Notch signaling and natural killer cell infiltration in tumor tissues underlie medulloblastoma prognosis.

Medulloblastoma is the most common embryonic brain tumor in children. We investigated a cohort of 52 Asian medulloblastoma patients aged between 0 and 19 years old, who received surgical resections and post-resection treatments in the Taipei Medical University Hospital and the Taipei Veterans General Hospital. Genome-wide RNA sequencing was performed on fresh-frozen surgical tissues. These data were analyzed using the CIBERSORTx immune deconvolution software. Two external clinical and molecular datasets from United States (n = 62) and Canada (n = 763) were used to evaluate the transferability of the gene-signature scores across ethnic populations. The abundance of 13 genes, including DLL1, are significantly associated with overall survival (All Cox regression P < 0.001). A gene-signature score was derived from the deep transcriptome, capable of indicating patients' subsequent tumor recurrence (Hazard Ratio [HR] 1.645, confidence interval [CI] 1.337-2.025, P < 0.001) and mortality (HR 2.720, CI 1.798-4.112, P < 0.001). After the adjustment of baseline clinical factors, the score remains indicative of recurrence-free survival (HR 1.604, CI 1.292-1.992, P < 0.001) and overall survival (HR 2.781, CI 1.762-4.390, P < 0.001). Patients stratified by this score manifest not only distinct prognosis but also different molecular characteristics: Notch signaling ligands and receptors are comparatively overexpressed in patients with poorer prognosis, while tumor infiltrating natural killer cells are more abundant in patients with better prognosis. Additionally, immunohistochemical staining showed the DLL1 protein, a major ligand in the Notch signaling pathway, and the NCAM1 protein, a representative biomarker of natural killer cells, are present in the surgical tissues of patients of four molecular subgroups, WNT, SHH, Group 3 and Group 4. NCAM1 RNA level is also positively associated with the mutation burden in tumor (P = 0.023). The gene-signature score is validated successfully in the Canadian cohort (P = 0.009) as well as its three molecular subgroups (SHH, Group 3 and Group 4; P = 0.047, 0.018 and 0.040 respectively). In conclusion, pediatric medullablastoma patients can be stratified by gene-signature scores with distinct prognosis and molecular characteristics. Ligands and receptors of the Notch signaling pathway are overexpressed in the patient stratum with poorer prognosis. Tumor infiltrating natural killer cells are more abundant in the patient stratum with better prognosis.

Experiences With Internet Triaging of 9498 Outpatients Daily at the Largest Public Hospital in Taiwan During the COVID-19 Pandemic: Observational Study.

BACKGROUND: During pandemics, acquiring outpatients' travel, occupation, contact, and cluster histories is one of the most important measures in assessing the disease risk among incoming patients. Previous means of acquiring this information in the examination room have been insufficient in preventing disease spread. OBJECTIVE: This study aimed to demonstrate the deployment of an automatic system to triage outpatients over the internet. METHODS: An automatic system was incorporated in the existing web-based appointment system of the hospital and deployed along with its on-site counterpart. Automatic queries to the virtual private network travel and contact history database with each patient's national ID number were made for each attempt to acquire the patient's travel and contact histories. Patients with relevant histories were denied registration or entry. Text messages were sent to patients without a relevant history for an expedited route of entry if applicable. RESULTS: A total of 127,857 visits were recorded. Among all visits, 91,195 were registered on the internet. In total, 71,816 of them generated text messages for an expedited route of entry. Furthermore, 65 patients had relevant histories, as revealed by the virtual private network database, and were denied registration or entry. CONCLUSIONS: An automatic triage system to acquire outpatients' relevant travel and contact histories was deployed rapidly in one of the largest academic medical centers in Taiwan. The updated system successfully denied patients with relevant travel or contact histories entry to the hospital, thus preventing long lines outside the hospital. Further efforts could be made to integrate the system with the electronic medical record system.

Visiting in disguise: Analysis of inpatient companions in the time of COVID-19.

BACKGROUND: As outbreak of COVID-19 infection, on April 3, 2020, it is stipulated that the number of inpatient companions is limited to one in Taiwan. All companions are required to register their real personal data with 14 days of travel history, occupation, contact history, and cluster history. We would like to evaluate the impact of the new regulations to the accompanying and visiting culture in Taiwan, via analyzing the appearance and characteristics of inpatient companions in this period. METHODS: Using intelligent technology, we designed a novel system in managing the inpatient companions (InPatients Companions Management System [IPCMS]), and the IPCMS was used to collect data about characteristics of inpatients and companions between April 27 and May 3, 2020. The database is built using MySQL software. Microsoft Excel 2016 and SPSS version 20.0 statistical software were used for data analysis, including the basic data of the companions, differential analysis of companions' gender, person-days and cumulative time, differential analysis of accompaniment-patient relationship, and frequency of accompaniment and cumulative hours. RESULTS: During study period, daily inpatient admissions ranged from 2242 to 2514, the number of companions per day ranged from 2048 to 2293, and the number of companions for one inpatient is 1 to 9 per day, with an average of 1.20 to 1.26. The companions were mostly family members, and most of them were the inpatients' children (32.9%), and spouse (26.13%). More females than males were noted in all categories of companionship with statistical significance. CONCLUSION: The data obtained in this study could be an important basis for the transformation and reform of the companions culture in Taiwan's hospitals and will also provide a glimpse into the attitudes and culture of companions who have long been ignorant and neglected. The experience gained in our IPCMS could also serve as a reference for other hospitals in Taiwan and worldwide.

Deployment of a computerized ward visitor registration system in coronavirus disease 2019 epidemic: Experiences of a large academic medical center in Taiwan.

BACKGROUND: Visitors to hospitalized patients during an epidemic might themselves be carriers and are therefore likely to spread the disease in wards. Although measures were taken to restrict hospital visits, traditional paper-based registration is insufficient to screen and monitor the numbers of visitors to a large hospital. METHODS: Throughout March 2020, during the coronavirus disease 2019 crisis, a computer system was deployed in the 2800-bed Taipei Veterans General Hospital (Taipei, Taiwan) to register, screen, and monitor inpatient visitors. This system comprised three parts: online registration form, entrance check-in interface, and registration database. The early utilization of this newly deployed system was then analyzed. RESULTS: A total of 22,336 visits were recorded between March 11, 2020, and March 31, 2020, with 1064 a day on average. Out of these visits, 18.1% (n = 4049) had made online reservations within 48 hours. On the other hand, of all 4941 online reservations, 18.1% (n = 892) were no-shows. In the last 12 days of the study period, eight prospective visitors were identified as ineligible by the computer system, and so their visits were denied. CONCLUSION: Using a computer system, the hospital was able to enforce restrictions on hospital visits. Although the online registration system had not been fully used yet in the early phase of adoption, its superiority from the standpoint of disease control should enable hospital managers to consider abolishing on-site visitor registration.

Hospital-Owned Apps in Taiwan: Nationwide Survey.

BACKGROUND: Over the last decade, the use of mobile phone apps in the health care industry has grown rapidly. Owing to the high penetration rate of Internet use in Taiwan, hospitals are eager to provide their own apps to improve the accessibility of medical care for patients. OBJECTIVE: The aims of this study were to provide an overview of the currently available hospital-owned apps in Taiwan and to conduct a cross-hospital comparison of app features. METHODS: In May 2017, the availability of apps from all 414 hospitals in Taiwan was surveyed from the hospital home pages and the Google Play app store. The features of the downloaded apps were then examined in detail and, for each app, the release date of the last update, download frequency, and rating score were obtained from Google Play. RESULTS: Among all the 414 hospitals in Taiwan, 150 (36.2%) owned Android apps that had been made available for public use, including 95% (18/19) of the academic medical centers, 77% (63/82) of the regional hospitals, and 22.0% (69/313) of the local community hospitals. Among the 13 different functionalities made available by the various hospital-owned apps, the most common were the doctor search (100%, 150/150), real-time queue monitoring (100%, 150/150), and online appointment scheduling (94.7%, 142/150) functionalities. The majority of apps (57.3%, 86/150) had a rating greater than 4 out of 5, 49.3% (74/150) had been updated at some point in 2017, and 36.0% (54/150) had been downloaded 10,000 to 50,000 times. CONCLUSIONS: More than one-third of the hospitals owned apps intended to increase patient access to health care. The most common app features might reflect the health care situation in Taiwan, where the overcrowded outpatient departments of hospitals operate in an open-access mode without any strict referral system. Further research should focus on the effectiveness and safety of these apps.

DriverDB: an exome sequencing database for cancer driver gene identification.

Exome sequencing (exome-seq) has aided in the discovery of a huge amount of mutations in cancers, yet challenges remain in converting oncogenomics data into information that is interpretable and accessible for clinical care. We constructed DriverDB (http://ngs.ym.edu.tw/driverdb/), a database which incorporates 6079 cases of exome-seq data, annotation databases (such as dbSNP, 1000 Genome and Cosmic) and published bioinformatics algorithms dedicated to driver gene/mutation identification. We provide two points of view, 'Cancer' and 'Gene', to help researchers to visualize the relationships between cancers and driver genes/mutations. The 'Cancer' section summarizes the calculated results of driver genes by eight computational methods for a specific cancer type/dataset and provides three levels of biological interpretation for realization of the relationships between driver genes. The 'Gene' section is designed to visualize the mutation information of a driver gene in five different aspects. Moreover, a 'Meta-Analysis' function is provided so researchers may identify driver genes in customer-defined samples. The novel driver genes/mutations identified hold potential for both basic research and biotech applications.

A base-calling algorithm for Tm-shifted melting curve SNP assay.

BACKGROUND: Tm-shifted melting curve SNP assays are a class of homogeneous, low-cost genotyping assays. Alleles manifest themselves as signal peaks in the neighbourhood of theoretical allele-specific melting temperatures. Base calling for these assays has mostly relied on unsupervised algorithm or human visual inspection to date. However, a practical clinical test needs to handle one or few individual samples at a time. This could pose a challenge for unsupervised algorithms which usually require a large number of samples to define alleles-representing signal clusters on the fly. METHODS: We presented a supervised base-calling algorithm and software for Tm-shifted melting curve SNP assays. The algorithm comprises a peak detection procedure and an ordinal regression model. The peak detection procedure is required for building models as well as handling new samples. Ordinal regression is proposed because signal intensities of alleles AA, AB, and BB usually follow an ordinal pattern with the heterozygous allele lie between two distinct homozygous alleles. Coefficients of the ordinal regression model are first trained and then used for base calling. RESULTS: A dataset of 12 SNPs of 44 unrelated persons was used for a demonstration purpose. The call rate is 99.6%. Among the base calls, 99.1% are identical to those made by the sequencing method. A small fraction of the melting curve signals (0.4%) is declared as "no call" for further human inspection. A software was implemented using the Java language, providing a graphical user interface for the visualization and handling of multiple melting curve signals. CONCLUSIONS: Tm-shifted melting curve SNP assays, together with the proposed base calling algorithm and software, provide a practical solution for genetic tests on a clinical setting. The software is available in http://www.bioinformatics.org/mcsnp/wiki/Main/HomePage.

A comparison between pulsed radiofrequency and electro-acupuncture for relieving pain in patients with chronic low back pain.

Many treatment options for chronic low back pain are available, including varied forms of electric stimulation. But little is known about the electricity effect between electro-acupuncture and pulsed radiofrequency. The objective of this study is to assess the difference in effectiveness of pain relief between pulsed radiofrequency and electro-acupuncture. Visual analog score (VAS) pain score, the Oswestry disability index (ODI) to measure a patient's permanent functional disability, and Short form 36 (SF-36) which is a survey used in health assessment to determine the cost-effectiveness of a health treatment, were used as rating systems to measure the pain relief and functional improvement effect of pulsed radiofrequency and electro-acupuncture, based on the methodological quality of the randomized controlled trials, the relevance between the study groups, and the consistency of the outcome evaluation. First, the baseline status before therapy shows no age and gender influence in the SF-36 and VAS score but it is significant in the ODI questionnaire. From ANOVA analyses, it is apparent that radiofrequency therapy is a significant improvement over electro-acupuncture therapy after one month. But electro-acupuncture also showed functional improvement in the lumbar spine from the ODI. This study provides sufficient evidence of the superiority of pulsed radiofrequency (PRF) therapy for low back pain relief compared with both electro-acupuncture (EA) therapy and the control group. But the functional improvement of the lumbar spine was proved under EA therapy only. Both therapies are related to electricity effects.