Broadly neutralizing ability is critical for developing the next-generation SARS-CoV-2 vaccine. We collected sera samples between December 2021-January 2022 from 113 Taiwan naïve participants after their second dose of homologous vaccine... more
Broadly neutralizing ability is critical for developing the next-generation SARS-CoV-2 vaccine. We collected sera samples between December 2021-January 2022 from 113 Taiwan naïve participants after their second dose of homologous vaccine (AZD1222, mRNA-1273, BNT162-b2, and MVC-COV1901) and compared the differences in serological responses of various SARS-CoV-2 vaccines. Compared to AZD1222, the two mRNA vaccines could elicit a higher level of anti-S1-RBD binding antibodies with higher broadly neutralizing ability evaluated using pseudoviruses of various SARS-CoV-2 lineages. The antigenic maps produced from the neutralization data implied that Omicron represents very different antigenic characteristics from the ancestral lineage. These results suggested that constantly administering the vaccine with ancestral Wuhan spike is insufficient for the Omicron outbreak. In addition, we found that anti-ACE2 autoantibodies were significantly increased in all four vaccinated groups compared to ...
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Enterovirus 71 (EV71) is a positive single-stranded RNA virus from the enterovirus genus of the Picornaviridae family. Most young children infected with EV71 develop mild symptoms of hand, foot and mouth disease, but some develop severe... more
Enterovirus 71 (EV71) is a positive single-stranded RNA virus from the enterovirus genus of the Picornaviridae family. Most young children infected with EV71 develop mild symptoms of hand, foot and mouth disease, but some develop severe symptoms with neurological involvement. Limb paralysis from EV71 infection is presumed to arise mainly from dysfunction of motor neurons in the spinal cord. However, EV71 also targets and damages skeletal muscle, which may also contribute to the debilitating symptoms. In this study, we have delineated the impacts of EV71 infection on skeletal muscle using a mouse model. Mouse pups infected with EV71 developed limb paralysis, starting at day 3 post-infection and peaking at day 5-7 post-infection. At later times, mice recovered gradually but not completely. Notably, severe disease was associated with high levels of myositis accompanied by muscle calcification and persistent motor end plate abnormalities. Interestingly, macrophages exhibited a dynamic c...
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Research Interests: Biology, Virology, Virus, P-glycoprotein, Capsid, and 5 moreAntibody, Antigen, Antigenicity, Antigenic Variation, and epitope
Respiratory viruses can be detected in 18.3 to 48.9% of critically ill adults with severe respiratory tract infections (RTIs). The present study aims to assess the clinical significance of respiratory viruses in pragmatically selected... more
Respiratory viruses can be detected in 18.3 to 48.9% of critically ill adults with severe respiratory tract infections (RTIs). The present study aims to assess the clinical significance of respiratory viruses in pragmatically selected adults in medical intensive care unit patients and to identify factors associated with viral respiratory viral tract infections (VRTIs). We conducted a prospective study on critically ill adults with suspected RTIs without recognized respiratory pathogens. Viral cultures with monoclonal antibody identification, in-house real-time polymerase chain reaction (PCR) for influenza virus, and FilmArray respiratory panel were used to detect viral pathogens. Multivariable logistic regression was applied to identify factors associated with VRTIs. Sixty-four (40.5%) of the included 158 critically ill adults had respiratory viruses detected in their respiratory specimens. The commonly detected viruses included influenza virus (20), followed by human rhinovirus/ent...
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Background: Non-dialysis-dependent chronic kidney disease (CKD-ND) patients are recommended to receive a one-dose influenza vaccination annually. However, studies investigating vaccine efficacy in the CKD-ND population are still lacking.... more
Background: Non-dialysis-dependent chronic kidney disease (CKD-ND) patients are recommended to receive a one-dose influenza vaccination annually. However, studies investigating vaccine efficacy in the CKD-ND population are still lacking. In this study, we aimed to evaluate vaccine efficacy between the one-dose and two-dose regimen and among patients with different stages of CKD throughout a 20-week follow-up period. Methods: We conducted a single-center, non-randomized, open-label, controlled trial among patients with all stages of CKD-ND. Subjects were classified as unvaccinated, one-dose, and two-dose groups (4 weeks apart) after enrollment. Serial changes in immunological parameters (0, 4, 8, and 20 weeks after enrollment), including seroprotection, geometric mean titer (GMT), GMT fold-increase, seroconversion, and seroresponse, were applied to evaluate vaccine efficacy. Results: There were 43, 84, and 71 patients in the unvaccinated, one-dose, and two-dose vaccination groups, re...
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Lots of automated molecular methods for detecting cytomegalovirus (CMV) DNA in the blood are available, but seldom for various clinical specimens. This study was designed to establish a highly sensitive automated assay to detect CMV DNA... more
Lots of automated molecular methods for detecting cytomegalovirus (CMV) DNA in the blood are available, but seldom for various clinical specimens. This study was designed to establish a highly sensitive automated assay to detect CMV DNA in non-blood specimens. We designed a new QMT assay using QIAGEN artus CMV RG polymerase chain reaction (Q-CMV PCR) kit applied on the BD MAX system and compared with the other assays, including an RGQ assay (LabTurbo auto-extraction combined Q-CMV PCR kit on Rotor-Gene-Q instrument), and in-house PCR assay. A total of 1067 various clinical samples, including 426 plasma, 293 respiratory tract specimens (RTS), 127 stool, 101 cerebral spinal fluid, 90 vitreous humours were analysed. Examining CMV DNA in simultaneous specimens of the same immunocompromised patient with respiratory symptoms, the detection rate of RTS (93.6%, 88/94) was significant higher than plasma (65.9%, 62/94). The positive rates for plasma samples with a low CMV viral load (<137 ...
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Cysteine protease of group A streptococci (GAS) is considered an important virulence factor. However, its role in invasiveness of GAS has not been investigated. We demonstrated in this study that two strains of protease-producing GAS had... more
Cysteine protease of group A streptococci (GAS) is considered an important virulence factor. However, its role in invasiveness of GAS has not been investigated. We demonstrated in this study that two strains of protease-producing GAS had the ability to invade A-549 human respiratory epithelial cells. Isogenic protease mutants were constructed by using integrational plasmids to disrupt the speB gene and confirmed by Southern hybridization and Western immunoblot analyses. No extracellular protease activity was produced by the mutants. The mutants had growth rates similar to those of the wild-type strains and produced normal levels of other extracellular proteins. When invading A-549 cells, the mutants had a two- to threefold decrease in activity compared to that of the wild-type strains. The invasion activity increased when the A-549 cells were incubated with purified cysteine protease and the mutant. However, blockage of the cysteine protease with a specific cysteine protease inhibit...
Research Interests: Microbiology, Biology, Medicine, Biological Sciences, Infection and immunity, and 15 moreCell line, Humans, Protease, Infection, Streptococcus Pyogenes, Epithelial cells, Growth rate, Cysteine endopeptidases, Virulence factor, Cysteine, Bacterial Adhesion, Extracellular, Intracellular, Cysteine Protease, and Medical and Health Sciences
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Viral aerosol infection through cough generates large amounts of viral aerosol and can result in many adverse health effects such as influenza flu and severe acute respiratory syndrome (SARS). To characterize the coughed viral aerosol,... more
Viral aerosol infection through cough generates large amounts of viral aerosol and can result in many adverse health effects such as influenza flu and severe acute respiratory syndrome (SARS). To characterize the coughed viral aerosol, the sampler needs to sample at higher flow rate and possess high physical collection efficiency as well as high viral preservation. However, most current inertia-based high flow bioaerosol samplers are not suited for viral aerosol sampling since the viability will be lost doing the sampling process. Current condensation growth methods only have good physical collection efficiency and viral preservation at low flow rate (< 10 LPM). In this study, we developed a viral aerosol sampling system using a cooler and steam-jet aerosol collector (SJAC) for bioaerosol collection for the first time. The system is based on mixing condensation growth method and has high viral preservation at a higher flow rate (12.5 LPM). We control the inlet aerosol flow temper...
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Annual influenza vaccination is recommended, but its efficacy in dialysis population is still controversial. Here we aimed to compare the dynamic changes of immune response between various influenza vaccination protocols in hemodialysis... more
Annual influenza vaccination is recommended, but its efficacy in dialysis population is still controversial. Here we aimed to compare the dynamic changes of immune response between various influenza vaccination protocols in hemodialysis patients. A 18-week open label, non-randomized, controlled trial was conducted during 2011–2012. The efficacy between unvaccinated, one- and two-dose regimens were evaluated in 175 hemodialysis patients. Immunogenic profiles were assessed by hemagglutination-inhibition assays. At 3–9 weeks post-vaccination, antibody responses were similar between the one- and two-dose regimens, while the seroprotection rates (antibody titer ≥1:40) for influenza A were 55.6–82.5% in the adult (18–60 years) and 33.3–66.7% in the elderly (>60 years). Meanwhile, the seroprotection rates for influenza B were low (4.0–25.0%). By 18 weeks post-vaccination, the seroprotection rates for influenza A and B declined (0.0–33.3%) in both the adult and elderly receiving one- or ...
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Hand, foot, and mouth disease (HFMD) and encephalomyelitis were two major clinical manifestations during the 1998 enterovirus 71 (EV71) epidemic in Taiwan. To investigate whether different clinical patterns were caused by alterations in... more
Hand, foot, and mouth disease (HFMD) and encephalomyelitis were two major clinical manifestations during the 1998 enterovirus 71 (EV71) epidemic in Taiwan. To investigate whether different clinical patterns were caused by alterations in EV71 genomes, the complete nucleotide sequences of four EV71 strains associated with HFMD or encephalomyelitis were compared. Among these viral strains, two or three nucleotide differences were found within the 5′‐noncoding region, and two or four amino acid differences were found within the regions encoding viral polyproteins; however, none of these differences were correlated with either clinical manifestation. Because coxsackievirus A16 was another major causative agent of HFMD, a reverse transcription‐polymerase chain reaction assay, with high sensitivity and specificity for identification of EV71 (both 100%) and coxsackievirus A16 (100 and 98.8%), was developed for the rapid differential identification of these two viruses in HFMD patients. J. M...
Research Interests: Microbiology, Medical Microbiology, Biology, Virology, Medicine, and 15 moreDisease Outbreaks, Humans, Sequence alignment, Taiwan, Genome, Medical virology, Genetic variation, Hand foot and mouth disease, Base Sequence, Outbreak, Encephalomyelitis, Enterovirus, Medical, Molecular Sequence Data, and reverse transcriptase polymerase chain reaction
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Research Interests: Biology, Adolescent, Clinical Virology, Cercopithecus aethiops, Cell line, and 15 moreDisease Outbreaks, Cerebrospinal Fluid, Brain, Child, Case Study, Animals, Clinical, Central Nervous System, Clinical Sciences, Amino Acid Profile, Amino Acid Sequence, Encephalitis, Aseptic meningitis, Brain stem, and Child preschool
Research Interests: Medical Microbiology, Virology, Medicine, Emerging Infectious Diseases, Serology, and 15 moreHumans, Virus, Taiwan, Clinical Sciences, Aged, Middle Aged, Antibody, Adult, Public health systems and services research, influenza A virus, Pandemics, Seasons, Pandemic, Child preschool, and Influenza vaccines
Research Interests: Pediatrics, Magnetic Resonance Imaging, Adolescent, Medicine, Biological Sciences, and 15 moreCercopithecus aethiops, Disease Outbreaks, Humans, Child, Female, Animals, Male, Infant, Retrospective Studies, Ataxia, Encephalitis, Clinical Infectious Diseases, Enterovirus, Child preschool, and Medical and Health Sciences
Due to the nature of RNA viruses, their high mutation rates produce a population of closely related but genetically diverse viruses, termed quasispecies. To determine the role of quasispecies in DENV disease severity, 22 isolates (10 from... more
Due to the nature of RNA viruses, their high mutation rates produce a population of closely related but genetically diverse viruses, termed quasispecies. To determine the role of quasispecies in DENV disease severity, 22 isolates (10 from mild cases, 12 from fatal cases) were obtained, amplified, and sequenced with Next Generation Sequencing using the Illumina MiSeq platform. Using variation calling, unique wildtype nucleotide positions were selected and analyzed for variant nucleotides between mild and fatal cases. The analysis of variant nucleotides between mild and fatal cases showed 6 positions with a significant difference of p < 0.05 with 1 position in the structural region, and 5 positions in the non-structural (NS) regions. All variations were found to have a higher percentage in fatal cases. To further investigate the genetic changes that affect the virus’s properties, reverse genetics (rg) viruses containing substitutions with the variations were generated and viral gro...
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Research Interests: Medical Microbiology, Adolescent, Medicine, Humans, Child, and 14 moreVirus, Taiwan, Female, Male, Infant, Clinical microbiology and infection control, Clinical Sciences, Prevalence, Human Metapneumovirus, Public health systems and services research, Respiratory Tract Infections, Infectious Diseases and Microbiology, Virus diseases, and Child preschool
Highly pathogenic avian influenza (HPAI) clade 2.3.4.4 viruses have been reported to be the source of infections in several outbreaks in the past decades. In a previous study, we screened out a broad-spectrum virus strain, H5N6-Sichuan... more
Highly pathogenic avian influenza (HPAI) clade 2.3.4.4 viruses have been reported to be the source of infections in several outbreaks in the past decades. In a previous study, we screened out a broad-spectrum virus strain, H5N6-Sichuan subtype, by using a lentiviral pseudovirus system. In this project, we aimed to investigate the potential of H5N6 virus-like particles (VLPs) serving as a broad-spectrum vaccine candidate against H5Nx viruses. We cloned the full-length M1 gene and H5, N6 genes derived from the H5N6-Sichuan into pFASTBac vector and generated the VLPs using the baculovirus-insect cell system. H5N6 VLPs were purified by sucrose gradient centrifugation, and the presence of H5, N6 and M1 proteins was verified by Western blot and SDS-PAGE. The hemagglutination titer of H5N6 VLPs after purification reached 5120 and the particle structure remained as viewed by electron microscopy. The H5N6 VLPs and 293T mammalian cell-expressed H5+N6 proteins were sent for mice immunization. ...
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BackgroundRespiratory viruses can be detected in 18.3% to 48.9% of critically ill adults with severe respiratory tract infections (RTIs). The present study aims to assess the clinical significance of respiratory viruses in pragmatically... more
BackgroundRespiratory viruses can be detected in 18.3% to 48.9% of critically ill adults with severe respiratory tract infections (RTIs). The present study aims to assess the clinical significance of respiratory viruses in pragmatically selected adults in medical intensive care unit patients and to identify factors associated with viral respiratory viral tract infections (VRTIs).MethodsWe conducted a prospective study on critically ill adults with suspected RTIs without recognized respiratory pathogens. Viral cultures with monoclonal antibody identification, in-house real-time polymerase chain reaction (PCR) for influenza virus, and FilmArray® respiratory panel were used to detect viral pathogens. Multivariable logistic regression was applied to identify factors associated with VRTIs.ResultsSixty-four (40.5%) of the included 158 critically ill adults had respiratory viruses detected in their respiratory specimens. The commonly detected viruses included influenza virus (20), followed...
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Background Influenza A virus (IAV) evolves strategies to counteract the host antiviral defense for establishing infection. The influenza A virus (IAV) non-structural protein 1 (NS1) is a key viral factor shown to counteract type I IFN... more
Background Influenza A virus (IAV) evolves strategies to counteract the host antiviral defense for establishing infection. The influenza A virus (IAV) non-structural protein 1 (NS1) is a key viral factor shown to counteract type I IFN antiviral response mainly through targeting RIG-I signaling. Growing evidence suggests that viral RNA sensors RIG-I, TLR3, and TLR7 function to detect IAV RNA in different cell types to induce type I IFN antiviral response to IAV infection. Yet, it remains unclear if IAV NS1 can exploit a common mechanism to counteract these RNA sensing pathways to type I IFN production at once, then promoting viral propagation in the host. Methods Luciferase reporter assays were conducted to determine the effect of NS1 and its mutants on the RIG-I and TLR3 pathways to the activation of the IFN-β and NF-κB promoters. Coimmunoprecipitation and confocal microscopic analyses were used to the interaction and colocalization between NS1 and TRAF3. Ubiquitination assays were ...
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Background Dengue virus causes a wide spectrum of disease, which ranges from subclinical disease to severe dengue shock syndrome. However, estimating the risk of severe outcomes using clinical presentation or laboratory test results for... more
Background Dengue virus causes a wide spectrum of disease, which ranges from subclinical disease to severe dengue shock syndrome. However, estimating the risk of severe outcomes using clinical presentation or laboratory test results for rapid patient triage remains a challenge. Here, we aimed to develop prognostic models for severe dengue using machine learning, according to demographic information and clinical laboratory data of patients with dengue. Methodology/Principal findings Out of 1,581 patients in the National Cheng Kung University Hospital with suspected dengue infections and subjected to NS1 antigen, IgM and IgG, and qRT-PCR tests, 798 patients including 138 severe cases were enrolled in the study. The primary target outcome was severe dengue. Machine learning models were trained and tested using the patient dataset that included demographic information and qualitative laboratory test results collected on day 1 when they sought medical advice. To develop prognostic models...
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Background Influenza A viruses cause epidemics/severe pandemics that pose a great global health threat. Among eight viral RNA segments, the multiple functions of nucleoprotein (NP) play important roles in viral replication and... more
Background Influenza A viruses cause epidemics/severe pandemics that pose a great global health threat. Among eight viral RNA segments, the multiple functions of nucleoprotein (NP) play important roles in viral replication and transcription. Methods To understand how NP contributes to the virus evolution, we analyzed the NP gene of H3N2 viruses in Taiwan and 14,220 NP sequences collected from Influenza Research Database. The identified genetic variations were further analyzed by mini-genome assay, virus growth assay, viral RNA and protein expression as well as ferret model to analyze their impacts on viral replication properties. Results The NP genetic analysis by Taiwan and global sequences showed similar evolution pattern that the NP backbones changed through time accompanied with specific residue substitutions from 1999 to 2018. Other than the conserved residues, fifteen sporadic substitutions were observed in which the 31R, 377G and 450S showed higher frequency. We found 31R and...
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Research Interests: Biology, Virology, Medicine, Multidisciplinary, Virus, and 3 morePLoS one, influenza A virus, and Tropism
Chronic hepatitis B virus (HBV) infection is the major cause of hepatocellular carcinoma (HCC). The pre-S mutant large HBV surface antigen (LHBS) is highly associated with HCC. This study analyzed the expression of the large form of... more
Chronic hepatitis B virus (HBV) infection is the major cause of hepatocellular carcinoma (HCC). The pre-S mutant large HBV surface antigen (LHBS) is highly associated with HCC. This study analyzed the expression of the large form of surface protein in tumors and evaluated the LHBS with mutations within the pre-S region as a high-risk recurrence marker in HCC patients after curative hepatic resection. By analyses using immunohistochemical staining (n = 12) and western blotting (n = 22), the HBV surface protein, which is mainly comprised of the major form of HBV surface antigen, was greatly diminished in the tumors. However, LHBS was not significantly decreased in tumorous regions, suggesting that LHBS maintains its expression in cancer development. A cohort of 175 patients with HBV-related HCC who underwent curative hepatic resection was analyzed for pre-S gene mutations using Pre-S Gene Chip. Results of the multivariate regression analysis showed that the serum pre-S mutant level an...
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RNA viruses accumulate mutations to rapidly adapt to environmental changes. Enterovirus A71 (EV-A71) causes various clinical manifestations with occasional severe neurological complications. However, the mechanism by which EV-A71 evolves... more
RNA viruses accumulate mutations to rapidly adapt to environmental changes. Enterovirus A71 (EV-A71) causes various clinical manifestations with occasional severe neurological complications. However, the mechanism by which EV-A71 evolves within the human body is unclear. Utilizing deep sequencing and haplotype analyses of viruses from various tissues of an autopsy patient, we sought to define the evolutionary pathway by which enterovirus A71 evolves fitness for invading the central nervous system in humans. Broad mutant spectra with divergent mutations were observed at the initial infection sites in the respiratory and digestive systems. After viral invasion, we identified a haplotype switch and dominant haplotype, with glycine at VP1 residue 31 (VP1-31G) in viral particles disseminated into the integumentary and central nervous systems. In vitro viral growth and fitness analyses indicated that VP1-31G conferred growth and a fitness advantage in human neuronal cells, whereas VP1-31D...
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Accurate, rapid, and early diagnosis of dengue virus (DENV) infections is essential for optimal clinical care. Here, we evaluated the efficacy of the quantitative real-time PCR (qRT-PCR)-LightMix dengue virus EC kit for DENV detection... more
Accurate, rapid, and early diagnosis of dengue virus (DENV) infections is essential for optimal clinical care. Here, we evaluated the efficacy of the quantitative real-time PCR (qRT-PCR)-LightMix dengue virus EC kit for DENV detection using samples from a dengue outbreak in Taiwan in 2015. Sera from patients with suspected DENV infection were analyzed and compared using the LightMix kit, a Dengue NS1 Ag + Ab Combo kit for detection of NS1 antigen and DENV-specific IgM and IgG antibodies, and an "in-house" qualitative DENV-specific RT-PCR assay. A total of 8,989, 8,954, and 1581 samples were subjected to NS1 antigen detection, IgM and IgG detection, and LightMix assays, respectively. The LightMix assay yielded a linear curve for viral loads (VL) between 102 and 106 copies/reaction, and the minimum detection limits for DENV serotype 1 (DENV1) and DENV2, DENV3, and DENV4 were 1, 10, and 100 focus forming units (FFU)/mL, respectively. There was 88.9% concordance between the re...
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Viral etiologies of respiratory tract infections (RTIs) have been less studied in adult than in pediatric populations. Furthermore, the ability of PCR/electrospray ionization mass spectrometry (PCR/ESI-MS) to detect enteroviruses and... more
Viral etiologies of respiratory tract infections (RTIs) have been less studied in adult than in pediatric populations. Furthermore, the ability of PCR/electrospray ionization mass spectrometry (PCR/ESI-MS) to detect enteroviruses and rhinoviruses in respiratory samples has not been well evaluated. We sought to use PCR/ESI-MS to comprehensively investigate the viral epidemiology of adult RTIs, including testing for rhinoviruses and enteroviruses.Nasopharyngeal or throat swabs from 267 adults with acute RTIs (212 upper RTIs and 55 lower RTIs) who visited a local clinic or the outpatient or emergency departments of a medical center in Taiwan between October 2012 and June 2013 were tested for respiratory viruses by both virus isolation and PCR/ESI-MS. Throat swabs from 15 patients with bacterial infections and 27 individuals without active infections were included as control samples.Respiratory viruses were found in 23.6%, 47.2%, and 47.9% of the 267 cases by virus isolation, PCR/ESI-MS...
Research Interests: Medicine, Humans, Taiwan, Female, Male, and 14 morePolymerase Chain Reaction, Coinfection, Clinical Sciences, Aged, Middle Aged, Human Metapneumovirus, Liquid Chromatography / Electrospray Ionization Mass Spectrometry, Outpatients, Adult, Respiratory Tract Infections, Rhinovirus, Enterovirus, Pharynx, and Throat
Periprosthetic joint infection (PJI) is a devastating complication after arthroplasty. Two-stage reimplantation procedure is the most common practice to prevent the reoccurrence of PJI. However, it should be assisted by a rapid, accurate... more
Periprosthetic joint infection (PJI) is a devastating complication after arthroplasty. Two-stage reimplantation procedure is the most common practice to prevent the reoccurrence of PJI. However, it should be assisted by a rapid, accurate and comprehensive bacteria detection tool. In this study, a new integrated microfluidic system capable of performing sample pre-treatment, a nanogold detection to provide live bacteria information (30 minutes) and a PCR reaction (further 40 minutes) to distinguished bacteria types for antibiotic treatment automatically without human intervention is proposed. The experimental results demonstrated that this powerful tool can serve as a base for clinical decision-making in the near future.
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The efficacy and effectiveness of influenza vaccines depend primarily on the vaccine recipient and the virus similarity to the endemic virus. Regulatory T cells (Tregs) and cytokines are known to restrict immune responses against viral... more
The efficacy and effectiveness of influenza vaccines depend primarily on the vaccine recipient and the virus similarity to the endemic virus. Regulatory T cells (Tregs) and cytokines are known to restrict immune responses against viral infections. We conducted this study to explore the role of Tregs, cytokines, and antibody production after influenza vaccination. The whole blood was collected from healthy subjects (n = 36) before and two weeks after influenza vaccine immunization for two or three consecutive years. The cell surface markers, intracellular staining of Foxp3(+) Tregs, and Th1/Th2 cytokines were determined. The antibody titer was detected using the hemagglutination inhibition test. The CD3(+), CD127(+), CD4(+)CD25(+) and CD4(+)Foxp3(+) cells were increased significantly post vaccination. The plasma level of the transforming growth factor (TGF-β), but not interleukin (IL)-2, IL-4, IL-5, IL-10, IFN-γ, TNF-α, was also found to increase significantly after vaccination. We f...
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Research Interests: Epidemiology, Death, Evolution, Public Health, Medicine, and 15 moreDisease Outbreaks, Complication, Humans, Infant, Incidence, New England, Hand foot and mouth disease, Hemorrhage, Outbreak, New England Journalof Medicine, Aseptic meningitis, Nino, Enterovirus, Child preschool, and Medical and Health Sciences
Innate immune response is important for viral clearance during influenza virus infection. Galectin-1, which belongs to S-type lectins, contains a conserved carbohydrate recognition domain that recognizes galactose-containing... more
Innate immune response is important for viral clearance during influenza virus infection. Galectin-1, which belongs to S-type lectins, contains a conserved carbohydrate recognition domain that recognizes galactose-containing oligosaccharides. Since the envelope proteins of influenza virus are highly glycosylated, we studied the role of galectin-1 in influenza virus infection in vitro and in mice. We found that galectin-1 was upregulated in the lungs of mice during influenza virus infection. There was a positive correlation between galectin-1 levels and viral loads during the acute phase of viral infection. Cells treated with recombinant human galectin-1 generated lower viral yields after influenza virus infection. Galectin-1 could directly bind to the envelope glycoproteins of influenza A/WSN/33 virus and inhibit its hemagglutination activity and infectivity. It also bound to different subtypes of influenza A virus with micromolar dissociation constant ( K d ) values and protected c...
Research Interests: Kinetics, Biology, Survival Analysis, Transmission Electron Microscopy, Medicine, and 15 moreBiological Sciences, Mice, Female, Animals, Surface plasmon resonance, Lung, Galectin, influenza A virus, Protein Binding, Antiviral Agents, Orthomyxoviridae Infections, Antibody dependent enhancement, Viral Load, Infectivity, and Medical and Health Sciences
A laboratory-based surveillance network of 11 clinical virological laboratories for influenza viruses was established in Taiwan under the coordination of the Center for Disease Control and Prevention (CDC), Taiwan. From October 2000 to... more
A laboratory-based surveillance network of 11 clinical virological laboratories for influenza viruses was established in Taiwan under the coordination of the Center for Disease Control and Prevention (CDC), Taiwan. From October 2000 to March 2004, 3,244 influenza viruses were isolated, including 1,969 influenza A and 1,275 influenza B viruses. The influenza infections usually occurred frequently in winter in the northern hemisphere. However, the influenza seasonality in Taiwan was not clear during the four seasons under investigation. For example, the influenza A viruses peaked during the winters of 2001, 2002, and 2003. However, some isolated peaks were also found in the summer and fall (June to November) of 2001 and 2002. An unusual peak of influenza B also occurred in the summer of 2002 (June to August). Phylogenetic analysis shows that influenza A isolates from the same year were often grouped together. However, influenza B isolates from the year 2002 clustered into different gr...
Research Interests: Microbiology, Biology, Virology, Medicine, Influenza virus, and 15 moreMolecular Epidemiology, Clinical Microbiology, Biological Sciences, Dogs, Phylogeny, Humans, Taiwan, Animals, Clinical, Laboratories, Seasonal Influenza, influenza A virus, Molecular Sequence Data, Sentinel surveillance, and Medical and Health Sciences
Genetic and antigenic analyses of influenza B virus field strains isolated in Taiwan from 1998 to 2005 were performed. To investigate the molecular evolution of influenza B viruses, sequence analysis of the hemagglutinin (HA1 subunit) and... more
Genetic and antigenic analyses of influenza B virus field strains isolated in Taiwan from 1998 to 2005 were performed. To investigate the molecular evolution of influenza B viruses, sequence analysis of the hemagglutinin (HA1 subunit) and neuraminidase genes was performed. All influenza B viruses isolated between 1998 and 2000 belonged to the B/Yamagata/16/88 lineage. The B/Victoria/2/87 lineage, which was cocirculating with the Yamagata lineage, was identified in Taiwan in March 2001. Concurrently, there was an increasing prevalence of this lineage in many parts of the world, including North America and Europe, during the 2001-2002 season. Since 2002, genetic reassortants of influenza B virus with the Victoria lineage of hemagglutinin and the Yamagata lineage of neuraminidase have been found at a rate of 46%. Therefore, in 2002, at least three sublineages of influenza B virus strains, the B/Shanghai/361/2002-like strain (Yamagata lineage), the B/Hong Kong/330/01-like strain (Victor...
Research Interests: Genetics, Microbiology, Molecular Evolution, Biology, Medicine, and 15 moreGenetic Diversity, Molecular Epidemiology, Clinical Microbiology, Biological Sciences, High Frequency, Phylogeny, Humans, influenza A, Clinical, Cluster Analysis, Neuraminidase, North America, Northern Hemisphere, Geographic distribution, and Medical and Health Sciences
The present study examined the association of specific virus infections with acute respiratory tract conditions among hospitalized and outpatient children in a subtropical country. A total of 2,295 virus infections were detected in 6,986... more
The present study examined the association of specific virus infections with acute respiratory tract conditions among hospitalized and outpatient children in a subtropical country. A total of 2,295 virus infections were detected in 6,986 patients between 1997 and 1999, including infections caused by respiratory syncytial virus (RSV) (1.7%), parainfluenza virus (2.0%), influenza B virus (2.6%), adenovirus (4.0%), herpes simplex virus type 1 (4.4%), influenza A virus (5.5%), and enterovirus (12.7%). There were 61 mixed infections, and no consistent seasonal variation was found. One or more viruses were detected among 24.8% of hospitalized patients and 35.0% of outpatients. The frequencies and profiles of detection of various viruses among in- and outpatients were different. The occurrence of enterovirus infections exceeded that of other viral infections detected in 1998 and 1999 due to outbreaks of enterovirus 71 and coxsackievirus A10. RSV was the most prevalent virus detected among ...
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Background. A novel swine-origin influenza A H1N1 virus (S-OIV) caused human infection and acute respiratory illness in 2009, resulting in an influenza pandemic.Objectives. This study characterized the immune responses of S-OIV infection... more
Background. A novel swine-origin influenza A H1N1 virus (S-OIV) caused human infection and acute respiratory illness in 2009, resulting in an influenza pandemic.Objectives. This study characterized the immune responses of S-OIV infection in pediatric patients at risk of pulmonary complications.Methods. All enrolled pediatric patients were confirmed virologically for S-OIV infection in 2009-2010, prospectively. Changes in cellular immunophenotypes were analyzed using flow cytometry. Plasma cytokine levels associated with S-OIV infection by pulmonary and without pulmonary complications were measured using cytokine cytometric bead assay kits.Results. A total of 85 patients with a mean age of 10.3 years were recruited. The level of C-reactive protein (CRP) was high in patients exhibiting pulmonary complications. The percentage of cellular immunophenotypes did not change between patients with and without pulmonary complications. The absolute numbers of peripheral blood mononuclear cells ...
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A novel pandemic influenza H1N1 (pH1N1) virus spread rapidly across the world in 2009. Due to the important role of antibody-mediated immunity in protection against influenza infection, we used an enzyme-linked immunosorbent assay-based... more
A novel pandemic influenza H1N1 (pH1N1) virus spread rapidly across the world in 2009. Due to the important role of antibody-mediated immunity in protection against influenza infection, we used an enzyme-linked immunosorbent assay-based microneutralization test to investigate cross-reactive neutralizing antibodies against the 2009 pH1N1 virus in 229 stored sera from donors born between 1917 and 2008 in Taiwan. The peak of cumulative geometric mean titers occurred in donors more than 90 years old and declined sharply with decreasing age. Sixteen of 27 subjects (59%) more than 80 years old had cross-reactive antibody titers of 160 or more against the 2009 pH1N1 virus, whereas none of the donors from age 9 to 49 had an antibody titer of 160 or more. Interestingly, 2 of 51 children (4%) from 6 months to 9 years old had an antibody titer of 40. We further tested the antibody responses in 9 of the 51 pediatric sera to three endemic seasonal influenza viruses isolated in 2006 and 2008 in T...
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Background Enterovirus 71 (EV71) is a major causative agent of hand-foot-and-mouth disease (HFMD), and infection of EV71 to central nerve system (CNS) may result in a high mortality in children less than 2 years old. Although there are... more
Background Enterovirus 71 (EV71) is a major causative agent of hand-foot-and-mouth disease (HFMD), and infection of EV71 to central nerve system (CNS) may result in a high mortality in children less than 2 years old. Although there are two highly glycosylated membrane proteins, SCARB2 and PSGL-1, which have been identified as the cellular and functional receptors of EV71, the role of glycosylation in EV71 infection is still unclear. Results We demonstrated that the attachment of EV71 to RD and SK-N-SH cells was diminished after the removal of cell surface sialic acids by neuraminidase. Sialic acid specific lectins, Maackia amurensis (MAA) and Sambucus Nigra (SNA), could compete with EV71 and restrained the binding of EV71 significantly. Preincubation of RD cells with fetuin also reduced the binding of EV71. In addition, we found that SCARB2 was a sialylated glycoprotein and interaction between SCARB2 and EV71 was retarded after desialylation. Conclusions In this study, we demonstrat...
Research Interests:
Research Interests: Archives, Biology, Medicine, Sequence Analysis, Molecular Epidemiology, and 15 moreBiological Sciences, Phylogeny, Humans, Respiratory Disease, Taiwan, Female, Male, Infant, Human Metapneumovirus, Genetic Divergence, Genetic variation, Amino Acid Sequence, Outbreak, Child preschool, and Medical and Health Sciences
In this letter, with an electric double layer on the surface of spherical viruses, we confirm that one of the microwave resonant absorption (MRA) mechanisms of viruses is through dipolar coupling with confined acoustic vibrations. By... more
In this letter, with an electric double layer on the surface of spherical viruses, we confirm that one of the microwave resonant absorption (MRA) mechanisms of viruses is through dipolar coupling with confined acoustic vibrations. By treating spherical virions as free homogeneous nanoparticles, we found that the MRA frequencies agree well with that of l=1 dipolar modes predicted by the elastic continuum theory. The magnitude of MRA was also found to change with the amount of adsorbed charges on the surface of virions. Our results provide a method to observe three-dimensionally confined acoustic vibrations in biological systems.