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Phrase-indexed question answering (PIQA) seeks to improve the inference speed of question answering (QA) models by enforcing complete independence of the document encoder from the question encoder, and it shows that the constrained model can achieve significant efficiency at the cost of its accuracy. In this paper, we aim to build a model under the PIQA constraint while reducing its accuracy gap with the unconstrained QA models. We propose a novel framework—AnsDR, which consists of an answer boundary detector (AnsD) and an answer candidate ranker (AnsR). More specifically, AnsD is a QA model under the PIQA architecture and it is designed to identify the rough answer boundaries; and AnsR is a lightweight ranking model to finely re-rank the potential candidates without losing the efficiency. We perform the extensive experiments on public datasets. The experimental results show that the proposed method achieves the state of the art on the PIQA task.

PURPOSE Impaired neurocognitive function (NCF) is extremely common in patients with higher grade primary brain tumor. We previously reported evidence of genetic variants associated with NCF in glioma patients prior to treatment. However, little is known about the effect of genetic variants on NCF decline after adjuvant therapy. METHODS Patients (N = 102) completed longitudinal NCF assessments that included measures of verbal memory, processing speed, and executive function. Testing was conducted in the postoperative period with an average follow up interval of 1.3 years. We examined polymorphisms in 580 genes related to five pathways (inflammation, DNA repair, metabolism, cognitive, and telomerase). RESULTS Five polymorphisms were associated with longitudinal changes in processing speed and 14 polymorphisms with executive function. Change in processing speed was strongly associated with MCPH1 rs17631450 (P = 2.2 × 10-7) and CCDC26 rs7005206 (P = 9.3 × 10-7) in the telomerase pathway; while change in executive function was more strongly associated with FANCF rs1514084 (P = 2.9 × 10-6) in the DNA repair pathway and DAOA rs12428572 (P = 2.4 × 10-5) in the cognitive pathway. Joint effect analysis found significant genetic-dosage effects for longitudinal changes in processing speed (Ptrend = 1.5 × 10-10) and executive function (Ptrend = 2.1 × 10-11). In multivariable analyses, predictors of NCF decline included progressive disease, lower baseline NCF performance, and more at-risk genetic variants, after adjusting for age, sex, education, tumor location, histology, and disease progression. CONCLUSION Our longitudinal analyses revealed that polymorphisms in telomerase, DNA repair, and cognitive pathways are independent predictors of decline in NCF in glioma patients.

In this work, a fully integrated phased array using multi‐layer printed circuit board (PCB) fabrication technologies is presented. This array is directly fed by 50 Ω coaxial cables, without balanced‐to‐unbalanced transitions. An asymmetric dipole is used to achieve stable input impedance. Furthermore, to broaden the operating bandwidth, a coupling patch is designed beneath the asymmetric dipole , which also eliminates the common‐mode resonance and decreases the array profile. In addition, three wide‐angle impedance matching (WAIM) layers with different structures are utilised to improve the scan range in all scanning planes. Infinite array simulations indicate that the proposed array can operate over a 5.1:1 bandwidth (2.4 ∼ 12.2 GHz) with an active voltage standing wave ratio below 3 while scanning up to ± 60° in H plane and ±75° in the E plane. Furthermore, the proposed antenna, whose cross‐polarization levels remain below −35 and −7.5 dB when scanning up to 75° in the E plane and 60° in the D plane, demonstrates the merits of high polarization purity. Array simulations are verified by the measurements of a 12 × 12 prototype, and good agreement is observed.

Emerging evidence suggests that elevated concentrations of triglyceride-rich lipoprotein remnants (TRLs) derived from hepatic and intestinal sources contribute to the risk of atherosclerotic cardiovascular events. Natural selection studies support a causal role for elevated concentrations of remnant cholesterol and the pathways contributing to perturbations in metabolic pathways regulating TRLs with an increased risk of atherosclerotic cardiovascular disease events. New therapies targeting select catalytic pathways in TRL metabolism reduce atherosclerosis in experimental models, and concentrations of TRLs in patients with a vast range of triglyceride levels. Clinical trials with inhibitors of angiopoietin-like 3 protein and apolipoprotein C-III will be required to provide further guidance on the potential contribution of these emerging therapies in the paradigm of cardiovascular risk management in patients with elevated remnant cholesterol.

In recent years, the motion capture system has received a lot of attention because of its wide application, such as movie animation, sport and medical applications. In the field of rehabilitation, motion capture systems are often used to collect the motion information of the patient when he/she is performing rehabilitation tasks. It can be used to quantify the patient’s rehabilitation effectiveness and provide the physician with more objective data as a reference. Using inertial sensors is one of motion capture methods. However, the major challenge to reconstruct accurate human posture with sensor measurements are signal noise, bias and inaccurate gyroscope estimation during long-term wearing. Based on the reason mentioned above, this paper proposes a graph convolutional network (GCN)-based deep learning architecture that uses effective information collected by inertial sensors to predict a sequence of position of each joint of a human’s lower limbs in the 3D space throughout the entire motion. Such motion prediction result based on the deep learning model is to reduce the joint’s tracking error relying only on direct calculations based on measurements of inertial sensors. In the final experiment, the lower limb motion trajectory during walking is used to verify that the method proposed in this work can actually outperform the traditional ones as just mentioned by achieving 2.9 mm drop in mean per joint position error (MPJPE) in 3.6M dataset, resulting in 12.2 mm in MPJPE, and mitigate the drift in real scenario. In our future work, we plan to verify the effectiveness of the proposed model and system for rehabilitation through clinical studies.

Objective Experimental studies of head-up positioning (HUP) during cardiopulmonary resuscitation (CPR) have had some degree of conflicting published results. The current study aim was to analyze and reconcile those discrepancies in order to better clarify the effects of HUP CPR compared to conventional supine (SUP) CPR. Methods Three databases (PubMed, EMBASE and Cochrane Library) were searched comprehensively (from each respective database's inception to May 2021) for articles addressing HUP CPR. The primary outcome to be observed was cerebral perfusion pressure (CerPP), and secondary outcomes were mean intracranial pressure (ICP), mean arterial pressure (MAP), coronary perfusion pressure (CoPP) and frequencies of return of spontaneous circulation (ROSC). Results Seven key studies involving 131 animals were included for analysis. Compared to SUP CPR, CerPP (MD 10.37; 95% CI 7.11–13.64; p I2 = 58%) and CoPP (MD 7.56; 95% CI 1.84–13.27, p = 0.01; I2 = 75%) increased significantly with HUP CPR, while ICP (MD − 13.66; 95% CI − 18.6 to –8.71; p I2 = 96%) decreased significantly. Combining all study methodologies, there were no significant differences detected in MAP (MD − 1.63; 95% CI − 10.77–7.52; p = 0.73; I2 = 93%) or frequency of ROSC (RR 0.9; 95% CI 0.31–2.60; p = 0.84; I2 = 65%). However, in contrast to worse outcomes in studies using immediate elevation of the head in a reverse Trendelenburg position, study outcomes were significantly improved when HUP (head and chest only) was introduced in a steady, graduated manner following a brief period of basic CPR augmented by active compression–decompression (ACD) and impedance threshold (ITD) devices. Conclusion In experimental models, gradually elevating the head and chest following a brief interval of circulatory priming with ACD and ITD devices can enhance CoPP, lower ICP and improve CerPP significantly while maintaining MAP. This effect is immediate, remains sustained and is associated with improved outcomes.

Oral cancers are the seventh most common cancer globally. While progresses in oral cancer treatment has been made, not all patients respond to these therapies in the same way. To overcome this difficulty, numerous studies have been devoted to identifying biomarkers, which enable early identification of patients who may benefit from a particular treatment modality or at risk for poor prognosis. Biomarkers are protein molecules, gene expression, DNA variants, or metabolites that are derived from tumors, adjacent normal tissue or bodily fluids, which can be acquired prior to treatment and during follow-up, thus extending their use to the evaluation of cancer progression and prediction of treatment outcome. In this review, we employed a basic significance level (< 0.05) as the minimal requirement for candidate biomarkers. Effect sizes of the biomarkers in terms of odds ratio, hazard ratio and area under the receiver operating characteristic curves were subsequently used to evaluate the potential of their clinical use. We identified the CCND1 from the tumor, human papillomavirus, HSP70, and IL-17 from the peripheral blood, and high density of CD45RO+ tumor-infiltrating lymphocytes as the clinically relevant biomarkers for oral cancers.

The recovery of other pathogens in patients with SARS-CoV-2 infection has been reported, either at the time of a SARS-CoV-2 infection diagnosis (co-infection) or subsequently (superinfection). However, data on the prevalence, microbiology, and outcomes of co-infection and superinfection are limited. The purpose of this study was to examine the occurrence of co-infections and superinfections and their outcomes among patients with SARS-CoV-2 infection.We searched literature databases for studies published from October 1, 2019, through February 8, 2021. We included studies that reported clinical features and outcomes of co-infection or superinfection of SARS-CoV-2 and other pathogens in hospitalized and non-hospitalized patients. We followed PRISMA guidelines, and we registered the protocol with PROSPERO as: CRD42020189763.Of 6639 articles screened, 118 were included in the random effects meta-analysis. The pooled prevalence of co-infection was 19% (95% confidence interval [CI]: 14%-25%, I2 = 98%) and that of superinfection was 24% (95% CI: 19%-30%). Pooled prevalence of pathogen type stratified by co- or superinfection were: viral co-infections, 10% (95% CI: 6%-14%); viral superinfections, 4% (95% CI: 0%-10%); bacterial co-infections, 8% (95% CI: 5%-11%); bacterial superinfections, 20% (95% CI: 13%-28%); fungal co-infections, 4% (95% CI: 2%-7%); and fungal superinfections, 8% (95% CI: 4%-13%). Patients with a co-infection or superinfection had higher odds of dying than those who only had SARS-CoV-2 infection (odds ratio = 3.31, 95% CI: 1.82-5.99). Compared to those with co-infections, patients with superinfections had a higher prevalence of mechanical ventilation (45% [95% CI: 33%-58%] vs. 10% [95% CI: 5%-16%]), but patients with co-infections had a greater average length of hospital stay than those with superinfections (mean = 29.0 days, standard deviation [SD] = 6.7 vs. mean = 16 days, SD = 6.2, respectively).Our study showed that as many as 19% of patients with COVID-19 have co-infections and 24% have superinfections. The presence of either co-infection or superinfection was associated with poor outcomes, including increased mortality. Our findings support the need for diagnostic testing to identify and treat co-occurring respiratory infections among patients with SARS-CoV-2 infection.

Background: Coronary allograft vasculopathy (CAV) is a devastating sequela of heart transplant in which arterial intimal thickening limits coronary blood flow. There are currently no targeted therapies to prevent or reduce this pathology that leads to transplant failure. Vascular smooth muscle cell (VSMC) phenotypic plasticity is critical in CAV neointima formation. TET2 (TET methylcytosine dioxygenase 2) is an important epigenetic regulator of VSMC phenotype, but the role of TET2 in the progression of CAV is unknown. Methods: We assessed TET2 expression and activity in human CAV and renal transplant samples. We also used the sex-mismatched murine aortic graft model of graft arteriopathy (GA) in wild-type and inducible smooth muscle–specific Tet2 knockout mice; and in vitro studies in murine and human VSMCs using knockdown, overexpression, and transcriptomic approaches to assess the role of TET2 in VSMC responses to IFNγ (interferon γ), a cytokine elaborated by T cells that drives CAV progression. Results: In the present study, we found that TET2 expression and activity are negatively regulated in human CAV and renal transplant samples and in the murine aortic graft model of GA. IFNγ was sufficient to repress TET2 and induce an activated VSMC phenotype in vitro. TET2 depletion mimicked the effects of IFNγ, and TET2 overexpression rescued IFNγ-induced dedifferentiation. VSMC-specific TET2 depletion in aortic grafts, and in the femoral wire restenosis model, resulted in increased VSMC apoptosis and medial thinning. In GA, this apoptosis was tightly correlated with proliferation. In vitro, TET2-deficient VSMCs undergo apoptosis more readily in response to IFNγ and expressed a signature of increased susceptibility to extrinsic apoptotic signaling. Enhancing TET2 enzymatic activity with high-dose ascorbic acid rescued the effect of GA-induced VSMC apoptosis and intimal thickening in a TET2-dependent manner. Conclusions: TET2 is repressed in CAV and GA, likely mediated by IFNγ. TET2 serves to protect VSMCs from apoptosis in the context of transplant vasculopathy or IFNγ stimulation. Promoting TET2 activity in vivo with systemic ascorbic acid reduces VSMC apoptosis and intimal thickening. These data suggest that promoting TET2 activity in CAV may be an effective strategy for limiting CAV progression.

We aimed to develop and validate a deep convolutional neural network (DCNN) model for preoperative prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) and its clinical outcomes using contrast-enhanced computed tomography (CECT) in a large population of candidates for surgery. This retrospective study included 1116 patients with HCC who had undergone preoperative CECT and curative hepatectomy. Radiological (R), DCNN, and combined nomograms were constructed in a training cohort (n = 892) respectively based on clinicoradiological factors, DCNN probabilities, and all factors; the performance of each model was confirmed in a validation cohort (n = 244). Accuracy and the AUC to predict MVI were calculated. Disease-free survival (DFS) and overall survival (OS) after surgery were recorded. The proportion of MVI-positive patients was respectively 38.8% (346/892) and 35.7 % (87/244) in the training and validation cohorts. The AUCs of the R, DCNN, and combined nomograms were respectively 0.809, 0.929, and 0.940 in the training cohorts and 0.837, 0.865, and 0.897 in the validation cohort. The combined nomogram outperformed the R nomogram in the training (p < 0.001) and validation (p = 0.009) cohorts. There was a significant difference in DFS and OS between the R, DCNN, and combined nomogram-predicted groups with and without MVI (p < 0.001). The combined nomogram based on preoperative CECT performs well for preoperative prediction of MVI and outcome. • A combined nomogram based on clinical information, preoperative CECT, and DCNN can predict MVI and clinical outcomes of patients with HCC. • DCNN provides added diagnostic ability to predict MVI. • The AUCs of the combined nomogram are 0.940 and 0.897 in the training and validation cohorts, respectively.

Current treatment options for men with metastatic castration-resistant prostate cancer (mCRPC) are noncurative, and median survival upon development of mCRPC is approximately 3 years. The novel hormonal agent enzalutamide has an established role in the mCRPC treatment paradigm, and emerging evidence suggests potential synergism with enzalutamide and the PD-1 inhibitor pembrolizumab in men with mCRPC. Here, we describe the design and rationale for the multicenter, randomized, double-blind, Phase III KEYNOTE-641 study, which will be conducted to compare the efficacy and safety of pembrolizumab plus enzalutamide with that of enzalutamide plus placebo in mCRPC. Clinical trial registration: NCT03834493 ( ClinicalTrials.gov )

Aims Ivabradine has been used in patients who have chronic heart failure (HF) with reduced ejection fraction (HFrEF) and concomitant sinus heart rate ≥70 bpm. This administration for acute HFrEF remains a concern. This study used a real‐world multicentre database to investigate the effects of ivabradine among patients with acute decompensated HFrEF before discharge. Methods and results This study retrospectively identified patients with acute decompensated HFrEF who were administered ivabradine at discharge from two multicentre HF databases. Propensity score matching was performed to adjust for confounders. Cardiovascular mortality, all‐cause mortality, and recurrent HF rehospitalization risks were then compared between those with and without ivabradine treatment. After 1:2 propensity score matching, 876 patients (age, 60.7 ± 14.6 years; female, 23.2%; left ventricular ejection fraction, 28.2% ± 7.8%; and heart rate at discharge, 84.3 ± 13.8 bpm) were included in the final analysis, including 292 and 584 patients with and without ivabradine treatment at discharge, respectively. No significant differences were observed in baseline characteristics between the two groups. At 1 year follow‐up, patients in the ivabradine group had significantly lower heart rates (77.6 ± 14.7 vs. 81.1 ± 16.3 bpm; P = 0.005) and lower HF severity symptoms (New York Heart Association Functional class, 2.1 ± 0.7 vs. 2.3 ± 0.9; P

Background To study the distribution of the birthplaces of very-low-birth-weight (VLBW) infants and examine whether delivery at different levels of hospital affects neonatal and infant mortality. Methods This population-based cohort study was retrieved from Taiwan Maternal and Child Health Database. Livebirth singleton VLBW infants born between 2011 and 2014, with BW between 500 and 1499 g and gestational age ≥22 weeks were enrolled. The main outcomes were risk-adjusted odds ratios (aOR) of neonatal and infant mortality by birthplace, which was categorized as medical center (MC), regional hospital (RH), district hospital (DH), and clinic (C) based on Taiwan's hospital accreditation system. Results Of 4560 VLBW infants enrolled, 3005 (66%) were born in MCs, 1181 (26%) in RHs, 213 (5%) in DHs, and 161 (4%) in Cs. Neonatal mortality rates were 10%, 15%, 16%, 17%, and infant mortality rates were 13%, 17%, 18%, 21%, if born in MCs, RHs, DHs and Cs, respectively. The aORs for neonatal and infant mortality were 1.94 (95% CI 1.53–2.48) and 1.67 (1.34–2.08) for those born in RHs, 2.26 (1.38–3.70) and 1.82 (1.16–2.86) for infants born in DHs/Cs, as compared to those born in MCs. For VLBW infants born in RHs, DHs, and Cs and postnatally transferred to MCs, the aORs of neonatal and infant mortality were lower than those who were not transferred. Conclusion VLBW infants born outside of MCs had higher neonatal and infant mortality and a two-fold higher risk of mortality than those born in MCs. When possible, VLBW infants should be born in MCs.

Background/purpose The incidence rate of oral and pharyngeal cancers in Taiwan has increased gradually over the past few decades. The standard treatment strategy for oral and pharyngeal cancers includes surgery or radiotherapy, with concurrent chemotherapy in certain types of tumors. Unfortunately, in-field recurrence is sometimes inexorable. Furthermore, re-irradiation of the recurrence site may cause severe complications due to the tolerance of normal tissue to radiation therapy. One fatal complication is carotid blowout syndrome (CBS). Boron neutron capture therapy (BNCT) is a new modality of radiation therapy, which is also mentioned as targeted radiotherapy. It is a feasible treatment that has the potential to spare normal tissue from being damaged by irradiation while simultaneously treating the primary tumor. In this presentation, we will share our experience with BNCT in treating recurrent head and neck cancers, as well as the prevention and management of CBS. Materials and methods We evaluated 4 patients with head and neck cancers treated by BNCT in Taiwan. All patients had undergone surgery previously and had received postoperative concurrent chemoradiotherapy. Results The 4 patients in this study were diagnosed with head and neck malignancies. The median follow-up period after the first course of BNCT was 15.1 months. After BNCT, 2 patients developed impending CBS, and 1 of them died. The remaining 3 patients survived until the last date of follow-up. Conclusion Pre-BNCT carotid artery evaluation through computed tomography angiography and early intervention if necessary is crucial when treating patients with recurrent head and neck cancers by BNCT.

Purpose: Infliximab (INX) has been approved for treating Crohn disease (CD) for many years, showing promis-ing efficacy in the clinic. However, the efficacy of the drug and the prognosis of CD vary significantly with dif-ferent locations of disease pathology. This study evaluated the efficacy of INX and prognosis in CD in different locations of disease pathology using systematic meta-analysis. Methods: We used “Infliximab OR Remicade OR Avakine OR Inflectra OR Renflexis OR Remsima OR IgG1k monoclonal antibody” AND “Crohn’s disease OR IBD OR inflammatory bowel disease” as search strategies for searching in PubMed, Wanfang and Embase. A systematic meta-analysis for overall proportions was used to analyze the data. Results: Twelve studies involving 1,978 patients were included. The results confirmed that treatment with INX led to high clinical remission rates (82%, 95% CI: 64%-92%) and low relapse rates (4%, 95% CI: 2%-9%) in patients with CD. Our results also indicated that use of INX in patients with colon only (L2) CD led to lower clinical remission rates, and use of INX in patients with ileum and colon (L3) CD led to higher relapse rates. Conclusion: Our findings show different remission rates depending on location of the disease and may be useful for clinicians’ choice of therapeutics.

Objective: Head-and-neck cancer (HNC) and its treatment impact patients' quality of life (QoL) and survival. The symptom burden of HNC survivors severely affects QoL, while hope serves as an impetus for adjustment that enables survivors to sustain basic QoL. This study investigated the change of QoL, symptom burden, and hope and the predictors of QoL change in HNC survivors from diagnosis to 3 months after concurrent chemoradiotherapy (CCRT) completing. Methods: This was a prospective, correlational study conducted between January 2016 and April 2017 at a medical center in northern Taiwan. Purposive sampling 54 adults newly diagnosed with HNC had completed the first CCRT. The questionnaires of Functional Assessment of Cancer Therapy-HNC Scale, M. D. Anderson Symptom Inventory, and Herth Hope Index were collected. The five measuring times were before CCRT (T1), the 3rd–4th week of CCRT (T2), the last week of CCRT (T3), and 1 month (T4) and 3 months (T5) after the completion of CCRT. Results: The change of QoL first declined and then rose at T2–T5. The change of symptom burden increased initially and then declined at T2–T5. The change of hope remained steady between T1 and T5. The change of symptom burden and hope significantly predicted the change of QOL over time. Conclusions: Clinicians are suggested to assess symptom burden and hope regularly in HNC during their CCRT and, if needed, promptly provide interprofessional care in time. Reducing symptom burden and maintaining a mindful hope could improve QoL in HNC survivors during CCRT.

Hypomethylating agents (HMAs) are effective therapies in myelodysplastic syndromes (MDS), but allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only way to cure MDS. According to the current literature, it is difficult to confirm whether HMAs bridging therapy is beneficial for MDS patients receiving allo-HSCT. Therefore, we tried to evaluate the effect of HMAs on long-term survival of the MDS patients. Databases, including PubMed, Embase Ovid, and the Cochrane Library, were searched for studies published up to January 10, 2021. Patients who accepted HMAs bridging to allo-HSCT were defined as experimental group, while patients who received the best supportive care (BSC) before allo-HSCT were control group. Overall survival (OS) was the primary end point. Seven studies were included in the final analysis. The final results showed no OS differences between patients accepted HMAs before allo-HSCT and those received BSC (HR = 0.86, 95% CI: 0.64–1.15, p = 0.32), indicating that MDS patients' long-term survival did not benefit from HMAs bridging therapy before allo-HSCT. This conclusion needs to be further verified by a large number of prospective randomized controlled trials, which have guiding significance for the treatment of MDS patients.

Background The expanded definition of liver-related deaths includes a wide range of etiologies and sequelae. We compared the changes in liver-related mortality by etiology and sequelae for different age groups between 2008 and 2018 in the USA using both underlying and multiple cause of death (UCOD and MCOD) data. Methods We extracted mortality data from the CDC WONDER. Both the absolute (rate difference) and relative (rate ratio and 95% confidence intervals) changes were calculated to quantify the magnitude of change using the expanded definition of liver-related mortality. Result Using the expanded definition including secondary liver cancer and according to UCOD data, we identified 68,037 liver-related deaths among people aged 20 years and above in 2008 (29 per 100,000) and this increased to 90,635 in 2018 (33 per 100,000), a 13% increase from 2008 to 2018. However, according to MCOD data, the number of deaths was 113,219 (48 per 100,000) in 2008 and increased to 161,312 (58 per 100,000) in 2018, indicating a 20% increase. The increase according to MCOD was mainly due to increase in alcoholic liver disease and secondary liver cancer (liver metastasis) for each age group and hepatitis C virus (HCV) and primary liver cancer among decedents aged 65–74 years. Conclusion The direction of mortality change (increasing or decreasing) was similar in UCOD and MCOD data in most etiologies and sequelae, except secondary liver cancer. However, the extent of change differed between UCOD and MCOD data.

In digital printing, the fabric print quality can only be evaluated through the color and pattern of printed fabric after printing. The influence of the physical properties of fabric on the printing effect remains unclear. In this paper, the digital print suitability of cotton fabric was defined, and 14 samples of plain cotton fabrics were taken as research objects. In addition, 11 evaluation indexes of cotton fabrics were selected. The evaluation and prediction model of cotton fabric printability was established by principal component analysis. Furthermore, the prediction results of the model were verified by analyzing the colorimetric data of cotton fabric after printing. The result demonstrated that the evaluation model of printing suitability was applicable and can be used to quickly evaluate the printability of cotton fabrics. Particularly, fabric thickness had the greatest influence on printing permeability. In the case of moderate wicking, the higher the whiteness of cotton fabric, the better the color reproducibility after printing. Additionally, the wicking effect also had a great influence on color performance.

Heart failure is a type of heart disease that causes increased pressure in the heart or a decrease in cardiac output. Unfortunately, despite seriousness of the condition there is a lack of effective early diagnostic markers or effective pharmacotherapy. Atractylodes is known as a tonic herb in ethno-medical systems in East Asia, especially in China, for the treatment of gastrointestinal dysfunction, cancer, osteoporosis, obesity, and fetal irritability. Atractylodes Lactone III is the main active component of Atractylodes rhizome. Atractylodes Lactone III increases the survival and inhibits apoptosis of H9C2 cells induced by angiotensin II. Angiotensin II is closely involved in apoptosis, hypertrophy, and fibrosis of cardiomyocytes, and may be an important cause of the deterioration of cardiovascular disease. Although, Atractylodes Lactone III reduces angiotensin II-induced H9C2 cell hypertrophy by activating the phosphatidylinositol 3-kinase/protein kinase B pathway, the detailed mechanism remains poorly understood. Additionally, inhibition of phosphatidylinositol 3-kinase/protein kinase B pathway inhibits the myocardial protective effect of Atractylodes Lactone III. We therefore hypothesized that Atractylodes Lactone III could serve as a promising therapeutic drug for the treatment of heart failure.

This paper provides an introduction to laboratory databases established by Taiwan National Health Insurance Administration (NHIA) since 2015 and released for research since June 2017. The National Health Insurance (NHI) is a government-run single-payer program introduced in 1995 that now covers more than 99% of 23 million Taiwanese citizens. To prevent duplication of medication prescriptions and laboratory test and examination prescriptions, contracted health care providers are required to upload the results of laboratory tests and reports of examinations to the NHIA. The cumulative number of laboratory test results was 5.64 billion from January 2015 to the end of August 2020 for 602 types of test. There are 35 variables for each laboratory test result stored in the databases that can be used for research. However, different hospitals might use different format in reporting the results. The researchers therefore have to develop algorithms to include and exclude incompatible records and to determine whether the results are positive or negative (normal or abnormal). The NHIA suggests that researchers release their source codes of algorithms so that other researchers can modify the codes to improve inter-study comparability. Through the unique personal identification number, the laboratory data can be linked to NHI inpatient and outpatient claims data for further value-added analyses. Non-Taiwanese researchers can collaborate with Taiwan researchers to access the NHI laboratory databases.

Background. Diabetic cardiomyopathy is one of the cardiac complications in diabetes patients, eventually resulting in heart failure and increasing morbidity and mortality. Oxidative stress is a critical pathological feature in diabetic hearts, contributing to the development of DCM. Forskolin (FSK) was shown to reduce oxidative stress. This study was aimed at investigating the effects of FSK on diabetic hearts and the relevant molecular mechanisms. Methods. Streptozotocin- (STZ-) induced diabetes in mice was treated with FSK through intraperitoneal injection. Cardiac functions were evaluated by echocardiography. Hematoxylin-eosin and Masson trichrome staining was employed to determine heart morphological changes and cardiac fibrosis, respectively. Cardiac fibrosis-related markers were detected by western blot. Superoxide dismutase activity, reduced/oxidized glutathione ratio, and malondialdehyde concentration in left ventricles were determined using respective commercial kits. Results. Abnormal cardiac diastolic dysfunction and cardiac fibrosis were observed in diabetic hearts. FSK treatment significantly improved the cardiac diastolic function and attenuated the abnormal morphological change in diabetic hearts. Moreover, FSK treatment in diabetic mice decreased the expression of fibronectin, collagen I, TGF-β, and α-SMA and reduced myocardial fibrosis. Furthermore, we observed that FSK significantly blocked oxidative stress in diabetic hearts. Conclusions. Our study demonstrates that FSK protects against the development of DCM in STZ-induced diabetes in mice. Our study suggests that FSK might be a potential target for drug development in treating DCM.

Aims Ivabradine and sacubitril/valsartan are second‐line therapies for patients with heart failure and reduced ejection fraction (HFrEF) based on guideline recommendations. We aimed to evaluate the synergistic effects of these two medications. Methods and results Patients' data were extracted from a multicentre database between 2016 and 2018. Patients were classified into (1) Simultaneous group: simultaneous prescription of ivabradine and sacubitril/valsartan within 6 weeks; (2A) Sequential group, ivabradine‐first: ivabradine was prescribed first, followed by sacubitril/valsartan; and (2B) Sequential group, sacubitril/valsartan‐first: sacubitril/valsartan was prescribed first, followed by ivabradine. A total of 464 patients with HFrEF were enrolled. Cardiovascular death and/or unplanned re‐hospitalizations for HF were less frequent (28.6% vs. 44.8%, P = 0.01), and the improvement of left ventricular ejection fraction (LVEF) was significantly greater in patients from the Simultaneous group than those from the Sequential group (∆LVEF 12.8 ± 12.9% vs. 9.3 ± 12.6%, P = 0.007). Among Sequential subgroups, the ivabradine‐first treatment decreased heart rate and increased systolic blood pressure (SBP) compared with sacubitril/valsartan‐first treatment (∆heart rate −9.1 ± 12.9 b.p.m. vs. 2.6 ± 16.0 b.p.m., P

We present the machine learning inspired design of two types of GaN zero contrast subwavelength gratings (SWGs): a polynomial-shaped grating and, for reference, a conventional rectangular grating, using the differential evolution algorithm to optimize the designs for high broadband reflectivity and separately for large fabrication tolerance. Two wavelength regimes with 500 nm and 1.55 μm center wavelengths (λcenter) are investigated. Our results indicate that both polynomial and rectangular grating designs can achieve comparable stopband widths of 170 nm (Δλ) for 500 nm (Δλ/λcenter = 34%). For the 1.55 μm center wavelength, the 482 nm (Δλ/λcenter = 31%) stopband width of the polynomial grating is slightly less than that of the rectangular grating at 498 nm (Δλ/λcenter = 32%). We also demonstrate design for enhanced fabrication tolerance while placing a minimum constraint on the stopband width. Our results show the rectangular grating exhibits slightly higher fabrication tolerances for grating parameters than the polynomial-shaped grating in general. This work also outlines the technique we have adopted for the inverse design of these gratings.

Background/Purpose To explore unmet needs for inpatient rehabilitation services and assess the relative preference of new technology versus current practice by a structured decision-making model. Methods The clinical needs for in-patient rehabilitation care were explored by an in-depth interview with the aid of a service blueprint in 2 affiliated hospitals of a university. A questionnaire was constructed according to the analytic hierarchical process (AHP) model to make pairwise comparison between the clinical needs for prioritization. The preference between traditional practice and new technology to fulfill the criteria was compared. Results Seven categories of unmet needs were summarized through focus group interviews to construct a questionnaire for the analytic hierarchical process. The results showed that assessment and recording ranked first as important applications, followed by clinical alerts, implementation of rehabilitation, patient/family education, team communication, schedule management and finally, the localization of patients/workers. The subjects from different professional disciplines had different rankings of preference weight, reflecting the individualized needs related to their practice. In addition, the subjects placed a higher preference on new technology than on current practice in all the categories. Conclusion The preference global weights on the needs to integrate new technologies into rehabilitation services aims to improve efficiency, safety and outcome. Further studies are needed to explore the needs from the perspective of the patients.

The superiority of convolutional neural network (CNN) has been proven in various object recognition tasks and has received much attention. However, the modern CNN approaches usually that assume the testing data and the training data belong to an identical category. Therefore, the current CNN approaches are not efficient for some applications with multisource data (i.e., the input data come from different sources), such as remote sensing scene. To increase the adaptability of the involved CNN approach, we first propose a $K$ -means-assisted scenario-aware reconfigurable convolutional neural network (KASR - CNN) mechanism. The KASR-CNN is composed of a fully convolutional autoencoder-based $K$ -means clustering (FCA-KC) and a reconfigurable convolutional neural network (RCNN), which are used to perform the coarse-grained classification and fine-grained classification to the input data, respectively. Furthermore, a Lego-like architecture design methodology is proposed to reduce the design complexity and improve computing flexibility. To show the adaptability, the KASR-CNN mechanism has been applied to different CNN models. In addition, the KASR-CNN has been verified on the Xilinx Zynq-ZC706 field-programmable gate array (FPGA) and implemented with TSMC 40-nm technology. Compared with the conventional approaches, the proposed KASR-CNN can help the involved CNN model to improve 3.73%–36.65% classification accuracy with only 0.38%–0.74% area overhead.

Automated detection of eye diseases using artificial intelligence techniques on optical coherence tomography (OCT) images is widely researched in the field of ophthalmology. Such detections are usually performed with the aid of computers. Using high-level simulations, this study investigates and evaluates three automated age-related macular degeneration (AMD) detection flows in terms of computation time and detection accuracy for future hardware-accelerated designs of intelligent and portable OCT systems. In this study, a block-matching and 3-Dimension filter (BM3DF), a hybrid median filter (HMF), and an adaptive wiener filter (AWF) are used to denoise the OCT images. Support vector machine (SVM), AlexNet, GoogLeNet, and Inception-ResNet are employed for AMD detection. Moreover, Local binary patterns, linear configuration patterns, and transfer learning techniques are used to extract image features. Simulation results reveal that machine-learning-based automated AMD detection realizes a high detection accuracy of 95.91% accompanied by low computation time when using the HMF rather than the BM3DF. When considering deep-learning-based automated AMD detection, the combination of HMF and Inception-ResNet achieves the highest detection accuracy of 98.64% but is accompanied by a dramatic increase in computation time. However, only AlexNet achieves a detection accuracy of 96.40%, accompanied by low computation time. In this study, the tradeoffs between the computation time and detection accuracy have been revealed by comparing the denoising methods for the distinct automated AMD detections.

To date, few reports have investigated the genetic alterations and clinicopathological features in gastric cancer (GC) according to sex. In total, 2673 GC patients receiving curative surgery were enrolled. Among the 2673 GC patients, 1979 (74.0%) patients were male. After propensity-score matching, 846 patients were enrolled for the analysis, including 423 males and 423 females. There was no significant difference in the clinicopathological features between the sexes. Regarding the initial recurrence pattern, the males were more likely to develop tumor recurrence and liver metastasis than the females, especially in stage III GC. Regarding the molecular analysis, the males had higher PD-L1 expression than the females, especially in stage III GC. In addition, the patients aged ≥ 65 years had higher PD-L1 expression than the patients younger than 65 years. The multivariate analysis demonstrated that sex was among the independent prognostic factors affecting overall survival (OS) and disease-free survival (DFS). Among the patients with liver metastases, PD-L1 expression was more common among the aged male patients. The males were associated with more tumor recurrence and higher PD-L1 expression than the females, especially in stage III GC. For GC patients with liver metastases, PD-L1 testing is recommended, especially among aged male patients.

Various reconstruction methods have been performed following distal gastrectomy; however, each reconstruction method has its own advantages and disadvantages. This study aims to compare the long-term outcomes between Billroth-I (B-I) and Roux-en-Y (RY) reconstruction after distal gastrectomy for gastric cancer. A total of 459 patients who underwent distal gastrectomy (B-I: 166, RY: 293) were included. Postoperative endoscopic findings and biliary tract stone formation were compared between the two groups. At 1 year and 2 years postoperatively, gastric residue was more common in the RY group, gastritis was similar between groups, and bile reflux was more common in the B-I group. At 5 years postoperatively, gastric residue was similar between the groups, while gastritis and bile reflux were more common in the B-I group. Gastroesophageal reflux was more common in the B-I group at 1 year postoperatively, but gastroesophageal reflux became not significantly different between the groups at 2 and 5 years postoperatively. Gallstone formation was more common in the RY group and in patients aged ≥ 65 years. During long-term follow-up, RY reconstruction was associated with lower incidence of bile reflux and gastritis, and higher incidence of gallstone formation than B-I reconstruction. The incidence of gastric residue was more common in the RY reconstruction group in the early postoperative period and became not significantly different between the two groups over time. For aged patients with RY reconstruction, cholecystectomy is recommended concurrently as gastrectomy.

Background Conjoined twins are a rare occurrence, and the majority of these malformations are detected during second trimester screening. Case summary Herein we report a case of conjoined twins, which was diagnosed by ultrasound at 8 wk gestation and was normal at 7 wk gestation. The two fetuses shared one heart and were diagnosed as thoracopagus twins. This is the first report of conjoined twins diagnosed at 8 wk gestation. The pregnancy was terminated electively at 9 wk gestation. Because some congenital malformations can be diagnosed earlier, a prenatal ultrasound examination at an early gestational stage cannot be dismissed. Conclusion This case demonstrates that a 7-8 wk gestation might be the earliest period when conjoined twins can be diagnosed by ultrasound.

An ultra-low quiescent current dual-mode buck converter system is designed for IoT application, which includes a double clock time (DCT) and a pulse-width-modulation (PWM) control modes. The proposed DCT mode can reduce the conversion loss over a wide loading range from nA-to-mA and achieve seamless mode transition from DCT to PWM control. Implemented in a $0.18\mu \text{m}$ CMOS, this converter achieves a peak efficiency of 92.7%/94.7% in DCT/PWM and >80% efficiency from $10~\mu $ A to 50 mA (5000x), with a wide input voltage from 2 V to 5 V. A quiescent current of 470 nA including bandgap voltage reference and internal oscillator is achieved. The DCT-to-PWM mode selection mechanism achieves an undershoot of 80 mV at $11~\mu \text{s}$ recovery time when load current jumps from $6.67~\mu \text{A}$ to 50 mA.

Background and Aim Screening upper endoscopy can detect esophagogastric (OG) cancers early with improved outcomes. Recent cost‐utility studies suggest that opportunistic upper endoscopy at the same setting of colonoscopy might be a useful strategy for screening of OG cancers, and it may be more acceptable to the patients due to cost‐saving and convenience. We aim to study the diagnostic performance of this screening strategy in a country with intermediate gastric cancer risk. Methods A retrospective cohort study using a prospective endoscopy database from 2015 to 2017 was performed. Patients included were individuals age > 40 who underwent opportunistic upper endoscopy at the same setting of colonoscopy without any OG symptoms. Neoplastic OG lesions are defined as cancer and high‐grade dysplasia. Pre‐neoplastic lesions include Barrett's esophagus (BE), intestinal metaplasia (IM), and atrophic gastritis (AG). Results The study population involved 1414 patients. Neoplastic OG lesions were detected in five patients (0.35%). Pre‐neoplastic lesions were identified in 174 (12.3%) patients. IM was found in 146 (10.3%) patients with 21 (1.4%) having extensive IM. The number needed to scope to detect a neoplastic OG lesion is 282.8 with an estimated cost of USD$141 400 per lesion detected. On multivariate regression, age ≥ 60 (RR: 1.84, 95% CI: 1.29–2.63) and first‐degree relatives with gastric cancer (RR: 1.64, 95% CI: 1.06–2.55) were independent risk factors for neoplastic or pre‐neoplastic OG lesion. Conclusion For countries with intermediate gastric cancer risk, opportunistic upper endoscopy may be an alternative screening strategy in a selected patient population. Prospective trials are warranted to validate its performance.

Studies from the United States have shown increasing incidence of autism spectrum disorder (ASD) with increasing socioeconomic status (SES), whereas in Scandinavian countries, no such relation was identified. We investigated how ASD risk in offspring varied according to parental SES in Taiwan, where there is universal health care. Through linking birth reporting data and data from Taiwan’s national health insurance program, we studied 706,111 singleton births from 2004 to 2007 and followed them until 2015. Parental SES was determined by monthly salary at the time of childbirth, and child neuropsychiatric outcomes were defined using International Classification of Diseases codes. We identified 7,323 ASD cases and 7,438 intellectual disability (ID) cases; 17% of ASD cases had co-occurring ID. In multivariable Cox regression analysis, higher SES was independently associated with higher risk of ASD after we took into account urbanization levels, child sex, parental age, and other covariates. By contrast, higher SES was independently associated with lower risk of ID. Besides the SES disparity in ASD case ascertainment and in the access to health care, findings from Taiwan suggest that other social, environmental, biological, and immunological factors linked with parental SES levels may contribute to the positive relation of SES and ASD risk.

Objective The Lauren classification is an important histologic classification of gastric cancer (GC) with different biological behaviors between histologic types. Background To date, there are few reports on the genetic alterations and survival differences between different histologic types according to the Lauren classification. Methods In total, 433 GC patients undergoing surgery were enrolled. The clinicopathologic features, prognoses, and genetic alterations of the different Lauren types were compared. Results Diffuse-type GC was associated with a younger age, female predominance, more Borrmann type 3 and 4 tumors, more advanced pathologic tumor (T) and node (N) categories, more tumor recurrences (especially peritoneal recurrence), and worse 5-year overall survival and disease-free survival rates than intestinal-type GC and mixed-type GC. Regarding genetic alterations, mixed-type GC was associated with more TP53 mutations than intestinal-type GC and diffuse-type GC. Multivariate analysis demonstrated the following independent prognostic factors: age, Lauren classification, and pathologic T and N categories. Regarding mixed-type GC, diffuse-type major tumors were associated with more lymphovascular invasion, a more advanced N category and tumor, node, metastasis stage, and fewer PI3K/AKT pathway mutations than intestinal-type major tumors. Conclusions Diffuse-type GC had unfavorable clinicopathologic features and a worse prognosis than intestinal-type GC. For mixed-type GC, the clinicopathologic features and genetic alterations were different between intestinal-type major tumors and diffuse-type major tumors.

To investigate and compare radiomics and clinical information for preoperative prediction of futile resection in intrahepatic cholangiocarcinoma (ICC). A total of 203 ICC patients from two centers were included and randomly allocated with a ratio of 7:3 into the training cohort and the validation cohort. Clinical characteristics and radiomics features were selected using random forest algorithm and logistic models to construct a clinical model and a radiomics model, respectively. A combined logistic model that incorporated the developed radiomics signature and clinical risk factors was then built. The performance of these models was evaluated and compared by plotting the receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC). The radiomics model showed a higher AUC than the clinical model in the validation cohort (AUC: 0.804 (95% CI: 0.697, 0.912) vs. 0.590 (95% CI: 0.415, 0.765), p = 0.043) for predicting futile resection in ICC. The radiomics model reached a sensitivity of 0.846 (95% CI: 0.546, 0.981) and a specificity of 0.771 (95% CI: 0.627, 0.880) in the validation cohort. Moreover, the radiomics model had comparable AUCs with the combined model in training and validation cohorts. We presented an internally validated radiomics model for the prediction of futile resection in ICC patients. Compared with clinical information, radiomics using CT images had greater potential for predicting futile resection accurately before surgery. • Radiomics model using CT images could predict futile resection in intrahepatic cholangiocarcinoma preoperatively. • Radiomics model using CT images was superior to clinical information for predicting futile resection accurately before surgery.

Background Gene therapy is the advanced therapeutics for supplying or replacing the genetic material in patients with inherited disorders. Recent clinical studies have made some progress in a wide range of applications, including monogenic disorders, neurodegenerative diseases, malignant tumors, and congenital diseases. Heart diseases, especially myocardial ischemia, remain one of the leading causes of mortality worldwide and usually result in irreparable cardiomyocyte damage and severe heart failure. Methods Most advances in induced pluripotent stem cell (iPSC) technologies for promoting regenerative medicine and stem cell research. However, the driver molecules of myocardial-lineage differentiation and the functional reconstruction capacity of iPSC-derived cardiomyocytes are still an open question. Nanomedicine-based gene delivery provided a crucial platform to carry on the biogenomic materials for equipping functionalities and engineering the living organ environment. Nanodiamond (ND), a carbon-based nanomaterial, has been discovered and shown the high biocompatible and less toxicity for transporting protein, drug, and genomic plasmids. Results Here, we applied ND as a gene delivery vehicle to carry microRNA (miR-181a), and then transfected into iPS to promote cardiomyocyte-lineage differentiation. Notably, miR-181a plays a key role in iPS-derived cardiomyocyte differentiation which directly targets Hox-A11, leading to elevated MyoD expression and enhanced cardiomyocyte differentiation. Conclusion Our study demonstrated that miR-181a promotes iPSC differentiation into functional cardiomyocytes. Delivery of NANO-DIAMOND-miR-181a may host clinical potential to enhance the differentiation and recovery of the cardiogenic function in injured cardiomyocytes.

This brief presents a successive-approximation-register (SAR) analog-to-digital converter (ADC) assisted DC-DC buck converter, which operates in discontinuous conduction mode (DCM) and achieves fast load transient recovery characteristics. The power inductor of the buck converter uses the bond-wire inductance. During the load transient, the dynamic low-power SAR ADC samples the converter’s undershoot/overshoot output voltage and controls the programmable current pump circuit to charge/discharge the output capacitor, thus speeding up and smoothing the load transient response. An additional compensation circuit is also designed to ensure the stability of the voltage mode control loop and the current pump. The chip fabricated in a 65-nm CMOS technology occupies an area of 1 mm2. The converter, switching at 100 MHz, achieves a peak power efficiency of 81% when $V_{IN}= 1.2$ V, $V_{OUT} = 1$ V and $I_{Load} = 50$ mA. When the load current steps from 2 mA to 50 mA, the measured undershoot/overshoot voltage is 101/92 mV, and the recovery time is 175/406 ns.

BACKGROUND: Doxorubicin (DOX) is one of the most effective anti-neoplastic drugs although its clinical use is limited by the severe cardiotoxicity. Apoptosis and defective autophagy are believed to contribute to DOX-induced cardiotoxicity. Here we explored the effect of curcumin (Cur) on DOX-induced cardiac injury and the mechanism involved with a focus on oxidative stress, autophagy and pyroptosis. METHODS: Kunming mice were challenged with DOX (3 mg·kg(−1), i.p. every other day) with cohorts of mice receiving Cur at 50, 100, 200 and 400 mg·kg(−1) via gavage daily. Serum levels of cardiac enzymes, such as aspartate amino transferase (AST), lactate dehydrogenase (LDH), creatine kinase (CK), and heart homogenate oxidative stress markers, such as superoxide dismutase (SOD) and malondialdehyde (MDA) were determined. Echocardiographic and cardiac contraction were examined. Apoptosis, pyroptosis, autophagy and Akt/mTOR-signalling proteins were detected using western blot or electron microscopy. Cardiac contractile properties were assessed including peak shortening, maximal velocity of shortening/relengthening (± dL/dt), time-to-PS, and time-to-90% relengthening (TR90). Superoxide levels were evaluated using DHE staining. GFP-LC3 was conducted to measure autophagosomes. RESULTS: Our study showed that Cur protected against cardiotoxicity manifested by a significant decrease in serum myocardial enzymes and improvement of anti-oxidative capacity. Cur inhibited autophagy and offered overt benefit for cardiomyocyte survive against DOX-induced toxicity. Cur attenuated DOX-induced cardiomyocyte pyroptosis as evidenced by NLR family pyrin domain containing 3 (NLRP3), Caspase-1, and interleukin-18 levels. DOX impaired cardiac function (reduced fractional shortening, ejection fraction, increased plasma cTnI level and TR90, decreased PS and ± dL/dt), the effects of which were overtly reconciled by 100 mg·kg(−1) but not 50 mg·kg(−1) Cur. H9c2 cells exposure to DOX displayed increased intracellular reactive oxygen species (ROS) and autophagy, the effects of which were nullified by Cur. Autophagy activator rapamycin cancelled off Cur-induced protective effects. CONCLUSIONS: Our finding suggested that Cur rescued against DOX-induced cardiac injury probably through regulation of autophagy and pyroptosis in a mTOR-dependent manner.

High-performance fiber-reinforced concrete (HPFRC) is an ideal energy dissipation material because of its high tensile ductility and multiple fine-crack development. An HPFRC energy dissipation wall was installed in a reinforced concrete (RC) frame to form a new RC frame-HPFRC energy dissipation wall aseismic structure. Two half-scale RC frame-HPFRC energy dissipation wall specimens were designed and constructed. Quasi-static tests were performed to study the failure mechanism, deformation performance, stiffness degradation, and energy dissipation performance. The effective stiffness of the RC frame-HPFRC energy dissipation wall at the peak load was analyzed. The test results indicate that RC frame-HPFRC energy dissipation wall structures can achieve the seismic fortification objective of being “repairable after major earthquake”. Compared with the RC frame with one energy dissipation wall, the lateral load capacity of the frame with two energy dissipation walls was improved by 38.3%, and the initial lateral stiffness increased by 1.78 times, while the post yield lateral stiffness increased by only 20% to 30%; the energy dissipation capacity at different damage states increased by 10% to 175%, while the lateral deformation capacity was basically the same. The energy dissipation mechanism of the RC frame-HPFRC energy dissipation wall structure includes the energy dissipation caused by the deformation of the wall, the slipping at the connections of the upper and lower ends of the wall with the frame beams, and the deformation of the RC frame. The effective stiffness coefficients of the RC frame and the HPFRC energy dissipation wall at the peak load are 0.11 and 0.13, respectively.

Background and Aim In China, clinical experience with direct‐acting antiviral treatments for hepatitis C virus (HCV) infection is still emerging. C‐CORAL is a phase 3, multinational, placebo‐controlled, double‐blind trial of elbasvir/grazoprevir (EBR/GZR) in participants with HCV infection from the Asia‐Pacific region and Russia. Here, we report the data from participants enrolled in China. Methods Treatment‐naive participants with chronic HCV genotype (GT) 1, GT4, or GT6 infection were randomly assigned to receive 50 mg EBR/100 mg GZR for 12 weeks (immediate‐treatment group, ITG) or placebo followed by deferred treatment with EBR/GZR (deferred‐treatment group, DTG). The primary efficacy end‐point was sustained virologic response at 12 weeks after completing treatment (SVR12), and the primary safety end‐point was a comparison of safety between participants receiving EBR/GZR and placebo (NCT02251990; Protocol PN‐5172‐067). Results A total of 152 participants in China were randomly assigned (ITG, n = 115; DTG, n = 37). SVR12 was achieved in 96.7% (146/151) participants overall and in 97.3% (142/146) of those with GT1b infection. Four participants relapsed (GT1b, n = 3; GT6a, n = 1). Drug‐related AEs were reported in 25 (21.7%) and 9 (24.3%) participants receiving EBR/GZR and placebo, respectively; no drug‐related serious adverse events (AEs) occurred. Two (1.7%) participants receiving EBR/GZR had late hepatic transaminase elevations. Patient‐reported outcomes indicate improved quality of life at follow‐up week 4 in participants receiving EBR/GZR compared to placebo. Conclusion EBR/GZR administered for 12 weeks represents a highly effective and safe treatment option for Chinese individuals with HCV GT1 infection., A sustained virologic response was achieved by 96.7% (146/151) of treatment‐naive participants with hepatitis c virus infection receiving elbasvir/grazoprevir (50 mg/100 mg) for 12 weeks. Patient‐reported outcomes indicate improved quality of life following clearance of HCV.

Gastric stump (&ldquo, remnant&rdquo, ) cancer is the development of a malignancy related to previous gastric surgery. Prognosis in gastric stump cancer, compared with that in primary gastric cancer, is still controversial. From January 1988 to December 2012 at a single medical centre in Taiwan, 105 patients with gastric stump cancer, including 85 with previous peptic ulcer disease and 20 with previous gastric cancer, were analyzed for clinicopathologic characteristics and overall survival (os). The 5-year os rates for patients with gastric stump cancer and with primary gastric cancer were 51.2% and 54.5% respectively (p = 0.035). Analysis of clinicopathologic characteristics indicated that, compared with patients having primary gastric cancer, those with gastric stump cancer had more lymph node metastasis (p < 0.001) and had been diagnosed at a more advanced stage (p = 0.047). Multivariate analysis with os as an endpoint showed that age [p = 0.015, hazard ratio (hr): 2.300, 95% confidence interval (ci): 1.173 to 4.509], tumour size (p = 0.037, hr: 1.700, 95% ci: 1.031 to 2.801), stromal reaction (p = 0.021, hr: 1.802, 95% ci: 1.094 to 2.969), and pathologic N category (p = 0.001, hr: 1.449, 95% ci: 1.161 to 1.807) were independent predictors in gastric stump cancer. The os rates for patients with gastric stump cancer who previously had gastric cancer or peptic ulcer disease were 72.9% and 50.0% respectively (p = 0.019). The Borrmann classification was more superficial (p = 0.005), lymph node metastases were fewer (p = 0.004), and staging was less advanced (p = 0.025) in patients with gastric stump cancer who previously had gastric cancer than in their counterparts who previously had peptic ulcer disease. Survival is poorer in patients with gastric stump cancer who previously had peptic ulcer disease than in those who previously had primary gastric cancer. Patients with gastric stump cancer who previously had gastric cancer and could receive curative gastrectomy tended to have a better prognosis because of a more superficial Borrmann classification. Regular follow-up in patients who have undergone gastric surgery is recommended for the early detection of gastric stump cancer.

The molecular aggregation of nonfullerene acceptors (NFA) can significantly affect the light absorption, charge generation, and power conversion efficiency (PCE) of organic solar cells (OSCs). In t...

Ultrasound (US) can be used to evaluate the brain structure and nervous system damage. Patients with neurologic symptoms need rapid, noninvasive imaging with high spatial resolution and tissue contrast. Magnetic resonance imaging is currently the most sensitive and specific imaging method for evaluating neuropathologic conditions. This approach does present some challenges, such as the need to transport patients who may be seriously ill to the magnetic resonance imaging suite and the need for patients to remain for a considerable time. Cranial US provides a very valuable imaging method for clinicians, which can make a rapid diagnosis and evaluation without ionizing radiation. The main disadvantage of cranial US is its low sensitivity and specificity for subtle/early lesions. In recent years, with the rapid development of anatomic and functional US technology, the practicability of US diagnosis and intervention has been greatly improved. Ultrasound elastography may have the potential to improve the sensitivity and specificity of various cranial nerve conditions. Ultrasound elastography has received considerable critical attention, and an increasing number of studies have recognized its critical role in evaluating brain diseases. At present, US elastography has been applied to the evaluation of traumatic brain injury, ischemic stroke, intraoperative brain tumors, and hypoxic ischemic encephalopathy. The latest animal experiments and human clinical trial developments in the applications of US elastography for brain diseases are summarized in this review.

Genetic factors have been demonstrated to play an important role in the pathology of ischemic stroke (IS). This study was conducted to explore the association between CYP2B6 polymorphisms and IS risk in a Chinese Han population. Four single-nucleotide polymorphisms (SNPs) in CYP2B6 from 477 cases and 495 controls were genotyped using the Agena MassARRAY. The odds ratio (OR) and 95% confidence interval (CI) were calculated under genetic models and haplotype analysis to assess the association between SNPs and IS risk. We found that rs2099361 was associated with an increased IS risk (CC vs. AA: overall: OR = 1.85, 95% CI: 1.16-2.93, P = 0.010; age ≤ 60: OR = 1.94, 95% CI: 1.02-3.70, P = 0.045; male: OR = 2.17, 95% CI: 1.22-3.86, P = 0.009). The GT genotype of rs4803420 was associated with a reduced IS risk (OR = 0.74, 95% CI: 0.57-0.98, P = 0.036); the GG genotype was associated with an increased IS risk in women (OR = 2.31, 95% CI: 1.00-5.31, P = 0.049). The rs1038376 polymorphism was associated with reduced IS risk for age ≤ 60 years (AT vs. TT: OR = 0.63, 95% CI: 0.40-0.99, P = 0.046). Interestingly, there were significant differences in some clinical indicator levels between case and control groups, and genotypes of SNPs. Our results indicated that CYP2B6 polymorphisms (rs2099361, rs4803420, and rs1038376) were associated with the risk of IS. Further studies are still needed to validate our findings with larger sample sizes.

We report a facil and robust strategy for fabricating flexible piezoelectric nanogenerator based on free-standing polydimethylsiloxane (PDMS) / ZnO nanowire (NW) hybrid film. Free-standing hybrid film was fabricated by mechanical exfoliation of ZnO NWs grown on a FR4 substrate. The free-standing ZnO/PDMS hybrid film is robust enough to be transferred into a flexible substrate of polyimide (Kapton) with Au sputtered. The nanogenerator based on the free-standing hybrid film exhibits stable output voltage about 0.7 V and current of 7 nA under pressing conditions. This facil and robust method should hold significant promise applications in efficient energy harvesting.

Rice blast is one of the most serious plant diseases. Many rice blast management approaches require know-how of experienced farmers or agronomists. Monitoring the farm for disease detection is labor intensive and time consuming. By using the Internet of Things (IoT) and artificial intelligence (AI), we are able to detect plant diseases more efficiently. Existing AI and IoT studies detect plant diseases by images or nonimage hyperspectral data, which require manual operations to obtain the photographs or data for analysis. Also, image detection typically is too late as rice blast may already spread to other plants. Based on an IoT platform for soil cultivation, we develop the RiceTalk project that utilizes nonimage IoT devices to detect rice blast. Unlike the image-based plant disease detection approaches, our agriculture sensors generate nonimage data that can be automatically trained and analyzed by the AI mechanism in real time. The beauty of RiceTalk is that the AI model is treated as an IoT device and is managed like other IoT devices. In this way, our approach significantly reduces the platform management cost to provide real-time training and predictions. We also propose an innovative spore germination mechanism as a new feature extraction model for agriculture. In the current implementation, the accuracy of the RiceTalk prediction on rice blast is 89.4%.

Background Mucinous gastric carcinoma (MGC) is rare and often associated with an advanced stage. The clinicopathological features and prognosis of MGC and non-MGC (NMGC) are controversial. Methods In total, 2637 gastric cancer (GC) patients receiving curative surgery were enrolled. The clinicopathological features and genetic alterations were compared between patients with MGC and NMGC. Results Among the 2637 GC patients, 92 (3.5%) had MGC. After propensity score matching, compared to patients with NMGC, patients with MGC had more poorly differentiated tumors, medullary stromal reaction-type tumors, tumors with infiltrating Ming's classification, diffuse-type tumors, more abnormal preoperative serum carbohydrate antigen 19-9 levels, and more advanced T categories. After propensity score matching, there were no significant differences between MGC and NMGC regarding the initial recurrence patterns, 5-year overall survival (OS), and disease-free survival (DFS) rates. Multivariate analysis demonstrated that the MGC cell type is not an independent prognostic factor of OS and DFS. No significant differences in microsatellite instability status, Epstein-Barr virus infection, Helicobacter pylori infection, or genetic mutations were observed between MGC and NMGC. The expression of programmed death-ligand 1 (PD-L1) was significantly higher in MGC than that in NMGC. MGC was diagnosed at a more advanced stage compared with NMGC. Conclusion MGC itself was not an independent prognostic factor of worse survival. MGC was correlated with higher PD-L1 expression than NMGC, which may have a clinical impact on the treatment of MGC in the future.

High efficiency and environmental stability are mandatory performance requirements for commercialization of perovskite solar cells (PSCs). Herein, efficient centimeter-scale PSCs with improved stability were achieved by incorporating an additive-free 2,2',7,7'-tetrakis[

Objective. The incidence of superficial organ diseases has increased rapidly in recent years. New methods such as computer-aided diagnosis (CAD) are widely used to improve diagnostic efficiency. Convolutional neural networks (CNNs) are one of the most popular methods, and further improvements of CNNs should be considered. This paper aims to develop a multiorgan CAD system based on CNNs for classifying both thyroid and breast nodules and investigate the impact of this system on the diagnostic efficiency of different preprocessing approaches. Methods. The training and validation sets comprised randomly selected thyroid and breast nodule images. The data were subgrouped into 4 models according to the different preprocessing methods (depending on segmentation and the classification method). A prospective data set was selected to verify the clinical value of the CNN model by comparison with ultrasound guidelines. Diagnostic efficiency was assessed based on receiver operating characteristic (ROC) curves. Results. Among the 4 models, the CNN model using segmented images for classification achieved the best result. For the validation set, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and area under the curve (AUC) of our CNN model were 84.9%, 69.0%, 62.5%, 88.2%, 75.0%, and 0.769, respectively. There was no statistically significant difference between the CNN model and the ultrasound guidelines. The combination of the two methods achieved superior diagnostic efficiency compared with their use individually. Conclusions. The study demonstrates the probability, feasibility, and clinical value of CAD in the ultrasound diagnosis of multiple organs. The use of segmented images and classification by the nature of the disease are the main factors responsible for the improvement of the CNN model. Moreover, the combination of the CNN model and ultrasound guidelines results in better diagnostic performance, which will contribute to the improved diagnostic efficiency of CAD systems.