High tumor mutational burden (TMB-H) is correlated with enhanced objective response rate (ORR) and progression-free survival (PFS) for certain cancers receiving immunotherapy. This study aimed to ...investigate the safety and efficacy of toripalimab, a humanized programmed death-1 (PD-1) antibody, in advanced gastric cancer (AGC), and the predictive survival benefit of TMB and PD-L1.
We reported on the AGC cohort of phase Ib/II trial evaluating the safety and activity of toripalimab in patients with AGC, oesophageal squamous cell carcinoma, nasopharyngeal carcinoma and head and neck squamous cell carcinoma. In cohort 1, 58 chemo-refractory AGC patients received toripalimab (3 mg/kg d1, Q2W) as a monotherapy. In cohort 2, 18 chemotherapy-naive AGC patients received toripalimab (360 mg d1, Q3W) with oxaliplatin 130 mg/m2 qd, d1, capecitabine 1000 mg/m2 b.i.d., d1–d14, Q3W as first-line treatment. Primary end point was ORR. Biomarkers such as PD-L1 and TMB were evaluated for correlation with clinical efficacy.
In cohort 1, the ORR was 12.1% and the disease control rate (DCR) was 39.7%. Median PFS was 1.9 months and median OS was 4.8 months. The TMB-H group showed significant superior OS than the TMB-L group 14.6 versus 4.0 months, HR = 0.48 (96% CI 0.24–0.96), P = 0.038, while PD-L1 overexpression did not correlate with significant survival benefit. A 77.6% of patients experienced at least one treatment-related adverse event (TRAE), and 22.4% of patients experienced a grade 3 or higher TRAE. In cohort 2, the ORR was 66.7% and the DCR was 88.9%. A 94.4% of patients experienced at least one TRAE and 38.9% of patients experienced grade 3 or higher TRAEs.
Toripalimab has demonstrated a manageable safety profile and promising antitumor activity in AGC patients, especially in combination with XELOX. High TMB may be a predictive marker for OS of AGC patients receiving toripalimab as a single agent.
ClinicalTrials.gov NCT02915432.
Icotinib has been previously shown to be non-inferior to gefitinib in non-selected advanced non-small-cell lung cancer patients when given as second- or further-line treatment. In this open-label, ...randomized, phase 3 CONVINCE trial, we assessed the efficacy and safety of first-line icotinib versus cisplatin/pemetrexed plus pemetrexed maintenance in lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) mutation.
Eligible participants were adults with stage IIIB/IV lung adenocarcinoma and exon 19/21 EGFR mutations. Participants were randomly allocated (1 : 1) to receive oral icotinib or 3-week cycle of cisplatin plus pemetrexed for up to four cycles; non-progressive patients after four cycles were maintained with pemetrexed until disease progression or intolerable toxicity. The primary end point was progression-free survival (PFS) assessed by independent response evaluation committee. Other end points included overall survival (OS) and safety.
Between January 2013 and August 2014, 296 patients were randomized, and 285 patients were treated (148 to icotinib, 137 to chemotherapy). Independent response evaluation committee-assessed PFS was significantly longer in the icotinib group (11.2 versus 7.9 months; hazard ratio, 0.61, 95% confidence interval 0.43-0.87; P = 0.006). No significant difference for OS was observed between treatments in the overall population or in EGFR-mutated subgroups (exon 19 Del/21 L858R). The most common grade 3 or 4 adverse events (AEs) in the icotinib group were rash (14.8%) and diarrhea (7.4%), compared with nausea (45.9%), vomiting (29.2%), and neutropenia (10.9%) in the chemotherapy group. AEs (79.1% versus 94.2%; P < 0.001) and treatment-related AEs (54.1% versus 90.5%; P < 0.001) were significantly fewer in the icotinib group than in the chemotherapy group.
First-line icotinib significantly improves PFS of advanced lung adenocarcinoma patients with EGFR mutation with a tolerable and manageable safety profile. Icotinib should be considered as a first-line treatment for this patient population.
We have clearly discriminated the single-, bilayer-, and multiple-layer graphene (<10 layers) on Si substrate with a 285 nm SiO2 capping layer by using contrast spectra, which were generated from the ...reflection light of a white light source. Calculations based on Fresnel's law are in excellent agreement with the experimental results (deviation 2%). The contrast image shows the reliability and efficiency of this new technique. The contrast spectrum is a fast, nondestructive, easy to be carried out, and unambiguous way to identify the numbers of layers of graphene sheet. We provide two easy-to-use methods to determine the number of graphene layers based on contrast spectra: a graphic method and an analytical method. We also show that the refractive index of graphene is different from that of graphite. The results are compared with those obtained using Raman spectroscopy.
The use of intrinsically conducting polymers (ICPs) like polythiophene (PTh), polypyrrole (PPy) and polyaniline (PANI) in devices and systems for electrochemical energy storage and conversion is ...briefly reviewed with a focus on an overview distinguishing between already established uses and potential applications. Basic principles in these three major fields are highlighted:•ICPs as active masses.•ICPs as conductance-enhancing additives.•ICPs as auxiliary materials beyond conductance.
Since the birth of the lithium ion battery in the early 1990s, its development has been very rapid and it has been widely applied as power source for a lot of light and high value electronics due to ...its significant advantages over traditional rechargeable battery systems. Recent research demonstrates the importance of surface structural features of electrode materials for their electrochemical performance, and in this paper the latest progress on this aspect is reviewed. Electrode materials are either anodic or cathodic ones. The former mainly include graphitic carbons, whose surfaces can be modified by mild oxidation, deposition of metals and metal oxides, coating with polymers and other kinds of carbons. Through these modifications, the surface structures of the graphitic carbon anodes are improved, and these improvements include: (1) smoothing the active edge surfaces by removing some reactive sites and/or defects on the graphite surface, (2) forming a dense oxide layer on the graphite surface, and (3) covering active edge structures on the graphite surface. Meanwhile, other accompanying changes occur: (1) production of nanochannels/micropores, (2) an increase in the electronic conductivity, (3) an inhibition of structural changes during cycling, (4) a reduction of the thickness of the SEI (solid-electrolyte-interface) layer, and (5) an increase in the number of host sites for lithium storage. As a result, the direct contact of graphite with the electrolyte solution is prevented, its surface reactivity with electrolytes, the decomposition of electrolytes, the co-intercalation of the solvated lithium ions and the charge-transfer resistance are decreased, and the movement of graphene sheets is inhibited. When the surfaces of cathode materials, mainly including LiCoO
2, LiNiO
2 and LiMn
2O
4, are coated with oxides such as MgO, Al
2O
3, ZnO, SnO
2, ZrO
2, Li
2O⋅2B
2O
3 glass and other electroactive oxides, the coating can prevent their direct contact with the electrolyte solution, suppress the phase transitions, improve the structural stability, and decrease the disorder of cations in the crystal sites. As a result, side reactions and the amount of the heat production during cycling are decreased. Simultaneously, other effects are observed such as: (1) suppression of the dissolution of Mn
2+, (2) higher conductivity, and (3) removal of HF from the electrolyte solution. Consequently, after the above-mentioned effective coating, marked improvements in the electrochemical performance of the electrode materials including the reversible capacity, the coulombic efficiency in the first cycle, the cycling behavior, and the high rate capability have been achieved. However, many surface science issues are still remaining open, e.g., mechanisms of these coatings and different actions of different coatings, and some further directions are suggested for the surface modification of the electrode materials.
Fast radio bursts (FRBs) are highly dispersed, millisecond-duration radio bursts1-3. Recent observations of a Galactic FRB4-8 suggest that at least some FRBs originate from magnetars, but the origin ...of cosmological FRBs is still not settled. Here we report the detection of1,863 bursts in 82 h over 54 days from the repeating source FRB 20201124A (ref.9). These observations show irregular short-time variation ofthe Faraday rotation measure (RM), which scrutinizes the density-weighted line-of-sight magnetic field strength, of individual bursts during the first 36 days, followed by a constant RM. We detected circular polarization in more than half of the burst sample, including one burst reaching a high fractional circular polarization of 75%. Oscillations in fractional linear and circular polarizations, as well as polarization angle as a function of wavelength, were detected. All of these features provide evidence for a complicated, dynamically evolving, magnetized immediate environment within about an astronomical unit (au; Earth-Sun distance) ofthe source. Our optical observations of its Milky-Way-sized, metal-rich host galaxy10-12 show a barred spiral, with the FRB source residing in a low-stellar-density interarm region at an intermediate galactocentric distance. This environment is inconsistent with a young magnetar engine formed during an extreme explosion of a massive star that resulted in a long gamma-ray burst or superluminous supernova.
Since the commercialization of lithium secondary batteries in the early of 1990s, their development has been rapid. Nowadays, improving the preparation technology and electrochemical performance of ...their electrode materials is a major focus in research and development of the materials, power sources and chemistry. Sol–gel methods are a promising way to prepare electrode materials due to their evident advantages over traditional methods, for example, homogeneous mixing at the atomic or molecular level, lower synthesis temperature, shorter heating time, better crystallinity, uniform particle distribution and smaller particle size at nanometer level. In this paper, latest progress in the preparation of electrode materials by sol–gel methods is reviewed, including cathodic ones, e.g., lithium cobalt oxides, lithium nickel oxides, spinel and layered lithium manganese oxides, vanadium oxides and ferrous phosphates, and anodic ones, e.g., tin oxides and titanium oxides. Compared with those prepared by traditional solid-state reaction, the structure stability of the prepared electrode materials and the behavior of lithium intercalation and de-intercalation are much improved. As a result, the prepared products provide better electrochemical performance including reversible capacity, cycling behavior and rate capability. In addition, sol–gel methods can be used to prepare new kinds of electrode materials such as nanowires of LiCoO
2 and nanotubes of V
2O
5, which cannot be easily created by the traditional methods. Further development and application of sol–gel methods will bring about new and better electrode materials, meaning a great promotion to lithium secondary batteries.
A composite polymer membrane is prepared by coating poly(vinylidene fluoride) (PVDF) on the surface of a membrane based on methyl cellulose (MC) which is environmentally friendly and cheap. Its ...characteristics are investigated by scanning electron microscopy, FT-IR, thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The outer PVDF layers are porous which results in high electrolyte uptake and the lithium ion transference number is much larger than that of the pure MC. Moreover, the cell based on Li//LiFePO4 delivers high discharge capacity and good rate behavior in the range of 4.2–2.5 V when the composite membrane is used as the separator and the host of a gel polymer electrolyte, lithium as the counter and reference electrode, and LiFePO4 as cathode. The obtained results suggest that this unique composite membrane shows great attraction in the lithium ion batteries with high safety and low cost.
A composite membrane, PVDF/MC/PVDF, is successfully made. As a host for gel polymer electrolyte, it delivers high lithium ion transference number and good mechanical performance. When used as separator in lithium ion batteries, it shows excellent rate behaviour and cycling performance. Display omitted
•Methyl cellulose (MC) is environmentally friendly and cheap.•A composite polymer membrane is prepared by coating PVDF on the surface of a membrane from MC.•The composite membrane is used as the separator and the host of a gel polymer electrolyte.•The prepared gel polymer electrolyte shows excellent electrochemical performance.
With the rapid growth of perishable food e-commerce businesses, there is a definite need for logistics services providers to manage parcel shipments with multi-temperature requirements. E-commerce ...characteristics, including time-critical delivery, fragmented orders, and high product variety, should be further considered to extend the ontology of multi-temperature joint distribution. However, traditional delivery route planning is insufficient because it merely minimises the cost of travelling between customer locations. Factors related to food quality and arrival time windows should also be considered. In addition, handling dynamic incident management, such as violations of handling requirements during delivery, is lacking. This leads to the likelihood of food deteriorating before it reaches the consumers, thereby impacting customer satisfaction. This paper proposes an Internet of Things-based multi-temperature delivery planning system (IoT-MTDPS), embedding a two-phase multi-objective genetic algorithm optimiser (2PMGAO). The formulation of delivery routing mainly considers product-dependent multi-temperature characteristics, service level, transportation cost, and number of trucks. Once there are unexpected incidents which are detected by Internet of Things technologies, 2PMGAO can optimise the membership functions of fuzzy logic for re-routing the e-commerce delivery plan. With using IoT-MTDPS, the capability of handling e-commerce orders is enhanced, while customer satisfaction can be maintained at a designated level.
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