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Objective: Previous studies have suggested that body mass index (BMI) should be considered when assessing the relationship between fatty liver (FL) and osteoporosis. The aim of this study was to investigate future fracture events in people with FL, focusing on the effect of BMI in both sexes. Methods: This retrospective cohort study, spanning from 2011 to 2019, enrolled 941 people, including 441 women and 500 men, aged 50 years or older who underwent liver imaging (ultrasound, computed tomography, or magnetic resonance image) and dual-energy X-ray absorptiometry (for bone mineral density measurements). The study examined predictors of osteoporosis in both sexes and the effect of different ranges of BMI (18.5–24, 24–27, and ≥27 kg/m2) on the risk of future fracture events in FL patients. Results: The average follow-up period was 5.3 years for women and 4.2 years for men. Multivariate analysis identified age and BMI as independent risk factors of osteoporosis in both sexes. Each unit increase in BMI decreased the risk of osteoporosis by ≥10%. In both women and men with FL, a BMI of 24–27 kg/m2 offered protection against future fractures, compared to those without FL and with a BMI of 18.5–24 kg/m2. Conclusion: The protective effect of a higher BMI against future fractures in middle-aged and elderly female and male patients with FL is not uniform and diminishes beyond certain BMI ranges.

Background/Objective: Resistance training (RT) and protein supplementation have beneficial effects on the human body. However, it is unknown if RT's health-promoting benefits are enhanced by food-borne protein, such as cheese supplements. This study investigated at how the body composition, lipid profile, muscle strength and intestinal microbiota changed following four weeks of RT combined with cheese supplementation. Methods: Thirty-five male and untrained adults were divided into 4 groups [control group (CON), low-dose group (LG), medium-dose group (MG), and high-dose group (HG)] and underwent a 4-week RT (3 times/week) in combination with cheese supplementation. Participants received 108 g (LG), 216 g (MG), or 324 g (HG) of cheese on the day of RT, and each serving (108 g) of cheese contained 6.7 g of food-borne protein. The RT program was a whole-body program with movements such as chest presses, leg presses, seated rowing, knee extensions and triceps pushdown. The exercise consisted of 3 sets of 8–12 repetitions at 70%RM, with a 120-s break in between. Body parameters (body composition, lipid profile and muscle strength) were assessed at baseline and after the 4 weeks of the intervention. The feces sample was taken every weekend. A two-way (group × time) mixed-design ANOVA was used to examine the body parameters. Independent one-way ANOVA was used to analyze the differences between groups in baseline characteristics and different values of each parameter. Results: HDL-C level was higher in MG than in LG. In comparison to LG, MG had lower levels of total cholesterol, low-density lipoprotein cholesterol, body weight, body mass index, body fat mass and body fat percentage. However, there was no difference in muscle strength between in the four groups. The abundance of Actinobacteria was higher in LG and Erysipelotrichaceae was lower in MG and HG. Conclusion: The findings suggest that cheese could be a readily available food-borne protein supplement to enhance the beneficial effects of RT on health. It may improve body composition and lipid profile by altering the proportion of intestinal microbiota. During the 4-week RT intervention, 13.4 g of foodborne protein in the form of cheese 3 times per week was the ideal dosage.

Objective To compare the neurodevelopmental outcomes of preterm infants before and during the COVID-19 pandemic.Design Premature infants born in 2018 were assigned to the pre-pandemic group, while those born in 2019 were assigned to the during-pandemic group.Setting Nationwide cohort study.Patients Very low birthweight premature infants registered in the Taiwan Premature Infant Follow-up Network database.Interventions Anti-epidemic measures, including quarantine and isolation protocols, social distancing, the closure of public spaces and restrictions on travel and gatherings during COVID-19 pandemic.Main outcome measures Outcomes were measured by Bayley Scales of Infant and Toddler Development Third Edition at corrected ages of 6, 12 and 24 months old. Generalised estimating equation (GEE) was applied to incorporate all measurements into a single model.Results Among the 1939 premature infants who were enrolled, 985 developed before the pandemic, while 954 developed during the pandemic. Premature infants whose development occurred during the pandemic exhibited better cognitive composite at the corrected age of 6 months (beta=2.358; 95% CI, 1.07 to 3.65; p

Abstract Purpose The prevalence of atopic diseases has increased in recent decades. A possible link between antibiotic use during pregnancy and childhood atopic disease has been proposed. The aim of this study is to explore the association of antibiotic exposure during pregnancy with childhood atopic diseases from a nationwide, population-based perspective. Methods This was a nationwide population-based cohort study. Taiwan’s National Health Insurance Research Database was the main source of data. The pairing of mothers and children was achieved by linking the NHIRD with the Taiwan Maternal and Child Health Database. This study enrolled the first-time pregnancies from 2004 to 2010. Infants of multiple delivery, preterm delivery, and death before 5 years old were excluded. All participants were followed up at least for 5 years. Antenatal antibiotics prescribed to mothers during the pregnancy period were reviewed. Children with more than two outpatient visits, or one admission, with a main diagnosis of asthma, allergic rhinitis, or atopic dermatitis were regarded as having an atopic disease. Results A total of 900,584 children were enrolled in this study. The adjusted hazard ratios of antibiotic exposure during pregnancy to childhood atopic diseases were 1.12 for atopic dermatitis, 1.06 for asthma, and 1.08 for allergic rhinitis, all of which reached statistical significance. The trimester effect was not significant. There was a trend showing the higher the number of times a child was prenatally exposed to antibiotics, the higher the hazard ratio was for childhood atopic diseases. Conclusions Prenatal antibiotic exposure might increase the risk of childhood atopic diseases in a dose-dependent manner.

Optical phased arrays (OPAs) serve as pivotal components for non-mechanical beam steering and find relevance in various applications. However, they necessitate correction of optical phase errors within the antenna array, arising from fabrication imperfections in waveguides. We introduce a novel weighted group phase compensation (w-GPC) algorithm to simplify phase compensation and beam steering for OPAs but also enhances sidelobe suppression. A key advantage lies in its reduced hardware requirements, enabling phase compensation with only half or a quarter of the original number of electrodes. Simulation-based verification confirms that beam steering remains achievable even with the reduced number of phase shifts. Consequently, this minimizes the necessary electrodes on the OPA chip and significantly streamlines control circuitry. This feature is especially beneficial for large-scale OPAs comprising hundreds or even thousands of phase shifters. The w-GPC’s phase compensation significantly outpaces traditional Genetic and PSO algorithms in computation speed. Applying the proposed algorithm with half controlled phases to optimize 64- and 1024-element OPAs yields impressive peak-to-sidelobe level (PSLL) enhancements, reaching up to 15 dB and 22 dB, respectively. Remarkably, PSLL remains over 19 dB even when only one sixteen of the phases are utilized to correct phase errors and steer the beam for a 1024-element OPA. These outcomes affirm that exceptional PSLL values can be achieved by great reduction in the number of control electrodes.

Background: The rate of preterm birth is increasing globally. It causes significant short-term and long-term health care burdens. A comprehensive recognition of the risk factors related to preterm births is important in the prevention of preterm birth. Our study is to investigate the incidence and maternal risk factors of preterm birth from a nationwide population-based perspective. Methods: This is a retrospective cohort study. All live births from 2004 to 2014 in Taiwan enrolled. The main data source was Taiwan’s Birth Certificate Application (BCA) database. The BCA database was linked with the National Health Insurance Research Database (NHIRD) to establish any links between information on newborns and maternal underlying disease. Results: A total of 1,385,979 births were included in the analysis. The incidence of preterm birth increased gradually in Taiwan from 8.85% in 2004 to 10.73% in 2014. Maternal age, socioeconomic status, maternal allergy and autoimmune diseases, gynecological diseases, and pregnancy-related complications were significant risk factors for preterm birth. Conclusion: The overall incidence of preterm births has gradually increased in Taiwan. Maternal age, socioeconomic status, certain underlying diseases, and pregnancy-related complications were risk factors for preterm birth.

Autophagy is a vital cellular process responsible for digesting various cytoplasmic organelles. This process plays a crucial role in maintaining cell survival and homeostasis, especially under conditions that cause nutrient deficiency, cellular damage, and oxidative stress. Neuroangiostrongyliasis is an infection caused by the parasitic nematode Angiostrongylus cantonensis and is considered as an emerging disease in many parts of the world. However, effective therapeutic strategies for neuroangiostrongyliasis still need to be further developed. In this study, we investigated the effects of benzaldehyde treatment on autophagy and sonic hedgehog (Shh) signaling in A. cantonensis-infected mice and its mechanisms. First, we found autophagosome generation in the central nervous system after A. cantonensis infection. Next, benzaldehyde combined with albendazole treatment reduced eosinophilic meningitis and upregulated the expression of Shh signaling- and autophagy-related molecules in A. cantonensis-infected mouse brains. In vitro experiments demonstrated that benzaldehyde could induce autophagy via the Shh signaling pathway in A. cantonensis excretory-secretory products (ESPs)-treated mouse astrocytes. Finally, benzaldehyde treatment also decreased lipid droplet accumulation and increased cholesterol production by activating the Shh pathway after ESPs treatment. In conclusion, these findings suggested that benzaldehyde treatment could alleviate brain damage by stimulating autophagy generation through the Shh signaling pathway.

The BOOST (Booster promotion for older outpatients using SMS text reminders) program at Taipei Veterans General Hospital assessed the effectiveness of text message reminders in enhancing COVID-19 booster vaccination rates among the elderly, guided by the Health Belief Model (HBM). Targeting patients aged 65 and above, eligible yet unvaccinated for a COVID-19 booster, this cohort study sent personalized reminders a week prior to their scheduled appointments between April 18, 2022, and May 12, 2022, acting as cues to action to enhance vaccination uptake by overcoming perceived barriers and raising awareness of benefits. Over 5 weeks, the study observed a 38% increase in vaccination rate among 3,500 eligible patients, markedly surpassing the concurrent national rate increase of 4% for the same demographic. The majority of vaccinations occurred within two weeks after the reminder, illustrating the effectiveness of the strategy. Cox regression analysis identified age and time since last vaccination as significant predictors of responsiveness, with those aged 65–74 and 75–84 showing higher uptake, particularly when reminders were sent within 4 months after the last dose. A single reminder proved to be effective. The findings of this study demonstrate the potential of SMS reminders to promote COVID-19 vaccination among the elderly through the strategic use of HBM principles, suggesting a feasible and effective approach to public health communication.

This study investigates the role of self-efficacy in an asynchronous online English course enriched with interactive features. Self-efficacy is a strong predictor of academic achievement in conventional classrooms. However, when learning happens in an online environment, the students’ learning achievement is also affected by their psychological perceptions of online learning. In this study, the relationship between self-efficacy and affective factors (i.e., learner autonomy, learner–content interaction, and perceptions toward transactional distance) was investigated. The aims of this study were to identify the influence of different levels of self-efficacy on these factors and to explore their relationships in an online EFL course. In total, 286 students were administered the questionnaires before and after the curriculum to probe their self-perception of these affective variables. When asynchronous interactive learning materials came into play, learners with different levels of self-efficacy make statistically different learning achievements. The statistically significant differences were also found between the student’s self-efficacy level, their learner autonomy, and their perception toward the interactive contents. However, the difference was not significant between self-efficacy and transactional distance. The cost of asynchronous learning is an increasing transactional distance due to the lack of instructor-learner interaction. This study suggests that interactive content triggered an opposite effect by making the instructor’s role invisible rather than absent. A good online course must balance the student’s self-determined learning and flexibility with the course structure. Interactive learning content can keep the balance between developing learner autonomy and fostering engagement by dissolving the teacher’s role into interactive course material.

We investigate an inverse boundary value problem of determination of a nonlinear law for reaction-diffusion processes, which are modeled by general form semilinear parabolic equations. We do not assume that any solutions to these equations are known a priori, in which case the problem has a well-known gauge symmetry. We determine, under additional assumptions, the semilinear term up to this symmetry in a time-dependent anisotropic case modeled on Riemannian manifolds, and for partial data measurements on ${\mathbb R}^n$ .

Abstract The immune synapse, a highly organized structure formed at the interface between T lymphocytes and antigen-presenting cells (APCs), is essential for T cell activation and the adaptive immune response. It has been shown that this interface shares similarities with the primary cilium, a sensory organelle in eukaryotic cells, although the roles of ciliary proteins on the immune synapse remain elusive. Here, we find that inositol polyphosphate-5-phosphatase E (INPP5E), a cilium-enriched protein responsible for regulating phosphoinositide localization, is enriched at the immune synapse in Jurkat T-cells during superantigen-mediated conjugation or antibody-mediated crosslinking of TCR complexes, and forms a complex with CD3ζ, ZAP-70, and Lck. Silencing INPP5E in Jurkat T-cells impairs the polarized distribution of CD3ζ at the immune synapse and correlates with a failure of PI(4,5)P2 clearance at the center of the synapse. Moreover, INPP5E silencing decreases proximal TCR signaling, including phosphorylation of CD3ζ and ZAP-70, and ultimately attenuates IL-2 secretion. Our results suggest that INPP5E is a new player in phosphoinositide manipulation at the synapse, controlling the TCR signaling cascade.

Abstract The development of acute kidney injury (AKI) and hepatorenal syndrome–acute kidney injury (HRS–AKI) in cirrhosis has been associated with intestinal barrier dysfunction and gut-kidney crosstalk. We use the related markers such as zonulin, lipopolysaccharides (LPS), and lipopolysaccharide-binding protein (LBP) to predict AKI and HRS–AKI in cirrhotic patients and evaluate their in vitro effects on intestinal (Caco-2) cells and renal tubular (HK-2) cells. From 2013 to 2020, we enrolled 70 cirrhotic patients and developed prediction models for AKI and HRS–AKI over a six-month period. There were 13 (18.6%) and 8 (11.4%) cirrhotic patients developed AKI and HRS–AKI. The prediction models incorporated zonulin, LPS, LBP, C-reactive protein, age, and history of hepatitis B for AKI, and zonulin, LPS, LBP, total bilirubin, and Child–Pugh score for HRS–AKI. The area under curve (AUC) for the prediction of AKI and HRS–AKI was 0.94 and 0.95, respectively. Furthermore, the conditioned medium of LPS+hrLBP pre-treated Caco-2 cells induced apoptosis, necrosis, and zonulin release in HK-2 cells, demonstrating the communication between them. This study found that zonulin, LPS, and LBP are potential practical markers for predicting AKI and HRS–AKI in cirrhotic patients, which may serve as potential targets for renal outcomes in cirrhotic patients.

Di-n-butyl phthalate (DBP) is a prevalent phthalate ester widely used as a plasticizer, leading to its widespread presence in various environmental matrices. This study presents an innovative microbial immobilization strategy utilizing biochar, calcium alginate (alginate-Ca, (C12H14CaO12)n), and waterborne polyurethane (WPU) composites to enhance the biodegradation efficiency of DBP. The results revealed that rice husk biochar, pyrolyzed at 300 °C, exhibits relatively safer and more stable physical and chemical properties, making it an effective immobilization matrix. Additionally, the optimal cultural conditions for Bacillus aquimaris in DBP biodegradation were identified as incubation at 30 °C and pH 7, with the supplementation of 0.15 g of yeast extract, 0.0625 g of glucose, and 1 CMC of Triton X-100. Algal biotoxicity results indicated a significant decrease in biotoxicity, as evidenced by an increase in chlorophyll a content in Chlorella vulgaris following DBP removal from the culture medium. Finally, microbial community analysis demonstrated that encapsulating B. aquimaris within alginate-Ca and WPU layers not only enhanced DBP degradation, but also prevented ecological competition from indigenous microorganisms. This novel approach showcases the potential of agricultural waste utilization and microbial immobilization techniques for the remediation of DBP-contaminated environments.

Bladder cancer (BC) is a malignant tumor of the urinary system with high mortality and recurrence rates. Proteasome subunit type 4 (PSMB4) is highly expressed and has been identified as having oncogenic properties in a variety of cancer types. This study aimed to explore the effect of PSMB4 knockdown on the survival, migration, and angiogenesis of human bladder cancer cells with different degrees of malignancy. We analyzed the effects of PSMB4 knockdown in bladder cancer cells and endothelial cells in the tumor microenvironment. PSMB4 was highly expressed in patients with low- and high-grade urothelial carcinoma. Inhibition of PSMB4 reduced protein expression of focal adhesion kinase (FAK) and myosin light chain (MLC), leading to reduced migration. Furthermore, the suppression of PSMB4 decreased the levels of vascular endothelial factor B (VEGF-B), resulting in lower angiogenic abilities in human bladder cancer cells. PSMB4 inhibition affected the migratory ability of HUVECs and reduced VEGFR2 expression, consequently downregulating angiogenesis. In the metastatic animal model, PSMB4 knockdown reduced the relative volumes of lung tumors. Our findings suggest the role of PSMB4 as a potential target for therapeutic strategies against human bladder cancer.

This study compared gut (fecal) microbiota profiles between pre-term and full-term infants, assuming that pre-term infants without feeding intolerance would have gut microbiota similar to those of full-term infants. A total of 13 pre-term infants (gestational age < 37 weeks, birthweight ≤ 2500 g) and 10 full-term infants were included. The pre-term infants were assigned to the feeding tolerance (FT) group (n = 7) if their daily intake exceeded 100 mL/kg/day at two weeks after birth, or the feeding intolerance (FI) group (n = 6). Microbial DNA from weekly fecal samples was analyzed. The microbiota profiles of the pre-term infants and full-term infants were significantly different (p = 0.0001), as well as the FT and FI groups (p = 0.0009). The full-term group had more diversity, with higher concentrations of facultative anaerobes such as Bifidobacteriaceae and Lactobacteriaceae. The FT group’s gut microbiota matured over four weeks, with higher levels of digestion-related bacteria, while the FI group had more pathogens. In the FI group, a significant difference was observed between the first and second weeks, with no significant differences noted between the first week and the third or fourth weeks. The delay in the development of the pre-term infants’ gut microbiota may be associated with the FI.

Abstract Background Increasing evidence suggests that glucagon-like peptide 1 (GLP-1) receptor agonists (RA) can stabilize glycemic variability (GV) and interfere with eating behavior. This study compared the impact of insulin, GLP-1 RA, and dietary components on GV using professional continuous glucose monitoring (CGM). Methods Patients with type 2 diabetes underwent CGM before and after switching from a twice-daily pre-mixed insulin treatment regimen to a GLP-1 RA (liraglutide) plus basal insulin regimen. The dietary components were recorded and analyzed by a certified dietitian. The interactions between the medical regimen, GV indices, and nutrient components were analyzed. Results Sixteen patients with type 2 diabetes were enrolled in this study. No significant differences in the diet components and total calorie intake between the two regimens were found. Under the pre-mixed insulin regimen, for increase in carbohydrate intake ratio, mean amplitude of glucose excursion (MAGE) and standard deviation (SD) increased; in contrast, under the new regimen, for increase in fat intake ratio, MAGE and SD decreased, while when the protein intake ratio increased, the coefficient of variation (CV) decreased. The impact of the food intake ratio on GV indices disappeared under the GLP-1 RA regimen. After switching to the GLP-1 RA regimen, the median MAGE, SD, and CV values decreased significantly. However, the significant difference in GV between the two regimens decreased during the daytime. Conclusion A GLP-1 RA plus basal insulin regimen can stabilize GV better than a regimen of twice-daily pre-mixed insulin, especially in the daytime, and can diminish the effect of food components on GV.

Abstract Background Insomnia and suicidal thoughts are two of the negative impacts that have been caused by the COVID-19 pandemic. Identifying the factors that contribute to these psychological problems may help develop strategies to sustain the mental health of the public. The present study examined the psychosocial impacts caused by the COVID-19 pandemic among different populations in Taiwan, and investigated the relationships between these psychosocial variables, insomnia, and suicidal thoughts. Methods Between September 2020 and May 2021, online questionnaires including psychometrically validated scales were distributed to a convenience sample of outpatients (n = 205), healthcare workers (HCWs) (n = 500), and individuals in the general population (n = 1200) in Taiwan to collect data regarding their insomnia severity, suicidal thoughts, fear of COVID-19, trust of information, and resilience. Multivariate logistic regression methods were used to identify variables associated with suicidal thoughts and insomnia. Results Greater fear of COVID-19 was significantly associated with suicidal thoughts: odds ratios (ORs) with 95% confidence interval (CI) = 1.155 (1.002–1.330) for outpatients; 1.127 (1.035–1.228) for HCWs; and 1.100 (1.130–1.222) for those in the general population. Higher resilience was significantly associated with lower insomnia: OR (95% CI) = 0.819 (0.725–0.926) for outpatients; 0.803 (0.728–0.887), for HCWs; 0.829 (0.785–0.875), and for those in the general population. In addition, there was a statistically significant association between insomnia diagnosis and greater fear of COVID-19 among HCWs (OR [95% CI] = 1.102 [1.062–1.144]) and those in the general population (OR [95% CI] = 1.079 [1.053–1.106]). Among outpatients, there was a statistically significant association between suicidal thoughts and lower trust of information (OR [95% CI] = 0.794 [0.646–0.976]), while among those in the general population there was a statistically significant association between suicidal thoughts and higher insomnia severity (OR [95% CI] = 1.175 [1.13–1.222]). A statistically significant association was also found between insomnia diagnosis and higher suicidal thoughts among those in the general population (OR [95% CI] = 3.455 [2.338–5.106]). Conclusions Trust of information, fear, and resilience were important factors for suppressing suicidal thoughts and insomnia among the three study populations. Health policies that monitor psychological status and build resiliency of the public are recommended to help develop tailored strategies for different populations affected by the COVID-19 pandemic.

Abstract Background Treatment protocols for two-stage revision arthroplasty with diabetes mellitus (DM) have not yet been established. The control of glycated hemoglobin (HbA1c) in two-stage revision arthroplasty is still debated. This study aimed to clarify the importance of preoperative HbA1c levels before each stage of revision arthroplasty and to analyze the risk factors for reinfection. Methods Five hundred eighty-eight patients suffered from first-time PJI and was treated in our institute from January 1994 to December 2010 were reviewed. The mean follow-up time was 13.8 (range, 10.2–24.8) years. Patients underwent two-stage revision arthroplasty with DM at presentation were included. The endpoint of the study was reinfection of the revision arthroplasty. Demographic, survivorship, and surgical variables were also analyzed. Results Eighty-eight patients were identified and grouped by HbA1c level before the first stage surgery: Groups 1 and 2 had HbA1c levels

Abstract Background Thymoma is a type of rare mediastinal tumor whose clinical characteristics and indicators of prognosis are poorly understood. This single‐institution retrospective study aimed to assess the predictive value of tumor, node, metastasis (TNM) staging incorporating tumor size in predicting the risk of thymoma recurrence after resection. Methods Four binary logistic regression models were developed. Models I and II included median tumor size and TNM stage, respectively. Model III included the above two variables. Model IV was model III containing these two variables and their interaction terms. All models were adjusted for WHO histological type, operational time, and adjuvant therapy. Results A total of 276 patients with a median age of 51.0, including 21 patients with thymoma recurrence, were included in this study. Models II or III showed a lower ‐2LogL and higher AUC (0.735 and 0.738 vs. 0.576) with significantly better discrimination than model I, and model III and model II shared similar discrimination. In model III, TNM stage was positively correlated with thymoma recurrence. The recurrence risk of patients with TNM stage IV was significantly higher than those with TNM stage I (OR of 11.03, p = 0.022). No significant correlation between the tumor size and recurrence risk (p = 0.779) and no interaction was found between medium tumor size and TNM stage in model IV. Conclusions This study suggests that the prediction contribution of the TNM stage combined with tumor size is similar to the TNM stage alone for tumor recurrence in patients with thymoma after surgical resection.

Background: Premature births account for around 11% of the world's live births. With the improvements in survival that have been achieved in recent years, the neurological outcomes of these infants have attracted greater attention. The aim of this study was to evaluate the association between postnatal weight loss and neurodevelopment outcomes of very low birth weight premature infants. Methods: This was a prospective cohort study that was conducted in a tertiary referral center. Premature infants of birth weight less than 1500 g born between October 2015 and January 2017 were enrolled. Perinatal-demographic characteristics, medical interventions, and nutrition records were collected. The Bayley III tests performed by licensed child psychiatrists at corrected ages 6, 12, and 24 months old were adopted as outcome measurements. Results: In total, 52 infants were enrolled. The mean birth weight was 1071 g and the mean gestational age was 29.0 weeks. According to the univariate analysis, the duration of postnatal weight loss had a significantly negative impact on motor outcomes at 12 and 24 months old. The negative impact remained robust after adjusting for confounding factors by multiple linear regression models. The effect of repeated measurement was further considered by generalized estimating equation (GEE) models. GEE models also demonstrated a negative association between the duration of body weight loss and motor scores. Conclusion: The duration of postnatal weight loss might have a negative influence on long-term motor development in premature infants. Further studies of nutrition status and motor development are needed to elucidate the precise underlying mechanism.

This research explores the innovative integration of OpenAI's GPT-3.5 within a university-level English as a Foreign Language (EFL) writing course, illustrating a novel approach to academic instruction. The course follows the ADDIE instructional design model, encompassing five systematic stages: analysis, design, development, implementation, and evaluation. This model serves as the backbone of the course structure, ensuring a comprehensive educational experience. The incorporation of the Technological Pedagogical Content Knowledge (TPACK) framework in this course facilitates the effective integration of GPT-3.5 by enabling instructors to align advanced AI capabilities with appropriate pedagogical strategies, thereby enhancing the learning experience. TPACK guides educators in applying GPT-3.5's features in a manner that is contextually relevant and pedagogically sound, ensuring the technology's use complements the course content. The findings from this research are significant. They reveal that GPT-3.5 addresses three fundamental challenges often encountered in academic writing courses. Firstly, it enhances efficiency by providing immediate feedback and generating content ideas, accelerating the writing process. Secondly, GPT-3.5 ensures cohesive organization within students' writing, guiding them to structure their thoughts more logically. Lastly, it serves as a reliable substitute for traditional peer reviewers, offering critical and objective feedback that students can use to refine their drafts. As students engage with AI, they enter a dynamic partnership. This collaboration with GPT-3.5 fosters critical thinking and empowers students to develop a distinctive writing voice. Through this interaction, students are not merely passive recipients of knowledge but active participants in a learning process that is augmented by cutting-edge technology. This study not only provides insight into the potential of AI-augmented academic writing but also highlights GPT-3.5's role in promoting writing proficiency. It demonstrates that the application of AI in education can enhance the learning experience without compromising the individuality of student expression.

Abstract Metabolic syndrome (MetS) is associated with cardiovascular diseases, type 2 diabetes, chronic renal diseases, and all-cause mortality. Furthermore, MetS is associated with poor health-related quality of life (HRQOL). However, the impact of dynamic changes in MetS on changes in the HRQOL was not previously explored. This was an eight-year, prospective cohort study in which 906 middle-aged adults from Shipai, Taipei in northern Taiwan were enrolled during 2009–2010 (baseline). Of those sampled, 427 participants completed the follow-up investigation after 8 years. The HRQOL was measured using the Short Form Health Survey (SF-36). Other variables including age, sex, marital status, level of education, smoking, alcohol consumption, baseline body mass index, and changes in physical activity were adjusted. Compared with adults who never experienced MetS, adults with persistent MetS had a negative change in mental HRQOL (β − 4.20, 95% CI − 7.54 to − 0.86, p = 0.01). The negative changes of persistent MetS on the HRQOL were in the domains of vitality and mental health (β − 4.42, 95% CI − 8.10 to − 0.73 and β − 3.47, 95% CI − 6.90 to − 0.04, respectively). Women and overweight adults were vulnerable to the detrimental effects of persistent MetS. For better HRQOL, more resources should be devoted to reversing MetS in public health.

Summary: Background: In double-blind randomized controlled trials (RCTs) of antidepressants, blinding can be broken due to the apparent side effects, and unsuccessful blinding can lead to overestimation of effect sizes. New generation antidepressants with less severe side effects may be less susceptible to broken blinding. However, successfulness of blinding in new generation antidepressant trials and its influence on trial effect size estimates remain unclear. Methods: Extending a previous systematic review assessing blinding successfulness in psychiatric trials (2000-2010), we searched PubMed/Medline for double-blinded antidepressant RCTs (2010-2020) for trials assessing blinding success. Our primary outcome was the degree of blinding successfulness, measured as kappa statistics between guesses and true allocations. We used random-effects meta-analysis to synthesize studies. We used meta-regression and Pearson's r to examine the relationship between blinding success and effect sizes. This study is registered with PROSPERO (CRD42021249973). Findings: Among 154 eligible studies, 11 (7·1%) contained information on blinding assessment between 2010 and 2020. Five studies were added from the previous review, and altogether nine of the 16 studies provided usable data. Agreement in individual studies ranged from κ=-0·14 to 0·38. The summary agreement between guesses and the truth was 0·21 (95% CI: 0·14 to 0·28) among patients and 0·17 (95% CI: 0·05 to 0·30) among assessors. Blinding success was not associated with effect size (patients: r = 0·37, p = 0·32; assessors: r = 0·28; p = 0·72). Meta-regression also failed to find a significant relationship between blinding success and depression effect sizes (β=0·06, p = 0·09). Interpretation: Less than 10% of the antidepressant RCTs reported blinding assessment. The results in new generation antidepressant trials indicated that patients and assessors were unlikely to be able to judge treatment allocation. There was little evidence that the extent of unblinding biased the effect size estimates of new generation antidepressants. Funding: None.

Antigen-specific lung-resident memory T cells (TRMs) constitute the first line of defense that mediates rapid protection against respiratory pathogens and inspires novel vaccine designs against infectious pandemic threats, yet effective means of inducing TRMs, particularly via non-viral vectors, remain challenging. Here, we demonstrate safe and potent induction of lung-resident TRMs using a biodegradable polymeric nanoshell that co-encapsulates antigenic peptides and TLR9 agonist CpG-oligodeoxynucleotide (CpG-ODN) in a virus-mimicking structure. Through subcutaneous priming and intranasal boosting, the combinatorial nanoshell vaccine elicits prominent lung-resident CD4+ and CD8+ T cells that surprisingly show better durability than live viral infections. In particular, nanoshells containing CpG-ODN and a pair of conserved class I and II major histocompatibility complex-restricted influenza nucleoprotein-derived antigenic peptides are demonstrated to induce near-sterilizing immunity against lethal infections with influenza A viruses of different strains and subtypes in mice, resulting in rapid elimination of replicating viruses. We further examine the pulmonary transport dynamic and optimal composition of the nanoshell vaccine conducive for robust TRM induction as well as the benefit of subcutaneous priming on TRM replenishment. The study presents a practical vaccination strategy for inducing protective TRM-mediated immunity, offering a compelling platform and critical insights in the ongoing quest toward a broadly protective vaccine against universal influenza as well as other respiratory pathogens.

Abstract Exosomes are extracellular vesicles that share components of their parent cells and are attractive in biotechnology and biomedical research as potential disease biomarkers as well as therapeutic agents. Crucial to realizing this potential is the ability to manufacture high‐quality exosomes; however, unlike biologics such as proteins, exosomes lack standardized Good Manufacturing Practices for their processing and characterization. Furthermore, there is a lack of well‐characterized reference exosome materials to aid in selection of methods for exosome isolation, purification, and analysis. This review informs exosome research and technology development by comparing exosome processing and characterization methods and recommending exosome workflows. This review also provides a detailed introduction to exosomes, including their physical and chemical properties, roles in normal biological processes and in disease progression, and summarizes some of the on‐going clinical trials.

Background For people who are overweight or obese, maintaining a metabolically healthy status can decrease the risks of developing cardiovascular diseases and Type 2 diabetes. Despite this, only a limited amount of research has discussed the metabolically healthy overweight and obesity (MHOO) population in Asia and the factors associated with them maintaining their metabolic health. Methods This study enrolled 195 MHOO participants from communities in northern Taiwan during 2009–2010 (baseline). Of the 195 participants, 89 completed the follow-up assessment after a median follow-up time of nine years. Body type was determined by body mass index (BMI, kg/m2). We defined overweight as a BMI ≥ 24 kg/m2 and

Abstract Background The study is aimed to propose an arthroscopic repair technique using a pre-tied suture device for peripheral TFCC (triangular fibrocartilage complex) tear with proximal component involvement. Methods Through a retrospective review in the medical records of patients who underwent unilateral arthroscopic repair for TFCC Palmer IB lesion between 2017 and 2019, 12 patients were arthroscopically diagnosed as proximal component tear and received more than 1 year follow-up postoperatively. The arthroscope was introduced from 6R portal to discriminate Atzei class II from III lesions by a “visualization test” and to supervise the repair procedure using pre-tied FasT-Fix suture device from 3-4 portal. Two poly-ether-ether-ketone (PEEK) blocks were further advanced along the device needle to finally seat outside the ulnar joint capsule, followed by gradually tightening the pre-tied suture loop until the TFCC periphery was securely repositioned and held stably. Results Operation time averaged 87 min. Hook test and DRUJ arthroscopy confirmed proximal component tear in all 12 wrists. Four patients were diagnosed to be Atzei class II lesion as full thickness tear of distal component was arthroscopically identified from 6R portal while the other 8 exhibited partial thickness tear and were categorized as class III lesion. Follow-up averaged 15 months with a range of 12 to 24 months. Mayo modified wrist score improved from an average of 61.3 preoperatively to 90.4 at the latest visit. Conclusions A modified technique for diagnosis and all-arthroscopic repair in TFCC Atzei class II and III lesions using a pre-tied suture device is a feasible and safe option with promising results.

IntroductionImmune thrombocytopenia (ITP) is one of the most common hematologic disorders in children. However, its etiology is still unclear. Epidemiological studies have shown that air pollution is a plausible risk factor in stimulation of oxidative stress, induction of inflammation, and onset of autoimmune diseases. The objective of this article is to examine the effects of prenatal exposure to air pollution on the occurrence of immune thrombocytopenia (ITP) in children.Materials and MethodsThis is a nationwide, population-based, matched case-control study. Using data from Taiwan’s Maternal and Child Health Database (MCHD), we identified 427 children with ITP less than 6 years of age and age-matched controls without ITP between 2004 and 2016. Levels of prenatal exposure to air pollutants were obtained from 71 Environmental Protection Administration monitoring stations across Taiwan according to the maternal residence during pregnancy. Patients who had outpatient visits or admission with diagnosis of ITP and subsequently received first-line treatment of intravenous immunoglobulin or oral glucocorticoids were defined as incidence cases.ResultsPrenatal exposure to particulate matter

PurposeThe novel coronavirus disease 2019 (COVID-19) caused psychological distress and changed human living styles. However, rare studies have examined the psychological distress and protective behaviors across different populations. Therefore, the present study aimed to assess psychological distress, protective behaviors, and potential predictors of psychological distress and protective behaviors across the Hong Kong general population, Taiwan healthcare workers, and Taiwan outpatients.MethodsA cross-sectional design was used to recruit participants from Hong Kong and Taiwan. Telephone interviews were carried out for Hong Kong participants (n = 1,067; 30.2% male participants); online surveys were used for Taiwan healthcare workers (n = 500; 8.0% male participants) and Taiwan outpatients (n = 192; 32.8% male participants). All the participants completed questions on psychological distress and protective behaviors. Multiple linear regressions and multivariable logistic regressions were employed to explore the potential predictors of psychological distress and protective behaviors, respectively.ResultsHong Kong participants had significantly lower levels of psychological distress than Taiwan participants [mean (SD) = 0.16 (0.39) vs. 0.47 (0.59) in healthcare workers and 0.46 (0.65) in outpatients; p < 0.001]. Hong Kong participants (51.7%) and Taiwan outpatients had more people showing fear of COVID-19 (52.0%) than Taiwan healthcare providers (40.8%; p < 0.001). Moreover, Hong Kong participants engaged the most in protective behaviors, followed by Taiwan healthcare providers and Taiwan outpatients (p < 0.001). Moreover, being a female, fear of COVID-19 and worry about personal savings were associated with protective behaviors in general.ConclusionsDespite the greater COVID-19 severity and fear of COVID-19 in Hong Kong, the general population in Hong Kong experienced less psychosocial distress with higher compliance to protective behaviors than the other groups in Taiwan.

Abstract Background Limited reference is available regarding surgical management in symptomatic ulnar styloid fractures with small bony avulsion. The study goal is to report the surgical outcomes using anchor suture fixation with comparison to traditional tension band wire fixation. Methods We retrospectively reviewed the medical records in patients who underwent surgical repair for unilateral ulnar styloid fractures with distal radioulnar instability between 2004 and 2017. A total of 31 patients were enrolled including two kinds of fixation methods. Anchor suture fixation plus distal radioulnar joint pinning was performed in ten patients with tiny avulsion bony fragments (group A); tension band wire fixation was performed in 21 patients with big styloid fracture fragments (group B). Patient characteristics and 2-year treatment outcomes were compared between two groups based on Mayo Modified Wrist Score (MMWS); Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH); visual analog scale (VAS), and surgical complication. Descriptive statistics were used for calculation of key variables; a p value of < 0.05 was considered statistically significant. Results Based on Gaulke classification, there were five subtypes in group A and three subtypes in group B. Incidence of concomitant distal radius fractures was significantly higher in group B; other patient characteristics including age, sex, injury side, and time to surgery showed no significant difference. Outcome assessment regarding MMWS, QuickDASH, and VAS was comparable between two groups. Bone-related complications including nonunion, DRUJ subluxation, and styloid resorption were analyzed; the difference was not significant. Incidence of implant-related complications including migration and secondary removal surgery was significantly higher in group B (p = 0.021). Conclusion Surgical fixation in symptomatic ulnar styloid fractures yields comparable treatment outcomes in both fracture patterns. Implant-related complication with secondary removal surgery is more common in tension band wire group. Anchor suture fixation is a feasible option for tiny styloid avulsion fragments with limited surgical complication.

Background: To improve railway construction and maintenance, a novel digital twin that helps stakeholders visualize, share data, and monitor the progress and the condition during services is required. Building Information Modelling (BIM) is a digitalization tool, which adopts an interoperable concept that benefits the whole life-cycle assessment (LCA) of the project. BIM’s applications create higher performance on cost efficiency and optimal time schedule, helping to reduce any unexpected consumption and waste over the life cycle of the infrastructure. Methods: The digital twin will be developed using BIM embedded by the lifecycle analysis method. A case study based on Taipei Metro (TM) has been conducted to enhance the performance in operation and maintenance. Life cycles of TM will be assessed and complied with ISO14064. Operation and maintenance activities will be determined from official records provided by TM. Material flows, stocks, and potential risks in the LCA are analyzed using BIM quantification embedded by risk data layer obtained from TM. Greenhouse emission, cost consumption and expenditure will be considered for integration into the BIM. Results: BIM demonstrated strong potential to enable a digital twin for managing railway maintenance and resilience. Based on the case study, a key challenge for BIM in Taiwan is the lack of insights, essential data, and construction standards, and thus the practical adoption of BIM for railway maintenance and resilience management is still in the design phase. Conclusions: This study exhibits a practical paradigm of the digital twin for railway maintenance and resilience improvement. It will assist all stakeholders to engage in the design, construction, and maintenance enhancing the reduction in life cycle cost, energy consumption and carbon footprint. New insight based on the Taipei Mass Rapid Transit system is highly valuable for railway industry globally by increasing the lifecycle sustainability and improving resilience of railway systems.

Glioblastoma is believed to be one of the most aggressive brain tumors in the world. ONX-0914 (PR957) is a selective inhibitor of proteasome subunit beta type-8 (PSMB8). Previous studies have shown that inhibiting PSMB8 expression in glioblastoma reduces tumor progression. Therefore, this study aimed to determine whether ONX-0914 has antitumor effects on human glioblastoma. The results indicated that ONX-0914 treatment inhibited survival in LN229, GBM8401, and U87MG glioblastoma cells. Cell cycle analysis showed that ONX-0914 treatment caused cell cycle arrest at the G1 phase and apoptosis in glioblastoma cells. The protein expression of BCL-2 was reduced and PARP was cleaved after ONX-0914 treatment. Furthermore, the levels of p53 and phosphorylated p53 were increased by ONX-0914 treatment in glioblastoma cells. ONX-0914 also induced autophagy in glioblastoma cells. Furthermore, the p53 inhibitor pifithrin attenuated apoptosis but enhanced autophagy caused by ONX-0914. In an orthotopic mouse model, TMZ plus ONX-0914 reduced tumor progression better than the control or TMZ alone. These data suggest that ONX-0914 is a novel therapeutic drug for glioblastoma.

Background: In extremely low birth weight (ELBW) infants, the patent ductus arteriosus (PDA) with left-to-right shunt and an increase in systemic artery resistance may cause increasing preload and afterload of the left ventricle. The immature myocardium in ELBW infants has a limited ability to respond to the change, which leads to hemorrhagic complications. In this study, we detected the hemodynamic change of cardiac performance and applied a clinical strategy to prevent PDA-associated hemorrhagic complications in ELBW infants.Methods: We enrolled ELBW infants at a single medical center in Taiwan. The customized circulatory management was performed by echocardiography after birth until the PDA closed. Inotropic agents were administrated according to the requirements of hemodynamic parameters or clinical conditions. The primary outcomes were hemorrhagic complications including pulmonary hemorrhage and intraventricular hemorrhage (IVH) greater than grade II. The secondary outcomes were the rate of surgical ligation of PDA, mortality, necrotizing enterocolitis, and bronchopulmonary dysplasia.Results: A total of 20 ELBW infants were evaluated by customized circulatory management from 2019 to 2020. We reviewed 35 ELBW infants born between 2017 and 2018 in our hospital, who served as the non-management group. The management group had a significantly lower incidence rate of IVH greater than grade 2 (p = 0.02). Other outcomes showed no significant differences. Dobutamine was prescribed in 8 cases in the management group, and end-systolic wall stress (ESWS) was significantly decreased after Dobutamine administration (p = 0.017).Conclusion: The incidence rate of IVH greater than grade II in ELBW infants decreased after use of customized circulatory management in our study. The strategy of customized circulatory management might be an effective “early target therapy” for hemodynamically significant PDA in high-risk ELBW infants. Inotropic therapy with Dobutamine could be a useful medical choice for improving cardiac function to prevent hemorrhagic complications.

Background: To improve railway construction and maintenance, a novel digital twin that helps stakeholders visualize, share data, and monitor the progress and the condition during services is required. Building Information Modelling (BIM) is a digitalization tool, which adopts an interoperable concept that benefits the whole life-cycle assessment (LCA) of the project. BIM’s applications create higher performance on cost efficiency and optimal time schedule, helping to reduce any unexpected consumption and waste over the life cycle of the infrastructure. Methods: The digital twin will be developed using BIM embedded by the lifecycle analysis method. A case study based on Taipei Metro (TM) has been conducted to enhance the performance in operation and maintenance. Life cycles of TM will be assessed and complied with ISO14064. Operation and maintenance activities will be determined from official records provided by TM. Material flows, stocks, and potential risks in the LCA are analyzed using BIM quantification embedded by risk data layer obtained from TM. Greenhouse emission, cost consumption and expenditure will be considered for integration into the BIM. Results: BIM demonstrated strong potential to enable a digital twin for managing railway maintenance and resilience. Based on the case study, a key challenge for BIM in Taiwan is the lack of insights, essential data, and construction standards, and thus the practical adoption of BIM for railway maintenance and resilience management is still in the design phase. Conclusions: This study exhibits a practical paradigm of the digital twin for railway maintenance and resilience improvement. It will assist all stakeholders to engage in the design, construction, and maintenance enhancing the reduction in life cycle cost, energy consumption and carbon footprint. New insight based on the Taipei Mass Rapid Transit system is highly valuable for railway industry globally by increasing the lifecycle sustainability and improving resilience of railway systems.

The adverse effect of COVID-19 pandemic among individuals has been very disturbing especially among healthcare workers. This study aims to examine the prevalence of post-traumatic stress disorder (PTSD) symptoms, sleep problems, and psychological distress among COVID-19 frontline healthcare workers in Taiwan. Hence, a total of 500 frontline healthcare workers were recruited to participate in this cross-sectional study. They responded to measures on fear of COVID-19, depression, anxiety, stress, insomnia, PTSD, perceived stigma, and self-stigma. The results indicated a prevalence rate of 15.4% for PTSD symptoms, 44.6% for insomnia, 25.6% for depressive symptoms, 30.6% for anxiety symptoms, and 23.4% for stress among the participants. There were significantly positive interrelationships between all these variables. Anxiety symptoms and fear of COVID-19 predicted PTSD whereas symptoms of anxiety, fear of COVID-19, and stress predicted insomnia. The prevalence rates of the psychological problems reveal a worrying view of mental health challenges among Taiwanese frontline healthcare workers. Anxiety symptoms and fear of COVID-19 are the common predictive factors of PTSD and sleep problems suggesting that mental healthcare services for them may help prevent future occurrence of psychological problems by allaying fears of healthcare workers. Therefore, there should be mental healthcare services for healthcare workers during the COVID-19 pandemic.

Our previous clinical trial showed that a novel concentrated herbal extract formula, YH1 (Rhizoma coptidis and Shen-Ling-Bai-Zhu-San), improved blood glucose and lipid control. This pilot observational study investigated whether YH1 affects microbiota, plasma, and fecal bile acid (BA) compositions in ten untreated male patients with type 2 diabetes (T2D), hyperlipidemia, and a body mass index ≥ 23 kg/m2. Stool and plasma samples were collected for microbiome, BA, and biochemical analyses before and after 4 weeks of YH1 therapy. As previous studies found, the glycated albumin, 2-h postprandial glucose, triglycerides, total cholesterol, and low-density lipoprotein cholesterol levels were significantly improved after YH1 treatment. Gut microbiota revealed an increased abundance of the short-chain fatty acid-producing bacteria Anaerostipes and Escherichia/Shigella. Furthermore, YH1 inhibited specific phylotypes of bile salt hydrolase-expressing bacteria, including Parabacteroides, Bifidobacterium, and Bacteroides caccae. Stool tauro-conjugated BA levels increased after YH1 treatment. Plasma total BAs and 7α-hydroxy-4-cholesten-3-one (C4), a BA synthesis indicator, were elevated. The reduced deconjugation of BAs and increased plasma conjugated BAs, especially tauro-conjugated BAs, led to a decreased glyco- to tauro-conjugated BA ratio and reduced unconjugated secondary BAs. These results suggest that YH1 ameliorates T2D and hyperlipidemia by modulating microbiota constituents that alter fecal and plasma BA compositions and promote liver cholesterol-to-BA conversion and glucose homeostasis.

Background: Esophageal squamous cell carcinoma (ESCC) is associated with poor survival despite surgical resection, and its pathogenesis has been broadly investigated in the past decade. Early growth response 1 (EGR-1) could involve regulating tumor development in ESCC cells. Methods: An attempt was made to examine the molecular and cellular influence of EGR-1 in esophageal cancer cells by RNA extraction, real-time PCR (qRT-PCR), cell culture, small interfering RNA (siRNA) knockdown, western blot, migration assay, and cell viability assay. One hundred and forty-four samples of ESCC were collected from our hospital and analyzed. Significantly higher EGR-1 expression was noted in tumor-adjacent normal tissue compared with tumor lesions. Results: The univariate analysis showed no significant impacts of EGR-1 expression on patients’ survival. However, after adjusting for the pathological stage, patients with EGR-1 expression > 68th percentile had lower risks of cancer-related death. Moreover, knockdown of EGR-1 significantly enhanced cell migration, invasion, and resistance to chemotherapeutic agents in two ESCC cell lines. Conclusions: EGR-1 plays a key role in tumor suppression involving tumor viability suppression and reflects the treatment effect of current chemotherapy for ESCC.

Purpose: The purpose of this study is to evaluate the outcome and prognosis of complete synovectomy performed under arthroscopic surgery in the treatment of diffuse pigmented villonodular synovitis (DPVNS) of the knee. Methods: We retrospectively reviewed 7 cases (6 female and 1 male) diagnosed with diffuse pigmented villonodular synovitis (DPVNS) of knee from 2013 to 2017. All of these cases were treated with knee arthroscopy-assisted complete synovectomy. The follow-up period ranged from 36 months to 60 months (average: 48.0 months). The pain score, range of motion and functional outcome of the knee joint were evaluated after surgery. Symptoms and signs were monitored and magnetic resonance imaging (MRI) were routinely requested to note for possible recurrence during clinical follow up. Results: During and after the surgeries of complete synovectomy under arthroscope by the same surgeon, no complications were noted in the ward or the clinic. Significant improvements were achieved in terms of the range of motion and Lysholm knee function score. There was no recurrence of DPVNS observed in our patients during a follow-up of 4 years. Conclusions: Intra-articular DPVNS of the knee can successfully be treated by complete synovectomy under arthroscope. This case series emphasized the technique of multiple portals and cycling different shavers to achieve satisfactory outcomes.

The effect of diet-induced obesity on intestinal B cell populations is not well understood despite emerging evidence of a critical role for the intestinal immune system in contributing to insulin resistance. Here, the authors show important functions of IgA in regulating metabolic disease and for intestinal immunity in modulating systemic glucose metabolism.

Abstract Background Diabetic nephropathy (DN) is a common complication of diabetes mellitus (DM) that imposes an enormous burden on the healthcare system. Although some studies show that traditional Chinese medicine (TCM) treatments confer a protective effect on DN, the long-term impact remains unclear. This study aims to examine end-stage renal disease (ESRD) and mortality rates among TCM users with DN. Methods A total of 125,490 patients with incident DN patients from 2004 to 2006 were identified from the National Health Insurance Research Database in Taiwan and followed until 2012. The landmark method was applied to avoid immortal time bias, and propensity score matching was used to select 1:1 baseline characteristics-matched cohort. The Kaplan–Meier method and competing-risk analysis were used to assess mortality and ESRD rates separately. Results Among all eligible subjects, about 60% of patients were classified as TCM users (65,812 TCM users and 41,482 nonusers). After 1:1 matching, the outcomes of 68,882 patients were analyzed. For the ESRD rate, the 8-year cumulative incidence was 14.5% for TCM users [95% confidence interval (CI): 13.9–15.0] and 16.6% for nonusers (95% CI: 16.0–17.2). For the mortality rate, the 8-year cumulative incidence was 33.8% for TCM users (95% CI: 33.1–34.6) and 49.2% for nonusers (95% CI: 48.5–49.9). After adjusting for confounding covariates, the cause-specific hazard ratio of ESRD was 0.81 (95% CI: 0.78–0.84), and the hazard ratio of mortality for TCM users was 0.48 (95% CI: 0.47–0.50). The cumulative incidence of mortality increased rapidly among TCM users with ESRD (56.8, 95% CI: 54.6–59.1) when compared with TCM users without ESRD (30.1, 95% CI: 29.4–30.9). In addition, TCM users who used TCM longer or initiated TCM treatments after being diagnosed with DN were associated with a lower risk of mortality. These results were consistent across sensitivity tests with different definitions of TCM users and inverse probability weighting of subjects. Conclusions The lower ESRD and mortality rates among patients with incident DN correlates with the use of TCM treatments. Further studies about specific TCM modalities or medications for DN are still needed.

Background: Chronic kidney disease (CKD) has become a worldwide burden due to the high co-morbidity and mortality. Diabetic nephropathy (DN) is one of the leading causes of CKD, and pre-dialysis is one of the most critical stages before the end-stage renal disease (ESRD). Although Chinese herbal medicine (CHM) use is not uncommon, the feasibility of using CHM among pre-dialysis DN patients remains unclear.Materials and methods: We analyzed a population-based cohort, retrieved from Taiwan’s National Health Insurance Research Database, to study the long-term outcome of using CHM among incident pre-dialysis DN patients from January 1, 2004, to December 31, 2007. All patients were followed up to 5 years or the occurrence of mortality. The risks of all-cause mortality and ESRD were carried out using Kaplan-Meier and competing risk estimation, respectively. Further, we demonstrated the CHM prescriptions and core CHMs using the Chinese herbal medicine network (CMN) analysis.Results: A total of 6,648 incident pre-dialysis DN patients were analyzed, including 877 CHM users and 5,771 CHM nonusers. With overlap weighing for balancing all accessible covariates between CHM users and nonusers, we found the use of CHM was associated with lower all-cause mortality (0.22 versus 0.56; log-rank test: p-value

ObjectivesTo examine the association between metabolic syndrome (MetS) and successful aging among community-dwelling older adults.MethodsAdults aged ≥ 65 years who participated in the senior health checkup program at National Taiwan University Hospital during 2011-2013 were recruited (N = 467 at baseline). The participants were followed after 4 years and 6 years. MetS was assessed at baseline. Successful aging was evaluated at baseline, 4-year follow-up, and 6-year follow-up. We adopted an extended definition of successful aging, which was defined as three major domains: physiological, psychological, and sociological and economic domains. Generalized linear mixed models were used to assess the association between MetS and successful aging adjusting for time (follow-up years), age, sex, years of education, alcohol consumption and MetS×time interaction term.ResultsThe mean age of the study population was 72.9 (SD 5.5) years. The absence of baseline MetS had a positive effect on the probability of successful aging over six years. The absences of abdominal obesity, hyperglycemia, reduced high-density lipoprotein cholesterol, and hypertension were associated with the physiological successful aging. The absence of hypertension was the most significant predictor of physiological successful aging [aOR (95% CI) = 2.76 (1.67-4.58), pConclusionsWe found that MetS is a risk factor of successful aging among community-dwelling older adults. Public health policy should aim at avoidance of MetS in order to facilitate successful aging in older population.

BackgroundBreast milk is the optimal choice for feeding premature babies. However, the prevalence rate of extrauterine growth restriction in preterm infants remains high.ObjectivesThe purpose of this study was to analyze the macronutrients present in human milk and the correlation with the growth of in-hospital preterm infants.MethodsThis prospective study is based on data from 99 in-hospital preterm infants younger than 37 weeks of gestational age on an exclusively human milk diet. Infants who had previously received parenteral nutrition were eligible, but they had to have reached full enteral feeding at the time that the samples were taken. A total of 3282 samples of raw human milk or donor pasteurized milk were collected. The levels of lactose, protein, fat, and energy in the samples were measured using a Miris human milk analyzer. The primary outcome was weight growth velocity (g/kg/day) which was obtained using two-point approach.ResultsThe mean (±standard deviation) macronutrient composition per 100 mL of milk was 7.2 (±0.3) g of lactose, 1.1 (±0.2) g of true protein, 3.5 (±0.9) g of fat, and 66.9 (±6.5) kcal of energy. The protein concentration in human milk had a positive, significant correlation with body weight gain, with a coefficient of 0.41 (p < 0.001). After adjusting for gestational age, postmenstrual age, small-for-gestational age, intraventricular hemorrhage, patent ductus arteriosus or congestive heart failure, duration of total parenteral nutrition support, bottle feeding or use of orogastric tube, and ventilator support, total daily protein intake was associated with body weight growth (p < 0.001).ConclusionBoth the protein concentration in human milk and the daily total protein intake had a positive correlation with the body weight gain of premature infants. Routine analysis of breast milk and individualized fortification might be indicated to optimize the growth of preterm infants.

Purpose. Interleukin-1α (IL-1α) is a potent cytokine that plays a role in inflammatory arthritis and bone loss. Decoy receptor 3 (DCR3) is an immune modulator of monocytes and macrophages. The aim of this study was to investigate the mechanism of DCR3 in IL-1α-induced osteoclastogenesis. Methods. We treated murine macrophages with DCR3 during receptor activator of nuclear factor kappa Β ligand- (RANKL-) plus IL-1α-induced osteoclastogenesis to monitor osteoclast formation by tartrate-resistant acid phosphatase (TRAP) staining. Osteoclast activity was assessed using a pit formation assay. The mechanisms of inhibition were studied by biochemical analyses, including RT-PCR, immunofluorescent staining, flow cytometry, an apoptosis assay, immunoblotting, and ELISA. Results. DCR3 suppresses IL-1α-induced osteoclastogenesis in both primary murine bone marrow-derived macrophages (BMM) and RAW264.7 cells as it inhibits bone resorption. DCR3 induces RANKL-treated osteoclast precursor cells to express IL-1α, secretory IL-1ra (sIL-1ra), intracellular IL-1ra (icIL-1ra), reactive oxygen species (ROS), and Fas ligand and to activate IL-1α-induced interleukin-1 receptor-associated kinase 4 (IRAK4). The suppression of DCR3 during RANKL- or IL-1α-induced osteoclastogenesis may be due to the abundant secretion of IL-1ra, accumulation of ROS, and expression of Fas ligand in apoptotic osteoclast precursor cells. Conclusions. We concluded that there is an inhibitory effect of DCR3 on osteoclastogenesis via ROS accumulation and ROS-induced Fas ligand, IL-1α, and IL-1ra expression. Our results suggested that the upregulation of DCR3 in preosteoclasts might be a therapeutic target in inflammatory IL-1α-induced bone resorption.

Objective: The objective of this study was to investigate the effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors on renal function in different stages of chronic kidney disease (CKD).Design and Methods: We conducted a retrospective cohort study using longitudinal claims data from May 2016–December 2017 from the Chang Gung Research Database. Patients who used one of the three types of SGLT2 inhibitor available at Chang Gung Memorial Hospital, namely empagliflozin 10 mg/tab (Empa10), empagliflozin 25 mg/tab (Empa25), and dapagliflozin 10 mg/tab (Dapa), were included, with the same number of matched non-users. Analysis of variance was used for continuous variables and the chi-square test was applied for categorical variables. Differences in data between two groups were analyzed using an independent t-test, and the basic data before and after treatment were analyzed using generalized estimating equation (GEE). The association among renal function changes was analyzed using a Cox proportional hazards model, with the results presented as unadjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs).Results: Among the 7,624 SGLT2 inhibitor users, 1,696 patients used Empa10, 2,654 used Empa25, and 3,274 used Dapa. Compared with non-users, dapagliflozin had the lowest risk of estimated glomerular filtration rate (eGFR) decrease over 40% from baseline within 1 year (HR 0.36, 95% CI 0.25–0.51). By using the ICD-10-CM code N179, the acute kidney injury (AKI)-related hospitalization rate was lower in Empa10 and Dapa users than in non-users (HR 0.65, 95% CI 0.49–0.86).Conclusion: Lower risk of eGFR decrease over 40% and AKI-related hospitalization was found in all SGLT2 inhibitor users across the different CKD stages.

The association between metabolically healthy obesity (MHO) and health-related quality of life (HRQOL) has not been thoroughly evaluated. This study enrolled 906 adult participants aged 35–55 years between 2009 and 2010 in Northern Taiwan; 427 participants were followed up after eight years. Normal weight, overweight, and obesity were evaluated via body mass index. Metabolic health was defined as the absence of cardiometabolic diseases and having ≤1 metabolic risk factor. HRQOL was evaluated using the 36-Item Short Form Health Survey (SF-36), Taiwan version. Generalized linear mixed-effects models were used to analyze the repeated, measured data with adjustment for important covariates. Compared with metabolically healthy normal weight individuals, participants with metabolically unhealthy normal weight and obesity had a significantly poorer physical component summary score (β (95% CI) = −2.17 (−3.38–−0.97) and −2.29 (−3.70–−0.87), respectively). There were no significant differences in physical and mental component summary scores among participants with metabolically healthy normal weight, overweight, and obesity. This study showed that metabolically healthy individuals with obesity and normal weight had similar HRQOL in physical and mental component summary scores. Maintaining metabolic health is an ongoing goal for people with obesity.

Multi-DOF motion is realized in the eyes and joints of robots mostly through the combination of multiple one-degree-of-freedom (1-DOF) motors. However, this results in reduced efficiency, a large volume, reduced response speed, and inaccurate positioning. To solve these problems, this study proposes a novel 3-DOF spherical voice coil motor (VCM). In this VCM, 16 coils and a radially oriented ring magnet are used to generate a Lorentz force to achieve motion. In particular, coils for Z-axis rotation are sandwiched between the coils for X- and Y-axis rotation. Furthermore, the proposed VCM can achieve 360° rotation about the Z-axis. The commercial software ANSYS was used to design and verify the performance of the proposed VCM. Simulation results indicate that this VCM affords improved power efficiency because only a suitable combination of coils, rather than all coils, needs to be powered on. The results demonstrate the feasibility of the proposed 3-DOF spherical VCM.

In keeping with consumers’ preferences for electromagnetic motors of ever smaller power consumption, it is necessary to improve the power efficiency of the electromagnetic motors used in unmanned aerial vehicles and robots without sacrificing their performance. Three-degree-of-freedom (3-DOF) spherical motors have been developed for these applications. Accordingly, this study modifies the 3-DOF spherical motor proposed by Hirata’s group in a previous study (Heya, A.; Hirata, K.; Niguchi, N., Dynamic modeling and control of three-degree-of-freedom electromagnetic actuator for image stabilization, IEEE Transactions on Magnetics 2018, 54, 8207905.) to accomplish a 3-DOF spherical motor for camera module with higher torque output in the large rotation angle. The main contribution of this study is to improve the static torque in the X- and Y-axes with an improved electromagnetic structure and a particular controlling strategy. In the structural design, eight symmetrical coils with specific coil combination are used instead of conventional four symmetrical coils. In this study, the development of the proposed 3-DOF spherical motor was constructed and verified by using a 3D finite-element method (3D FEM). The simulation results show that the proposed 3-DOF spherical motor has higher torque output in the large rotation angle when compared to the original 3-DOF spherical motor.

One of the main goals of the English as a Foreign Language (EFL) course is to facilitate the development of learners' reading comprehension and reflective skills in English, which can be developed with appropriate instruction. However, in EFL courses, many students are inactive in reflecting on their reading and are disengaged from learning. To fill this gap, a reflective reading-based e-learning approach was proposed to explore the impact of the suggested approach on reading comprehension, reflective thinking, and behavioral engagement. The study aimed to improve the comprehension of the student's reading using the proposed reflective e-learning approach. The study employed a quasi-experimental design in which the experimental group used reflective reading-based e-learning (n = 51) and the control group used conventional e-learning (n = 50) for a total of 13 weeks of participation. The experiment was designed to examine reading comprehension, reflective thinking, and behavioral engagement (e.g., reading time, Marker list, Quiz score, Memo list). The results revealed that the reflective reading-based e-learning approach could improve the comprehension and reflective thinking of the learners and promote behavioral engagement. These findings can be valuable for educators designing strategies to improve students' reading comprehension skills and stimulate behavioral engagement in e-learning systems.