Adjuvant chemotherapy after surgery improves survival of patients with stage II–III, resectable gastric cancer. However, the overall survival benefit observed after adjuvant chemotherapy is moderate, ...suggesting that not all patients with resectable gastric cancer treated with adjuvant chemotherapy benefit from it. We aimed to develop and validate a predictive test for adjuvant chemotherapy response in patients with resectable, stage II–III gastric cancer.
In this multi-cohort, retrospective study, we developed through a multi-step strategy a predictive test consisting of two rule-based classifier algorithms with predictive value for adjuvant chemotherapy response and prognosis. Exploratory bioinformatics analyses identified biologically relevant candidate genes in gastric cancer transcriptome datasets. In the discovery analysis, a four-gene, real-time RT-PCR assay was developed and analytically validated in formalin-fixed, paraffin-embedded (FFPE) tumour tissues from an internal cohort of 307 patients with stage II–III gastric cancer treated at the Yonsei Cancer Center with D2 gastrectomy plus adjuvant fluorouracil-based chemotherapy (n=193) or surgery alone (n=114). The same internal cohort was used to evaluate the prognostic and chemotherapy response predictive value of the single patient classifier genes using associations with 5-year overall survival. The results were validated with a subset (n=625) of FFPE tumour samples from an independent cohort of patients treated in the CLASSIC trial (NCT00411229), who received D2 gastrectomy plus capecitabine and oxaliplatin chemotherapy (n=323) or surgery alone (n=302). The primary endpoint was 5-year overall survival.
We identified four classifier genes related to relevant gastric cancer features (GZMB, WARS, SFRP4, and CDX1) that formed the single patient classifier assay. In the validation cohort, the prognostic single patient classifier (based on the expression of GZMB, WARS, and SFRP4) identified 79 (13%) of 625 patients as low risk, 296 (47%) as intermediate risk, and 250 (40%) as high risk, and 5-year overall survival for these groups was 83·2% (95% CI 75·2–92·0), 74·8% (69·9–80·1), and 66·0% (60·1–72·4), respectively (p=0·012). The predictive single patient classifier (based on the expression of GZMB, WARS, and CDX1) assigned 281 (45%) of 625 patients in the validation cohort to the chemotherapy-benefit group and 344 (55%) to the no-benefit group. In the predicted chemotherapy-benefit group, 5-year overall survival was significantly improved in those patients who had received adjuvant chemotherapy after surgery compared with those who received surgery only (80% 95% CI 73·5–87·1 vs 64·5% 56·8–73·3; univariate hazard ratio 0·47 95% CI 0·30–0·75, p=0·0015), whereas no such improvement in 5-year overall survival was observed in the no-benefit group (72·9% 66·5–79·9 in patients who received chemotherapy plus surgery vs 72·5% 65·8–79·9 in patients who only had surgery; 0·93 0·62–1·38, p=0·71). The predictive single patient classifier groups (chemotherapy benefit vs no-benefit) could predict adjuvant chemotherapy benefit in terms of 5-year overall survival in the validation cohort (pinteraction=0·036 in univariate analysis). Similar results were obtained in the internal evaluation cohort.
The single patient classifiers validated in this study provide clinically important prognostic information independent of standard risk-stratification methods and predicted chemotherapy response after surgery in two independent cohorts of patients with resectable, stage II–III gastric cancer. The single patient classifiers could complement TNM staging to optimise decision making in patients with resectable gastric cancer who are eligible for adjuvant chemotherapy after surgery. Further validation of these results in prospective studies is warranted.
Ministry of ICT and Future Planning; Ministry of Trade, Industry, and Energy; and Ministry of Health and Welfare.
The thermal expansion coefficient (TEC) of single-layer graphene is estimated with temperature-dependent Raman spectroscopy in the temperature range between 200 and 400 K. It is found to be strongly ...dependent on temperature but remains negative in the whole temperature range with a room temperature value of (−8.0 ± 0.7) × 10–6 K–1. The strain caused by the TEC mismatch between graphene and the substrate plays a crucial role in determining the physical properties of graphene, and hence its effect must be accounted for in the interpretation of experimental data taken at cryogenic or elevated temperatures.
Organic solar cells based on bulk heterojunctions (BHJs) are attractive energy‐conversion devices that can generate electricity from absorbed sunlight by dissociating excitons and collecting charge ...carriers. Recent breakthroughs attained by development of nonfullerene acceptors result in significant enhancement in power conversion efficiency (PCEs) exceeding 17%. However, most of researches have focused on pursuing high efficiency of small‐area (<1 cm2) unit cells fabricated usually with spin coating. For practical application of organic photovoltaics (OPVs) from lab‐scale unit cells to industrial products, it is essential to develop efficient technologies that can extend active area of devices with minimized loss of performance and ensured operational stability. In this progress report, an overview of recent advancements in materials and processing technologies is provided for transitioning from small‐area laboratory‐scale devices to large‐area industrial scale modules. First, development of materials that satisfy requirements of high tolerability in active layer thickness and large‐area adaptability is introduced. Second, morphology control using various coating techniques in a large active area is discussed. Third, the recent research progress is also underlined for understanding mechanisms of OPV degradation and studies for improving device long‐term stability along with reliable evaluation procedures.
Recent advances in organic photovoltaic (OPV) materials and processing technologies are promising for transitioning of OPV devices from laboratory‐scale to large‐area industrial scale modules. Recent breakthroughs attained by development of nonfullerene acceptors have led to significant enhancement in power conversion efficiency. It is essential to elucidate degradation mechanisms of OPV devices for improving device long‐term stability.
Under homogeneous uniaxial strains, the Raman 2D band of graphene involving two-phonon double-resonance scattering processes splits into two peaks and they altogether redshift strongly depending on ...the direction and magnitude of the strain. Through polarized micro-Raman measurements and first-principles calculations, the effects are shown to originate from significant changes in resonant conditions owing to both the distorted Dirac cones and anisotropic modifications of phonon dispersion under uniaxial strains. Quantitative agreements between the calculation and experiment enable us to determine the dominant double-resonance Raman scattering path, thereby answering a fundamental question concerning this key experimental analyzing tool for graphitic systems.
Arabidopsis thaliana homeobox 12 (ATHB12), a homeodomain‐leucine zipper class I (HD‐Zip I) gene, is highly expressed in leaves and stems, and induced by abiotic stresses, but its role in development ...remains obscure. To understand its function during plant development, we studied the effects of loss and gain of function. Expression of ATHB12 fused to the EAR‐motif repression domain (SRDX) – P₃₅S::ATHB12SRDX (A12SRDX) and PATHB₁₂::ATHB12SRDX – slowed both leaf and root growth, while the growth of ATHB12‐overexpressing seedlings (A12OX) was accelerated. Microscopic examination revealed changes in the size and number of leaf cells. Ploidy was reduced in A12SRDX plants, accompanied by decreased cell expansion and increased cell numbers. By contrast, cell size was increased in A12OX plants, along with increased ploidy and elevated expression of cell cycle switch 52s (CCS52s), which are positive regulators of endoreduplication, indicating that ATHB12 promotes leaf cell expansion and endoreduplication. Overexpression of ATHB12 led to decreased phosphorylation of Arabidopsis thaliana ribosomal protein S6 (AtRPS6), a regulator of cell growth. In addition, induction of ATHB12 in the presence of cycloheximide increased the expression of several genes related to cell expansion, such as EXPANSIN A10 (EXPA10) and DWARF4 (DWF4). Our findings strongly suggest that ATHB12 acts as a positive regulator of endoreduplication and cell growth during leaf development.
Flexible capacitive pressure sensors with a simple structure and low power consumption are attracting attention, owing to their wide range of applications in wearable electronic devices. However, it ...is difficult to manufacture pressure sensors with high sensitivity, wide detection range, and low detection limits. We developed a highly sensitive and flexible capacitive pressure sensor based on the porous Ecoflex, which has an aligned airgap structure and can be manufactured by simply using a mold and a micro-needle. The existence of precisely aligned airgap structures significantly improved the sensor sensitivity compared to other dielectric structures without airgaps. The proposed capacitive pressure sensor with an alignment airgap structure supports a wide range of working pressures (20–100 kPa), quick response time (≈100 ms), high operational stability, and low-pressure detection limit (20 Pa). Moreover, we also studied the application of pulse wave monitoring in wearable sensors, exhibiting excellent performance in wearable devices that detect pulse waves before and after exercise. The proposed pressure sensor is applicable in electronic skin and wearable medical assistive devices owing to its excellent functional features.
•Carbon enwrapped with bimetallic Ni@ZnO was decorated on carbon nanofibers via chemical surface treatment.•The composite electrode showed highly stable electrochemical performance during long-term ...cycling.•The superior performance is attributed to synergy of Ni@ZnO (high capacity) and carbon (stability).
We present a uniform rhombohedral Ni@ZnO bimetallic oxide host over carbon nanofibers (CNF) as an anode material for Li-ion batteries. Ni@ZnO was produced by annealing a Ni@zeolitic imidazolate framework (ZIF-8) hierarchically decorated over CNFs. The rationally-designed freestanding composite exhibited promising stability in electrochemical performance. A first reversible capacity of 1051 mA·h·g−1 was measured at a current density of 100 mA·g−1, and 88% of this capacity was retained after 100 cycles. We attribute this high capacity retention to the hierarchical structure of the Ni@ZnO-enwrapped carbon framework encapsulating the conductive CNFs, as demonstrated by scanning and transmission electron microscopy. The composite electrode also showed a high specific capacity of ∼497 mA·h·g−1 in high-rate testing at 1000 mA·g−1, because the cage-like framework of the material allowed rapid charge transfer and Li-ion diffusion in the anode.
Addictions have recently been classified as substance use disorder (SUD) and behavioral addiction (BA), but the concept of BA is still debatable. Therefore, it is necessary to conduct further ...neuroscientific research to understand the mechanisms of BA to the same extent as SUD. The present study used machine learning (ML) algorithms to investigate the neuropsychological and neurophysiological aspects of addictions in individuals with internet gaming disorder (IGD) and alcohol use disorder (AUD).
We developed three models for distinguishing individuals with IGD from those with AUD, individuals with IGD from healthy controls (HCs), and individuals with AUD from HCs using ML algorithms, including L1-norm support vector machine, random forest, and L1-norm logistic regression (LR). Three distinct feature sets were used for model training: a unimodal-electroencephalography (EEG) feature set combined with sensor- and source-level feature; a unimodal-neuropsychological feature (NF) set included sex, age, depression, anxiety, impulsivity, and general cognitive function, and a multimodal (EEG + NF) feature set.
The LR model with the multimodal feature set used for the classification of IGD and AUD outperformed the other models (accuracy: 0.712). The important features selected by the model highlighted that the IGD group had differential delta and beta source connectivity between right intrahemispheric regions and distinct sensor-level EEG activities. Among the NFs, sex and age were the important features for good model performance.
Using ML techniques, we demonstrated the neurophysiological and neuropsychological similarities and differences between IGD (a BA) and AUD (a SUD).
•The multimodal model with LR outperformed in distinguishing IGD and AUD.•Highlighting neurophysiological and neuropsychological similarities and differences.•IGD had differential delta and beta source connectivity compared with AUD.•IGD exhibited distinct sensor-level EEG activities in contrast to AUD.•IGD and AUD have similar neuropsychological symptoms.
Graphene produced by exfoliation has not been able to provide an ideal graphene with performance comparable to that predicted by theory, and structural and/or electronic defects have been proposed as ...one cause of reduced performance. We report the observation of domains on exfoliated monolayer graphene that differ by their friction characteristics, as measured by friction force microscopy. Angle-dependent scanning revealed friction anisotropy with a periodicity of 180° on each friction domain. The friction anisotropy decreased as the applied load increased. We propose that the domains arise from ripple distortions that give rise to anisotropic friction in each domain as a result of the anisotropic puckering of the graphene.
Adjuvant chemotherapy after D2 gastrectomy is standard for resectable locally advanced gastric cancer (LAGC) in Asia. Based on positive findings for perioperative chemotherapy in European phase III ...studies, the phase III PRODIGY study (ClinicalTrials.gov identifier: NCT01515748) investigated whether neoadjuvant docetaxel, oxaliplatin, and S-1 (DOS) followed by surgery and adjuvant S-1 could improve outcomes versus standard treatment in Korean patients with resectable LAGC.
Patients 20-75 years of age, with Eastern Cooperative Oncology Group performance status 0-1, and with histologically confirmed primary gastric or gastroesophageal junction adenocarcinoma (clinical TNM staging: T2-3N+ or T4Nany) were randomly assigned to D2 surgery followed by adjuvant S-1 (40-60 mg orally twice a day, days 1-28 every 6 weeks for eight cycles; SC group) or neoadjuvant DOS (docetaxel 50 mg/m
, oxaliplatin 100 mg/m
intravenously day 1, S-1 40 mg/m
orally twice a day, days 1-14 every 3 weeks for three cycles) before D2 surgery, followed by adjuvant S-1 (CSC group). The primary objective was progression-free survival (PFS) with CSC versus SC. Two sensitivity analyses were performed: intent-to-treat and landmark PFS analysis.
Between January 18, 2012, and January 2, 2017, 266 patients were randomly assigned to CSC and 264 to SC at 18 Korean study sites; 238 and 246 patients, respectively, were treated (full analysis set). Follow-up was ongoing in 176 patients at data cutoff (January 21, 2019; median follow-up 38.6 months interquartile range, 23.5-62.1). CSC improved PFS versus SC (adjusted hazard ratio, 0.70; 95% CI, 0.52 to 0.95; stratified log-rank
= .023). Sensitivity analyses confirmed these findings. Treatments were well tolerated. Two grade 5 adverse events (febrile neutropenia and dyspnea) occurred during neoadjuvant treatment.
PRODIGY showed that neoadjuvant DOS chemotherapy, as part of perioperative chemotherapy, is effective and tolerable in Korean patients with LAGC.
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