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Background: Alzheimer's disease (AD) is complicated by multiple environmental and polygenetic factors. The accuracy of artificial neural networks (ANNs) incorporating the common factors for identifying AD has not been evaluated. Methods: A total of 184 probable AD patients and 3773 healthy individuals aged 65 and over were enrolled. AD-related genes (51 SNPs) and 8 environmental factors were selected as features for multilayer ANN modeling. Random Forest (RF) and Support Vector Machine with RBF kernel (SVM) were also employed for comparison. Model results were verified using traditional statistics. Results: The ANN achieved high accuracy (0.98), sensitivity (0.95), and specificity (0.96) in the intrinsic test for AD classification. Excluding age and genetic data still yielded favorable results (accuracy: 0.97, sensitivity: 0.94, specificity: 0.96). The assigned weights to ANN features highlighted the importance of mental evaluation, years of education, and specific genetic variations (CASS4 rs7274581, PICALM rs3851179, and TOMM40 rs2075650) for AD classification. Receiver operating characteristic analysis revealed AUC values of 0.99 (intrinsic test), 0.60 (TWB-GWA), and 0.72 (CG-WGS), with slightly lower AUC values (0.96, 0.80, 0.52) when excluding age in ANN. The performance of the ANN model in AD classification was comparable to RF, SVM (linear kernel), and SVM (RBF kernel). Conclusion: The ANN model demonstrated good sensitivity, specificity, and accuracy in AD classification. The top-weighted SNPs for AD prediction were CASS4 rs7274581, PICALM rs3851179, and TOMM40 rs2075650. The ANN model performed similarly to RF and SVM, indicating its capability to handle the complexity of AD as a disease entity.

BackgroundA causal connection between oxidative stress and inflammation in diabetes, along with its associated renal and cardiovascular complications, has been established. Sixteen prescribed potentially renoprotective Chinese herbal medicines for diabetic kidney disease (PRCHMDKD), which are scientific Chinese medicine (botanical drug) and categorized into five classes (clearing heat, nourishing yin, dampness dispelling, tonifying qi, and harmonizing formulas), exhibit shared antioxidative properties and target multiple oxidative stress pathways. However, the time-response, cumulative effects, and safety (hyperkalemia risk) of these sixteen PRCHMDKD on cardiorenal and survival outcomes in patients with overall and advanced DKD remain unresolved.MethodsThis retrospective cohort study analyzed national health insurance claims data in 2000–2017. Four statistical methods, including Cox proportional hazards models, complementary restricted mean survival time (RMST), propensity score matching, and competing risk analysis for end-stage renal disease (ESRD), were employed to investigate this relationship. The study included 43,480 PRCHMDKD users and an equal number of matched nonusers within the overall DKD patient population. For advanced DKD patients, the cohort comprised 1,422 PRCHMDKD users and an equivalent number of matched nonusers.ResultsPRCHMDKD use in overall and advanced, respectively, DKD patients was associated with time-dependent reductions in adjusted hazard ratios for ESRD (0.66; 95% CI, 0.61–0.70 vs. 0.81; 0.65–0.99), all-cause mortality (0.48; 0.47–0.49 vs. 0.59; 0.50–0.70), and cardiovascular mortality (0.50; 0.48–0.53 vs. 0.61; 0.45–0.82). Significant differences in RMST were observed in overall and advanced, respectively, DKD patients, favoring PRCHMDKD use: 0.31 years (95% CI, 0.24–0.38) vs. 0.61 years (0.13–1.10) for ESRD, 2.71 years (2.60–2.82) vs. 1.50 years (1.03–1.98) for all-cause mortality, and 1.18 years (1.09–1.28) vs. 0.59 years (0.22–0.95) for cardiovascular mortality. Additionally, hyperkalemia risk did not increase. These findings remained consistent despite multiple sensitivity analyses. Notably, the cumulative effects of utilizing at least four or five classes and multiple botanical drugs from the sixteen PRCHMDKD provided enhanced renoprotection for patients with both overall and advanced DKD. This suggests that there is involvement of multiple targets within the oxidative stress pathways associated with DKD.ConclusionThis real-world study suggests that using these sixteen PRCHMDKD provides time-dependent cardiorenal and survival benefits while ensuring safety for DKD patients.

Objective: The aim of this study was to investigate the correlation between hormone receptor levels and telomere length (TL) in infertile women with and without polycystic ovary syndrome (PCOS). Materials and methods: This prospective cohort study recruited a total of 431 cumulus oocyte complex (COC) from 88 infertile women between July 2012 and June 2014. The participants were divided into three groups: young age (

This work aims to build a reservoir computing system to recognize signals with the help of brainwaves as the input signals. The brainwave signals were acquired as the participants were listening to the signals. The human brain in this study can be regarded as the assistant neural networks or non-linear activation function to improve the signal recognition. We showed that within the brainwave frequency ranges from 14 to 16, 20, 30, and 32 Hz, the mean squared errors of the input signal recognition were lower than those without brainwaves. This result has demonstrated that the reservoir computing system with the help of human responses can obtain more precise results.

Background: Systemic lupus erythematosus (SLE) significantly links to LN, a type of CKD with high mortality despite modern Western treatments. About 70% of SLE patients develop LN, and 30% advance to end-stage renal disease (ESRD). Concerns about glucocorticoid side effects and LN worsening due to oxidative stress prompt alternative treatment searches. In Taiwan, over 85% of SLE patients opt for complementary methods, especially Chinese herbal medicine (CHM). We pinpointed seventeen CHMs for SLE (PRCHMSLE) with antioxidative and anti-inflammatory properties from national health insurance data (2000–2017). Our primary aim was to assess their impact on renal and survival outcomes in SLE patients progressing to CKD (SLE-CKD), with a secondary focus on the risks of hospitalization and hyperkalemia.Methods: We established a propensity-matched cohort of 1,188 patients with SLE-CKD, comprising 594 PRCHMSLE users and 594 nonusers. We employed Cox proportional hazards models and restricted mean survival time (RMST) analyses to assess the renal and survival outcomes of PRCHMSLE users. Moreover, we performed pooling and network analyses, specifically focusing on the renal effects linked to PRCHMSLE.Results: PRCHMSLE use was associated with decreased adjusted hazard ratios for ESRD (0.45; 95% confidence interval, 0.25–0.79, p = 0.006), all-cause mortality (0.56; 0.43–0.75, p < 0.0001), non-cardiovascular mortality (0.56; 0.42–0.75, p < 0.0001), and hospitalization (0.72; 0.52–0.96, p = 0.009). Hyperkalemia risk did not increase. Significant differences in RMST were observed: 0.57 years (95% confidence interval, 0.19–0.95, p = 0.004) for ESRD, 1.22 years (0.63–1.82, p < 0.0001) for all-cause mortality, and 1.21 years (0.62–1.80, p < 0.0001) for non-cardiovascular mortality, favoring PRCHMSLE use. Notably renoprotective PRCHMSLE included Gan-Lu-Ying, Anemarrhena asphodeloides Bunge [Asparagaceae; Rhizoma Anemarrhenae] (Zhi-Mu), Rehmannia glutinosa (Gaertn.) DC. [Orobanchaceae; Radix Rehmanniae] (Sheng-Di-Huang), Jia-Wei-Xiao-Yao-San, and Paeonia suffruticosa Andr. [Paeoniaceae; Cortex Moutan] (Mu-Dan-Pi). Network analysis highlighted primary treatment strategies with central components like Liu-Wei-Di-Huang-Wan, Paeonia suffruticosa Andr. [Paeoniaceae; Cortex Moutan] (Mu-Dan-Pi), Anemarrhena asphodeloides Bunge [Asparagaceae; Rhizoma Anemarrhenae] (Zhi-Mu), Rehmannia glutinosa (Gaertn.) DC. [Orobanchaceae; Radix Rehmanniae] (Sheng-Di-Huang), and Zhi-Bai-Di-Huang-Wan.Conclusion: This work underscores the pronounced renal and survival benefits associated with the seventeen PRCHMSLE in the treatment of SLE-CKD, concurrently mitigating the risks of hospitalization and hyperkalemia. This highlights their potential as alternative treatment options for individuals with this condition.

Abstract Electrical impulses from cardiac pacemaker cardiomyocytes initiate cardiac contraction and blood pumping and maintain life. Abnormal electrical impulses bring patients with low heart rates to cardiac arrest. The current therapy is to implant electronic devices to generate backup electricity. However, complications inherent to electronic devices remain unbearable suffering. Therefore, cardiac biological pacing has been developed as a hardware-free alternative. The approaches to generating biological pacing have evolved recently using cell reprogramming technology to generate pacemaker cardiomyocytes in-vivo or in-vitro. Different from conventional methods by electrical re-engineering, reprogramming-based biological pacing recapitulates various phenotypes of de novo pacemaker cardiomyocytes and is more physiological, efficient, and easy for clinical implementation. This article reviews the present state of the art in reprogramming-based biological pacing. We begin with the rationale for this new approach and review its advances in creating a biological pacemaker to treat bradyarrhythmia.

Histoplasmosis is a global infection caused by the thermally dimorphic fungus, Histoplasma capsulatum complex. It is endemic in the United States, as well as in Central and South America. In Taiwan, histoplasmosis is rare, with the first reported case not occurring until 1977. We summarized a total of 17 cases reported in Taiwan over the past 40 years and provided detailed descriptions for four probable indigenous cases. Due to the lack of rapid diagnostic tools and clinical suspicion, histoplasmosis may be underdiagnosed in Taiwan. We recognize that a limitation of our review is the lack of data on the environmental surveillance for H. capsulatum complex in Taiwan. Conducting a further phylogenetic analysis on both environmental and clinical isolates would provide valuable evidence for the region.

Objectives: To evaluate the effect of intrauterine infusion and hysteroscopic injection of autologous platelet-rich plasma (PRP) in patients with a persistent thin endometrium (EM) undergoing euploid frozen embryo transfer (EFET) cycles. Methods: This prospective case–control study enrolled 116 infertile women with thin EM (Results: After receiving intrauterine infusion and hysteroscopic injection of PRP, 78.2% and 55.3% of patients, respectively, showed an EM thickness exceeding 7 mm, followed by embryo transfer. The hysteroscopic injection group demonstrated significantly higher IR (52%), a higher trend of CPR (52%), and a higher live birth rate (38%) than the control group (18%, 22%, and 4%). Conclusions: Intrauterine infusion and hysteroscopic injection of autologous PRP may be effective methods to increase EM thickness in HRT cycles. According to our results, both methods could increase EM thickness, while hysteroscopic injection appeared to provide more significant assistance in increasing IR, CPR, and live birth rate after EFET in patients with persistent thin EM.

BackgroundSugar-sweetened beverages (SSBs) are the main cause of excessive sugar intake and increased health risks. Food companies usually use social media to market SSBs in order to increase consumers’ purchase intentions. To reduce excessive added sugar consumption from hand-shaken tea drinks, Taiwan has implemented a mandatory policy requiring clear sugar content labeling. This study aimed to investigate the sugar label information and online marketing strategies for hand-shaken tea drinks in northern Taiwan.MethodsIn this cross-sectional study, content analysis was employed to investigate the sugar labeling information and the current situation of online marketing in hand-shaken tea drink brands based in northern Taiwan. Seventy-two hand-shaken tea drink brands’ stores were visited to record their sugar labeling presentation methods, with brands lacking labeling, presenting incomplete labeling, or not offering customized sugar levels being excluded, resulting in 60 brands being chosen for the subsequent data collection process. The sugar and energy contents in 1,581 hand-shaken tea drinks were recorded and calculated. Subsequently, the sugar contents were assessed in accordance with World Health Organization (WHO) sugar recommendations (25 g/day), warning label criteria, and Taiwan’s regulations for low-sugar packaged beverages. Seven brands that had high online impressions were further selected and their marketing strategies in 560 Facebook posts were analyzed.ResultsThe presentation methods of labeling varied among the 60 brands, and only 42 brands had obvious and easily accessible labeling. The most common labeling presentation method was posters (n = 28). After converting the sugar content of half-sugar and low-sugar hand-shaken tea drinks, it was found that 60.2% of half-sugar beverages and 13.0% of low-sugar beverages exceeded 25 g of sugar per cup. Over 90% of brands had Facebook and Instagram accounts. The top marketing strategies for tea drink brands on Facebook were specific beverage information, brand information, and nutrition and health marketing. Most posts promoted sugar-sweetened beverages.ConclusionNot all hand-shaken tea drink brands in this study followed Taiwan’s labeling regulations. Moreover, high sugar contents in hand-shaken tea drinks labeled as half-sugar and low-sugar could potentially lead people to unconsciously consume excessive amounts of sugar. Future research should explore the impact of online marketing strategies on SSBs consumption behavior and ways to mitigate it among the Taiwanese public.

Abstract Background Coronary artery calcification (CAC) burden assessed by Agatston score (AS) is currently recommended to stratify patients at risk for future acute coronary syndrome (ACS). Besides the CAC burden, the biostructure of CAC may also play a vital role in the vulnerability of CAC, which CT radiomics could reveal. Propensity-score matching of the traditional risk factors and CAC burden between the ACS and asymptomatic groups could radically remove biases and allow the exploration of characteristic features of CAC in ACS. Methods We retrospectively identified 77 patients with ACS who had a CAC scan before percutaneous coronary intervention between 2016 and 2019. These 77 patients were one-to-two propensity-score matched for traditional risk factors of ACS and AS ranks to select 154 subjects from 2890 asymptomatic subjects. A validation cohort of 30 subjects was also enrolled. Radiomics features of each plaque were extracted and averaged in each person. Conditional logistic regression and area-under-curve analysis were used for statistical analysis. Results A higher number of coronary segments involved, lower mean, median, first quartile, and standard deviation of attenuation, and increased kurtosis of attenuation of CAC were associated with the ACS group compared to the control group (p

Abstract In modern technology, recent advances in multi-functional devices are rapidly developed for the diverse demands of human beings. Meanwhile, durability and adaptability to extreme environmental conditions are also required. In this study, a flexible magnetoelectric (ME) heterostructure based on CoFe2O4/Pb(Zr,Ti)O3 composite thin film on muscovite is presented, with two geometries of the constituents, namely laminar heterostructure, and vertical nanostructure, adopted for the comparison. On the other hand, credited to the mechanical flexibility of muscovite, the impact of flexibility on ME properties is also discussed with a series of bending tests. Moreover, the ME response sustains for 10,000 times bending without significant decrease, validating the mechanical durability of this heterostructure on muscovite. With these advantages, a flexible proximity sensor based on this heterostructure is demonstrated for motion detection. It is expected to offer a pathway for creating the next-generational flexible devices, showing potential for future practical application.

Self-assembled nanocomposites present opportunities for a range of phase morphologies and desirable properties. Here authors present tuneable self-assembled nanostructures in the SnO2:NiO system; the double-percolated system expands the design of self-assembled oxides for practical applications, e.g. in optoelectronics.

Background Individuals who self-harm have increased suicide rates. Brief interventions are associated with reduced repeated suicide attempts. However, very few previous studies investigated the acceptability of brief interventions before implementing new trials. Aims We aimed to explore the perceptions of individuals who self-harm toward a brief intervention, the Chinese version of the volitional help sheet (VHS-C), which encourages people to link a critical situation with an appropriate response. Method Fourteen participants who presented to hospitals with self-harm were interviewed about their perspectives regarding the acceptability of the paper- and web-based VHS-C. Data were analysed with the framework method. Results The participants could understand the intended goal of the VHS-C by reading the written instructions, but indicated that having verbal instructions would also help. They shared the reasons why they felt the VHS-C was helpful (e.g. relatable contents, useful coping strategies and appropriate instructions that made them feel understood) or unhelpful (e.g., being not specific enough, not useful during the crisis and triggering negative emotional responses). Some indicated that the VHS-C might not be applicable to people experiencing ongoing distress in emergency departments. Most participants preferred the web-based to the paper-based VHS-C, and suggested that the format and frequency of follow-up reminders could leave the patient to decide. Conclusions The contents of the VHS-C were acceptable for people who presented to hospitals with self-harm. The VHS-C may be more helpful before individuals encounter suicidal thoughts than when they have an ongoing crisis.

Abstract Background Lignocellulosic resources are promising feedstocks for the manufacture of bio-based products and bioenergy. However, the inherent recalcitrance of biomass to conversion into simple sugars currently hinders the deployment of advanced bioproducts at large scale. Lignin is a primary contributor to biomass recalcitrance as it protects cell wall polysaccharides from degradation and can inhibit hydrolytic enzymes via non-productive adsorption. Several engineering strategies have been designed to reduce lignin or modify its monomeric composition. For example, expression of bacterial 3-dehydroshikimate dehydratase (QsuB) in poplar trees resulted in a reduction in lignin due to redirection of metabolic flux toward 3,4-dihydroxybenzoate at the expense of lignin. This reduction was accompanied with remarkable changes in the pools of aromatic compounds that accumulate in the biomass. Results The impact of these modifications on downstream biomass deconstruction and conversion into advanced bioproducts was evaluated in the current study. Using ionic liquid pretreatment followed by enzymatic saccharification, biomass from engineered trees released more glucose and xylose compared to wild-type control trees under optimum conditions. Fermentation of the resulting hydrolysates using Rhodosporidium toruloides strains engineered to produce α-bisabolene, epi-isozizaene, and fatty alcohols showed no negative impact on cell growth and yielded higher titers of bioproducts (as much as + 58%) in the case of QsuB transgenics trees. Conclusion Our data show that low-recalcitrant poplar biomass obtained with the QsuB technology has the potential to improve the production of advanced bioproducts.

Abstract Background Clarithromycin-based therapy is important for Helicobacter pylori eradication treatment. However, clarithromycin may increase cardiovascular risk. Hence, we investigated the association between clarithromycin use and outcomes in adults with stable coronary heart disease (CHD) and subsequent peptic ulcer disease (PUD). Methods This nationwide cohort study used a national health insurance database to screen 298,417 Taiwanese residents who were diagnosed with coronary heart disease from 2001 to 2015 for eligibility in the study and to evaluate select eligible patients with CHD–PUD from 2004 to 2015. Data were obtained from new users of clarithromycin (n = 4183) and nonusers of clarithromycin (n = 24,752) during follow-up. A total of 4070 eligible clarithromycin users and 4070 nonusers were subject to final analysis by 1:1 propensity score matching. Participants were followed up after receiving clarithromycin or at the corresponding date until the occurrence of cardiovascular morbidity in the presence of competing mortality, overall mortality and cardiovascular mortality, or through the end of 2015. The incidence rates and risks of overall mortality and cardiovascular outcomes were evaluated. The associations between clarithromycin and arrhythmia risk, as well as its dose and duration and overall mortality and cardiovascular outcomes were also addressed. Results Clarithromycin users were associated with adjusted hazard ratios of 1.08 (95% confidence interval, 0.93–1.24; 21.5 compared with 21.2 per 1000 patient-years) for overall mortality, 0.95 (0.57–1.59; 1.5 compared with 1.8 per 1000 patient-years) for cardiovascular mortality, and 0.94 (0.89–1.09; 19.6 compared with 20.2 per 1000 patient-years) for cardiovascular morbidity in the presence of competing mortality, as compared with nonusers. We found no relationship between dose and duration of clarithromycin and overall mortality and cardiovascular outcomes and no increased risk of arrhythmia during follow-up period. After inclusion of arrhythmia events to re-estimate the risks of all study outcomes, the results remained insignificant. Conclusion Concerning overall mortality, cardiovascular mortality, and cardiovascular morbidity, our results suggest clarithromycin-based therapy for Helicobacter pylori eradication may be safe in patients with stable CHD and subsequent PUD.

Abstract Background Interprofessional collaborative practice is essential for meeting patients’ needs and improving their health outcomes; thus, the effectiveness of interprofessional education (IPE) should be clearly identified. There is insufficient evidence in the literature to determine the outcomes of IPE compared to traditional single-profession education (SPE). This study aimed to compare the outcomes of IPE and SPE during a simulation training course. Methods The study design was a mixed-methods, incorporated cross-over design and a qualitative survey. A total of 54 students including 18 medical students and 36 nursing students were recruited from March to April 2019. The 4-week simulation course was designed based on Kolb’s experimental learning theory and Bandura’s social learning theory. Participants were evenly divided into group 1 (received IPE-learning followed by SPE-learning), and group 2 (received SPE-learning followed by IPE-learning). Students’ medical task performance, team behavior performance, teamwork attitude, and patient safety attitude were collected at pretest, mid-test, and posttest. Descriptive statistics and repeated measures analysis of variance were used. End-of-study qualitative feedback was collected, and content analysis was performed. Results Both groups demonstrated moderate-to-large within-group improvements for multiple learning outcomes at mid-test. Group 1 students’ medical task performance (F = 97.25; P

Introduction: RNA sequencing (RNA-seq) data from space biology experiments promise to yield invaluable insights into the effects of spaceflight on terrestrial biology. However, sample numbers from each study are low due to limited crew availability, hardware, and space. To increase statistical power, spaceflight RNA-seq datasets from different missions are often aggregated together. However, this can introduce technical variation or “batch effects”, often due to differences in sample handling, sample processing, and sequencing platforms. Several computational methods have been developed to correct for technical batch effects, thereby reducing their impact on true biological signals.Methods: In this study, we combined 7 mouse liver RNA-seq datasets from NASA GeneLab (part of the NASA Open Science Data Repository) to evaluate several common batch effect correction methods (ComBat and ComBat-seq from the sva R package, and Median Polish, Empirical Bayes, and ANOVA from the MBatch R package). Principal component analysis (PCA) was used to identify library preparation method and mission as the primary sources of batch effect among the technical variables in the combined dataset. We next quantitatively evaluated the ability of each of the indicated methods to correct for each identified technical batch variable using the following criteria: BatchQC, PCA, dispersion separability criterion, log fold change correlation, and differential gene expression analysis. Each batch variable/correction method combination was then assessed using a custom scoring approach to identify the optimal correction method for the combined dataset, by geometrically probing the space of all allowable scoring functions to yield an aggregate volume-based scoring measure.Results and Discussion: Using the method described for the combined dataset in this study, the library preparation variable/ComBat correction method pair out ranked the other candidate pairs, suggesting that this combined dataset should be corrected for library preparation using the ComBat correction method prior to downstream analysis. We describe the GeneLab multi-study analysis and visualization portal which will allow users to access the publicly available space biology ‘omics data, select multiple studies to combine for analysis, and examine the presence or absence of batch effects using multiple metrics. If the user chooses to perform batch effect correction, the scoring approach described here can be implemented to identify the optimal correction method to use for their specific combined dataset prior to analysis.

Switchgrass (Panicum virgatum L.) is a promising perennial bioenergy crop that achieves high yields with relatively low nutrient and energy inputs. Modification of cell wall composition for reduced recalcitrance can lower the costs of deconstructing biomass to fermentable sugars and other intermediates. We have engineered overexpression of OsAT10, encoding a rice BAHD acyltransferase and QsuB, encoding dehydroshikimate dehydratase from Corynebacterium glutamicum, to enhance saccharification efficiency in switchgrass. These engineering strategies demonstrated low lignin content, low ferulic acid esters, and increased saccharification yield during greenhouse studies in switchgrass and other plant species. In this work, transgenic switchgrass plants overexpressing either OsAT10 or QsuB were tested in the field in Davis, California, USA for three growing seasons. No significant differences in the content of lignin and cell wall-bound p-coumaric acid or ferulic acid were detected in transgenic OsAT10 lines compared with the untransformed Alamo control variety. However, the transgenic overexpressing QsuB lines had increased biomass yield and slightly increased biomass saccharification properties compared to the control plants. This work demonstrates good performance of engineered plants in the field, and also shows that the cell wall changes in the greenhouse were not replicated in the field, emphasizing the need to validate engineered plants under relevant field conditions.

Background: Based on their anti-oxidative and anti-fibrotic properties, Angelica sinensis (Oliv.) Diels roots [Apiaceae; Radix Angelicae sinensis] (Danggui [abbreviated as S in the context]), Astragalus membranaceus (Fisch.) Bunge [Fabaceae; Astragalus membranaceus] (Huangqi [A]), Rheum palmatum L. [Polygonaceae; Rheum palmatum] (Dahuang [R]), and Salvia miltiorrhiza Bunge [Lamiaceae; Salvia miltiorrhiza Bunge radix et rhizoma] (Danshen [D]) are potential renoprotective Chinese herbal medicines (CHMs). Renoprotection using ARD alone for the treatment of chronic kidney disease (CKD) has been documented in pre-clinical, clinical, and meta-analysis research; however, only pre-clinical data are available for the use of S alone. Moreover, with an increasing number of CKD patients taking prescribed CHMs, hyperkalemia risk remains unclear.Methods: This study retrospectively analyzed national health insurance claims data in 2001–2017. Propensity score matching was used to analyze renal and survival outcomes and the dose-response effects of S without ARD use in 18,348 new S users, 9,174 new ARD users, and 36,696 non-users. Cox proportional hazard regression was used to investigate adjusted hazard ratios (aHRs) for end-stage renal disease (ESRD) in the presence of competing mortality and death. The additive effect of the S herb in single form to compounds was also analyzed. Additionally, to analyze hyperkalemia risk, an exact match on each covariate was used to include 42,265 new CHM users and non-users, while Poisson regression was used to estimate adjusted incidence rate ratios (aIRRs) of hyperkalemia of prescribed CHMs.Results: S users and ARD users were associated with aHRs of 0.77 (95% confidence interval; 0.69–0.86) and 1.04 (0.91–1.19), respectively, for ESRD and 0.55 (0.53–0.57) and 0.71 (0.67–0.75), respectively, for death. The renal and survival benefits of S use were consistent in several sensitivity analyses. The dose- and time-dependent renoprotection and dose-dependent survival benefits were observed for S use. The top two additive renoprotective collocations of the S herb in compounds were Xue-Fu-Zhu-Yu-Tang and Shen-Tong-Zhu-Yu-Tang, followed by Shu-Jing-Huo-Xue-Tang and Shen-Tong-Zhu-Yu-Tang. Moreover, CHM users were associated with aIRRs of 0.34 (0.31–0.37) for hyperkalemia.Conclusion: This study suggests dose- and time-dependent renoprotection and dose-dependent survival benefits of the S herb in compounds and no increased hyperkalemia risk of the prescribed CHMs in CKD patients.

The scarcity of dietary guidance for renal transplant recipients (RTRs) raises concerns regarding obesity and associated comorbidities, including impaired renal function. This two-stage cross-sectional study examined longitudinal changes in dietary nutrient intake in the same individuals over a 5-year interval. This study involved two stages: T1 (September 2016 to June 2018) and T2 (July 2022 to August 2023). The average duration between the two data collection stages was 6.17 ± 0.42 (range 5.20–6.87) years. The study included 227 RTRs with an average age and time since transplant of 49.97 ± 12.39 and 9.22 ± 7.91 years, respectively. Of the 35 patients who participated in both phases, fewer than half met the recommended intakes for energy, dietary fiber, and most vitamins and minerals, as set in the Dietary Reference Intakes (DRIs) or by the Dietitian Association Australia (DAA). Over half exceeded the DRI recommended intake for total protein, and more than 80% of the protein consumed per kilogram of body weight exceeded the DAA’s recommendations. In the T2 stage, the RTRs had a significantly higher blood urea nitrogen level, lower albumin level, and estimated glomerular filtration rate. These findings indicate that deteriorating dietary intake in RTRs can adversely affect their nutritional status and transplanted kidney function over a 5-year period.

As heterogeneous catalysis is a practical method for activating Oxone, the immobilization of transition metals (e.g., Co, Fe) on carbonaceous supports is a promising platform. Thus, this study attempts to develop a carbon-supported metallic catalyst by growing Co/Fe on carbon foam (CF) via adopting melamine foam as a readily available template which could be transferred to nitrogen-doped CF with marcoporous structures. Specifically, a unique adornment of Co/Fe species on this CF is facilely fabricated through a complexation of Co/Fe with a plant extract, tannic acid, on melamine foam, followed by carbonization to produce nano-needle-like Co/Fe on N-doped CF, forming a magnetic CF (MCF). This resultant MCF exhibits a much higher surface area of 54.6 m2/g than CF (9.5 m2/g), and possesses a much larger specific capacitance of 9.7 F/g, than that of CF as 4.0 F/g. These superior features of MCF enable it to accelerate Oxone activation in order to degrade an emerging contaminant, bis(4-hydroxyphenyl)methanone (BHPM). Furthermore, MCF + Oxone exhibits a lower activation energy as 18.6 kJ/mol for BHPM elimination and retains its effectiveness in eliminating BHPM over multiple rounds. More importantly, the CF is also prepared and directly compared with the MCF to study the composition-structure-property relationship to provide valuable insights for further understanding of catalytic behaviors, surficial characteristics, and application of such a functional carbon material.

It is challenging to construct lateral homostructures with controllable geometry and repeated alternating configurations. Here the authors develop a generic approach for fabricating twisted lateral homostructures with tunable crystal orientation, epitaxial constrain, and phase stability.

Optimizing endometrial thickness (EMT) is crucial for successful embryo implantation, but enhancing thin endometrium remains a significant challenge. Platelet-rich plasma (PRP)-derived therapies have emerged as a promising approach in reproductive medicine due to their capacity to facilitate tissue repair and regeneration. This study aims to identify the risk factors associated with the failure of intrauterine PRP infusion for thin endometrium in women with recurrent implantation failure (RIF). We retrospectively reviewed data from 77 women with RIF, all exhibiting an EMT of p = 0.04, OR: 3.16; 95% CI: 1.03–9.67). Additionally, the number of previous uterine surgeries emerged as a prognostic factor for pregnancy failure following PL infusion (p = 0.02, OR: 2.02; 95% CI: 1.12–3.64). Our findings suggest that an extremely thin EMT and a history of numerous uterine surgeries can impede successful pregnancy, even when an optimal EMT is achieved following PRP infusion.

Several dietary indices assess the impacts of the Dietary Approaches to Stop Hypertension (DASH) diet on health outcomes. We explored DASH adherence and renal function among 85 Taiwanese renal transplant recipients (RTRs) in a cross-sectional study. Data collection included demographics, routine laboratory data, and 3-day dietary records. Three separate DASH indices, that defined by Camões (based on nine nutrients), that defined by Fung (using seven food groups and sodium), and that modified by Fung (as above but separated for men and women) were used. Renal function was ascertained through the estimated glomerular filtration rate (eGFR) from patients’ medical records. Participants’ mean age was 49.7 ± 12.6 years and eGFR was 54.71 ± 21.48 mL/min/1.73 m2. The three established DASH diet indices displayed significant correlations (r = 0.50–0.91) and indicated the nutritional adequacy of the diet. Multiple linear regressions indicated a significant positive association between higher DASH scores for each index and increased eGFR. In addition, RTRs in the highest DASH score tertile had higher eGFR rates than those in the lowest tertile, regardless of confounding variables. Adherence to a DASH-style diet correlated with better renal function among RTRs. Educating RTRs about the DASH diet may prevent graft function deterioration.

Objective: Sorting-related receptor with type A repeats (SORLA) is a neuronal sorting receptor that prevents accumulation of amyloid-beta peptides, the main constituent of senile plaques in Alzheimer disease. Recent transcriptomic studies show that SORLA transcripts are also found in beta cells of pancreatic islets, yet the role of SORLA in islets is unknown. Based on its protective role in reducing the amyloid burden in the brain, we hypothesized that SORLA has a similar function in the pancreas via regulation of amyloid formation from islet amyloid polypeptide (IAPP). Methods: We generated human IAPP transgenic mice lacking SORLA (hIAPP:SORLA KO) to assess the consequences of receptor deficiency for islet histopathology and function in vivo. Using both primary islet cells and cell lines, we further investigated the molecular mechanisms whereby SORLA controls the cellular metabolism and accumulation of IAPP. Results: Loss of SORLA activity in hIAPP:SORLA KO resulted in a significant increase in islet amyloid deposits and associated islet cell death compared to hIAPP:SORLA WT animals. Aggravated islet amyloid deposition was observed in mice fed a normal chow diet, not requiring high-fat diet feeding typically needed to induce islet amyloidosis in mouse models. In vitro studies showed that SORLA binds to and mediates the endocytic uptake of proIAPP, but not mature IAPP, delivering the propeptide to an endolysosomal fate. Conclusions: SORLA functions as a proIAPP-specific clearance receptor, protecting against islet amyloid deposition and associated cell death caused by IAPP.

In vertebrates, several forms of memory-relevant synaptic plasticity involve postsynaptic rearrangements of glutamate receptors. In contrast, previous work indicates that Drosophila and other invertebrates store memories using presynaptic plasticity of cholinergic synapses. Here, we provide evidence for postsynaptic plasticity at cholinergic output synapses from the Drosophila mushroom bodies (MBs). We find that the nicotinic acetylcholine receptor (nAChR) subunit α5 is required within specific MB output neurons for appetitive memory induction but is dispensable for aversive memories. In addition, nAChR α2 subunits mediate memory expression and likely function downstream of α5 and the postsynaptic scaffold protein discs large (Dlg). We show that postsynaptic plasticity traces can be induced independently of the presynapse, and that in vivo dynamics of α2 nAChR subunits are changed both in the context of associative and non-associative (familiarity) memory formation, underlying different plasticity rules. Therefore, regardless of neurotransmitter identity, key principles of postsynaptic plasticity support memory storage across phyla.

BackgroundClarithromycin is widely used to treat various bacterial infections and has been reported to have potential cardiovascular risk. However, it is uncertain whether this association was dose dependent and confounded by indication bias in patients with stable coronary heart disease (CHD).MethodsThis cohort study retrospectively analyzed a national health insurance claims data from Taiwan’s 2005 Longitudinal Generation Tracking Database. We used a new-user design and 1:1 propensity score matching. A total of 9,631 eligible clarithromycin users and 9,631 non-users in 2004–2015 were subject to final analysis. All patients were followed-up after receiving clarithromycin or on the matched corresponding date until occurrence of cardiovascular morbidity in the presence of competing mortality, all-cause and cause-specific mortality, or through the end of 2015. The effect of cumulative dose, exposure duration, and indications of clarithromycin on cardiovascular outcomes were also addressed.ResultsClarithromycin use, compared with non-use, was associated with higher risk for all-cause [adjusted hazard ratios (aHR), 1.43; 95% confidence interval, 1.29–1.58], cardiovascular (1.35; 1.09–1.67), and non-cardiovascular (1.45; 1.29–1.63) mortality, but not for overall cardiovascular morbidity. Further analysis of individual cardiovascular morbidity demonstrated major risk for heart events (1.25; 1.04–1.51) in clarithromycin users than non-users. However, there was no relationship of cumulative dose, exposure duration, and indications of clarithromycin on cardiovascular outcomes. Analyses of the effects over time showed that clarithromycin increased cardiovascular morbidity (1.21; 1.01–1.45), especially heart events (1.39; 1.10–1.45), all-cause (1.57; 1.38–1.80), cardiovascular (1.58; 1.20–2.08), and non-cardiovascular (1.57; 1.35–1.83) mortality during the first 3 years. Thereafter, clarithromycin effect on all outcomes almost dissipated.ConclusionClarithromycin use was associated with increased risk for short-term cardiovascular morbidity (especially, heart events) and mortality without a dose-response relationship in patients with stable CHD, which was not dose dependent and confounded by indications. Hence, patients with stable CHD while receiving clarithromycin should watch for these short-term potential risks.

Background: Antimicrobial resistance is a public health problem that threatens the efficacy of antibiotics. Incorrect knowledge of antibiotics may lead to their inappropriate use, hinder their effectiveness, and cause antibiotic resistance. Population-based educational campaigns have been found to have either mixed or no effect on improving knowledge and appropriate antibiotic practices, suggesting the need for more targeted approaches in tailoring education for specific subpopulations. Women are the primary caregivers of their families and are more willing to contact healthcare providers. They had greater knowledge of antibiotics and better adherence to the completion of the antibiotic regimen. Therefore, they are suitable for prioritization in a campaign program.Objective: This study examined the knowledge and practices of female visitors to health centers in Malang, Indonesia with respect to antibiotic use.Methods: This cross-sectional study was conducted in Malang, Indonesia, in July and August 2018. Data were collected from 677 women. Multivariate logistic regression was performed to identify the potential factors associated with antibiotic knowledge, self-medication, and completion of antibiotic regimens.Results: Overall, 82.7% of respondents were aware that antibiotics are used against bacteria, while 38.4% reported self-medication with antibiotics and 51.7% reported completing antibiotic regimens. Women with higher education, previous antibiotic use experience, and very easy accessibility to primary doctors were more likely to have high antibiotic knowledge than those with primary education, no antibiotic use in the previous year, and easy/other level of accessibility to primary doctors. Subjects residing in urban areas and with less accessibility to primary doctors were more likely to self-medicate with antibiotics. Additionally, the completion of antibiotic regimens was positively associated with access to a primary care doctor and high antibiotic knowledge.Conclusion: IF Policymakers tend to reduce inappropriate antibiotic use among women. Priority advocates are recommended for urban residents who have experiences of antibiotic use in the previous year. It is therefore important to increase their awareness, particularly regarding diseases against which antibiotics are effective, and activities such as unnecessary use of antibiotics in healthy animals, which may affect their overall effectiveness among humans. More communication channels should be included in the overall scheme to improve the public awareness and accessibility of health professionals.

Objective: Double-low CT aortography (DLCTA) is increasingly used in follow-up studies of aortic aneurysm after endovascular aneurysm repair (EVAR). However, whether DLCTA can reliably detect the presence of endoleak is not clear. Methods: From February 2014 to October 2019, patients who received EVAR, underwent CT surveillance, and had at least one standard CTA protocol (120 kVp, 400 mg I/kg) and one DLCTA (70–80 kVp, 200 mg I/kg) were included. The integrated findings of the standard CTA and sequential change were considered as the reference standard for the presence of endoleak. Results: In all, 36 patients received TEVAR and 24 patients received EVAR; 62 standard CTA and 167 DLCTA results were analyzed. There were 2 type I (3.3%) and 12 type II (20.0%) endoleaks in 14 patients (23.3%). The performance of DLCTA in the diagnosis of endoleak reached 100% accuracy compared to that of standard CTA in case of the correction of CT findings by an expert second reading. Compared to the standard CTA, DLCTA scan reduced the radiation dose by 71% and the iodine dose by 50%. Conclusions: DLCTA with 70–80 kVp and 200 mg I/kg can reliably detect the presence of endoleak after TEVAR/EVAR.

Dysmenorrhea causes pain and inconvenience during menstruation. In addition to medication, natural compounds are widely used to relieve various types of pain. In this study, we aimed to assess the effects of vitamin D (vit. D) supplementation in relieving the symptoms of primary dysmenorrhea. A comprehensive systematic database search of randomized controlled trials (RCTs) was performed. Oral forms of vit. D supplementation were included and compared with a placebo or standard care. The degree of dysmenorrhea pain was measured with a visual analogue scale or numerical rating scale. Outcomes were compared using the standardized mean difference (SMD) and 95% confidence intervals (CIs) in a meta-analysis. RCTs were assessed using the Cochrane risk-of-bias v2 (RoB 2) tool. The meta-analysis included 8 randomized controlled trials involving 695 participants. The results of the quantitative analysis showed a significantly lower degree of pain in the vit. D versus placebo in those with dysmenorrhea (SMD: −1.404, 95% CI: −2.078 to −0.731). The results of subgroup analysis revealed that pain lessened when the average weekly dose of vit. D was over 50,000 IU, in which dysmenorrhea was relieved regardless of whether vit. D was administered for more or less than 70 days and in any dose interval. The results revealed that vit. D treatment substantially reduced the pain level in the primary dysmenorrhea population. We concluded that vit. D supplementation is an alternative treatment for relieving the pain symptoms of dysmenorrhea.

A loss of functional beta cell mass is a final etiological event in the development of frank type 2 diabetes (T2D). To preserve or expand beta cells and therefore treat/prevent T2D, growth factors have been considered therapeutically but have largely failed to achieve robust clinical success. The molecular mechanisms preventing the activation of mitogenic signaling pathways from maintaining functional beta cell mass during the development of T2D remain unknown. We speculated that endogenous negative effectors of mitogenic signaling cascades impede beta cell survival/expansion. Thus, we tested the hypothesis that a stress-inducible epidermal growth factor receptor (EGFR) inhibitor, mitogen-inducible gene 6 (Mig6), regulates beta cell fate in a T2D milieu. To this end, we determined that: (1) glucolipotoxicity (GLT) induces Mig6, thereby blunting EGFR signaling cascades, and (2) Mig6 mediates molecular events regulating beta cell survival/death. We discovered that GLT impairs EGFR activation, and Mig6 is elevated in human islets from T2D donors as well as GLT-treated rodent islets and 832/13 INS-1 beta cells. Mig6 is essential for GLT-induced EGFR desensitization, as Mig6 suppression rescued the GLT-impaired EGFR and ERK1/2 activation. Further, Mig6 mediated EGFR but not insulin-like growth factor-1 receptor nor hepatocyte growth factor receptor activity in beta cells. Finally, we identified that elevated Mig6 augmented beta cell apoptosis, as Mig6 suppression reduced apoptosis during GLT. In conclusion, we established that T2D and GLT induce Mig6 in beta cells; the elevated Mig6 desensitizes EGFR signaling and induces beta cell death, suggesting Mig6 could be a novel therapeutic target for T2D.

Globally, anemia affects 56 million pregnant women, especially women with a low household income. Functional erythropoiesis requires a constant supply of micronutrients, and the demands significantly increase during fetal development. This study aims to identify dietary patterns for preventing gestational erythropoiesis-associated micronutrient deficiencies (e.g., iron, folic acid, and vitamin B12). A Nationwide Nutrition and Health Survey in Pregnant Women, Taiwan (NAHSIT-PW), was conducted between 2017 and 2019. Data on baseline information, diet, anthropometrics, and blood biochemistry were collected during a prenatal visit. Dietary patterns were identified using a reduced rank regression (RRR). Erythropoiesis-related micronutrient deficiencies were defined as single, double, and triple micronutrient deficiencies of an iron deficiency, folate depletion, and a vitamin B12 deficiency. In total, 1437 singleton pregnancies aged ≥20–48 years were included in the analysis. Prevalences of normal nutrition, and single, double, and triple erythropoiesis-related micronutrient deficiencies were 35.7%, 38.2%, 18.6%, and 7.5%, respectively. Anemic pregnant women with a low household income had the highest prevalence rates of double (32.5%) and triple (15.8%) erythropoiesis-related micronutrient deficiencies. Dietary pattern scores were positively correlated with nuts and seeds, fresh fruits, total vegetables, breakfast cereals/oats and related products, soybean products, and dairy products but negatively correlated with processed meat products and liver, organs, and blood products. After adjusting for covariates, the dietary pattern had 29% (odds ratio (OR): 0.71; 95% confidence interval (CI): 0.055–0.091, p = 0.006)) and 43% (OR: 0.57; 95% CI: 0.41–0.80, p = 0.001)) reduced odds of having double and triple erythropoiesis-related micronutrient deficiencies for those pregnant women with a low household income. For those women with anemia, dietary patterns had 54% (OR: 046, 95% CI: 0.27–0.78) and 67% (OR: 0.33; 95% CI: 0.170.64) reduced odds of double and triple erythropoiesis-related micronutrient deficiencies. In conclusion, increased consumption of breakfast cereals and oats, nuts, and seeds, fresh fruits and vegetables, soybean products, and dairy products may protect women against erythropoiesis-related micronutrient deficiencies during pregnancy.

During the coronavirus disease 2019 (COVID-19) pandemic, global vaccination efforts declined due to the burden on health systems and community resistance to epidemic control measures. Influenza and pneumococcal vaccines have been recommended for vulnerable populations to prevent severe pneumonia. We investigated community response towards influenza and pneumococcal vaccines (pneumococcal conjugate vaccine and pneumococcal polysaccharide vaccine) after the COVID-19 outbreak in Taiwan. We retrospectively included adults who visited Chang Gung Memorial Hospital (CGMH) institutions for influenza or pneumococcal vaccination from January 2018 to December 2021. The first case of COVID-19 in Taiwan was detected in January 2020; therefore, in this study, hospitalized cases from January 2018 to December 2019 were defined as “before COVID-19 outbreak,” and hospitalized cases from January 2020 to December 2021 were defined as “after COVID-19 outbreak”. A total of 105,386 adults were enrolled in the study. An increase in influenza vaccination (n = 33,139 vs. n = 62,634) and pneumococcal vaccination (n = 3035 vs. n = 4260) were observed after the COVID-19 outbreak. In addition, there was an increased willingness to receive both influenza and pneumococcal vaccinations among women, adults without underlying disease and younger adults. The COVID-19 pandemic may have increased awareness of the importance of vaccination in Taiwan.

Vitamin D is involved in the pathophysiology of anemia. This cross-sectional study was conducted using the Nationwide Nutrition and Health Survey in Pregnant Women in Taiwan database. We investigated associations among dietary patterns (DPs), vitamin D, and iron-related biomarkers in pregnant women. The principal component analysis revealed four DPs. Linear and logistic regression analyses were performed to investigate the association of DPs with anemia-related biomarkers. Plant-based, carnivore, and dairy and nondairy alternatives DPs were positively associated with serum vitamin D levels. After adjusting covariates, the pregnant women consuming plant-based DPs at the mid-tertile (T2) were associated with reduced risks of low serum folate and vitamin D levels, and those consuming carnivore DPs at higher tertiles (T2 and/or T3) were correlated with an increased risk of low serum iron levels but decreased risks of low serum transferrin saturation, vitamin B12, and vitamin D levels. The pregnant women consuming dairy and nondairy alternatives DPs at the highest tertile (T3) were associated with reduced risks of low serum folate and vitamin B12 levels. However, the processed food DP was not correlated with anemia-related biomarkers. Thus, plant-based, carnivore, and dairy and nondairy alternatives DPs were associated with the risk of low-serum-anemia-related variables.

Background: Oxidative stress could participate in the pathogenesis of Parkinson's disease (PD). However, the role of genetic variation of superoxide dismutase 2 (SOD2), an important regulator against oxidative stress, in PD remains to be elucidated. Methods: We screened SOD2 gene variation by sequencing cDNA from 72 patients with early onset PD. A cohort of PD (n = 609) and ethnically matched controls (n = 681) were further examined for the identified sequence variant by PCR and NaeI restriction analysis. Results: Only a reported c.47T>C polymorphism (rs4880, SOD2 p.V16A) was found by cDNA sequencing. Case-control study of c.47T>C revealed that genotype and allele frequencies were in Hardy–Weinberg equilibrium in both patients and healthy controls. In a recessive model, those with CC genotype had a 2.61-fold increased risk of PD (95% CI: 1.08–6.30, P = 0.03) compared to subjects with TT and TC genotypes. Significant association between CC genotype and PD in non-smokers was also observed after stratification according to the history of smoking (3.54-fold increased risk of PD, 95% CI: 1.17–10.72, P = 0.02). Meta-analysis by combining studies of Chinese in China, Singapore, and Taiwan (total 2302 cases and 2029 controls) consistently showed CC genotype with increased risk of PD (OR = 1.77, 95% CI: 1.15–2.71, P = 0.01). Conclusion: Our findings demonstrate that SOD2 p.V16A may play a role in the susceptibility of PD in Han Chinese.

Abstract Immediate postoperative intensive care unit (ICU) admission can increase the survival rate in patients undergoing high-risk surgeries. Nevertheless, less than 15% of such patients are immediately admitted to the ICU due to no reliable criteria for admission. The surgical Apgar score (SAS) (0–10) can be used to predict postoperative complications, mortality rates, and ICU admission after high-risk intra-abdominal surgery. Our study was performed to determine the relationship between the SAS and postoperative ICU transfer after all surgeries. All patients undergoing operative anesthesia were retrospectively enrolled. Among 13,139 patients, 68.4% and

Otosclerosis is an early adult-onset disease that is associated with 5–9% and 18–22% of all cases of hearing and conductive hearing loss, respectively, and it is suspected to have a viral etiology. However, the role of viral infection in otosclerosis is still inconclusive. This study aimed to investigate whether rubella infection was associated with otosclerosis risk. We conducted a nationwide case-control study in Taiwan. Data were retrospectively analyzed from the Taiwan National health Insurance Research Database. Cases consisted of all patients who were aged ≥6 years and had a first-time diagnosis of otosclerosis for the period between 2001 and 2012. The controls were exact matched to cases in a 4:1 ratio by birth year, sex, and must survive in the index year of their matched cases. Adjusted odds ratio (OR) and 95% confidence interval (CI) were estimated by using conditional logistic regression. We examined 647 otosclerosis cases and 2588 controls without otosclerosis. Among the 647 patients with otosclerosis, 241 (37.2%) were male and 406 (62.8%) were female, with most aged between 40 and 59 years, with a mean age of 44.9 years. After adjusting for age and sex, conditional logistic regression revealed that exposure to rubella was not associated with a significant increase in otosclerosis risk (adjusted OR, 2.0; 95% CI, 0.18–22.06, p = 0.57). In conclusion, this study did not show that rubella infection was associated with the risk of otosclerosis in Taiwan.

Background: Vitamin D deficiency (VDD) is a global micronutrient issue that commonly occurs in pregnant women, leading to adverse health outcomes. We examined the role of sunlight-related factors and dietary vitamin D intake on vitamin D concentrations among pregnant women in different climate zones. Methods: We conducted a nationwide cross-sectional survey in Taiwan between June 2017 and February 2019. The data of 1502 pregnant women were collected, including sociodemographic information and characteristics related to pregnancy, diet, and sun exposure. Serum 25-hydroxyvitamin D concentrations were measured, and VDD was assessed as a concentration of less than 20 ng/mL. Logistic regression analyses were used to explore the factors associated with VDD. Furthermore, the area under the receiver operating characteristic (AUROC) curve was used to analyze the contribution of sunlight-related factors and dietary vitamin D intake to vitamin D status stratified by climate zones. Results: The prevalence of VDD was 30.1% and was the highest in the north. Sufficient intake of red meat (odds ratio (OR): 0.50, 95% confidence interval (CI): 0.32–0.75; p = 0.002), vitamin D and/or calcium supplements (OR: 0.51, 95% CI: 0.39–0.66; p < 0.001), sun exposure (OR: 0.75, 95% CI: 0.57–0.98; p = 0.034), and blood draw during sunny months (OR: 0.59, 95% CI: 0.46–0.77; p < 0.001) were associated with a lower likelihood of VDD. Additionally, in northern Taiwan, which is characterized by a subtropical climate, dietary vitamin D intake (AUROC: 0.580, 95% CI: 0.528–0.633) had a greater influence on vitamin D status than did sunlight-related factors (AUROC: 0.536, 95% CI: 0.508–0.589) with a z value = 51.98, p < 0.001. By contrast, sunlight-related factors (AUROC: 0.659, 95% CI: 0.618–0.700) were more important than dietary vitamin D intake (AUROC: 0.617, 95% CI, 0.575–0.660) among women living in tropical areas of Taiwan (z value = 54.02, p < 0.001). Conclusions: Dietary vitamin D intake was essential to alleviate VDD in the tropical region, whereas sunlight-related factors played a greater role in subtropical areas. Safe sunlight exposure and adequate dietary vitamin D intake should be promoted appropriately as a strategic healthcare program.

Translocase of outer mitochondrial membrane 40 (TOMM40) is located in the outer membrane of mitochondria. TOMM40 is essential for protein import into mitochondria. TOMM40 genetic variants are believed to increase the risk of Alzheimer’s disease (AD) in different populations. In this study, three exonic variants (rs772262361, rs157581, and rs11556505) and three intronic variants (rs157582, rs184017, and rs2075650) of the TOMM40 gene were identified from Taiwanese AD patients using next-generation sequencing. Associations between the three TOMM40 exonic variants and AD susceptibility were further evaluated in another AD cohort. Our results showed that rs157581 (c.339T > C, p.Phe113Leu, F113L) and rs11556505 (c.393C > T, p.Phe131Leu, F131L) were associated with an increased risk of AD. We further utilized cell models to examine the role of TOMM40 variation in mitochondrial dysfunction that causes microglial activation and neuroinflammation. When expressed in BV2 microglial cells, the AD-associated mutant (F113L) or (F131L) TOMM40 induced mitochondrial dysfunction and oxidative stress-induced activation of microglia and NLRP3 inflammasome. Pro-inflammatory TNF-α, IL-1β, and IL-6 released by mutant (F113L) or (F131L) TOMM40-activated BV2 microglial cells caused cell death of hippocampal neurons. Taiwanese AD patients carrying TOMM40 missense (F113L) or (F131L) variants displayed an increased plasma level of inflammatory cytokines IL-6, IL-18, IL-33, and COX-2. Our results provide evidence that TOMM40 exonic variants, including rs157581 (F113L) and rs11556505 (F131L), increase the AD risk of the Taiwanese population. Further studies suggest that AD-associated mutant (F113L) or (F131L) TOMM40 cause the neurotoxicity of hippocampal neurons by inducing the activation of microglia and NLRP3 inflammasome and the release of pro-inflammatory cytokines.

Background: Prior research has shown preliminary evidence that calligraphy activity improves various body functions and decreases severity of psychotic symptoms in individuals with schizophrenia. However, major limitations of earlier studies include small and heterogeneous samples. The current large-scale randomized controlled trial examined effects of calligraphy activity on cognition (including attention), emotions, psychotic symptoms, quality of life, and mood in people with schizophrenia. Methods: One-hundred-and-fifty patients with schizophrenia were randomly allocated to the treatment group (receiving calligraphy activity) or the control group (receiving general activity), both of which lasted for 24 weeks (70 minutes per session; one session per week). Assessments were conducted at pretest, posttest, and three-month follow-up. The Montreal Cognitive Assessment, Chu’s Attention Test, Depression, Anxiety, and Stress Scale, Positive and Negative Syndrome Scale, World Health Questionnaire on the Quality of Life-Brief Form, and Visual Analogue Scale were used. Results: Improved cognition and attention were found in both groups, although no group effects were shown. The treatment group appeared to show lower severity of positive symptoms at follow-up than posttest, whereas the control group appeared to show the opposite pattern. Improved mood was found in the treatment group. Conclusion: This study provides evidence regarding effects of calligraphy activity on increasing cognition and potentially decreasing severity of positive symptoms in patients with schizophrenia. Calligraphy activity can be incorporated in clinical occupational therapy and may be provided to supplement medication treatment. Trial Registration: ClinicalTrials.gov NCT03882619; https://clinicaltrials.gov/ct2/show/NCT03882619

Abstract Background Pregabalin is approved for the treatment of neuropathic pain, fibromyalgia, and seizure disorders, although the pivotal trials were mostly carried out in Europe or North America. The prescribing patterns among different indications in Asia have rarely been explored. Methods This was a population-based retrospective cohort study based on the National Health Insurance Research Database in Taiwan. Prescriptions of pregabalin were identified, and data regarding demographics, indications, co-existing diagnoses, and concomitant medications were extracted. Pregabalin users were followed for at least one year, and factors associated with persistence at one year were determined by using multivariate logistic regression analysis. Results Between June 2012 and December 2016, 114,437 pregabalin users (mean age 60.7 ± 15.4 years, 57.8% female) were identified. The indications included post-herpetic neuralgia (PHN) (30.5%), musculoskeletal diseases other than fibromyalgia (21.2%), fibromyalgia (18.4%), diabetic peripheral neuropathic pain (DPNP) (11.7%) and epilepsy (2.9%). Overall, 62.5% and 6.4% of patients achieved a maximum dose of ≥150 and ≥ 300 mg/day, respectively. The median duration of persistent pregabalin use was 28 days (interquartile range 14–118 days). The one-year persistence rate was 12.1%, and the indications associated with the highest and lowest persistence rates were epilepsy (42.4%) and PHN (6.1%), respectively. Male gender (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.09–1.18), older age (OR 1.01 per year, 95% CI 1.01–1.01), indications other than PHN, especially epilepsy (OR 8.04, 95% CI 7.33–8.81, PHN as reference), and a higher initial dose (OR 1.12 per 75 mg, 95% CI = 1.10–1.15) were associated with persistence at one year, whereas the initial concomitant use of antiviral agents decreased the likelihood (OR 0.41, 95% CI 0.35–0.47). Conclusions Pregabalin prescriptions for pain disorders were limited to short-term use, which is consistent around the world. However, the average prescribed dose in Taiwan was lower than those in Western countries, and was frequently below the recommended ranges. Potential causes included the duration of natural history of PHN, and off-label prescriptions for pain in acute herpes zoster, rather than PHN, as well as intolerance to the side effects.

Image synthesis for stereoscopic displays shall carefully control its depth of field to enhance perception while reduce visual fatigue due to accommodation-vergence mismatch. Existing approaches suffer from either lower quality due to occluding contour error, or high computational complexity. To meet above demands, this paper proposes a perceptual oriented defocus blur that reduces complexity with the depth layer processing and improves quality with transparency degree oriented superposition and edge enhancement. The simulation results show that the proposed approach has better quality than the conventional defocus blur methods and achieves similar quality compared to the deep learning based methods but with much lower complexity.

The vaccination of all children may be one of the most important public health measures for preventing a wider spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the community. Therefore, the purpose of this study was to investigate the attitude, intention, decision making, and psychological well-being among the caregivers of children who received SARS-CoV-2 vaccination in Taiwan. The caregivers of children (98 preschool children, 191 school-age children, and 154 adolescents) who received COVID-19 vaccination were invited to fill in the following questionnaires: Adopting Self-Protective Behavior Scale, Drivers of COVID-19 Vaccination Acceptance Scale, Impact of Event Scale, Chinese Health Questionnaire, and Parental Bonding Instrument. Compared to the caregivers of adolescents, the caregivers of preschool children exhibited more protective behaviors toward the COVID-19 pandemic. The caregivers of preschool children also displayed a higher emotional impact than those of adolescents and took a greater interest in the family’s opinion about vaccination. Finally, we found that COVID-19 ideological invasion and protective parenting style were significantly related to the prevalence of mental illness among caregivers. The results of this study can be used as an important reference for vaccination health care and policy formulation for adolescents with regard to COVID-19.

We thank Li and colleagues for their insightful comments [...]

Angiogenesis plays an important role in the development of bone and bone regeneration to provide the required molecules. Mesenchymal stem cells (MSCs) are pluripotent, self-renewing, and spindle-shaped cells, which can differentiate into multiple lineages such as chondrocytes, osteocytes, and adipocytes. MSCs derived from bone marrow (BMMSCs), adipose tissue (ADMSCs), and Wharton’s jelly (UCMSCs) are popular in the field of tissue regeneration. MSCs have been proposed that can promote bone regeneration by enhancing vascularization. In this study, the angiogenic potential of secretomes of undifferentiated and osteo-differentiated BMMSCs, ADMSCs, and UCMSCs seeded on human decellularized allogeneic bone were compared. Human umbilical vein endothelial cells (HUVECs) were treated with MSC secretomes. Cell growth, cell migration, and angiogenesis of HUVECs were analyzed by MTT, wound healing, and tube formation assays. Angiogenic gene expression levels of MSCs were evaluated using real-time quantitative PCR. Antibody neutralization was performed to validate the candidate target. Our study demonstrates that the angiogenic gene expression profile is tissue-dependent and the angiogenic ability of secretomes is independent of the state of differentiation. We also explore that IL-1b is important for MSC angiogenic potential. Taken together, this study proves that IL-1b in the secretomes plays a vital role in angiogenesis.

The spin-to-charge conversion in Permalloy (Py)/Cu/Bi2Se3 is tunable by changing the Cu layer thickness. The conversion rate was studied using the spin pumping technique. The inverse Edelstein effect (IEE) length λIEE is found to increase up to ~2.7 nm when a 7 nm Cu layer is introduced. Interestingly, the maximized λIEE is obtained when the effective spin-mixing conductance (and thus Js) is decreased due to Cu insertion. The monotonic increase in λIEE with decreasing Js suggests that the IEE relaxation time (τ) is enhanced due to the additional tunnelling barrier (Cu layer) that limits the interfacial transmission rate. The results demonstrate the importance of interface engineering in the magnetic heterostructure of Py/topological insulators (TIs), the key factor in optimizing spin-to-charge conversion efficiency.