Background: Mutations of the epidermal growth factor receptor (EGFR) gene in non-small-cell lung cancer (NSCLC) patients predict the patients who will respond to EGFR tyrosine kinase inhibitor (TKI) ...treatment. A recent study has suggested that 33% of NSCLC showed primary tumor/metastasis discordance of EGFR expression by immunohistochemistry analysis. We intended to find out whether the EGFR mutations of primary lung cancers are concordant to that of corresponding metastatic tumors. Materials and methods: We analyzed EGFR exons 18–21 from paired primary and metastatic tumors in 67 lung cancer patients who had not received TKI before tissues were sampled. Results: Using the direct sequencing method, 9 of 18 (50%) patients with EGFR mutation-positive primary lung tumors had lost the mutations in metastases. For 26 patients who were EGFR mutation positive in the metastatic tumors, 17 (65%) were negative in the primary tumors. We analyzed these paired tissues with discrepant EGFR mutations by the Scorpion Amplified Refractory Mutation System assay. Finally, the discordant rate reached 27% (18 of 67 cases). Conclusion: EGFR mutations in primary lung tumors do not always reflect the same situation in metastases. Analysis of EGFR mutations in the primary lung tumor would be inadequate for planning the use of TKI for advanced NSCLC.
Scedosporium spp. is the most common mold infection in pneumonia resulting from near‐drowning. Three fatal scedosporiosis cases developed after solid organ transplantation, probably transmitted from ...the nearly‐drowned donor. One heart transplant recipient and two kidney transplant recipients developed fatal scedosporiosis following deceased donor transplantation from the same donor, a nearly‐drowned victim of a suicide attempt. Genotypically, indistinguishable strains of Scedosporium auratiacum were recovered from the three recipients. Two liver transplant recipients from the same donor received prophylactic voriconazole without any subsequent signs of infection. To determine the safety of donation from nearly‐drowned donors, a national traceback investigation was also performed of the causes of deaths in all transplant recipients who received organs from drowned donors between 2001 and 2013. Over 13 years, 2600 deceased donor transplants were performed in Korea. Among these 2600 deceased donor transplants, 27 (1%) victims of drowning donated their organs. From these 27 donors, 84 patients received organ transplants and 18 died, including the above three. We found no microbiologic evidence of invasive mold transmission from the nearly‐drowned donors to the other 15 recipients. Although disseminated infection in the donor could not be demonstrated by culture, undiagnosed disseminated donor infection and transmission of Scedosporium spp. should be considered in near‐drowning events.
The authors describe their experience of one heart recipient and two kidney recipients with fatal scedosporiosis following deceased donor transplantation from the same donor, a nearly drowned victim of a suicide attempt.
The hypothesis of cancer stem cells has been proposed to explain the therapeutic failure in a variety of cancers including lung cancers. Previously, we demonstrated acquisition of ...epithelial-mesenchymal transition, a feature highly reminiscent of cancer stem-like cells, in gefitinib-resistant A549 cells (A549/GR). Here, we show that A549/GR cells contain a high proportion of CXCR4+ cells that are responsible for having high potential of self-renewal activity in vitro and tumorigenicity in vivo. A549/GR cells exhibited strong sphere-forming activity and high CXCR4 expression and SDF-1α secretion compared with parent cells. Pharmacological inhibition (AMD3100) and/or siRNA transfection targeting CXCR4 significantly suppressed sphere-forming activity in A549 and A549/GR cells, and in various non-small cell lung cancer (NSCLC) cell lines. A549/GR cells showed enhanced Akt, mTOR and STAT3 (Y705) phosphorylation. Pharmacological inhibition of phosphatidyl inositol 3-kinase or transfection with wild-type PTEN suppressed phosphorylation of Akt, mTOR and STAT3 (Y705), sphere formation, and CXCR4 expression in A549/GR cells, whereas mutant PTEN enhanced these events. Inhibition of STAT3 by WP1066 or siSTAT3 significantly suppressed the sphere formation, but not CXCR4 expression, indicating that STAT3 is a downstream effector of CXCR4-mediated signaling. FACS-sorted CXCR4+ A549/GR cells formed many large spheres, had self-renewal capacity, demonstrated radiation resistance in vitro and exhibited stronger tumorigenic potential in vivo than CXCR4- cells. Lentiviral-transduction of CXCR4 enhanced sphere formation and tumorigenicity in H460 and A549 cells, whereas introduction of siCXCR4 suppressed these activities in A549/GR cells. Our data indicate that CXCR4+ NSCLC cells are strong candidates for tumorigenic stem-like cancer cells that maintain stemness through a CXCR4-medated STAT3 pathway and provide a potential therapeutic target for eliminating these malignant cells in NSCLC.
In 2018, Kīlauea Volcano experienced its largest lower East Rift Zone (LERZ) eruption and caldera collapse in at least 200 years. After collapse of the Pu'u 'Ō'ō vent on 30 April, magma propagated ...downrift. Eruptive fissures opened in the LERZ on 3 May, eventually extending ~6.8 kilometers. A 4 May earthquake moment magnitude (
) 6.9 produced ~5 meters of fault slip. Lava erupted at rates exceeding 100 cubic meters per second, eventually covering 35.5 square kilometers. The summit magma system partially drained, producing minor explosions and near-daily collapses releasing energy equivalent to
4.7 to 5.4 earthquakes. Activity declined rapidly on 4 August. Summit collapse and lava flow volume estimates are roughly equivalent-about 0.8 cubic kilometers. Careful historical observation and monitoring of Kīlauea enabled successful forecasting of hazardous events.
We present microlensing planet OGLE-2017-BLG-0173Lb, with planet-host mass ratio of either or , the lowest or among the lowest ever detected. The planetary perturbation is strongly detected, Δχ2 ∼ ...10000, because it arises from a bright (therefore, large) source passing over and enveloping the planetary caustic: a so-called "Hollywood" event. The factor ∼2.5 offset in q arises because of a previously unrecognized discrete degeneracy between Hollywood events in which the caustic is fully enveloped and those in which only one flank is enveloped, which we dub "Cannae" and "von Schlieffen," respectively. This degeneracy is "accidental" in that it arises from gaps in the data. Nevertheless, the fact that it appears in a Δχ2 = 10000 planetary anomaly is striking. We present a simple formalism to estimate the sensitivity of other Hollywood events to planets and show that they can lead to detections close to, but perhaps not quite reaching, the Earth/Sun mass ratio of . This formalism also enables an analytic understanding of the factor ∼2.5 offset in q between the Cannae and von Schlieffen solutions. The Bayesian estimates for the host mass, system distance, and planet-host projected separation are , , and , respectively. The two estimates of the planet mass are and . The measured lens-source relative proper motion will permit imaging of the lens in about 15 years or at first light on adaptive-optics imagers on next-generation telescopes. These will allow one to measure the host mass but probably will not be able to resolve the planet-host mass-ratio degeneracy.
We report the analysis of the microlensing event OGLE-2018-BLG-0677. A small feature in the light curve of the event leads to the discovery that the lens is a star-planet system. Although there are ...two degenerate solutions that could not be distinguished for this event, both lead to a similar planet-host mass ratio. We perform a Bayesian analysis based on a Galactic model to obtain the properties of the system and find that the planet corresponds to a super-Earth/sub-Neptune with a mass of . The host star has a mass of . The projected separation for the inner and outer solutions are au and au respectively. At , this is by far the lowest Δχ2 for any securely detected microlensing planet to date, a feature that is closely connected to the fact that it is detected primarily via a "dip" rather than a "bump."
Friction stir processing (FSP) has been applied to incorporate 5–10
vol.% nano-sized SiO
2 into an AZ61Mg alloy matrix to form bulk composites. The nano-particles were uniformly dispersed after four ...FSP passes, and the average grain sizes of the composites varied within 0.5–2
μm. The composites nearly doubled the hardness of the base material and exhibited high strain rate superplasticity.
We report direct-detection constraints on light dark matter particles interacting with electrons. The results are based on a method that exploits the extremely low levels of leakage current of the ...DAMIC detector at SNOLAB of 2–6×10−22 A cm−2. We evaluate the charge distribution of pixels that collect <10e− for contributions beyond the leakage current that may be attributed to dark matter interactions. Constraints are placed on so-far unexplored parameter space for dark matter masses between 0.6 and 100 MeV c−2. We also present new constraints on hidden-photon dark matter with masses in the range 1.2–30 eV c−2.
We present a comprehensive study of the nonproportionality of NaI(Tl) scintillation detectors within the context of dark matter search experiments. Our investigation, which integrates COSINE-100 data ...with supplementary
γ
spectroscopy, measures light yields across diverse energy levels from full-energy
γ
peaks produced by the decays of various isotopes. These
γ
peaks of interest were produced by decays supported by both long and short-lived isotopes. Analyzing peaks from decays supported only by short-lived isotopes presented a unique challenge due to their limited statistics and overlapping energies, which was overcome by long-term data collection and a time-dependent analysis. A key achievement is the direct measurement of the 0.87 keV light yield, resulting from the cascade following electron capture decay of
22
Na
from internal contamination. This measurement, previously accessible only indirectly, deepens our understanding of NaI(Tl) scintillator behavior in the region of interest for dark matter searches. This study holds substantial implications for background modeling and the interpretation of dark matter signals in NaI(Tl) experiments.
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