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  1. Drug repositioning has drawn significant attention for drug development in pharmaceutical research and industry, because of its advantages in cost and time compared with the de novo drug development. The availability of biomedical databases and online health-related information, as well as the high-performance computing, empowers the development of computational drug repositioning methods. In this work, we developed a systematic approach that identifies repositioning drugs based on heterogeneous network mining using both pharmaceutical databases (PharmGKB and SIDER) and online health community (MedHelp). By utilizing adverse drug reactions (ADRs) as the intermediate, we constructed a heterogeneous health network containing drugs, diseases, and ADRs, and developed path-based heterogeneous network mining approaches for drug repositioning. Additionally, we investigated on how the data sources affect the performance on drug repositioning. Experiment results showed that combining both PharmKGB and MedHelp identified 479 repositioning drugs, which are more than the repositioning drugs discovered by other alternatives. In addition, 31% of the 479 of the discovered repositioning drugs were supported by evidence from PubMed. 
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  2. Abstract

    The difference between North Atlantic subpolar gyre sea surface temperatures (SPG SSTs) and hemispheric‐ or global‐scale surface temperatures has been utilized as an index of centennial‐timescale changes in Atlantic Meridional Overturning Circulation (AMOC) strength. Here, using Community Earth System Model ensembles, we show that surface temperature‐based indices (STIs) proposed to date largely reflect global‐scale temperature trends and thus do not reflect dynamical relationships with AMOC. More broadly, we find that relationships between STIs, SPG SSTs, and AMOC strength differ greatly in significance and magnitude over different time periods because they are dependent upon the nature of external forcing. In the twentieth century, characterized by offsetting greenhouse gas and aerosol forcing, the relationship between SSTs and AMOC strength varies widely and changes sign across a 20‐member ensemble. We conclude that STIs and SPG SSTs are poor predictors of centennial‐timescale AMOC strength variations.

     
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  3. Classical results in sparse recovery guarantee the exact reconstruction of s-sparse signals under assumptions on the dictionary that are either too strong or NP-hard to check. Moreover, such results may be pessimistic in practice since they are based on a worst-case analysis. In this paper, we consider the sparse recovery of signals defined over a graph, for which the dictionary takes the form of an incidence matrix. We derive necessary and sufficient conditions for sparse recovery, which depend on properties of the cycles of the graph that can be checked in polynomial time. We also derive support-dependent conditions for sparse recovery that depend only on the intersection of the cycles of the graph with the support of the signal. Finally, we exploit sparsity properties on the measurements and the structure of incidence matrices to propose a specialized sub-graph-based recovery algorithm that outperforms the standard l1 -minimization approach. 
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  4. Off-label drug use is an important healthcare topic as it is quite common and sometimes inevitable in medical practice. Though gaining information about off-label drug uses could benefit a lot of healthcare stakeholders such as patients, physicians, and pharmaceutical companies, there is no such data repository of such information available. There is a desire for a systematic approach to detect off-label drug uses. Other than using data sources such as EHR and clinical notes that are provided by healthcare providers, we exploited social media data especially online health community (OHC) data to detect the off-label drug uses, with consideration of the increasing social media users and the large volume of valuable and timely user-generated contents. We adopted tensor decomposition technique, CP decomposition in this work, to deal with the sparsity and missing data problem in social media data. On the basis of tensor decomposition results, we used two approaches to identify off-label drug use candidates: (1) one is via ranking the CP decomposition resulting components, (2) the other one is applying a heterogeneous network mining method, proposed in our previous work [9], on the reconstructed dataset by CP decomposition. The first approach identified a number of significant off-label use candidates, for which we were able to conduct case studies and found medical explanations for 7 out of 12 identified off-label use candidates. The second approach achieved better performance than the previous method [9] by improving the F1-score by 3%. It demonstrated the effectiveness of performing tensor decomposition on social media data for detecting off-label drug use. 
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  5. Classical results in sparse representation guarantee the exact recovery of sparse signals under assumptions on the dictionary that are either too strong or NP hard to check. Moreover, such results may be too pessimistic in practice since they are based on a worst-case analysis. In this paper, we consider the sparse recovery of signals defined over a graph, for which the dictionary takes the form of an incidence matrix. We show that in this case necessary and sufficient conditions can be derived in terms of properties of the cycles of the graph, which can be checked in polynomial time. Our analysis further allows us to derive location dependent conditions for recovery that only depend on the cycles of the graph that intersect this support. Finally, we exploit sparsity properties on the measurements to a specialized sub-graph-based recovery algorithm that outperforms the standard $l_1$-minimization. 
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  6. Off-label drug use refers to using marketed drugs for indications that are not listed in their FDA labeling information. Such uses are very common and sometimes inevitable in clinical practice. To some extent, off-label drug uses provide a pathway for clinical innovation, however, they could cause serious adverse effects due to lacking scientific research and tests. Since identifying the off-label uses can provide a clue to the stakeholders including healthcare providers, patients, and medication manufacturers to further the investigation on drug efficacy and safety, it raises the demand for a systematic way to detect off-label uses. Given data contributed by health consumers in online health communities (OHCs), we developed an automated approach to detect off-label drug uses based on heterogeneous network mining. We constructed a heterogeneous healthcare network with medical entities (e.g. disease, drug, adverse drug reaction) mined from the text corpus, which involved 50 diseases, 1,297 drugs, and 185 ADRs, and determined 13 meta paths between the drugs and diseases. We developed three metrics to represent the meta-path-based topological features. With the network features, we trained the binary classifiers built on Random Forest algorithm to recognize the known drug-disease associations. The best classification model that used lift to measure path weights obtained F1-score of 0.87, based on which, we identified 1,009 candidates of off-label drug uses and examined their potential by searching evidence from PubMed and FAERS. 
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