Leptomeningeal metastases (LM) are more frequent in non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. Due to limited access to leptomeningeal lesions, the ...purpose of this study was to explore the potential role of cerebrospinal fluid (CSF) as a source of liquid biopsy in patients with LM.
Primary tumor, CSF, and plasma in NSCLC with LM were tested by next-generation sequencing. In total, 45 patients with suspected LM underwent lumbar puncture, and those with EGFR mutations diagnosed with LM were enrolled.
A total of 28 patients were enrolled in this cohort; CSF and plasma were available in 26 patients, respectively. Driver genes were detected in 100% (26/26), 84.6% (22/26), and 73.1% (19/26) of samples comprising CSF cell-free DNA (cfDNA), CSF precipitates, and plasma, respectively; 92.3% (24/26) of patients had much higher allele fractions in CSF cfDNA than the other two media. Unique genetic profiles were captured in CSF cfDNA compared with those in plasma and primary tissue. Multiple copy number variations (CNVs) were mainly identified in CSF cfDNA, and MET copy number gain identified in 47.8% (11/23) of patients was the most frequent one, while other CNVs included ERBB2, KRAS, ALK, and MYC. Moreover, loss of heterozygosity (LOH) of TP53 was identified in 73.1% (19/26) CSF cfDNA, which was much higher than that in plasma (2/26, 7.7%; P<0.001). There was a trend towards a higher frequency of concomitant resistance mutations in patients with TP53 LOH than those without (70.6% versus 33.3%; P=0.162). EGFR T790M was identified in CSF cfDNA of 30.4% (7/23) of patients who experienced TKI progression.
CSF cfDNA could reveal the unique genetic profiles of LM and should be considered as the most representative liquid biopsy medium for LM in EGFR-mutant NSCLC.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
CTONG0806 assessed the efficacy of pemetrexed versus gefitinib as second-line treatment in advanced nonsquamous nonsmall-cell lung cancer (NSCLC) harboring wild-type epidermal growth factor receptor ...(EGFR).
Patients with locally advanced or metastatic nonsquamous NSCLC harboring wild-type EGFR, detected by direct sequencing, and previously treated with platinum-based chemotherapy were randomized to receive gefitinib (250 mg/day) orally or pemetrexed (500 mg/m2) i.v. on day 1 of a 21-day cycle until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS). The Independent Review Committee (IRC) evaluated all pictorial data.
From February 2009 to August 2012, 161 patients were enrolled, and 157 were assessable (81 in the gefitinib arm, 76 in the pemetrexed arm). Baseline characteristics were balanced between the two arms. The median PFSs were 4.8 versus 1.6 months in the pemetrexed and gefitinib arms, respectively hazard ratio (HR) 0.54, 95% confidence interval (CI) 0.40–0.75, P < 0.001 as confirmed by IRC evaluation (5.6versus 1.7 months, HR 0.53, 95% CI 0.38–0.75, P < 0.001). The median overall survival (OS) showed a trend of superiority in the pemetrexed arm (12.4 versus 9.6 months, HR 0.72, 95% CI 0.49–1.04, P = 0.077). Quality-of-life assessment showed no marked difference between the arms. No unexpected adverse events were found. Of 108 patients with sufficient DNA samples, EGFR mutation status was re-tested by Scorpion amplification refractory mutation system (ARMS); 32 (29.6%) tested positive (19 in the pemetrexed arm, 13 in the gefitinib arm; median PFS: 8.1 versus 7.0 months, HR 0.94, 95% CI 0.43–2.08, P = 0.877).
CTONG0806 is the first trial to show significant improvement in PFS and an improved OS trend with pemetrexed compared with gefitinib as second-line setting treatment of EGFR wild-type advanced nonsquamous NSCLC. ARMS is superior to direct sequencing in excluding false-negative patients.
NCT00891579.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•LaFe11.6Si1.4/Pr2Co7 composites were fabricated by SPS followed by annealing.•10 wt% Pr2Co7 addition and medium LaFe11.6Si1.4 powders were conducive to 1:13 phase formation.•The diffusion of Pr/Co ...into the 1:13 phase improves the TC of these composites.•The composites exhibit excellent (σbc)max of 930–1405 MPa and λ of 14–20.90 W/m∙K.•These composites are promising candidates for near RT cooling applications.
A series of LaFe11.6Si1.4/xwt%Pr2Co7 (x = 0, 5, 10) composites, with a range of particle size of LaFe11.6Si1.4 powders, were successfully fabricated by spark plasma sintering (SPS), followed by annealing. The influence of the particle size of the LaFe11.6Si1.4 powders and the Pr2Co7 binder content on the phase constitution, microstructure, thermal, mechanical, magnetic and magnetocaloric properties were studied. The Pr2Co7 binder content (10 wt%) and the particle size of LaFe11.6Si1.4 powders (100–200 µm) were chosen to be conducive to the formation of the desired 1:13 phase. The magnetic and magnetocaloric properties were influenced by the synergistic effects of Pr and Co atomic diffusion as well by the particle size of the LaFe11.6Si1.4 majority phase powders. The values of TC, (ΔSM)max and RC for the sample could be tuned in the range of 230–297 K, 1.90–3.70 J/kg·K and 84–149 J/kg (ΔH=2 T), respectively, by tuning the Pr2Co7 content and the particle size of the LaFe11.6Si1.4 powders. Significantly, this TC range covers a wide variety of near room temperature cooling applications. The excellent values of thermal conductivity, maximum compressive strength and strain were in the range of 14–20.90 W/m·K, 930–1405 MPa and 5.9–7.9%, respectively. These features make these materials very promising candidates for near room temperature magnetic cooling applications.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Large-scale CuO nanowires were in situ grown on Cu substrate by a very simple catalyst-free thermal oxidation process in atmosphere. The structure characterization revealed that these nanowires are ...monoclinic structured single crystallites with mean diameters of 60–200
nm. The effects of growth time and temperature on the morphology of the nanowires were investigated. It is found that the growth time has an important effect on the length and density of the nanowires, whereas the growth temperature has a distinct influence on the nanowire diameter. Different from the vapor–solid (V–S) mechanism, the growth of nanowires is found to be based on the Cu ion diffusion. The ethanol-sensing properties of these CuO nanowires were also studied based on a self-designed prototype and the results indicated that these large-scale nanowires are indeed a good candidate for gas-sensing applications.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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•High density La-Fe-Si based composites were fabricated by short time SPS followed by annealing.•The magnetocaloric and mechanical properties could be tuned by changing the SPS ...temperature.•The optimum process was SPS@1273 K/5min followed by annealing@1323 K/24 h.•Excellent (σbc)max ∼ 1GPa, λ ∼ 17.68 W/m∙K and large (−ΔSM)max ∼ 2.3 J/kg‧K@2T were obtained.
La(Fe,Si)13 based magnetocaloric composites were prepared by spark plasma sintering (SPS), followed by annealing. The microstructure, mechanical and magnetocaloric properties were investigated. With increasing SPS temperature (TSPS) below 1373 K, the content of (La,Pr)(Fe,Co,Si)13 majority phase increased, while the content of minority phase α-Fe decreased. The increase of TSPS from 973 K to 1373 K greatly improved the composite density, and the density sharply increased from ∼ 68 % to 98 %. After SPS at 1273 K/5 min followed by 1323 K/24 h annealing, high content of 89.35 wt% of the desired (La,Pr)(Fe,Co,Si)13 phase was obtained in LaFe11.6Si1.4/10wt%Pr2Co7 composites. A large increase of Curie temperature (TC) from 196 K to 297 K was observed. The maximum magnetic entropy change (−ΔSM)max reached 2.3 J/(kg‧K) under 2 T magnetic field. ∼ 97 % of full density, excellent compressive strength of ∼ 1GPa and high thermal conductivity of 17.68 W/m∙K were exhibited. Thus, a route to produce high density La-Fe-Si based magnetocaloric composites with excellent mechanical properties and thermal conductivity, good (−ΔSM)max and adjustable TC by short time spark plasma sintering followed by annealing was demonstrated.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The complicated structure of the neutron cannot be calculated using first-principles calculations due to the large colour charge of quarks and the self-interaction of gluons. Its simplest structure ...observables are the electromagnetic form factors1, which probe our understanding of the strong interaction. Until now, a small amount of data has been available for the determination of the neutron structure from the time-like kinematical range. Here we present measurements of the Born cross section of electron–positron annihilation reactions into a neutron and anti-neutron pair, and determine the neutron’s effective form factor. The data were recorded with the BESIII experiment at centre-of-mass energies between 2.00 and 3.08 GeV using an integrated luminosity of 647.9 pb−1. Our results improve the statistics on the neutron form factor by more than a factor of 60 over previous measurements, demonstrating that the neutron form factor data from annihilation in the time-like regime is on par with that from electron scattering experiments. The effective form factor of the neutron shows a periodic behaviour, similar to earlier observations of the proton form factor. Future works—both theoretical and experimental—will help illuminate the origin of this oscillation of the electromagnetic structure observables of the nucleon.Form factors encode the structure of nucleons. Measurements from electron–positron annihilation at BESIII reveal an oscillating behaviour of the neutron electromagnetic form factor, and clarify a long-standing photon–nucleon interaction puzzle.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
Objective and design
Cisplatin-based chemotherapy has been widely used in the perioperative period of cancer surgery, which exacerbates the risk of renal injury. In this study, we examined whether ...dexmedetomidine (DEX), a commonly used anesthetic adjuvant, shows a protective effect against cisplatin-induced acute kidney injury.
Materials
Acute kidney injury in mice was induced by cisplatin.
Treatments
Mice were administered with DEX 25 μg/kg or atipamezole 250 μg/kg (once a day, for 3 days) after cisplatin treatment.
Methods
The renal function and tubular damage score were evaluated at 72 h following cisplatin administration. Apoptotic tubular cells were detected by TUNEL assay. Caspase-3, p53, Bax, F4/80
+
macrophages, CD3
+
T cells, and NF-κB were examined by immunohistochemistry staining or Western blot. Tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and monocyte chemoattractant protein (MCP)-1 in kidney were measured using real-time polymerase chain reaction.
Results
DEX treatment preserved renal function and reduced tubular damage score of mice after cisplatin administration. Mice treated with DEX exhibited less apoptotic tubular cells in response to cisplatin insult, which was associated with decreased Bax and reduced activation of p53 and caspase-3. DEX suppressed the infiltration of macrophages and T cells into the kidneys following cisplatin treatment, which was involved in the inhibition of NF-κB activation and decreased expression of TNF-α, IL-1β, IL-6, and MCP-1. Furthermore, we showed that the renoprotective effect conferred by DEX may be related to α
2
adrenoceptor-dependent pathway.
Conclusion
We demonstrate that DEX protects the kidney against cisplatin-induced AKI by the regulation of apoptosis and inflammatory response.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
A phase III trial was conducted to compare the safety and efficacy of erlotinib with that of gefitinib in advanced non-small cell lung cancer harbouring epidermal growth factor receptor mutations in ...exon 19 or 21.
Eligible patients were randomised to receive erlotinib (150 mg per day) or gefitinib (250 mg per day) orally until disease progression or unacceptable toxicity. We aimed to determine whether erlotinib is superior to gefitinib in efficacy. The primary end point was progression-free survival.
A total of 256 patients were randomised to receive erlotinib (N=128) or gefitinib (N=128). Median progression-free survival was not better with erlotinib than with gefitinib (13.0 vs 10.4 months, 95% confidence interval (CI) 0.62-1.05, P=0.108). The corresponding response rates and median overall survival were 56.3% vs 52.3% (P=0.530) and 22.9 vs 20.1 months (95% CI 0.63-1.13, P=0.250), respectively. There were no significant differences in grade 3/4 toxicities between the two arms (P=0.172).
The primary end point was not met. Erlotinib was not significantly superior to gefitinib in terms of efficacy in advanced non-small cell lung cancer with epidermal growth factor receptor mutations in exon 19 or 21, and the two treatments had similar toxicities.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
To balance the utilization of rare earth (RE) resource and develop Ce-based permanent magnets with high performance/cost ratio, the role of La substitution in the melt-spun (Ce
1−
x
La
x
)
y
Fe
14
B ...(
x
= 0–0.4, and 0.5;
y
= 2–4) alloys has been investigated. It has been confirmed that the hard magnetic properties of Ce-based magnets can be effectively enhanced by partial substitution of La. The maximum (
BH
)
max
of (Ce,La)–Fe–B alloys can be obtained at a Ce:La atomic ratio of 7:3. The lattice parameters and Curie temperature of the hard magnetic (Ce/La)
2
Fe
14
B phase increase linearly with increasing La content. Three different alloy systems with
y
= 2, 2.5 and 3 show similar behavior of magnetic properties dependences on La. In the RE-rich compositions, La substitution for Ce can effectively inhibit the precipitation of the CeFe
2
phase. A solid solution, Ce(La) phase with a space group of Fm-3m, appears in the (Ce
0.7
La
0.3
)
y
Fe
14
B alloys with
y
≥ 3.5. A good combination of magnetic properties with
H
cj
= 345 kA/m,
J
5T
= 1.03 T,
J
r
= 0.60 T, and (
BH
)
max
= 6.3 MGOe is obtained in (Ce
0.7
La
0.3
)
2.5
Fe
14
B alloy. In addition, 30 at.% La substitution for Ce can significantly refine the grains, resulting in the enhancement of exchange coupling interaction. The present finding is beneficial for designing new and low-cost magnetic materials.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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