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OBJECTIVE Type 1 diabetes (T1D) has been linked to enterovirus infection in small population-based epidemiological studies. We investigated the secular relationship of T1D incidence with enterovirus infection and enterovirus species using nationwide population-based analysis. RESEARCH DESIGN AND METHODS We accessed the National Health Insurance Research Database of Taiwan to identify T1D and enterovirus infection cases from 2001 to 2015. Enterovirus serotype isolation rates were obtained from the nationwide laboratory surveillance systems. Negative binomial regression models assessed the incidence trend, and extended Cox proportional hazards models analyzed the association of enterovirus infection with T1D incidence. Spearman correlation coefficients evaluated the correlation between T1D incidence and circulating enterovirus species. RESULTS T1D incidence rates in youth younger than 20 years were 6.30 and 5.02 per 100,000 person-years in 2001 and 2015 (P = 0.287), respectively. T1D incidence increased significantly in children aged 0–6 years (P < 0.001) but decreased in adolescents aged 13–19 years (P = 0.011). The T1D risk in children aged 0–6 years with enterovirus infection was significantly higher than that in noninfected subjects (hazard ratio 1.46; 95% CI 1.35–1.58; P < 0.001). Additionally, TID incidence in children aged 0–6 years was significantly correlated with the isolation rates of coxsackievirus A species (r = 0.60; P = 0.017), but no association was found beyond the age of 7. CONCLUSIONS We demonstrated that T1D incidence increased in children aged 0–6 years but decreased in adolescents aged 13–19 years in Taiwan. Enterovirus-infected subjects younger than 7 years had a higher risk of T1D than noninfected subjects.

Anemia is associated with severe outcomes in adult community-acquired pneumonia (CAP), but few studies investigated its association with pediatric CAP. Hence, we tried to delineate the association of anemia with the clinical outcomes of CAP in children.This retrospective cohort study was conducted from 2010 to 2019 in a medical center. Inpatients aged 6 months to 17 years who were diagnosed with CAP and without major underlying diseases were included. The subjects' clinical data within 24 h of admission and clinical outcomes were collected. We accessed the rates of adverse outcomes and the adjusted odds ratios (ORs) of these outcomes between anemic and nonanemic patients, as well as among patients with different types of anemia.In this study of 3601 patients, the prevalence of anemia was 11.6% (418/3601). Anemic patients had higher rates of intensive care (16.8% vs. 3.6%; p 0.001), endotracheal intubation (11.0% vs. 1.3%; p 0.001), and empyema (8.6% vs. 0.6%; p 0.001) than nonanemic patients. In addition, anemia was independently associated with intensive care (adjusted OR, 3.00; 95% confidence interval [CI], 2.03-4.42), endotracheal intubation (adjusted OR, 3.79; 95% CI, 2.17-6.63), and empyema (adjusted OR, 4.72; 95% CI, 2.30-9.69). Iron-deficiency anemia (IDA) and normocytic anemia were associated with these adverse outcomes but not with anemia due to thalassemia trait.Anemia is a biomarker associated with poor outcomes in pediatric CAP, and patients with IDA or normocytic anemia should be carefully monitored and managed since they may have higher disease severity.

This study uses an intersectionality lens to understand the inequality of medical use at the intersection of age and air pollution. Using national databases from Taiwan, the results show that the increase of the level of air pollution and age is related to higher percentage of high medical use. Through stratified analysis, we found that there is no significant difference in medical use among different age groups in low AQI (Air Quality Index) areas, Yet, in areas with increasing amounts of polluted air, the elderly have a significantly higher percentage in frequent medical use. Our results show that the elderly people are more susceptible to air pollution, and suggest that, to protect their health and reduce the use of medical care, not only is there a need to reduce air pollution, but also maintain the annual average AQI level to under the value of 50.

An abnormal growth of Cu3Sn through the grain boundaries of Cu6Sn5 formed in Ni/Sn/Cu ternary diffusion couples is reported in this study. The Ni/Sn/Cu diffusion couples are prepared by thermal compression bonding, with the Sn thickness controlled at 10 μm. The diffusion couples are aged at 200 °C for different periods of time. Due to the thinness of the initial Sn layer, the entire Sn layer ware converted into Cu6Sn5 and Cu3Sn only after 52 h or aging. At this stage, both compounds exhibit the layered structure. Afterward, as the reaction continues, Cu3Sn grows thicker at the expense of Cu6Sn5. Interestingly Cu3Sn now preferably grows along the grain boundaries of Cu6Sn5. The rationalization for this abnormal growth pattern is discussed.

Hepatitis B virus (HBV), hepatitis C virus (HCV), human papilloma virus (HPV), Epstein-Barr virus (EBV), human T-cell lymphotropic virus type 1 (HTLV-1), Kaposi's sarcoma-associated herpesvirus (KSHV), and Merkel cell polyomavirus (MCV) contribute to about 10-15% global burden of human cancers. Conventional chemotherapy or molecular target therapies have been used to treat virus-associated cancers. However, a more proactive approach would be the use of antiviral treatment to suppress or eliminate viral infections to prevent the occurrence of cancer in the first place. Antiviral treatments against chronic HBV and HCV infection have achieved this goal, with significant reduction in the incidence of hepatocellular carcinoma in treated patients. Antiviral treatments for EBV, KSHV, and HTLV-1 had limited success in treating refractory EBV-associated lymphoma and post-transplant lymphoproliferative disorder, KSHV-associated Kaposi's sarcoma in AIDS patients, and HTLV-1-associated acute, chronic, and smoldering subtypes of adult T-cell lymphoma, respectively. Therapeutic HPV vaccine and RNA interference-based therapies for treating HPV-associated infection or cervical cancers also showed some encouraging results. Taken together, antiviral therapies have yielded promising results in cancer prevention and treatment. More large-scale studies in a real-world setting are necessary to confirm the efficacy of antiviral therapy. Further investigation for more effective and convenient antiviral regimens warrants more attention.

Hepatitis B virus (HBV), hepatitis C virus (HCV), human papilloma virus (HPV), Epstein-Barr virus (EBV), human T-cell lymphotropic virus type 1 (HTLV-1), Kaposi's sarcoma-associated herpesvirus (KSHV), and Merkel cell polyomavirus (MCV) contribute to about 10-15% global burden of human cancers. Conventional chemotherapy or molecular target therapies have been used to treat virus-associated cancers. However, a more proactive approach would be the use of antiviral treatment to suppress or eliminate viral infections to prevent the occurrence of cancer in the first place. Antiviral treatments against chronic HBV and HCV infection have achieved this goal, with significant reduction in the incidence of hepatocellular carcinoma in treated patients. Antiviral treatments for EBV, KSHV, and HTLV-1 had limited success in treating refractory EBV-associated lymphoma and post-transplant lymphoproliferative disorder, KSHV-associated Kaposi's sarcoma in AIDS patients, and HTLV-1-associated acute, chronic, and smoldering subtypes of adult T-cell lymphoma, respectively. Therapeutic HPV vaccine and RNA interference-based therapies for treating HPV-associated infection or cervical cancers also showed some encouraging results. Taken together, antiviral therapies have yielded promising results in cancer prevention and treatment. More large-scale studies in a real-world setting are necessary to confirm the efficacy of antiviral therapy. Further investigation for more effective and convenient antiviral regimens warrants more attention.

The reaction within Ni/Sn/Cu microjoints has been investigated with a 10 μm initial thickness of Sn so that Sn was quickly consumed in the early stage of the reaction, transforming the joints into full intermetallic joints. Accordingly, the emphasis of the present study is on the materials interactions in such full intermetallic joints. Ni/Sn/Cu sandwiches were prepared by thermal compression bonding. High-temperature storage tests were conducted at 150°C, 180°C, and 200°C for different time periods. The hardness and Young’s modulus of the intermetallic joints were measured using nanoindentation. The key finding of this study is that, once Sn was exhausted, the originally planar (Cu,Ni)3Sn grew preferably along the grain boundary of (Cu,Ni)6Sn5, creating a highly nonuniform (Cu,Ni)3Sn growth front. Both the hardness and elastic modulus increased with the Ni concentration in the intermetallics.

Enterovirus 71 (EV71) is one of the major pathogens that cause severe enteroviral infections. Our aim was to study the behavioral and household risk factors for its serious complications.Between May 2011 and November 2012, we enrolled children who had symptoms of EV71 infection from six hospitals in Taiwan. The caregivers of each patient were interviewed to determine their hand hygiene habits in relation to EV71 infection. The severity of EV71 infection was classified as follows: Stage 1, hand-foot-mouth disease or herpangina; Stage 2, meningitis or myoclonic jerk; Stage 3A, encephalitis; Stage 3B, cardiopulmonary failure. Stages 2 to 3B were defined as severe EV71 infection. Children with Stages 3A and 3B infection were designated as the critical group.A total of 399 patients had laboratory-confirmed EV71 infection. Three risks factors were associated with the different degrees of severity in EV71 infection. Children2 years old had much greater risks for severe EV71 infection [odds ratio (OR) 1.8; 95% confidence interval (CI), 1.2-2.8], delayed medical evaluation for critical infection (OR 9.4; 95% CI, 3.6-24.1), and developmental retardation for cardiopulmonary failure (OR 8.3; 95% CI, 2.0-33.7). Among all the habits and household factors, caregivers in the critical group had a significantly lower rate in terms of cleaning the faucet after washing their hands (OR 2.63; 95% CI, 1.14-6.08).Children2 years old, developmental retardation, and delayed medical intervention were associated with severe EV71 infection. Cleaning water faucets after hand washing was a protective habit that reduced the risk of complications.

This protocol describes the process forthe neutralizing antibody test of EV-D68.

Background During recent 20 years, enterovirus 71 (EV71) has emerged as a major concern among children, particularly in the Asia-Pacific region. To understand current EV71 serostatus, to find risk factors associated with EV71 infection and to establish future EV71 vaccine policy, we performed a seroepidemiology study in Taiwan in 2017. Methods After informed consent was obtained, we enrolled preschool children, 6–15-year-old students, 16–50-year-old people. They received a questionnaire and a blood sample was collected to measure the EV71 neutralization antibody. Results Altogether, 920 subjects were enrolled with a male-to-female ratio of 1.03. The EV71 seropositive rate was 10% (8/82) in infants, 4% (6/153) in 1-year-old children, 8% (7/83) in 2-year-old children, 8% (13/156) in 3–5-year-old children, 31% (38/122) in 6–11-year-old primary school students, 45% (54/121) in 12–15-year-old high school students and 75% (152/203) in 16-50-year-old people. Risk factors associated with EV71 seropositivity in preschool children were female gender, having siblings, more siblings, and contact with herpangina or hand-foot-and-mouth disease. The risk factor with EV71 seropositivity in 16–50-year-old people was having children in their families in addition to older age (p

Background Early life stress is a significant environmental factor for Major Depressive Disorder (MDD). Recent animal studies have shown that the long-term effect of early life stress might influence the combination of intestinal microbiota in the adult. The present study examined the association between early life stress and the microbiota features in the fecal sample of adult participants. Methods We recruited 7 MDD patients and 11 healthy controls, and the Childhood Trauma Questionnaire was used to examine the status of each dimension of childhood maltreatment. The fecal samples were examined by Illumina Miniseq or Miseq platform for 16 s rRNA sequencing of microbiota features. Linear discriminant analysis effect size (LEfSe) was applied to test associations between early life stress and microbiota. Results We used the average score of sexual abuse by all participants as a cut-off point. The abundance of Phascolarctobacterium, Deltaproteobacteria, Bilophila, Thiothrix, Thiotrichaceae, and Thiotrichales significantly increased in the adult participants with childhood trauma of sexual abuse. After adjusted for MDD status, the groups of microbiota still significantly increased in abundance of Bilophila, Thiothrix, Thiotrichaceae, and Thiotrichales. Discussion The replication data with 15 MDD patients and 25 healthy controls is underway. Our study revealed the association between the early life stress and the microbiota features.

Background Glutamic acid dehydrogenase 1 (GAD1) serves as the rate-limiting enzyme for synthesizing GABA, and is reported to be associated with several psychiatric disorders. The present study examined the effects of GAD1 genetic variants on bipolar disorder (BD) and its subtypes. Moreover, we investigated functional interactions between genetic variants and miRNAs via algorithm prediction and experimental validation. Methods A case-control study was conducted with 280 BD patients and 200 healthy controls. Eight tag SNPs in GAD1 were genotyped. For associated markers, we performed in silico prediction for their potential functions through SNP-miRNA interactions by establishing a scoring system to combine information from several miRNA predictive algorithms. We then tested allelic expression differences using Dual-Glo luciferase reporter assays for the selected SNP-miRNA pair. Lastly, we examined the associations of the GAD1 gene and BD in two additional independent datasets with a few thousand samples for replication. Results Marker rs3749034 was associated with BD, in particular the BD-II subtype. According to our scoring system, several candidate miRNAs were predicted to interact with rs3749034, and hsa-miR-504 had the highest score. Findings from an in vitro experiment revealed a non-statistically significant trend for lower gene expression level with the A allele of rs3749034 compared with the G allele. The association between rs3749034 and BD was not replicated in either of the independent datasets. Instead, other rarer genetic variants in GAD1 showed suggestive signals (e.g. rs575441409, p-value = 3.8*10 −4 , D′ = 1 with rs3749034) with BD in the Taiwanese dataset. Limitations The present study considered common genetic variants only. In addition, we only used a 293 T cell-line in conducting luciferase reporter assays, as no primary cell-lines from patient samples were available to differentiate the effects between BD subtypes. Conclusions Our results demonstrate a weak effect of the GAD1 gene on the risk of bipolar illness, and the associated marker might represent a proxy for real signals of rare variants.

Background: Tumor-infiltrating leukocytes (TILs) are immune cells surrounding tumor cells, and several studies have shown that TILs are potential survival predictors in different cancers. However, few studies have dissected the differences between hepatitis B- and hepatitis C-related hepatocellular carcinoma (HBV&minus, HCC and HCV&minus, HCC). Therefore, we aimed to determine whether the abundance and composition of TILs are potential predictors for survival outcomes in HCC and which TILs are the most significant predictors. Methods: Two bioinformatics algorithms, ESTIMATE and CIBERSORT, were utilized to analyze the gene expression profiles from 6 datasets, from which the abundance of corresponding TILs was inferred. The ESTIMATE algorithm examined the overall abundance of TILs, whereas the CIBERSORT algorithm reported the relative abundance of 22 different TILs. Both HBV&minus, HCC were analyzed. Results: The results indicated that the total abundance of TILs was higher in non-tumor tissue regardless of the HCC type. Alternatively, the specific TILs associated with overall survival (OS) and recurrence-free survival (RFS) varied between subtypes. For example, in HBV&minus, HCC, plasma cells (hazard ratio [HR] = 1.05, 95% CI 1.00&ndash, 1.10, p = 0.034) and activated dendritic cells (HR = 1.08, 95% CI 1.01&ndash, 1.17, p = 0.03) were significantly associated with OS, whereas in HCV&minus, HCC, monocytes (HR = 1.21) were significantly associated with OS. Furthermore, for RFS, CD8+ T cells (HR = 0.98) and M0 macrophages (HR = 1.02) were potential biomarkers in HBV&minus, HCC, whereas neutrophils (HR = 1.01) were an independent predictor in HCV&minus, HCC. Lastly, in both HBV&minus, HCC, CD8+ T cells (HR = 0.97) and activated dendritic cells (HR = 1.09) had a significant association with OS, while &gamma, delta T cells (HR = 1.04), monocytes (HR = 1.05), M0 macrophages (HR = 1.04), M1 macrophages (HR = 1.02), and activated dendritic cells (HR = 1.15) were highly associated with RFS. Conclusions: These findings demonstrated that TILs are potential survival predictors in HCC and different kinds of TILs are observed according to the virus type. Therefore, further investigations are warranted to elucidate the role of TILs in HCC, which may improve immunotherapy outcomes.

Background Growing evidence suggests the link between gut microbiota and mood regulation. While previous studies reported several microbiota targets for Major Depressive Disorder (MDD), the influence of dietary patterns is not considered. The current study aims to identify microbiota targets for MDD depression in two independent Taiwanese datasets while taking nutrient elements into consideration. Methods We separately analyzed fecal samples from two independent datasets. The discovery set consisted of 9 MDD patients and 11 healthy controls while replication set comprised of 15 MDD patients and 25 healthy controls. Illumina Miniseq or Miseq platform were applied for 16 s rRNA sequencing. We further assessed food frequency questionnaires and Beck depression inventory to obtain the information of nutrients and depressive status. We applied linear discriminant analysis effect size (LEfSe) to test associations between depression and microbiota and adjusted for nutrient status. Results In the discovery data, the microbiota exhibited significant group differences in genus level, including increased abundance of Bilophila and Gillisia, and decreased abundance of Clostridium. The results remained significant after adjusted levels of carbohydrates, protein and fat intake. The replication study is underway. Discussion Our results revealed novel targets to be associated with depression and are independent of dietary influences. These results awaiting replication and further validation for depression.