Background
The aim of this study was to evaluate whether adjuvant chemotherapy is associated with improved survival in patients with resectable gastric neuroendocrine carcinomas (G‐NECs) or mixed ...adenoneuroendocrine carcinomas (G‐MANECs).
Methods
The study included patients with G‐NECs or G‐MANECs who underwent surgery in one of 21 centres in China between 2004 and 2016. Propensity score matching analysis was used to reduce selection bias, and overall survival (OS) in different treatment groups was estimated by the Kaplan–Meier method.
Results
In total, 804 patients with resectable G‐NECs or G‐MANECs were included, of whom 490 (60·9 per cent) received adjuvant chemotherapy. After propensity score matching, OS in the chemotherapy group was similar to that in the no‐chemotherapy group. Among patients with G‐NECs, survival in the fluorouracil (5‐FU)‐based chemotherapy group and the non‐5‐FU‐based chemotherapy group was similar to that in the no‐chemotherapy group. Similarly, etoposide plus cisplatin or irinotecan plus cisplatin was not associated with better OS in patients with G‐NECs. Among patients with G‐MANECs, OS in the non‐5‐FU‐based chemotherapy group was worse than that in the no‐chemotherapy group. Patients with G‐MANECs did not have better OS when platinum‐based chemotherapy was
used.
Conclusion
There was no survival benefit in patients who received adjuvant chemotherapy for G‐NECs or G‐MANECs.
Antecedentes
El objetivo de este estudio fue evaluar si la quimioterapia adyuvante mejoraba la supervivencia en pacientes con carcinomas gástricos resecables neuroendocrinos (gastric neuroendocrine carcinomas, G‐NECs) y carcinomas adenoneuroendocrinos mixtos (mixed adenoneuroendocrine carcinomas, G‐MANECs).
Métodos
Se incluyeron pacientes con G‐NECs y G‐MANECs tratados quirúrgicamente en 21 centros en China entre 2004 y 2016. Se utilizó un análisis de emparejamiento por puntaje de propensión para reducir el sesgo de selección y el método de Kaplan‐Meier para estimar la supervivencia global (overall survival, OS) de los pacientes en los diferentes grupos de tratamiento.
Resultados
En total, se incluyeron en el estudio 804 pacientes con G‐NECs y G‐MANECs resecables y 490 pacientes (60,9%) recibieron quimioterapia adyuvante. Después del emparejamiento por puntaje de propensión, la OS del grupo con quimioterapia fue similar a la del grupo sin quimioterapia. En los pacientes con G‐NECs, la supervivencia en los grupos con quimioterapia basada en 5‐FU (fluorouracilo) y de quimioterapia sin 5‐FU fue similar a la del grupo sin quimioterapia. Asimismo, la combinación de etopósido y cisplatino o de irinotecán y cisplatino no se asoció con una mejor OS en pacientes con G‐NECs. En pacientes con G‐MANECs, la OS del grupo con quimioterapia sin 5‐FU fue peor que la del grupo sin quimioterapia. Los pacientes con G‐MANECs no presentaron una mejor OS cuando se administró quimioterapia basada en platinos.
Conclusión
La administración de quimioterapia adyuvante en pacientes con G‐NECs y G‐MANECs no mejoró la supervivencia.
This multicentre study enrolled 804 patients with resectable gastric neuroendocrine carcinomas and gastric mixed adenoneuroendocrine carcinomas. In propensity score matching analysis, there were no associations between the use of adjuvant chemotherapy and improved overall survival. Similar results were obtained in stratified analysis according to different chemotherapy regimens.
No benefit
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Alloy design based on single-principal-element systems has approached its limit for performance enhancements. A substantial increase in strength up to gigapascal levels typically causes the premature ...failure of materials with reduced ductility. Here, we report a strategy to break this trade-off by controllably introducing high-density ductile multicomponent intermetallic nanoparticles (MCINPs) in complex alloy systems. Distinct from the intermetallic-induced embrittlement under conventional wisdom, such MCINP-strengthened alloys exhibit superior strengths of 1.5 gigapascals and ductility as high as 50% in tension at ambient temperature. The plastic instability, a major concern for high-strength materials, can be completely eliminated by generating a distinctive multistage work-hardening behavior, resulting from pronounced dislocation activities and deformation-induced microbands. This MCINP strategy offers a paradigm to develop next-generation materials for structural applications.
Genetic evidence for anatomically modern humans (AMH) out of Africa before 75 thousand years ago (ka) and in island southeast Asia (ISEA) before 60 ka (93-61 ka) predates accepted archaeological ...records of occupation in the region. Claims that AMH arrived in ISEA before 60 ka (ref. 4) have been supported only by equivocal or non-skeletal evidence. AMH evidence from this period is rare and lacks robust chronologies owing to a lack of direct dating applications, poor preservation and/or excavation strategies and questionable taxonomic identifications. Lida Ajer is a Sumatran Pleistocene cave with a rich rainforest fauna associated with fossil human teeth. The importance of the site is unclear owing to unsupported taxonomic identification of these fossils and uncertainties regarding the age of the deposit, therefore it is rarely considered in models of human dispersal. Here we reinvestigate Lida Ajer to identify the teeth confidently and establish a robust chronology using an integrated dating approach. Using enamel-dentine junction morphology, enamel thickness and comparative morphology, we show that the teeth are unequivocally AMH. Luminescence and uranium-series techniques applied to bone-bearing sediments and speleothems, and coupled uranium-series and electron spin resonance dating of mammalian teeth, place modern humans in Sumatra between 73 and 63 ka. This age is consistent with biostratigraphic estimations, palaeoclimate and sea-level reconstructions, and genetic evidence for a pre-60 ka arrival of AMH into ISEA. Lida Ajer represents, to our knowledge, the earliest evidence of rainforest occupation by AMH, and underscores the importance of reassessing the timing and environmental context of the dispersal of modern humans out of Africa.
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IJS, KISLJ, NUK, SBMB, UL, UM, UPUK
We investigate polarization-dependent ultrafast photocurrents in the Weyl semimetal TaAs using terahertz (THz) emission spectroscopy. Our results reveal that highly directional, transient ...photocurrents are generated along the noncentrosymmetric c axis regardless of incident light polarization, while helicity-dependent photocurrents are excited within the ab plane. This is consistent with earlier static photocurrent experiments, and demonstrates on the basis of both the physical constraints imposed by symmetry and the temporal dynamics intrinsic to current generation and decay that optically induced photocurrents in TaAs are inherent to the underlying crystal symmetry of the transition metal monopnictide family of Weyl semimetals.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM
ABSTRACT
High time resolution and accuracy are of critical importance in the studies of timing analysis and time delay localization of gamma-ray bursts (GRBs), soft gamma-ray repeaters (SGRs) and ...pulsars. The Gravitational wave high-energy Electromagnetic Counterpart All-sky Monitor (GECAM) consisting of two micro-satellites, GECAM-A and GECAM-B, launched on 2020 December 10, is aimed at monitoring and locating X-ray and GRBs all over the sky. To achieve its scientific goals, GECAM is designed to have the highest time resolution (0.1 $\mu {\rm s}$) among all GRB detectors ever flown. Here, we make a comprehensive time calibration campaign including both on-ground and on-orbit tests to derive not only the relative time accuracy of GECAM satellites and detectors, but also the absolute time accuracy of GECAM-B. Using the on-ground calibration with a $\rm ^{22}Na$ radioactive source, we find that the relative time accuracy between GECAM-A and GECAM-B is about 0.15 $\mu {\rm s}$ (1σ). To measure the relative time accuracy between all detectors of a single GECAM satellite, cosmic-ray events detected on orbit are utilized since they could produce many secondary particles simultaneously record by multiple detectors. We find that the relative time accuracy among all detectors onboard GECAM-B is about 0.12 $\mu {\rm s}$ (1σ). Finally, we use the novel Li-CCF method to perform the absolute time calibration with Crab pulsar and SGR J1935+2154, both of which were jointly observed by GECAM-B and Fermi/GBM, and obtain that the time difference between GECAM-B and Fermi/GBM is 3.06 ± 6.04 $\mu {\rm s}$ (1σ).
During the Upper Paleolithic, lions become an important theme in Paleolithic art and are more frequent in anthropogenic faunal assemblages. However, the relationship between hominins and lions in ...earlier periods is poorly known and primarily interpreted as interspecies competition. Here we present new evidence for Neanderthal-cave lion interactions during the Middle Paleolithic. We report new evidence of hunting lesions on the 48,000 old cave lion skeleton found at Siegsdorf (Germany) that attest to the earliest direct instance of a large predator kill in human history. A comparative analysis of a partial puncture to a rib suggests that the fatal stab was delivered with a wooden thrusting spear. We also present the discovery of distal lion phalanges at least 190,000 old from Einhornhöhle (Germany), representing the earliest example of the use of cave lion skin by Neanderthals in Central Europe. Our study provides novel evidence on a new dimension of Neanderthal behavioral complexity.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
In order to study the temporal and spatial variations of PM2.5 and its chemical compositions in the region of Beijing, Tianjin, and Hebei (BTH), PM2.5 samples were collected at four urban sites in ...Beijing (BJ), Tianjin (TJ), Shijiazhuang (SJZ), and Chengde (CD), and also one site at Shangdianzi (SDZ) regional background station over four seasons from 2009 to 2010. The samples were weighted for mass concentrations and analyzed in the laboratory for chemical profiles of 19 elements (Al, As, Ba, Ca, Cd, Co, Cr, Cu, Fe, K, Mg, Mn, Ni, P, Pb, Sr, Ti, V, and Zn), eight water-soluble inorganic ions (Na+ , NH4+ , K+ , Mg2+ , Ca2+ , Cl- , NO3- , and SO42- , and carbon fractions (OC and EC). The concentrations of PM2.5 and its major chemical species were season dependent and showed spatially similar characteristics in the plain area of BTH. The average annual concentrations of PM2.5 were 71.8-191.2 μg m-3 at the five sites, with more than 90% of sampling days exceeding 50 μg m-3 at BJ, TJ, and SJZ. PM2.5 pollution was most serious at SJZ, and the annual concentrations of PM2.5 , secondary inorganic ions, OC, EC, and most crustal elements were all highest. Due to stronger photochemical oxidation, the sum of concentrations of secondary inorganic ions (NH4+ , NO3- , and SO42- was highest in the summer at SDZ, BJ, TJ, and CD. Analysis of electric charges of water-soluble inorganic ions indicated the existence of nitric acid or hydrochloric acid in PM2.5 . For all five sites, the concentrations of OC, EC and also secondary organic carbon (SOC) in the spring and summer were lower than those in the autumn and winter. SOC had more percentages of increase than primary organic carbon (POC) during the winter. The sums of crustal elements (Al, Ca, Fe, Mg, Ti, Ba, and Sr) were higher in the spring and autumn owing to more days with blowing or floating dust. The concentrations of heavy metals were at higher levels in the BTH area by comparison with other studies. In Shijiazhuang and Chengde, the PM2.5 pollution was dominated by coal combustion. Motor vehicle exhausts and coal combustion emissions both played important roles in Tianjin PM2.5 pollution. However, motor vehicle exhausts had played a more important role in Beijing owing to the reduction of coal consumption and sharp increase of cars in recent years. At SDZ, regional transportation of air pollutants from southern urban areas was significant.
To clone and characterize genes encoding novel cellulases from metagenomes of buffalo rumens. A ruminal metagenomic library was constructed and functionally screened for cellulase activities and 61 ...independent clones expressing cellulase activities were isolated. Subcloning and sequencing of 13 positive clones expressing endoglucanase and MUCase activities identified 14 cellulase genes. Two clones carried two gene clusters that may be involved in the degradation of polysaccharide nutrients. Thirteen recombinant cellulases were partially characterized. They showed diverse optimal pH from 4 to 7. Seven cellulases were most active under acidic conditions with optimal pH of 5·5 or lower. Furthermore, one novel cellulase gene, C67-1, was overexpressed in Escherichia coli, and the purified recombinant enzyme showed optimal activity at pH 4·5 and stability in a broad pH range from pH 3·5 to 10·5. Its enzyme activity was stimulated by dl-dithiothreitol. The cellulases cloned in this work may play important roles in the degradation of celluloses in the variable and low pH environment in buffalo rumen. This study provided evidence for the diversity and function of cellulases in the rumen. The cloned cellulases may at one point of time offer potential industrial applications.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
We aimed to investigate the efficacy and tolerability of sorafenib combined with cisplatin and 5-fluorouracil (5-FU) in patients with recurrent or metastatic nasopharyngeal carcinoma (NPC).
It was a ...Simon two-stage designed trial. Chemotherapy-naive patients with recurrent or metastatic disease were enrolled. The regimen was sorafenib 400 mg orally b.i.d., cisplatin 80 mg/m2 i.v. day 1, and 5-FU 1000 mg/m2/day CIV for 4 days, repeated every 21 days. After a maximum of six cycles of chemotherapy, patients received maintenance of sorafenib.
In total, 54 patients were enrolled. The objective response rate reached 77.8%, including 1 complete response and 41 partial responses. The median progression-free survival was 7.2 months (95% CI 6.8–8.4 months), and the median overall survival was 11.8 months (95% CI 10.6–18.7 months). Major toxic effects included hand–foot skin reaction, myelosuppression, and gastrointestinal (GI) reaction. The incidence of hemorrhage was 22.2%, and one patient with liver metastases died of GI bleeding. Contrast-enhanced ultrasonography was carried out in a subset of patients with liver metastases.
Combination of sorafenib, cisplatin (80 mg/m2) and 5-FU (3000 mg/m2) was tolerable and feasible in recurrent or metastatic NPC. Further randomized trials to compare sorafenib plus cisplatin and 5-FU with standard dose of cisplatin plus 5-FU in NPC are warranted.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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