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Abstract This study evaluated the effectiveness of intraovarian platelet-rich plasma (PRP) injection in improving ovarian response and embryo quality in IVF patients with poor embryo quality in previous controlled ovarian hyperstimulation (COH) cycles. 74 patients participated, with 30 in the control group and 44 in the PRP group. PRP was injected during the follicular phase for the PRP group. The control group completed two COH cycles, while the PRP group underwent COH cycles before and after the PRP injection. In the first COH cycle, there were no significant differences between groups. However, in the second COH cycle, the PRP group showed significant improvements: the number of fertilized oocytes increased (5.2 ± 3.6 vs. 3.3 ± 3.5, p = 0.011), total blastocysts (1.7 ± 1.5 vs. 0.5 ± 0.7, p

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 (

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.

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.

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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

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.

Self-regulatory learning skills are recognized as an essential factor motivating students to learn. The lack of self-regulatory learning skills could reduce students' learning performance. Therefore, engaging students in making learning plans, executing the plans, and reflecting on their learning remains a challenge for teachers. To address this problem, this study proposes a gamified mobile self-regulated learning approach which provides multiple gamified rewards to motivate students' self-regulatory learning skills. Gamified elements were integrated into students' self-regulated learning stages to guide them in efficiently exploring how to achieve their goals and making deep learning reflections. To investigate the effect of this proposed approach on students' learning outcomes, two classes of students were recruited to conduct the experiment. The learning approach was used by the experimental group (N = 22) while the conventional mobile self-regulated learning approach was used by the control group (N = 22). Both groups of students' performance on the mathematics learning achievement test, SRL learning sheets, and goal-achieving intentions were collected and analyzed. The results showed that the gamification mechanism improved the students' learning achievement as well as their goal-setting and reflection performance. However, the students who used the proposed approach reached similar monitoring performance as those students who learned without gamification. This study confirmed the feasibility of introducing a gamification mechanism into self-regulated learning, and revealed how to apply multiple game elements in instructional activities to enhance students' learning intentions.

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.

Abstract Background Multiple interplays between viral and host factors are involved in influenza virus replication and pathogenesis. Several small RNAs have recently emerged as important regulators of host response to viral infections. The aim of this study was to characterize the functional role of hsa-miR-1975, a Y5 RNA-derived small RNA, in defending influenza virus and delineate the mechanisms. Methods We performed high throughput sequencing of small RNAs in influenza virus-infected cells to identify up- or down- regulated small RNA species. The expression of the most abundant RNA species (hsa-miR-1975) was validated by stem-loop reverse transcription-polymerase chain reaction (RT-PCR). Antiviral effects of hsa-miR-1975 were confirmed by Western Blot, RT-PCR and plaque assay. In vitro perturbation of hsa-miR-1975 combined with exosomes isolation was used to elucidate the role and mechanism of hsa-miR-1975 in the context of antiviral immunity. Results Small RNA sequencing revealed that hsa-miR-1975 was the most up-regulated small RNA in influenza virus-infected cells. The amount of intracellular hsa-miR-1975 increased in the late stage of the influenza virus replication cycle. The increased hsa-miR-1975 was at least partially derived from degradation of Y5RNA as a result of cellular apoptosis. Unexpectedly, hsa-miR-1975 mimics inhibited influenza virus replication while hsa-miR-1975 sponges enhanced the virus replication. Moreover, hsa-miR-1975 was secreted in exosomes and taken up by the neighboring cells to induce interferon expression. Conclusions Our findings unravel a critical role of Y-class small RNA in host’s defense against influenza virus infection and reveal its antiviral mechanism through exosome delivery. This may provide a new candidate for targeting influenza virus.

Abstract Variations at the six nucleotides −3279 (T > G), −53 (A[TA]6TAA > A[TA]7TAA), 211 (G > A), 686 (C > A), 1091 (C > T), and 1456 (T > G) in the UDP‐glucuronosyltransferase 1A1 (UGT1A1) gene were determined in 178 Taiwanese patients with Gilbert's syndrome and in 200 healthy adults. Every subject was classified as a genotype depending on variation status of the six nucleotides in the UGT1A1 gene. The UGT1A1 activity for each genotype was calculated and then those genotypes were divided into 10 subgroups (Q1~Q10) according to their UGT1A1 activities, by using 10% as an interval. There were 24 genotypes observed, with UGT1A1 activity ranged 9%~100% of normal. There were two and six subjects with Gilbert's syndrome and none of healthy controls carrying genotypes in the Q1 and Q2 subgroups, respectively. The odds of developing Gilbert's syndrome were significantly higher for subjects carrying genotypes in the Q3, Q4, and Q5 subgroups than for those with genotype in the Q10 subgroup (odds ratios: 240.22, 59.80, and 14.67, respectively, P

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.

The risk of developing coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) depends on factors related to the host, virus, and treatment. However, many hospitals have modified their existing rooms and adjusted airflow to protect healthcare workers from aerosolization, which may increase the risk of Aspergillus exposure. This study aimed to quantitatively investigate airborne fungal levels in negative and slightly negative pressure rooms for COVID-19 patients. The air in neutral pressure rooms in ordinary wards and a liver intensive care unit with high-efficiency particulate air filter was also assessed for comparison. We found the highest airborne fungal burden in recently renovated slightly negative air pressure rooms, and a higher airborne fungal concentration in both areas used to treat COVID-19 patients. The result provided evidence of the potential environmental risk of CAPA by quantitative microbiologic air sampling, which was scarcely addressed in the literature. Enhancing environmental infection control measures to minimize exposure to fungal spores should be considered. However, the clinical implications of a periodic basis to determine indoor airborne fungal levels and further air sterilization in these areas remain to be defined.

Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are two major alcohol-metabolizing enzymes. Moderate alcohol intake is a protective modified factor in Alzheimer’s disease (AD) while heavy alcohol intake and abstinence increased dementia risk. The associations between Alzheimer’s disease and alcohol-metabolizing genes are uncertain. This study examined the association of AD with seven ADH/ALDH single-nucleotide polymorphisms (SNPs), ADH1C rs2241894, ADH1B rs1229984, ALDH1B1 rs2073478, ALDH2 rs886205, rs4767944, rs4648328, and rs671. We enrolled 157 AD and 168 age- and sex-matched control subjects in pilot study to examine the association of AD with ADH/ALDH SNPs. Reconstructed ALDH2 haplotypes were performed. We measured plasma level of ADH1C and checked the interaction effect of AD–rs2241894 genotype on plasma ADH1C level. In extension study, we further examined 339 AD and 2,504 healthy control from the Taiwan Biobank. In pilot study, we observed that ADH1C rs2241894 TT genotype was negatively associated with AD in a recessive genetic model (OR = 0.25, 95% CI 0.09–0.75, p < 0.0001) in women. A strong linkage disequilibrium was observed among the four examined SNPs of ALDH2. No haplotype was related to AD. The plasma ADH1C level in AD was higher than that in control. After adjusted by age, sex, hypertension, diabetes mellitus, and alcohol, we found a significant interaction effect of AD–rs2241894 genotype on plasma ADH1C level (p = 0.04). This interaction effect was attributable to the association between AD and plasma ADH1C level (β estimate = 366, 95% CI 92.7∼639.4, p = 0.009). The genetic distribution of ADH1C rs2241894 showed strong ethnic heterogeneity, in which the T allele was the minor allele accounting for 28.5% in our study and 23.6% in East Asians, while it was a major allele in Americans, Europeans, and the global populations. No association was discovered between AD and the five SNPs: rs2241894, rs1229984, rs2073478, rs886205, and rs671 in the extension study. In summary, this study revealed a suggestive association between ADH1C rs2241894 and female AD in the pilot study, but failed to confirm this finding in a population database. Further age-matched and large sample size case-control studies are needed before rs2241894 can be interpreted as a protective genetic factor of AD.

Summary: To understand the physiological changes that occur in response to spaceflight, mice are transported to the International Space Station (ISS) and housed for variable periods of time before euthanasia on-orbit or return to Earth. Sample collection under such difficult conditions introduces confounding factors that need to be identified and addressed. We found large changes in the transcriptome of mouse tissues dissected and preserved on-orbit compared with tissues from mice euthanized on-orbit, preserved, and dissected after return to Earth. Changes due to preservation method eclipsed those between flight and ground samples, making it difficult to identify spaceflight-specific changes. Follow-on experiments to interrogate the roles of euthanasia methods, tissue and carcass preservation protocols, and library preparation methods suggested that differences due to preservation protocols are exacerbated when coupled with polyA selection. This has important implications for the interpretation of existing datasets and the design of future experiments.

This study aimed to determine the real-world, long-term prognostic impacts, and adverse effects (AEs) of bevacizumab (BEV) in Asian patients with ovarian/tubal/peritoneal cancers. We retrospectively reviewed the medical records of consecutive patients with ovarian/tubal/peritoneal cancer on front-line chemotherapy with or without BEV (Cohort 1) and those who relapsed following chemotherapy and/or BEV (Cohort 2) between 2011 and 2018 in a tertiary medical centre. Patient characteristics, BEV dosages, clinical outcomes, and AEs were analyzed. Hazard ratios for disease progression and death were analyzed using a cox proportional regression model. Benefits of BEV used throughout triweekly, in terms of improved progression-free survival (PFS) and overall survival (OS), were observed at a dosage of 7.5–15 mg/kg among advanced-stage Cohort 1 patients. A progression-free interval of

Wound infections after venomous snakebites are clinically important. Information regarding the nature and antibiotic susceptibilities of snake oral bacterial flora could support empiric antibiotic therapy. Wild venomous snakes were collected from southern Taiwan: a total of 30 each of Bungarus multicinctus, Naja atra, Protobothrops mucrosquamatus, and Trimeresurus stejnegeri; 3 Deinagkistrodon acutus; and 4 Daboia siamensis. The species and antibiotic susceptibilities of their oral bacteria were determined. Aerobic gram-negative bacteria, especially Pseudomonas aeruginosa and Proteus vulgaris, were the most abundant. Proteus vulgaris were more abundant in B. multicinctus, N. atra, and P. mucrosquamatus than in T. stejnegeri (40%, 43.3%, and 40% vs. 13.3%, respectively). The gram-negative species were less susceptible to first- and second-generation cephalosporins and ampicillin-sulbactam than to third-generation cephalosporins, fluoroquinolones, carbapenems, or piperacillin-tazobactam. The most abundant aerobic gram-positive species cultured was Enterococcus faecalis, which was more abundant in N. atra than in other snakes (p < 0.001) and was highly susceptible to ampicillin, high-level gentamicin, penicillin, teicoplanin, and vancomycin. Bacteroides fragilis and Clostridium species were the most common anaerobic bacteria. The anaerobic organisms were highly susceptible to metronidazole and piperacillin. As a reference for empiric antimicrobial therapy, third-generation cephalosporins, fluoroquinolones, carbapenems, or piperacillin-tazobactam can be initiated in venomous snakebites wound infections.

Cryptococcal meningoencephalitis (CM) is a treatable condition, but it leads to excessive morbidity and mortality. We collected 115 non-duplicated Cryptococcus clinical isolates during 2013–2020 in southern Taiwan to perform antifungal susceptibility testing. Multi-locus sequence typing was performed on 96 strains from patients with CM (n = 47) or cryptococcemia (n = 49). In addition, the epidemiological and clinical characteristics of patients with CM during 2013–2020 (n = 47) were compared with those during 2000–2010 (n = 46). During 2013–2020, only one C. neoformans isolate (0.9%) had a fluconazole minimum inhibitory concentration of >8 μg/mL. Amphotericin B (AMB), flucytosine (5FC), and voriconazole were highly active against all C. neoformans/C. gattii isolates. The most common sequence type was ST5. Among these 47 patients with CM, cerebrospinal fluid cryptococcal antigen (CSF CrAg) titer >1024 was a significant predictor of death (odds ratio, 48.33; 95% CI, 5.17–452.06). A standard induction therapy regimen with AMB and 5FC was used for all patients during 2013–2020, but only for 2.2% of patients in 2000–2010. The in-hospital CM mortality rate declined from 39.1% during 2000–2010 to 25.5% during 2013–2020, despite there being significantly younger patients with less CSF CrAg >1024 during 2000–2010. The study provides insight into the genetic epidemiology and antifungal susceptibility of Cryptococcus strains in southern Taiwan. The recommended antifungal drugs, AMB, 5FC, and FCZ, remained active against most of the Cryptococcus strains. Early diagnosis of patients with CM and adherence to the clinical practice guidelines cannot be overemphasized to improve the outcomes of patients with CM.

Background: Patients with polytrauma are expected to have a higher risk of mortality than the summation of expected mortality for their individual injuries. This study was designed to investigate the outcome of polytrauma patients, diagnosed by abbreviated injury scale (AIS) ≥ 3 for at least two body regions, at a level I trauma center. Methods: Detailed data of 694 polytrauma patients and 2104 non-polytrauma patients with an overall Injury Severity Score (ISS) ≥ 16 and hospitalized between January 1, 2009, and December 31, 2014 for treatment of all traumatic injuries, were retrieved from the Trauma Registry System. Two-sided Fisher exact or Pearson chi-square tests were used to compare categorical data. The unpaired Student t-test was used to analyze normally distributed continuous data, and the Mann–Whitney U-test was used to compare non-normally distributed data. Propensity-score matching in a 1:1 ratio was performed using NCSS software with logistic regression to evaluate the effect of polytrauma on in-hospital mortality. Results: There was no significant difference in short-term mortality between polytrauma and non-polytrauma patients, regardless of whether the comparison was made among the total patients (11.4% vs. 11.0%, respectively; p = 0.795) or among the selected propensity score-matched groups of patients following controlled covariates including sex, age, systolic blood pressure, co-morbidities, Glasgow Coma Scale scores, injury region based on AIS. Conclusions: Polytrauma defined by AIS ≥3 for at least two body regions failed to recognize a significant difference in short-term mortality among trauma patients. Keywords: Polytrauma, Abbreviated injury scale, Injury severity, Monotrauma, Multiple trauma, Mortality