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  • Jacobson Dueholm posted an update 1 day ago

    BACKGROUND Bevacizumab and aflibercept are currently the mainstay of antiangiogenic therapy for metastatic colorectal carcinoma (mCRC). They are often used in sequence with first- and second-line chemotherapy, especially in patients with RAS-mutated tumours. OBJECTIVE The aim of the present study was to investigate the outcomes of patients with mCRC treated with the bevacizumab-aflibercept sequence in real-world clinical practice. PATIENTS AND METHODS Data from a national clinical registry of targeted therapies for mCRC were analysed retrospectively. Overall, there were 366 patients with valid data who received first-line treatment with bevacizumab and chemotherapy followed by aflibercept with chemotherapy. The majority of the patients (n = 296, 80.8%) had RAS mutated tumours. RESULTS Median cumulative progression-free survival (PFS) from the start of the bevacizumab-containing regimen to progression on aflibercept was 18.2 months (95% CI 16.8-19.5). Median PFS for bevacizumab and aflibercept was 10.6 months (95% CI 9.5-11.7) and 5.6 months (95% CI 5.1-6.1), respectively. Longer PFS on aflibercept was associated with metachronous metastatic disease and longer PFS on bevacizumab. Median overall survival (OS) from the start of first-line bevacizumab was 32.0 months (95% CI 26.6-37.5). The presence of metastatic disease at diagnosis was associated with worse OS. CONCLUSIONS Patients treated with aflibercept in real-world clinical practice achieved similar survival outcomes as those treated within randomised trials. Cumulative survival data provide a benchmark for future studies and enable indirect comparisons with other treatment sequences used in mCRC.BACKGROUND Immunotherapy based on programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors has revolutionized the treatment of non-small cell lung cancer (NSCLC). Patients with high PD-L1 expression or DNA mismatch repair deficiency (dMMR)/microsatellite instability-high (MSI-H) cancer are reported to benefit from PD-1/PD-L1 inhibitors. However, additional biomarkers are needed, and whether tumor mutation burden (TMB) can be a robust biomarker or not is still controversial. OBJECTIVE We conducted this study to assess TMB as a biomarker for PD-1/PD-L1 inhibitor treatment in advanced NSCLC patients in a real-world setting. PATIENTS AND METHODS Chinese NSCLC patients who received a PD-1/PD-L1 inhibitor at the People’s Liberation Army General Hospital and who had pathological tissues available for TMB were retrospectively analyzed. Demographic and clinical information were evaluated. Targeted next-generation sequencing (NGS) of the tumor tissue was performed. The relationship between TMThe widespread use of zinc oxide nanoparticles (ZnO NPs), the second most produced nanomaterial, inevitably leads to their release into the environment. In this study, dissolution and transformation of ZnO NPs in the presence of δ-MnO2, an abundant and ubiquitous manganese (Mn) oxide mineral, was investigated via a suite of techniques covering bulk to molecular scales. Dissolution kinetics indicated that the presence of δ-MnO2 significantly affected ZnO NP dissolution rate/trend and equilibrium Zn2+ concentration, which were found to be mainly dependent on the concentration and mass ratio of ZnO NPs and δ-MnO2. Approximately 300 mg ZnO NPs per g δ-MnO2 was expected for ZnO NP uptake at pH 7.0 via ZnO NP dissolution and surface Zn2+ adsorption. X-ray diffraction (XRD), ζ potential, high-resolution transmission electron microscopy (HR-TEM), and Zn K-edge X-ray absorption spectroscopy (XAS) results revealed that when the mole content of ZnO NPs was less than the total adsorption sites of δ-MnO2 surface, ZnO NPs were completely dissolved and adsorbed on δ-MnO2 surface in the form of inner-sphere complexes. A fraction of ZnO NPs persisted when the mole ratio of ZnO to δ-MnO2 further increased. These results suggest that the transformation and fate of ZnO NPs is affected by environment-relevant minerals such as Mn oxides due to their huge capacity of fixing dissolved metal cations at the surface or interlayer structure.The chlordecone (CLD) and the β-hexachlorocyclohexane (β-HCH) are persistent organic pollutants with a great environmental stability that cause severe affectations to health. The concentration of these pesticides in the environment is low, which represent a problem for their determination, even for the modern analytical methods. The labeling of these compounds with an iodine radioisotope for their use as radiotracers is a potential solution to this problem. The present work studies the interaction of 1-iodochlordecone (I-CLD) and β-1-iodo-pentachlorocyclohexane (I-β-HCH) with cyclodextrins (CDs), during the formation of molecular inclusion complexes pesticide@CDs. The methodology of multiple minima hypersurfaces, quantic calculations based on density functional theory and a topologic study of electronic density were used to corroborate the stability of I-CLD@CDs and I-β-HCH@CDs complexes. Three main types of guest-host complexes in relation to the occlusion grade were observed with total occlusion, with partial occlusion and external interaction without occlusion. The more stable complexes are obtained when the γ-CD is the host molecule. The formed complexes with radiolabelled pollutants are analogous with the ones reported in previous works. selleck These results confirm the utility of these complexes for the removal of organochlorine pesticides from polluted water and, also, demonstrate the possibility of using the I-CLD and the I-β-HCH as possible radiotracers for these pollutants in further studies with environmental proposes.A field experiment in Yangtze River delta of China was conducted to investigate the effects of four treatments (conventional chemical fertilizers (CF), chemical fertilizers incorporated with wheat straw (CF-WS), slow-release urea fertilizer incorporated with wheat straw (SCF-WS), and no fertilizers (Non-F)) on methane emission, rice grain yield, and straw biomass in three (2013, 2014, and 2015) consecutive growing seasons. Similar air temperature and precipitation were recorded in 2014 and 2015 normal seasons; however, the 2013 season with a 2.1-2.3 °C higher mean air temperature and a 61-64% lower precipitation than the normal seasons was considered as a warm-and-dry season.No significant differences in seasonal total methane emissions across all treatments were observed in 2014 and 2015 seasons. Seasonal total methane emissions were 58-294% higher in 2013 season compared to 2014 and 2015 seasons, which suggests that higher ambient temperatures increase methane emissions from paddy fields. The enhanced methane emission was seen mainly during the mid-to-late growth stages after mid-season drainage.

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