The Cancer Genome Atlas (TCGA) project recently uncovered four molecular subtypes of gastric cancer: Epstein-Barr virus (EBV), microsatellite instability (MSI), genomically stable (GS), and ...chromosomal instability (CIN). However, their clinical significances are currently unknown. We aimed to investigate the relationship between subtypes and prognosis of patients with gastric cancer.
Gene expression data from a TCGA cohort (
= 262) were used to develop a subtype prediction model, and the association of each subtype with survival and benefit from adjuvant chemotherapy was tested in 2 other cohorts (
= 267 and 432). An integrated risk assessment model (TCGA risk score) was also developed.
EBV subtype was associated with the best prognosis, and GS subtype was associated with the worst prognosis. Patients with MSI and CIN subtypes had poorer overall survival than those with EBV subtype but better overall survival than those with GS subtype (
= 0.004 and 0.03 in two cohorts, respectively). In multivariate Cox regression analyses, TCGA risk score was an independent prognostic factor HR, 1.5; 95% confidence interval (CI), 1.2-1.9;
= 0.001. Patients with the CIN subtype experienced the greatest benefit from adjuvant chemotherapy (HR, 0.39; 95% CI, 0.16-0.94;
= 0.03) and those with the GS subtype had the least benefit from adjuvant chemotherapy (HR, 0.83; 95% CI, 0.36-1.89;
= 0.65).
Our prediction model successfully stratified patients by survival and adjuvant chemotherapy outcomes. Further development of the prediction model is warranted.
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.
It is challenging to develop alloying anodes with ultrafast charging and large energy storage using bulk anode materials because of the difficulty of carrier‐ion diffusion and fragmentation of the ...active electrode material. Herein, a rational strategy is reported to design bulk Bi anodes for Na‐ion batteries that feature ultrafast charging, long cyclability, and large energy storage without using expensive nanomaterials and surface modifications. It is found that bulk Bi particles gradually transform into a porous nanostructure during cycling in a glyme‐based electrolyte, whereas the resultant structure stores Na ions by forming phases with high Na diffusivity. These features allow the anodes to exhibit unprecedented electrochemical properties; the developed Na–Bi half‐cell delivers 379 mA h g−1 (97% of that measured at 1C) at 7.7 A g−1 (20C) during 3500 cycles. It also retained 94% and 93% of the capacity measured at 1C even at extremely fast‐charging rates of 80C and 100C, respectively. The structural origins of the measured properties are verified by experiments and first‐principles calculations. The findings of this study not only broaden understanding of the underlying mechanisms of fast‐charging anodes, but also provide basic guidelines for searching battery anodes that simultaneously exhibit high capacities, fast kinetics, and long cycling stabilities.
With the difficulty in simultaneously achieving a large capacity, ultrafast charging capability, and long cycling stability in a battery anode, a bulk Bi anode is presented for Na‐ion batteries that provides a simple yet practical route to address this issue without using expensive nanoscale materials and additional complex modifications.
The lithium–sulfur (Li–S) battery is considered as a promising future energy storage device owing to its high theoretical energy density, low cost of the raw active material (sulfur), and its ...environmental friendliness. On the other hand, there are still challenging issues for the practical applications of Li–S batteries, including low sulfur utilization, poor cyclability, and rate capability. Although considerable efforts are made to overcome the current obstacles in Li–S batteries, one is still far from meeting the requirements for the commercialization of Li–S batteries. This review outlines the recent progress in Li–S batteries based on novel configurations, such as incorporating functional interlayers/separators beyond the approach for preparing novel cathodes, and discusses the role of the configuration in Li–S batteries. The functions of the newly introduced functional interlayer/separator are highlighted to address the problems of Li–S batteries. From classification of the functions, the perspectives and outlook are presented to rationally design a novel functional interlayer/separator for high‐performance Li–S batteries.
The literature on functional interlayers/separators for Li–S batteries is revisited in terms of the functions such as PS‐, e‐, and k‐functions. The related fundamental and practical issues are discussed, and the trade‐off relationships of PS‐, e‐, and k‐functions are drawn out. Based on the discussion, the design rules for balancing the three functions are suggested.
Aqueous zinc ion batteries (ZIBs) are promising energy storage devices due to the high ionic conductivity of the aqueous electrolyte as well as the safety, eco‐friendliness, and low cost. Vanadium ...oxide‐based materials are attractive cathode materials for aqueous ZIBs because of their high capacity from their layered structure and multiple valences. However, it is difficult to achieve high cycle stability and rate capability due to the low electrical conductivity and trapping of diffused electrolyte cations within the crystal structure, limiting the commercialization of aqueous ZIBs. In this study, the authors propose a facile sonochemical method for controlling the interlayer of the vanadate nanofiber crystal structure using poly(3,4‐ethylene dioxythiophene) (PEDOT) to overcome the shortcomings of vanadium oxide‐based materials. In addition, the electrochemical correlation between the interplanar distance of the expanded vanadate layers by the insertion of PEDOT and the behavior of Zn2+ ions is investigated. As a result, the intercalation of the conducting polymer increases the electron pathway and extends the distance of the vanadate layers, which helps to increase the number of active sites inside the vanadate and accelerate the zinc ion intercalation/de‐intercalation process. Their findings may guide research on the next generation of ZIBs that can replace lithium ion batteries.
The controlling interlayer of the vanadate nanofiber crystal structure using intercalation of conducting polymers is fabricated via a facile sonochemical method and used as a cathode material in zinc ion batteries. Intercalated conducting polymers act as strong pillars and facilitate rapid Zn2+ ion diffusion and electron transport, resulting in reversible electrochemical reactions and high rate performance.
Objectives
To evaluate radiomics studies according to radiomics quality score (RQS) and Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) to ...provide objective measurement of radiomics research.
Materials and methods
PubMed and Embase were searched for studies published in high clinical imaging journals until December 2018 using the terms “radiomics” and “radiogenomics.” Studies were scored against the items in the RQS and TRIPOD guidelines. Subgroup analyses were performed for journal type (clinical vs. imaging), intended use (diagnostic vs. prognostic), and imaging modality (CT vs. MRI), and articles were compared using Fisher’s exact test and Mann-Whitney analysis.
Results
Seventy-seven articles were included. The mean RQS score was 26.1% of the maximum (9.4 out of 36). The RQS was low in demonstration of clinical utility (19.5%), test-retest analysis (6.5%), prospective study (3.9%), and open science (3.9%). None of the studies conducted a phantom or cost-effectiveness analysis. The adherence rate for TRIPOD was 57.8% (mean) and was particularly low in reporting title (2.6%), stating study objective in abstract and introduction (7.8% and 16.9%), blind assessment of outcome (14.3%), sample size (6.5%), and missing data (11.7%) categories. Studies in clinical journals scored higher and more frequently adopted external validation than imaging journals.
Conclusions
The overall scientific quality and reporting of radiomics studies is insufficient. Scientific improvements need to be made to feature reproducibility, analysis of clinical utility, and open science categories. Reporting of study objectives, blind assessment, sample size, and missing data is deemed to be necessary.
Key Points
• The overall scientific quality and reporting of radiomics studies is insufficient.
• The RQS was low in demonstration of clinical utility, test-retest analysis, prospective study, and open science.
• Room for improvement was shown in TRIPOD in stating study objective in abstract and introduction, blind assessment of outcome, sample size, and missing data categories.
Exposure to microplastics (MP) in aquatic environment leads to bioaccumulation in fish, with MP size being a major factor in determining the accumulation profile. MPs absorbed into the fish body ...enter the circulatory system and affect hematological properties, changing the blood physiology. MPs also induce an imbalance in reactive oxygen species (ROS) production and antioxidant capacity, causing oxidative damage. In addition, MPs impact immune responses due to physical and chemical toxicity, and cause neurotoxicity, altering AchE activity. Here, the toxic effects of MPs in fish through various indicators were examined, including bioaccumulation, hematological parameters, antioxidant responses, immune responses, and neurotoxicity in relation to MP exposure, facilitating the identification of biomarkers of MP toxicity following exposure of fish.
Display omitted
•MPs exposure caused bioaccumulation of major tissues in fish.•MPs exposure affected circulatory system and hematological parameters.•ROS-induced by MPs exposure induced oxidative injury to target tissues.•Immuno- and neuro-toxicity were induced by exposure to MPs.
Genomic profiling can provide prognostic and predictive information to guide clinical care. Biomarkers that reliably predict patient response to chemotherapy and immune checkpoint inhibition in ...gastric cancer are lacking. In this retrospective analysis, we use our machine learning algorithm NTriPath to identify a gastric-cancer specific 32-gene signature. Using unsupervised clustering on expression levels of these 32 genes in tumors from 567 patients, we identify four molecular subtypes that are prognostic for survival. We then built a support vector machine with linear kernel to generate a risk score that is prognostic for five-year overall survival and validate the risk score using three independent datasets. We also find that the molecular subtypes predict response to adjuvant 5-fluorouracil and platinum therapy after gastrectomy and to immune checkpoint inhibitors in patients with metastatic or recurrent disease. In sum, we show that the 32-gene signature is a promising prognostic and predictive biomarker to guide the clinical care of gastric cancer patients and should be validated using large patient cohorts in a prospective manner.
Plasmonic nanostructures possessing unique and versatile optoelectronic properties have been vastly investigated over the past decade. However, the full potential of plasmonic nanostructure has not ...yet been fully exploited, particularly with single-component homogeneous structures with monotonic properties, and the addition of new components for making multicomponent nanoparticles may lead to new-yet-unexpected or improved properties. Here we define the term “multi-component nanoparticles” as hybrid structures composed of two or more condensed nanoscale domains with distinctive material compositions, shapes, or sizes. We reviewed and discussed the designing principles and synthetic strategies to efficiently combine multiple components to form hybrid nanoparticles with a new or improved plasmonic functionality. In particular, it has been quite challenging to precisely synthesize widely diverse multicomponent plasmonic structures, limiting realization of the full potential of plasmonic heterostructures. To address this challenge, several synthetic approaches have been reported to form a variety of different multicomponent plasmonic nanoparticles, mainly based on heterogeneous nucleation, atomic replacements, adsorption on supports, and biomolecule-mediated assemblies. In addition, the unique and synergistic features of multicomponent plasmonic nanoparticles, such as combination of pristine material properties, finely tuned plasmon resonance and coupling, enhanced light-matter interactions, geometry-induced polarization, and plasmon-induced energy and charge transfer across the heterointerface, were reported. In this review, we comprehensively summarize the latest advances on state-of-art synthetic strategies, unique properties, and promising applications of multicomponent plasmonic nanoparticles. These plasmonic nanoparticles including heterostructured nanoparticles and composite nanostructures are prepared by direct synthesis and physical force- or biomolecule-mediated assembly, which hold tremendous potential for plasmon-mediated energy transfer, magnetic plasmonics, metamolecules, and nanobiotechnology.
Gastric cancer is a heterogeneous cancer, making treatment responses difficult to predict. Here we show that we identify two distinct molecular subtypes, mesenchymal phenotype (MP) and epithelial ...phenotype (EP), by analyzing genomic and proteomic data. Molecularly, MP subtype tumors show high genomic integrity characterized by low mutation rates and microsatellite stability, whereas EP subtype tumors show low genomic integrity. Clinically, the MP subtype is associated with markedly poor survival and resistance to standard chemotherapy, whereas the EP subtype is associated with better survival rates and sensitivity to chemotherapy. Integrative analysis shows that signaling pathways driving epithelial-to-mesenchymal transition and insulin-like growth factor 1 (IGF1)/IGF1 receptor (IGF1R) pathway are highly activated in MP subtype tumors. Importantly, MP subtype cancer cells are more sensitive to inhibition of IGF1/IGF1R pathway than EP subtype. Detailed characterization of these two subtypes could identify novel therapeutic targets and useful biomarkers for prognosis and therapy response.
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