Reprogramming Antagonizes the Oncogenicity of HOXA13-Long Noncoding RNA HOTTIP Axis in Gastric Cancer Cells.

Reprogramming of cancer cells into induced pluripotent stem cells (iPSCs) is a compelling idea for inhibiting oncogenesis, especially through modulation of homeobox proteins in this reprogramming process. We examined the role of various long noncoding RNAs (lncRNAs)-homeobox protein HOXA13 axis on the switching of the oncogenic function of bone morphogenetic protein 7 (BMP7), which is significantly lost in the gastric cancer cell derived iPS-like cells (iPSLCs). BMP7 promoter activation occurred through the corecruitment of HOXA13, mixed-lineage leukemia 1 lysine N-methyltransferase, WD repeat-containing protein 5, and lncRNA HoxA transcript at the distal tip (HOTTIP) to commit the epigenetic changes to the trimethylation of lysine 4 on histone H3 in cancer cells. By contrast, HOXA13 inhibited BMP7 expression in iPSLCs via the corecruitment of HOXA13, enhancer of zeste homolog 2, Jumonji and AT rich interactive domain 2, and lncRNA HoxA transcript antisense RNA (HOTAIR) to various cis-element of the BMP7 promoter. Knockdown experiments demonstrated that HOTTIP contributed positively, but HOTAIR regulated negatively to HOXA13-mediated BMP7 expression in cancer cells and iPSLCs, respectively. These findings indicate that the recruitment of HOXA13-HOTTIP and HOXA13-HOTAIR to different sites in the BMP7 promoter is crucial for the oncogenic fate of human gastric cells. Reprogramming with octamer-binding protein 4 and Jun dimerization protein 2 can inhibit tumorigenesis by switching off BMP7. Stem Cells 2017;35:2115-2128.

Positive Feedback Loop of OCT4 and c-JUN Expedites Cancer Stemness in Liver Cancer.

The network of stemness genes and oncogenes in human patient-specific reprogrammed cancer stem cells (CSCs) remains elusive, especially in liver cancer. HepG2-derived induced pluripotent stem cell-like cells (HepG2-iPS-like cells) were generated by introducing Yamanaka factors and the knockdown vector shTP53. They exhibited features of stemness and a higher tumorigenesis after xenograft transplantation compared with HepG2 cells. The cancerous mass of severe combined immunodeficiency (SCID) mice derived from one colony was dissected and cultured to establish reprogrammed HepG2-derived CSC-like cells (designated rG2-DC-1C). A single colony exhibited 42% occurrence of tumors with higher proliferation capacities. rG2-DC-1C showed continuous expression of the OCT4 stemness gene and of representative tumor markers, potentiated chemoresistance characteristics, and invasion activities. The sphere-colony formation ability and the invasion activity of rG2-DC-1C were also higher than those of HepG2 cells. Moreover, the expression of the OCT4 gene and the c-JUN oncogene, but not of c-MYC, was significantly elevated in rG2-DC-1C, whereas no c-JUN expression was observed in HepG2 cells. The positive-feedback regulation via OCT4-mediated transactivation of the c-JUN promoter and the c-JUN-mediated transactivation of the OCT4 promoter were crucial for promoting cancer development and maintaining cancer stemness in rG2-DC-1C. Increased expression of OCT4 and c-JUN was detected in the early stage of human liver cancer. Therefore, the positive feedback regulation of OCT4 and c-JUN, resulting in the continuous expression of oncogenes such as c-JUN, seems to play a critical role in the determination of the cell fate decision from iPS cells to CSCs in liver cancer. Stem Cells 2016;34:2613-2624.

Importance-Performance Analysis of Personal Health Records in Taiwan: A Web-Based Survey.

BACKGROUND: Empowering personal health records (PHRs) provides basic human right, awareness, and intention for health promotion. As health care delivery changes toward patient-centered services, PHRs become an indispensable platform for consumers and providers. Recently, the government introduced "My health bank," a Web-based electronic medical records (EMRs) repository for consumers. However, it is not yet a PHR. To date, we do not have a platform that can let patients manage their own PHR. OBJECTIVE: This study creates a vision of a value-added platform for personal health data analysis and manages their health record based on the contents of the "My health bank." This study aimed to examine consumer expectation regarding PHR, using the importance-performance analysis. The purpose of this study was to explore consumer perception regarding this type of a platform: it would try to identify the key success factors and important aspects by using the importance-performance analysis, and give some suggestions for future development based on it. METHODS: This is a cross-sectional study conducted in Taiwan. Web-based invitation to participate in this study was distributed through Facebook. Respondents were asked to watch an introductory movie regarding PHR before filling in the questionnaire. The questionnaire was focused on 2 aspects, including (1) system functions, and (2) system design and security and privacy. The questionnaire would employ 12 and 7 questions respectively. The questionnaire was designed following 5-points Likert scale ranging from 1 ("disagree strongly") to 5 ("Agree strongly"). Afterwards, the questionnaire data was sorted using IBM SPSS Statistics 21 for descriptive statistics and the importance-performance analysis. RESULTS: This research received 350 valid questionnaires. Most respondents were female (219 of 350 participants, 62.6%), 21-30 years old (238 of 350 participants, 68.0%), with a university degree (228 of 350 participants, 65.1%). They were still students (195 out of 350 participants, 56.6%), with a monthly income of less than NT $30,000 (230 of 350 participants, 65.7%), and living in the North Taiwan (236 of 350 participants, 67.4%), with a good self-identified health status (171 of 350 participants, 48.9%). After performing the importance-performance analysis, we found the following: (1) instead of complex functions, people just want to have a platform that can let them integrate and manage their medical visit, health examination, and life behavior records; (2) they do not care whether their PHR is shared with others; and (3) most of the participants think the system security design is not important, but they also do not feel satisfied with the current security design. CONCLUSIONS: Overall, the issues receiving the most user attention were the system functions, circulation, integrity, ease of use, and continuity of the PHRs, data security, and privacy protection.

Metadata Correction: Importance-Performance Analysis of Personal Health Records in Taiwan: A Web-Based Survey.

[This corrects the article DOI: .].

SEMRES - A Triple Security Protected Blockchain Based Medical Record Exchange Structure.

BACKGROUND AND OBJECTIVE: COVID-19, a serious infectious disease outbreak started in the end of 2019, has caused a strong impact on the overall medical system, which reflects the gap in the volume and capacity of medical services and highlights the importance of clinical data ex-change and application. The most important concerns of medical records in the medical field include data privacy, data correctness, and data security. By realizing these three goals, medical records can be made available to different hospital information systems to achieve the most complete medical care services. The privacy and protection of health data require detailed specification and usage requirements, which is particularly important for cross-agency data exchange. METHODS: This research is composed of three main modules. "Combined Encryption and Decryption Architecture", which includes the hybrid double encryption mechanism of AES and RSA, and encrypts medical records to produce "Secured Encrypted Medical Record". "Decentralize EMR Repository", which includes data decryption and an exchange mechanism. After a data transmission is completed, the content verification and data decryption process will be launched to confirm the correctness of the data and obtain the data. A blockchain architecture is used to store the hash value of the encrypted EMR, and completes the correctness verification of the EMR after transmission through the hash value. RESULTS: The results of this study provide an efficient triple encryption mechanism for electronic medical records. SEMRES ensures the correctness of data through the non-repudiation feature of a blockchain open ledger, and complete integrated information security protection and data verification architecture, in order that medical data can be exchanged, verified, and applied in different locations. After the patient receives medical services, the medical record is re-encrypted and verified and stored in the patient's medical record. The blockchain architecture is used to ensure the verification of non-repudiation of medical service, and finally to complete the payment for medical services. CONCLUSIONS: The main aim of this study was to complete a security architecture for medical data, and develop a triple encryption authentication architecture to help data owners easily and securely share personal medical records with medical service personnel.

Building a portable data and information interoperability infrastructure-framework for a standard Taiwan Electronic Medical Record Template.

Traditional electronic health record (EHR) data are produced from various hospital information systems. They could not have existed independently without an information system until the incarnation of XML technology. The interoperability of a healthcare system can be divided into two dimensions: functional interoperability and semantic interoperability. Currently, no single EHR standard exists that provides complete EHR interoperability. In order to establish a national EHR standard, we developed a set of local EHR templates. The Taiwan Electronic Medical Record Template (TMT) is a standard that aims to achieve semantic interoperability in EHR exchanges nationally. The TMT architecture is basically composed of forms, components, sections, and elements. Data stored in the elements which can be referenced by the code set, data type, and narrative block. The TMT was established with the following requirements in mind: (1) transformable to international standards; (2) having a minimal impact on the existing healthcare system; (3) easy to implement and deploy, and (4) compliant with Taiwan's current laws and regulations. The TMT provides a basis for building a portable, interoperable information infrastructure for EHR exchange in Taiwan.