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Background: Lung adenocarcinoma (LUAD) has a complex tumor heterogeneity. This study aimed to identify LUAD subtypes and build a reliable prognostic signature based on the activity changes of the hallmark and immunologic gene sets. Methods: Changes in the activities of the hallmark and immunologic gene sets were analyzed based on The Cancer Genome Atlas (TCGA)-LUAD dataset, followed by identification of prognosis-related differential gene sets (DGSs) and their related LUAD subtypes. Survival analysis, correlation with clinical characteristics, and immune microenvironment assessment for subtypes were performed. Moreover, the DGSs among different subtypes were identified, followed by the construction and evaluation of a prognostic risk score model and nomogram. The tumor mutation burden (TMB) of different risk groups wascompared. Results: Two LUAD subtypes were identified based on the activity changes of the hallmark and immunologic gene sets. Cluster 2 had worse prognosis, more advanced tumorand clinical stages, and higher immune infiltration than cluster 1. Moreover, a prognostic risk score signaturewas established using two LUAD subtype-related DGSs, which could stratify patients at different risk levels. A shorter survival time and higher TMB levels were observed in the high-risk patients. The established nomogram accurately predicted the survival outcomes. Conclusions: Our findings revealed that our constructed prognostic signature could accurately predict the survival outcomes and immune microenvironment of patients with LUAD, which was helpful in predicting the prognosis and guiding personalized therapeutic strategies for LUAD.

Fuel cell hybrid power system is a prospective power source for electrical vehicles. To reduce hydrogen consumption and enhance dynamic performance of the system, Action Dependent Heuristic Dynamic Programming (ADHDP) energy management strategy for the fuel cell hybrid power system was proposed. Firstly, topology of the system was analyzed and mathematical model was established through mechanism analysis. Secondly, framework of the ADHDP algorithm was presented, and it was followed by training algorithm for evaluating network and executing network of ADHDP based on Back Propagation (BP) algorithm. Finally, hardware-in-the-loop (HIL) simulation of the fuel cell hybrid power system was carried out to demonstrate the proposed ADHDP algorithm under real operating conditions. The results show that evaluating network and executing network of ADHDP have good convergence performance under different operating conditions. Compared with the other algorithms, the proposed ADHDP energy management strategy has better fuel economy and dynamic performance.

Summary Background The addition of camrelizumab to gemcitabine and cisplatin showed promising activity as first-line therapy in patients with recurrent or metastatic nasopharyngeal carcinoma in a phase 1 trial. We therefore compared camrelizumab plus gemcitabine and cisplatin with placebo plus gemcitabine and cisplatin in a randomised phase 3 trial. Methods In this randomised, double-blind, phase 3 trial done at 28 hospitals in China, patients were eligible if they were aged 18–75 years, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1, and had previously untreated recurrent or metastatic nasopharyngeal carcinoma. Patients were randomly assigned (1:1; using an interactive web-response system with a block size of four) to receive either camrelizumab (200 mg on day 1) or matching placebo intravenously, plus gemcitabine and cisplatin (gemcitabine 1000 mg/m2 on days 1 and 8; cisplatin 80 mg/m2 on day 1) intravenously every 3 weeks for four to six cycles, followed by maintenance therapy with camrelizumab or placebo, until radiographic progression, unacceptable toxicity, start of new anticancer treatment, investigator decision, or withdrawal of consent. Stratification factors used in randomisation were liver metastases, previous radical concurrent chemoradiotherapy, and ECOG performance status. The allocation sequence was generated by an independent randomisation group. The primary endpoint was progression-free survival per independent review committee. The significance threshold for independent review committee-assessed progression-free survival was p=0·0086 (one-sided) at the interim analysis. Efficacy and safety analyses included all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov , NCT03707509 , and is closed for enrolment but is ongoing. Findings Between Nov 13, 2018, and Nov 29, 2019, 343 patients were screened and 263 were eligible and were randomly assigned to the camrelizumab group (n=134) or placebo group (n=129). At the prespecified interim analysis (June 15, 2020), independent review committee-assessed progression-free survival was significantly longer in the camrelizumab group (median 9·7 months [95% CI 8·3–11·4]) than in the placebo group (median 6·9 months [5·9–7·3]; hazard ratio 0·54 [95% CI 0·39–0·76]; one-sided p=0·0002). As of Dec 31, 2020, the most common grade 3 or worse adverse events of any cause were decreased white blood cell count (89 [66%] of 134 patients in the camrelizumab group vs 90 [70%] of 129 patients in the placebo group), decreased neutrophil count (86 [64%] vs 85 [66%]), anaemia (53 [40%] vs 57 [44%]), and decreased platelet count (53 [40%] vs 52 [40%]). Serious adverse events were reported in 59 (44%) of 134 patients in the camrelizumab group and 48 (37%) of 129 patients in the placebo group. Treatment-related deaths occurred in five (4%) patients in the camrelizumab group (two unknown cause of death, one multiple organ dysfunction syndrome, one pharyngeal haemorrhage, and one arrhythmia) and one ( Interpretation Our findings suggest that camrelizumab plus gemcitabine and cisplatin could be a new standard of care for patients with recurrent or metastatic nasopharyngeal carcinoma in the first-line setting. Longer follow-up is needed to confirm this conclusion. Funding Jiangsu Hengrui Pharmaceuticals (formerly Jiangsu Hengrui Medicine). Translation For the Chinese translation of the abstract see Supplementary Materials section.

Air compressor of proton exchange membrane fuel cell (PEMFC) system is usually nonlinear and strong coupled. It is difficult to establish a online optimization oriented model. In order to solve this problem, this paper proposed a nonlinear autoregressive moving average with exogenous inputs (NARMAX) model for air compressor of PEMFC system. The NARMAX model is an equivalent time-varying linear model, and the time-varying parameters are identified by recurrent neural network (RNN). Simulation results show that the proposed method has small fitting error, the error of air flow and pressure ratio approximate zero, while the mean square error (MSE) of air flow and pressure ratio are 1.5171e-07 and 6.3767e-05, respectively. Therefore, the established air compressor model is accurate and effective.

Oxygen excess ratio (OER) is closely correlated with the power generation efficiency and dynamic performance of proton exchange membrane fuel cell (PEMFC) system. As OER changes with varying load, it is prone to oxygen starvation and slow response to OER reference value, and great challenges to OER control technology are brought. To this end, a dual closed-loop weighted fusion control for PEMFC system is proposed. The outer loop is utilized to obtain the optimal OER reference value, and the inner loop is utilized to track the OER reference value. This inner loop combines the merits of active disturbance rejection control (ADRC) algorithm and fuzzy self-tuned PID (FSTPID) method. Simulation results reveal that the proposed approach is superior to the other three methods in reducing the overshoot, settling time and avoiding oxygen starvation issues, and also in improving several key performance indices, such as integrated absolute error, settling time, etc.

Being one of the most lethal cancers that exhibit high levels of heterogeneity, hepatocellular carcinoma (HCC) is associated with diverse oncogenic pathways underpinned by varied driver genes. HCC can be induced by different etiological factors including virus infection, toxin exposure or metabolic disorders. Consequently, patients may display varied genetic profiles, and may respond differently to the treatments involving inhibition of target pathways. These DNA/RNA mutations, copy number variations, chromatin structural changes, aberrant expression of non-coding RNAs and epigenetic modifications were considered as biomarkers in the application of precision medication. To explore how genetic testing could contribute to early diagnosis, prognosis, treatment and postoperative monitoring of HCC, we conducted a systematic review of genetic markers associated with different pathologies. Moreover, we summarized on-going clinical trials for HCC treatment, including the trials for multiple kinase inhibitors and immune checkpoint blockade (ICB). The efficacy of ICB treatment in HCC is not as good as what was observed in lung cancer and melanoma, which might be due to the heterogeneity of the microenvironment of the liver.

Platinum-based chemotherapy is the standard first-line treatment for advanced esophageal squamous cell carcinoma (ESCC). In this phase 3 study (ClinicalTrial.gov: NCT03829969), 514 patients with treatment-naïve advanced ESCC were randomized (1:1) to receive toripalimab or placebo in combination with paclitaxel plus cisplatin (TP) every 3 weeks for up to 6 cycles, followed by toripalimab or placebo maintenance. At the prespecified final analysis of progression-free survival (PFS), a significant improvement in PFS is observed for the toripalimab arm over the placebo arm (hazard ratio [HR] = 0.58; 95% CI, 0.46-0.74; p 0.0001). The prespecified interim analysis of overall survival (OS) also reveals a significant OS improvement for patients treated with toripalimab plus TP over placebo plus TP (HR = 0.58; 95% CI, 0.43-0.78; p = 0.0004). The incidences of grade ≥3 treatment-emergent adverse events are similar between the two arms. Toripalimab plus TP significantly improves PFS and OS in patients with treatment-naïve, advanced ESCC, with a manageable safety profile.

High-performance artificial synaptic devices are key building blocks for developing efficient neuromorphic computing systems. However, the nonlinear and asymmetric weight update of existing devices has restricted their practical applications. Herein, floating gate nonvolatile memory (FG NVM) devices based on two-dimensional (2D) ${\mathrm{Hf}\mathrm{S}}_{2}$/$h$-BN/FG-graphene heterostructures have been designed and investigated as multifunctional NVM and artificial optoelectronic synapses. Benefiting from the FG architecture, the ${\mathrm{Hf}\mathrm{S}}_{2}$-based NVM device exhibits competitive performances, such as a high on:off ratio ($g{10}^{5}$), large memory window (approximately 100 V), excellent charge retention ability ($g{10}^{4}\phantom{\rule{0.2em}{0ex}}\mathrm{s}$), and robust durability ($g{10}^{3}$ cycles). Notably, the artificial optoelectronic synapses based on ${\mathrm{Hf}\mathrm{S}}_{2}$ FG NVM show an impressive large conductance margin and good linearity, owing to the ultrahigh photoresponsivity and photogain of ${\mathrm{Hf}\mathrm{S}}_{2}$. The energy consumption of per spike in our artificial synapse is as low as 0.2 pJ. Therefore, a high recognition accuracy up to 91.5% of the artificial neural network on the basis of our ${\mathrm{Hf}\mathrm{S}}_{2}$-based optoelectronic synapse at the system level has been achieved, which is superior to other reported 2D artificial optoelectronic synapses. This work paves the way forward for all 2D material-based memory for developing efficient optogenetics-inspired neuromorphic computing in brain-inspired intelligent systems.

Background: The epidermal growth factor receptor (EGFR) is one of the most commonly altered genes in non-small cell lung cancer(NSCLC). Of these, insertion mutation in 20 exon (Ex20ins) of the EGFR occurs less frequently. In comparison with the common EGFR mutations (19Del/L858R), the NSCLC patients with Ex20ins have a worse prognosis. Recently, the FDA approved targeted oral therapeutic agent for NSCLC patients with EX20ins mutation, which has markedly improved their survival. Here we carry out a complete analysis of the frequency and types of EGFR 20 Exon insertion mutations in the large-scale NSCLC cohort of the Chinese population. Methods: From January 2020 to October 2021, a total of 4,091 patients were confirmed as NSCLC were included in the study. The Next-generation sequencing was utilized for detecting genetic mutations. Results: Among the 4,091 NSCLC patients, 2,411 (58.9%) experienced EGFR mutations. In which we identified 90 patients(2.2%) with Ex20ins. All of the Ex20ins were localized between amino acids S767-V774, and after C-helix of the EGFR kinase domain. Different from the exon 19 deletion, we found that Ex20ins exhibits various types of mutations. A total of 34 Ex20ins types were detected, with the most common A767_V769dupASV and S768_D770dupSVD mutations, accounting for 26% and 22.2% respectively. In addition, H773dupH (6.67%), H773_V774dupHV(5.56%), H773_V774insAH (2.22%), D770_N771insG (2.22%), and N771_P772insG(2.22%) were also observed in the NSCLC patients. Conclusions: We described the landscape of EGFR Ex20ins in Chinese NSCLC patients cohort. Based on the large sample size, the frequency of the Ex20ins mutation in Chinese NSCLC patients was 2.2%, and the types of EGFR Ex20ins mutation were highly heterogeneous. Citation Format: shun xu, Zhichao Fu. The landscape of EGFR exon 20 insertion mutations in Chinese patients with non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5838.

Background: Many patients with cancer have benefited from immunotherapy represented by the blockade of immune checkpoint PD-1/PD-L1. However, about 4-29% of cancer patients treated with immunotherapy developed hyper-progressive diseases(HPD) with accelerated tumor growth. MDM2/MDM4 amplification was suggested as genomic correlates for elevated risk hyperprogression. The objective of this study was to evaluate the frequency of amplification of MDM2/MDM4 in the Chinese solid tumor patients and to provide advice on the selecting of optimal treatment decisions. Methods: Tumor or blood samples were collected from 2,937 patients with solid cancer, genetic mutations and amplification was detected using the next-generation sequencing(NGS). Results: A total 112 patients with MDM2/MDM4 amplification were identified, including lung cancer 50.9% (57/112), colorectal cancer 14.3% (16/112), gastric cancer 8.0% (9/112), liver cancer 5.4% (6/112), Biliary tract cancers 4.5% (5/112), breast cancer 2.7% (3/112), and pancreatic ductal adenocarcinoma 2.7% (3/112). TMB value was identified, The median TMB for lung cancer was 9.13 mutations/Mb, median TMB for colorectal cancer was 13.8 mutations/Mb, a high TMB value in gastric cancer (median TMB=20.22 mutations/Mb), and median TMB for liver cancer was 17.9 mutations/Mb. Meanwhile, MSI was detected in 8% of patients with MDM2/MDM4 amplification, of which 3 in lung cancer, 5 in colorectal cancer, and 1in gastric cancer. Conclusions: Although amplification of MDM2/MDM4 was observed only in a small proportion of patients, it demonstrated an association with high TMB in several common cancer types. In addition, our data indicate that amplification of MDM2/MDM4 in different types of cancer is heterogeneous and that an appropriate immunotherapy strategy for patients with solid cancer should be noted. Citation Format: xiangyu sun, Zhichao Fu. A comprehensive pan-cancer analysis of MDM2/MDM4 gene amplification in Chinese solid cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5844.

Background: Gene fusion is one of the common types of pathogenic mutation in non-small cell lung cancer(NSCLC). Numerous fusion genes have been identified as important biomarkers and therapeutic targets in NSCLC. The identification and analysis of fusion genes will provide important insights into the mechanisms of NSCLC development and devise novel therapeutic strategies. Here, our primary objective was to describe the landscape of fusion in Chinese patients with NSCLC to explore the new treatment option in NSCLC. Methods: A total of 1192 pathologically confirmed NSCLC samples were collected. The fusion genes were detected using next-generation sequence(NGS). Results: A total of 168 fusion events (14.1%) were identified in 1,192 patients with NSCLC. The most common type of fusion was ALK (64.9%), RET (25%), ROS (8.93%), NTRK1 (3.57%), and FGFR3 (3.57%). In these cases, 109 patients exhibited ALK fusion, including EML4/ALK (97.2%), KIF5B/ALK (0.92%), KLC1/ALK (0.92%), and STRN/ALK (0.92%). A total of 42 patients had RET fusions, of which 83.3%, 11.9%, 2.38%, and 2.38% with KIF5B, CCDC6, GOPC, and TET1 respectively. Notably, RET gene fusions with GOPC (GOPC/RET1), TET1 (TET1/RET1) were first reported in NSCLC and the two novel fusions retained the complete kinase domain of RET. We also found three types of ROS fusions in 15 patients, CD74/ROS1(66.7%) and EZR/ROS1(20%) were the common fusions. Additionally, a new fusion LRIG3/ROS1 which retained the complete kinase domain was identified for the first time in NSCLC patients. Conclusions: We conducted a comprehensive review of fusion genes in Chinese patients with NSCLC. With the exception of common gene fusions, we found three cases of rare fusion mutations, which help to understand the potential pathogenic mechanisms of NSCLC and translate into therapeutic applications. Citation Format: qiuju lin, Zhichao Fu. The fusion gene landscape in Chinese patients with non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5845.

e15117 Background: Fibroblast growth factor receptors (FGFRs) are highly conserved transmembrane tyrosine kinase receptors (RTKS) that regulating several cellular processes such as proliferation, differentiation, migration and survival. In recent years, some studies have documented that signaling through FGFRs impact progression of cancer and the survival of patients with cancer. As a potential therapeutic target, exploring the mutation frequency of FGFRs in more different cancers are necessary. Here we performed a comprehensive analysis of the frequency and types of FGFRs mutations in Chinese cancer patients and provided reference for targeted therapy development. Methods: From January 2020 to December 2021, a total of 4,102 patients with nine common cancers were included in the study. The next-generation sequencing was utilized for detecting genetic mutations. Results: A total 328 patients (7.9%) with FGFR mutation were identified. The FGFR 3 was the most frequently gene in our cohort. Among all the cancer patients, the highest frequency of FGFR mutations was observed in bladder cancer (32.5%) and the percentages in FGFR1, FGFR2 and, FGFR3 were 2.7%, 1.35%, and 6.76% respectively. Furthermore, the proportion of FGFR mutation in lung carcinoma, cholangiocarcinoma, colorectal carcinoma, melanoma, breast carcinoma and ovarian carcinoma was 8.64%, 11.58%, 13%, 16.7%, 9.62% and 10.81% respectively. Additionally, FGFR mutation have been detected in other tumor types, including renal cell carcinoma (5.63%), prostate cancer (5.45%), and gastric carcinoma (13.72%). Conclusions: The present study provided the comprehensive FGFR mutation data of Chinese cancer patients. A high frequency mutation in FGFR have been found in Chinese patients with different cancers, which mean that patients with multiple cancer types might benefit from development of efficient EGFR inhibitors.

e20539 Background: In recent years, the advent of immunotherapy had provided a new approach for non-small cell lung cancer (NSCLC) patients. However, only a small subset of patients can benefit from immune checkpoint inhibitors (ICIs) and the majority of patients still show poorly durable responses. Although some biomarker for predicting clinical efficacy of immunotherapy has been reported, the more proper predictive biomarker is required to screen dominant populations for ICI efficacy. Methods: A total of three publicly available datasets of NSCLC patients treated with immunotherapy were collected for analysis. The discovery contained 57 NSCLC patients sequenced by WES from Miao et al. and another cohort of 75 patients with clinical data and WES data download from Hellman et al. studies. We collected two MSK-IMPACT cohorts including 240 and 350 NSCLC immunotherapy patients used as validation set from cBioPortal(www.cbioportal.org). Results: We detected 79 mutation genes (mutation frequency > 5% cases) associated with a better progressive free survival PFS (HR < 1, P value < 0.05) by univariate Cox regression analysis in the discovery cohort. The survival analysis results indicated that patients who carried co-occurring mutations of GRIN2A, FAT1, FLT1, ASXL2, PTPRS , and DDR pathway showed a longer PFS (p = 0.004, HR = 0.37, 95% Cl 0.235-0.644). Notably, comparing with the non-co-mutation group, the higher tumor mutation burden (TMB)(P < 0.01) and more durable clinical benefit(P < 0.05) have been detected in the co-mutations group. Next, we validated our findings using two independent validation cohorts who received ICI therapies from MSKCC, the results showed that PFS was significantly prolonged in the co-mutation group (p = 0.036, HR = 0.67, 95%CI 0.47-0.97), and with no significant difference in overall survival. Additionally, the TMB was significantly higher in the co-mutation group than that harbored non-co-mutation in two validation cohorts(p < 0.01). Conclusions: In this study, we found that co-occurring mutations in five genes and DDR pathways can predict a better immunotherapy efficacy of NSCLC. Therefore, the co-mutation signature may have great potential as a biomarker for guiding immunotherapy of NSCLC.

e15517 Background: Colorectal cancer is a common malignant tumor in the gastrointestinal tract and represents the third deadliest cancer worldwide. Recently, the advent of immune checkpoint inhibitors (ICIs) has provided significant survival benefit for colorectal cancer(CRC) patients with MSI-H/dMMR. However, the majority of MSS/pMMR CRC patients show poorly durable responses of immunotherapy, and more proper predictive biomarker is required to guiding immunotherapy treatment for these CRC cancer patients. The purpose of the present study was to explore the role of Homologous recombination (HR) pathway alternations in predicting the prognosis of MSS/pMMR CRC patients treated with ICIs. Methods: All data of patients undergoing immunotherapy were obtained from the cBioPortal database (https://www. cbioportal.org), which include genomic sequencing datasets and clinical data for eight diverse cancers from MSKCC, and RNAseq data and clincial data for CRC from International Cancer Genome Consortium (TCGA). Results: In the MSKCC cohort, HR mutation was analyzed by univariate Cox regression in nine different cancers, the analysis performed revealed HR mutation were associated with a better prognosis of colcrectal cancer (p = 0.003; HR, 0.24; 95%Cl, 0.09-0.62) and melanoma (p = 0.042; HR,0.66; 95% Cl, 0.09-0.62), with no significant correlations in other cancers. By doing survival analysis of the CRC patients without MSI-H/dMMR status by Kaplan–Meier (KM) method. The results showed that the OS of the patients with HR-MT was signifcantly longer than that of patients with HR-WT (P = 0.0029), and no significance association has been identified between Tumor Mutational Burden (TMB) and overall prognosis of patients without MSI-H/dMMR. Notably, in TCGA CRC dataset, we found TMB and Neoantigens were significantly higher in HR-MT patients than that of HR-WT patients(p < 0.0001), and a higher-level expression of CD8 T cell were also observed in the HR-MT patients patients in TCGA dataset (p = 0.036). Conclusions: Our study results showed that HR-mutation is a favorable prognostic factor in these CRC patients with MSS/pMMR, which can be used as a potential biomarker for predicting the immunotherapy efficacy of these patients.

Objective: To explore the effectiveness and safety of apatinib in patients with malignant glioma. Methods: This is a retrospective case-control study in a single center. Patients with new postoperative pathological diagnosis of malignant glioma (WHO Ⅲ~Ⅳ) were selected. Enrolled patients received concurrent chemoradiotherapy (60Gy/30f/6w; TMZ75mg/m2,po,d1-d42)combined with or without apatinib (250mg, po, d1-d42,qd), then maintain 6 cycles(28 days a cycle)of TMZ chemotherapy(200mg/m2, d1-d5) .The primary endpoints were progression free survival (PFS) and the grade of peritumoral brain edema (PTBE) evaluated by edema index(EI). The secondary endpoint was overall survival(OS). Hazard ratios of PFS and OS were compared between trials in a Cox proportional hazards model.Results: 48 patients (24 in apatinib group and 24 in control group) were enrolled in this study. The results elucidated that the mPFS of the apatinib group was longer than control group, but the difference was not statistically significant(9.63 vs. 7.33 months; P=0.073).As for mOS, the results of two groups were almost similar.(15.47 vs. 14.70 months, P=0.612). Cox multivariate regression model revealed that Apatinib was not a prognostic factor for PFS and OS (P>0.05). Multivariate analysis showed that tumor grade was an important risk factor for PFS and OS.The grade of PTBE was improved in 15 of 23 patients (65.2%) in apatinib group versus 6 of 24 (25%) in control group. There was no grade 3 or 4 adverse events and serious adverse events.Conclusion: Apatinib group can improve mPFS by 2.3 months in patients with malignant glioma,but there was no statistical significance (P>0.05).The results also indicated that apatinib conferred a significant beneficial effect on PTBE improvement. All occurred adverse reactions were moderate and controllable.

Phase-locked loop (PLL) is commonly used for three-phase grid-connected inverters to obtain the information of grid synchronization, and PLL dynamics are the key factors for stable operation of the inverters. Under weak grid conditions, the coupling between PLL and grid impedance can result in harmonic resonance, or even instability in the system. In this paper, the effect of PLL dynamics and grid impedance on the stability of three-phase grid-connected inverters is studied with the d – q impedance model. Besides, the variable transfer relationship is used to analyze the influence of PLL perturbations on output current under weak grid conditions. To suppress low-order harmonics of the network current caused by PLL perturbations under weak grid conditions, a novel feedforward control method is proposed to compensate PLL perturbations and revise the output impedance, where the operation of the inverter and PLL dynamics have been taken into account in the design process. By analyzing the impedance characteristic of the system, it can be demonstrated that the proposed method can enhance the stability of grid-connected inverters under weak grid conditions and reduce the impact of PLL perturbations on grid-connecting current. The experimental results indicate that the low-order harmonics of the network current can be suppressed effectively, which verifies the analysis.

Proton exchange membrane fuel cell (PEMFC) is an environmentally friendly and efficient power generation device. It offers promising advantages over conventional power sources in backup power supplies, distributed generation and vehicle power. A rapid response to the actual power required by load is of great significance to improve the economy and efficiency of the system. However, due to various uncertainties such as frequent disturbances and inaccurate model, the net power control has certain challenges. Therefore, a data-driven nonlinear subspace identification method is developed to build the model of net power. A segmented and consecutive step response of net power for PEMFC system are identified and analyzed, the models are verified by high-fidelity simulation data. Data-driven active disturbance rejection control (ADRC) algorithm is developed to control the model. Internal and external disturbances are considered as a total term, which is estimated and compensated by real-time input-output data and ADRC, respectively. Compared with the integral absolute error of the conventional proportion integral and proportion integral derivative control, the performance of ADRC is improved by about 89.81 % and 78.92%, respectively. Therefore, the proposed ADRC can improve the dynamic performance of PEMFC system in terms of set-point tracking performance, disturbance rejection performance and robustness.

Summary Background Patients with advanced or metastatic oesophageal squamous cell carcinoma have poor prognosis and few treatment options after first-line therapy. We aimed to assess efficacy and safety of the anti-PD-1 antibody camrelizumab versus investigator's choice of chemotherapy in previously treated patients. Methods ESCORT is a randomised, open-label, phase 3 study of patients aged 18 to 75 years with a histological or cytological diagnosis of advanced or metastatic oesophageal squamous cell carcinoma done at 43 hospitals in China. Eligible patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and had progressed on, or were intolerant to, first-line standard therapy. Patients were randomly assigned (1:1) to camrelizumab (200 mg every 2 weeks) or chemotherapy with docetaxel (75 mg/m2 every 3 weeks) or irinotecan (180 mg/m2 every 2 weeks), all given intravenously. Central randomisation was done using the Randomization and Trial Supply Management system with block size randomly generated as four or six and stratified by disease and ECOG performance status. The primary endpoint was overall survival, assessed in randomised patients who had received at least one dose of treatment. Safety was assessed in all treated patients. The trial is registered with ClinicalTrials.gov , NCT03099382 , and is closed to new participants. Findings From May 10, 2017, to July 24, 2018, 457 (75%) of 607 screened patients were randomly assigned to treatment, of whom 228 received camrelizumab treatment and 220 received chemotherapy. As of data cutoff on May 6, 2019, with a median follow-up time of 8·3 months (IQR 4·1–12·8) in the camrelizumab group and 6·2 months (3·6–10·1) in the chemotherapy group, median overall survival was 8·3 months (95% CI 6·8–9·7) in the camrelizumab group and 6·2 months (5·7–6·9) in the chemotherapy group (hazard ratio 0·71 [95% CI 0·57–0·87]; two-sided p=0·0010). The most common treatment-related adverse events of grade 3 or worse were anaemia (camrelizumab vs chemotherapy: six [3%] vs 11 [5%]), abnormal hepatic function (four [2%] vs one [ Interpretation Second-line camrelizumab significantly improved overall survival in patients with advanced or metastatic oesophageal squamous cell carcinoma compared with chemotherapy, with a manageable safety profile. It might represent a potential option of standard second-line treatment for patients with oesophageal squamous cell carcinoma in China. Funding Jiangsu Hengrui Medicine.

The accuracy of OCR is usually affected by the quality of the input document image and different kinds of marred document images hamper the OCR results. Among these scenarios, the low-resolution image is a common and challenging case. In this paper, we propose the cascaded networks for document image super-resolution. Our model is composed by the Detail-Preserving Networks with small magnification. The loss function with perceptual terms is designed to simultaneously preserve the original patterns and enhance the edge of the characters. These networks are trained with the same architecture and different parameters and then assembled into a pipeline model with a larger magnification. The low-resolution images can upscale gradually by passing through each Detail-Preserving Network until the final high-resolution images. Through extensive experiments on two scanning document image datasets, we demonstrate that the proposed approach outperforms recent state-of-the-art image super-resolution methods, and combining it with standard OCR system lead to signification improvements on the recognition results.

Standard first-line therapy for advanced or metastatic esophageal carcinoma is chemotherapy, but the prognosis remains poor. Camrelizumab (an anti-programmed death receptor 1 [PD-1] antibody) showed antitumor activity in previously treated advanced or metastatic esophageal squamous cell carcinoma.To evaluate the efficacy and adverse events of camrelizumab plus chemotherapy vs placebo plus chemotherapy as a first-line treatment in advanced or metastatic esophageal squamous cell carcinoma.This randomized, double-blind, placebo-controlled, multicenter, phase 3 trial (ESCORT-1st study) enrolled patients from 60 hospitals in China between December 3, 2018, and May 12, 2020 (final follow-up, October 30, 2020). A total of 751 patients were screened and 596 eligible patients with untreated advanced or metastatic esophageal squamous cell carcinoma were randomized.Patients were randomized 1:1 to receive either camrelizumab 200 mg (n = 298) or placebo (n = 298), combined with up to 6 cycles of paclitaxel (175 mg/m2) and cisplatin (75 mg/m2). All treatments were given intravenously every 3 weeks.Coprimary end points were overall survival (significance threshold, 1-sided P .02) and progression-free survival (significance threshold, 1-sided P .005).Of the 596 patients randomized (median age, 62 years [interquartile range, 56-67 years]; 523 men [87.8%]), 1 patient in the placebo-chemotherapy group did not receive planned treatment. A total of 490 patients (82.2%) had discontinued the study treatment. The median follow-up was 10.8 months. The overall survival for the camrelizumab-chemotherapy group was a median of 15.3 months (95% CI, 12.8-17.3; 135 deaths) vs a median of 12.0 months (95% CI, 11.0-13.3; 174 deaths) for the placebo-chemotherapy group (hazard ratio [HR] for death, 0.70 [95% CI, 0.56-0.88]; 1-sided P = .001). Progression-free survival for camrelizumab plus chemotherapy was a median of 6.9 months (95% CI, 5.8-7.4; 199 progression or deaths) vs 5.6 months (95% CI, 5.5-5.7; 229 progression or deaths) for the placebo-chemotherapy group (HR for progression or death, 0.56 [95% CI, 0.46-0.68]; 1-sided P .001). Treatment-related adverse events of grade 3 or higher occurred in 189 patients (63.4%) in the camrelizumab-chemotherapy group and 201 (67.7%) in the placebo-chemotherapy group, including treatment-related deaths among 9 patients (3.0%) and 11 patients (3.7%), respectively.Among patients with advanced or metastatic esophageal squamous cell carcinoma, the addition of camrelizumab to chemotherapy, compared with placebo and chemotherapy, significantly improved overall survival and progression-free survival.ClinicalTrials.gov Identifier: NCT03691090.

6000 Background: Camrelizumab plus gemcitabine and cisplatin (GP) showed promising preliminary anticancer activity as first line (1L) therapy in patients (pts) with recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) in a phase 1 trial ( W Fang et al; Lancet Oncol 2018). Here, we compared the efficacy and safety of camrelizumab with placebo plus GP as 1L therapy for pts with R/M NPC in a phase 3 trial. Methods: Eligible pts with previously untreated R/M NPC were randomized (1:1) to receive either camrelizumab (200 mg on day 1) plus gemcitabine (1000 mg/m2 on days 1, 8) and cisplatin (80 mg/m2 on day 1) or placebo plus the same chemotherapy regimens intravenously Q3W for a maximum of 6 cycles, followed by maintenance therapy with camrelizumab or placebo. The primary end point was progression-free survival (PFS) per independent review committee (IRC). Secondary end points included investigator-assessed PFS, objective response rate (ORR), disease control rate (DCR), duration of response (DOR), overall survival (OS) and tolerability. This trial is registered with ClinicalTrials.gov, number NCT03707509. Results: From Nov 2018 to Nov 2019, 263 pts from 28 centers were randomized to camrelizumab plus GP (n = 134, camrelizumab arm) or placebo plus GP (n = 129, placebo arm). At data cutoff on Dec 31, 2020 (67.7% maturity), 178 IRC-assessed PFS events occurred, and the median follow-up was 15.6 months (range 1.3-25.5). The median PFS per IRC was 10.8 months (95% CI 8.5-13.6) in the camrelizumab arm and 6.9 (95% CI 5.9-7.9) in the placebo arm (HR 0.51 [95% CI 0.37-0.69]; one-sided P < 0.0001). Investigator-assessed PFS showed similar results. IRC-assessed ORR was 88.1% (95% CI 81.3-93.0) in the camrelizumab arm and 80.6% (95% CI 72.7-87.1) in the placebo arm, with a median DOR of 9.9 (95% CI 7.7-12.5) and 5.7 months (95% CI 5.2-6.9; HR 0.48 [95% CI 0.34-0.68]), respectively. The DCR was 96.3% (95% CI 91.5-98.8) in the camrelizumab arm and 94.6% (95% CI 89.1-97.8) in the placebo arm. 18-month PFS rate was 34.8% (95% CI 25.7-44.1) vs 12.7% (95% CI 6.8-20.5), respectively. OS benefit was observed in the camrelizumab arm vs placebo arm (median not reached vs 22.6 months; HR 0.67 [95% CI 0.41-1.11]). Grade ≥3 treatment-related adverse events (TRAEs) occurred in 93% of pts in the camrelizumab arm and 90% in the placebo arm. The most common grade ≥3 TRAEs were decreased white blood cell count (66% vs 70%), decreased neutrophil count (64% vs 65%), decreased platelet count (40% vs 40%), and anemia (39% vs 43%). None of the differences were statistically significant. The safety profile was as expected, with no new signals observed. Conclusions: Addition of camrelizumab to GP significantly prolonged PFS as 1L therapy for R/M NPC, with a manageable safety profile. These data suggest that first line treatment with camrelizumab plus GP could be a standard of care for R/M NPC. Clinical trial information: NCT03707509.