Summary Background Therapy for chronic hepatitis B reduces the risk of progressing to hepatocellular carcinoma (HCC); however, there is no suitable and accurate means to assess risk. This study aimed ...to develop and validate a simple scoring system to predict HCC risk in patients with chronic hepatitis B. Methods The development cohort consisted of 3584 patients without cirrhosis from the community-based Taiwanese REVEAL-HBV study (of whom 131 developed HCC during follow-up), and a validation cohort of 1505 patients from three hospitals in Hong Kong and South Korea (of whom 111 developed HCC during follow-up). We used Cox multivariate proportional hazards model to predict risk of HCC at 3, 5, and 10 years. Variables included in the risk score were sex, age, serum alanine aminotransferase concentration, HBeAg status, and serum HBV DNA level. We calculated the area under receiver operating curve (AUROC) and calibration of predicted and observed HCC risk. Findings A 17-point risk score was developed, with HCC risk ranging from 0·0% to 23·6% at 3 years, 0·0% to 47·4% at 5 years, and 0·0% to 81·6% at 10 years for patients with the lowest and highest HCC risk, respectively. AUROCs to predict risk were 0·811 (95% CI 0·790–0·831) at 3 years, 0·796 (0·775–0·816) at 5 years, and 0·769 (0·747–0·790) at 10 years in the validation cohort, and 0·902 (0·884–0·918), 0·783 (0·759–0·806), and 0·806 (0·783–0·828), respectively, after exclusion of 277 patients in the validation cohort with cirrhosis. Predicted risk was well calibrated with Kaplan-Meier observed HCC risk. Interpretation A simple-to-use risk score that uses baseline clinical variables was developed and validated. The score accurately estimates the risk of developing HCC at 3, 5, and 10 years in patients with chronic hepatitis B. Clinicians can use this score to assess risk of HCC in patients with chronic hepatitis B and subsequently make evidence-based decisions about their clinical management. Funding The Academia Sinica; the National Health Research Institute, Taiwan; and Bristol-Myers Squibb.
Although graphene films have a strong potential to replace indium tin oxide anodes in organic light-emitting diodes (OLEDs), to date, the luminous efficiency of OLEDs with graphene anodes has been ...limited by a lack of efficient methods to improve the low work function and reduce the sheet resistance of graphene films to the levels required for electrodes. Here, we fabricate flexible OLEDs by modifying the graphene anode to have a high work function and low sheet resistance, and thus achieve extremely high luminous efficiencies (37.2 lm W-1 in fluorescent OLEDs, 102.7 lm W-1 in phosphorescent OLEDs), which are significantly higher than those of optimized devices with an indium tin oxide anode (24.1 lm W-1 in fluorescent OLEDs, 85.6 lm W-1 in phosphorescent OLEDs). We also fabricate flexible white OLED lighting devices using the graphene anode. These results demonstrate the great potential of graphene anodes for use in a wide variety of high-performance flexible organic optoelectronics.
An equiatomic CoCrFeMnNi high entropy alloy (HEA) coating layer was prepared via a cold spray (CS) process. In order to control the microstructure and nano-indentation properties of the CS HEA, heat ...treatments were employed. CS HEA coating layer showed a heterogeneous microstructure where ultra-fine grains were formed at the particle interfaces, while coarse grains were formed inside the particles. Furthermore, deformation twins (DTs) were also formed inside the particles due to severe plastic deformation (SPD) in each particle generated during the CS deposition. For the 550 °C heat treatment (HT), fine Cr-rich precipitates were additionally formed at the grain boundary and particle boundary. By contrast, recrystallization occurred during 850 °C HT, while the size of the Cr-rich precipitate increased. The nano-indentation hardness of the CS HEA coating layer was 10.9 GPa, which was ~ 3 times higher than that of the conventional cast HEA. The superior hardness of the CS HEA might has been enabled due to the combination of the high dislocation density, DTs, and ultra-fine grains. Based on the results above, the strategy to control the microstructure and mechanical properties through HT of the equiatomic CoCrFeMnNi HEA coating layer prepared via the CS process has been discussed.
Graphic Abstract
Background
Inactivation of
TP53
, a tumor suppressor gene, is associated with the development of several malignancies, including gastric cancer (GC). The present study aimed to evaluate the ...correlation between the overexpression of p53 and survival in different Lauren-type GCs.
Methods
From May 2003 to December 2019, 3608 GC patients treated endoscopically or surgically at the Seoul National University Bundang Hospital were enrolled for the study. Immunohistochemical staining for p53 was performed on all endoscopic and surgical gastric specimens. Clinicopathologic characteristics with Lauren classification, survival rate, and cancer recurrence were analyzed according to p53 overexpression.
Results
Among 3608 GC patients, p53 overexpression was seen in 1334 patients (37%). p53 overexpression was associated with lower depth of invasion (
P
= 0.026) and Early gastric cancer (
P
= 0.044) in intestinal-type GC, and with advanced TNM stage (
P
< 0.001) and Advanced gastric cancer (
P
< 0.001) in diffuse-type GC. The overall survival (OS) and GC-specific survival (GCSS) were significantly lower in p53 overexpression positive patients. This significance was more pronounced and enhanced in the diffuse-type GC and was absent in the intestinal-type GC. In multivariate analyses, p53 overexpression was associated with poor OS in both subtypes of GC and cancer recurrence in diffuse-type GC. (OS in intestinal-type: adjusted hazard ratio aHR = 1.423,
P
= 0.022; OS in diffuse-type: aHR = 1.401
P
= 0.035; cancer recurrence in diffuse-type: aHR = 1.502,
P
= 0.039).
Conclusion
p53 overexpression was associated with poor prognosis in GC, especially in diffuse-type. In addition, p53 overexpression was associated with early stage disease in intestinal-type GC and with advanced stage disease in diffuse-type GC.
Background
There are few data on the clinical implications of immunosuppressive protein expression in tumors and immune cell infiltration within the tumor microenvironment in patients with gastric ...cancer (GC).
Methods
In this study, 243 patients with curatively resected GC were included. The levels of immunosuppressive protein expression programmed cell death 1 ligand 1 (PD-L1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), and indoleamine 2,3-dioxygenase (IDO) in tumors and the densities of immune cells CD3(+), CD4(+), CD8(+), or PD-1(+) cells within the tumor microenvironment were measured using immunohistochemical analysis.
Results
Positive PD-L1, CTLA-4, and IDO expression was observed in 43.6, 65.8, and 47.7 % of the patients, respectively. Expression of PD-L1, CTLA-4, and IDO was related to less advanced stage, intestinal type, and well/moderately differentiated adenocarcinoma (
P
< 0.05). PD-L1 expression was related to better disease-free survival (DFS) and overall survival (OS) in GC PD-L1(+) vs. PD-L1(−) tumors: 5-year DFS rate, 82.6 vs. 66.9 %; 5-year OS rate, 83.0 vs. 69.1 % (
P
values <0.05). Survival outcomes were also better in patients with a higher density of CD3(+) cells within the tumor microenvironment than in those with a lower density of CD3(+) cells 5-year DFS rate, 80.9 vs. 67.0 %; 5-year OS rate, 82.5 vs. 68.0 % (
P
values <0.05). In multivariate analysis, these two immune markers had a prognostic impact on survival, independent of other clinical variables.
Conclusions
GC patients with immunosuppressive protein expression (PD-L1, CTLA-4, or IDO) had distinct clinicopathological characteristics. PD-L1(+) expression and a high-CD3 tumor microenvironment are favorable prognostic markers in GC.
Objective
To investigate the quality of life (QOL) of patients after laparoscopic sentinel node navigation surgery (SNNS) compared to conventional laparoscopy-assisted distal gastrectomy (LADG) in ...early gastric cancer patients.
Methods
Patients recruited for laparoscopic SNNS surgery between July 2010 and April 2013 were assessed for their QOL. A historical control group was established, consisting of patients who underwent conventional LADG with radical lymphadenectomy from the same institution. QOL questionnaire was taken serially from preoperative week 1 until 12 months postoperatively (1, 3, 6, and 12 months) using the Korean version of the European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaire-core (QLQ-C30) and gastric cancer-specific questionnaire (STO22).
Results
A total of 80 prospectively gathered patients who received SNNS were categorized into the comparison group (SNNS group). The QOL was compared with 78 patients identified to have received LADG from the gastric cancer database of our institution and were sorted into the control group (LADG group). In QLQ-C30, SNNS group showed better functioning scales in all except role functioning and better scores from the symptom scales in fatigue, insomnia, and diarrhea compared to the LADG group. In QLQ-STO22, scores on dysphagia, eating restriction, anxiety, and body image disturbance were better in SNNS group.
Conclusions
Postoperative QOL in laparoscopic gastrectomy combined with SNNS is superior compared to conventional laparoscopic distal gastrectomy in patients with stage I gastric cancer.
Chronic hepatitis B virus(HBV) infection is a major cause of cirrhosis and hepatocellular carcinoma(HCC). Applying the same strategies for antiviral therapy and HCC surveillance to all chronic ...hepatitis B(CHB) patients would be a burden worldwide. To properly manage CHB patients, it is necessary to identify and classify the risk for HCC development in such patients. Several HCC risk scores based on risk factors such as cirrhosis, age, male gender, and high viral load have been used, and have negative predictive values of ≥ 95%. Most of these have been derived from, and internally validated in, treatment-na?ve Asian CHB patients. Herein, we summarized various HCC prediction models, including IPM(Individual Prediction Model), CU-HCC(Chinese University-HCC), GAG-HCC(Guide with Age, Gender, HBV DNA, Core Promoter Mutations and Cirrhosis-HCC), NGM-HCC(NomogramHCC), REACH-B(Risk Estimation for Hepatocellular Carcinoma in Chronic Hepatitis B), and Page-B score. To develop a noninvasive test of liver fibrosis, we also introduced a new scoring system that uses liver stiffness values from transient elastography, including an LSM(Liver Stiffness Measurement)-based model, LSM-HCC, and mR EACH-B(modified REACH-B).
The industrial scale application of graphene and other functional materials in the field of electronics has been limited by inherent defects, and the lack of simple deposition methods. A simple spray ...deposition method is developed that uses a supersonic air jet for a commercially available reduced graphene oxide (r‐GO) suspension. The r‐GO flakes are used as received, which are pre‐annealed and pre‐hydrazine‐treated, and do not undergo any post‐treatment. A part of the considerable kinetic energy of the r‐GO flakes entrained by the supersonic jet is used in stretching the flakes upon impact with the substrate. The resulting “frozen elastic strains” heal the defects (topological defects, namely Stone‐Wales defect and C2 vacancies) in the r‐GO flakes, which is reflected in the reduced ratio of the intensities of the D and G bands in the deposited film. The defects can also be regenerated by annealing.
Deposition of r‐graphene oxide (r‐GO) onto a glass slide. r‐GO sheets stretch upon impact. Pentagonal and heptagonal r‐GO sheets undergo bond translation. The resulting “frozen elastic strains” heal the defects (topological defects, namely Stone‐Wales and C2 vacancies) in the r‐GO flakes, which is reflected in the reduced ratio of the intensities of the D and G bands in the deposited film.
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