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提升及抑制免疫调节细胞表达之方法
No full text[[abstract]]本发明系提供一种于体外提升免疫调节细胞之表达之方法，系包括以IL‑25处理该免疫调节细胞以增加PD‑L1之表达。本发明亦提供一种藉由前述方法治疗免疫异常之方法。本发明亦提供一种抑制免疫调节细胞表达之方法，系包括抑制PD‑L1之表达。该免疫调节细胞可为人类单核细胞或人类间叶干细胞。本发明亦提供一种藉由前述方法抑制免疫调节细胞表达而治疗免疫逃避相关疾病之方法
[[alternative]]Method to predict risk of offspring with alzheimer's disease
No full text[[abstract]]本發明係關於一種預測阿茲海默症子代罹患風險之方法，所述方法係利用高通量西方墨點微陣列系統分析健康對照組、阿茲海默症患者以及未發病之阿茲海默症子女，其三者群體之血清中蛋白質的表達量，以找出具有差異性之蛋白質，並利用該等具有差異性之蛋白質建立風險預測公式；當所述風險預測公式計算所得之分數越高，其阿茲海默症子代罹患阿茲海默症之風險也越高
Long term outcomes of adjuvant radiation in early-stage breast cancer women with 65 years or older after breast-conserving surgery
No full text[[abstract]]Purpose/Objective(s): The benefit of postoperative radiotherapy for early-stage breast cancer in elderly Asian population remains unclear. This study aimed to investigate the role of adjuvant radiotherapy in early-stage breast cancer considering various clinical factors including age. Materials/Methods: A total of 1202 patients diagnosed with AJCC stage I-IIA breast cancer and tumor less than 3 cm were enrolled from the Taiwan Cancer Registry, between January 2011 and December 2020. We used multivariable Cox proportional-hazards models to control for clinical factors and propensity score matching for sensitivity analysis. The overall survival (OS) and recurrence-free survival (RFS) were estimated with the Kaplan–Meier method and log rank test method. Results: After covariate adjustment, OS and RFS did improve significantly in patients over 70 years old receiving adjuvant hormone therapy and radiotherapy. The 5-year OS rates were 93% and 73% for those with and without adjuvant radiotherapy, respectively (hazard ratio [H = 0.50, 95% CI = 0.32-0.79, p<0.001). For hormone-negative early breast cancer, the benefit of adjuvant radiotherapy to OS for patients with age more than 70 was not observed; while RFS was improved significantly (HR = 0.047, 95% CI = 0.01-0.32, p<0.001). Conclusion: Adjuvant radiotherapy did improve the clinical outcomes of elderly patients with early breast cancer in Asia irrespective of hormone status. The results should be further clarified in larger population
Real-world insights from comprehensive genomic profiling across multiple cancer types
No full text[[abstract]]Background: This retrospective study was conducted to analyze tumor tissue profiling data to assess the potential of applying comprehensive genomic profiling (CGP) in patient care across diverse solid tumors. Methods: Patients with newly diagnosed or recurrent stage IIIB or IV lung adenocarcinoma with the null immunophenotype, esophageal, gastric, pancreatic, or bile duct cancer between January 2020 and July 2023 at two medical centers in Taiwan were included in the National Biobank Consortium of Taiwan project. The tumor samples were subjected to CGP using FoundationOneCDx, with therapeutic implications determined using OncoKB classification. Results: FoundationOneCDx testing of 574 patients was successful in 456 (79.4%) patients. Clinically actionable genomic alterations were detected in 21.1% (96/456) of the patients, including 17.5%, 2.9%, and 0.7% of patients at evidence levels 1, 2, and 3, respectively. Lung adenocarcinoma accounted for the largest proportion of samples with at least one actionable gene alteration (63.2%), followed by bile duct (26.9%), gastric (17.6%), esophageal (4.0%), and pancreatic (3.1%) cancer. Based on the CGP results, 43 patients (9.4%) received matched targeted therapy. The median overall survival of patients who received matched therapy or not was 26.1 months (95% confidence interval (CI), 16.7–35.5 months) and 10.6 months (95% CI, 8.1–13.1 months; hazard ratio, 0.28, 95% CI, 0.14–0.55, p < 0.001), respectively. Conclusions: This study provides comprehensive insights into genomic profiling across diverse cancers in Taiwan, highlighting the crucial role of CGP in identifying actionable genomic alterations and guiding effective therapeutic strategies in real-world practice
Real world clinical outcomes when discontinued denosumab or bisphosphonates in surgically managed patients with osteoporotic vertebral compression fracture: A population-based cohort study
No full text[[abstract]]Objective: The optimal osteoporosis treatment for patients with surgically treated osteoporotic vertebral compression fractures (OVCFs) is less investigated. This study compared the osteoporosis treatment outcomes between denosumab and bisphosphonates concerning subsequent osteoporotic fractures and mortality. Methods: We conducted a retrospective nationwide cohort study using the National Health Insurance Research Database. Patients aged ≥ 50 y, admitted for surgical interventions for OVCF between 2012–2016, and subsequently received denosumab or bisphosphonates for one year were included. Patients were stratified according to their anti-osteoporosis medications and treatment adherence. A multivariable, time-varying Cox proportional hazards model was applied to evaluate the risks of osteoporotic fractures, vertebral fractures, non-vertebral fractures, and death. Results: In this study of 2858 participants, denosumab (1123 patients) and bisphosphonates (1735 patients) were compared. Non-persistent denosumab users, persistent bisphosphonate users, and non-persistent bisphosphonate users had elevated risks of osteoporotic fractures (hazard ratios: 1.82, 1.78, 1.55). Non-vertebral fractures were significantly higher for non-persistent denosumab users, persistent bisphosphonate users, and non-persistent users (hazard ratios: 2.09, 1.86, 1.47). Only non-persistent bisphosphonate users showed an increased risk of vertebral fractures (hazard ratio: 1.72). Notably, non-persistent denosumab users had a significantly higher risk of death compared to persistent users (hazard ratio: 3.12). Conclusion: Among patients with OVCFs requiring hospitalized and surgical intervention, those receiving ongoing denosumab treatment had less risk of developing subsequent osteoporotic fractures than those receiving bisphosphonates or non-persistent denosumab treatment. On the other hand, discontinuation of denosumab was associated with a significantly increased risk for subsequent fractures and death. Thus, adherence to the therapy is crucial for OVCF patients who initiated denosumab
Comprehensive pathogen identification and antimicrobial resistance prediction from positive blood cultures using nanopore sequencing technology
No full text[[abstract]]BackgroundBlood cultures are essential for diagnosing bloodstream infections, but current phenotypic tests for antimicrobial resistance (AMR) provide limited information. Oxford Nanopore Technologies introduces nanopore sequencing with adaptive sampling, capable of real-time host genome depletion, yet its application directly from blood cultures remains unexplored. This study aimed to identify pathogens and predict AMR using nanopore sequencing.MethodsIn this cross-sectional genomic study, 458 positive blood cultures from bloodstream infection patients in central Taiwan were analyzed. Parallel experiments involved routine microbiologic tests and nanopore sequencing with a 15-h run. A bioinformatic pipeline was proposed to analyze the real-time sequencing reads. Subsequently, a comparative analysis was performed to evaluate the performance of species identification and AMR prediction.ResultsThe pipeline identified 76 species, with 88 Escherichia coli, 74 Klebsiella pneumoniae, 43 Staphylococcus aureus, and 9 Candida samples. Novel species were also discovered. Notably, precise species identification was achieved not only for monomicrobial infections but also for polymicrobial infections, which was detected in 23 samples and further confirmed by full-length 16S rRNA amplicon sequencing. Using a modified ResFinder database, AMR predictions showed a categorical agreement rate exceeding 90% (3799/4195) for monomicrobial infections, with minimal very major errors observed for K. pneumoniae (2/186, 1.1%) and S. aureus (1/90, 1.1%).ConclusionsNanopore sequencing with adaptive sampling can directly analyze positive blood cultures, facilitating pathogen detection, AMR prediction, and outbreak investigation. Integrating nanopore sequencing into clinical practices signifies a revolutionary advancement in managing bloodstream infections, offering an effective antimicrobial stewardship strategy, and improving patient outcomes
Tumor-associated microglia secrete extracellular ATP to support glioblastoma progression
No full text[[abstract]]Glioblastoma (GBM) is a highly aggressive brain tumor with poor prognosis and high recurrence rates. The complex immune microenvironment of GBM is highly infiltrated by tumor-associated microglia and macrophages (TAM). TAMs are known to be heterogeneous in their functional and metabolic states and can transmit either protumoral or antitumoral signals to glioma cells. Here, we performed bulk RNA sequencing and single-cell RNA sequencing on samples from patients with GBM, which revealed increased ATP synthase expression and oxidative phosphorylation activity in TAMs located in the tumor core relative to the tumor periphery. Both in vitro and in vivo models displayed similar trends of augmented TAM mitochondrial activity, along with elevated mitochondrial fission, glucose uptake, mitochondrial membrane potential, and extracellular ATP (eATP) production by TAMs in the presence of GBM cells. Tumor-secreted factors, including GM-CSF, induced the increase in TAM eATP production. Elevated eATP in the GBM microenvironment promoted glioma growth and invasion by activating the P2X purinoceptor 7 (P2X7R) on glioma cells. Inhibition of the eATP-P2X7R axis attenuated tumor cell viability in vitro and reduced tumor size and prolonged survival in glioma-bearing mouse models. Overall, this study revealed elevated TAM-derived eATP in GBM and provided the basis for targeting the eATP-P2X7R signaling axis as a therapeutic strategy in GBM.Significance: Glioblastoma-mediated metabolic reprogramming in tumor-associated microglia increases ATP secretion that supports cancer cell proliferation and invasion by activating P2X7R, which can be inhibited to attenuate tumor growth
Sequential regulation of Lck K63-ubiquitination and autophosphorylation by the E3 ligase UBR2 and the phosphatase DUSP22 in TCR signaling
No full text[[abstract]]Dual-specificity phosphatase 22 (DUSP22, also named JKAP) downregulation in peripheral blood T cells is correlated with human SLE nephritis and T-cell leukemia. DUSP22 also dephosphorylates and inactivates Lck in the turn-off stage of TCR signaling, leading to suppression of autoimmune disease. We found that DUSP22 dephosphorylated the E3 ligase UBR2, leading to SCF E3 ubiquitin complex-mediated UBR2 ubiquitination and degradation. Remarkably, UBR2 induced Lck K63-linked ubiquitination, leading to subsequent Lck Tyr394 autophosphorylation and activation upon TCR signaling. Thus, DUSP22 also can inactivate Lck indirectly by inducing UBR2 degradation. Moreover, the proinflammatory cytokine induction and inflammatory responses in DUSP22 KO mice was blocked by knocking out UBR2 in DUSP22/UBR2 double KO mice. The UBR2-Lck interaction and Lck Lys63-linked ubiquitination were indeed induced in T cells of human SLE patients. Taken together, DUSP22 dephosphorylates UBR2 and induces its degradation, leading to inactivation of Lck and suppression of inflammation. Overall, our results reveal a novel activation mechanism of Lck by K63-linked ubiquitination in TCR signaling
The relationship between resilience and mental health status among nurses with workplace violence experiences: A cross-sectional study
No full text[[abstract]]Nurses encounter many stressors and challenges at work, which can negatively affect their mental and physical health. Modern theories of resilience suggest that resilience is a dynamic process of positive adaptation to adversity. This process involves personal growth through adversity, developing effective coping strategies and inculcating the ability to cope with stress. The resilience process involves individual characteristics, social support and environmental factors, including workplace culture. Strengthening nurses' resilience can help them cope with adversity, maintain their mental health and well-being and support their provision of care. The aim of this study was to examine the associations between workplace characteristics, resilience and mental health status among nurses with experiences of workplace violence. The study objectives were to analyse the relationships between workplace characteristics, resilience and mental health status among nurses with experiences of workplace violence and to investigate the effects of resilience on nurses' mental health outcomes. In this cross-sectional study, full-time nurses at a medical centre in Taiwan completed a questionnaire survey. Of 600 distributed questionnaires, 334 nurses were identified to have experienced workplace violence. The questionnaires included items on workplace violence, resilience, metal health status (burnout and mental distress), sleep quality, work characteristics (job control, psychological job demands and workplace justice) and demographic characteristics. Data were analysed through chi-square tests and multivariate logistic regression. Nurses with low resilience tended to be younger, work more rotating/night shifts and perceive lower levels of job control and workplace justice. They also reported higher risks of burnout and mental distress and lower sleep quality. Multivariate logistic regression revealed that psychological job demands, workplace justice and resilience significantly influenced nurses' mental health status. Nurses with high resilience exhibited a lower risk of mental distress and higher sleep quality. However, resilience was not associated with burnout. The findings revealed how workplace factors and resilience influence nurses' mental health. The findings help nurse managers and policymakers develop strategies to promote nurses' resilience and mental health and mitigate the adverse effects of negative workplace events
Genomic surveillance of SARS-CoV-2 in taiwan: A perspective on evolutionary data interpretation and sequencing issues
No full text[[abstract]]This review presents a comprehensive perspective on the genomic surveillance of SARS-CoV-2 in Taiwan, with a focus on next-generation sequencing and phylogenetic interpretation. This article aimed to explore how Taiwan has utilized genomic sequencing technologies and surveillance to monitor and mitigate the spread of COVID-19. We examined databases and sources of genomic sequences and highlighted the role of data science methodologies in the explanation and analyses of evolutionary data. This review addressed the challenges and limitations inherent in genomic surveillance, such as concerns regarding data quality and the necessity for interdisciplinary expertise for accurate data interpretation. Special attention was given to the unique challenges faced by Taiwan, including its high population density and major transit destination for international travelers. We underscored the far-reaching implications of genomic surveillance data for public health policy, particularly in influencing decisions regarding travel restrictions, vaccine administration, and public health decision-making. Studies were examined to demonstrate the effectiveness of using genomic data to implement public health measures. Future research should prioritize the integration of methodologies and technologies in evolutionary data science, particularly focusing on phylodynamic analytics. This integration is crucial to enhance the precision and applicability of genomic data. Overall, we have provided an overview of the significance of genomic surveillance in tracking SARS-CoV-2 variants globally and the pivotal role of data science methodologies in interpreting these data for effective public health interventions