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SYNOPSIS Extant accounting research based on data from the United States, Europe, and Australia finds that increases in carbon emissions are associated with lower firm value. However, recent research indicates that investor perspectives on corporate social responsibility (CSR) in other parts of the world differ from those of Western investors. This study investigates whether increases in carbon emissions, as one indicator of poor CSR performance, are also associated with a lower firm value in Taiwan. Using carbon disclosure data from Taiwanese-listed companies between 2012 and 2016, we find that firm value is positively associated with carbon emissions, which contrasts with the findings of extant research. Likewise, firm value is not associated with a combined measure of financial information and carbon emissions in Taiwan. Our findings suggest that international generalizations of the findings of the extant research on the relationship between carbon emissions and firm value should be undertaken with caution. JEL Classifications: G32; M4; M48; Q56.

Focused ion beam (FIB) techniques have been frequently used to section metal-halide perovskites for microstructural investigations. However, the ion beams directly irradiated to the sample surface may alter the properties far different from pristine, potentially leading to modified deterioration mechanisms under aging stressors. Here, we combine complementary approaches to measure the subsurface characteristics of polished perovskite and identify the chemical species responsible for the measured properties. Analysis of the experimental results in conjunction with Monte Carlo simulations indicates that atomic displacements and local heating occur in the subsurface of methylammonium lead iodide (MAPbI3) by glazing Ar+ beam irradiation (15 nm by 4 kV at 3 degree). The lead-rich, iodine-deficient surface promotes rapid phase segregation under thermal aging conditions. On the other hand, despite the subsurface modification, our experiments confirm the rest of the MAPbI3 bulk retains the material integrity. Our observation supports that polished perovskites could serve in studying the properties of bulk or buried junctions far away from the altered subsurface with care., Comment: six figures

BackgroundLimited studies have assessed the association of motor vehicle crashes (MVCs) during pregnancy with adverse maternal outcomes using a population-based nationwide dataset that covers all MVCs.MethodsA total of 20 844 births from women who had been involved in MVCs during pregnancy were obtained from the National Birth Notification (BN) Database in Taiwan. We randomly selected 83 274 control births from women in the BN matched on age, gestational age and crash date. All study subjects were linked to medical claims and the Death Registry to identify the maternal outcomes after crashes. Conditional logistic regression models were used to estimate the adjusted odds ratio (aOR) and 95% CI of adverse outcomes associated with MVCs during pregnancy.ResultsPregnant women involved in MVCs had significantly higher risks of placental abruption (aOR=1.51, 95% CI 1.30 to 1.74), prolonged uterine contractions (aOR=1.31, 95% CI 1.11 to 1.53), antepartum haemorrhage (aOR=1.19, 95% CI 1.12 to 1.26) and caesarean delivery (aOR=1.05, 95% CI 1.02 to 1.09) than the controls. Such elevated risks tended to be higher in the MVCs with greater severity. Scooter riders had higher ORs of various adverse maternal outcomes than car drivers.ConclusionsWomen involved in MVCs during pregnancy were at increased risk of various adverse maternal outcomes, especially in those with severe MVCs and riding scooters at MVCs. These findings suggest that clinicians should be aware of these effects, and educational materials that include the above information should be provided as part of prenatal care.

Prostate cancer is one of the most commonly diagnosed malignancies among males worldwide. It has been shown that MMP-7 gene is closely correlated with prostate carcinogenesis. However, the role of the MMP-7 genotypes has been seldom examined among prostate cancer patients. Therefore, the purpose of the study was to evaluate the contribution of MMP-7 promoter genotypes A-181G (rs11568818) and C-153T (rs11568819) to prostate cancer risk in Taiwan.Two hundred and eighteen prostate cancer patients and 436 sex- and age-matched healthy controls were genotyped for MMP-7 rs11568818 and rs11568819 by polymerase chain reaction-restriction fragment length polymorphism and direct sequencing methodologies.The percentages of wild-type AA, and variant AG and GG genotypes on MMP-7 rs11568818 were 85.3, 13.5, and 1.2% among the prostate cancer cases and 87.6, 10.1, and 2.3% among the healthy controls, respectively (p for trend=0.2557). Interestingly, no MMP-7 rs11568819 genotypes were identified among Taiwanese. The allelic frequency distribution also showed that the variant G allele of MMP-7 rs11568818 seemed not to be a determinant of prostate cancer risk (p=0.7977). There was no joint effect between the genotypes of MMP-7 rs11568818 and age and smoking status on prostate cancer risk.rs11568818 and rs11568819 at MMP-7 promoter region, played no role in determining personal susceptibility to prostate cancer in Taiwan.

Bakery products are a must-have food for many people every day. According to the survey, the annual global bakery market exceeds 300 billion US dollars, how to stand out in a highly competitive environment is a business issue for every bakery shop. Whether it is a chain bakery shop or an independent bakery shop, it must face strict selection of customers. The decision of which store to buy for customers may include factors such as product, location, interior decoration, price, service, advertisement, etc. Therefore, how to focus on the most important factor to increase customers' willingness to buy is the only way for bakery shops to win the competition. This research uses the Delphi method to conduct expert surveys. From the four aspects of product, sales, store design and service methods, three rounds of questionnaire are conducted on experts. The results show that the "taste of bakery products" and "appearance (style, size, color) of bakery products" on the product side, the "brightness of the physical storefront" on the store design and the "sales attitude of the service staff" and "whether to provide accumulated reward points", are considered by experts to be the most critical success factors for bakery shops. JEL classification numbers: M10, M30. Keywords: Bakery shop, Critical success factors, Delphi method, Expert survey.

Despite the plausibility that diabetes may increase the risk of motor vehicle crashes (MVCs) due to various diabetes related complications and co-morbidity, findings from epidemiological studies on the relationship between diabetes and MVCs remained inclusive mainly due to heterogeneity in the study design and failure to complete consideration of potential confounders. This study re-visited this putative association with an improved study design.This study employed a controlled before-after study design and included 1,264,280 people aged 18-75 years with T2D newly diagnosed from 2009-2014 and an equal number of age-, sex-, and time-matched controls. The rate ratios (RRs) of vehicle type-specific incidence rates of MVCs in the 1 and 2 years before and after diabetes diagnosis (or the matched dates) were compared between the individuals with type 2 diabetes (T2D) and their matched controls.The rate of MVCs increased slightly among people with T2D over 1 and 2 years following diabetes diagnosis, with RRs of 1.04 (95% confidence interval [CI]=1.02-1.07) and 1.11 (95% CI=1.09-1.13), respectively. These RRs were comparable to those obtained for controls (1.06 and 1.12, respectively). By contrast, the RRs of scooter crashes were significantly higher in the T2D group than in the control group during the 1 year (1.28 vs. 1.08, p 0.001) and 2 years (1.32 vs. 1.08, p 0.001) following diabetes diagnosis.T2D diagnosis was associated with a moderate but significant increase in the risk of MVCs among scooter drivers, but not among car drivers.

Background: Chronic mTORC1 activation in skeletal muscle is linked with age-associated loss of muscle mass and strength, known as sarcopenia. Genetic activation of mTORC1 by conditionally ablating mTORC1 upstream inhibitor TSC1 in skeletal muscle accelerates sarcopenia development in adult mice. Conversely, genetic suppression of mTORC1 downstream effectors of protein synthesis delays sarcopenia in natural aging mice. mTORC1 promotes protein synthesis by activating ribosomal protein S6 kinases (S6Ks) and inhibiting eIF4E-binding proteins (4EBPs). Whole-body knockout of S6K1 or muscle-specific over-expression of a 4EBP1 mutant transgene (4EBP1mt), which is resistant to mTORC1-mediated inhibition, ameliorates muscle loss with age and preserves muscle function by enhancing mitochondria activities, despite both transgenic mice showing retarded muscle growth at a young age. Why repression of mTORC1-mediated protein synthesis can mitigate progressive muscle atrophy and dysfunction with age remains unclear. Methods: Mice with myofiber-specific knockout of TSC1 (TSC1mKO), in which mTORC1 is hyperactivated in fully differentiated myofibers, were used as a mouse model of sarcopenia. To elucidate the role of mTORC1-mediated protein synthesis in regulating muscle mass and physiology, we bred the 4EBP1mt transgene or S6k1 floxed mice into the TSC1mKO mouse background to generate 4EBP1mt-TSC1mKO or S6K1-TSC1mKO mice, respectively. Functional and molecular analyses were performed to assess their role in sarcopenia development. Results: Here, we show that 4EBP1mt-TSC1mKO, but not S6K1-TSC1mKO, preserved muscle mass (36.7% increase compared with TSC1mKO, P

An efficient host immune response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) appears to be crucial for controlling and resolving this viral infection. However, many studies have reported autoimmune characteristics in severe COVID-19 patients. Moreover, clinical observations have revealed that COVID-19-associated acute distress respiratory syndrome shares many features in common with inflammatory myopathy including interstitial lung disease (ILD), most particularly rapidly progressive (RP)-ILD. This study explored this phenomenon by seeking to identify and characterize myositis-specific and related autoantibodies in 25 COVID-19 patients with mild or severe symptoms. Line blot analysis with the EUROLINE Myopathies Ag kit identified 9 (36%) patients with COVID-19 with one or more autoantibodies against several myositis-related antigens (Jo-1, Ku, Mi-2β, PL-7, PL-12, PM-Scl 75, PM-Scl 100, Ro-52, and SRP); no anti-MDA5 antibodies were detected. As the presence of antibodies identified by line blots was unrelated to disease severity, we further characterized the autoantibodies by radioimmunoassay, in which [

Increasing interest in three-dimensional nanostructures adds impetus to electron microscopy techniques capable of imaging at or below the nanoscale in three dimensions. We present a reconstruction algorithm that takes as input a focal series of four-dimensional scanning transmission electron microscopy (4D-STEM) data. We apply the approach to a lead iridate, PbIrO, and yttrium-stabilized zirconia, YZrO, heterostructure from data acquired with the specimen in a single plan-view orientation, with the epitaxial layers stacked along the beam direction. We demonstrate that Pb–Ir atomic columns are visible in the uppermost layers of the reconstructed volume. We compare this approach to the alternative techniques of depth sectioning using differential phase contrast scanning transmission electron microscopy (DPC-STEM) and multislice ptychographic reconstruction.

BACKGROUND AND OBJECTIVE Studies have reported an increased tuberculosis (TB) incidence among patients with end-stage renal disease (ESRD). This nationwide nested Case-control study investigated the risk of active TB due to nosocomial exposure and its correlation with the delay in TB treatment in hemodialysis patients. METHODS Adult (aged ≥20 years) patients with incident ESRD over 2000-2010 were identified from Taiwan National Health Insurance Research Database; 2331 patients with incident active TB (Case) were matched with 11,655 patients without TB (control) by age, sex, year of ESRD onset, Charlson comorbidity index, chronic obstructive pulmonary disease, and diabetes mellitus, at a 1:5 case-to-control ratio. RESULTS Compared with the control group, the Case group had greater nosocomial exposure to index patients with pulmonary TB (2.36 vs. 0.11 month of exposure, p

Historically, African American women have experienced racial disparities in miscarriage, stillbirth, and infant mortality rates. Yet, little attention has been given to stressors that African American women may experience prior to, during, and after experiencing fetal/infant loss. This study provided an opportunity for African American women to describe their lived experiences of stressors prior to, during, and after experiencing each type of fetal/infant loss. Semi-structured interviews were conducted with seven African American women. Each participant experienced miscarriage, stillbirth, and infant mortality and were 18 years of age or older. Recruitment occurred in 2019 in a county in Northeast Ohio and data were analyzed using descriptive coding and thematic analysis. Four themes identified how these African American women navigated stressors prior to, during, and after experiencing each type of fetal/infant loss: (a) social support, (b) grief, (c) internal conflict, and (d) pregnancy, delivery, and death of child. Our findings expand the literature by being an innovative study may bring awareness and influence programs that assist African American women during their experience with fetal/infant loss.

Background Improper endotracheal tube (ETT) positioning is frequently observed and potentially hazardous in the intensive care unit. The authors developed a deep learning–based automatic detection algorithm detecting the ETT tip and carina on portable supine chest radiographs to measure the ETT–carina distance. This study investigated the hypothesis that the algorithm might be more accurate than frontline critical care clinicians in ETT tip detection, carina detection, and ETT–carina distance measurement. Methods A deep learning–based automatic detection algorithm was developed using 1,842 portable supine chest radiographs of 1,842 adult intubated patients, where two board-certified intensivists worked together to annotate the distal ETT end and tracheal bifurcation. The performance of the deep learning–based algorithm was assessed in 4-fold cross-validation (1,842 radiographs), external validation (216 radiographs), and an observer performance test (462 radiographs) involving 11 critical care clinicians. The performance metrics included the errors from the ground truth in ETT tip detection, carina detection, and ETT–carina distance measurement. Results During 4-fold cross-validation and external validation, the median errors (interquartile range) of the algorithm in ETT–carina distance measurement were 3.9 (1.8 to 7.1) mm and 4.2 (1.7 to 7.8) mm, respectively. During the observer performance test, the median errors (interquartile range) of the algorithm were 2.6 (1.6 to 4.8) mm, 3.6 (2.1 to 5.9) mm, and 4.0 (1.7 to 7.2) mm in ETT tip detection, carina detection, and ETT–carina distance measurement, significantly superior to that of 6, 10, and 7 clinicians (all P < 0.05), respectively. The algorithm outperformed 7, 3, and 0, 9, 6, and 4, and 5, 5, and 3 clinicians (all P < 0.005) regarding the proportions of chest radiographs within 5 mm, 10 mm, and 15 mm error in ETT tip detection, carina detection, and ETT–carina distance measurement, respectively. No clinician was significantly more accurate than the algorithm in any comparison. Conclusions A deep learning–based algorithm can match or even outperform frontline critical care clinicians in ETT tip detection, carina detection, and ETT–carina distance measurement. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Introduction: Autologous hematopoietic stem cell transplantation (ASCT) is a well-established treatment for patients with multiple myeloma (MM), and adequate stem cell collection must be assured before ASCT. However, prediction of poor mobilizers (PMs) is still difficult despite several risk factors for mobilization failure having been identified. Methods: We retrospectively analyzed MM patients at Taipei Veterans General Hospital in Taiwan who underwent stem cell collection between October 2006 and August 2020. A CD34+ cell collection of 6 cells/kg was defined as a mobilization failure. The primary endpoint was mobilization failure. The secondary endpoint was overall survival (OS). Odds ratios (ORs) and 95% confidence intervals (CIs) for mobilization failure were calculated using a logistic regression model. The cumulative incidence of mortality was estimated using the Kaplan-Meier method. Results: In the multivariate analysis, absolute monocyte count p = 0.009), platelet count p = 0.001) before mobilization, and time interval from diagnosis to stem cell harvest ≥180 days (adjusted OR 7.69, 95% CI: 1.61–36.87, p = 0.011) were risk factors for PMs. PM patients had poorer OS compared to patients with successful stem cell collection in the univariate analysis (log-rank test p = 0.027). The predicted probability of PMs was estimated by the multiple logistic regression model with a sensitivity of 84.6% and a specificity of 84.0%. Conclusion: Absolute monocyte count

BackgroundSuccessful weaning from mechanical ventilation is important for patients admitted to intensive care units. However, models for predicting real-time weaning outcomes remain inadequate. Therefore, this study aimed to develop a machine-learning model for predicting successful extubation only using time-series ventilator-derived parameters with good accuracy.MethodsPatients with mechanical ventilation admitted to the Yuanlin Christian Hospital in Taiwan between August 2015 and November 2020 were retrospectively included. A dataset with ventilator-derived parameters was obtained before extubation. Recursive feature elimination was applied to select the most important features. Machine-learning models of logistic regression, random forest (RF), and support vector machine were adopted to predict extubation outcomes. In addition, the synthetic minority oversampling technique (SMOTE) was employed to address the data imbalance problem. The area under the receiver operating characteristic (AUC), F1 score, and accuracy, along with the 10-fold cross-validation, were used to evaluate prediction performance.ResultsIn this study, 233 patients were included, of whom 28 (12.0%) failed extubation. The six ventilatory variables per 180 s dataset had optimal feature importance. RF exhibited better performance than the others, with an AUC value of 0.976 (95% confidence interval [CI], 0.975–0.976), accuracy of 94.0% (95% CI, 93.8–94.3%), and an F1 score of 95.8% (95% CI, 95.7–96.0%). The difference in performance between the RF and the original and SMOTE datasets was small.ConclusionThe RF model demonstrated a good performance in predicting successful extubation in mechanically ventilated patients. This algorithm made a precise real-time extubation outcome prediction for patients at different time points.

Despite recent advances in understanding the pathophysiology of cancer cachexia, prevention/treatment of this debilitating disease remains an unmet medical need.We developed an integrated, multi-tiered strategy involving both in vitro and in vivo muscle atrophy platforms to identify traditional Chinese medicine (TCM)-based anti-cachectic agents. In the initial screening, we used inflammatory cytokine-induced atrophy of C2C12 myotubes as a phenotypic screening platform to assess the protective effects of TCMs. The selected TCMs were then evaluated for their abilities to protect Caenorhabditis elegans from age-related reduction of mobility and contractility, followed by the C-26 colon adenocarcinoma mouse model of cachexia to confirm the anti-muscle atrophy effects (body/skeletal muscle weights, fibre size distribution, grip strengths, and serum IL-6). Transcriptome analysis, quantitative real-time polymerase chain reaction, and immunoblotting were performed to gain understanding of the potential mechanism(s) by which effective TCM protected against C26 tumour-induced muscle atrophy.Of 29 widely used TCMs, Dioscorea radix (DR) and Mu Dan Pi (MDP) showed a complete protection (all P values, 0.0002) vis-à-vis C26 conditioned medium control in the myotube atrophy platform. MDP exhibited a unique ability to ameliorate age-associated decreases in worm mobility, accompanied by improved total body contractions, relative to control (P 0.0001 and0.01, respectively), which, however, was not noted with DR. This differential in vivo protective effect between MDP and DR was also confirmed in the C-26 mouse model. MDP at 1000 mg/kg (MDP-H) was effective in protecting body weight loss (P 0.05) in C-26 tumour-bearing mice without changing food or water intake, accompanied by the restoration of the fibre size distribution of hindleg skeletal muscles (P 0.0001) and the forelimb grip strength (P 0.05). MDP-treated C-26-tumour-bearing mice were alert, showed normal posture and better body conditions, and exhibited lower serum IL-6 levels (P = 0.06) relative to vehicle control. This decreased serum IL-6 was associated with the in vitro suppressive effect of MDP (25 and 50 μg/mL) on IL-6 secretion into culture medium by C26 cells. RNA-seq analysis, followed by quantitative real-time polymerase chain reaction and/or immunoblotting, shows that MDP's anti-cachectic effect was attributable to its ability to reverse the C-26 tumour-induced re-programming of muscle homoeostasis-associated gene expression, including that of two cachexia drivers (MuRF1 and Atrogin-1), in skeletal muscles.All these findings suggest the translational potential of MDP to foster new strategies for the prevention and/or treatment of cachexia. The protective effect of MDP on other types of muscle atrophy such as sarcopenia might warrant investigations.

Cardiogenic shock (CS) often occurs in patients suffering from rapidly progressing end-stage heart failure or acute myocardial infarction. Mechanical circulatory support may be used for patients who do not respond to medication or revascularization to stabilize hemodynamics. Extracorporeal ventricular assist device (Extra-VAD) has been reported to be successful for patients with cardiogenic shock. This study aimed to evaluate the 30-day in-vivo performance and safety of a newly developed Extra-VAD with maglev centrifugal pump technology, MoyoAssist®.The study was conducted with 6 healthy ovine models, weighing 43.2 ~ 59.6 kg. Cannulation was performed with a 34 Fr venous cannula surgically connected to the left arterial appendage and a 24 Fr arterial cannula inserted into descending aorta. The pump flow rate was maintained at 2 ~ 3 L/min to provide sufficient cardiac support without suction. Activated clotting time was maintained within the range of 150 ~ 250 s.No device-related adverse events occurred throughout the study. Plasma-free hemoglobin results were within the acceptable range of ventricular assist device therapy (40 mg/dl). MGS01 had an anticoagulation management related bleeding event and was terminated on day 29. All other sheep's biochemical test results were stable. The autopsy showed no embolism or thrombus formation and no end-organ damage.This study demonstrated that the MoyoAssist® Extra-VAD is able to provide cardiac support effectively and safely and may provide a new alternative choice for patients with CS in China.

RTL1/PEG11, which has been associated with anxiety disorders, is a retrotransposon-derived imprinted gene in the placenta. However, imprinting patterns and functions of RTL1 in the brain have not been well-investigated. We found Rtl1 was paternally, but not maternally, expressed in brain stem, thalamus, and hypothalamus of mice, and imprinting status of RTL1 was maintained in human brain. Paternal Rtl1 knockout (Rtl1m+/p-) mice had higher neonatal death rates due to impaired suckling, and low body weights beginning on embryonic day 16.5. High paternal expression of Rtl1 was detected in the locus coeruleus (LC) and Rtl1m+/p- mice showed an increased delay in time of onset for action potentials and inward currents with decreased neuronal excitability of LC neurons. Importantly, Rtl1m+/p- mice exhibited behaviors associated with anxiety, depression, fear-related learning and memory, social dominance, and low locomotor activity. Taken together, our findings demonstrate RTL1 is imprinted in brain, mediates emotional and social behaviors, and regulates excitability in LC neurons.

In this study, the duration of high-pressure processing (HPP) required to achieve a 5 log reduction of Escherichia coli O157:H7 in fruit purees was evaluated. Banana, cantaloupe, and dragon fruit purees were subjected to HPP at 600 MPa for 300, 270, and 270 s, respectively, and their physicochemical properties and enzyme activities were then analysed. Diabetic mice were fed fresh and HPP-treated purees to observe their effects on the glycemic index (GI) and postprandial blood glucose response.Compared with their fresh counterparts, the HPP-treated banana and dragon fruit purees exhibited significantly higher viscosities, lower glucose concentrations, and higher glucose dialysis retardation indices and showed disrupted sucrose invertase and polygalacturonase activities. The GI and postprandial blood glucose response were not significantly different between the fresh and HPP-treated cantaloupe purees. By contrast, the peak time of glucose response (THPP can change the physicochemical properties of fruit purees, resulting in stabilized blood glucose levels and lower GIs after consumption. Therefore, purees processed in this manner would benefit consumers and patients with diabetes/pre-diabetes who need to maintain stable blood glucose levels (Fig. S1). © 2022 Society of Chemical Industry.

The critical size limit of voltage-switchable electric dipoles has extensive implications for energy-efficient electronics, underlying the importance of ferroelectric order stabilized at reduced dimensionality. We report on the thickness-dependent antiferroelectric-to-ferroelectric phase transition in zirconium dioxide (ZrO 2 ) thin films on silicon. The emergent ferroelectricity and hysteretic polarization switching in ultrathin ZrO 2 , conventionally a paraelectric material, notably persists down to a film thickness of 5 angstroms, the fluorite-structure unit-cell size. This approach to exploit three-dimensional centrosymmetric materials deposited down to the two-dimensional thickness limit, particularly within this model fluorite-structure system that possesses unconventional ferroelectric size effects, offers substantial promise for electronics, demonstrated by proof-of-principle atomic-scale nonvolatile ferroelectric memory on silicon. Additionally, it is also indicative of hidden electronic phenomena that are achievable across a wide class of simple binary materials.

Dietary restriction (DR) is known to promote autophagy to exert its longevity effect. While SAMS-1 (S-adenosyl methionine synthetase-1) has been shown to be a key mediator of the DR response, little is known about the roles of S-adenosyl methionine (SAM) and SAM-dependent methyltransferase in autophagy and DR-induced longevity. In this study, we show that DR and SAMS-1 repress the activity of SET-2, a histone H3K4 methyltransferase, by limiting the availability of SAM. Consequently, the reduced H3K4me3 levels promote the expression and activity of two transcription factors, HLH-30/TFEB and PHA-4/FOXA, which both regulate the transcription of autophagy-related genes. We then find that HLH-30/TFEB and PHA-4/FOXA act collaboratively on their common target genes to mediate the transcriptional response of autophagy-related genes and consequently the lifespan of the animals. Our study thus shows that the SAMS-1-SET-2 axis serves as a nutrient-sensing module to epigenetically coordinate the activation of HLH-30/TFEB and PHA-4/FOXA transcription factors to control macroautophagy/autophagy and longevity in response to DR. Abbreviations: ChIP: chromatin immunoprecipitation; ChIP-seq: chromatin immuno precipitation-sequencing; COMPASS: complex of proteins associated with Set1; DR: dietary restriction; GO: gene ontology; SAM: S-adenosyl methionine; SAMS-1: S-adenosyl methionine synthetase-1; TSS: transcription start site; WT: wild-type.

With the scaling of lateral dimensions in advanced transistors, an increased gate capacitance is desirable both to retain the control of the gate electrode over the channel and to reduce the operating voltage1. This led to a fundamental changein the gate stack in 2008,the incorporation of high-dielectric-constant HfO2(ref.2), which remains the material of choiceto date. Here we report HfO2-ZrO2 superlattice heterostructures as a gate stack, stabilized with mixed ferroelectric-antiferroelectric order, directly integrated onto Si transistors, and scaled down to approximately 20 ångströms, the same gate oxide thickness required for high-performance transistors. The overall equivalent oxide thickness in metal-oxide-semiconductor capacitors is equivalent to an effective SiO2 thickness of approximately 6.5 ångströms. Such a low effective oxide thickness and the resulting large capacitance cannot be achieved in conventional HfO2-based high-dielectric-constant gate stacks without scavenging the interfacial SiO2, which has adverse effects on the electron transport and gate leakage current3. Accordingly, our gate stacks, which do not require such scavenging, provide substantially lower leakage current and no mobility degradation. This work demonstrates that ultrathin ferroic HfO2-ZrO2 multilayers, stabilized with competing ferroelectric-antiferroelectric order in the two-nanometre-thickness regime, provide a path towards advanced gate oxide stacks in electronic devices beyond conventional HfO2-based high-dielectric-constant materials.

Androgen deprivation therapy (ADT) is the major treatment for metastatic prostate cancer (PCa), but few studies have investigated the effects of ADT on thyroid diseases.This population-based, nationwide cohort study utilized the Taiwan National Health Insurance Research Database (NHIRD) with 17,192 PCa patients between 1997 and 2013. We used the Cox proportional hazards models and propensity score-matched analysis to analyze the association between ADT and the development of thyroid diseases.A total of 17,192 newly diagnosed men with PCa were selected from the NHIRD. There were 6200 ADT users and 6200 non-ADT users after 1:1 propensity score matching. There was a significantly decreased risk of thyroid diseases among ADT users compared with non-ADT users (adjusted hazard ratio (aHR): 0.79, 95% confidence interval (CI): 0.65-0.95, p 0.001). Further analysis showed a significantly decreased risk of thyroid diseases with increasing ADT duration (p 0.001).The result showed that ADT use in men with PCa was associated with a decreased risk of thyroid disease development.

Agricultural exports are an important source of economic profit for many countries. Accurate predictions of a country's agricultural exports month on month are key to understanding a country's domestic use and export figures and facilitate advance planning of export, import, and domestic use figures and the resulting necessary adjustments of production and marketing. This study proposes a novel method for predicting the rise and fall of agricultural exports, called agricultural exports time series-long short-term memory (AETS-LSTM). The method applies Jieba word segmentation and Word2Vec to train word vectors and uses TF-IDF and word cloud to learn news-related keywords and finally obtain keyword vectors. This research explores whether the purchasing managers' index (PMI) of each industry can effectively use the AETS-LSTM model to predict the rise and fall of agricultural exports. Research results show that the inclusion of keyword vectors in the PMI values of the finance and insurance industries has a relative impact on the prediction of the rise and fall of agricultural exports, which can improve the prediction accuracy for the rise and fall of agricultural exports by 82.61%. The proposed method achieves improved prediction ability for the chemical/biological/medical, transportation equipment, wholesale, finance and insurance, food and textiles, basic materials, education/professional, science/technical, information/communications/broadcasting, transportation and storage, retail, and electrical and machinery equipment categories, while its performance for the electrical and optical categories shows improved prediction by combining keyword vectors, and its accuracy for the accommodation and food service, and construction and real estate industries remained unchanged. Therefore, the proposed method offers improved prediction capacity for agricultural exports month on month, allowing agribusiness operators and policy makers to evaluate and adjust domestic and foreign production and sales.

Okara is a by-product of tofu or soymilk production processes. The disposal of huge quantities of okara is a significant issue. Based on previous reports, protein hydrolysis can release excess free amino acids and small peptides from okara and exhibit anti-fatigue function. We aimed to investigate the anti-fatigue effect of okara protein hydrolysate (OPH)

Purpose This study aims to analyze why listed Taiwanese firms uniquely rejected the early adoption of International Financial Reporting Standards (IFRS) in 2012. It investigates the underlying decision-making processes behind this policy reluctance to further understand the continuous phenomenon of rare voluntary IFRS adoption. Design/methodology/approach It reports on fieldwork evidence obtained in situ by in-depth interviewing in Mandarin. It uses qualitative methods, complemented by quantitative cost-benefit metrics of IFRS adoption. It presents five diverse illustrative case-study vignettes, using a judgment sample based on expert opinion. Findings While the net-benefits of implementing IFRS varied across firms, this study’s unanimous finding was that no firms (in the sample or population) adopted IFRS early, despite stated intentions to the contrary. The key reasons for shunning early IFRS adoption were found to be frequent changes in regulations, insufficient benefits from adopting IFRS and the undermining of comparability across companies, compounded with scarce preparation time. Further, this study found that the Taiwanese accounting regulator’s reluctance toward IFRS adoption, partly caused by a long-standing US influence, contributed to this anomalous outcome. Practical implications This study recommends two critical policy changes: more realistic timelines and less frequent regulatory changes. Originality/value To the best of the authors’ knowledge, this is the first study to investigate the reasons behind the anomaly of no early adoption of IFRS in Taiwan, using new primary data and illustrative case studies. Its novelty lies in extending understanding beyond the existing quantitative literature on accounting standards, using new “thick” qualitative evidence on motives for such choices and decision-making processes, which have been neglected in previous work.

Background The T790M mutation is the major resistance mechanism to first- and second-generation TKIs in EGFR-mutant NSCLC. This study aimed to investigate the utility of droplet digital PCR (ddPCR) for detection of T790M in plasma circulating tumor DNA (ctDNA), and explore its impact on prognosis. Methods This prospective study enrolled 80 advanced lung adenocarcinoma patients treated with gefitinib, erlotinib, or afatinib for TKI-sensitizing mutations between 2015 and 2019. Plasma samples were collected before TKI therapy and at tri-monthly intervals thereafter. Genotyping of ctDNA for T790M was performed using a ddPCR EGFR Mutation Assay. Patients were followed up until the date of death or to the end of 2021. Results Seventy-five of 80 patients experienced progressive disease. Fifty-three (71%) of 75 patients underwent rebiopsy, and T790M mutation was identified in 53% (28/53) of samples. Meanwhile, plasma ddPCR detected T790M mutation in 23 (43%) of 53 patients. The concordance rate of T790M between ddPCR and rebiopsy was 76%, and ddPCR identified 4 additional T790M-positive patients. Ten (45%) of 22 patients who did not receive rebiopsy tested positive for T790M by ddPCR. Serial ddPCR analysis showed the time interval from detection of plasma T790M to objective progression was 1.1 (0–4.1) months. Compared to 28 patients with rebiopsy showing T790M, the overall survival of 14 patients with T790M detected solely by ddPCR was shorter(41.3 [95% CI, 36.6–46.0] vs. 26.6 months [95% CI, 9.9–43.3], respectively). Conclusion Plasma ddPCR-based genotyping is a useful technology for detection and monitoring of the key actionable genomic alteration, namely, T790M, in patients treated with gefitinib, erlotinib, or afatinib for activating mutations, to achieve better patient care and outcome.

Chirality or handedness of a material can be used as an order parameter to uncover emergent electronic properties for quantum information science. Conventionally, chirality is found in naturally occurring biomolecules and magnetic materials. Chirality can be engineered in a topological polar vortex ferroelectric/dielectric system via atomic-scale symmetry-breaking operations. We use four-dimensional scanning transmission electron microscopy (4D-STEM) to map out topology-driven three-dimensional domain walls, where the handedness of two neighbor topological domains change or remain the same. The nature of the domain walls is governed by the interplay of local perpendicular (lateral) and parallel (axial) polarization with respect to the tubular vortex structures. Unique symmetry-breaking operations and the finite nature of domain walls results in a triple point at the junction of chiral and achiral domain walls. The unconventional nature of the domain walls with triple point pairs may result in unique electrostatic and magnetic properties potentially useful for quantum sensing applications.

BackgroundAccording to a report from the World Health Organization, traumatic brain injury (TBI) will surpass many diseases by 2020 and become the main cause of death and disability. It is estimated that 10 million people are affected by TBI every year, and the burden of death and morbidity disease is imposed on society, making TBI urgent public health and medical problem (Hyder et al., 2007).In Taiwan, for every 100,000 emergency patients, there are 333 patients with traumatic brain injury, and the predominant group is 15-24 years old, and the mortality rate is 9 per 10,000.The survivors caused a lot of troubles in life because of the remaining obstacles, especially health and socio-economic problems (Wang et al., 2012).Therefore, post-acute care (PAC) is immediately given active integrated care during the golden period of post-acute care to restore its function, which will reduce the medical expenses of subsequent rehospitalization and reduce the burden of family and social care.ObjectiveThe purpose of this study was to exploring the effectiveness of post -acute care for the patients with traumatic brain injury.MethodsThis is a retrospective cohort study that enrolled 168 patients over 18 years of age (inclusive) about before and after PAC. The differences between the before and after receiving PAC were collected about the Barthel Index (ADL), Lawton-Brody IADL Scale (IADL), and EuroQoL-5D(EQ-5D) by using purposive sampling. The Statistics SPSS 25.0 package software was used to test the Paired Samples t-test, Pearson correlation coefficient, Chi-square Test for statistical analysis.ResultsThe results showed that this study predicts that the functional recovery of patients with traumatic brain injury receiving PAC treatment will be effective. The optimal length of hospitalization for rehabilitation was predicted by the Barthel Index(ADL), Lawton-Brody IADL Scale (IADL), and EuroQoL-5D(EQ-5D).ConclusionThe results of this study can confirm that PAC has important effects. This result can be used as a reference for national planning health policies and cross-disciplinary professional design cases and family PAC intervention plans, in order to restore activity functions as soon as possible, improve the quality of life, and reduce the burden of family and social care.

Dielectric electrostatic capacitors, due to their ultrafast charge-discharge capability, are attractive for high power energy storage applications. Along with ultrafast operation, on-chip integration can enable miniaturized energy storage devices for emerging autonomous microelectronics and microsystems. Additionally, state-of-the-art electrochemical miniaturized energy storage systems – microsupercapacitors and microbatteries – currently face safety, packaging, materials, and microfabrication challenges preventing on-chip technological readiness, leaving an opportunity for electrostatic microcapacitors. Here we report record-high energy storage density (ESD) and power density (PD) across all electrostatic systems in HfO2-ZrO2 (HZO)-based thin film microcapacitors integrated directly on silicon, through a three-pronged approach. First, to increase intrinsic energy storage, atomic-layer-deposited antiferroelectric HZO films are engineered near a field-driven ferroelectric phase transition to exhibit amplified charge storage via the negative capacitance (NC) effect, which enhances volumetric-ESD beyond the best-known back-end-of-the-line (BEOL) compatible dielectrics (115 J-cm−3). Second, to increase overall stored energy, superlattice engineering of amorphous-templated HZO-Al2O3 heterostructures scales-up the high-storage antiferroelectric-NC behavior to the 100 nm regime, which overcomes the conventional thickness limitations of HZO-based (anti)ferroelectricity (10-nm regime). Third, to increase storage-per-footprint, the superlattices are conformally integrated into three-dimensional (3D) capacitors, which boosts areal-ESD (areal-PD) 9-times (170-times) the best known 3D electrostatic capacitors: 80 mJ-cm−2 (300 kW-cm−2). This simultaneous demonstration of ultrahigh ESD and PD overcomes the traditional capacity-speed trade-off across the electrostatic-electrochemical energy storage hierarchy. Furthermore, integration of ultrahigh-density and ultrafast charging thin films within a BEOL-compatible process enables monolithic integration of on-chip microsupercapacitors, which opens the door for substantial energy storage and power delivery for electronic microsystems.

IntroductionMechanical circulatory support (MCS) can help to maintain hemodynamic stability, improve cardiac function, reduce cardiac load, and is an important method for the treatment of advanced heart failure. However, traditional MCS systems [IABP, Impella, TandemHerat, veno-arterial extracorporeal membrane oxygenation (VA-ECMO)] are associated with limitations including trauma, a high rate of complications (hemolysis, bleeding) and require complex care from nurses.Case summaryWe report a case of left heart failure resulting from dilated cardiomyopathy in a 24 years-old man. A catheter was placed through the right jugular vein and a drainage tube was positioned under ultrasound guidance through the superior vena cava, right atrium, atrial septum, to the left atrium, and returned to the axillary artery using an extracorporeal magnetic levitation ventricular assist device (VAD). The patient was successfully supported for 10 days and bridged to heart transplant.DiscussionTo the best of our knowledge, this is the first report of the use of an extracorporeal magnetic levitation VAD for MCS via a percutaneous approach. Our findings support the wider use of this strategy for patients awaiting myocardial recovery or who require heart bridging or transplantation.

Caenorhabditis elegans (C. elegans) is a popular and excellent model for studies of aging due to its short lifespan. Methods for precisely measuring the physiological age of C. elegans are critically needed, especially for antiaging drug screening and genetic screening studies. The effects of various antiaging interventions on the rate of aging in the early stage of the aging process can be determined based on the quantification of physiological age. However, in general, the age of C. elegans is evaluated via human visual inspection of morphological changes based on personal experience and subjective judgment. For example, the rate of motor activity decay has been used to predict lifespan in early- to mid-stage aging. Using image processing, the physiological age of C. elegans can be measured and then classified into periods or classes from childhood to elderhood (e.g., 3 periods comprising days 0-2, 4-6 and 10-12) by using texture entropy (Shamir, L. et al., 2009). Our dataset consists of 913 microscopic images of C. elegans, with approximately 60 images per day from day 1 to day 14 of adulthood. We present quantitative methods to measure the physiological age of C. elegans with convolution neural networks (CNNs), which can measure age with a granularity of days rather than periods. The methods achieved a mean absolute error (MAE) of less than 1 day for the measured age of C. elegans. In our experiments, we found that after training and testing our dataset, 5 popular CNN models, 50-layer residual network (ResNet50), InceptionV3, InceptionResNetV2, 16-layer Visual Geometry Group network (VGG16) and MobileNet, measured the physiological age of C. elegans with an average testing MAE of 1.58 days. Furthermore, based on the results, we propose two models, one model for linear regression analysis and the other model for logistic regression, that combine a CNN model and a new attribute: curved_or_straight. The linear regression analysis model achieved a test MAE of 0.94 days; the logistic regression model achieved an accuracy of 84.78 percent with an error tolerance of 1 day.

Tissue-resident macrophages are essential to protect from pathogen invasion and maintain organ homeostasis. The ability of thymic macrophages to engulf apoptotic thymocytes is well appreciated, but little is known about their ontogeny, maintenance, and diversity. Here, we characterized the surface phenotype and transcriptional profile of these cells and defined their expression signature. Thymic macrophages were most closely related to spleen red pulp macrophages and Kupffer cells and shared the expression of the transcription factor SpiC with these cells. Single-cell RNA sequencing showed that the macrophages in the adult thymus are composed of two populations distinguished by the expression ofTimd4andCx3cr1. Remarkably,Timd4+cells were located in the cortex, whileCx3cr1+macrophages were restricted to the medulla and the cortico-medullary junction. Using shield chimeras, transplantation of embryonic thymuses, and genetic fate mapping, we found that the two populations have distinct origins.Timd4+thymic macrophages are of embryonic origin, whileCx3cr1+macrophages are derived from adult hematopoietic stem cells. Aging has a profound effect on the macrophages in the thymus.Timd4+cells underwent gradual attrition, whileCx3cr1+cells slowly accumulated with age and, in older mice, were the dominant macrophage population in the thymus. Altogether, our work defines the phenotype, origin, and diversity of thymic macrophages.

Stroke is the third largest cause of death both worldwide and in Taiwan. Among the various stroke subtypes, lacunae strokes account for 20 to 30% of the total stroke population. Through vigorous risk control factors, the effective prevention and the long-term functional outcome remains are yet to be investigated. Carotid duplex is a non-invasive neuroimaging modality that is routinely applied to stroke patients. In the current research, we correlate baseline carotid duplex examination parameters with functional outcome assessment in an attempt to ascertain important variables for early outcome prediction.We retrospectively recruited lacunae ischemic stroke patients from the Department of Neurology, Changhua Christian Hospital. Patient baseline demographics, biochemistry, neuroimaging, and outcome assessments were thoroughly evaluated via a modified Rankin Scale (mRS), NIHSS, and Barthel index scores, both prior and subsequent to patient discharge for a period of up to one year. Patients were divided into two groups based on their functional recovery status. This current study utilizes the Kaplan-Meier method to draw the survival curve and adopts the Cox proportional hazards model to estimate the hazard ratio between the two groups. The risk modeling method is also applied to formulate the best fit in seeking and identifying the variables, which has the most impact on determining theoutcome predictor. All statistical analyses were performed using R for Windows (version 3.6.3), withOne hundred forty-one ischemic lacunae stroke patients are included in the study, of which the follow-ups of 69 patients showed no physical functionality improvement, whereas 72 patients demonstrated favorable functional outcomes. In terms of underlying diseases, more than 80% of the patients suffered from hyperlipidemia upon hospitalization and more than 40% of the patients suffered from diabetes mellitus and heart disease. There was a significant difference in pulmonary disease between improvement and non-improvement in disability (1.4% vs 10.1%,In the current study, the most suitable length of stay in hospital for lacunae stroke patients to fully recuperate is ten days. Additionally, CCA EDV might be the key determinant, with baseline diabetes mellitus acting in a medium role, capable of altering long-term outcome functionality and recovery.

Hyperuricemia (HC) was one of the important risk factors for gout, arteriosclerosis, and cardiovascular disease. Animal studies have shown that Lactobacillus plantarum can improve the microbiota, immune regulation, and inhibit the uric acid production. However, it was not clear whether L. plantarum can improve HC and intestinal microbiota. We used potassium oxonate (PO) to induce HC in male SD rats, and then treated L. plantarum TCI227 in a dose dependent (HC+LD, HC+MD, HC+HD) for 4 weeks, and examined weight organs, biochemical examination of blood and urine, and analyzed the intestinal microbiota in feces by 16s rDNA sequence analysis. In this study, TCI227 improved body weight, decreased creatinine, serum uric acid, and increased urine uric acid compared to the HC group. Furthermore, TCI227 increased short-chain fatty acids (SCFAs). In fecal microbiota (family), TCI227 increased the level of Lactobacillaceae, and then decreased the level of Deferribacteres and Prevotellaceae compared to the HC group. Finally, in fecal microbiota (genus), TCI227 decreased the level of Prevotella, and then increased the level of Lactobacillus and Ruminococcus compared to the HC group. This study suggested that TCI227 can improve HC and change the compositions of the intestinal microbiota in PO induced male HC SD rats.

To explore the complex genetic architecture of common diseases and traits, we conducted comprehensive PheWAS of ten diseases and 34 quantitative traits in the community-based Taiwan Biobank (TWB). We identified 995 significantly associated loci with 135 novel loci specific to Taiwanese population. Further analyses highlighted the genetic pleiotropy of loci related to complex disease and associated quantitative traits. Extensive analysis on glycaemic phenotypes (T2D, fasting glucose and HbA1c) was performed and identified 115 significant loci with four novel genetic variants (HACL1, RAD21, ASH1L and GAK). Transcriptomics data also strengthen the relevancy of the findings to metabolic disorders, thus contributing to better understanding of pathogenesis. In addition, genetic risk scores are constructed and validated for absolute risks prediction of T2D in Taiwanese population. In conclusion, our data-driven approach without a priori hypothesis is useful for novel gene discovery and validation on top of disease risk prediction for unique non-European population.

Nanobeam electron diffraction can probe local structural properties of complex crystalline materials including phase, orientation, tilt, strain, and polarization. Ideally, each diffraction pattern from a projected area of a few unit cells would produce clear a Bragg diffraction pattern, where the reciprocal lattice vectors can be measured from the spacing of the diffracted spots, and the spot intensities are equal to the square of the structure factor amplitudes. However, many samples are too thick for this simple interpretation of their diffraction patterns, as multiple scattering of the electron beam can produce a highly nonlinear relationship between the spot intensities and the underlying structure. Here, we develop a stacked Bloch wave method to model the diffracted intensities from thick samples with structure that varies along the electron beam. Our method reduces the large parameter space of electron scattering to just a few structural variables per probe position, making it fast enough to apply to very large fields of view. We apply our method to SrTiO$_3$/PbTiO$_3$/SrTiO$_3$ multilayer samples, and successfully disentangle specimen tilt from the mean polarization of the PbTiO$_3$ layers. We elucidate the structure of complex vortex topologies in the PbTiO$_3$ layers, demonstrating the promise of our method to extract material properties from thick samples.

Purpose Helicobacter pylori (H. pylori) is a major risk factor for gastric cancer and may affect androgen activity in men. The association between H. pylori and androgen deprivation therapy (ADT) in patients with prostate cancer (PCa) remains unclear. Methods This retrospective cohort study linked National Health Insurance (NHI) data to Taiwan Cancer Registry (TCR) and Taiwan Death Registry (TDR) between 1995 and 2016. PCa patients who received ADT were classified into H. pylori infection and non‐H. pylori infection groups. The outcomes were overall mortality, prostate cancer‐specific mortality, and castration‐resistant prostate cancer (CRPC). Propensity score matching was adopted for the primary analysis and inverse probability of treatment weighting (IPTW) was used for the sensitivity analysis. Results Of the 62,014 selected PCa patients, 23,701 received ADT, of whom 3516 had H. pylori infections and 20,185 did not. After matching, there were 3022 patients in the H. pylori infection group and 6044 patients in the non‐H. pylori infection group. The mean follow‐up period for the matched cohort was 4.8 years. Compared to the non‐H. pylori group, the H. pylori group was significantly associated with decreased risks of all‐cause mortality (hazard ratio [HR] 0.90; 95% confidence interval [CI] 0.84–0.96) and prostate cancer‐specific mortality (HR 0.88; 95% CI 0.81–0.95) in the matched analysis. Conclusions H. pylori infection was associated with a reduced risk of mortality in PCa patients receiving ADT.

Heart failure is a major health risk, and with limited availability of donor organs, there is an increasing need for developing cardiac assist devices (CADs). Mock circulatory loops (MCL) are an important in-vitro test platform for CAD’s performance assessment and optimisation. The MCL is a lumped parameter model constructed out of hydraulic and mechanical components aiming to simulate the native cardiovascular system (CVS) as closely as possible. Further development merged MCLs and numerical circulatory models to improve flexibility and accuracy of the system; commonly known as hybrid MCLs. A total of 128 MCLs were identified in a literature research until 25 September 2020. It was found that the complexity of the MCLs rose over the years, recent MCLs are not only capable of mimicking the healthy and pathological conditions, but also implemented cerebral, renal and coronary circulations and autoregulatory responses. Moreover, the development of anatomical models made flow visualisation studies possible. Mechanical MCLs showed excellent controllability and repeatability, however, often the CVS was overly simplified or lacked autoregulatory responses. In numerical MCLs the CVS is represented with a higher order of lumped parameters compared to mechanical test rigs, however, complex physiological aspects are often simplified. In hybrid MCLs complex physiological aspects are implemented in the hydraulic part of the system, whilst the numerical model represents parts of the CVS that are too difficult to represent by mechanical components per se. This review aims to describe the advances, limitations and future directions of the three types of MCLs.