Learning Deep Latent Spaces for Multi-Label Classification

Multi-label classification is a practical yet challenging task in machine learning related fields, since it requires the prediction of more than one label category for each input instance. We propose a novel deep neural networks (DNN) based model, Canonical Correlated AutoEncoder (C2AE), for solving this task. Aiming at better relating feature and label domain data for improved classification, we uniquely perform joint feature and label embedding by deriving a deep latent space, followed by the introduction of label-correlation sensitive loss function for recovering the predicted label outputs. Our C2AE is achieved by integrating the DNN architectures of canonical correlation analysis and autoencoder, which allows end-to-end learning and prediction with the ability to exploit label dependency. Moreover, our C2AE can be easily extended to address the learning problem with missing labels. Our experiments on multiple datasets with different scales confirm the effectiveness and robustness of our proposed method, which is shown to perform favorably against state-of-the-art methods for multi-label classification.Comment: published in AAAI-201

Generating Dialogue Responses from a Semantic Latent Space

Existing open-domain dialogue generation models are usually trained to mimic the gold response in the training set using cross-entropy loss on the vocabulary. However, a good response does not need to resemble the gold response, since there are multiple possible responses to a given prompt. In this work, we hypothesize that the current models are unable to integrate information from multiple semantically similar valid responses of a prompt, resulting in the generation of generic and uninformative responses. To address this issue, we propose an alternative to the end-to-end classification on vocabulary. We learn the pair relationship between the prompts and responses as a regression task on a latent space instead. In our novel dialog generation model, the representations of semantically related sentences are close to each other on the latent space. Human evaluation showed that learning the task on a continuous space can generate responses that are both relevant and informative.Comment: EMNLP 202

Cytochrome P450 Metabolism of Betel Quid-Derived Compounds: Implications for the Development of Prevention Strategies for Oral and Pharyngeal Cancers

Betel quid (BQ) products, with or without tobacco, have been classified by the International Agency for Research on Cancer (IARC) as group I human carcinogens that are associated with an elevated risk of oral potentially malignant disorders (OPMDs) and cancers of the oral cavity and pharynx. There are estimated 600 million BQ users worldwide. In Taiwan alone there are 2 million habitual users (approximately 10% of the population). Oral and pharyngeal cancers result from interactions between genes and environmental factors (BQ exposure). Cytochrome p450 (CYP) families are implicated in the metabolic activation of BQ- and areca nut-specific nitrosamines. In this review, we summarize the current knowledge base regarding CYP genetic variants and related oral disorders. In clinical applications, we focus on cancers of the oral cavity and pharynx and OPMDs associated with CYP gene polymorphisms, including CYP1A1, CYP2A6, CYP2E1, and CYP26B1. Our discussion of CYP polymorphisms provides insight into the importance of screening tests in OPMDs patients for the prevention of oral and pharyngeal cancers. Future studies will establish a strong foundation for the development of chemoprevention strategies, polymorphism-based clinical diagnostic tools (e.g., specific single-nucleotide polymorphism (SNP) “barcodes”), and effective treatments for BQ-related oral disorders

Hospital Mortality of Septic Acute Kidney Injury Requiring Renal Replacement Therapy in the Postoperative Elderly

SummaryBackgroundSeptic acute kidney injury (AKI) is a common complication in intensive care units (ICU), it and portends a higher risk of morbidity and death than nonseptic AKI. However, its outcome and prognostic factors among elderly postoperative patients remain unknown. We aimed to determine the risk factors and predictors of mortality among postoperative elderly patients (≥ 65 years) with septic AKI requiring acute dialysis.MethodsThe study protocol was based on that of a clinical cohort study of renal failure patients in the database of the National Taiwan University Surgical ICU Acute Renal Failure (NSARF) Study Group. From January 2002 to July 2009, patients (aged > 18 years) with postoperative AKI requiring renal replacement therapy (RRT) were recruited for this study. Each case of septic AKI before operation was identified and patients with end-stage renal disease were excluded.ResultsA total of 292 postoperative patients with septic AKI requiring dialysis were identified during the study period. The mean (SD) age was 65.9 (11.9) years and 68.2% were men. Abdominal surgery was the most common type of surgery (42.8%), followed by cardiovascular (28.8%) and chest surgery (15.4%). The most common indications for RRT in this study cohort were azotemia in 223 patients (76.4%) and fluid overload in 62 patients (21.2%); 92 (31.5%) patients had one indication, 170 (58.2%) had two indications, and 30 (10.3%) had more than three indications. The elderly patients (those ≥ 65 years) had anemia, underwent abdominal surgery, and received dialysis for fluid overload more frequently than the young adults. By contrast, the young adults were more likely to present with shock requiring vasopressor use and have abnormal liver functions. In the elderly subgroup, the outcome was found to be associated with mechanical ventilator use, but not with disease severity, comorbidities, types of surgery and the indication for dialysis.ConclusionsThe hospital mortality of postoperative elderly patients with septic AKI was more than 60% and was not affected by age. Mechanical ventilator use was the major risk factor and prognostic factor for elderly patients in this clinical setting

An Immunoassay for Dibutyl Phthalate Based on Direct Hapten Linkage to the Polystyrene Surface of Microtiter Plates

BACKGROUND: Dibutyl phthalate (DBP) is predominantly used as a plasticizer inplastics to make them flexible. Extensive use of phthalates in both industrial processes and other consumer products has resulted in the ubiquitous presence of phthalates in the environment. In order to better determine the level of pollution in the environment and evaluate the potential adverse effects of exposure to DBP, immunoassay for DBP was developed. METHODOLOGY/PRINCIPAL FINDINGS: A monoclonal antibody specific to DBP was produced from a stable hybridoma cell line generated by lymphocyte hybridoma technique. An indirect competitive enzyme-linked immunosorbent assay (icELISA) employing direct coating of hapten on polystyrene microtiter plates was established for the detection of DBP. Polystyrene surface was first oxidized by permanganate in dilute sulfuric acid to generate carboxyl groups. Then dibutyl 4-aminophthalate, which is an analogue of DBP, was covalently linked to the carboxyl groups of polystyrene surface with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC). Compared with conjugate coated format (IC(50)=106 ng/mL), the direct hapten coated format (IC(50)=14.6 ng/mL) improved assay sensitivity after careful optimization of assay conditions. The average recovery of DBP from spiked water sample was 104.4% and the average coefficient of variation was 9.95%. Good agreement of the results obtained by the hapten coated icELISA and gas chromatography-mass spectrometry further confirmed the reliability and accuracy of the icELISA for the detection of DBP in certain plastic and cosmetic samples. CONCLUSIONS/SIGNIFICANCE: The stable and efficient hybridoma cell line obtained is an unlimited source of sensitive and specific antibody to DBP. The hapten coated format is proposed as generally applicable because the carboxyl groups on modified microtiter plate surface enables stable immobilization of aminated or hydroxylated hapten with EDC. The developed hapten coated icELISA can be used as a convenient quantitative tool for the sensitive and accurate monitoring DBP in water, plastic and cosmetic samples

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Publisher Copyright: © 2022, The Author(s).Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.Peer reviewe