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Abstract Tylophorine-based compounds exert broad spectral, potent inhibition of coronaviruses. NF-κB activation is a common pro-inflammatory response of host cells to viral infection. The aims of this study were to (i) find an effective combination treatment for coronaviral infections through targeting of the virus per se and cellular NF-κB activity; and (ii) to study the underling mechanisms. We found that tylophorine-based compounds target the TGEV viral RNA and effectively inhibit TGEV replication. NF-κB inhibition also leads to anti-TGEV replication. NF-κB activation induced by TGEV infection was found to be associated with two convergent pathways, IKK-2_IκBα/p65 and JAK2 mediated p65 phosphorylation, in swine testicular cells. JAK2 inhibition either by CYT387 (a JAK family inhibitor) or by silencing JAK2-expression revealed a dominant JAK2 mediated p65 phosphorylation pathway for NF-κB activation and resulted in NF-κB inhibition, which overrode the IκBα regulation via the IKK-2. Finally, tylophorine-based compounds work cooperatively with CYT387 to impart comprehensive anti-TGEV activities. The combination treatment, wherein a tylophorine compound targets TGEV and a JAK2 inhibitor blocks the alternative dominant NF-κB activation mediated by JAK2, is more effective and comprehensive than either one alone and constitutes a feasible approach for the treatment of SARS-CoV or MERS-CoV.

Abstract Background Small extracellular vesicle (sEV) analysis can potentially improve cancer detection and diagnostics. However, this potential has been constrained by insufficient sensitivity, dynamic range, and the need for complex labeling. Methods In this study, we demonstrate the combination of PANORAMA and fluorescence imaging for single sEV analysis. The co-acquisition of PANORAMA and fluorescence images enables label-free visualization, enumeration, size determination, and enables detection of cargo microRNAs (miRs). Results An increased sEV count is observed in human plasma samples from patients with cancer, regardless of cancer type. The cargo miR-21 provides molecular specificity within the same sEV population at the single unit level, which pinpoints the sEVs subset of cancer origin. Using cancer cells-implanted animals, cancer-specific sEVs from 20 µl of plasma can be detected before tumors were palpable. The level plateaus between 5–15 absolute sEV count (ASC) per µl with tumors ≥8 mm3. In healthy human individuals (N = 106), the levels are on average 1.5 ASC/µl (+/− 0.95) without miR-21 expression. However, for stage I–III cancer patients (N = 205), nearly all (204 out of 205) have levels exceeding 3.5 ASC/µl with an average of 12.2 ASC/µl (±9.6), and a variable proportion of miR-21 labeling among different tumor types with 100% cancer specificity. Using a threshold of 3.5 ASC/µl to test a separate sample set in a blinded fashion yields accurate classification of healthy individuals from cancer patients. Conclusions Our techniques and findings can impact the understanding of cancer biology and the development of new cancer detection and diagnostic technologies.

Cinnamomum kanehirae Hayata, belonging to Lauraceae family, is an indigenous and endangered species of considerable economic importance in Taiwan. It plays a crucial role as the host for the economically valuable saprotrophic fungus, Taiwanofungus camphorates. However, accurate species identification poses a challenge due to the similarity in morphological features and frequent natural hybridization with closely related species. Acquiring high-quality and pure leaf oils becomes imperative for precise species identification and producing superior goods. In this study, our objective was to establish methodologies for analyzing the chemical composition of leaf essential oils and subsequently apply this knowledge to differentiate among three Cinnamomum species. Gas chromatography-mass spectrometry (GC/MS) was employed to scrutinize the chemical makeup of leaf essential oils from three closely related species: C. kanehirae, C. micranthum, and C. camphora. We utilized Steam Distillation (SD) and steam distillation-solvent extraction (SDSE) methods, with the SDSE-Hexane approach chosen for optimization, enhancing extraction efficiency and ensuring essential oil purity. Through the SDSE-Hexane method, we identified seventy-four compounds distributed across three major classes: monoterpenes hydrocarbons (0.0–7.0 %), oxygenated monoterpenes (3.8–90.9 %), sesquiterpenes hydrocarbons (0.0–28.3 %), and oxygenated sesquiterpenes (1.6–88.1 %). Our findings indicated the presence of more than one chemotype in both C. kanehirae and C. camphora, whereas no specific chemotype could be discerned in C. micranthum. Furthermore, clustering based on chemotypes allowed for the differentiation of samples from the three species. Notably, we demonstrated that the chemical compositions of grafted C. kanehirae remained largely unaffected by the rootstock. Conversely, natural hybrids between C. kanehirae and C. camphora exhibited profiles more closely aligned with C. kanehirae. The optimized extraction method and the chemotype-based classification system established in this study present valuable tools for essential oil preparation, species identification, and further exploration into the genetic variation of Cinnamomum.

Abstract Purpose The objective of this study was to investigate the potential of arthroscopic scapholunate ligament repair and dorsal capsulodesis with suture anchor as a treatment option for patients experiencing symptomatic acute and subacute ( .01).The Wilcoxon signed-rank test was used to compare the results: grip force improved significantly with 14.7% improvement of that on the normal side (P

Blood‐circulating exosomes as a disease biomarker have great potential in clinical applications as they contain molecular information about their parental cells. However, label‐free characterization of exosomes is challenging due to their small size. Without labeling, exosomes are virtually indistinguishable from other entities of similar size. Over recent years, several techniques have been developed to overcome the existing challenges. This article demonstrates a new label‐free approach based on dynamic PlAsmonic NanO‐apeRture lAbel‐free iMAging (D‐PANORAMA), a bright‐field technique implemented on arrayed gold nanodisks on invisible substrates (AGNIS). PANORAMA provides high surface sensitivity and has been shown to count single 25 nm polystyrene beads previously. Herein, it is shown that using the dynamic imaging mode, D‐PANORAMA can yield 3D, subdiffraction limited localization of individual 25 nm beads. Furthermore, D‐PANORAMA's capability to size, count, and localize the 3D, subdiffraction limited position of individual exosomes is demonstrated as they bind to the AGNIS surface. The importance of both the in‐plane and out‐of‐plane localization, which exploit the synergy of 2D imaging and the intensity contrast, is emphasized.

Abstract Background This study was designed to analyze the clinical follow-up results (minimum of 2 years) in patients with stable nonunion, unstable nonunion, or nonunion of the scaphoid with early degenerative radioscaphoid arthritis (Lichtman classification stage I–III) treated with arthroscopic osteosynthesis with autogenous bone graft. Methods We retrospectively recruited 44 consecutive patients with scaphoid fracture nonunion treated with arthroscopy-assisted percutaneous internal fixation with autogenous bone grafts from January 2010 to November 2019. We recorded union and return to activity and analyzed data with regular clinical follow-up at a mean duration of 33 months (range 24–46 months). Clinical (i.e., visual analog scale pain score, grip strength, and range of motion), radiographic, and functional (Mayo Modified Wrist Score (MMWS)) outcomes at the final follow-up were compared with the preoperative assessments and analyzed in patients with different stages. Results We confirmed union in 39 of the 44 patients (88.6%) after a mean 15.4 weeks post-operatively according to clinical examinations and standard radiography. All clinical parameters improved significantly. For the MMWS, there were 25 excellent and 14 good results. Of the 44 patients, 40 (90.9%) returned to work or sports activities at their preinjury levels. Comparisons of the outcomes between patients in different stages of scaphoid nonunion revealed no significant difference in the aspect of union rate, VAS pain score, and functional score improvement. Conclusions Arthroscopic osteosynthesis with autogenous bone grafts is a reliable and minimally invasive method for achieving nonunion healing and improving clinical outcomes in stage I–III scaphoid nonunion. Level of Evidence: Level IV, case series.

Summary: Genomic researchers increasingly utilize commercial cloud service providers (CSPs) to manage data and analytics needs. CSPs allow researchers to grow Information Technology (IT) infrastructure on demand to overcome bottlenecks when combining large datasets. However, without adequate security controls, the risk of unauthorized access may be higher for data stored on the cloud. Additionally, regulators are mandating data access patterns and specific security protocols for the storage and use of genomic data. While CSP provides tools for security and regulatory compliance, building the necessary controls required for cloud solutions is not trivial. Research Assets Provisioning and Tracking Online Repository (RAPTOR) by the Genome Institute of Singapore is a cloud-native genomics data repository and analytics platform that implements a “five-safes” framework to provide security and governance controls to data contributors and users, leveraging CSP for sharing and analysis of genomic datasets without the risk of security breaches or running afoul of regulations.

(1) Background: Many studies have revealed a relationship between serum 25-hydroxy vitamin D and physical activity. This study aimed to investigate the relationship between self-reported sitting time and serum 25-hydroxy vitamin D levels in middle-aged and elderly adults in Taiwan. (2) Methods: A total of 396 people were enrolled in our study during a community health examination in Taiwan in 2019. We grouped participants from low to high according to their tertile of serum 25-hydroxy vitamin D levels, using the following categories: deficiency, insufficiency, and sufficiency. Parameters including self-reported sitting time were analyzed between each group. Pearson correlation coefficients were calculated to explore the relationships of serum 25-hydroxy vitamin D levels with age-adjusted risk factors. A scatter plot demonstrated the relationship between serum 25-hydroxy vitamin D levels and self-reported sitting time. The association between serum 25-hydroxy vitamin D levels and self-reported sitting time was assessed by multivariate linear regression with adjustment for age, sex, waist circumference, low-density lipoprotein, triglycerides, and smoking and drinking status. (3) Results: We analyzed the data from 396 participants. A total of 41.4% of participants were male, and the average age of all participants was 64.91 (±8.80) years. The participants in the high serum 25-hydroxy vitamin D group were more likely to have shorter self-reported sitting time. Serum 25-hydroxy vitamin D was negatively correlated (Pearson’s r) with self-reported sitting time, even after adjustment for age. According to the results of multivariate linear regression, vitamin D levels showed a negative association with self-reported sitting time (β = −0.131, p = 0.006) after adjustment for age, sex, waist circumference, low-density lipoprotein, triglycerides, and smoking and drinking status. (4) Conclusions: According to our research, self-reported sitting time was inversely correlated with serum 25-hydroxy vitamin D in middle-aged and elderly people in Taiwan. Meanwhile, longer self-reported sitting time can be an independent risk factor for lower serum 25-hydroxy vitamin D levels.

The genus Lasiodiplodia, a member of the family Botryosphaeriaceae, is an important fungal disease genus in agriculture. However, the Lasiodiplodia species survey and genetic diversity in Taiwan remain unclear. This study aimed to investigate the Lasiodiplodia species associated with various fruit species to explore the cryptic Lasiodiplodia species diversity, validate species delimitation, and unveil cryptic genetic diversity. Overall, six Lasiodiplodia species were identified, with several new records of infection identified. Additionally, phylogenetic analyses indicated that the relations of all isolates of L. theobromae might be paraphyletic. They were grouped with L. brasiliense based on Automatic Barcode Gap Discovery (ABGD), Automatic Partitioning (ASAP) and structure-based clustering analyses. These analyses did not provide conclusive evidence for L. brasiliensis as a stable species. It may be necessary to gather more information to clarify the species delineation. The multiple new records of Lasiodiplodia species with high genetic diversity and differentiation revealed that the diversity of Lasiodiplodia in Taiwan was underestimated in the past. We found that L. theobromae has the highest number of haplotypes but the lowest number of haplotype and nucleotide diversities, indicating a recent population expansion. This was supported by the significant negative Tajima’s D and Fu and Li’s D* tests. The high genetic diversity, low gene flow, and host-associated differentiation of Lasiodiplodia species indicate that they might harbour powerful evolutionary potential in Taiwan. This study provided critical insights into genetic variation, host-associated differentiation, and demography of Lasiodiplodia species, which would be helpful for disease management of related pathogens.

BackgroundAssociation of sedentary behavior and plasma leptin levels is a popular topic in recent research. Aged populations often suffer from cardiometabolic diseases, and leptin is considered a novel marker for many cardiometabolic diseases. To further explore this topic, our research investigates the relationship between sedentary time and serum leptin levels in middle-aged and older populations.MethodsA total of 396 middle-aged and older adult Taiwanese participants were included in this study. We recorded their self-reported sitting time as sedentary time. Participants were categorized into low leptin, medium leptin group, and high leptin groups according to the tertile of serum leptin level in the study. We also analyzed the anthropometric and cardiometabolic parameters between the three groups. Spearman's correlation coefficient was used to analyze the correlation between leptin level, sedentary time, and other cardiometabolic risk factors. The relationsip between leptin and sedentary time was also shown in a scatter plot. Multivariate linear regression was performed to determine the association between serum leptin levels and sedentary time after adjusting for age, sex, alcohol consumption, smoking, triglycerides, body mass index (BMI), fasting plasma glucose, systolic blood pressure, uric acid, creatinine, and alanine transaminase (ALT).ResultsIn our study, data from a total of 396 participants were analyzed. The average age of participants was 64.75 (±8.75) years, and ~41.4% were male. A longer period of sedentary time was observed in the high leptin group. A positive correlation was found between serum leptin level and sedentary time in Spearman's correlation, in all BMI groups. Serum leptin levels were positively associated with sedentary time (B = 0.603, p = 0.016) in the multivariate linear regression after adjusting for age, sex, alcohol consumption, smoking, triglycerides, BMI, fasting plasma glucose, systolic blood pressure, uric acid, creatinine, and ALT.ConclusionProlonged sedentary time can be an independent risk factor for high serum leptin levels, and high leptin levels can be a novel marker in future healthcare to screen the individual with prolonged sedentary time. Furthermore, based on our study, future research can further explore the relationship between leptin levels and health promotion, especially decreasing sedentary time in the middle-aged and elder population, which is vulnerable to cardiometabolic diseases.

BackgroundPlasma leptin is considered a risk factor for obesity and cardio-metabolic disease, but the link between serum leptin and renal function is still under evaluation. In our study, we focused on the relationship between serum leptin and renal function, and we investigated the relationship in more detail.MethodsThe 396 middle-aged and elderly Taiwanese adults recruited for our health survey were the subject of our research. All participants agreed to participate and signed a consent form before they joined and completed our study. We divided the participants into three groups according to eGFR tertiles and analyzed the parameters between each group. Then, we used Pearson’s correlation test to investigate the relationship between eGFR levels and cardio-metabolic risk factors with adjustment for age. The scatter plot indicates the trend between serum leptin levels and eGFR levels. Participants were reclassified into three subgroups according to their leptin levels and the bar chart reveals the prevalence of chronic kidney disease (CKD) in each group. Finally, we used multivariate linear regression to evaluate the relationship between serum leptin and eGFR levels with adjustment for age, sex, smoking status, drinking status, body mass index (BMI), uric acid levels, hypertension (HTN), diabetes mellitus (DM), and dyslipidemia.ResultsIn our study, we analyzed the data from 396 eligible participants. A total of 41.4% of the participants were male, and the average age of all participants was 64.81 years ( ± 8.78). The participants in the high eGFR group were more likely to have lower serum leptin levels. Furthermore, eGFR values were negatively correlated with serum leptin levels even after adjustment for age. The prevalence of CKD in the high serum leptin group was higher than that in the low serum leptin group. Serum leptin levels showed significant negative correlations with eGFR levels (β=-0.14, p

Nipa (Nypa fruticans Wurmb.) is an important mangrove palm species, but it is understudied due to lack of information on genetic patterns within its distribution range. In this study, we identified 18 informative microsatellite markers to assess genetic variations among local populations in the Indo-West Pacific (IWP). Results showed population stratification based on high genetic differentiation (FST = 0.22131) with the Mantel test indicating significance to isolation-by-distance. We found a pronounced differentiation between the west populations in Sri Lanka and east populations in Southeast Asia. The east populations around the South China Sea were more genetically similar than those along the Malacca Strait and Java Sea. These genetic clines were shaped by ocean circulations and seasonal monsoon reversals as plausible factors. The Malacca Strait was confirmed as both a genetic and a geographic barrier rather than a corridor according to the Monmonier plot. Simulations of directional migration indicated a statistically strong contemporary genetic connectivity from west to east where Sri Lankan immigrants were detected as far as central Philippines via long-distance dispersal. This is the first report on the recent migration patterns of nipa using microsatellites. Assignment of first-generation (F0) immigrants suggested Mainland Southeast Asia as a melting pot due to the admixture associated with excess of homozygosity. The western populations were recent expansions that emerged in rapid succession based on a phylogram as supported by footprints of genetic drift based on bottleneck tests.

BackgroundHyperhomocysteinemia is an important factor for endothelial cell damage and a risk factor for cardiovascular diseases. Chronic kidney disease (CKD) is recognized as a leading burden in Taiwan’s healthcare system. This study aimed to investigate the association between homocysteine levels and CKD in middle-aged and elderly adults from a community in northern Taiwan.MethodsA total of 396 middle-aged and elderly Taiwanese adults were enrolled and completed the health survey. We divided participants according to tertiles of homocysteine levels as first group (homocysteine level ≤ 11.1 μmol/L), second group (homocysteine level 11.2∼14.3 μmol/L), and third group (homocysteine level > 14.3 μmol/L). CKD was defined as estimated glomerular filtration rate (eGFR) < 60 (mL/min/1.73 m2) or urine albumin to creatinine ratio > 30 (mg/g). Pearson correlation was calculated between eGFR and other related risk factors after adjustment for age. The risk of CKD in the second and third groups compared to that in the first group was assessed by multivariate logistic regression after adjustment for age, sex, smoking, hypertension (HTN), diabetes mellitus (DM), body mass index (BMI), dyslipidemia, and uric acid. The Youden index and receiver operating characteristic (ROC) curve were calculated for the optimized cutoff value.ResultsElevated plasma homocysteine levels were more likely to lower the eGFR and increase the prevalence of CKD. Pearson correlation showed a positive correlation between eGFR and high-density lipoprotein cholesterol, while a negative correlation was observed between homocysteine levels, waist circumference, systolic blood pressure, uric acid levels and BMI (all p < 0.05). In the logistic regression analysis, the prevalence of CKD increased, as well as the homocysteine level. The odds ratio of CKD under 95% confidence interval was 2.655 (1.284–5.490) for the third group compared with the first group after adjusting for age, sex, smoking, DM, HTN, dyslipidemia, uric acid, and BMI (p = 0.008). The area under the ROC curve was 0.662, and a cutoff value of 15.15 μmol/L for the homocysteine level was obtained for detecting subjects with CKD.ConclusionOur study findings revealed that elevated homocysteine levels were significantly associated with CKD and could be used as an indicator of CKD among the middle-aged and elderly populations in Taiwan.

Abstract Background A conformational epitope (CE) is composed of neighboring amino acid residues located on an antigenic protein surface structure. CEs bind their complementary paratopes in B-cell receptors and/or antibodies. An effective and efficient prediction tool for CE analysis is critical for the development of immunology-related applications, such as vaccine design and disease diagnosis. Results We propose a novel method consisting of two sequential modules: matching and prediction. The matching module includes two main approaches. The first approach is a complete sequence search (CSS) that applies BLAST to align the sequence with all known antigen sequences. Fragments with high epitope sequence identities are identified and the predicted residues are annotated on the query structure. The second approach is a spiral vector search (SVS) that adopts a novel surface spiral feature vector for large-scale surface patch detection when queried against a comprehensive epitope database. The prediction module also contains two proposed subsystems. The first system is based on knowledge-based energy and geometrical neighboring residue contents, and the second system adopts combinatorial features, including amino acid contents and physicochemical characteristics, to formulate corresponding geometric spiral vectors and compare them with all spiral vectors from known CEs. An integrated testing dataset was generated for method evaluation, and our two searching methods effectively identified all epitope regions. The prediction results show that our proposed method outperforms previously published systems in terms of sensitivity, specificity, positive predictive value, and accuracy. Conclusions The proposed method significantly improves the performance of traditional epitope prediction. Matching followed by prediction is an efficient and effective approach compared to predicting directly on specific surfaces containing antigenic characteristics.

Abstract Background Our study aimed to determine the association between homocysteine levels and cardiovascular disease (CVD) risk in middle-aged and elderly adults in a community in northern Taiwan. Methods Participants in our study included adults aged 50 to 85 years old during community health examinations in 2019. A total of 396 people were enrolled, the ethnicity of all participants is Chinese. We divided participants according to tertiles of ln[homocysteine] level (low, middle and high groups). The CVD risk was calculated by the Framingham cardiovascular risk score (FRS). An FRS ≥ 20% indicated high CVD risk. Pearson correlation coefficients were calculated between homocysteine level and other cardio-metabolic risk factors while adjusting for age. Multivariate logistic regression analysis was used to determine the association of high and middle ln[homocysteine] groups with high CVD risk after adjusting age, sex, uric acid, creatinine, and body mass index (BMI). The Youden index and receiver operating characteristic (ROC) curves were performed to determine the optimized cut-off value. Results There were 396 people enrolled for analysis; 41.4% of participants were male, and the average age was 64.79 (± 8.76). In our study, we showed a positive correlation of homocysteine with FRS. In the logistic regression models, higher ln[homocysteine] levels was associated with higher CVD risk with a odds ratio (OR) of 2.499 and 95% confidence interval (CI) of 1.214 to 5.142 in the high homocysteine level group compared with the low homocysteine group after adjusting for traditional CVD risk factors. The area under the ROC curve was 0.667, and a ln[homocysteine] cut-off value of 2.495 µmol/L was determined. Conclusions Middle-aged and elderly people with increased homocysteine levels were associated with higher FRSs in this Taiwan community. Furthermore, homocysteine was an independent risk factor for high CVD risk in this study.

Helicobacter pylori (H. pylori) can be eradicated immediately via local application of single-dose medicament on endoscopic examination. In our previous report, “the eradication rate of intraluminal therapy for H. pylori infection (ILTHPI) is 53.7% (51/95) using medicament containing amoxicillin, metronidazole, and clarithromycin”. We aimed to evaluate the efficacy and adverse events of medicament containing tetracycline, metronidazole, and bismuth and to improve the efficacy of stomach acid control before ILTHPI. After usage of dexlansoprazole (60 mg b.i.d.) or vonoprazan (20 mg q.d.) for 3 days before ILTHPI, 103 of 104 (99.1%) symptomatic H. pylori-infected treatment-naïve patients achieved levels of stomach pH ≥ 6. Patients were randomized to receive ILTHPI with medicaments containing tetracycline, metronidazole, and bismuth (Group A, n = 52) or amoxicillin, metronidazole, and clarithromycin (Group B, n = 52). The eradication rate of ILTHPI was similar between Group A (76.5%; 39/51) and Group B (84.6%, 44/52) (p = 0.427) and the adverse event was mild diarrhea (2.9%; 3/104). The eradication rate significantly increased from 53.7% (51/95) to 84.6% (44/52) after acid control (p = 0.0004) for Group B patients. The overall eradication rates of successful ILTHPI plus 7-day non-bismuth (Group A) or 7-day bismuth (Group B) oral quadruple therapy for ILTHPI failure patients were both excellent (96.1% for Group A and 98.1% for Group B).

Background/Objectives: This paper undertakes an investigation into the implications of premature progesterone rise (PPR) on pregnancy outcomes in freeze-all strategy cycles. Methods: A retrospective cohort study encompassing 675 IVF/ICSI cycles using a freeze-all strategy was enrolled. The cycles were categorized into two groups based on serum progesterone levels at the time of hCG administration: 526 cycles had levels below 1.5 ng/mL, while 149 cycles had levels equal to or above 1.5 ng/mL. Results: The findings revealed a significantly higher number of mature follicles and retrieved oocytes in patients with PPR across all AMH categories. Multiple analyses revealed factors influencing PPR, including the duration of induction and the number of retrieved oocytes. Within the same oocyte retrieval number group, patients with PPR demonstrated non-inferior pregnancy outcomes compared to non-PPR patients. Upon adjustment for age, AMH, and total follicle-stimulating hormone (FSH) dosage, PPR maintained a positive correlation with the cumulative live birth rate (LBR). Conclusions: The study showed that PPR correlates with an increase in retrieved oocytes while maintaining similar embryo quality and oocyte retrieval rates and results in a higher cumulative LBR. [ABSTRACT FROM AUTHOR]

(1) Background: Metabolic syndrome has become a serious health problem in society. Homocysteine is a biomarker for cardiovascular disease. We investigated the relationship between homocysteine levels and metabolic syndrome. (2) Methods: A total of 398 middle-aged and elderly individuals were included in our study. First, we divided the participants into two groups: the metabolic syndrome group and the nonmetabolic syndrome group. Second, according to tertiles of homocysteine levels from low to high, the participants were divided into first, second, and third groups. Pearson’s correlation was then calculated for homocysteine levels and metabolic factors. Scatterplots are presented. Finally, the risk of metabolic syndrome in the second and third groups compared with the first group was assessed by multivariate logistic regression. (3) Results: In our study, the metabolic syndrome group had higher homocysteine levels, and the participants in the third group were more likely to have metabolic syndrome. Multivariate logistic regression revealed that the third group, which had the highest homocysteine level, was associated with metabolic syndrome with an odds ratio of 2.32 compared with the first group after adjusting for risk factors. (4) Conclusions: We concluded that high plasma homocysteine levels were independently associated with MetS in our study population.

Background: Traditional medicine (TM) is widely used in South Korea and Taiwan, and both societies have similar systems for the management of TM. This study aimed to compare the TM systems in South Korea and Taiwan. Methods: We searched for studies on the TM systems and collected statistical data from the websites of relevant government agencies in both countries. Interviews were conducted with experts on TM and officials from government agencies. The two TM systems were described and examined in terms of policies, resources, utilization, licensing, and educational systems. Results: Both South Korea and Taiwan have a dual system that separates the administration, licensing and educational systems between TM and Western Medicine (WM), and the TM systems are well established and highly standardized. Comparing with South Korea, however, Taiwan has a more flexible dual medical system in which education courses for producing dual licensure are provided. Additionally, in the system in Taiwan, dual license holders can use both TM and WM methods without limitations and WM doctors can apply acupuncture under some circumstances. Because of the strict dual medical system in South Korea, TM and WM conflict with each other on most health issues. Conclusion: Both South Korea and Taiwan have the advantages of preserving TM, as TM and WM are systemically independent and together provide a more holistic approach. The institutionalization of TM in South Korea and Taiwan may be a good reference for countries considering modernization of their TM.

Yellow water lily (Nuphar shimadai Hayata) is a critically endangered species in Taiwan. Here, we examined genetic structures of four extant populations, WP, GPa, GPb and GPn, using 39 simple sequence repeat (SSR) markers. Positive genetic correlation was observed within 50 m, beyond which no correlation was detected due to isolation by distance according to Mantel correlogram. This suggests a significant genetic structuring of the species. Besides, multilocus genotype (MLG) analysis revealed that GPa was a panmictic population and the species’ putative center of origin. Genetic exchange was observed between GPa and GPb populations, which likely resulted from their geographic proximity. Nevertheless, there was a strong asymmetric migration detected from GPa to WP, but a recent genetic barrier prevented dispersal further northward (WP). Geneland estimated the best number of clusters as K = 2, where WP distinctly separated from the rest of the populations. In STRUCTURE output of K = 3, a third cluster was abundant only in WP. We suggest to consider GPn and WP as separate conservation units, being far from GPa. There is indeed a need to investigate these populations; as predicted, Ne = 1.6 to 3.0 is considered low and that may put the species at risk of extinction.

Abstract Background The Iridoviridae family is categorized into five genera and clustered into two subfamilies: Alphairidovirinae includes Lymphocystivirus, Ranavirus (GIV), and Megalocystivirus (TGIV), which infect vertebrate hosts and Betairidovirinae includes Iridovirus and Chloriridovirus, which infect invertebrate hosts. Clustered Iridoviridae subfamilies possess host-specific characteristics, which can be considered as exclusive features for in-silico prediction of effective epitopes for vaccine development. A voting mechanism-based linear epitope (LE) prediction system was applied to identify and endorse LE candidates with a minimum length requirement for each clustered subfamily Results The experimental results showed that four conserved epitopes among the Iridovirideae family, one exclusive epitope for invertebrate subfamily and two exclusive epitopes for vertebrate family were predicted. These predicted LE candidates were further validated by ELISA assays for evaluating the strength of antigenicity and cross antigenicity. The conserved LEs for Iridoviridae family reflected high antigenicity responses for the two subfamilies, while exclusive LEs reflected high antigenicity responses only for the host-specific subfamily Conclusions Host-specific characteristics are important features and constraints for effective epitope prediction. Our proposed voting mechanism based system provides a novel approach for in silico LE prediction prior to vaccine development, and it is especially powerful for analyzing antigen sequences with exclusive features between two clustered groups.

Background: Nodaviridae infection is one of the leading causes of death in commercial fish. Although many vaccines against this virus family have been developed, their efficacies are relatively low. Nodaviridae are categorized into three subfamilies: alphanodavirus (infects insects), betanodavirus (infects fish), and gammanodavirus (infects prawns). These three subfamilies possess host-specific characteristics that could be used to identify effective linear epitopes (LEs). Methodology: A multi-expert system using five existing LE prediction servers was established to obtain initial LE candidates. Based on the different clustered pathogen groups, both conserved and exclusive LEs among the Nodaviridae family could be identified. The advantages of undocumented cross infection among the different host species for the Nodaviridae family were applied to re-evaluate the impact of LE prediction. The surface structural characteristics of the identified conserved and unique LEs were confirmed through 3D structural analysis, and concepts of surface patches to analyze the spatial characteristics and physicochemical propensities of the predicted segments were proposed. In addition, an intelligent classifier based on the Immune Epitope Database (IEDB) dataset was utilized to review the predicted segments, and enzyme-linked immunosorbent assays (ELISAs) were performed to identify host-specific LEs. Principal findings: We predicted 29 LEs for Nodaviridae. The analysis of the surface patches showed common tendencies regarding shape, curvedness, and PH features for the predicted LEs. Among them, five predicted exclusive LEs for fish species were selected and synthesized, and the corresponding ELISAs for antigenic feature analysis were examined. Conclusion: Five identified LEs possessed antigenicity and host specificity for grouper fish. We demonstrate that the proposed method provides an effective approach for in silico LE prediction prior to vaccine development and is especially powerful for analyzing antigen sequences with exclusive features among clustered antigen groups.

Seasonal Influenza H3N2 virus poses a great threat to public health, but its vaccine efficacy remains suboptimal. One critical step in influenza vaccine production is the viral passage in embryonated eggs. Recently, the strength of egg passage adaptation was found to be rapidly increasing with time driven by convergent evolution at a set of functionally important codons in the hemagglutinin (HA1). In this study, we aim to take advantage of the negative correlation between egg passage adaptation and vaccine effectiveness (VE) and develop a computational tool for selecting the best candidate vaccine virus (CVV) for vaccine production. Using a probabilistic approach known as mutational mapping, we characterized the pattern of sequence evolution driven by egg passage adaptation and developed a new metric known as the adaptive distance (AD) which measures the overall strength of egg passage adaptation. We found that AD is negatively correlated with the influenza H3N2 vaccine effectiveness (VE) and ~75% of the variability in VE can be explained by AD. Based on these findings, we developed a computational package that can Measure the Adaptive Distance and predict vaccine Effectiveness (MADE). MADE provides a powerful tool for the community to calibrate the effect of egg passage adaptation and select more reliable strains with minimum egg-passaged changes as the seasonal A/H3N2 influenza vaccine.

Abstract Background The overlapping symptoms and pathophysiological similarities between burn injury and chronic fatigue syndrome (CFS) are noteworthy. Thus, this study explores the possible association between burn injury and the subsequent risk of CFS. Method We used data from the Taiwan National Health Insurance system to address the research topic. The exposure cohort comprised of 17,204 patients with new diagnoses of burn injury. Each patient was frequency matched according to age, sex, index year, and comorbidities with four participants from the general population who did not have a history of CFS (control cohort). Cox proportional hazards regression analysis was conducted to estimate the relationship between burn injury and the risk of subsequent CFS. Result The incidence of CFS in the exposure and control cohorts was 1.61 and 0.86 per 1000 person-years, respectively. The exposure cohort had a significantly higher overall risk of subsequent CFS than did the control cohort (adjusted hazard ratio [HR] = 1.48, 95% confidence interval [CI] = 1.41–1.56). The risk of CFS in patients with burn injury in whichever stratification (including sex, age, and comorbidity) was also higher than that of the control cohort. Conclusion The findings from this population-based retrospective cohort study suggest that thermal injury is associated with an increased risk of subsequent CFS and provided a point of view suggesting burn injuries in sun- exposed areas such as the face and limbs had greater impact on subsequent development of CFS compared with trunk areas. In addition, extensively burned areas and visible scars were predictors of greater physiological and psychosocial that are needed to follow-up in the long run.

Background Acute kidney injury (AKI) is one of the most severe complications of burn injury. AKI with severe burn injury causes high mortality. This study aims to investigate the incidence of and predisposing factors for AKI in burn patients. Methods This is a single-center, retrospective, descriptive criterion standard study conducted from June 27, 2015, to March 8, 2016. We used Kidney Disease Improving Global Outcomes criteria to define and select patients with AKI. The study was conducted by recruiting in hospital patients who suffered from the flammable cornstarch-based powder explosion and were treated under primary care procedures. A total of 49 patients who suffered from flammable dust explosion-related burn injury were enrolled and admitted on June 27, 2015. The patients with more than 20% total body surface area of burn were transferred to the intensive care unit. Patients received fluid resuscitation in the first 24 hours based on the Parkland formula. The primary measurements were the incidence of and predisposing factors for AKI in these patients. Demographic characteristics, laboratory data, and inpatient outcomes were also evaluated. The incidence of AKI in this cohort was 61.2% (n = 30). The mortality rate was 2.0% (n = 1) during a 59-day follow-up period. The multivariate analysis revealed inhalation injury (adjusted OR = 22.0; 95% CI [1.4–358.2]) and meeting ≥3 American Burn Association (ABA) sepsis criteria (adjusted OR = 13.7; 95% CI [1.7–110.5]) as independent risk factors for early advanced AKI. Conclusions The incidence rate of AKI was higher in this cohort than in previous studies, possibly due to the flammable dust explosion-related burn injury. However, the mortality was lower than that expected. In clinical practice, indicators of inflammation, including ABA sepsis criteria may help in predicting the risk of AKI in patients with burn injury.

BACKGROUND AND AIMS:The aim of this study was to investigate the association between walking speed and cardiovascular disease (CVD) risk among community-dwelling middle-aged and elderly populations in Taiwan. METHODS:This was a cross-sectional and community-based study with 400 participants aged 50 years and over recruited from a community health promotion project in 2014 in Guishan district, Taoyuan city. We excluded 91 people, and a total of 309 participants were eligible for analysis. The statistical methods used in this study were one-way ANOVA and the Chi-square test, Pearson's correlation test and logistic regression model. RESULTS:In total, 309 participants (98 males and 211 females) aged 50 to 74 (62.05 ± 6.21) years without a CVD history were enrolled in this study. The walking speed gradually decreased from the low CVD risk group to the high CVD risk group (p < 0.05). A significant inverse association between walking speed and CVD risk was confirmed with a Pearson's correlation coefficient of-0.143 (p < 0.05) in middle-aged people, but this significant inverse association was not shown in elderly people. The multivariate logistic regression model for predicting CVD risk and walking speed with an adjusted odds ratio (OR) was 0.127 (95% CI = 0.021-0.771) in middle-aged people with adjustment for sex, age, waist circumference (WC), hypertension (HTN), diabetes mellitus (DM), and hyperlipidemia (p < 0.05). CONCLUSION:Our study clearly shows that slow walking speed is associated with an increased risk of CVD in middle-aged people rather than in elderly people.

Background and aimsPurchasing Chinese herbal medicine (CHM) without a physician's prescription may have adverse effects on health. However, the recent status of purchasing non-prescribed CHM and the associated factors are not completely understood. We aimed to report the prevalence of purchasing CHM and associated factors.MethodsUsing data from the 2017 Taiwan Survey of Family Income and Expenditure, we identified 16,528 individuals (householders) aged 18 years and older. Sociodemographic factors, expenditures on medical services and health behaviours were compared between people with and without a history of purchasing non-prescribed CHM by calculating adjusted odds ratios (ORs) and 95% confidence intervals (CIs) in a multiple logistic regression analysis.ResultsThe one-year prevalence of purchasing non-prescribed CHM was 74.8% in Taiwan. In addition to sociodemographics, marital status (OR 2.14, 95% CI 1.88-2.44), the use of traditional Chinese medicine (OR 3.62, 95% CI 3.30-3.97), the purchasing of non-prescribed biochemical medications (OR 3.09, 95% CI 2.75-3.48), the purchasing of health foods (OR 2.59, 95% CI 2.33-2.86), the use of folk therapy (OR 2.27, 95% CI 1.95-2.64), and a high level of expenditure on alcohol (OR 3.79, 95% CI 3.29-4.36) were strongly correlated with purchasing non-prescribed CHM.ConclusionThe one-year prevalence of purchasing non-prescribed CHM is very high in Taiwan and is correlated with sociodemographics, health behaviours, and the utilization of medical care. The interaction of non-prescribed CHM with physician-prescribed herbal medicine and biomedical medications requires more attention.

Objective(s): Diabetes mellitus (DM) is a widespread metabolic disorder worldwide. Clinical physicians have found diabetic patients have mild to middle cognitive dysfunction and an alteration of brain monoaminergic function. This study explored the change in various patterns of behavioral models and brain monoamine function under streptozotocin (STZ)-induced type 1 diabetes.Materials and Methods: We established a type 1 DM model via intravenous injection with STZ (65 mg/kg) in rats. Three weeks after the STZ injection, various behavioral measurements including the inhibitory avoidance test, active avoidance test and Morris water maze were conducted. Finally, all rats were dissected and the concentrations of monoamines and their metabolites in cortex and hippocampus were measured by high performance liquid chromatography with electrochemical detection.Results: We found that STZ induced type 1 diabetes (hyperglycemia and lack of insulin) in rats. STZ-induced diabetic rats had cognitive impairment in acquisition sessions and long-term retention of the active avoidance test. STZ-induced diabetic rats also had cognitive impairment in spatial learning, reference and working memory of the Morris water maze. STZ significantly reduced concentrations of norepinephrine (NE) in the cortex and dopamine (DA) in the hippocampus, but increased concentrations of DA and serotonin (5-HT) in the cortex 35 days after injection. The concentration of 5-HT in the hippocampus was also significantly increased.Conclusion: The data suggested that this cognitive impairment after a short-term period of STZ injection might be related to cortical NE dysfunction, differential alteration of cortical and hippocampal DA function, and brain 5-HT hyperfunction.

Summary: Background: Endoscopic ultrasound guided fine needle aspiration has become a standard procedure in diagnosis of pancreatic neoplasms with a high diagnosis yield. However, the clinical application focusing on the elderly population is scanty. Methods: Consecutive procedures for EUS-FNA diagnosis of pancreatic neoplasms at a tertiary referral center from March 2014 to December 2015 were analyzed retrospectively. The procedures were divided into two groups according to their age, the control group consisted of patients ≤60 years old and the elderly groups consisted of patients >60 years old. The primary outcome is the accuracy of the diagnosis in the two groups. The secondary outcome is the safety during the procedure. Results: A total of 28 EUS-FNA procedures were performed. The mean age of the control group was 48.7 years (n = 14) versus 70.2 years (n = 14) for the elderly cohort. Diagnostic accuracy of the EUS-FNA procedure in detecting malignant (true positive) and benign (true negative) lesions were higher in the control group (nonelderly: 85.7% vs. elderly: 50%; P = 0.046). There were two mild acute pancreatitis associated to the EUS-FNA procedures in the control group. Conclusion: Although EUS-FNA is safe and well tolerated in the elderly patients, our study showed a lower EUS-FNA diagnosis accuracy in this group. Focal fibrotic changes in the pancreas associated with the elderly patients resembled that of chronic pancreatitis microscopically. Keywords: EUS-FNA, pancreatic neoplasms, elderly, endoscopy, diagnosis

Summary: Background: Difficult mask ventilation (DMV) leading to oxygen and ventilation failure can cause complications and fatal consequences in airway management, but has rarely been studied as a primary outcome in the emergency department (ED). This study aimed to determine the incidence and predictors of DMV in the ED. Methods: A specially designed form recording potential risk factors for DMV was designed and subsequently completed by a research nurse and physicians who had performed the procedure for all mask ventilation attempts over a one-year period in the ED of a large hospital in Taipei, Taiwan. Univariate associations between patient characteristics and DMV were measured, and a risk assessment scale was created according to the independent risk factors for DMV ascertained by adjusted regression models. Results: One hundred ten mask ventilation attempts were recorded during the study period. DMV occurred frequently in the ED (45.9% of mask ventilation attempts). Significantly elevated rates of DMV were observed in patients aged 65 years or older those lacking teeth, with sunken cheeks, a double chin or a thick short neck. In adjusted analyses, three easily recognizable predictors, namely lack of teeth, sunken cheeks, and a double chin were found to be independent risk factors for DMV, and accordingly a risk assessment scale- LSD method was made. Conclusion: DMV is a frequent challenge in EDs. An easy-to-use LSD risk scale is created for clinicians to rapidly identify and appropriately manage the risk patients of DMV. Keywords: airway management, emergency physician, endotracheal intubation

MicroRNAs (miRNAs) can regulate the expression of genes involved in the establishment of the window of implantation (WOI) in the endometrium. Recent studies indicated that cell-free miRNAs in uterine fluid and blood samples could act as alternative and non-invasive sample types for endometrial receptivity analysis. In this study, we attempt to systematically evaluate whether the expression levels of cell-free microRNAs in blood samples could be used as non-invasive biomarkers for assessing endometrial receptivity status. We profiled the miRNA expression levels of 111 blood samples using next-generation sequencing to establish a predictive model for the assessment of endometrial receptivity status. This model was validated with an independent dataset (n = 73). The overall accuracy is 95.9%. Specifically, we achieved accuracies of 95.9%, 95.9%, and 100.0% for the pre-receptive group, the receptive group, and the post-respective group, respectively. Additionally, we identified a set of differentially expressed miRNAs between different endometrial receptivity statuses using the following criteria: p-value < 0.05 and fold change greater than 1.5 or less than −1.5. In conclusion, the expression levels of cell-free miRNAs in blood samples can be utilized in a non-invasive manner to distinguish different endometrial receptivity statuses. [ABSTRACT FROM AUTHOR]

The structure and function surrounding the airway change by the age, which may ultimately result in having anatomic features of difficult airways in the elderly. Hence, we reviewed the literature focusing on the age-related anatomic changes and accordingly to compare the characteristics of difficult airways. With age, teeth wear and loss, protein and collagen synthesis reduction, and bone loss and muscle atrophy results in aged face (chin protrusion, cheek retraction and drooping), jaw restriction (temporo-madibular joint disc displacement and osteoarthritis), neck and back stiffness, and kyphotic deformities (degeneration of spinal articular cartilage, intervertebral discs, and spinal osteoporosis). These age-related changes in anatomy are compatible with the predictors of a difficult airway. We hope that these age-related anatomic approaches will prospectively allow a detailed understanding of the hallmarks resulting in geriatric-focused difficult airways in the future studies.