Accuracy of long-form data in the Taiwan cancer registry Kao, Chia-Wen; Chiang, Chun-Ju; Lin, Li-Ju ...
Journal of the Formosan Medical Association,
November 2021, 2021-11-00, 20211101, 2021-11-01, Volume:
120, Issue:
11
Journal Article
Peer reviewed
Open access
The Taiwan Cancer Registry (TCR) is a nationwide population-based registry that collects the data of patients with newly diagnosed cancer from hospitals with ≥50 beds. TCR data are high quality in ...terms of completeness and timeliness. However, accuracy is also a crucial quality indicator. This study evaluated the accuracy rates of selected 55 major items in the long-form TCR data between 2014 and 2016 with 700 reported cases randomly selected from 25 long-form-reporting hospitals. We calculated the accuracy rates of the reported data by employing a reabstracted chart review. Among the 55 items, the accuracy rates of 38 (69%) were at least 95%, those of 10 (18%) were between 90% and 95%, those of 5 (9%) were between 85% and 90%, and the remaining 2 (4%) were between 80% and 85%. This demonstrates a high degree of accuracy in the TCR long-form data.
CCCH-type zinc-finger antiviral protein (ZAP) is a host factor that restricts the infection of many viruses mainly through RNA degradation, translation inhibition and innate immune responses. So far, ...only one flavivirus, yellow fever virus, has been reported to be ZAP-resistant. Here, we investigated the antiviral potential of human ZAP (isoform ZAP-L and ZAP-S) against three flaviviruses, Japanese encephalitis virus (JEV), dengue virus (DENV) and Zika virus (ZIKV). Infection of JEV but not DENV or ZIKV was blocked by ZAP overexpression, and depletion of endogenous ZAP enhanced JEV replication. ZAP hampered JEV translation and targeted viral RNA for 3'-5' RNA exosome-mediated degradation. The zinc-finger motifs of ZAP were essential for RNA targeting and anti-JEV activity. JEV 3'-UTR, especially in the region with dumbbell structures and high content of CG dinucleotide, was mapped to bind ZAP and confer sensitivity to ZAP. In summary, we identified JEV as the first ZAP-sensitive flavivirus. ZAP may act as an intrinsic antiviral factor through specific RNA binding to fight against JEV infection.
The COVID-19 pandemic presents an unprecedented challenge to global public health. Rapid development and deployment of safe and effective vaccines are imperative to control the pandemic. In the ...current study, we applied our adjuvanted stable prefusion SARS-CoV-2 spike (S-2P)-based vaccine, MVC-COV1901, to hamster models to demonstrate immunogenicity and protection from virus challenge. Golden Syrian hamsters immunized intramuscularly with two injections of 1 µg or 5 µg of S-2P adjuvanted with CpG 1018 and aluminum hydroxide (alum) were challenged intranasally with SARS-CoV-2. Prior to virus challenge, the vaccine induced high levels of neutralizing antibodies with 10,000-fold higher IgG level and an average of 50-fold higher pseudovirus neutralizing titers in either dose groups than vehicle or adjuvant control groups. Six days after infection, vaccinated hamsters did not display any weight loss associated with infection and had significantly reduced lung pathology and most importantly, lung viral load levels were reduced to lower than detection limit compared to unvaccinated animals. Vaccination with either 1 μg or 5 μg of adjuvanted S-2P produced comparable immunogenicity and protection from infection. This study builds upon our previous results to support the clinical development of MVC-COV1901 as a safe, highly immunogenic, and protective COVID-19 vaccine.
Dengue is one of the most important arboviral diseases caused by infection of four serotypes of dengue virus (DEN). We found that activation of interferon regulatory factor 3 (IRF3) triggered by ...viral infection and by foreign DNA and RNA stimulation was blocked by DEN-encoded NS2B3 through a protease-dependent mechanism. The key adaptor protein in type I interferon pathway, human mediator of IRF3 activation (MITA) but not the murine homologue MPYS, was cleaved in cells infected with DEN-1 or DEN-2 and with expression of the enzymatically active protease NS2B3. The cleavage site of MITA was mapped to LRR↓(96)G and the function of MITA was suppressed by dengue protease. DEN replication was reduced with overexpression of MPYS but not with MITA, while DEN replication was enhanced by MPYS knockdown, indicating an antiviral role of MITA/MPYS against DEN infection. The involvement of MITA in DEN-triggered innate immune response was evidenced by reduction of IRF3 activation and IFN induction in cells with MITA knockdown upon DEN-2 infection. NS2B3 physically interacted with MITA, and the interaction and cleavage of MITA could be further enhanced by poly(dA:dT) stimulation. Thus, we identified MITA as a novel host target of DEN protease and provide the molecular mechanism of how DEN subverts the host innate immunity.
During the outbreak of coronavirus disease 2019 (COVID-19), consistent and considerable differences in disease severity and mortality rate of patients treated in Hubei province compared to those in ...other parts of China have been observed. We sought to compare the clinical characteristics and outcomes of patients being treated inside and outside Hubei province, and explore the factors underlying these differences.
Collaborating with the National Health Commission, we established a retrospective cohort to study hospitalised COVID-19 cases in China. Clinical characteristics, the rate of severe events and deaths, and the time to critical illness (invasive ventilation or intensive care unit admission or death) were compared between patients within and outside Hubei. The impact of Wuhan-related exposure (a presumed key factor that drove the severe situation in Hubei, as Wuhan is the epicentre as well the administrative centre of Hubei province) and the duration between symptom onset and admission on prognosis were also determined.
At the data cut-off (31 January 2020), 1590 cases from 575 hospitals in 31 provincial administrative regions were collected (core cohort). The overall rate of severe cases and mortality was 16.0% and 3.2%, respectively. Patients in Hubei (predominantly with Wuhan-related exposure, 597 (92.3%) out of 647) were older (mean age 49.7
44.9 years), had more cases with comorbidity (32.9%
19.7%), higher symptomatic burden, abnormal radiologic manifestations and, especially, a longer waiting time between symptom onset and admission (5.7
4.5 days) compared with patients outside Hubei. Patients in Hubei (severe event rate 23.0%
11.1%, death rate 7.3%
0.3%, HR (95% CI) for critical illness 1.59 (1.05-2.41)) have a poorer prognosis compared with patients outside Hubei after adjusting for age and comorbidity. However, among patients outside Hubei, the duration from symptom onset to hospitalisation (mean 4.4
4.7 days) and prognosis (HR (95%) 0.84 (0.40-1.80)) were similar between patients with or without Wuhan-related exposure. In the overall population, the waiting time, but neither treated in Hubei nor Wuhan-related exposure, remained an independent prognostic factor (HR (95%) 1.05 (1.01-1.08)).
There were more severe cases and poorer outcomes for COVID-19 patients treated in Hubei, which might be attributed to the prolonged duration of symptom onset to hospitalisation in the epicentre. Future studies to determine the reason for delaying hospitalisation are warranted.
Syk increases NLRP3 inflammasome formation through phosphorylation of ASC and enhancement of ASC oligomerization.
NLRP3 is the most crucial member of the NLR family, as it detects the existence of ...pathogen invasion and self‐derived molecules associated with cellular damage. Several studies have reported that excessive NLRP3 inflammasome‐mediated caspase‐1 activation is a key factor in the development of diseases. Recent studies have reported that Syk is involved in pathogen‐induced NLRP3 inflammasome activation; however, the detailed mechanism linking Syk to NLRP3 inflammasome remains unclear. In this study, we showed that Syk mediates NLRP3 stimuli‐induced processing of procaspase‐1 and the consequent activation of caspase‐1. Moreover, the kinase activity of Syk is required to potentiate caspase‐1 activation in a reconstituted NLRP3 inflammasome system in HEK293T cells. The adaptor protein ASC bridges NLRP3 with the effector protein caspase‐1. Herein, we find that Syk can associate directly with ASC and NLRP3 by its kinase domain but interact indirectly with procaspase‐1. Syk can phosphorylate ASC at Y146 and Y187 residues, and the phosphorylation of both residues is critical to enhance ASC oligomerization and the recruitment of procaspase‐1. Together, our results reveal a new molecular pathway through which Syk promotes NLRP3 inflammasome formation, resulting from the phosphorylation of ASC. Thus, the control of Syk activity might be effective to modulate NLRP3 inflammasome activation and treat NLRP3‐related immune diseases.
Nitrogen, an essential macronutrient for plants, regulates many aspects of plant growth and development. Nitrate is one of the major forms of nitrogen taken up by plants from the soil. Nitrate and ...nitrogen have been reported to regulate flowering; while some studies have shown that lower nitrate/nitrogen promoted flowering, others have reported the opposite trend. To elucidate how nitrate/nitrogen affects flowering, we reviewed the existing literature and conducted experiments to examine flowering time under a wide range of nitrate concentrations using two growth systems. From the literature review and our experiments, we established that differing nitrate availability results in a U-shaped flowering curve, with an optimal concentration of nitrate facilitating flowering and concentrations above or below this optimal concentration delaying flowering. The role of nitrate and nitrogen in regulating flowering has been elucidated by several transcriptomic and mutant studies, which have suggested close interactions between nitrate/nitrogen, phosphate, the circadian clock, photosynthesis, and, potentially, hormones. We discuss several possible molecular mechanisms underlying the U-shaped flowering response.
A
bstract
We propose a graph-based approach to 5d superconformal field theories (SCFTs) based on their realization as M-theory compactifications on singular elliptic Calabi-Yau threefolds. ...Field-theoretically, these 5d SCFTs descend from 6d
N
= (1
,
0) SCFTs by circle compactification and mass deformations. We derive a description of these theories in terms of graphs, so-called Combined Fiber Diagrams, which encode salient features of the partially resolved Calabi-Yau geometry, and provides a combinatorial way of characterizing all 5d SCFTs that descend from a given 6d theory. Remarkably, these graphs manifestly capture strongly coupled data of the 5d SCFTs, such as the superconformal flavor symmetry, BPS states, and mass deformations. The capabilities of this approach are demonstrated by deriving all rank one and rank two 5d SCFTs. The full potential, how- ever, becomes apparent when applied to theories with higher rank. Starting with the higher rank conformal matter theories in 6d, we are led to the discovery of previously unknown flavor symmetry enhancements and new 5d SCFTs.
MicroRNAs (miRNAs) are small non-coding RNAs of approximately 22 nucleotides, which negatively regulate the gene expression at the post-transcriptional level. This study describes an update of the ...miRTarBase (http://miRTarBase.mbc.nctu.edu.tw/) that provides information about experimentally validated miRNA-target interactions (MTIs). The latest update of the miRTarBase expanded it to identify systematically Argonaute-miRNA-RNA interactions from 138 crosslinking and immunoprecipitation sequencing (CLIP-seq) data sets that were generated by 21 independent studies. The database contains 4966 articles, 7439 strongly validated MTIs (using reporter assays or western blots) and 348 007 MTIs from CLIP-seq. The number of MTIs in the miRTarBase has increased around 7-fold since the 2014 miRTarBase update. The miRNA and gene expression profiles from The Cancer Genome Atlas (TCGA) are integrated to provide an effective overview of this exponential growth in the miRNA experimental data. These improvements make the miRTarBase one of the more comprehensively annotated, experimentally validated miRNA-target interactions databases and motivate additional miRNA research efforts.
PDF
