Showing papers by "National Cheng Kung University published in 2020"

Asymptomatic carrier state, acute respiratory disease, and pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): Facts and myths.

Abstract: Since the emergence of coronavirus disease 2019 (COVID-19) (formerly known as the 2019 novel coronavirus [2019-nCoV]) in Wuhan, China in December 2019, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), more than 75,000 cases have been reported in 32 countries/regions, resulting in more than 2000 deaths worldwide. Despite the fact that most COVID-19 cases and mortalities were reported in China, the WHO has declared this outbreak as the sixth public health emergency of international concern. The COVID-19 can present as an asymptomatic carrier state, acute respiratory disease, and pneumonia. Adults represent the population with the highest infection rate; however, neonates, children, and elderly patients can also be infected by SARS-CoV-2. In addition, nosocomial infection of hospitalized patients and healthcare workers, and viral transmission from asymptomatic carriers are possible. The most common finding on chest imaging among patients with pneumonia was ground-glass opacity with bilateral involvement. Severe cases are more likely to be older patients with underlying comorbidities compared to mild cases. Indeed, age and disease severity may be correlated with the outcomes of COVID-19. To date, effective treatment is lacking; however, clinical trials investigating the efficacy of several agents, including remdesivir and chloroquine, are underway in China. Currently, effective infection control intervention is the only way to prevent the spread of SARS-CoV-2.

Neratinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in HER2-Positive Metastatic Breast Cancer Previously Treated With >= 2 HER2-Directed Regimens: Phase III NALA Trial

Abstract: PURPOSENALA (ClinicalTrials.gov identifier: NCT01808573) is a randomized, active-controlled, phase III trial comparing neratinib, an irreversible pan-HER tyrosine kinase inhibitor (TKI), plus capec...

Reliable Accuracy Estimates from k -Fold Cross Validation

Abstract: It is popular to evaluate the performance of classification algorithms by k -fold cross validation. A reliable accuracy estimate will have a relatively small variance, and several studies therefore suggested to repeatedly perform k -fold cross validation. Most of them did not consider the correlation among the replications of k -fold cross validation, and hence the variance could be underestimated. The purpose of this study is to explore whether k -fold cross validation should be repeatedly performed for obtaining reliable accuracy estimates. The dependency relationships between the predictions of the same instance in two replications of k -fold cross validation are first analyzed for k -nearest neighbors with $k= 1$ k = 1 . Then, statistical methods are proposed to test the strength of the dependency level between the accuracy estimates resulting from two replications of k -fold cross validation. The experimental results on 20 data sets show that the accuracy estimates obtained from various replications of k -fold cross validation are generally highly correlated, and the correlation will be higher as the number of folds increases. The k -fold cross validation with a large number of folds and a small number of replications should be adopted for performance evaluation of classification algorithms.

Osimertinib plus savolitinib in patients with EGFR mutation-positive, MET-amplified, non-small-cell lung cancer after progression on EGFR tyrosine kinase inhibitors: interim results from a multicentre, open-label, phase 1b study.

Abstract: Summary Background Preclinical data suggest that EGFR tyrosine kinase inhibitors (TKIs) plus MET TKIs are a possible treatment for EGFR mutation-positive lung cancers with MET-driven acquired resistance. Phase 1 safety data of savolitinib (also known as AZD6094, HMPL-504, volitinib), a potent, selective MET TKI, plus osimertinib, a third-generation EGFR TKI, have provided recommended doses for study. Here, we report the assessment of osimertinib plus savolitinib in two global expansion cohorts of the TATTON study. Methods In this multi-arm, multicentre, open-label, phase 1b study, we enrolled adult patients (aged ≥18 years) with locally advanced or metastatic, MET-amplified, EGFR mutation-positive non-small-cell lung cancer, who had progressed on EGFR TKIs. We considered two expansion cohorts: parts B and D. Part B consisted of three cohorts of patients: those who had been previously treated with a third-generation EGFR TKI (B1) and those who had not been previously treated with a third-generation EGFR TKI who were either Thr790Met negative (B2) or Thr790Met positive (B3). In part B, patients received oral osimertinib 80 mg and savolitinib 600 mg daily; after a protocol amendment (March 12, 2018), patients who weighed no more than 55 kg received a 300 mg dose of savolitinib. Part D enrolled patients who had not previously received a third-generation EGFR TKI and were Thr790Met negative; these patients received osimertinib 80 mg plus savolitinib 300 mg. Primary endpoints were safety and tolerability, which were assessed in all dosed patients. Secondary endpoints included the proportion of patients who had an objective response per RECIST 1.1 and was assessed in all dosed patients and all patients with centrally confirmed MET amplification. Here, we present an interim analysis with data cutoff on March 29, 2019. This study is registered with ClinicalTrials.gov , NCT02143466 . Findings Between May 26, 2015, and Feb 14, 2019, we enrolled 144 patients into part B and 42 patients into part D. In part B, 138 patients received osimertinib plus savolitinib 600 mg (n=130) or 300 mg (n=8). In part D, 42 patients received osimertinib plus savolitinib 300 mg. 79 (57%) of 138 patients in part B and 16 (38%) of 42 patients in part D had adverse events of grade 3 or worse. 115 (83%) patients in part B and 25 (60%) patients in part D had adverse events possibly related to savolitinib and serious adverse events were reported in 62 (45%) patients in part B and 11 (26%) patients in part D; two adverse events leading to death (acute renal failure and death, cause unknown) were possibly related to treatment in part B. Objective partial responses were observed in 66 (48%; 95% CI 39–56) patients in part B and 23 (64%; 46–79) in part D. Interpretation The combination of osimertinib and savolitinib has acceptable risk–benefit profile and encouraging antitumour activity in patients with MET-amplified, EGFR mutation-positive, advanced NSCLC, who had disease progression on a previous EGFR TKI. This combination might be a potential treatment option for patients with MET-driven resistance to EGFR TKIs. Funding AstraZeneca.

Quantum-limit Chern topological magnetism in TbMn6Sn6.

Abstract: The quantum-level interplay between geometry, topology and correlation is at the forefront of fundamental physics1–15. Kagome magnets are predicted to support intrinsic Chern quantum phases owing to their unusual lattice geometry and breaking of time-reversal symmetry14,15. However, quantum materials hosting ideal spin–orbit-coupled kagome lattices with strong out-of-plane magnetization are lacking16–21. Here, using scanning tunnelling microscopy, we identify a new topological kagome magnet, TbMn6Sn6, that is close to satisfying these criteria. We visualize its effectively defect-free, purely manganese-based ferromagnetic kagome lattice with atomic resolution. Remarkably, its electronic state shows distinct Landau quantization on application of a magnetic field, and the quantized Landau fan structure features spin-polarized Dirac dispersion with a large Chern gap. We further demonstrate the bulk–boundary correspondence between the Chern gap and the topological edge state, as well as the Berry curvature field correspondence of Chern gapped Dirac fermions. Our results point to the realization of a quantum-limit Chern phase in TbMn6Sn6, and may enable the observation of topological quantum phenomena in the RMn6Sn6 (where R is a rare earth element) family with a variety of magnetic structures. Our visualization of the magnetic bulk–boundary–Berry correspondence covering real space and momentum space demonstrates a proof-of-principle method for revealing topological magnets. Scanning tunnelling microscopy is used to reveal a new topological kagome magnet with an intrinsic Chern quantum phase, which shows a distinct Landau fan structure with a large Chern gap.

GCAN: Graph-aware Co-Attention Networks for Explainable Fake News Detection on Social Media

Abstract: This paper solves the fake news detection problem under a more realistic scenario on social media. Given the source short-text tweet and the corresponding sequence of retweet users without text comments, we aim at predicting whether the source tweet is fake or not, and generating explanation by highlighting the evidences on suspicious retweeters and the words they concern. We develop a novel neural network-based model, Graph-aware Co-Attention Networks (GCAN), to achieve the goal. Extensive experiments conducted on real tweet datasets exhibit that GCAN can significantly outperform state-of-the-art methods by 16% in accuracy on average. In addition, the case studies also show that GCAN can produce reasonable explanations.

Work-related COVID-19 transmission in six Asian countries/areas: A follow-up study.

Abstract: Objective There is limited evidence of work-related transmission in the emerging coronaviral pandemic. We aimed to identify high-risk occupations for early coronavirus disease 2019 (COVID-19) local transmission. Methods In this observational study, we extracted confirmed COVID-19 cases from governmental investigation reports in Hong Kong, Japan, Singapore, Taiwan, Thailand, and Vietnam. We followed each country/area for 40 days after its first locally transmitted case, and excluded all imported cases. We defined a possible work-related case as a worker with evidence of close contact with another confirmed case due to work, or an unknown contact history but likely to be infected in the working environment (e.g. an airport taxi driver). We calculated the case number for each occupation, and illustrated the temporal distribution of all possible work-related cases and healthcare worker (HCW) cases. The temporal distribution was further defined as early outbreak (the earliest 10 days of the following period) and late outbreak (11th to 40th days of the following period). Results We identified 103 possible work-related cases (14.9%) among a total of 690 local transmissions. The five occupation groups with the most cases were healthcare workers (HCWs) (22%), drivers and transport workers (18%), services and sales workers (18%), cleaning and domestic workers (9%) and public safety workers (7%). Possible work-related transmission played a substantial role in early outbreak (47.7% of early cases). Occupations at risk varied from early outbreak (predominantly services and sales workers, drivers, construction laborers, and religious professionals) to late outbreak (predominantly HCWs, drivers, cleaning and domestic workers, police officers, and religious professionals). Conclusions Work-related transmission is considerable in early COVID-19 outbreaks, and the elevated risk of infection was not limited to HCW. Implementing preventive/surveillance strategies for high-risk working populations is warranted.

Screening and eradication of Helicobacter pylori for gastric cancer prevention: the Taipei global consensus

Abstract: Objective A global consensus meeting was held to review current evidence and knowledge gaps and propose collaborative studies on population-wide screening and eradication of Helicobacter pylori for prevention of gastric cancer (GC). Methods 28 experts from 11 countries reviewed the evidence and modified the statements using the Delphi method, with consensus level predefined as ≥80% of agreement on each statement. The Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach was followed. Results Consensus was reached in 26 statements. At an individual level, eradication of H. pylori reduces the risk of GC in asymptomatic subjects and is recommended unless there are competing considerations. In cohorts of vulnerable subjects (eg, first-degree relatives of patients with GC), a screen-and-treat strategy is also beneficial. H. pylori eradication in patients with early GC after curative endoscopic resection reduces the risk of metachronous cancer and calls for a re-examination on the hypothesis of ‘the point of no return’. At the general population level, the strategy of screen-and-treat for H. pylori infection is most cost-effective in young adults in regions with a high incidence of GC and is recommended preferably before the development of atrophic gastritis and intestinal metaplasia. However, such a strategy may still be effective in people aged over 50, and may be integrated or included into national healthcare priorities, such as colorectal cancer screening programmes, to optimise the resources. Reliable locally effective regimens based on the principles of antibiotic stewardship are recommended. Subjects at higher risk of GC, such as those with advanced gastric atrophy or intestinal metaplasia, should receive surveillance endoscopy after eradication of H. pylori. Conclusion Evidence supports the proposal that eradication therapy should be offered to all individuals infected with H. pylori. Vulnerable subjects should be tested, and treated if the test is positive. Mass screening and eradication of H. pylori should be considered in populations at higher risk of GC.

Lipids and Alzheimer's Disease.

Abstract: Lipids, as the basic component of cell membranes, play an important role in human health as well as brain function. The brain is highly enriched in lipids, and disruption of lipid homeostasis is related to neurologic disorders as well as neurodegenerative diseases such as Alzheimer’s disease (AD). Aging is associated with changes in lipid composition. Alterations of fatty acids at the level of lipid rafts and cerebral lipid peroxidation were found in the early stage of AD. Genetic and environmental factors such as apolipoprotein and lipid transporter carrying status and dietary lipid content are associated with AD. Insight into the connection between lipids and AD is crucial to unraveling the metabolic aspects of this puzzling disease. Recent advances in lipid analytical methodology have led us to gain an in-depth understanding on lipids. As a result, lipidomics have becoming a hot topic of investigation in AD, in order to find biomarkers for disease prediction, diagnosis, and prevention, with the ultimate goal of discovering novel therapeutics.

Mapping essential urban land use categories in China (EULUC-China): preliminary results for 2018

Abstract: Land use reflects human activities on land. Urban land use is the highest level human alteration on Earth, and it is rapidly changing due to population increase and urbanization. Urban areas have widespread effects on local hydrology, climate, biodiversity, and food production. However, maps, that contain knowledge on the distribution, pattern and composition of various land use types in urban areas, are limited to city level. The mapping standard on data sources, methods, land use classification schemes varies from city to city, due to differences in financial input and skills of mapping personnel. To address various national and global environmental challenges caused by urbanization, it is important to have urban land uses at the national and global scales that are derived from the same or consistent data sources with the same or compatible classification systems and mapping methods. This is because, only with urban land use maps produced with similar criteria, consistent environmental policies can be made, and action efforts can be compared and assessed for large scale environmental administration. However, despite of the fact that a number of urban-extent maps exist at global scales [3,4], more detailed urban land use maps do not exist at the same scale. Even at big country or regional levels such as for the United States, China and European Union, consistent land use mapping efforts are rare.

Pretreatment methods for lignocellulosic biofuels production: current advances, challenges and future prospects.

Abstract: Lignocellulosic biomass has been recognized as promising feedstock for biofuels production. However, the high cost of pretreatment is one of the major challenges hindering large-scale production of biofuels from these abundant, indigenously-available, and economic feedstock. In addition to high capital and operation cost, high water consumption is also regarded as a challenge unfavorably affecting the pretreatment performance. In the present review, advances in lignocellulose pretreatment technologies for biofuels production are reviewed and critically discussed. Moreover, the challenges faced and future research needs are addressed especially in optimization of operating parameters and assessment of total cost of biofuel production from lignocellulose biomass at large scale by using different pretreatment methods. Such information would pave the way for industrial-scale lignocellulosic biofuels production. Overall, it is important to ensure that throughout lignocellulosic bioethanol production processes, favorable features such as maximal energy saving, waste recycling, wastewater recycling, recovery of materials, and biorefinery approach are considered.

Electro-optically Tunable Multifunctional Metasurfaces.

Abstract: Shaping the flow of light at the nanoscale has been a grand challenge for nanophotonics over decades. It is now widely recognized that metasurfaces represent a chip-scale nanophotonics array technology capable of comprehensively controlling the wavefront of light via appropriately configuring subwavelength antenna elements. Here, we demonstrate a reconfigurable metasurface that is multifunctional, i.e., notionally capable of providing diverse optical functions in the telecommunication wavelength regime, using a single compact, lightweight, electronically controlled array with no moving parts. By electro-optical control of the phase of the scattered light from each identical individual metasurface element in an array, we demonstrate a single prototype multifunctional programmable metasurface that is capable of both dynamic beam steering and reconfigurable light focusing. Reconfigurable multifunctional metasurfaces with arrays of tunable optical antennas thus can perform arbitrary optical functions by programmable array-level control of scattered light phase, amplitude, and polarization, similar to dynamic and programmable memories in electronics.

Long-Term Outcomes and Retreatment Among Patients With Previously Treated, Programmed Death-Ligand 1‒Positive, Advanced Non‒Small-Cell Lung Cancer in the KEYNOTE-010 Study.

Abstract: PURPOSEIn the KEYNOTE-010 study, pembrolizumab improved overall survival (OS) versus docetaxel in previously treated, programmed death-ligand 1 (PD-L1)‒expressing advanced non‒small-cell lung cance...

Unconventional ferroelectricity in moiré heterostructures

Abstract: The constituent particles of matter can arrange themselves in various ways, giving rise to emergent phenomena that can be surprisingly rich and often cannot be understood by studying only the individual constituents. Discovering and understanding the emergence of such phenomena in quantum materials-especially those in which multiple degrees of freedom or energy scales are delicately balanced-is of fundamental interest to condensed-matter research1,2. Here we report on the surprising observation of emergent ferroelectricity in graphene-based moire heterostructures. Ferroelectric materials show electrically switchable electric dipoles, which are usually formed by spatial separation between the average centres of positive and negative charge within the unit cell. On this basis, it is difficult to imagine graphene-a material composed of only carbon atoms-exhibiting ferroelectricity3. However, in this work we realize switchable ferroelectricity in Bernal-stacked bilayer graphene sandwiched between two hexagonal boron nitride layers. By introducing a moire superlattice potential (via aligning bilayer graphene with the top and/or bottom boron nitride crystals), we observe prominent and robust hysteretic behaviour of the graphene resistance with an externally applied out-of-plane displacement field. Our systematic transport measurements reveal a rich and striking response as a function of displacement field and electron filling, and beyond the framework of conventional ferroelectrics. We further directly probe the ferroelectric polarization through a non-local monolayer graphene sensor. Our results suggest an unconventional, odd-parity electronic ordering in the bilayer graphene/boron nitride moire system. This emergent moire ferroelectricity may enable ultrafast, programmable and atomically thin carbon-based memory devices.

A phase 3 study of nivolumab in previously treated advanced gastric or gastroesophageal junction cancer (ATTRACTION-2): 2-year update data

Abstract: Nivolumab showed improvement in overall survival (OS) in ATTRACTION-2, the first phase 3 study in patients with gastric/gastroesophageal junction (G/GEJ) cancer treated with ≥ 2 chemotherapy regimens. The 2-year follow-up results of ATTRACTION-2 are presented herein. ATTRACTION-2 was a randomized, double-blind, placebo-controlled, phase 3 trial (49 sites; Japan, South Korea, and Taiwan). The median (min–max) follow-up period was 27.3 (24.1–36.3) months. The primary endpoint was OS. A subanalysis of OS was performed based on best overall response and tumor-programmed death ligand-1 (PD-L1) expression status. Overall, 493 of 601 screened patients were randomized (2:1) to receive nivolumab (330) or placebo (163). OS (median [95% confidence interval; CI]) was significantly longer in the nivolumab group (5.26 [4.60–6.37] vs 4.14 [3.42–4.86] months in placebo group) at the 2-year follow-up (hazard ratio [95% CI], 0.62 [0.51–0.76]; P < 0.0001). A higher OS rate was observed in the nivolumab vs placebo group at 1 (27.3% vs 11.6%) and 2 years (10.6% vs 3.2%). The OS benefit was observed regardless of tumor PD-L1 expression. Among patients with a complete or partial response (CR or PR) in the nivolumab group, the median OS (95% CI) was 26.6 (21.65—not applicable) months; the OS rates at 1 and 2 years were 87.1% and 61.3%, respectively. No new safety signals were identified. Nivolumab treatment resulted in clinically meaningful long-term improvements in OS in patients with previously treated G/GEJ cancer. The long-term survival benefit of nivolumab was most evident in patients with a CR or PR.

Application of Ceria in CO2 Conversion Catalysis

Abstract: The growing threat of global climate change has received increasing attention in recent years. The conversion of CO2 to fuels and chemicals is vital for reducing emissions of greenhouse gases and n...