Objective To report a novel cell-surface autoantigen of encephalitis that is a critical regulatory subunit of the Kv4.2 potassium channels. Methods Four patients with encephalitis of unclear etiology and antibodies with a similar pattern of neuropil brain immunostaining were selected for autoantigen characterization. Techniques included immunoprecipitation, mass spectrometry, cell-base experiments with Kv4.2 and several dipeptidyl-peptidase-like protein-6 (DPPX) plasmid constructs, and comparative brain immunostaining of wild-type and DPPX-null mice. Results Immunoprecipitation studies identified DPPX as the target autoantigen. A cell based assay confirmed that all 4 patients, but not 210 controls, had DPPX antibodies. Symptoms included agitation, confusion, myoclonus, tremor, and seizures (one case with prominent startle response). All patients had pleocytosis, and three had severe prodromal diarrhea of unknown etiology. Given that DPPX “tunes up” the Kv4.2 potassium channels (involved in somatodendritic signal integration and attenuation of dendritic backpropagation of action potentials), we determined the epitope distribution in DPPX, DPP10 (a protein homologous to DPPX) and Kv4.2. Patients’ antibodies were found specific for DPPX, without reacting with DPP10 or Kv4.2. The unexplained diarrhea led to demonstrate a robust expression of DPPX in the myenteric plexus, which strongly reacted with patients’ antibodies. The course of neuropsychiatric symptoms was prolonged and often associated with relapses while decreasing immunotherapy. Long-term follow-up showed substantial improvement in 3 patients (1 is lost to follow-up). Interpretation Antibodies to DPPX associate with a protracted encephalitis characterized by CNS hyperexcitability (agitation, myoclonus, tremor, seizures), pleocytosis, and frequent diarrhea at symptom onset. The disorder is potentially treatable with immunotherapy.

Objective This article methodically reviews the literature on deep learning (DL) for natural language processing (NLP) in the clinical domain, providing quantitative analysis to answer 3 research questions concerning methods, scope, and context of current research. Materials and Methods We searched MEDLINE, EMBASE, Scopus, the Association for Computing Machinery Digital Library, and the Association for Computational Linguistics Anthology for articles using DL-based approaches to NLP problems in electronic health records. After screening 1,737 articles, we collected data on 25 variables across 212 papers. Results DL in clinical NLP publications more than doubled each year, through 2018. Recurrent neural networks (60.8%) and word2vec embeddings (74.1%) were the most popular methods; the information extraction tasks of text classification, named entity recognition, and relation extraction were dominant (89.2%). However, there was a “long tail” of other methods and specific tasks. Most contributions were methodological variants or applications, but 20.8% were new methods of some kind. The earliest adopters were in the NLP community, but the medical informatics community was the most prolific. Discussion Our analysis shows growing acceptance of deep learning as a baseline for NLP research, and of DL-based NLP in the medical community. A number of common associations were substantiated (eg, the preference of recurrent neural networks for sequence-labeling named entity recognition), while others were surprisingly nuanced (eg, the scarcity of French language clinical NLP with deep learning). Conclusion Deep learning has not yet fully penetrated clinical NLP and is growing rapidly. This review highlighted both the popular and unique trends in this active field.

Neural network-based representations ("embeddings") have dramatically advanced natural language processing (NLP) tasks, including clinical NLP tasks such as concept extraction. Recently, however, more advanced embedding methods and representations (e.g., ELMo, BERT) have further pushed the stateof-the-art in NLP, yet there are no common best practices for how to integrate these representations into clinical tasks. The purpose of this study, then, is to explore the space of possible options in utilizing these new models for clinical concept extraction, including comparing these to traditional word embedding methods (word2vec, GloVe, fastText). Both offthe-shelf, open-domain embeddings and pretrained clinical embeddings from MIMIC-III are evaluated. We explore a battery of embedding methods consisting of traditional word embeddings and contextual embeddings, and compare these on four concept extraction corpora: i2b2 2010, i2b2 2012, SemEval 2014, and SemEval 2015. We also analyze the impact of the pre-training time of a large language model like ELMo or BERT on the extraction performance. Last, we present an intuitive way to understand the semantic information encoded by contextual embeddings. Contextual embeddings pre-trained on a large clinical corpus achieves new state-of-the-art performances across all concept extraction tasks. The best-performing model outperforms all state-of-the-art methods with respective F1measures of 90. 25, 93.18 (partial), 80.74, and 81.65. We demonstrate the potential of contextual embeddings through the state-of-the-art performance these methods achieve on clinical concept extraction. Additionally, we demonstrate that contextual embeddings encode valuable semantic information not accounted for in traditional word representations.

Despite the recent advances in automatically describing image contents, their applications have been mostly limited to image caption datasets containing natural images (e.g., Flickr 30k, MSCOCO). In this paper, we present a deep learning model to efficiently detect a disease from an image and annotate its contexts (e.g., location, severity and the affected organs). We employ a publicly available radiology dataset of chest x-rays and their reports, and use its image annotations to mine disease names to train convolutional neural networks (CNNs). In doing so, we adopt various regularization techniques to circumvent the large normalvs-diseased cases bias. Recurrent neural networks (RNNs) are then trained to describe the contexts of a detected disease, based on the deep CNN features. Moreover, we introduce a novel approach to use the weights of the already trained pair of CNN/RNN on the domain-specific image/text dataset, to infer the joint image/text contexts for composite image labeling. Significantly improved image annotation results are demonstrated using the recurrent neural cascade model by taking the joint image/text contexts into account.

Lexical and contextual features proved to be very important in relation extraction from medical texts. When they are not available to the classifier, the F1 score decreases by 3.7%. In addition, features based on similarity contribute to a decrease of 1.1% when they are not available.

Abstract TREC-COVID is an information retrieval (IR) shared task initiated to support clinicians and clinical research during the COVID-19 pandemic. IR for pandemics breaks many normal assumptions, which can be seen by examining 9 important basic IR research questions related to pandemic situations. TREC-COVID differs from traditional IR shared task evaluations with special considerations for the expected users, IR modality considerations, topic development, participant requirements, assessment process, relevance criteria, evaluation metrics, iteration process, projected timeline, and the implications of data use as a post-task test collection. This article describes how all these were addressed for the particular requirements of developing IR systems under a pandemic situation. Finally, initial participation numbers are also provided, which demonstrate the tremendous interest the IR community has in this effort.

Providing access to relevant biomedical literature in a clinical setting has the potential to bridge a critical gap in evidence-based medicine. Here, our goal is specifically to provide relevant articles to clinicians to improve their decision-making in diagnosing, treating, and testing patients. To this end, the TREC 2014 Clinical Decision Support Track evaluated a system's ability to retrieve relevant articles in one of three categories (Diagnosis, Treatment, Test) using an idealized form of a patient medical record. Over 100 submissions from over 25 participants were evaluated on 30 topics, resulting in over 37k relevance judgments. In this article, we provide an overview of the task, a survey of the information retrieval methods employed by the participants, an analysis of the results, and a discussion on the future directions for this challenging yet important task.

No abstract