 0.78 (95% CI [0.69-0.86]), 0.72 (95% CI [0.63-0.81]), and 0.72 (95% CI [0.62-0.82]) on the internally prepared, externally prepared, and temporal validation sets, respectively. While MSI-H status is significantly correlated with Gleason score, the model remained predictive within each Gleason score subgroup. In summary, we developed and validated an AI-based MSI-H diagnostic model on a large real-world cohort of routine H&E slides, which effectively generalized to externally stained and scanned samples and a temporally independent validation cohort. This algorithm has the potential to direct prostate cancer patients toward immunotherapy and to identify MSI-H cases secondary to Lynch syndrome.
The reasoning capabilities of LLM (Large Language Model) are widely acknowledged in recent research, inspiring studies on tool learning and autonomous agents. LLM serves as the "brain" of agent, orchestrating multiple tools for collaborative multi-step task solving. Unlike methods invoking tools like calculators or weather APIs for straightforward tasks, multi-modal agents excel by integrating diverse AI models for complex challenges. However, current multi-modal agents neglect the significance of model selection: they primarily focus on the planning and execution phases, and will only invoke predefined task-specific models for each subtask, making the execution fragile. Meanwhile, other traditional model selection methods are either incompatible with or suboptimal for the multi-modal agent scenarios, due to ignorance of dependencies among subtasks arising by multi-step reasoning. To this end, we identify the key challenges therein and propose the $\textit{M}^3$ framework as a plug-in with negligible runtime overhead at test-time. This framework improves model selection and bolsters the robustness of multi-modal agents in multi-step reasoning. In the absence of suitable benchmarks, we create MS-GQA, a new dataset specifically designed to investigate the model selection challenge in multi-modal agents. Our experiments reveal that our framework enables dynamic model selection, considering both user inputs and subtask dependencies, thereby robustifying the overall reasoning process. Our code and benchmark: //github.com/LINs-lab/M3.
Different conflicting optimization criteria arise naturally in various Deep Learning scenarios. These can address different main tasks (i.e., in the setting of Multi-Task Learning), but also main and secondary tasks such as loss minimization versus sparsity. The usual approach is a simple weighting of the criteria, which formally only works in the convex setting. In this paper, we present a Multi-Objective Optimization algorithm using a modified Weighted Chebyshev scalarization for training Deep Neural Networks (DNNs) with respect to several tasks. By employing this scalarization technique, the algorithm can identify all optimal solutions of the original problem while reducing its complexity to a sequence of single-objective problems. The simplified problems are then solved using an Augmented Lagrangian method, enabling the use of popular optimization techniques such as Adam and Stochastic Gradient Descent, while efficaciously handling constraints. Our work aims to address the (economical and also ecological) sustainability issue of DNN models, with a particular focus on Deep Multi-Task models, which are typically designed with a very large number of weights to perform equally well on multiple tasks. Through experiments conducted on two Machine Learning datasets, we demonstrate the possibility of adaptively sparsifying the model during training without significantly impacting its performance, if we are willing to apply task-specific adaptations to the network weights. Code is available at //github.com/salomonhotegni/MDMTN.
Biomarker detection is an indispensable part in the diagnosis and treatment of low-grade glioma (LGG). However, current LGG biomarker detection methods rely on expensive and complex molecular genetic testing, for which professionals are required to analyze the results, and intra-rater variability is often reported. To overcome these challenges, we propose an interpretable deep learning pipeline, a Multi-Biomarker Histomorphology Discoverer (Multi-Beholder) model based on the multiple instance learning (MIL) framework, to predict the status of five biomarkers in LGG using only hematoxylin and eosin-stained whole slide images and slide-level biomarker status labels. Specifically, by incorporating the one-class classification into the MIL framework, accurate instance pseudo-labeling is realized for instance-level supervision, which greatly complements the slide-level labels and improves the biomarker prediction performance. Multi-Beholder demonstrates superior prediction performance and generalizability for five LGG biomarkers (AUROC=0.6469-0.9735) in two cohorts (n=607) with diverse races and scanning protocols. Moreover, the excellent interpretability of Multi-Beholder allows for discovering the quantitative and qualitative correlations between biomarker status and histomorphology characteristics. Our pipeline not only provides a novel approach for biomarker prediction, enhancing the applicability of molecular treatments for LGG patients but also facilitates the discovery of new mechanisms in molecular functionality and LGG progression.
Bipolar Disorder (BD) is a psychiatric condition diagnosed by repetitive cycles of hypomania and depression. Since diagnosing BD relies on subjective behavioral assessments over a long period, a solid diagnosis based on objective criteria is not straightforward. The current study responded to the described obstacle by proposing a hybrid GAN-CNN model to diagnose BD from 3-D structural MRI Images (sMRI). The novelty of this study stems from diagnosing BD from sMRI samples rather than conventional datasets such as functional MRI (fMRI), electroencephalography (EEG), and behavioral symptoms while removing the data insufficiency usually encountered when dealing with sMRI samples. The impact of various augmentation ratios is also tested using 5-fold cross-validation. Based on the results, this study obtains an accuracy rate of 75.8%, a sensitivity of 60.3%, and a specificity of 82.5%, which are 3-5% higher than prior work while utilizing less than 6% sample counts. Next, it is demonstrated that a 2- D layer-based GAN generator can effectively reproduce complex 3D brain samples, a more straightforward technique than manual image processing. Lastly, the optimum augmentation threshold for the current study using 172 sMRI samples is 50%, showing the applicability of the described method for larger sMRI datasets. In conclusion, it is established that data augmentation using GAN improves the accuracy of the CNN classifier using sMRI samples, thus developing more reliable decision support systems to assist practitioners in identifying BD patients more reliably and in a shorter period
Recent artificial intelligence (AI) systems have reached milestones in "grand challenges" ranging from Go to protein-folding. The capability to retrieve medical knowledge, reason over it, and answer medical questions comparably to physicians has long been viewed as one such grand challenge. Large language models (LLMs) have catalyzed significant progress in medical question answering; Med-PaLM was the first model to exceed a "passing" score in US Medical Licensing Examination (USMLE) style questions with a score of 67.2% on the MedQA dataset. However, this and other prior work suggested significant room for improvement, especially when models' answers were compared to clinicians' answers. Here we present Med-PaLM 2, which bridges these gaps by leveraging a combination of base LLM improvements (PaLM 2), medical domain finetuning, and prompting strategies including a novel ensemble refinement approach. Med-PaLM 2 scored up to 86.5% on the MedQA dataset, improving upon Med-PaLM by over 19% and setting a new state-of-the-art. We also observed performance approaching or exceeding state-of-the-art across MedMCQA, PubMedQA, and MMLU clinical topics datasets. We performed detailed human evaluations on long-form questions along multiple axes relevant to clinical applications. In pairwise comparative ranking of 1066 consumer medical questions, physicians preferred Med-PaLM 2 answers to those produced by physicians on eight of nine axes pertaining to clinical utility (p < 0.001). We also observed significant improvements compared to Med-PaLM on every evaluation axis (p < 0.001) on newly introduced datasets of 240 long-form "adversarial" questions to probe LLM limitations. While further studies are necessary to validate the efficacy of these models in real-world settings, these results highlight rapid progress towards physician-level performance in medical question answering.
Few-shot Knowledge Graph (KG) completion is a focus of current research, where each task aims at querying unseen facts of a relation given its few-shot reference entity pairs. Recent attempts solve this problem by learning static representations of entities and references, ignoring their dynamic properties, i.e., entities may exhibit diverse roles within task relations, and references may make different contributions to queries. This work proposes an adaptive attentional network for few-shot KG completion by learning adaptive entity and reference representations. Specifically, entities are modeled by an adaptive neighbor encoder to discern their task-oriented roles, while references are modeled by an adaptive query-aware aggregator to differentiate their contributions. Through the attention mechanism, both entities and references can capture their fine-grained semantic meanings, and thus render more expressive representations. This will be more predictive for knowledge acquisition in the few-shot scenario. Evaluation in link prediction on two public datasets shows that our approach achieves new state-of-the-art results with different few-shot sizes.
Named entity recognition (NER) in Chinese is essential but difficult because of the lack of natural delimiters. Therefore, Chinese Word Segmentation (CWS) is usually considered as the first step for Chinese NER. However, models based on word-level embeddings and lexicon features often suffer from segmentation errors and out-of-vocabulary (OOV) words. In this paper, we investigate a Convolutional Attention Network called CAN for Chinese NER, which consists of a character-based convolutional neural network (CNN) with local-attention layer and a gated recurrent unit (GRU) with global self-attention layer to capture the information from adjacent characters and sentence contexts. Also, compared to other models, not depending on any external resources like lexicons and employing small size of char embeddings make our model more practical. Extensive experimental results show that our approach outperforms state-of-the-art methods without word embedding and external lexicon resources on different domain datasets including Weibo, MSRA and Chinese Resume NER dataset.
Multi-relation Question Answering is a challenging task, due to the requirement of elaborated analysis on questions and reasoning over multiple fact triples in knowledge base. In this paper, we present a novel model called Interpretable Reasoning Network that employs an interpretable, hop-by-hop reasoning process for question answering. The model dynamically decides which part of an input question should be analyzed at each hop; predicts a relation that corresponds to the current parsed results; utilizes the predicted relation to update the question representation and the state of the reasoning process; and then drives the next-hop reasoning. Experiments show that our model yields state-of-the-art results on two datasets. More interestingly, the model can offer traceable and observable intermediate predictions for reasoning analysis and failure diagnosis, thereby allowing manual manipulation in predicting the final answer.