Deep learning for named entity recognition on Chinese electronic medical records: Combining deep transfer learning with multitask bi-directional LSTM RNN.

Specific entity terms such as disease, test, symptom, and genes in Electronic Medical Record (EMR) can be extracted by Named Entity Recognition (NER). However, limited resources of labeled EMR pose a great challenge for mining medical entity terms. In this study, a novel multitask bi-directional RNN model combined with deep transfer learning is proposed as a potential solution of transferring knowledge and data augmentation to enhance NER performance with limited data. The proposed model has been evaluated using micro average F-score, macro average F-score and accuracy. It is observed that the proposed model outperforms the baseline model in the case of discharge datasets. For instance, for the case of discharge summary, the micro average F-score is improved by 2.55% and the overall accuracy is improved by 7.53%. For the case of progress notes, the micro average F-score and the overall accuracy are improved by 1.63% and 5.63%, respectively

A multitask bi-directional RNN model for named entity recognition on Chinese electronic medical records

Abstract Background Electronic Medical Record (EMR) comprises patients’ medical information gathered by medical stuff for providing better health care. Named Entity Recognition (NER) is a sub-field of information extraction aimed at identifying specific entity terms such as disease, test, symptom, genes etc. NER can be a relief for healthcare providers and medical specialists to extract useful information automatically and avoid unnecessary and unrelated information in EMR. However, limited resources of available EMR pose a great challenge for mining entity terms. Therefore, a multitask bi-directional RNN model is proposed here as a potential solution of data augmentation to enhance NER performance with limited data. Methods A multitask bi-directional RNN model is proposed for extracting entity terms from Chinese EMR. The proposed model can be divided into a shared layer and a task specific layer. Firstly, vector representation of each word is obtained as a concatenation of word embedding and character embedding. Then Bi-directional RNN is used to extract context information from sentence. After that, all these layers are shared by two different task layers, namely the parts-of-speech tagging task layer and the named entity recognition task layer. These two tasks layers are trained alternatively so that the knowledge learned from named entity recognition task can be enhanced by the knowledge gained from parts-of-speech tagging task. Results The performance of our proposed model has been evaluated in terms of micro average F-score, macro average F-score and accuracy. It is observed that the proposed model outperforms the baseline model in all cases. For instance, experimental results conducted on the discharge summaries show that the micro average F-score and the macro average F-score are improved by 2.41% point and 4.16% point, respectively, and the overall accuracy is improved by 5.66% point. Conclusions In this paper, a novel multitask bi-directional RNN model is proposed for improving the performance of named entity recognition in EMR. Evaluation results using real datasets demonstrate the effectiveness of the proposed model

Live attenuated Salmonella typhimurium vaccines delivering SaEsxA and SaEsxB via type III secretion system confer protection against Staphylococcus aureus infection

Abstract Background Staphylococcus aureus (S. aureus) causes a wide range of infectious diseases in human and animals. The emergence of antibiotic-resistant strains demands novel strategies for prophylactic vaccine development. In this study, live attenuated S. enterica subsp. enterica serotype Typhimurium (S. Typhimurium) vaccine against S. aureus infection was developed, in which Salmonella Pathogenesis Island-1 Type 3 Secretion System (SPI-1 T3SS) was employed to deliver SaEsxA and SaEsxB, two of ESAT-6-like (Early Secreted Antigenic Target-6) virulence factors of S. aureus. Methods Antigens SaEsxA and SaEsxB were fused with the N-terminal secretion and translocation domain of SPI-1 effector SipA. And cytosolic delivery of Staphylococcal antigens into macrophages was examined by western blot. BALB/c mice were orally immunized with S. Typhimurium-SaEsxA and S. Typhimurium-SaEsxB vaccines. Antigen-specific humoral and Th1/Th17 immune responses were examined by ELISA and ELISPOT assays 7–9 days after the 2nd booster. For ELISPOT assays, the statistical significance was determined by Student’s t test. The vaccine efficacy was evaluated by lethal challenge with two S. aureus clinical isolates Newman strain and USA 300 strain. Statistical significance was determined by Log rank (Mantel-Cox) analysis. And a P value of < 0.05 was considered statistically significant. Results Oral administration of S. Typhimurium-SaEsxA and S. Typhimurium-SaEsxB vaccines induced antigen-specific humoral and Th1/Th17 immune responses, which increased the survival rate for vaccinated mice when challenged with S. aureus strains. Conclusions The newly developed S. Typhimurium-based vaccines delivering SaEsxA and SaEsxB by SPI-1 T3SS could confer protection against S. aureus infection. This study provides evidence that translocation of foreign antigens via Salmonella SPI-1 T3SS into the cytosol of antigen presenting cells (APCs) could induce potent immune responses against pathogens

Additional file 2: of Live attenuated Salmonella typhimurium vaccines delivering SaEsxA and SaEsxB via type III secretion system confer protection against Staphylococcus aureus infection

Table S2. Evaluation of cellular immune response against rSaEsxA and rSaEsxB by ELISPOT. The spot-forming cells were counted using an immunospot reader system. The spot numbers were shown. (XLSX 41 kb

Additional file 3: of Live attenuated Salmonella typhimurium vaccines delivering SaEsxA and SaEsxB via type III secretion system confer protection against Staphylococcus aureus infection

Table S3. Survival curves of vaccinated mice after lethal challenge with two clinical S. aureus strains. Mouse numbers were shown after challenge with S. aureus strains. (XLSX 35 kb

Additional file 1: of Live attenuated Salmonella typhimurium vaccines delivering SaEsxA and SaEsxB via type III secretion system confer protection against Staphylococcus aureus infection

Table S1. Evaluation of humoral and mucosal immune responses against rSaEsxA and rSaEsxB by ELISA. Readout at OD450 was shown. (XLSX 49 kb

PSCA and MUC1 in non-small-cell lung cancer as targets of chimeric antigen receptor T cells

© 2017 Taylor & Francis Group, LLC. In recent years, immunotherapies, such as those involving chimeric antigen receptor (CAR) T cells, have become increasingly promising approaches to non-small-cell lung cancer (NSCLC) treatment. In this study, we explored the antitumor potential of prostate stem cell antigen (PSCA)-redirected CAR T and mucin 1 (MUC1)-redirected CAR T cells in tumor models of NSCLC. First, we generated patient-derived xenograft (PDX) mouse models of human NSCLC that maintained the antigenic profiles of primary tumors. Next, we demonstrated the expression of PSCA and MUC1 in NSCLC, followed by the generation and confirmation of the specificity and efficacy of PSCA- and MUC1-targeting CAR T cells against NSCLC cell lines in vitro. Finally, we demonstrated that PSCA-targeting CAR T cells could efficiently suppress NSCLC tumor growth in PDX mice and synergistically eliminate PSCA + MUC1 + tumors when combined with MUC1-targeting CAR T cells. Taken together, our studies demonstrate that PSCA and MUC1 are both promising CAR T cell targets in NSCLC and that the combinatorial targeting of these antigens could further enhance the antitumor efficacy of CAR T cells.Link_to_subscribed_fulltex

CD215+ Myeloid Cells Respond to Interleukin 15 Stimulation and Promote Tumor Progression

Interleukin 15 (IL-15) regulates the development, survival, and functions of multiple innate and adaptive immune cells and plays a dual role in promoting both tumor cell growth and antitumor immunity. Here, we demonstrated that the in vivo injection of recombinant human IL-15 (200 mu g/kg) or murine IL-15 (3 mu g/kg) to tumor-bearing NODSCID- IL2Rg-/-(NSI) mice resulted in increased tumor progression and CD45+ CD11b+ Gr-1+ CD215+ cell expansion in the tumors and spleen. In B16F10-bearing C57BL/6 mice model, we found that murine IL-15 has antitumoral effect since the activation and expansion of CD8+ T cells with murine IL-15 treatment. But no enhanced or reduced tumor growth was observed in mice when human IL-15 was used. However, both murine and human IL-15 promote CD45+ CD11b+ Gr-1+ CD215+ cells expansion. In xenograft tumor models, CD215+ myeloid cells, but not CD215-cells, responded to human IL-15 stimulation and promoted tumor growth. Furthermore, we found that human IL-15 mediated insulin-like growth factor-1 production in CD215+ myeloid cells and blocking IGF-1 reduced the tumor-promoting effect of IL-15. Finally, we observed that higher IGF-1 expression is an indicator of poor prognosis among lung adenocarcinoma patients. These findings provide evidence that IL-15 may promote tumor cell progression via CD215+ myeloid cells, and IGF-1 may be an important candidate that IL-15 facilitates tumor growth