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The force-electric coupling relationship of the mechanical and electrical properties of piezoelectric composites has been the main factor in the research and development of piezoelectric composites in practical application. A novel orthotropic piezoelectric composite material (OPCM) element is studied in this paper. The properties of the piezoelectric phase and the polymer phase and the influence of the geometrical dimensions of the OPCM on the longitudinal wave drive element are analyzed from the perspective of mechanics and electric power, respectively, and the structural design is optimized. This provides a theoretical basis for the development of OPCM and of new longitudinal ultrasonic phased array actuators.

In complex Industrial Internet of Things (IIoT) application systems, there may exist a variety of functional sub-systems which provide divergent services to the users and the relationship among these services could be strong, which is evidently very common in practice. As one such IoT application, the smart city is designed to use intelligent services in an environment where transport, environment, energy, living, governance, and civic components are integrated to operate the city in a smart and efficient manner. Surprisingly, however, the current state-of-the-art on blockchain does not show the progress on diversified services of the complex IIoT applications. This paper tends to fill the gap and presents a scalable block graph platform and consensus protocol for the complex IIoT applications by adopting the limited resources of IIoT devices. The platform and consensus protocol are generic in the sense that they can support any practical service. The directed acyclic graph represents a significant exhibition in improving the scalability of blockchains and supports our proposed consensus protocol in substance; moreover, the detailed syntax of the block graph is defined. The consensus protocol is showed to be secure against disloyal voting, sybil attack, and 51% attack. The real use case of smart city demonstrates the effectiveness of the proposal.

Background Single agent of PD-1 or PD-L1 inhibitor has been explored recently for resectable patients before surgery. However, the effectiveness and safety of neoadjuvant PD-1 blockade combine with platinum-based doublet chemotherapy has not been fully investigated. Methods 21 patients with squamous cell lung cancer accepted neoadjuvant therapy followed by surgery in Beijing Cancer Hospital were involved. 8 patients accepted two cycles of neoadjuvant platinum-based doublet chemotherapy combine with anti-PD-1 therapy, while 13 patients accepted two cycles of neoadjuvant platinum doublet chemotherapy. Besides baseline tumor staging, chest CT was repeated two to three weeks before surgery. Adverse events were monitored. Peripheral lymphocytes counting was tested during whole treatment. The residual viable tumor cells were counted after surgery to decide a major pathological response (MPR) rate. Selected specimen was sent for immunohistochemical, multiplex immunofluorescence analyses, and T-cell receptor DNA sequencing. Results Comparing with neoadjuvant chemotherapy alone, combination with PD-1 blockade and chemotherapy increased the pathological complete response rate (37·5% Vs. 7·69%) and MPR rate (50% Vs. 38·46%). The pathological evaluation is not consistent with that of radiological evaluation. Although peripheral lymphocyte counting was influenced by neoadjuvant therapy, no unknown adverse effects were reported for all the patients. The tumor infiltrating lymphocytes were observed more in patients accepted PD-1 blockade, and seem infiltrated more in relative “non-responders”. No special pathological features associated with PD-1 blockade were found. Multiplexed immunofluorescence analyses revealed potential immune suppression status in the peritumoral spaces around the residual tumor cells. T-cell receptor DNA sequencing found although some amino acids were shared in primary tumor and lymph nodes in single patients, they are hardly shared among different patients. Conclusions Neoadjuvant chemotherapy combine with PD-1 blockade is safe and feasible for patients with potentially resectable squamous cell lung cancer, to improve the clinical and pathological outcome. Even with PD-1 blockade, the immune suppressive status around the residual tumor cells still exists. The squamous cell lung cancers, and corresponding immune responses are extremely highly individualized. The treatment needs to be designed accordingly. The combination strategy of traditional neoadjuvant chemotherapy with current anti-PD-1 inhibitor are still need further investigation.

Background This study aimed to assess the different survival outcome of stage I-IIIA NSCLC patients who received right-sided and left-sided pneumonectomy, and to further develop the most appropriate treatment strategies. Methods We accessed data from the Surveillance, Epidemiology, and End Results database in the United States for the present study. An innovative propensity score matching analysis was used to minimize the variance between groups. Results For 2,683 patients who received pneumonectomy, cancer-specific survival (HR=0.863, 95%CI: 0.771 to 0.965, P=0.010) and overall survival (OS) (HR=0.875, 95%CI: 0.793 to 0.967, P=0.008) were significantly superior of left-sided pneumonectomy compared with right-sided pneumonectomy. Cancer-specific survival (HR=0.847, 95%CI: 0.745 to 0.963, P=0.011) and OS (HR=0.858, 95%CI: 0.768 to 0.959, P=0.007) were also significantly longer with left-sided over opposite-sided pneumonectomy after matching analysis for 2,050 patients. Adjuvant therapy could significantly prolong cancer-specific survival (67 versus 51 months, HR=1.314, 95%CI: 1.093 to 1.579, P=0.004) and OS (46 versus 30 months, HR=1.458, 95%CI: 1.239 to 1.715, P

An antibacterial Ag nanocluster-based hydrogel (Ag NC@BC) is prepared by the in situ formation of Ag NCs on the nanofibers of a natural bacterial-cellulose (BC) hydrogel. The Ag NC@BC exhibits superior, broad-spectrum antimicrobial performance against both Gram-positive and Gram-negative bacteria, and has a long-acting bactericidal efficacy compared to pristine Ag NCs due to its controlled-release feature for Ag species. Moreover, this fabricated hydrogel also possesses excellent biocompatibility. All of these advantages of Ag NC@BC endow it with great potentials in battling bacterial infections.

The subtle structural change of hydrophilic ligands on the size control of metal nanoclusters (NCs) is unclear but critically important for fundamental understanding. Herein, we report our findings that subtle changes of isomeric ligands lead to a dramatic difference in the size of water-soluble Au NCs. By using isomeric para-mercaptobenzoic acid (p-MBA), m-MBA, and o-MBA as model ligands, it was found that both the steric hindrance and the electronic effect of isomeric ligands significantly influences the size of Au NCs, resulting in the formation of different sized Au44(p-MBA)26 NCs, Au25(m-MBA)18 NCs, and Au37/43(o-MBA)22/26 NCs. Besides this, by collocating any two of the isomeric MBAs as ligand pairs to compare their protecting capability for Au NCs, the protecting abilities of such ligands were found to follow the trend: m-MBA > o-MBA > p-MBA. In addition, the growth process of Au44(p-/o-MBA)26 NCs from Au(I)-MBA complexes in the NaBH4 reduction system was also monitored by real-time UV-vis absorption spectroscopy and ESI mass spectrometry, which complies with the 2e− hopping growth principle, indicating the universal applicability of this principle in the synthesis of thiolated metal NCs. This study provides a fundamental understanding of the effect of ligands’ steric hindrance and electronic factors on the size control of water-soluble metal NCs and sheds light on the formation of metal NCs in the NaBH4 reduction system.

In this paper, a design of active elastic metamaterial that possesses negative density and tunable bulk modulus is presented for the negative refraction of in-plane elastic waves at deep subwavelength scale. The metamaterial is fabricated in an aluminum plate, and the resonant structure in a unit cell of the metamaterial composes of a coated steel that functions as a translational resonator and a radially polarized piezoelectric transducer shunted with negative capacitance. Based on effective continuum theory, the effective mass density and bulk modulus are numerically determined. The passive and active elements work together to generate broad band double-negative material properties. Simulation results verified and demonstrated the negative refraction of elastic waves at the interface between proposed elastic metamaterials and natural solids. The proposed elastic metamaterial may thus be used as a flat lens with broad working frequency regime for in-plane elastic wave focusing.

Over 75% of hospital-acquired or nosocomial urinary tract infections are initiated by urinary catheters, which are used during the treatment of 16% of hospitalized patients. Taking the United States as an example, the costs of catheter-associated urinary tract infections (CAUTI) are in excess of $451 million dollars/year. The biofilm formation by pathogenic microbes that protects pathogens from host immune defense and antimicrobial agents is the leading cause for CAUTI. Thus, tremendous efforts have been devoted to antimicrobial coating for urinary catheters in the past few decades, and it has been demonstrated to be one of the most direct and efficient strategies to reduce infections. In this article, we briefly summarize the current methods for preparation of antimicrobial coatings based on different stages in the biofilm formation, highlight recent progress in the urinary catheter coating material design and selection, discuss approaches to improving their long-term antimicrobial efficacy, biocompatibility, multidrug resistance and recurrent infections, and finally outline future requirements and prospects in antimicrobial coating material design. The scope of the works surveyed is confined to antimicrobial urinary catheters. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 445-467, 2019.

The CAPTRA-Lung study (NCT03334864) is a prospective observational study that will capture real-world data of patients with advanced or metastatic non-small cell lung cancer (NSCLC) across China. The study aims to complement the results from current therapeutic regimens to improve the standard of diagnosis and treatment, evaluate the effectiveness and safety of systemic therapy, and determine the factors influencing the outcomes and responses to treatment. From January 2018 to December 2023, eligible patients with advanced or metastatic NSCLC who are receiving treatment and participating in follow-up at 16 institutions in China, will be enrolled. The demographic, clinical, laboratory, and treatment characteristics and responses to treatment will be recorded in a case report form and transcribed into an electronic data capture system. Overall survival, progression-free survival, overall response rate, and incidence of adverse events will be calculated from the time of initial enrolment until progression evaluated by physicians, last contact, date of death, or analysis cutoff date, respectively. Based on the disease characteristics and treatment strategies, four sub-cohorts will also be established. This study cohort could serve as a pool of patients with advanced or metastatic NSCLC to support further research.

Background We evaluated topoisomerase I (TOPO1) expression in patients with small cell lung cancer (SCLC) and identified predictive factors for the efficacy of second-line topotecan chemotherapy. Methods We retrospectively evaluated the records of SCLC patients treated in our department from January 2007 to December 2016 who received second-line topotecan chemotherapy. Patients with archived tumor samples were enrolled. TOPO1 expression levels were evaluated by immunohistochemistry, and the relationships between TOPO1 expression, clinical factors, chemotherapy efficacy, and survival were analyzed. Results Of the 78 patients enrolled, 67 showed TOPO1 expression (85.9%). Patients were divided into strong (n = 43) or weak (n = 35) expression groups based on staining intensity. Disease control rates for topotecan were 39.5% and 14.3% in the strong and weak groups, respectively (P = 0.014). Second-line median progression-free survival was 2.2 and 2.0 months (P = 0.057), and median overall survival was 8.1 and 6.0 months (P = 0.199) in the strong and weak positive groups, respectively. Patients were also divided into sensitive (n = 47) and refractory (n = 31) disease groups according to the duration from the onset of first-line therapy to relapse. Median second-line progression-free survival was 2.2 and 1.8 months in the sensitive and refractory relapse groups, respectively (P = 0.005). Conclusions TOPO1 expression was prevalent in SCLC patients. Strong expression was associated with an elevated disease control rate after second-line topotecan chemotherapy. Patients with sensitive disease that relapsed after first-line chemotherapy had better survival than refractory patients who received second-line topotecan chemotherapy.

BACKGROUND The PD-L1 antibody atezolizumab has shown promising efficacy in patients with advanced non-small cell lung cancer. But the predictive marker of clinical benefit has not been identified. OBJECTIVE This study aimed to search for potential predictive factors in circulating blood of patients receiving atezolizumab. METHODS Ten patients diagnosed with advanced non-small cell lung cancer were enrolled in this open-label observing study. Circulating immune cells and plasma tumor markers were examined in peripheral blood from these patients before and after atezolizumab treatment respectively. Relation between changes in circulating factors and anti-tumor efficacy were analyzed. RESULTS Blood routine test showed that atezolizumab therapy induced slightly elevation of white blood cells count generally. The lymphocyte ratio was increased slightly in disease controlled patients but decreased prominently in disease progressed patients in response to atezolizumab therapy. Flow cytometric analysis revealed changes in percentage of various immune cell types, including CD4+ T cell, CD8+ T cell, myeloid-derived suppressor cell, regulatory T cell and PD-1 expressing T cell after atezolizumab. Levels of plasma tumor marker CEA, CA125 and CA199 were also altered after anti-PD-L1 therapy. In comparison with baseline, the disease progressed patients showed sharp increase in tumor marker levels, while those disease controlled patients were seen with decreased regulatory T cell and myeloid-derived suppressor cell ratios. CONCLUSIONS The circulating immune cell ratios and plasma tumor marker levels were related with clinical efficacy of atezolizumab therapy. These factors could be potential predictive marker for anti-PD-L1 therapy in advanced non-small cell lung cancer.

In this paper, an elastic metamaterial is proposed by integrating a two-dimensionally periodic honeycomb lattice and tetrachiral metamaterial inclusions for low-frequency wave applications. Plane wave propagation in infinite periodic cells is investigated through using Floquet–Bloch principles and the finite element method. Two separate negative pass bands induced by different mechanisms appear in the band structures of wave propagation in the proposed elastic metamaterial. The working mechanisms of those two negative pass bands are revealed though analyzing the eigenmodes of the unit cell and the dynamic effective material properties. Numerical examples validate the proposed model and show that negative refraction of elastic waves in the elastic metamaterial has been obtained. The design concept of this type of elastic may be of use for the design of broadband flat lenses for elastic wave focusing.

In this paper, we propose and study a single-phase elastic metamaterial with periodic chiral local resonator, which is composed of cylindrical central core surrounded by evenly distributed ligaments and embedded in the matrix in a square lattice. Based on the analytical and numerical analysis, we prove that the translational resonance of the unit cell can lead to negative effective mass density, and the rotational resonance of it can produce negative effective modulus. They can also work together to generate double-negative effective material properties. The wave attenuation of elastic waves in this elastic metamaterial is also demonstrated, which is owing to the negative effective mass density. In addition, the damping of the base material is also considered in the simulation. We finally examine the existence of negative band, and this leads to the physics of negative refraction, which is induced by simultaneous translational and rotational resonance of the unit cell. Our work can serve as the theoretical foundation for the design of single-phase elastic metamaterials.

Metal nanoclusters (MNCs) have ultrasmall size (≤3 nm), precise molecular structure, strong luminescence, size-sensitive physicochemical properties, engineerable metallic composition, and rich yet tailorable surface chemistry, enabling them to be promising for the construction of luminescent sensors for diversified sensing applications in fields of environmental protection, food safety, agriculture, disease diagnosis, biomarker identification, etc. However, a systematic summary is urgently needed to correlate the physicochemical properties of MNCs with their influences on sensing applications, to summarize the synthetic strategies of highly luminescent MNCs towards sensor construction, and to discuss the general configurations and sensing mechanisms of MNCs-based luminescent probes. In this review, we first discuss relevant physicochemical properties of MNCs that may have major influences on the sensing mechanisms/performance of MNCs-based luminescent sensors, and then summarize the main synthetic strategies of highly luminescent MNCs. Then, we briefly illustrate the general configurations of MNCs-based sensors, and elaborately clarify their sensing mechanisms with the exemplification of representative sensing applications. We conclude the review with our perspectives on the opportunities/challenges of MNCs-based luminescent sensors. It is believed that this review will shed light on the design of MNCs-based luminescent sensors for future sensing applications.

Developing highly efficient electrical-driven desalination techniques with minimum energy consumption and high stability is urgently required to settle the global water shortage. Herein, MoS2 nanoflakes-coated carbon nanofibers (CNFs@MoS2) are synthesized via electrospinning and subsequent hydrothermal reaction. The CNFs@MoS2 shows excellent dual-mode capacitive performance, and the CNFs@MoS2-based RCDI exhibits excellent desalination performances (desalination capacity: 53.03 mg g−1; desalination rate: 0.157 mg g−1 s−1) with good long-term stability (11.2% reduction in 30 cycles). The superior desalination performance should be ascribed to the dual-mode capacitive behavior of the CNFs@MoS2 and the rational cell architecture (the ion intercalation/deintercalation capacity of “rocking-chair” capacitive deionization is more balanced than that of the asymmetrical cells like hybrid capacitive deionization). This study is interesting since it exemplifies the critical importance of both dual-mode capacitance electrode materials and rational cell architecture, which could cast light on the further development of high-efficiency electrochemical desalination systems.

In this paper, a manufacturer is considered who is regulated by the cap-and-trade scheme and sells products on an e-business (EB) platform. When this manufacturer is capital-constrained, funds can be accessed via EB platform financing mode, supplier credit financing mode, and mixed financing mode, where the manufacturer accesses funds from both the supplier and the EB platform. Considering the exogenous retail price, this paper develops optimizing models under all three financing modes to investigate the manufacturer's emission reduction, production quantities, and financing strategies. The financing strategy of a slightly capital-constrained manufacturer depends on the usage fee charged by the EB platform. The manufacturer prefers non-financing support if the usage fee rate is too high; otherwise, the manufacturer prefers accessing funds from the EB platform. A moderately capital-constrained manufacturer prefers EB platform financing if the financing rate charged by the EB platform financing is slightly higher than that charged by the supplier. Also, a moderately capital-constrained manufacturer prefers EB platform financing if the usage fee rate is relatively low; otherwise, supplier credit financing is preferred. Furthermore, a heavily capital-constrained manufacturer prefers mixed financing if the financing rate charged by the EB platform is higher than that charged by the supplier; otherwise, the manufacturer prefers EB platform financing. When the usage fee is endogenous, the EB platform financing mode is better than the non-financing mode for both the capital-constrained manufacturer and the EB platform. Furthermore, the above conclusions are robust when the retail price is endogenous.

Ensartinib, an oral tyrosine kinase inhibitor of anaplastic lymphoma kinase (ALK), has shown systemic and central nervous system efficacy for patients with ALK-positive non-small cell lung cancer (NSCLC).To compare ensartinib with crizotinib among patients with advanced ALK-positive NSCLC who had not received prior treatment with an ALK inhibitor.This open-label, multicenter, randomized, phase 3 trial conducted in 120 centers in 21 countries enrolled 290 patients between July 25, 2016, and November 12, 2018. Eligible patients were 18 years of age or older and had advanced, recurrent, or metastatic ALK-positive NSCLC.Patients were randomized (1:1) to ensartinib, 225 mg once daily, or crizotinib, 250 mg twice daily.The primary end point was blinded independent review committee-assessed progression-free survival (PFS). Secondary end points included systemic and intracranial response, time to central nervous system progression, and overall survival. Efficacy was evaluated in the intent-to-treat (ITT) population as well as a prespecified modified ITT (mITT) population consisting of patients with central laboratory-confirmed ALK-positive NSCLC.A total of 290 patients (149 men [51.4%]; median age, 54 years [range, 25-90 years]) were randomized. In the ITT population, the median PFS was significantly longer with ensartinib than with crizotinib (25.8 [range, 0.03-44.0 months] vs 12.7 months [range, 0.03-38.6 months]; hazard ratio, 0.51 [95% CI, 0.35-0.72]; log-rank P .001), with a median follow-up of 23.8 months (range, 0-44 months) for the ensartinib group and 20.2 months (range, 0-38 months) for the crizotinib group. In the mITT population, the median PFS in the ensartinib group was not reached, and the median PFS in the crizotinib group was 12.7 months (95% CI, 8.9-16.6 months; hazard ratio, 0.45; 95% CI, 0.30-0.66; log-rank P .001). The intracranial response rate confirmed by a blinded independent review committee was 63.6% (7 of 11) with ensartinib vs 21.1% (4 of 19) with crizotinib for patients with target brain metastases at baseline. Progression-free survival for patients without brain metastases was not reached with ensartinib vs 16.6 months with crizotinib as a result of a lower central nervous system progression rate (at 12 months: 4.2% with ensartinib vs 23.9% with crizotinib; cause-specific hazard ratio, 0.32; 95% CI, 0.16-0.63; P = .001). Frequencies of treatment-related serious adverse events (ensartinib: 11 [7.7%] vs crizotinib: 9 [6.1%]), dose reductions (ensartinib: 34 of 143 [23.8%] vs crizotinib: 29 of 146 [19.9%]), or drug discontinuations (ensartinib: 13 of 143 [9.1%] vs crizotinib: 10 of 146 [6.8%]) were similar, without any new safety signals.In this randomized clinical trial, ensartinib showed superior efficacy to crizotinib in both systemic and intracranial disease. Ensartinib represents a new first-line option for patients with ALK-positive NSCLC.ClinicalTrials.gov Identifier: NCT02767804.

BACKGROUND Gemcitabine plus cisplatin (GP) is commonly used to treat lung squamous cell carcinoma (SCC); however, it is not clear which subgroup of lung SCC patients could benefit most from GP treatment. We explored the predictive factors in lung SCC patient cohorts. METHODS Seventy-eight lung SCC patients treated with a first-line GP regimen were enrolled in this retrospective cohort study. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Classification tree models were used to explore the risk factors for PFS and OS in these patients. RESULTS The median PFS and OS in SCC patients treated with a GP regimen were 6.0 and 13.6 months, respectively. Three terminal subgroups were formed for both PFS and OS. The subgroup with a body mass index (BMI) > 23.94 kg/m2 and aged ≤ 54.5 had the longest PFS (9.0 months); the subgroup with a BMI < 23.94 kg/m2 and aged ≤ 54.5 had the shortest PFS (4.05 months). Patients with an objective response (partial or complete response) to treatment had the longest OS (20.0 months), while patients with a BMI ≤ 26.92 kg/m2 and stable or progressive disease as the best response had the shortest OS (11.2 months). CONCLUSIONS BMI and age may be predictors of PFS in lung SCC patients who receive GP treatment. BMI and best response to GP treatment predicts OS in such patients. Patients' clinical pathological characteristics may be used to predict the therapeutic efficacy of chemotherapy and survival.

This study presents a Probability based Impact Localization (PIL) method for plate structures. To this aim, an Error Index (EI) is introduced based on the Time of Arrivals (TOAs) of impact induced flexural waves. Due to dispersive characteristic of flexural waves and also presence of noise in real practices, the exact determination of TOAs is complicated and requires the interpretation of signals. This limits the application of impact localization methods for active systems. To overcome this obstacle, a novel TOA prediction method is developed based on the energy of signals till different times. The proposed PIL method has the following advantages: (a) it can be applied to isotropic/anisotropic plate structures; (b) it doesn’t require any signal interpretation, making it attractive for active impact monitoring systems; (c) for anisotropic materials it doesn’t require the accurate knowledge of the wave velocity in all directions of propagation; (d) it doesn’t need a reference database; and (e) it remains effective even in the presence of noise. The accuracy of the proposed PIL method is experimentally assessed by dropping a steel ball on a carbon fibre composite plate with existing piezoelectric transducers that can also be used for other structural health monitoring applications. It is shown that the proposed PIL method is able to highlight impact location on different regions of composite plate even when 20% of sensors are damaged and receive false signals.

Over the past three decades, business managers and academic researchers have shown considerable interest in understanding how information systems (IS) can lead to competitive advantages for firms. Although in the United States researchers have found that IS competences lead to competitive advantages, it remains unknown whether firms working in emerging economies can capitalize on IS competence for competitive advantages. This article examines the moderating effect of the learning intensity of organizations on the relationship between IS competence and competitive advantages in 122 Chinese firms. Data were collected from a mailed survey of 122 information-technology (IT) managers. The results indicate that flexibility of IT infrastructure, IT business skills, and learning intensity have significant effects on competitive advantages. The learning intensity of organizations positively moderates the relationship between IS business skills and competitive advantages, but has no moderating effect on the relationship between the flexibility of IT infrastructure and competitive advantages.

A facile and low-cost strategy has been demonstrated in this paper for the synthesis of copper sulfides with different shapes and chemical compositions via an one-step hydrothermal method. Various CuSs were fabricated through changing the reaction temperature and further systematically characterized by XRD, EDS, SEM, TEM HAADF-STEM and SAED in details (crooked sheets for CuS-140 (Cu7.2S4), nanoparticles for CuS-160 (Cu7.2S4), tentaculiform for CuS-180 (Cu1.81S)). Encouragingly, the obtained samples also respectively display excellent electrochemical performance as electrodes for supercapacitors and CuS-140 shows the highest capacitance of 1000.2 F/g as compared to 725.8 F/g for CuS-160 and 520.1 F/g for CuS-180 at 1 A/g. The capacitance decreases as the current density range from 1 to 5 A/g and CuS-160 decreased by 80.89% at the current density of 5 A/g, indicating excellent rate property. Particularly, the three as-prepared electrodes also reveal excellent cycling stabilities and the specific capacitance still maintains 94.7%, 90.6% and 100% for CuS-140, CuS-160 and CuS-180 after the completion of 1000 cycles. Therefore, this work provides a promising pathway for the fabrication of high-performance electrode materials for SCs.

Additional file 1: eTable S1. Proportional Subdistribution Hazards Models of Death Rate. eTable S2. Prognostic factors for overall survival by multivariable Cox regression. eFigure S1. Lung cancer related, other cancer related and non-cancer related death rates by (A) age, (B) gender, (C) race and (D) primary tumor location. eFigure S2. Lung cancer related, other cancer related and non-cancer related death rates by (E) Anatomic sites, (F) histology subtype, (G) differentiation and (H) clinical stage. eFigure S3. Lung cancer related, other cancer related and non-cancer related death rates by (I) tumor size, (J) tumor extent, (K) lymph node involvement and (L) examined lymph nodes. eFigure S4. Lung cancer related, other cancer related and non-cancer related death rates by (M) positive lymph nodes, (N) surgery, (O) chemotherapy and (P) radiotherapy. eFigure S5. Schoenfeld−type residuals of a proportional subdistribution hazard model for lung cancer related deaths.

Additional file 1.

With the development of cancer immunotherapy, the combination strategy is becoming prevalent. Multiple relevant clinical trials are ongoing in this field. However, immune-related adverse events (irAEs) occurred more frequently, showing a different pattern from single-agent therapy. It is necessary for clinicians to learn about the characteristics of AEs from combination immunotherapy, and master the skills to deal with them. In this article, we reviewed presently published data about AEs from combination immunotherapy of cancers. We believe a full-scale view about this new treatment strategy will facilitate oncologists to better understand tumor immune response. With cutting edge knowledge, an experienced team can minimize these AEs and help patients to achieve high-quality long-term survival.

Purpose: The optimal systemic treatment for pulmonary large-cell neuroendocrine carcinoma (LCNEC) is still under debate. Previous studies showed that LCNEC with different genomic characteristics might respond differently to different chemotherapy regimens. In this study, we sought to investigate genomic subtyping using cell-free DNA (cfDNA) analysis in advanced LCNEC and assess its potential prognostic and predictive value. Experimental Design: Tumor DNA and cfDNA from 63 patients with LCNEC were analyzed by target-captured sequencing. Survival and response analyses were applied to 54 patients with advanced stage incurable disease who received first-line chemotherapy. Results: The mutation landscape of frequently mutated cancer genes in LCNEC from cfDNA closely resembled that from tumor DNA, which led to a 90% concordance in genomic subtyping. The 63 patients with LCNEC were classified into small-cell lung cancer (SCLC)-like and non–small cell lung cancer (NSCLC)-like LCNEC based on corresponding genomic features derived from tumor DNA and/or cfDNA. Overall, patients with SCLC-like LCNEC had a shorter overall survival than those with NSCLC-like LCNEC despite higher response rate (RR) to chemotherapy. Furthermore, treatment with etoposide-platinum was associated with superior response and survival in SCLC-like LCNEC compared with pemetrexed-platinum and gemcitabine/taxane-platinum doublets, while treatment with gemcitabine/taxane-platinum led to a shorter survival compared with etoposide-platinum or pemetrexed-platinum in patients with NSCLC-like LCNEC. Conclusions: Genomic subtyping has potential in prognostication and therapeutic decision-making for patients with LCNEC and cfDNA analysis may be a reliable alternative for genomic profiling of LCNEC.

Ultrasonic linear phased array actuator for electric-acoustic conversion is the key component of the ultrasonic phased array test system. Focusing on the existing deficiency of using phased array ultrasonic testing technology into complex engineering structure, using the 2D orthotropic piezoelectric composite materials (2D-OPCM) into the research of linear phased array actuator can achieve orientable exciting. The single OPCM element and its array actuator was designed and their mechanical properties of focusing were tested by experiment. The experimental results show that 2D-OPCM ultrasound phased array actuator can achieve precise phased array focusing and deflection, which might be of great promising in the nondestructive evaluation engineering application.

Background Malignant pleural mesothelioma (MPM) is a rare but aggressive tumor that originates from the pleura and has a poor prognosis. Eligible patients can benefit from surgery, but their survival is affected by many factors. Therefore, we created a graphic model that could predict the prognosis of surgically treated patients. Methods We retrospectively analyzed data from the Surveillance, Epidemiology, and End Results database from 2004 to 2014 to identify the key factors affecting the prognosis of surgically treated MPM patients. On this basis we built a nomogram to predict survival. We then evaluated the performance of the nomogram in a validation cohort. Results In a training cohort of 828 cases, independent prognostic factors, including age, gender, histological type, differentiation, N stage, chemotherapy, type of surgery, and lymph node dissection, were identified. We then developed a nomogram to evaluate individual patient survival. In Kaplan-Meier analysis, a higher score in the nomogram was associated with a worse prognosis. We also used a validation cohort consisting of 312 patients to evaluate the performance of the nomogram, which was well calibrated and had good discrimination ability, with concordance indices of 0.715 and 0.656 for the training and validation cohorts, respectively. Conclusion This study has improved our understanding of resected MPM and shown that key factors, including age and histological type, are associated with overall survival. The nomogram is a reliable tool that can help clinicians turn individualized prediction into reality and maximize patient benefit by identifying the most beneficial treatment approach.

Background: Patients (pts) with advanced squamous NSCLC (sqNSCLC) have very limited second-line treatment options after failure of the platinum-based doublet chemotherapy. ORIENT-3 was conducted to compare the efficacy and safety of sintilimab, an anti-PD-1 antibody, with docetaxel in second-line treatment in sqNSCLC. (NCT03150875) Method: Pts with stage IIIB/IIIC or IV (ineligible for radical chemo-radiotherapy) sqNSCLC who have disease progression during or after first-line platimum-based chemotherapy were enrolled and randomized 1:1 to receive sintilimab 200mg (Sin arm) or docetaxel 75mg/m2 (Doc arm) intravenously, Q3W until disease progression or intolerable toxicity. Stratification factor was ECOG score (0 vs. 1). The primary endpoint was overall survival (OS). Results: As of July 31, 2020, 290 pts were enrolled with 145 in each treatment group. Efficacy analysis was based on FAS (n=280), and safety analysis was based on safety set (n=274). Baseline characteristics were well balanced between treatment groups, and most pts in efficacy analysis (75.9% in Sin arm, 77.0% in Doc arm) had ECOG PS score of 1. Pts received a median of 8.0 cycles (range: 1-45) of sintilimab, and 2.0 cycles of docetaxel (range: 1-15). With a median follow-up of 23.56 months, sintilimab had a significant improvement in OS versus docetaxel (median: 11.79 m [95% CI 10.28-15.57] vs. 8.25 m [95% CI 6.47-9.82]; HR 0.74, [95%CI 0.56-0.96], P = 0.02489). The median PFS was also significantly superior in Sin arm (4.30 m, 95% CI 4.04-5.78) to that in Doc arm (2.79 m, 95% CI 1.91-3.19) (HR 0.52, 95% CI 0.39-0.68, P Citation Format: Yuankai Shi, Lin Wu, Xinmin Yu, Yan Wang, Puyuan Xing, Jianying Zhou, Airong Wang, Jianhua Shi, Yi Hu, Ziping Wang, Guangyu An, Yong Fang, Sanyuan Sun, Caicun Zhou, Changli Wang, Feng Ye, Xingya Li, Junye Wang, Mengzhao Wang, Yunpeng Liu, Yanqiu Zhao, Jifeng Feng. ORIENT-3: A randomized, open-label, phase 3 study of sintilimab versus docetaxel in previously treated advanced/metastatic squamous non-small-cell lung cancer (sqNSCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT041.

Results From RATIONALE 303: A Global Phase 3 Study of Tislelizumab (TIS) vs Docetaxel (TAX) as Second- or Third-Line Therapy for Patients With Locally Advanced or Metastatic NSCLC Background: Anti-PD-1/L1 therapies have improved OS by 2-4 mo vs TAX in patients (pts) with advanced NSCLC who progressed after platinum regimens. TIS is an anti-PD-1 antibody engineered to minimize FcγR binding on macrophages, a mechanism of T-cell clearance and potential anti-PD-1 resistance. Methods: RATIONALE 303 (BGB-A317-303; NCT03358875) compared efficacy and safety of TIS vs TAX as 2 or 3L therapy for pts with advanced NSCLC. Patients without oncogenic driver mutation who failed at least 1 prior systemic therapy including a platinum regimen were randomized 2:1 to receive TIS 200 mg IV Q3W (Arm A) or TAX 75 mg/m2 IV Q3W (Arm B). Dual primary endpoints were OS in the ITT analysis set and OS in the PD-L1 high (≥25% TC) analysis set. A prespecified interim analysis (IA) was conducted after ≈426 deaths (76% of planned events); in the IA, formal OS superiority testing was conducted only in the ITT. The IA results are presented. Results: Overall, 805 pts were randomized (n=535, TIS; n=270, TAX); demographics were generally balanced between arms. With a 19-mo median follow-up (441 OS events), median OSITT was significantly longer in Arm A vs B (17.2 vs 11.9 mo; HR=0.64 [95% CI: 0.53, 0.78]; P Conclusions: RATIONALE 303 demonstrated that, as 2 or 3L therapy in pts with advanced NSCLC, TIS was tolerable and prolonged OS by 5-7 mo with improved PFS and ORR vs TAX regardless of histology or PD-L1 expression. ITT Analysis Set (N=805)Arm A Tislelizumab (n=535)Arm B Docetaxel (n=270)EfficacyMedian OS, mo17.211.9OS difference, mo5.3HR (95% CI)a0.64 (0.53, 0.78)P-valuea,b Citation Format: Caicun Zhou, Dingzhi Huang, Xinmin Yu, Yunpeng Liu, Yun Fan, Yongqian Shu, Zhiyong Ma, Ziping Wang, Ying Cheng, Jie Wang, Sheng Hu, Zhihua Liu, Mikhail Dvorkin, Elena Poddubskaya, Umut Disel, Andrey Akopov, Yiyuan Ma, Yan Wang, Zhenyu Pan, Cunjing Yu, Gareth Rivalland. Results from RATIONALE 303: A global phase 3 study of tislelizumab (TIS) vs docetaxel (TAX) as second- or third-line therapy for patients with locally advanced or metastatic NSCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT039.

9013 Background: Au is a novel, irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) with favorable pharmacologic properties that selectively inhibits both EGFR sensitizing and resistance mutations. Au has been approved in China for treatment of patients (pts) with EGFR mutant NSCLC with EGFR T790M upon progression of disease on previous EGFR TKIs (Proc. AACR 2020, Abstract CT190). This Phase III trial assessed the efficacy and safety of Au versus G as initial treatment of patients with advanced NSCLC with EGFRm. Methods: Pts with previously untreated metastatic or locally advanced NSCLC and EGFR exon 19 deletion or L858R were randomly assigned in a 1:1 ratio to receive either Au (110 mg once daily) or G (250 mg once daily). The primary endpoint was progression-free survival (PFS) by RECIST v1.1 per investigator assessment. At 262 PFS events, the study had 90% power to detect a PFS HR = 0.67. Secondary endpoints included overall survival (OS), objective response rate (ORR), duration of response (DoR) and safety. Results: Between Nov 30, 2018 and Sept 6, 2019, 429 patients across 53 sites in China were enrolled and randomized. Pt. characteristics were well-balanced. At the planned final event-driven PFS analysis, Au significantly prolonged PFS (median 19.3 vs 9.9 months, HR 0.46, p-value

e21072 Background: Penpulimab is a human IgG1 monoclonal antibody (mAb) directed against human programmed cell death-1 (PD-1). Penpulimab, with its unique binding epitope, was engineered to eliminate Fc-mediated effector function that compromises anti-tumor immune cell function, and to optimize receptor occupancy by improving duration of drug binding. As a promising multi-target tyrosine kinase inhibitor (TKI), anlotinib significantly improved overall survival in advanced NSCLC patients (pts) in the phase 3 trial ALTER0303. Antiangiogenesis therapy combined with PD-1/PD-L1 inhibitors has shown excellent efficacy in advanced NSCLC pts. This is the trial evaluating chemo-free combination of penpulimab plus anlotinib in treatment-naive advanced NSCLC pts regardless of PD-L1 expression (NCT03866980). Methods: Pts with previously untreated, stage IIIB/IIIC/IV non-squamous NSCLC without sensitizing mutation of the epidermal growth factor receptor (EGFR) gene or translocation of the anaplastic lymphoma kinase (ALK) gene were enrolled. Eligible pts received penpulimab 200mg Q3W in combination with anlotinib 12mg QD (2 weeks on 1 week off) until loss of clinical benefit or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). Secondary endpoints included ORR, disease control rate (DCR), duration of response (DoR) and overall survival. Results: As of January 13, 2021, 26 pts had received the combination therapy of penpulimab plus anlotinib (median age 59.5yrs [range 30-71], 76.9% male, 76.9% ECOG PS 1), with a median treatment duration of 3.5 months. Of 21 pts who have had at least one tumor assessment, the ORR was 57.1% (12 PRs) and DCR was 90.5% (12 PRs, 7 SDs). Median PFS has not been reached, and eleven responders remain in response. Treatment-related adverse events (TRAEs) occurred in 53.8% of pts (≥G3 TRAEs occurred in 15.4% [4/26]). Treatment-related SAEs occurred in 15.4% [4/26], and 7.7% of pts [2/26] had drug interruption or discontinuation due to TRAEs. Most common TRAEs (≥15%) were ALT increased, AST increased, hyperthyroidism and hypertension (15.4% each). Conclusions: The combination of penpulimab plus anlotinib as first-line treatment for locally advanced/metastatic NSCLC showed the promising efficacy with a manageable safety profile, thereby suggesting that this combination therapy may be a viable chemo-free treatment strategy for locally advanced/metastatic NSCLC pts. Clinical trial information: NCT03866980.

e21053 Background: VEGF promotes an immunosuppressive microenvironment and contributes to resistance of immune checkpoint inhibitors in cancer treatment. VEGF inhibitors have been shown to enhance efficacy of checkpoint inhibitors in clinical studies. Vorolanib (CM082) is a multi-target tyrosine kinase inhibitor including VEGF, PDGF, c-kit, and Flt-3. Toripalimab (JS001) is a humanized IgG4 mAb against programmed death-1 (PD-1). This phase II study aims to evaluate efficacy and safety of the combination of vorolanib and JS001 in non-small cell lung cancer (NSCLC) patients who progressed with prior first-line standard therapy. Methods: This single-arm, single-center, phase II study (NCT03848611) enrolls NSCLC patients with measurable disease (RECIST 1.1) and Eastern Cooperative Oncology Group performance status ≤ 1, regardless of PD-L1 status. 15 patients received 150 mg oral CM082 daily plus 240 mg intravenous JS001 every 3 weeks while 3 patients received 100 mg oral CM082 daily plus 240 mg intravenous JS001 every 3 weeks until disease progression or intolerable toxicity. The primary endpoint is objective response rate (ORR). Results: Between April 2019 and July 2020, 18 patients were enrolled. Median age was 64 years. 9 of 18 patients (50%) were adenocarcinoma and 9 of 18 patients (50%) were squamous. Males account for 83% (15/18) with 4 non-smokers among the male patients. At the data cutoff (January 11, 2021), we observed 2 (11%) confirmed and 1 (6%) unconfirmed partial response (PR), 6 (33%) stable disease (SD) and 9 (50%, including 2 PR of the target lesions) progression disease (PD). Tumor shrinkage was seen in 6 (33%) of the 18 patients. Two (11%) patients were still on the study drugs. Interestingly, all the patients with confirmed PR or PR of the target lesions were squamous histology. The most common treatment-related adverse events were proteinuria (67%), elevated ALT (60%), elevated AST (53%), hypertension (40%), and increased bilirubin (40%). Grade 3 adverse events include elevated ALT (20%), elevated AST (20%), liver function damage (13%), elevated GGT (7%), fatigue (7%), bellyache (7%), ruptured and infected tumor (7%), and dysphagia (7%). One Grade 4 adverse event was pulmonary embolism. Conclusions: Vorolanib with toripalimab showed a promising antitumor activity with acceptable safety profiles for patients with NSCLC. We hypothesized that the potential benefits of combination therapy for patients with squamous cell carcinoma may be better than those for patients with adenocarcinoma, and the study is ongoing. Clinical trial information: NCT03848611.

Objective Adjuvant chemotherapy (AC) after curative resection is known to improve the survival of patients with non-small cell lung cancer (NSCLC); however, few studies have reported the correlation between the time to initiation of AC (TTAC) and survival in NSCLC patients. Methods The clinical data of 925 NSCLC patients who received curative resection and post-operative AC at the Cancer Hospital of Chinese Academy of Medical Sciences between 2003 and 2013 were retrospectively analyzed. TTAC was measured from the date of surgery to the initiation of AC. Disease-free survival (DFS) was defined as the duration from surgery to the time of tumor recurrence or last follow-up evaluation. The optimal cut-off value of TTAC was determined by maximally selected log-rank statistics. The DFS curve was estimated using the Kaplan-Meier method, and the Cox proportional hazards regression model was used to identify risk factors independently associated with DFS. Propensity score matching (PSM) was performed for survival analysis using the match data. Results The optimal discriminating cut-off value of TTAC was set at d 35 after curative resection based on which the patients were assigned into two groups: group A (≤35 d) and group B (>35 d). There was no significant difference in the DFS between the two groups (P=0.246), indicating that the TTAC is not an independent prognostic factor for DFS. A further comparison continued to show no significant difference in the DFS among 258 PSM pairs (P=0.283). Conclusions There was no significant correlation between the TTAC and DFS in NSCLC patients. Studies with larger samples are needed to further verify this conclusion.

Based on the resource-based view (RBV) and the transaction cost economics (TCE) theories, we study the impact of IT capability on the performance of port supply chain using an IT-enabled transaction cost frontier model where the IT capability is modeled as a unique production input and as an endogenous transaction attribute as well. By examining the optimal levels of IT capability for different port systems from the viewpoint of production cost and transaction cost, we find theoretical evidence to explain why a port system with a horizontal competitive governance mode less successful at integrating a port IT system in practice. Moreover, we find that the optimal IT capability of an individual port operator is lower than the IT capability in an integrated heterogeneous system. We further investigate how to improve IT capability to the desired system level through different forms of an incentive system that includes a subsidy offered by the port authority to coordinate the entire port system. The fixed subsidy is found to be the most cost effective and the easiest to implement. In addition, considering that information about effort cost for IT capability can be private under a market or hybrid governance mode, we study the performance of a direct revelation mechanism when revealing the port operator's private information and true cost to the port authority. This article is protected by copyright. All rights reserved.

Adjuvant chemotherapy (ACT) after radical surgery is known to improve the survival of patients with non–small cell lung cancer (NSCLC). However, there are few studies reporting the impact of age on the efficacy of ACT in NSCLC patients. All patients who received postoperative ACT in the Cancer Hospital, the Chinese Academy of Medical Sciences, between 2001 and 2013 with complete records in the database of the hospital and met the inclusion criteria were enrolled in this study for analysis. The primary end point was disease‐free survival (DFS) in terms of age. Survival analysis was performed using Kaplan–Meier estimates, log‐rank tests, and Cox's proportional hazards regression analysis. Propensity score matching (PSM) was used, survival analysis and subgroup analysis of the match data were carried out. Of 1095 patients with stage IB to stage IIIA NSCLC who underwent radical resection, 865 cases who met the inclusion criteria were analyzed. Of them, 156 (18.0%) patients were 65 years old or older, and the remaining 709 (82.0%) patients were younger than 65. The DFS between the younger group and the elderly group was not significantly different neither before PSM (100.714 weeks [95% CI: 84.421, 117.007] vs. 99.571 weeks [95% CI: 82.621, 116.522]; P = 0.555) nor after PSM (104.857 weeks [95% CI: 81.495, 128.220] vs. 97.429 weeks [95% CI: 81.743, 113.114]; P = 0.328) using the Kaplan–Meier method.The results suggest that the benefit on DFS was similar regardless of age of NSCLC patients. ACT should not be withheld from elderly patients. However, these conclusions are limited by the nature of this retrospective study, and therefore prospective trials are required for further verification.

Poor prognosis of advanced non‐small‐cell lung cancer (NSCLC) patients and the promising therapeutic effect of platinum urge the oncologists to evaluate the role of platinum doublet as second‐line chemotherapy and establish the definition of platinum sensitivity in NSCLC. We retrospectively analyzed 364 advanced NSCLC patients who received platinum‐doublet regimens as second‐line chemotherapy after platinum‐based first‐line treatment. Patients were divided into four groups by their time‐to‐progression (TTP) after first‐line chemotherapy: 0–3, 4–6, 7–12, and >12‐month group, respectively. Treatment efficacy of patients' overall survival (OS), progression‐free survival (PFS), and response rate (RR), as well as treatment‐related toxicity, were compared among the four groups. A prognosis score system and a nomogram were established by Cox proportional hazard model, and validated by concordance index (c‐index). Median OS was 14.0, 16.0, 20.0, 25.0 months for patients in the 0–3, 4–6, 7–12, >12‐month group, respectively. Age ≤60 years (P = 0.002), female (P = 0.019), and TTP>12 months (P = 0.003) were independent prognostic factors. Prognostic score was calculated by adding 1 point each for any of the above three indicators, with a c‐index of 0.590 (95% confidential interval [CI], 0.552–0.627). Median OS were equal to 25.0, 16.0, and 11.0 months for best (2–3 points), intermediate (1 point) and worst (0 point) category, respectively (P

To observe drug-induced hepatotoxicity by long-term gefitinib administration in the treatment of non-small-cell lung cancer. The data of 101 patients with locally advanced or metastatic non-small-cell lung cancer, for which gefitinib had been used orally for 3 months or longer, were retrospectively analyzed. The median duration of gefitinib administration was 14 months (3-60 months). Forty patients (39.6%) developed abnormal hepatic function, among whom 30 patients (29.7%) had grade I hepatotoxicity, six patients (5.9%) had grade II, and four patients (4.0%) had grade III, respectively. The median time from starting gefitinib oral therapy to developing liver dysfunction was 4 months (1-23 months) for the entire cohort. The incidence of hepatotoxicity in the group with a duration of more than 14 months was much higher than that in the group with a duration of less than 14 months (52.0 vs. 27.5%, P=0.012). In thirty-two patients (32/40), abnormal liver function resolved with hepatoprotective treatment, whereas eight patients (8/40) had persistent grade I hepatotoxicity until the last follow-up. Our study showed that long-term gefitinib-induced hepatotoxicity was a common adverse event, especially for the cohort with a duration of longer than 14 months. In most patients with hepatotoxicity, normal liver function was restored and discontinuation of gefitinib was not necessary.

Background Although programmed cell death protein-1 (PD-1)/programmed death ligand-1 (PD-L1) checkpoint inhibitors have shown prominent efficacy for treatment of advanced lung cancer, the outcomes of metastatic lung cancer remain poor throughout the world. Although progression-free survival (PFS) and overall survival (OS) have improved in the first- and second-line therapy settings for advanced lung cancer, the response rates to PD-1/PD-L1 inhibition range from 20% to 40%. Furthermore, patients may be at risk for immune-related adverse events (irAEs); hence, appropriate patient selection is crucial. This study aimed to identify a panel of plasma cytokines representing prognostic and predictive biomarkers of the response to anti-PD-1/PD-L1 treatment. Methods We prospectively studied 32 lung cancer patients who received anti-PD-1/PD-L1 antibody immunotherapy. Plasma cytokines in peripheral blood samples were evaluated and analyzed using flow cytometry at the time of diagnosis and at 2 months after the initiation of PD-1/PD-L1 inhibition. Results The baseline plasma concentrations of interleukin-18 (IL-18) and C-X-C motif chemokine ligand 10 (CXCL10) were correlated with the degree of tumor response. Moreover, the magnitude of plasma IL-18 and CXCL10 level fluctuations were correlated significantly with the objective tumor response to anti-PD-1/PD-L1 immunotherapy, and patients with high CXCL10 expression had significantly shorter PFS than those with low CXCL10 expression. A strong positive correlation between the fluctuation of IL-18 and interleukin-8 (IL-8) levels was detected, as was a negative correlation between the fluctuation of IL-18 and CXCL10 levels. The level of plasma C-C motif chemokine ligand 5 (CCL5) was significantly higher in patients with irAEs than in those without irAEs. Conclusions Plasma cytokines are related to the clinical efficacy of PD-1/PD-L1 inhibitors. IL-18 and CXCL10 are potential predictive markers for anti-PD-1/PD-L1 therapy in lung cancer patients and may play an important role in selecting patients who would benefit from PD-1/PD-L1 inhibitors.

Rocking-chair Capacitive Deionization (RCDI) is one of the most promising cell architectures for highly efficient capacitive deionization (CDI) to address the fresh-water shortage, and developing Cl−-removal electrode materials of RCDI toward highly-efficient desalination (with high capacity and rate) is of utmost urgency. Herein we report our design on high-performance Cl−-removal electrode material via controllable anchoring of bismuth oxychloride nanostructures (BiOCl; such as nanoplates, nanoflowers, and nanospheres) on electrospun carbon nanofibers (BiOCl-CNF) for RCDI. The BiOCl-CNF based RCDI system displays excellent Cl− storage capacitance as well as freestanding characteristics, which enables it to be a perfect electrode candidate for RCDI. By properly tailoring the composition of the hybrid material, the BiOCl-CNF based RCDI displays outstanding desalination efficacy in terms of desalination capacity (124 mg∙g−1), energy consumption (66.8 Wh∙m−3), and desalination rate (0.52 mg‧g−1‧s−1), which are far more superior than the existing systems from the literatures, exemplifying the critical importance of delicate design in the Cl−-removal electrode materials for improving the desalination performance.

Background: Almonertinib (HS-10296) is an oral, potent, high selective third generation EGFR-tyrosine kinase inhibitor (EGFR-TKI) for sensitizing mutations and EGFR T790M mutation. The preliminary clinical data of almonertinib reported in WCLC showed favorable efficacy and safety in target populations. Here, we presented the latest efficacy data, including the subgroup analysis of central nervous system (CNS) response. Methods: Patients aged at least 18 years with centrally confirmed EGFR T790M mutation, locally advanced or metastatic non-small cell lung cancer (NSCLC) progressing on prior EGFR-TKI treatment, received almonertinib 110 mg orally once daily until disease progression. Patients with asymptomatic, stable brain metastases not requiring steroids were enrolled. The primary endpoint was objective response rate (ORR) by independent central review (ICR) using RECIST v1.1. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), duration of response (DOR), depth of response (DepOR), overall survival (OS) and safety. Response endpoints were assessed in full analysis set (NCT02981108). Results: From May 2018 to October 2018, 244 patients entered study in 36 sites in mainland China (189 patients) and Taiwan (55 patients). Of 88 patients with CNS metastases on baseline brain scans, 23 had at least one intracranial measurable target lesion. At cutoff date (Aug 1, 2019), the median duration of follow-up for progression-free survival was 11.8 months. 168 of 244 patients achieved confirmed partial responses. The ORR was 68.9% (95% CI: 62.6, 74.6). The DCR was 93.4% (95% CI: 89.6, 96.2). The mPFS (48.0% maturity) and mDOR were 12.3 (95% CI: 9.6, 13.8) and 12.4 (95% CI: 11.3, NA) months, respectively. The confirmed CNS ORR and DCR were 60.9% (95% CI: 38.5, 80.3) and 91.3% (95% CI: 72.0, 98.9), respectively. The CNS mPFS (47.8% maturity) was 10.8 (95% CI: 5.5, 12.6) months. The safety profile was consistent with the previous report. The most common grade 3 and 4 adverse reactions were increased blood creatine phosphokinase (17 [7.0%]) and pulmonary embolism (6 [2.5%]). There was no interstitial lung disease reported. Conclusions: Almonertinib demonstrated progression-free survival benefit in EGFR T790M positive NSCLC patients who had progressed after previous EGFR-TKI treatment, especially showed clinically meaningful efficacy against CNS metastases, and the safety profile was consistent with that reported previously. A randomized, controlled, double-blinded, phase III study is ongoing comparing almonertinib with gefinitib in first-line treatment of advanced NSCLC patients. Citation Format: Shun Lu, Qiming Wang, Guojun Zhang, Xiaorong Dong, Cheng-Ta Yang, Yong Song, Gee-Chen Chang, You Lu, Hongming Pan, Chao-Hua Chiu, Zhehai Wang, Jifeng Feng, Jianying Zhou, Xingxiang Xu, Renhua Guo, Jianhua Chen, Haihua Yang, Yuan Chen, Zhuang Yu, Her-Shyong Shiah, Chin-Chou Wang, Nong Yang, Jian Fang, Ping Wang, Kai Wang, Yanping Hu, Jianxing He, Ziping Wang, Jianhua Shi, Shaoshui Chen, Qiong Wu, Changan Sun, Chuan Li, Hongying Wei, Ying Cheng, Wu-Chou Su, Te-Chun Hsia, Jiuwei Cui, Yuping Sun, James Chih-Hsin Yang. A multicenter, open-label, single-arm, phase II study: The third generation EGFR tyrosine kinase inhibitor almonertinib for pretreated EGFR T790M-positive locally advanced or metastatic non-small cell lung cancer (APOLLO) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT190.

Background The number of deaths worldwide caused by coronavirus disease (COVID-19) is increasing rapidly. Information about the clinical characteristics of patients with COVID-19 who were not admitted to hospital is limited. Some risk factors of mortality associated with COVID-19 are controversial (eg, smoking). Moreover, the impact of city closure on mortality and admission rates is unknown. Objective The aim of this study was to explore the risk factors of mortality associated with COVID-19 infection among a sample of patients in Wuhan whose conditions were reported on social media. Methods We enrolled 599 patients with COVID-19 from 67 hospitals in Wuhan in the study; 117 of the participants (19.5%) were not admitted to hospital. The demographic, epidemiological, clinical, and radiological features of the patients were extracted from their social media posts and coded. Telephone follow-up was conducted 1 month later (between March 15 and 23, 2020) to check the clinical outcomes of the patients and acquire other relevant information. Results The median age of patients with COVID-19 who died (72 years, IQR 66.5-82.0) was significantly higher than that of patients who recovered (61 years, IQR 53-69, P Conclusions Older age, diffuse distribution, and hypoxemia are factors that can help clinicians identify patients with COVID-19 who have poor prognosis. Our study suggests that aggregated data from social media can also be comprehensive, immediate, and informative in disease prognosis.