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This paper presents a tool for drawing dynamic geometric figures by understanding the texts of geometry problems. With the tool, teachers and students can construct dynamic geometric figures on a web page by inputting a geometry problem in natural language. First we need to build the knowledge base for understanding geometry problems. With the help of the knowledge base engine InfoMap, geometric concepts are extracted from an input text. The concepts are then used to output a multistep JavaSketchpad script, which constructs the dynamic geometry figure on a web page. Finally, the system outputs the script as an HTML document that can be visualized and read with an internet browser. Furthermore, a preliminary evaluation of the tool showed that it produced correct dynamic geometric figures for over 90% of problems from textbooks. With such high accuracy, the system produced by this study can support distance learning for geometry students as well as distance learning in producing geometry content for instructors. (Contains 4 tables and 13 figures.)

Previous research has explored theories regarding the vertical transmission of human papillomavirus (HPV) infection and its association with adverse pregnancy and perinatal outcomes. However, the impact of maternal HPV infection on congenital anomalies (CAs) in offspring remains relatively understudied. We conducted a population‐based cohort study linking the Taiwan Birth Registry, Taiwan Death Registry, and National Health Insurance Research Database, in which newborns born in Taiwan between 2009 and 2015 were included. We established a maternal HPV infection cohort comprising 37 807 newborns and matched them with a comparison group of 151 228 newborns at a 1:4 ratio based on index year, age, and sex. The study examined a composite outcome and subgroups of different types of congenital malformations. Differences in cumulative incidence of CAs were assessed using Kaplan–Meier curves and log‐rank tests. Adjusted hazard ratios (aHRs) were estimated using Cox proportional hazard regressions. No significant association was found between HPV infection and the broad spectrum of CAs (aHR: 1.04, 95% confidence interval [CI]: 0.98–1.10; log‐rank test p = 0.14). However, we observed a 19% increased risk of musculoskeletal CAs in the maternal HPV infection group (aHR: 1.19; 95% CI: 1.05–1.34) compared to those without maternal HPV exposure. Other factors, including the type of HPV (aHR: 0.65; 95% CI: 0.16–2.63), the timing of exposure (during or before pregnancy), and maternal age (aHR for <30 years: 1.02, 95% CI: 0.94–1.1; aHR for 30–39 years: 1.05, 95% CI: 0.99–1.11; aHR for ≥40 years: 0.88, 95% CI: 0.67–1.17), did not significantly affect the risk for any CA. In conclusion, gestation detection of HPV infection was associated with musculoskeletal CAs but not other major CAs. Prospective studies are warranted to elucidate the necessity of prenatal screening in populations at risk. [ABSTRACT FROM AUTHOR]

Background: Studies comparing the effectiveness of either adjuvant oral uracil‐tegafur (UFT) or intravenous chemotherapy on early‐stage (stage I and II) non‐small cell lung cancer (NSCLC) patients treated with complete surgical treatment remain limited. Methods: From January 2011 to December 2017, patients with early‐stage NSCLC (defined as tumor size >3 cm without mediastinal lymph node involvement or any distant metastasis) receiving either adjuvant oral UFT or intravenous chemotherapy after surgical resection were identified from the Taiwan Cancer Registry. Overall survival (OS) and relapse‐free survival (RFS) were the primary and secondary outcomes, respectively. Propensity matching was used for controlling confounders. Results: A total of 840 patients receiving adjuvant therapy after surgery (including 595 oral UFT and 245 intravenous chemotherapy) were enrolled. Before matching, patients using oral UFT had significantly longer OS (HR: 0.69, 95% CI: 0.49–0.98, p = 0.0387) and RFS (HR: 0.79, 95% CI: 0.61–0.97, p = 0.0392) than those with intravenous chemotherapy. A matched cohort of 352 patients was created using 1:1 propensity score‐matching. In the Cox regression analysis, the UFT and the matched chemotherapy groups had similar OS (HR: 0.80, 95% CI: 0.48–1.32, p = 0.3753) and RFS (HR: 0.98, 95% CI: 0.72–1.34, p = 0.9149). Among subgroup analysis, oral UFT use was associated with longer RFS among the subgroups of non‐drinker (HR: 0.66, 95% CI: 0.34–0.99, p = 0.0478) and patients with stage IB disease (HR: 0.67, 95% CI: 0.42–0.97, p = 0.0341). Conclusions: This population‐based study in the real‐world setting of Taiwan demonstrates comparable effectiveness between oral UFT and intravenous chemotherapy in terms of clinical outcomes for early‐stage NSCLC patients after surgery. [ABSTRACT FROM AUTHOR]

Geometry theorem proving involves skills that are difficult to learn. Instead of working with abstract and complicated representations, students might start with concrete, graphical representations. A proof tree is a graphical representation of a formal proof, with each node representing a proposition or given conditions. A computer-assisted learning environment called MR Geo is proposed to help students in learning to do theorem proving, with the help of multiple representations including problem description, static figure, dynamic geometry figure, formal proof and proof tree. Empirical results indicated that medium-achievement students enjoyed most in interacting with these representations and found them most helpful in learning geometry proofs while low-achievement students changed their attitudes of hating geometry theorem proving. (Contains 4 figures and 4 tables.)

Patients with viral infections are susceptible to osteoporosis. This cohort study investigated the correlation between human papillomavirus (HPV) infections and the risk of osteoporosis via 12,936 patients with new-onset HPV infections and propensity score-matched non-HPV controls enrolled in Taiwan. The primary endpoint was incident osteoporosis following HPV infections. Cox proportional hazards regression analysis and the Kaplan-Meier method was used to determine the effect of HPV infections on the risk of osteoporosis. Patients with HPV infections presented with a significantly high risk of osteoporosis (adjusted hazard ratio, aHR = 1.32, 95% CI = 1.06–1.65) after adjusting for sex, age, comorbidities and co-medications. Subgroup analysis provided that populations at risk of HPV-associated osteoporosis were females (aHR = 1.33; 95% CI = 1.04–1.71), those aged between 60 and 80 years (aHR = 1.45, 95% CI = 1.01–2.08 for patients aged 60–70; aHR = 1.51; 95% CI = 1.07–2.12 for patients aged 70–80), and patients with long-term use of glucocorticoids (aHR = 2.17; 95% CI = 1.11–4.22). HPV-infected patients who did not receive treatments for HPV infections were at a greater risk (aHR = 1.40; 95% CI = 1.09–1.80) of osteoporosis, while the risk of osteoporosis in those who received treatments for HPV infections did not reach statistical significance (aHR = 1.14; 95% CI = 0.78–1.66). Patients with HPV infections presented with a high risk of subsequent osteoporosis. Treatments for HPV infections attenuated the risk of HPV-associated osteoporosis. [ABSTRACT FROM AUTHOR]

Background: Autism spectrum disorder (ASD) is a neurodevelopmental problem that presents with limited interests, repetitive behaviors, and deficits in reciprocal communication and social interactions. Mounting evidence indicates that an imbalanced gut microbiota contributes to autism via the gut-brain axis. Constipation may result in alteration of the gut microbiota. The clinical influence of constipation on ASD has not been fully researched. Thus, in this study we aimed to evaluate whether early childhood constipation influenced the risk of developing ASD using a nationwide population-based cohort study. Methods: We identified 12,935 constipated children aged 3 years or younger from the National Health Insurance Research Database (NHIRD) in Taiwan from 1997 to 2013. Non-constipated children were also selected from the database and propensity score matching of age, gender, and underlying comorbidities was conducted with a ratio of 1:1. Kaplan-Meier analysis was applied to determine different levels of constipation severity and cumulative incidence of autism. Subgroup analysis was also applied in this study. Results: The incidence rate of ASD was 12.36 per 100,000 person-months in the constipation group, which was higher than the rate of 7.84 per 100,000 personmonths noted in the non-constipation controls. Constipated children had a significantly higher risk of autism when compared to the non-constipation group (crude relative risk = 1.458, 95% CI = 1.116-1.904; adjusted hazard ratio = 1.445, 95% CI = 1.095-1.907). Moreover, among constipated children, a higher number of laxative prescriptions, male gender, constipation during infancy, and atopic dermatitis were significantly associated with higher risks of ASD when compared to the non-constipation group. Conclusion: Constipation in early childhood was correlated with a significantly increased risk of ASD. Clinicians should pay attention to the possibility of ASD in constipated children. Further research is necessary to study the possible pathophysiological mechanisms of this association. [ABSTRACT FROM AUTHOR]

Background: To determine whether patients who had undergone tonsillectomy would have higher risks of postoperative periodontitis.Methods: Data were collected from the Taiwan Longitudinal Health Insurance Dataset from 1999 to 2013, a population-based cohort study consisting of cases of newly-onset sleep apnoea, chronic diseases of tonsils and adenoids, peritonsillar abscess, and periodontal diseases. A total of 1482 tonsillectomy cases and 14,796 non-tonsillectomy controls were selected. Propensity score matching37 between the tonsillectomy group and the non-tonsillectomy group was conducted to exclude the confounding effect resulting from indications of tonsillectomy. Cox proportional hazard model and subgroup analyses were conducted to identify subpopulations at risk of tonsillectomy-associated periodontitis, and a sub-outcome analysis was applied to identify the subtype of tonsillectomy-associated periodontitis.Results: A total of 648 patients who had undergone tonsillectomy and 648 out of 6509 propensity score-matched controls were retrieved, among which 230 cases in the tonsillectomy group were associated with post-surgical periodontitis (adjusted HR = 1.31, 95% CI = 1.08 to 1.59). The association persisted in a subpopulation of patients with periodontitis who received mechanical and surgical treatments for periodontitis (adjusted HR = 1.33, 95% CI = 1.09 to 1.63). The incidence of periodontitis was significantly high in the individuals who underwent tonsillectomy and was particularly high in those that were below 12 years of age (HR = 1.58, 95% CI = 1.10 to 2.27). The risk of periodontitis increased 4 years after tonsillectomy (HR = 1.82; 95% CI = 1.29 to 2.59). The majority of post-tonsillectomy periodontitis was aggressive and acute periodontitis (HR = 1.37; 95% CI = 1.10 to 1.71).Conclusions: Tonsillectomy performed in pediatric patients of < 12 years old, increased the risk of developing periodontitis. Aggressive and acute periodontitis as a long-term, postoperative adverse event took place at 4 years or longer after tonsillectomy. [ABSTRACT FROM AUTHOR]

Previously, language teaching has been focused on the passive learning of the alphabet. In addition, the research on teaching listening and speaking skills was limited. Listening skill is the key to learning a language, and speaking is the first explicit behavior of language. In order to improve language skills which are emphasized in new curriculum guidelines, student-centered thematic language teaching is considered as valuable. Through this, the concepts of multiple intelligences and curriculum integration were re-emphasized. An experimental design was adopted in the current study. This study was conducted with the participation of 224 students from the Department of Multimedia Design in universities in the south of Taiwan. The research data were collected between September 2021 and December 2021. The implementation process took 16 weeks (a total of 48 h) of thematic language teaching. The research results revealed 1. significant positive effects of thematic language teaching on listening, 2. significant positive effects of thematic language teaching on speaking skill, and 3. significant negative effects of thematic language teaching on learning anxiety. According to the results, it is expected that this study can help multimedia design students improve their listening and speaking skills as well as core language skills. [ABSTRACT FROM AUTHOR]

Objectives: Lung cancer in never-smokers is a distinct disease associated with a different genomic landscape, pathogenesis, risk factors, and immune checkpoint inhibitor responses compared to those observed in smokers. This study aimed to identify novel single nucleotide polymorphisms (SNPs) of programmed death-1 (encoded by PDCD1) and its ligands, programmed death ligand 1 (CD274) and 2 (PDCD1LG2), associated with lung cancer risk in never-smoking women. Materials and Methods: During September 2002 and July 2012, we enrolled never-smoking female patients with lung adenocarcinoma (LUAD) (n=1153) and healthy women (n=1022) from six tertiary hospitals in Taiwan. SNP data were obtained and analyzed from the genome-wide association study dataset and through an imputation method. The expression quantitative trait loci (eQTL) analysis was performed in both tumor and non-tumor tissues for the correlation between genetic expression and identified SNPs. Results: A total of 12 PDCD1LG2 SNPs related to LUAD risk were identified in never-smoking women, including rs2381282, rs4742103, rs4237162, rs4742104, rs12237624, rs78096119, rs6476988, rs7857315, rs10975178, rs7854413, rs56001683, and rs7858319. Among them, six tagged PDCD1LG2 SNPs rs2381282, rs4742103, rs4237162, rs4742104, rs78096119, and rs56001683 were significantly associated with LUAD risk. Specifically, two PDCD1LG2 SNPs, rs12237624 and rs78096119, were associated with previous pulmonary tuberculosis infection in relation to LUAD susceptibility. Through an eQTL assay, we found that rs2381282 (p < 0.001), rs12237624 (p = 0.019), and rs78096119 (p = 0.019) were associated with the expression levels of programed death ligand 2. Conclusions: Novel SNPs of programed death ligand 2 associated with lung adenocarcinoma risk were identified. Among them, two SNPs were associated with pulmonary tuberculosis infection in relation to lung adenocarcinoma susceptibility. These SNPs may help to stratify high-risk populations of never-smokers during lung cancer screening. [ABSTRACT FROM AUTHOR]

Tonsillectomy is a commonly performed surgical procedure worldwide; however, the possible long-term consequences have not been fully explored. The tonsils are secondary lymphoid tissue providing a defensive barrier against pathogens. There are few data in the literature on the relationship between prior tonsillectomy and the risk of irritable bowel syndrome (IBS). The aim of this study was to evaluate the risk of developing IBS in patients who underwent tonsillectomy using a nationwide longitudinal population-based cohort. We identified 1300 patients with tonsillectomy and 2600 matched controls from the Longitudinal Health Insurance Research Database of the National Health Insurance Research Database in Taiwan. Propensity score analysis was used for matching age, gender, comorbidities, medications, and index year at a ratio of 1:2. Multiple Cox regression analysis was used to estimate the adjusted hazard ratio of IBS. Furthermore, sensitivity tests and a stratified analysis were conducted. The incidence of IBS was 3 per 1,000 person-years in tonsillectomy patients, which was higher than the rate of 1.8 per 1,000 person-years found in non-tonsillectomy patients. After adjustment for patients' age, gender, comorbidities, and medications, patients who underwent tonsillectomy had a 1.84-fold risk of developing IBS compared to those without tonsillectomy (adjusted hazard ratio [HR]:1.84; 95% CI, 1.09–3.09). Stratified analysis revealed that a higher adjusted HR of 3.79 (95% CI, 1.35–10.64) in patients ≥50 years old, and there was a marginally significantly higher adjusted HR of 1.98 (95% CI, 0.99–3.95) of developing IBS when the follow-up period was longer than 3 years. Tonsillectomy was associated with a higher risk of developing IBS. Physicians should provide appropriate monitoring of IBS in patients undergoing tonsillectomy. [ABSTRACT FROM AUTHOR]

Background. Vancomycin, the first line antibiotic for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia, is often administered inappropriately when MIC is greater than 2 µg/mL, including ‘susceptible’ strains. This study assessed the discordance of vancomycin minimum inhibitory concentration (MIC) for methicillin-resistant Staphylococcus aureus (MRSA). Methods. In total, 229 MRSA isolates from blood cultures collected between 2009 and 2015 at a tertiary hospital in Taiwan were examined. The MICs of vancomycin were measured using Vitek 2, E-test, and standard broth microdilution at the level of 2 µg/mL. Results. The geometric mean of the MICs of hospital-acquired MRSA was higher than that of community-acquired MRSA (P < 0.001), with the exact agreement rates (with broth microdilution) at 2 µg/mL being 53.6% in Vitek 2 and 86.7% in E-test. Overall, E-test (98.1%) had more categorical accordance than did Vitek 2 (94.0%; P = 0.026). Vitek 2 had a tendency to overestimate MRSA in high-MIC isolates, whereas E-test inclined underestimation in low-MIC isolates. Surprisingly, the discordance rates of MRSA vancomycin MICs were higher in hospital-acquired isolates (13.3%–17.0%) than in community-acquired isolates (6.2%–7.0%). Conclusion. The Infectious Diseases Society of America recommends the use of alternative antimicrobial agents when vancomycin MIC is ≥ 2 µg/mL; in this study, only 53.6% of the isolates tested using Vitek 2 showed a high MIC in the broth microdilution method. Accurate identification of the resistance profile is a key component of antimicrobial stewardship programs. Therefore, to reduce inappropriate antibiotic use and mitigate the emergence of resistant strains, we recommend using complementary tests such as E-test or Broth microdilution to verify the MIC before administering second-line antibiotics. Strengths. (1) We compared the categorical agreement between different methods measuring MRSA MICs level. (2) Physicians should incorporate this information and consider a complementary test to verify the appropriateness of the decision of shifting vancomycin to second-line antibiotic treatment to improve patients’ prognosis. (3) MRSA-vancomycin MICs at a cutoff of 2 µg/mL obtained using Vitek II exhibited a higher sensitivity level and negative predictive value than those obtained using E-test in the prediction of categorical agreement with standard broth microdilution. Limitation. (1) Our research was based on a single hospital-based study. (2) The MRSA strains in this study were stored for more than 12 months after isolation. (3) We did not collect information on clinical prognosis. [ABSTRACT FROM AUTHOR]

Galectin-3 is a beta-galactoside-binding lectin which is involved in modulating inflammation and apoptosis. Elevated expression of galectin-3 has been demonstrated in synovium of rheumatoid arthritis (RA). The aim of our study is to investigate the genetic polymorphisms of galectin-3 in association with RA. Polymorphisms of galectin-3 gene ( LGALS3) were compared between 151 RA patients and 182 healthy subjects in Taiwan. Variants at two LGALS3 single nucleotide polymorphism (SNP) sites (rs4644 and rs4652, corresponding to LAGLS3 +191 and +292) were genotyped by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP) and sequence-specific oligonucleotide probe hybridization, respectively. The allelic carriage of LGALS3 +292C was increased in patients with RA (66.9% in RA vs. 52.7% in controls, odds ratio = 1.8, 95% confidence interval = 1.2-2.8, p = 0.009). These results implicate that the genetic polymorphisms in galectin-3 gene may contribute to development of RA. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented about the incidence of the Japanese encephalitis virus (JEV) in Taiwan.

A letter to the editor about the imported cases of chikungunya disease in Taiwan from 2006 to 2009 is presented.

Bats are natural reservoirs of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome CoV (MERS-CoV). Scotophilus bat CoV-512 demonstrates potential for cross-species transmission because its viral RNA and specific antibodies have been detected in three bat species of Taiwan. Understanding the cell tropism of Scotophilus bat CoV-512 is the first step for studying the mechanism of cross-species transmission. In this study, a lentivirus-based pseudovirus was produced using the spike (S) protein of Scotophilus bat CoV-512 or SARS-CoV as a surface protein to test the interaction between coronaviral S protein and its cell receptor on 11 different cells. Susceptible cells expressed red fluorescence protein (RFP) after the entry of RFP-bound green fluorescence protein (GFP)-fused S protein of Scotophilus bat CoV-512 (RFP-Sco-S-eGFP) or RFP-SARS-S pseudovirus, and firefly luciferase (FLuc) activity expressed by cells infected with FLuc-Sco-S-eGFP or FLuc-SARS-S pseudovirus was quantified. Scotophilus bat CoV-512 pseudovirus had significantly higher entry efficiencies in Madin Darby dog kidney epithelial cells (MDCK), black flying fox brain cells (Pabr), and rat small intestine epithelial cells (IEC-6). SARS-CoV pseudovirus had significantly higher entry efficiencies in human embryonic kidney epithelial cells (HEK-293T), pig kidney epithelial cells (PK15), and MDCK cells. These findings demonstrated that Scotophilus bat CoV-512 had a broad host range for cross-species transmission like SARS-CoV. [ABSTRACT FROM AUTHOR]

Cationic amphiphilic antihistamines have been shown to improve patient outcomes in immunogenic tumours, but whether they can augment and improve response to immunotherapy is unknown. We aim to evaluate the effect of cationic amphiphilic antihistamines in patients receiving immune checkpoint inhibitors (ICIs). We conducted a retrospective propensity score-matched cohort study at two tertiary referral centres in Taiwan between January 2015 and December 2021. Patients who received desloratadine, cyproheptadine, and ebastine were classified as cationic amphiphilic antihistamine users. The primary outcome was overall survival, and the secondary outcomes were progression-free survival and clinical benefit rate. Patients treated with cationic amphiphilic antihistamines were matched to patients who received non-cationic amphiphilic antihistamines based on variables including age, cancer type, stage, and history of allergic diseases. A total of 734 ICI-treated patients were included. After matching, 68 cationic amphiphilic antihistamine and non-cationic amphiphilic antihistamine users remained for analysis. Compared with non-cationic amphiphilic antihistamine users, patients who received cationic amphiphilic antihistamines had a significantly longer median overall survival (24.8 versus 10.4 months; Log-rank, p = 0.018) and progression-free survival (10.6 versus 4.93 months; Log-rank, p = 0.004). The use of cationic amphiphilic antihistamines was associated with an approximately 50% lower risk of all-cause mortality (HR, 0.55 [95% CI: 0.34–0.91]). Survival benefits were not seen in patients who received cationic amphiphilic antihistamines before immune checkpoint blockade. These survival benefits were observed regardless of the generation of cationic amphiphilic antihistamines. The use of cationic amphiphilic antihistamines was associated with improved survival among patients treated with immunotherapy. • Study evaluating the effects of cationic amphiphilic antihistamines on immune checkpoint inhibitor therapy. • Cationic amphiphilic antihistamines were associated with survival benefits. • Effects not seen in patients who took cationic amphiphilic antihistamines before immune checkpoint inhibitor. • Benefits observed regardless of the generation of cationic amphiphilic antihistamines. [ABSTRACT FROM AUTHOR]

Background: Recently, several studies revealed a much higher prevalence of later onset Fabry disease (FD) than previously expected. It suggested that later onset FD might present as an important hidden health issue in certain ethnic or demographic populations in the world. However, the natural history of its phenotype has not been systemically investigated, especially the cardiac involvement.Objectives: The study analyzed a large-scale newborn screening program for FD to understand the natural course of later onset FD.Methods: To date, 916,383 newborns have been screened for FD in Taiwan, including more than 1,200 individuals with the common, later onset IVS4+919G>A (IVS4) mutation. Echocardiography was performed in 620 adults with the IVS4 mutation to analyze the prevalence of left ventricular hypertrophy (LVH), and gadolinium-enhanced cardiac magnetic resonance imaging was performed in 129 patients with FD, including 100 IVS4 adults.Results: LVH was observed in 67% of men and 32% of women older than 40 years. Imaging evidenced significant late gadolinium enhancement in 38.1% of IVS4 men and 16.7% of IVS4 women with the IVS4 mutation but without LVH. Seventeen patients underwent endomyocardial biopsies, which revealed significant globotriaosylceramide substrate accumulation in their cardiomyocytes.Conclusions: Significant cardiomyocyte substrate accumulation in IVS4 patients led to severe and irreversible cardiac fibrosis before development of LVH or other significant cardiac manifestations. Thus, it might be too late to start enzyme replacement therapy after the occurrence of LVH or other significant cardiac manifestations in patients with later onset FD. This study also indicated the importance of newborn screening for early detection of the insidious, ongoing, irreversible cardiac damage in patients with later onset FD. [ABSTRACT FROM AUTHOR]

Abstract: Shigella sonnei replaced Shigella flexneri to become the predominant species for shigellosis in 2001 to 2003 in central Taiwan. A total of 425 S. sonnei isolates collected from 1996 to 2004 were available for characterization by pulsed-field gel electrophoresis (PFGE), inter-IS1 spacer typing (IST), and antimicrobial susceptibility testing. The results showed that at least 21 IST clones had emerged for the S. sonnei infections in 1996 to 2004. Most IST clones lasted for a short time; some circulated for 2 to 3 years. An IST1 clone, detected for the first time in 2000, was the most prevalent and responsible for the shigellosis epidemic in 2001 to 2003. Over 3 years of sustained transmission, the IST1 clone evolved into many strains with different PFGE genotypes and antibiograms. The ancestor, with a J16N09.0019 PFGE genotype, remained to be the predominant circulating strain in the period studied; however, new strains with certain PFGE genotypes and antibiograms could become major circulating strains for subsequent infections. [Copyright &y& Elsevier]

Objectives: The association of migraine with the risk of certain cancer has been reported. The aim of this pilot study was to examine the associations between migraine and the onset of head and neck cancers (HNC)., Materials and Methods: A total of 1755 individuals were identified through a nationwide population-based cohort registry in Taiwan between 2000 and 2013. The primary end point variable was new-onset head and neck cancers in patients with migraine versus non-migraine controls. Cox proportional hazard regression was used to derive the risk of HNC. Subgroup analyses were performed to determine subpopulations at risk of migraine-associated HNC. Sub-outcome analyses were carried out to provide the subtypes of migraine-associated HNC. Propensity score matching was utilized to validate the findings., Results: A total of four patients out of 351 patients with migraine and seven out of 1404 non-migraine controls developed HNC. The incidence of HNC was higher in patients with migraine than that in non-migraine controls (108.93 vs. 48.77 per 100,000 person-years) (adjusted hazard ratio, aHR = 2.908, 95% CI = 0.808-10.469; p = 0.102). The risk of HNC in patients with migraine with aura (aHR = 5.454, 95% CI = 0.948-26.875; p = 0.264) and without aura (aHR = 2.777, 95% CI = 0.755-8.473; p = 0.118) was revealed. The incidence of non-nasopharyngeal HNC secondary to migraine (112.79 per 100,000 person-years) was higher than that of nasopharyngeal cancer secondary to migraine (105.33 per 100,000 person-years)., Conclusion: A higher incidence of HNC was observed in a small sample of patients with migraine, especially in those with migraine with aura. Migraine-associated HNC included non-nasopharyngeal HNC. Studies with a larger sample are needed to confirm the finding of the high risk of HNC in people with migraine., (© 2023 Wiley Periodicals LLC.)

Background: Major depressive disorder (MDD) and dementia are both major contributors to the global burden of disease. Despite existing literature on the association between MDD and dementia, there is a lack of a nationwide longitudinal cohort study that considers the competing risk of death. Therefore, this study assessed the bidirectional associations between MDD and dementia over an 11-year period in population-based settings, accounting for death as a competing risk., Methods: We conducted two population-based retrospective cohort studies in Taiwan. We identified 80,742 patients diagnosed with MDD in 2009-2010 and matched them with patients without MDD by sex, age, and year of diagnosis to assess the relative risk of dementia. We also identified 80,108 patients diagnosed with dementia in 2009-2010 and matched them with patients without dementia by sex, age, and year of diagnosis to assess the relative risk of MDD. All patients were followed until they received a diagnosis of new onset MDD or new onset dementia, their death, or the end of 2019. Cause-specific hazards models were used to estimate adjusted hazard ratios (aHRs)., Results: The incidence density (ID) of dementia was higher in patients with MDD than in patients without MDD (7.63 vs. 2.99 per 1000 person-years), with an aHR of 2.71 (95% confidence interval [CI]: 2.55-2.88). The ID of MDD was higher in patients with dementia than in patients without dementia (12.77 vs. 4.69 per 1000 person-years), with an aHR of 2.47 (95% CI: 2.35-2.59)., Conclusions: This population-based study found a bidirectional association between MDD and dementia. Our findings suggest the need to identify dementia in patients with MDD and vice versa., Competing Interests: Declaration of Competing Interest The authors claimed no conflict of interest for publication of this study., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Methods synthesizing multiple data sources without prospective datasets have been proposed for absolute risk model development. This study proposed methods for adapting risk models for another population without prospective cohorts, which would help alleviate the health disparities caused by advances in absolute risk models. To exemplify, we adapted the lung cancer risk model PLCOM2012, well studied in the west, for Taiwan., Methods: Using Taiwanese multiple data sources, we formed an age-matched case-control study of ever-smokers (AMCCSE), estimated the number of ever-smoking lung cancer patients in 2011-2016 (NESLP2011), and synthesized a dataset resembling the population of cancer-free ever-smokers in 2010 regarding the PLCOM2012 risk factors (SPES2010). The AMCCSE was used to estimate the overall calibration slope, and the requirement that NESLP2011 equals the estimated total risk of individuals in SPES2010 was used to handle the calibration-in-the-large problem., Results: The adapted model PLCOT-1 (PLCOT-2) had an AUC of 0.78 (0.75). They had high performance in calibration and clinical usefulness on subgroups of SPES2010 defined by age and smoking experience. Selecting the same number of individuals for low-dose computed tomography screening using PLCOT-1 (PLCOT-2) would have identified approximately 6% (8%) more lung cancers than the US Preventive Services Task Forces 2021 criteria. Smokers having 40+ pack-years had an average PLCOT-1 (PLCOT-2) risk of 3.8% (2.6%)., Conclusions: The adapted PLCOT models had high predictive performance., Impact: The PLCOT models could be used to design lung cancer screening programs in Taiwan. The methods could be applicable to other cancer models., (©2022 The Authors; Published by the American Association for Cancer Research.)

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection produces more severe symptoms and a higher mortality in men than in women. The role of biological sex in the immune response to SARS-CoV-2 is believed to explain this sex disparity. However, the contribution of gender factors that influence health protective behaviors and therefore health outcomes, remains poorly explored., Methods: We assessed the contributions of gender in attitudes towards the COVID-19 pandemic, using a hypothetical influenza pandemic data from the 2019 Taiwan Social Change Survey. Participants were selected through a stratified, three-stage probability proportional-to-size sampling from across the nation, to fill in questionnaires that asked about their perception of the hypothetical pandemic, and intention to adopt health protective behaviors., Results: A total of 1,990 participants (median age = 45·92 years, 49% were women) were included. Significant gender disparities (p < .001) were observed. The risk perception of pandemic (OR = 1·28, 95% CI [1·21 - 1·35], p < .001), older age (OR = 1·06, 95% CI [1·05 - 1·07], p < .001), female gender (OR = 1·18, 95% CI [1·09-1·27], p < .001), higher education (OR = 1·10, 95% CI [1·06 - 1·13], p < .001), and larger family size (OR = 1·09, 95% CI [1·06 - 1·15], p < .001) were positively associated with health protective behaviors. The risk perception of pandemic (OR = 1·25, 95% CI [1·15 - 1·36]), higher education (OR = 1·07, 95% CI [1·02 - 1·13], p < .05), being married (OR = 1·17, 95% CI [1·01-1·36, p < .05), and larger family size (OR = 1·33, 95% CI [1·25 - 1·42], p < .001), were positively associated with intention to receive a vaccine. However, female gender was negatively associated with intention to receive a vaccine (OR = 0·85, 95% CI [0·75 - 0·90], p < ·01) and to comply with contact-tracing (OR = 0·95, 95% CI [0·90 - 1·00], p < .05) compared to men. Living with children was also negatively associated with intention to receive vaccines (OR = 0·77, 95% CI [0·66 - 0·90], p < .001)., Conclusion: This study unveils gender differences in risk perception, health protective behaviors, vaccine hesitancy, and compliance with contact-tracing using a hypothetical viral pandemic. Gender-specific health education raising awareness of health protective behaviors may be beneficial to prevent future pandemics., (© 2022. The Author(s).)

The Fabry disease-causing mutation, the GLA IVS4+919G>A (designated GLA IVS4), is very prevalent in patients with hypertrophic cardiomyopathy in Taiwan. This X-linked mutation has also been found in patients in Kyushu, Japan and Southeast Asia. To investigate the age and the possible ancestral origin of this mutation, a total of 33 male patients with the GLA IVS4+919G>A mutation, born in Taiwan, Japan, Singapore, Malaysia, Vietnam, and the Fujian and Guangdong provinces of China, were studied. Peripheral bloods were collected, and the Ilumina Infinium CoreExome-24 microarray was used for dense genotyping. A mutation-carrying haplotype was discovered which was shared by all 33 patients. This haplotype does not exist in 15 healthy persons without the mutation. Rather, a wide diversity of haplotypes was found in the vicinity of the mutation site, supporting the existence of a single founder of the GLA IVS4 mutation. The age of the founder mutation was estimated by the lengths of the mutation-carrying haplotypes based on the linkage-disequilibrium decay theory. The first, second, and third quartile of the age estimates are 800.7, 922.6, and 1068.4 years, respectively. We concluded that the GLA IVS4+919G>A mutation originated from a single mutational event that occurred in a Chinese chromosome more than 800 years ago.

Background: In the current literature, studies assessing the role of Helicobacter pylori (HP) infection in psoriasis have reported conflicting data. Therefore, we investigated the association between HP infection and psoriasis using a nationwide population-based longitudinal cohort study., Methods: We identified 41,539 patients with HP infection and 83,078 matched controls between 2000 and 2013 from the Longitudinal Health Insurance Research Database of the National Health Insurance Research Database in Taiwan. Propensity score analysis was used to match age, sex, comorbidities, and medical visits at a ratio of 1:2. Multiple Cox regression analysis was used to estimate the adjusted hazard ratio of psoriasis. Furthermore, sensitivity tests and a stratified analysis were conducted., Results: The incidence rates of psoriasis did not differ significantly between the HP and control cohorts (4.58 vs 4.20 per 100,000 person-months, crude relative risk: 1.092, 95% confidence interval: 0.917-1.302). After multivariate adjustment, no significant difference in psoriasis risk was observed in patients with HP infection (adjusted hazard ratio: 1.081, 95% confidence interval: 0.907-1.288). Risk of psoriasis was significantly higher in men and the elderly, and in those with diabetes, hyperlipidemia, chronic obstructive pulmonary disease, or tuberculosis. Stratified analysis also confirmed that HP infection was not correlated with an increased risk of psoriasis based on follow-up duration, sex, and age., Conclusion: This retrospective population-based longitudinal cohort study, conducted in Taiwan, found no association between HP infection and risk of psoriasis. Further research may be warranted.

Background: High disease burden suggests the desirability to identify high-risk Asian never-smoking females (NSF) who may benefit from low-dose CT (LDCT) screening. In North America, one is eligible for LDCT screening if one satisfies the U.S. Preventive Services Task Force (USPSTF) criteria or has model-estimated 6-year risk greater than 0.0151. According to two U.S. reports, only 36.6% female patients with lung cancer met the USPSTF criteria, while 38% of the ever-smokers ages 55 to 74 years met the USPSTF criteria., Methods: Using data on NSFs in the Taiwan Genetic Epidemiology Study of Lung Adenocarcinoma and the Taiwan Biobank before August 2016, we formed an age-matched case-control study consisting of 1,748 patients with lung cancer and 6,535 controls. Using these and an estimated age-specific lung cancer 6-year incidence rate among Taiwanese NSFs, we developed the Taiwanese NSF Lung Cancer Risk Models using genetic information and simplified questionnaire (TNSF-SQ). Performance evaluation was based on the newer independent datasets: Taiwan Lung Cancer Pharmacogenomics Study (LCPG) and Taiwan Biobank data after August 2016 (TWB2)., Results: The AUC based on the NSFs ages 55 to 70 years in LCPG and TWB2 was 0.714 [95% confidence intervals (CI), 0.660-0.768]. For women in TWB2 ages 55 to 70 years, 3.94% (95% CI, 2.95-5.13) had risk higher than 0.0151. For women in LCPG ages 55 to 74 years, 27.03% (95% CI, 19.04-36.28) had risk higher than 0.0151., Conclusions: TNSF-SQ demonstrated good discriminative power. The ability to identify 27.03% of high-risk Asian NSFs ages 55 to 74 years deserves attention., Impact: TNSF-SQ seems potentially useful in selecting Asian NSFs for LDCT screening., (©2019 American Association for Cancer Research.)

Background: While chronic rhinosinusitis is a common complication of allergic rhinitis, the link between acute rhinosinusitis and allergic rhinitis is unclear. The aim of this study was to evaluate the risk of incident acute rhinosinusitis among pediatric patients with allergic rhinitis, using a nationwide, population-based health claims research database., Methods: Newly diagnosed allergic rhinitis patients aged 5-18 years were identified from the health claim records of the Longitudinal Health Insurance Database 2000 of Taiwan's National Health Insurance Research Database. A comparison cohort was assembled by randomly selecting patients from the same database with frequency matching by sex, age group, and index year. All patients were followed until a diagnosis of acute rhinosinusitis or the end of the follow-up period. Cox proportional hazards model was used to assess the association between allergic rhinitis and acute rhinosinusitis., Results: Of the 43,588 pediatric patients included in this study, 55.4% were male and 43.9% were between the ages of 5.0-7.9 years. The risk of acute rhinosinusitis was significantly higher in pediatric patients with allergic rhinitis compared to those without the condition (adjusted hazard ratio = 3.03, 95% confidence interval = 2.89-3.18). Similar hazard ratios were observed between male and female pediatric patients., Conclusions: This secondary cohort study using a nationwide, population-based health claim data of the Taiwan's NHIRD showed that allergic rhinitis was significantly associated with a higher risk of acute rhinosinusitis among pediatric patients., Competing Interests: The authors have declared that no competing interests exist.

The clinical characteristics of 89 patients with Lactobacillus bacteraemia treated at a university-affiliated hospital in northern Taiwan during 2000-2014 were retrospectively evaluated. Lactobacillus spp. were identified by 16S rRNA sequencing analysis and matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF/MS). Antimicrobial susceptibilities of the isolates were determined by broth microdilution. The most commonly isolated species was Lactobacillus salivarius (n = 21), followed by Lactobacillus paracasei (n = 16) and Lactobacillus fermentum (n = 13). Excluding three isolates with lower 16S rRNA sequence similarity, MALDI-TOF/MS provided correct identification for 84.9% (73/86) of Lactobacillus isolates. Concordant identification was lowest for Lactobacillus casei (11%). The main infection foci were intra-abdominal infection (49%) and catheter-related bloodstream infection (17%). Only one-half of the patients received adequate antibiotic treatment during the bacteraemic episode. The majority of patients with Lactobacillus bacteraemia were immunocompromised. The 7-day and in-hospital mortality rates were 21% and 62%, respectively, and underlying malignancy was associated with a higher in-hospital mortality rate (odds ratio = 2.666). There were no significant differences in mortality (7-day, 14-day, 30-day and in-hospital) among patients with bacteraemia due to different Lactobacillus spp. Minimum inhibitory concentrations were highest for glycopeptides, cephalosporins and fluoroquinolones and were lowest for carbapenems and aminopenicillins. Lactobacillus bacteraemia was associated with a high mortality rate, and patient outcome was associated with underlying malignancy. MALDI-TOF/MS was able to accurately identify 84.9% of the Lactobacillus isolates, and L. salivarius was the predominant pathogen. The accuracy rate for identification of Lactobacillus spp. by MALDI-TOF/MS was lowest for L. casei., (Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)

Background: To evaluate if a severity score could differentiate the severity of children with nontyphoid salmonellosis; clinical outcomes of antimicrobial therapy in nontyphoid salmonellosis children with different severities., Methods: Admitted children with nontyphoid salmonellosis from 1996 to 2009 were monitored. Enrolled patients were divided into no antibiotics, concordant, and discordant therapies. Besides, the patients were classified into mild, moderate, and severe group according to the severity score. Clinical outcomes were compared among them., Results: A total of 558 patients were enrolled. In no therapy subset, compared with mild group, patients had worse clinical outcomes and more complications in severe group. Patients receiving no therapy had better clinical outcomes in mild group. However, patients receiving concordant therapy (ceftriaxone) had better clinical outcomes in severe group., Conclusions: The severity score and local antibiotic susceptibility could serve as guides for antibiotic prescription for severe nontyphoid salmonellosis in children. Inappropriate antibiotic use would worsen clinical outcomes in children with mild nontyphoid salmonellosis., (© The Author(s) 2014.)

Mycobacterium abscessus complex (M. abscessus subsp. abscessus and M. abscessus subsp. bolletii) is an emerging pathogen causing various human infections. However, few studies have focused on M. abscessus complex bacteraemia with detailed species differentiation. The clinical characteristics of patients with bacteraemia due to M. abscessus complex treated at National Taiwan University Hospital from 2005-2012 were evaluated. Species identification was performed by molecular methods, and minimum inhibitory concentrations (MICs) were determined using a Sensititre RAPMYCO Panel Test for preserved M. abscessus complex isolates. During the study period, 15 patients with M. abscessus complex bacteraemia were found but only 14 isolates from 13 patients were preserved for analysis. One patient had two episodes of bacteraemia (one caused by M. abscessus subsp. bolletii and one by M .abscessus subsp. abscessus with a 9-month interval). Of the remaining 12 patients, 9 patients had M. abscessus subsp. bolletii bacteraemia and 3 had M .abscessus subsp. abscessus bacteraemia. Patients were mainly middle-aged adults with various co-morbidities. Steroid usage and malignancy (5/15) were the most common immunocompromised statuses, followed by diabetes mellitus (4/15). Surgical wound infection was the most common infection foci in all patients (5/15), particularly in M. abscessus subsp. bolletii bacteraemia patients. Clarithromycin and tigecycline exhibited good in vitro activities. Overall, the 14-day mortality was 20% (3/15). M. abscessus complex bacteraemia should be considered an emerging opportunistic infection in immunocompromised hosts. Clarithromycin and tigecycline have potent in vitro activities and are promising agents for treating infections due to M. abscessus complex., (Copyright © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)

The growth arrest-specific 6 (GAS6) gene product participates in platelet activation and granulocyte interaction with the endothelium. Our case-control study aimed to determine whether polymorphism of GAS6 was associated with predisposing risk or specific clinical manifestations of systemic lupus erythematosus (SLE). Two of the single-nucleotide polymorphisms (SNPs) of the GAS6 gene, GAS6 834 + 7G/A (rs8191974) and GAS6 +1332C/T (rs1803628), were investigated in 83 SLE patients and 89 non-lupus control subjects. We demonstrated that among lupus patients, the GAS6 +1332 T allele was more prevalent in patients with cutaneous vasculitis (allele T 41.7 % in patients with cutaneous vasculitis compared with 18.3 % in patients without vasculitis, odds ratio (OR) 3.2, 95 % confidence interval 1.3-8.0, p = 0.016). In conclusion, GAS6 polymorphism is positively associated with cutaneous vasculitis in SLE patients, which suggests that GAS6 polymorphism could be a genetic marker for SLE with cutaneous vasculitis.

Scrub typhus is a rickettsial disease transmitted to humans through the bite of chigger mites infected with Orientia tsutsugamushi, and is an endemic disease in Taiwan. To elucidate the molecular epidemiology of O. tsutsugamushi, the complete open reading frame of the 56-kDa type-specific antigen gene sequence of strains isolated from scrub typhus patients were determined and analyzed. A total of 116 isolates of O. tsutsugamushi were successfully isolated from patients infected in diverse geographic origins including Taiwan and three offshore islets, Kinmen, Matsu, and Penghu between May 2006 and December 2007. Sequence analysis revealed that 22 distinct sequence types could be identified that were broadly distributed in different clusters of the phylogenetic tree. Most of the isolates belong to Karp, Kawasaki, and Kuroki genotypes and are closely related to strains from Thailand, Japan, and Korea, whereas unique isolates different from other countries were also found in Taiwan. Distinct seasonal distributions were found in different sequence types. Some sequence types caused disease in the cold season, whereas others caused disease in the warm season.

Objectives: This retrospective study evaluates the role of pharmacogenomic determinants in the treatment of childhood acute lymphoblastic leukemia (ALL) in the Taiwanese population., Methods: A total of 105 childhood ALL patients received combined chemotherapy of different intensities based on risk-directed Taiwan Pediatric Oncology Group (TPOG)-ALL-93 protocols. Seventeen genetic polymorphisms in 13 pharmacogenomic targets were analyzed by PCR-based restriction fragment length polymorphism (RFLP) and sequence-specific oligonucleotide (SSO) probe hybridization. Pharmacogenomic polymorphisms were correlated with event-free survival (EFS) of patients, with confounding effects adjusted by multivariate regression., Results: Three polymorphic alleles in the multi-drug resistance 1 (MDR1) ABCB1 gene, and homozygotic MDR1 2677GG, 3435CC, and 2677G-3435C genotypes were highly associated with a significant reduction in EFS in those patients treated by the standard risk (SR) protocol (TPOG-ALL-93-SR). The hazard ratios were 6.8 (p = 0.01), 21.7 (p = 0.009), and 6.8 (p = 0.01), respectively., Conclusions: Independent pharmacogenomic determinants associated with treatment outcome were identified in subsets of Taiwanese ALL patients., ((c) 2009 Wiley-Liss, Inc.)