Acevedobyskov2959

Formation of dissolved metal particles ( less then 450 nm) in mining-impacted environments is a concern because of their potential for greater mobility and ecotoxicity compared to free ion and(or) sediment-bound metals. Metal-contaminated environments may produce soluble metal(loid) particles whose stability and transportability are determined by environmental conditions and particle composition. The Coeur d'Alene River Basin of northern Idaho, USA, is impacted by legacy mine waste-estimated 56 million tonnes of waste rock containing 900,000 t of Pb and 700,000 t of Zn were discharged into the Coeur d'Alene River and its tributaries during mining of argentiferous galena-sphalerite deposits. These legacy disposal practices resulted in substantial metal contamination-including As, Cd, Fe, Pb, Mn, and Zn-of floodplain sediments. Monthly lakewater samples and sediment cores were collected along the shoreline of a metal-contaminated lateral lake of the Coeur d'Alene River. Porewater was extracted from upper and losummer transition that induces redox changes and increases particle stability. The presence of mining-related minerals and seasonal changes in environmental conditions allow for formation of dissolved metal particles, but the limited stability of the particles and/or low permeability of the sediments appear to limit, but not fully restrict, possible transport of metal particles to the overlying lakewater.Objective Patient-derived xenografts (PDX) are useful preclinical models to study cancer biology and mechanisms of drug response/resistance, particularly in molecularly targetable tumors. However, PDX engraftment may not be stochastic. We investigated clinical, histological and molecular features associated with PDX engraftment in a large cohort of EGFR-mutated lung adenocarcinoma (LUAD). Material and methods Samples were collected by different methods from patients at various disease stages and phases of treatment. PDX engraftment was defined as an ability to passage tumors twice in NOD-SCID mice. Uni- and multivariate logistic regression evaluated factors associated with engraftment. Results Among 138 EGFR-mutated LUAD implanted into NOD-SCID mice, the overall engraftment rate was only 10% (14/138). However, engraftment was significantly higher in specimens from surgical resections or core-needle biopsies collected from metastatic sites (5/5; 100%) or from patients who had progressed on EGFR-inhibitors (7/10; 70%). Engrafted tumors usually showed poor histological differentiation, a solid morphologic pattern, and presence of either EGFR T790 M and/or TP53 mutations. Conclusions Population level analyses of mutant EGFR-PDX show that these models might not fully recapitulate the inter-patient heterogeneity of EGFR-LUAD. However, mutant EGFR-PDXs may be useful to address key clinical questions, notably development of resistance to EGFR-inhibitors and disease progression to distant metastases.Objectives Many MET rearrangements have been identified in various tumor types. However, the frequencies and characteristics of MET rearrangements are not well defined in non-small-cell lung cancer (NSCLC). We sought to illustrate the distribution of MET kinase domain rearrangements (KDREs) in NSCLC, and to uncover novel targets for further drug development in these patients. Materials and methods Targeted sequencing using a 1021-gene panel or a 59-gene panel was performed in 5965 NSCLC cases. We sequenced all MET exons and used bioinformatics techniques to identify fusions. Results Fifteen MET KDREs were identified from all patients. The incidence of MET KDRE was 0.26% (15/5695) in the cohort; 60% (9/15) of the fused partners were the genes upstream or downstream of MET. All the fusions of the MET gene with upstream genes or specific regions within them were due to inversions, while the fusions with downstream genes or their encompassed regions were caused by duplications or intra-chromosomal translocations. In the MET KDRE-positive NSCLC cases who did not receive targeted therapies, 75% (6/8) harbored no actionable mutation referring to the NCCN guideline. Conclusion Our study illustrated the MET KDRE in NSCLC cases among the Chinese population and unearthed novel targets to develop new effective therapies for patients with MET KDRE.Objective Investigate the spectrum of radiographic patterns of radiation pneumonitis (RP) in lung cancer patients and identify imaging markers for high-grade RP and RP-related death. Methods Eighty-two patients with lung cancer treated with conventional chest radiotherapy who had symptomatic RP were identified from the radiation oncology database. The imaging features of RP were studied for association with high-grade RP (Grade ≥3) and RP-related death (Grade 5). Results RP was Grade 2 in 60 (73%), Grade 3 in 15 (18%), and Grade 5 in 7 patients (9%). Lower performance status (p = 0.04), squamous cell histology (p = 0.03), and FEV1 ≤ 2 (p = 0.009) were associated with high-grade pneumonitis. learn more Older age (p = 0.03) and squamous cell histology (p = 0.03) were associated with RP-related death. The CT findings included ground-glass and reticular opacities in all patients, with traction bronchiectasis in 77 (94%) and consolidation in 74 (90%). The most common radiographic pattern of RP was cryptogenic organizing pneumonia (COP) pattern (n = 54), followed by acute interstitial pneumonia (AIP)/acute respiratory distress syndrome (ARDS) pattern (n = 10). Higher extent of lung involvement, diffuse distribution, and AIP/ARDS pattern were associated with high-grade pneumonitis and RP-related death. AIP/ARDS pattern was a significant factor for high-grade pneumonitis (OR12.62, p = 0.01) in multivariable analyses adjusting for clinical variables. Conclusion COP pattern was the most common radiographic pattern for symptomatic RP in lung cancer patients. AIP/ARDS pattern was significantly associated with high-grade RP and RP-related deaths, and was an independent marker for high-grade RP. The recognition of the radiographic patterns of RP can help to effectively contribute to patient management.Mepanipyrim is a widely used fungicide, and residues of mepanipyrim are frequently detected in commodities. However, the neurotoxicity and underlying mechanisms of mepanipyrim are still insufficiently understood. In this study, zebrafish embryos at 0.5-1.0 post-fertilization hours (hpf) were exposed to 0.1, 1, 10 and 100 μg/L mepanipyrim for 7 days. Our results showed that mepanipyrim could cause the locomotor hyperactivity and increase the concentration of γ-amino butyric acid (GABA) and the Na+/K+- and Ca2+-ATPase activities in zebrafish larvae. We have conducted the RNA-sequence and RT-qPCR to analyze the gene expressions. The mRNA expression levels of calcium/sodium ion conduction associated genes were observably up-regulated, demonstrating that mepanipyrim could enhance the cell energy metabolism, the synaptic transmission and skeletal muscle contraction, which were consistent with the locomotor hyperactivity. Meanwhile, exposure to mepanipyrim could significantly change the gene expression levels of gad1, bdnf, nlgn1, and type A and B GABA receptors in zebrafish larvae.