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Rationale: Cross-sectional human data suggest that enrichment of oral anaerobic bacteria in the lung is associated with an increased T-helper cell type 17 (Th17) inflammatory phenotype.Objectives: ...

In lung cancer, enrichment of the lower airway microbiota with oral commensals commonly occurs, and ex vivo models support that some of these bacteria can trigger host transcriptomic signatures associated with carcinogenesis. Here, we show that this lower airway dysbiotic signature was more prevalent in the stage IIIB–IV tumor–node–metastasis lung cancer group and is associated with poor prognosis, as shown by decreased survival among subjects with early-stage disease (I–IIIA) and worse tumor progression as measured by RECIST scores among subjects with stage IIIB–IV disease. In addition, this lower airway microbiota signature was associated with upregulation of the IL17, PI3K, MAPK, and ERK pathways in airway transcriptome, and we identified Veillonella parvula as the most abundant taxon driving this association. In a KP lung cancer model, lower airway dysbiosis with V. parvula led to decreased survival, increased tumor burden, IL17 inflammatory phenotype, and activation of checkpoint inhibitor markers. Significance: Multiple lines of investigation have shown that the gut microbiota affects host immune response to immunotherapy in cancer. Here, we support that the local airway microbiota modulates the host immune tone in lung cancer, affecting tumor progression and prognosis. See related commentary by Zitvogel and Kroemer, p. 224. This article is highlighted in the In This Issue feature, p. 211

Social-distancing to combat the COVID-19 pandemic has led to widespread reductions in air pollutant emissions. Quantifying these changes requires a business as usual counterfactual that accounts for the synoptic and seasonal variability of air pollutants. We use a machine learning algorithm driven by information from the NASA GEOS-CF model to assess changes in nitrogen dioxide (NO$_{2}$) and ozone (O$_{3}$) at 5,756 observation sites in 46 countries from January through June 2020. Reductions in NO$_{2}$ correlate with timing and intensity of COVID-19 restrictions, ranging from 60% in severely affected cities (e.g., Wuhan, Milan) to little change (e.g., Rio de Janeiro, Taipei). On average, NO$_{2}$ concentrations were 18% lower than business as usual from February 2020 onward. China experienced the earliest and steepest decline, but concentrations since April have mostly recovered and remained within 5% to the business as usual estimate. NO$_{2}$ reductions in Europe and the US have been more gradual with a halting recovery starting in late March. We estimate that the global NO$_{x}$ (NO+NO$_{2}$) emission reduction during the first 6 months of 2020 amounted to 2.9 TgN, equivalent to 5.1% of the annual anthropogenic total. The response of surface O$_{3}$ is complicated by competing influences of non-linear atmospheric chemistry. While surface O$_{3}$ increased by up to 50% in some locations, we find the overall net impact on daily average O$_{3}$ between February - June 2020 to be small. However, our analysis indicates a flattening of the O$_{3}$ diurnal cycle with an increase in night time ozone due to reduced titration and a decrease in daytime ozone, reflecting a reduction in photochemical production. The O$_{3}$ response is dependent on season, time scale, and environment, with declines in surface O$_{3}$ forecasted if NO$_{x}$ emission reductions continue., 32 pages, 17 figures

Simulation modelling offers a great potential for modelling and analyzing business processes and, therefore, reduce the risk associated with business process change. This paper presents a study of the use of discrete event simulation to improve the operational performance of equipment rental businesses. With the purpose of reducing the turndowns due to the lack of equipment, several inventory level scenarios and maintenance management rules were tested. Simulation results show that better performance indicators are possible even without financial investment. Simulation has proved to be a powerful tool to improve the decision making by allowing to quantify the relationship between inventory levels, repair activities and turndowns.

3107 Background: Enrichment of the lower airway microbiota with oral commensals has been associated with transcriptomic changes affecting several inflammatory pathways associated with non-small cell lung cancer (NSCLC) development and progression. Using a mouse model of NSCLC, we evaluated the effects of lower airway dysbiosis on tumor progression and host transcriptomics. Methods: Preclinical model of lung cancer was constructed by introducing luminescence-tagged Kras mutated cells into C57/B6 mice, causing lung cancer to develop. Lower airway dysbiosis was induced by weekly intratracheal challenge with either PBS or Veillonella parvula in wild type and lung cancer mice. Experiments were repeated twice to evaluate for survival as well as lower airway host response using flow cytometry and RNA sequencing (HiSeq). Sequence data was processed using a validated mouse gene expression signature matrix with cibersort from https://cibersort.stanford.edu and DESeq using FDR correction. Results: In wild type mice, lower airway dysbiosis with Veillonella did not affect the survival, weight gain or airway lumen diameter. Among lung cancer mice, dysbiosis led to increased mortality, weight loss, and tumor burden. Multiple transcriptomic signatures were identified among the dysbiosis groups (both in WT and lung cancer mice). Unsupervised hierarchical clustering of immune cell profiles using cibersort on whole transcriptome showed near perfect separation between the four experimental conditions. Amongst the most differentially enriched immune cell subsets, we identified that lung dysbiosis upregulates genes annotated to Th1 and Th2 cells (p < 0.01, q < 0.2). Using flow cytometry, we identified that PD-1, IL-17, and ROR-gamma are differentially expressed in CD4+ cells in dysbiosis conditions, and these patterns are consistent in whole RNA transcriptome. Conclusions: Transcriptomic signatures reveal immune profiles associated with dysbiosis, an experimental condition associated with worse outcomes in lung cancer. This investigation provides novel insights into how disruption of the lower airway microbiome may contribute to the pathogenesis of NSCLC.

The X-ray image analysis technique is a precise method that enables examination of regions that are damaged and/or altered in seed and their location and extension. It is a non-destructive method allowing the X-ray treated seed to be submitted to quality physiological tests. The objective of this study was to use X-ray image analysis technique to identify mechanical and stink bug damages in soybean seed. Seeds from different batches of the BRS184 cultivar were sorted by X-ray test and then were tested for germination with the aim to relate the damage with possible seed viability loss. Alternatively, the tetrazolium test was carried out to be compared with the X-ray test. Damage severity and location were considered for the interpretive analysis of X-ray images. The results showed that the X-ray image analysis technique was effective in detecting mechanical and stink bug damage in soybean seed.

Made available in DSpace on 2022-04-28T21:24:25Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-01-01 Soybean seeds may show low germination when evaluated by the paper towel germination test due to high percentages of abnormal seedlings, typical of imbibition damage. This research evaluated the effect of initial seed moisture content (SMC) of different soybean cultivars and production locations on the occurrence of imbibition damage. Treatments consisted of seedlots of four cultivars (Embrapa 48, BRS 184, BRS 232 and BRS 245RR) from 4 Brazilian production locations (Ponta Grossa-PR, Londrina-PR, Maui da Serra-PR and Orlandia-SP). Seed moisture content was adjusted to 9%, 11%, 13%, 15% and 17% prior to the evaluation of imbibition damage. A completely randomized experimental design was used with four replications. Analysis of variance and mean comparison by the Tukey and the Dunnet tests (P < 0.05) were applied for statistical analysis. It was concluded that the increase of seed moisture content is affected by cultivar and initial seed quality. Additionally, it was observed that imbibition damage is not detected when initial seed moisture is equal to or higher than 15%. Department of Crop Science College of Agricultural Sciences Sao Paulo State University, CP. 237, 18610-307, Botucatu, SP Embrapa Soja, CP. 231, 86001-970, Londrina, PR Department of Crop Science College of Agricultural Sciences Sao Paulo State University, CP. 237, 18610-307, Botucatu, SP

6 ABSTRACT - Soybeans grown under water stress associated with high temperatures during seed maturation and pre-harvest may produce green seed (GS) with expressive reduction in seed quality. The objectives of this study were to evaluate the response of different soybean cultivars grown under these stressful conditions regarding their susceptibility to GS production and to determine the chlorophyll retention levels and the chlorophyllase activity in the seeds. Seeds of four soybean cultivars (BRS 133, CD 206, MG/BR 46 (Conquista) and BRSMG 251 (Robusta)) were grown under greenhouse conditions until R 5.5 . At R 6 , the plants were transferred to phytotrons under temperature stress (from 28oC to 36oC) and with water stresses of 10% gravimetric moisture, no water and normal supply. Seeds were harvested at R 9 when the percentage of GS and weight of 100 seeds were determined. The contents of a, b and total chlorophylls and the chlorophyllase activity were also determined. The expression of GS production under these conditions varied among cultivars: Conquista and Robusta were considered more susceptible to the production of GS compared to 'BRS 133' and 'CD 206'. These cultivars produced lower GS levels, lower chlorophyll retention and higher chlorophyllase activity compared to Robusta and Conquista. Soybean plants submitted to water and temperature stresses produced high levels of GS, which were small, light and had high chlorophyll contents and low chlorophyllase activity. The contents of a, b and total chlorophylls in GS were inversely proportional to the chlorophyllase activity.

Most Brazilian Yersinia pestis isolates display a typical plasmid profile composed of the three classical plasmids: pYV, pPst and pFra. However, some cultures lack at least one of these plasmids, while a few of them harbour atypical DNA bands of molecular weight ranging from 147 to 11.5 kb. To investigate whether Y. pestis displaying atypical plasmid content could be propagated among rodents in nature through flea bites, we carried out studies with fleas (Xenopsylla cheopis) and rodents (Calomys callosus) reared in the laboratory and five Y. pestis cultures differing in plasmid content. The results suggest that: (1) the single presence of pYV is not sufficient for the transmission of Y. pestis by fleas, (2) pPst is not essential for transmission, (3) two atypical DNA bands of molecular weight of 30 kb and >90 kb have no biological role, and (4) pFra is required for the transmission of Y. pestis by flea bites. Other studies are needed to determine whether this plasmid alone is sufficient for transmission.

Aim: NICE trial showed that combination of chemoradiation and nimotuzumab, a humanized antibody against EGFR, is safe and appears to increase the combined complete response (cCR) rate, defined as endoscopic and/or pathologic CR, in pts with locally advanced esophageal cancer (ASCO 2014). Here we present the results of the exploratory analyses of molecular markers and their correlation to clinical outcomes. Methods: Tumor samples were obtained before chemoradiation with or without nimotuzumab. All samples were formalin-fixed and paraffin-embedded. Tumor areas were selected and macrodissected, followed by whole DNA extraction and amplification by PCR. Mutations and single nucleotide polymorphisms (SNPs) were searched in codons 12 and 13 of exon 2 for KRAS, and exons 18 to 24 for EGFR through DNA sequencing by Sangeŕs methodology. Fisher's exact test was used to compare groups. Results: Molecular analyses were performed in tumor samples from 51 of the 107 randomized patients, 18 from the control arm (chemoradiation) and 37 from the experimental arm (chemoradiation plus nimotuzumab). No mutations or SNPs were identified in KRAS among the 48 samples analyzed. Indeed, no mutations were found in EGFR, but some SNPs were identified. Except for exon 21, for all other sequenced exons at least one patient had one SNP identified, more frequently in exons 20 and 23. SNPs identified in exon 20 included 167339G > A (rs10251977) and 167339G > A (rs1050171). The latter was the most frequent detected SNP and it was identified in 11 patients (3 in the control group and 8 in the nimotuzumab group). Within each treatment arm, the cCR rates were similar between patients whose tumors harboring or not the SNP rs1050171. Although not statistically significant (P = 0.074), in the nimotuzumab group, cCR rate of tumors harboring rs1050171 was nominally higher than the rate observed for tumors without this SNP (87.5% [7/8] vs. 42.9% [6/14]). Conclusions: No mutations were found in KRAS or EGFR. Several EGFR SNPs were identified, being rs1050171 in exon 20 the most frequently found. Although exploratory, these results suggest an association between response to nimotuzumab and tumor biologic characteristics. Further exploration of this hypothesis is planned in a phase III trial. Disclosure: L.P.D.G. Neusquen: Clinical Research Department of Eurofarma S.A. All other authors have declared no conflicts of interest.

e17530 Background: Adjuvant chemotherapy is generally recommended in most patients with resected non–small cell lung cancer (NSCLC), with some restrictions according to tumor stage and size. Howeve...