BackgroundThe discovery of novel anticancer drugs is critical for the pharmaceutical research and development, and patient treatment. Repurposing existing drugs that may have unanticipated effects as potential candidates is one way to meet this important goal. Systematic investigation of efficient anticancer drugs could provide valuable insights into trends in the discovery of anticancer drugs, which may contribute to the systematic discovery of new anticancer drugs.ResultsIn this study, we collected and analyzed 150 anticancer drugs approved by the US Food and Drug Administration (FDA). Based on drug mechanism of action, these agents are divided into two groups: 61 cytotoxic-based drugs and 89 target-based drugs. We found that in the recent years, the proportion of targeted agents tended to be increasing, and the targeted drugs tended to be delivered as signal drugs. For 89 target-based drugs, we collected 102 effect-mediating drug targets in the human genome and found that most targets located on the plasma membrane and most of them belonged to the enzyme, especially tyrosine kinase. From above 150 drugs, we built a drug-cancer network, which contained 183 nodes (150 drugs and 33 cancer types) and 248 drug-cancer associations. The network indicated that the cytotoxic drugs tended to be used to treat more cancer types than targeted drugs. From 89 targeted drugs, we built a cancer-drug-target network, which contained 214 nodes (23 cancer types, 89 drugs, and 102 targets) and 313 edges (118 drug-cancer associations and 195 drug-target associations). Starting from the network, we discovered 133 novel drug-cancer associations among 52 drugs and 16 cancer types by applying the common target-based approach. Most novel drug-cancer associations (116, 87%) are supported by at least one clinical trial study.ConclusionsIn this study, we provided a comprehensive data source, including anticancer drugs and their targets and performed a detailed analysis in term of historical tendency and networks. Its application to identify novel drug-cancer associations demonstrated that the data collected in this study is promising to serve as a fundamental for anticancer drug repurposing and development.

Existing general clinical natural language processing (NLP) systems such as MetaMap and Clinical Text Analysis and Knowledge Extraction System have been successfully applied to information extraction from clinical text. However, end users often have to customize existing systems for their individual tasks, which can require substantial NLP skills. Here we present CLAMP (Clinical Language Annotation, Modeling, and Processing), a newly developed clinical NLP toolkit that provides not only state-of-the-art NLP components, but also a user-friendly graphic user interface that can help users quickly build customized NLP pipelines for their individual applications. Our evaluation shows that the CLAMP default pipeline achieved good performance on named entity recognition and concept encoding. We also demonstrate the efficiency of the CLAMP graphic user interface in building customized, high-performance NLP pipelines with 2 use cases, extracting smoking status and lab test values. CLAMP is publicly available for research use, and we believe it is a unique asset for the clinical NLP community.

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.

Using a dyadic panel data set that links U.S. suppliers with their major buyers, we study how trade credit responds to various types of competition in supply chains, as well as the impact of trade credit on firm performance. We find that suppliers with smaller market share are associated with more trade credit, confirming that suppliers with weak market power use trade credit as a competitive tool. Next, we find that buyers with larger market share are associated with more trade credit, whereas suppliers selling to a concentrated buyer base are associated with less trade credit; by differentiating competition in buyers’ markets from competition between supply chain partners, we show that the two types of competition have different impacts on trade credit. In studying the impact of trade credit on firm performance, we make the distinction between an industry-average trade credit and an individual supply chain’s deviation from such an industry average. When suppliers offer trade credit at their industry-average level, this action facilitates trade and, thus, is positively associated with both parties’ performance; conversely, when suppliers are more aggressive in their trade credit strategy than the industry average, then the excess trade credit is negatively associated with buyer performance. One managerial message from our research is that buyers should be cautious about trade credit far exceeding the industry-average level. The online appendix is available at https://doi.org/10.1287/msom.2017.0640 . This paper has been accepted for the Manufacturing & Service Operations Management Special Issue on Interface of Finance, Operations, and Risk Management.

Mining chemical-induced disease relations embedded in the vast biomedical literature could facilitate a wide range of computational biomedical applications, such as pharmacovigilance. The BioCreative V organized a Chemical Disease Relation (CDR) Track regarding chemical-induced disease relation extraction from biomedical literature in 2015. We participated in all subtasks of this challenge. In this article, we present our participation system Chemical Disease Relation Extraction SysTem (CD-REST), an end-to-end system for extracting chemical-induced disease relations in biomedical literature. CD-REST consists of two main components: (1) a chemical and disease named entity recognition and normalization module, which employs the Conditional Random Fields algorithm for entity recognition and a Vector Space Model-based approach for normalization; and (2) a relation extraction module that classifies both sentence-level and document-level candidate drug–disease pairs by support vector machines. Our system achieved the best performance on the chemical-induced disease relation extraction subtask in the BioCreative V CDR Track, demonstrating the effectiveness of our proposed machine learning-based approaches for automatic extraction of chemical-induced disease relations in biomedical literature. The CD-REST system provides web services using HTTP POST request. The web services can be accessed from http://clinicalnlptool.com/cdr. The online CD-REST demonstration system is available at http://clinicalnlptool.com/cdr/cdr.html.Database URL: http://clinicalnlptool.com/cdr; http://clinicalnlptool.com/cdr/cdr.html