Miracle-dz/UniFAR-FTUs huggingface dataset:
Future prospects of EGFR-TKIs and surgery for non-small-cell lung cancer

J Thorac Dis 2022 | https://dx.doi. org/10.21037/jtd-22-57 Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have improved the prognosis of patients with non-small-cell lung cancers (NSCLCs). Genetic testing by next-generation sequencing (NGS) has been used in multiple companion diagnoses or cancer genome profiling. This advance in genetic testing yielded new insights into the treatment of patients with NSCLC with mutations resistant to EGFR-TKIs. Recent studies have also reported the efficacy of EGFR-TKIs in the perioperative period. In this issue, we will briefly summarize new findings on adjuvant and neoadjuvant EGFR-TKIs and treatment for resistance to EGFR-TKIs. Subsequently, we will introduce seven papers on these topics. A randomized controlled trial of osimertinib as adjuvant therapy (ADAURA study) showed that disease-free survival (DFS) in the osimertinib arm was significantly prolonged in patients with stage IB to IIIA EGFR mutationpositive NSCLC (1,2). Currently, a NeoADAURA study (ClinicalTrials.gov Identifier: NCT04351555, JapicCTI-205325) using osimertinib as neoadjuvant therapy is ongoing. In many patients with EGFR-mutated advanced NSCLC, EGFR-TKIs as first-line therapy resulted in the acquisition of resistance within 1 year. In 50–60% of resistant cases, there was a T790M mutation in the exon 20 region of the EGFR gene (3). In a phase III AURA3 study comparing osimertinib with platinum-based chemotherapy in T790M mutation-positive NSCLC patients, osimertinib significantly prolonged progression-free survival (PFS) (median PFS; 10.1 vs. 4.4 months, hazard rate =0.30) (4). Furthermore, in a phase III FLAURA study comparing osimertinib with gefitinib or erlotinib as a first-line treatment for locally advanced EGFR mutation-positive NSCLC, PFS, and overall survival (OS) with osimertinib were significantly prolonged, and its toxicity was significantly reduced (5). Osimertinib was also effective Editorial
Can Government Direct Bailout Intervention Relieve the Crisis Sentiment in the Context of the COVID-19 Pandemic

It has been increasingly common for the government to adopt non-market approaches to manage or interfere with the market during a stock market crisis. Taking Chinese government’s bailout of the market during the COVID-19 epidemic as the research object, this paper examines the impact of Chinese government’s direct bailout intervention on investors’ crisis psychology. The findings are as follows: (1) The government “buy-in” bailout effectively smooths investors’ crisis sentiment; (2) There is a downside of the government “buy-in” bailout, which compromises the market pricing effect and aggravates the herding effect; (3) For stocks not bought by the government, the government’s “verbal” intervention can relieve investors’ crisis sentiment in the short term; (4) Stocks with different characteristics are affected by the government’s “verbal” intervention to different degrees, with financial stocks and problematic stocks more susceptible to it.
The Activation of GPR27 Increases Cytosolic L-Lactate in 3T3 Embryonic Cells and Astrocytes

G-protein-coupled receptors (GPCRs) represent a family with over 800 members in humans, and one-third of these are targets for approved drugs. A large number of GPCRs have unknown physiologic roles. Here, we investigated GPR27, an orphan GPCR belonging to the family of super conserved receptor expressed in the brain, with unknown functions. Cytosolic levels of L-lactate ([lactate]i), the end product of aerobic glycolysis, were measured with the Laconic fluorescence resonance energy transfer nanosensor. In single 3T3 wild-type (WT) embryonic cells, the application of 8535 (1 µM), a surrogate agonist known to activate GPR27, resulted in an increase in [lactate]i. Similarly, an increase was recorded in primary rat astrocytes, a type of neuroglial cell abundant in the brain, which contain glycogen and express enzymes of aerobic glycolysis. In CRISPR-Cas9 GPR27 knocked out 3T3 cells, the 8535-induced increase in [lactate]i was reduced compared with WT controls. Transfection of the GPR27-carrying plasmid into the 3T3KOGPR27 cells rescued the 8535-induced increase in [lactate]i. These results indicate that stimulation of GPR27 enhances aerobic glycolysis and L-lactate production in 3T3 cells and astrocytes. Interestingly, in the absence of GPR27 in 3T3 cells, resting [lactate]i was increased in comparison with controls, further supporting the view that GPR27 regulates L-lactate homeostasis.
Improving Wet and Dry Deposition of Aerosols in WRF‐Chem: Updates to Below‐Cloud Scavenging and Coarse‐Particle Dry Deposition

Wet and dry depositions of aerosols in WRF‐Chem are revisited and updated based on recent observational findings. Traditionally, in‐cloud scavenging was thought to play a more dominant role in aerosol wet removal than below‐cloud scavenging. However, recent field measurements indicated a considerable contribution of below‐cloud scavenging of 50%–60% to total wet deposition. In contrast, the simulated contribution of in‐cloud scavenging in the previous version of WRF‐Chem was too large, exhibiting 88%–95%, likely due to the binary representation of cloud fraction. To reduce the model bias, this study adopts a continuous‐type cloud fraction and implements a semi‐empirical below‐cloud scavenging parameterization. Simulation results with the new scheme show that the contribution of below‐cloud (in‐cloud) scavenging is increased to 63%–66% (decreased to 34%–37%), well capturing the observational estimates. The magnitude of total wet deposition is increased by 18.2% for SO4, 7.16% for NO3, and 14.8% for NH4, showing better agreements with observations particularly for SO4 and NH4 deposition. The increased wet removal with the new scheme reduces and so better reproduces surface PM2.5 and PM10 concentrations, which is also partly attributed to the increased contribution of below‐cloud scavenging. It is found that dry deposition velocity in the previous version was too high for coarse mode particles when friction velocity is large, which underestimates surface PM10 concentration. The updated dry deposition scheme that is constrained by observations effectively improves PM10 performance by reducing the dry deposition velocity for coarse mode particles.
Integrating Walking for Transportation and Physical Activity for Sedentary Office Workers in Texas

Integrating Walking for Transportation and Physical Activity for Sedentary Office Workers in Texas. (August 2009) Kathleen Meghan Wieters, B.A., Trinity University; M.S.C.R. P, University of Texas at Austin Co-Chairs of Advisory Committee: Dr. Chanam Lee Dr. Walter Gillis Peacock The workplace is considered a strategic location for health promotion. According to the Texas Workforce Commission, office workers represent up to 40% of the workforce in Texas and the general nature of the type of work is sedentary. Additional study is needed on how the built environment near the worksite area impacts walking behaviors and to determine interventions effective in increasing walking as part of daily routines among office workers. The two aims of this dissertation were: 1) investigate the differences that urban and suburban settings may have on walking behavior (walk trips, walk duration, total step count) of office workers in Texas and 2) to examine the impact of a simple intervention in increasing walking within the respective land use settings. This study utilized on-line survey and travel diary, pedometer, and Geographic Information System to capture the study variables, which included personal, social and cultural, organizational, and built environmental factors. Results showed that urban office workers walk, on average, 600 steps more per day than the suburban office workers. Office workers in both land use settings on
Efficacy of Stem Cell Therapy in Large Animal Models of Ischemic Cardiomyopathies: A Systematic Review and Meta-Analysis

Simple Summary The present work focuses on stem-cell assessment as a therapeutic approach on cardiovascular diseases, both in terms of safety and efficacy. In particular, this is a systematic review of the relevant literature about the use of stem-cell treatment against acute or chronic ischemic cardiomyopathies in large animal models and a meta-analysis on collected data with regard to the left ventricular ejection fraction (LVEF) as functional parameter. This approach is compliant with the “3Rs” (replacement, reduction and refinement) principle about the use of animal experimentation in preclinical trials to predict evidences and perform the future translational researches. Abstract Stem-cell therapy provides a promising strategy for patients with ischemic heart disease. In recent years, numerous studies related to this therapeutic approach were performed; however, the results were often heterogeneous and contradictory. For this reason, we conducted a systematic review and meta-analysis of trials, reporting the use of stem-cell treatment against acute or chronic ischemic cardiomyopathies in large animal models with regard to Left Ventricular Ejection Fraction (LVEF). The defined research strategy was applied to the PubMed database to identify relevant studies published from January 2011 to July 2021. A random-effect meta-analysis was performed on LVEF mean data at follow-up between control and stem-cell-treated animals. In order to improve the definition of the effect measure and to analyze the factors that could influence the outcomes, a subgroup comparison was conducted. Sixty-six studies (n = 1183 animals) satisfied our inclusion criteria. Ischemia/reperfusion infarction was performed in 37 studies, and chronic occlusion in 29 studies; moreover, 58 studies were on a pig animal model. The meta-analysis showed that cell therapy increased LVEF by 7.41% (95% Confidence Interval 6.23–8.59%; p < 0.001) at follow-up, with significative heterogeneity and high inconsistency (I2 = 82%, p < 0.001). By subgroup comparison, the follow-up after 31–60 days (p = 0.025), the late cell injection (>7 days, p = 0.005) and the route of cellular delivery by surgical treatment (p < 0.001) were significant predictors of LVEF improvement. This meta-analysis showed that stem-cell therapy may improve heart function in large animal models and that the swine specie is confirmed as a relevant animal model in the cardiovascular field. Due to the significative heterogeneity and high inconsistency, future translational studies should be designed to take into account the evidenced predictors to allow for the reduction of the number of animals used.
Extended high step-up structure for multilevel converter

This study presents a new high step-up multilevel converter topology. The proposed multilevel converter comprises of two dc voltage sources, several capacitors, unidirectional switches, and power diodes. The proposed topology can increase the values of input dc voltage sources substantially. The voltage gain of the proposed topology depends on the number of used capacitors. The proposed topology is simple and can be extended to produce higher-output voltage levels. The values of two used dc voltage sources can be selected as symmetric and asymmetric. In symmetric type, the values of two dc sources are similar. However, the dc sources magnitudes in asymmetric type are unequal and their values are obtained based on mathematical method. Inherent voltage balancing of used capacitors is an important feature of the proposed topology. The proposed topology is compared with other recently proposed high step-up multilevel converters and conventional topologies in terms of the number of used switches, capacitors, dc sources, and voltage on switches. It is indicated that the proposed structure requires the least number of devices and the voltage rating on power switches is low. The performance of the proposed topology and theoretical analysis are confirmed using experimental works.
BRET-Based Biosensors to Measure Agonist Efficacies in Histamine H1 Receptor-Mediated G Protein Activation, Signaling and Interactions with GRKs and β-Arrestins

The histamine H1 receptor (H1R) is a G protein-coupled receptor (GPCR) and plays a key role in allergic reactions upon activation by histamine which is locally released from mast cells and basophils. Consequently, H1R is a well-established therapeutic target for antihistamines that relieve allergy symptoms. H1R signals via heterotrimeric Gq proteins and is phosphorylated by GPCR kinase (GRK) subtypes 2, 5, and 6, consequently facilitating the subsequent recruitment of β-arrestin1 and/or 2. Stimulation of a GPCR with structurally different agonists can result in preferential engagement of one or more of these intracellular signaling molecules. To evaluate this so-called biased agonism for H1R, bioluminescence resonance energy transfer (BRET)-based biosensors were applied to measure H1R signaling through heterotrimeric Gq proteins, second messengers (inositol 1,4,5-triphosphate and Ca2+), and receptor-protein interactions (GRKs and β-arrestins) in response to histamine, 2-phenylhistamines, and histaprodifens in a similar cellular background. Although differences in efficacy were observed for these agonists between some functional readouts as compared to reference agonist histamine, subsequent data analysis using an operational model of agonism revealed only signaling bias of the agonist Br-phHA-HA in recruiting β-arrestin2 to H1R over Gq biosensor activation.
Warning students of the consequences of examination failure: An effective strategy for promoting student engagement?

In the context of high-stakes qualifications, teachers may warn students of the negative consequences of failure as a tactic designed to increase engagement and ultimately achievement. Previous studies have shown that these types of messages, namely fear appeals, are indirectly related to engagement and achievement in different ways depending on how they are evaluated by the student. When fear appeals are evaluated as a challenge, they are positively related to engagement and achievement. When evaluated as a threat, fear appeals are negatively related to engagement and achievement. In the present study, we offer a robust test of these relations in a multi-level model that controls for autoregressive and concurrent relations in the domain of mathematics. Self-reported data were collected from 1,530 participants, aged 14-16 years, at two time points over the final two years of secondary education. These data were linked to prior and subsequent achievement. Results showed that students who attended to fear appeals and evaluated them as a challenge showed higher subsequent engagement, and students who showed higher engagement showed higher achievement. Accordingly, it may be beneficial to identify those students likely to evaluate fear appeals as a threat and intervene in order to enhance the likelihood of a challenge evaluation (e.g., building confidence through strategy focused feedback and strengthening beliefs in the value of effort). Given the difficulties associated with teachers judging students’ motivation and emotion as private experiences, methods to access student voice should be considered.
Efficient Use of Graphene Oxide in Layered Cement Mortar

Graphene oxide (GO) has been found to be an attractive nanomaterial to improve the properties of cementitious composites. However, the use of GO in the industry is limited by its high cost. To achieve a higher cost/performance ratio, GO can be strategically applied in certain parts of cementitious composites structure according to the principle of functionally graded materials. In this study, graded distribution of GO in cement mortar was achieved by sequentially casting a fresh GO-incorporated cement layer on another cement mortar layer. The mechanical properties, especially flexural strength, of layered cement mortar were found to be dependent on the GO content, the delay time, and the interface formed due to layering fabrication. With the GO incorporated in the tensile region only (30% of the total depth), the flexural strength of the layered beam attained 90.91% of that of the beam, with GO uniformly distributed throughout the sample. Based on the results of rapid chloride migration tests, when 12 mm GO-incorporated cement mortar layer was used, the chloride migration coefficient was reduced by 21.45%. It was also found that the measured chloride migration coefficient of layered cement mortar agreed with the series model. The present investigation provides an efficient approach to use GO in cement-based materials from the perspective of mechanical and durability properties.
Sanguinarine-Chelerythrine Fraction of Coptis chinensis Exerts Anti-inflammatory Activity in Carrageenan Paw Oedema Test in Rats and Reveals Reduced Gastrotoxicity

Inflammatory diseases are a common therapeutic problem and nonsteroidal anti-inflammatory drugs are not deprived of side effects, of which ulcerogenic activity is one of the most frequent. The aim of the study was to evaluate the anti-inflammatory activity of the sanguinarine-chelerythrine (SC) fraction of Coptis chinensis and its influence on the integrity of gastric mucosa. The study was conducted on sixty male rats randomly divided into six experimental groups: two control groups (a negative control group CON and a positive control group CAR); three groups receiving an investigational fraction of C. chinensis (1, 5, 10 mg/kg i.g.) named SC1, SC5, and SC10, respectively; and a group receiving indomethacin (IND) (10 mg/kg i.g.) as a reference drug. In all animals, the carrageenan-induced paw oedema was measured; PGE2 release, TNFα production, and MMP-9 concentration in inflamed tissue were determined. Additionally, the macroscopic and microscopic damage of gastric mucosa was evaluated. Administration of SC dose-dependently inhibited the second phase of carrageenan rat paw oedema and PGE2 release, decreased the production of TNFα, and reduced the concentration of MMP-9, and the efficacy of the highest dose was comparable to the effect of IND. Contrary to IND, no gastrotoxic activity of SC was detected. The investigated sanguinarine-chelerythrine fraction of C. chinensis seems to be a promising candidate for further research on new anti-inflammatory and analgesic drugs characterized with a safer gastric profile compared to existing NSAIDs.
Predicting Adolescent Internet Gaming Addiction from Perceived Discrimination, Deviant Peer Affiliation and Maladaptive Cognitions in the Chinese Population: A Two-Year Longitudinal Study

A robust positive association between perceived discrimination and Internet gaming addiction (IGA) among adolescents has been demonstrated by existing research; however, the mediating mechanisms underlying this relationship remain largely unknown. This study, grounded in the cognitive–behavioral and social development models, examined whether deviant peer affiliation and maladaptive cognitions mediated the predictive effect of perceived discrimination on adolescent IGA. Six-hundred-and-sixty students (Meanage = 13.43 years; 367 female participants) recruited from southern China participated in four assessments (fall 7th grade, spring 7th grade, fall 8th grade, spring 8th grade). Participants completed a self-administered questionnaire that assessed their demographics, as well as questionnaire measures of perceived discrimination, deviant peer affiliation, maladaptive cognitions, and IGA. The structural equation model showed that fall 7th grade’s perceived discrimination positively predicted spring 7th grade’s deviant peer affiliation, which, in turn, increased fall 8th grade’s maladaptive cognitions, ultimately increasing spring 8th grade’s IGA. Moreover, the indirect effect of fall 7th grade’s perceived discrimination on spring 8th grade’s IGA via spring 7th grade’s deviant peer affiliation was also significant. The results suggested deviant peer affiliation and maladaptive cognitions as potential mediating mechanisms linking perceived discrimination to adolescent IGA. These findings have important implications for the prevention and intervention of adolescent IGA.
A Powerful Paradigm for Cardiovascular Risk Stratification Using Multiclass, Multi-Label, and Ensemble-Based Machine Learning Paradigms: A Narrative Review

Abstract Background and Motivation: Cardiovascular disease (CVD) causes the highest mortality globally. With escalating healthcare costs, early non-invasive CVD risk assessment is vital. Conventional methods have shown poor performance compared to more recent and fast-evolving Artificial Intelligence (AI) methods. The proposed study reviews the three most recent paradigms for CVD risk assessment, namely multiclass, multi-label, and ensemble-based methods in (i) office-based and (ii) stress-test laboratories. Methods: A total of 265 CVD-based studies were selected using the preferred reporting items for systematic reviews and meta-analyses (PRISMA) model. Due to its popularity and recent development, the study analyzed the above three paradigms using machine learning (ML) frameworks. We review comprehensively these three methods using attributes, such as architecture, applications, pro-and-cons, scientific validation, clinical evaluation, and AI risk-of-bias (RoB) in the CVD framework. These ML techniques were then extended under mobile and cloud-based infrastructure. Findings: Most popular biomarkers used were office-based, laboratory-based, image-based phenotypes, and medication usage. Surrogate carotid scanning for coronary artery risk prediction had shown promising results. Ground truth (GT) selection for AI-based training along with scientific and clinical validation is very important for CVD stratification to avoid RoB. It was observed that the most popular classification paradigm is multiclass followed by the ensemble, and multi-label. The use of deep learning techniques in CVD risk stratification is in a very early stage of development. Mobile and cloud-based AI technologies are more likely to be the future. Conclusions: AI-based methods for CVD risk assessment are most promising and successful. Choice of GT is most vital in AI-based models to prevent the RoB. The amalgamation of image-based strategies with conventional risk factors provides the highest stability when using the three CVD paradigms in non-cloud and cloud-based frameworks.
Assay for Evaluating the Abundance of Vibrio cholerae and Its O1 Serogroup Subpopulation from Water without DNA Extraction

Cholera is a severe diarrheal disease caused by Vibrio cholerae, a natural inhabitant of brackish water. Effective control of cholera outbreaks depends on prompt detection of the pathogen from clinical specimens and tracking its source in the environment. Although the epidemiology of cholera is well studied, rapid detection of V. cholerae remains a challenge, and data on its abundance in environmental sources are limited. Here, we describe a sensitive molecular quantification assay by qPCR, which can be used on-site in low-resource settings on water without the need for DNA extraction. This newly optimized method exhibited 100% specificity for total V. cholerae as well as V. cholerae O1 and allowed detection of as few as three target CFU per reaction. The limit of detection is as low as 5 × 103 CFU/L of water after concentrating biomass from the sample. The ability to perform qPCR on water samples without DNA extraction, portable features of the equipment, stability of the reagents at 4 °C and user-friendly online software facilitate fast quantitative analysis of V. cholerae. These characteristics make this assay extremely useful for field research in resource-poor settings and could support continuous monitoring in cholera-endemic areas.