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[[alternative]]Cpg-oligodeoxynucleotide, immunogenic composition including the same, and use of preparing medical for inducing immune response by the same
[[abstract]]本發明提供一種CpG寡脫氧核苷酸(CpG-ODN)。CpG-ODN包含一或多個重複的GTCGTT序列、一或多個重複的GTT序列、以及一或多個重複的TTTT序列,其中至少一重複的GTCGTT序列係編碼於GTT序列及TTTT序列之間。再者,本發明亦包含CpG-ODN的免疫組成物及其在製備治療或預防宿主之疾病的免疫反應之藥物的用途
Cytotoxicity-guided isolation of elatostemanosides I-VI from Elatostema tenuicaudatum W. T. Wang and their cytotoxic activities
[[abstract]]Elatostema tenuicaudatum W. T. Wang, a medicinal plant traditionally utilized in herbal remedies, was explored for its cytotoxic properties. Bioassay-guided fractionation led to the discovery of six novel compounds, designated as elatostemanosides I-VI, with their structures elucidated through advanced spectroscopic methods and DP4+ analysis. Among these, compounds 2, 5, and 6 demonstrated moderate cytotoxicity against the human liver cancer cell line HepG2, exhibiting IC50 values of 18.2 +/- 2.1, 32.1 +/- 0.4, and 57.6 +/- 1.3 mu M, respectively. Notably, compound 6 also displayed significant activity against the human breast cancer cell line HCC1806, with an IC50 value of 35.4 +/- 0.3 mu M. Mechanistic studies revealed these compounds induced apoptosis by modulating the Bax/Bcl-2 ratio. Furthermore, structure-activity relationship (SAR) analysis underscored the importance of specific functional groups in mediating cytotoxic effects
Antibiotic treatment of Stenotrophomonas maltophilia bacteraemia: Does trimethoprim/sulfamethoxazole dose affect clinical outcomes?
[[abstract]]Objectives: The benefit of high-dose trimethoprim/sulfamethoxazole (trimethoprim component >= 8 mg/kg/day) treatment for Stenotrophomonas maltophilia infections remains unclear. We aimed to evaluate the effect of high-dose trimethoprim/sulfamethoxazole treatment on outcomes in patients with S. maltophilia bacteraemia. Patients and methods: We conducted a single-centre retrospective cohort study (2004-23) that included patients treated with trimethoprim/sulfamethoxazole for monomicrobial S. maltophilia bacteraemia. The patients were categorized into two groups based on the trimethoprim/sulfamethoxazole dose: high-dose (trimethoprim component >= 8 mg/kg/day) and low-dose (trimethoprim component < 8 mg/kg/day) groups for comparison. The primary endpoint was 30-day mortality. Adverse drug events between groups were also compared. Multivariable logistic regression and inverse probability of treatment weighting (IPTW) analysis were performed. Results: A total of 143 patients treated with trimethoprim/sulfamethoxazole for S. maltophilia bacteraemia were included: 41 (28.7%) received the high-dose regimen, and 102 (71.3%) received the low-dose regimen. There was no significant difference in 30-day mortality between the high- and low-dose group (39.0% versus 26.5%; P = 0.139). Multivariable regression revealed that high-dose trimethoprim/sulfamethoxazole therapy was not associated with mortality (adjusted OR 1.96, 95% CI 0.75-5.10; P = 0.167) after adjustment. The IPTW-adjusted regression yielded consistent results. More adverse drug events were reported in the high-dose group (31.7% versus 12.7%, P = 0.008). Conclusions: High-dose trimethoprim/sulfamethoxazole for S. maltophilia bacteraemia was not associated with improved outcomes while more frequent adverse drug events were observed. The sample size and retrospective design limit the study's conclusions. Future studies that address these limitations are needed to confirm the results
Anxiety, depression, and their associations with COVID-19-related knowledge, attitudes, and practices among healthcare professionals: A multinational cross-sectional survey
[[abstract]]OBJECTIVE: To investigate the levels of anxiety and depression (A&D) and the association with knowledge, attitudes, and practices among healthcare professionals (HCPs) in Taiwan, Indonesia, and Vietnam. METHODS: A multinational cross-sectional survey was performed to collect data from 3,556 HCPs through online platforms. The Likert scale questionnaire covered sociodemographic factors, work-related information, and COVID-19-related domains, including knowledge, attitudes, practices, working conditions and availability of personal protective equipment, changes in work and life routines due to the COVID-19 pandemic, and experiences of A&D. Multiple logistic regression models were used to evaluate the potential impact of the aforementioned domains on the levels of A&D across and between countries. RESULTS: Distinct A&D profiles emerged among the three countries. Taiwan exhibited higher A&D scores (average 2.31) than Vietnam (1.61) and Indonesia (1.93) (p < 0.001). Taiwan also showed elevated knowledge and attitudes scores. Consistent patterns were observed in responses on practices, working conditions, and pandemic impact on daily routines. Multivariate analysis showed that higher knowledge and attitudes scores were significantly associated with reduced A&D risk in Taiwan. Experiencing the greatest changes in work and daily routines was strongly linked to higher A&D risk, with adjusted odds ratios of 3.64 (95% CI: 1.41-9.45) in Indonesia, 4.13 (95% CI: 2.96-5.75) in Taiwan, and 5.14 (95% CI: 3.18-8.31) in Vietnam. Further analysis revealed that factors such as transportation, work dynamics, family time, dietary habits, and income level, but not leisure time, had varying impacts on A&D across the three countries. CONCLUSION: A&D and COVID-19-related knowledge, attitudes, and practices vary across countries. Thus, personalized support mechanisms and interventions are needed to address the diverse needs of HCPs within specific policy and country contexts
Classification of internet addiction using machine learning on electroencephalography synchronization and functional connectivity
[[abstract]]Background Internet addiction (IA) refers to excessive internet use that causes cognitive impairment or distress. Understanding the neurophysiological mechanisms underpinning IA is crucial for enabling an accurate diagnosis and informing treatment and prevention strategies. Despite the recent increase in studies examining the neurophysiological traits of IA, their findings often vary. To enhance the accuracy of identifying key neurophysiological characteristics of IA, this study used the phase lag index (PLI) and weighted PLI (WPLI) methods, which minimize volume conduction effects, to analyze the resting-state electroencephalography (EEG) functional connectivity. We further evaluated the reliability of the identified features for IA classification using various machine learning methods.Methods Ninety-two participants (42 with IA and 50 healthy controls (HCs)) were included. PLI and WPLI values for each participant were computed, and values exhibiting significant differences between the two groups were selected as features for the subsequent classification task.Results Support vector machine (SVM) achieved an 83% accuracy rate using PLI features and an improved 86% accuracy rate using WPLI features. t-test results showed analogous topographical patterns for both the WPLI and PLI. Numerous connections were identified within the delta and gamma frequency bands that exhibited significant differences between the two groups, with the IA group manifesting an elevated level of phase synchronization.Conclusions Functional connectivity analysis and machine learning algorithms can jointly distinguish participants with IA from HCs based on EEG data. PLI and WPLI have substantial potential as biomarkers for identifying the neurophysiological traits of IA
The alterations of molecular repertoire of the RANKL-induced osteoclastogenesis in the M1 macrophage-derived inflammatory milieu
[[abstract]]Inflammation have been linked to bone diseases such as osteoporosis or bone destruction. However, whether M1 inflammatory stimuli exert a stimulatory or inhibitory effect on the differentiation of osteoclasts remained controversial. Also, how inflammatory milieu influence cell proliferation and survival during osteoclastogenesis have not been determined. Here we reported the molecular repertoire alterations of RANKL-stimulated osteoclastogenesis from RAW264.7 at different stages in the inflammatory environments. Adding conditioned medium collected from LPS-stimulated macrophage, which are the primary source of extracellular inflammatory mediators, resulted in a biphasic change in cell number among differentiating preosteoclasts. The inflammatory milieu induced a transient proliferation of preosteoclasts during the initial 48 h, which was followed by a significant decline in cell numbers from the fourth day onwards. Proliferation-related AKT and ERK were transiently activated in the inflammatory environments, which also upregulated the expressions of c-myc, a major transcription factor for osteoclast differentiation, and pro-inflammatory genes, such as Tnf-a and Nos2. Following prolonged exposure to an inflammatory environment, undifferentiated osteoclast precursors undergo apoptosis. Our findings suggest that short-term inflammatory exposure transiently promotes the proliferation and differentiation of preosteoclasts, whereas long-term exposure leads to apoptosis, potentially due to the enhancement of inflammatory signals
Predictive models for type 2 diabetes mellitus in han Chinese with insights into cross-population applicability and demographic specific risk factors
[[abstract]]BACKGROUND: The rising global incidence of type 2 diabetes mellitus (T2DM) underscores the need for predictive models that enhance early detection and prevention across diverse populations. This study aimed to identify predictors of incident T2DM within a Han Chinese population, assess their impact across various age and sex demographics, and explore their applicability to European populations. METHODS: Using data from about 65,000 participants in the Taiwan Biobank (TWB), we developed a predictive model, achieving an area under the receiver operating characteristic curve of 90.58%. Key predictors were identified through LASSO regression within the TWB cohort and validated using over 4 million records from Taiwan's Adult Preventive Healthcare Services (APHS) program and the UK Biobank (UKB). RESULTS: Our analysis highlighted 13 significant predictors, including established factors like glycosylated hemoglobin (HbA1c) and blood glucose levels, and less conventionally considered variables such as peak expiratory flow. Notable differences in the effects of HbA1c levels and polygenic risk scores between the TWB and UKB cohorts were observed. Additionally, age and sex-specific impacts of these predictors, detailed through APHS data, revealed significant variances; for instance, waist circumference and diagnosed mixed hyperlipidemia showed greater impacts in younger females than in males, while effects remained uniform across male age groups. CONCLUSION: Our findings offer novel insights into the diagnosis and management of diabetes for the Han Chinese and potentially for broader East Asian populations, highlighting the importance of ethnic and demographic diversity in developing predictive models for early detection and personalized intervention strategies
Association between post-stroke cognitive impairment and gut microbiota in patients with ischemic stroke
[[abstract]]More than half of stroke survivors have post-stroke cognitive impairment (PSCI). The role of gut microbiota, which can communicate with the brain through the gut-brain axis and affect inflammation, has been receiving increased attention. This cross-sectional study aimed to investigate the association of PSCI, gut microbiota, and inflammatory markers. Patients with first ischemic stroke and complete 3-month and 1-year follow-up data were included and divided into PSCI and non-PSCI groups according to the Montreal Cognitive Assessment (MoCA) score at the above time points. PSCI was defined as having a MoCA less than 23 at either 3 months or 1 year, or a decrease of more than 2 points at both time points. Gut microbiota was assessed by 16 S rRNA gene sequencing and Next Generation Sequencing analysis. The inflammatory markers included interleukins (ILs), eotaxin, G-CSF, TNF-α, IFNγ, sCD40L, and MCP-1. There were 95 ischemic stroke patients (mean age, 60.5 ± 12.1 years; male, 68.4%), including 30 with PSCI and 65 with non-PSCI. In gut microbiota analysis, the PSCI group had a higher abundance of Bacteroidaceae and Clostridiaceae, and the non-PSCI group had a higher abundance of Prevotellaceae, Ruminococcaceae, Oscillibacter, and Faecalibacterium. Ruminococcaceae family under the Oscillospirales order remains significantly different in the two groups in logistic regression model adjusting confounding variables (p = 0.044). In an analysis of inflammatory markers, the plasma levels of eotaxin (p = 0.041) and IL-12p40 (p = 0.031) were significantly higher in the PSCI group than those in the non-PSCI group, and the plasma level of eotaxin was significantly positively correlated with the amount of Clostridiaceae (rho = 0.389, p = 0.045). The study found that PSCI was associated with certain gut microbiota, and these gut microbiotas correlated with the pro-inflammatory marker eotaxin. This suggests that gut microbiota might play a role in the development of cognitive impairment after ischemic stroke
Synthesis and characterization of at-home dental bleaching gel incorporating Ge/GeO2-x nanoparticles
[[abstract]]Dental bleaching is a widely utilized, noninvasive, and cost-effective approach for treating vital dentition, with hydrogen peroxide predominantly serving as the active bleaching agent. However, such interventions may lead to adverse effects, including enamel demineralization and toxicity to oral tissues, due to the high concentrations of hydrogen peroxide. This study introduces a novel dental bleaching formulation, termed Ge/GeO2-x-CP gel, which incorporates germanium oxide, carbamide peroxide, and carboxymethyl cellulose to mitigate these adverse effects while maintaining therapeutic efficacy. Through the synthesized dual-phase Ge/GeO2-x material, the bleaching gel can effectively generate free electrons under ambient light exposure. These electrons react with the O2 released from carbamide peroxide to produce reactive oxygen species, thereby enhancing the bleaching results. In the evaluation of bleaching efficacy on bovine teeth, the bleaching gel demonstrated effective whitening while minimizing enamel surface degradation, preserving microhardness, and exhibiting low cytotoxicity. The Ge/GeO2-x-CP gel effectively removes extrinsic stains from the dental surface without inducing toxicity or enamel damage and is exclusively activated by ambient light. Consequently, this formulation represents a promising candidate for tooth whitening
Impact of disease type and temporal trends on the proximity of palliative care initiation to death in older adults: A population-based study
[[abstract]]Background Chronic conditions like heart disease and dementia have surpassed cancer as leading causes of death in aging populations. Non-cancer patients, despite similar palliative care needs, often face delayed initiation or limited access. This study investigated the proximity of palliative care initiation to death among older adults with different diagnoses and influencing factors.Methods This cross-sectional study used Taiwan's National Health Insurance and Multiple Causes of Death databases (2010-2020), including individuals aged >= 65 who received specialist palliative care before death. Multinomial logistic regression analysed the association of cancer status and year of death with the proximity of palliative care initiation to death.Results Among 177 403 decedents, 82.41% had cancer and 17.59% non-cancer diagnoses. While median proximity was similar (cancer: 29 days; non-cancer: 28 days), non-cancer decedents had significantly higher adjusted odds ratios (aORs) for late palliative care initiation, particularly <= 3 days (aOR: 1.45, 95% CI: 1.36-1.54) and 4-7 days before death (aOR: 1.34, 95% CI: 1.27-1.41). Over time, the proportion of decedents who initiated palliative care at least 181 days before death increased. Those who died in 2020 were significantly more likely to receive earlier palliative care than those who died in 2010 (aOR: 7.64, 95% CI: 5.78-10.10).Conclusions Despite a trend towards earlier initiation for both groups, non-cancer patients in Taiwan are more likely to have palliative care initiated in the final days of life. Targeted policies are needed to ensure equitable, needs-based palliative care across diagnoses for improved end-of-life outcomes for older adults