Risk factors for adverse events induced by immune checkpoint inhibitors in patients with non-small-cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) can cause serious immune-related adverse events (irAEs). This study aimed to identify risk factors for all types of irAEs induced by ICIs in patients with non-small-cell lung cancer (NSCLC), by systematic review and meta-analyses. METHODS: A systematic search was performed in Pubmed, Embase and Web of Science by two independent reviewers. Studies were selected that included patients with NSCLC and evaluated characteristics of patients with and without irAEs induced by ICIs. Quality and risk of bias of the selected studies were assessed. Random effects meta-analyses were conducted to estimate pooled odds ratios (ORs) for risk factors of developing all type of irAEs, and separately for pneumonitis, interstitial lung disease and severe irAEs. With the objective of exploring sources of heterogeneity, stratified analyses were performed by quality and region. RESULTS: 25 studies met the inclusion criteria. In total, the data of 6696 patients were pooled. 33 different risk factors for irAEs were reported. irAEs of interest were reported for 1653 (25%) of the patients. Risk factors related to the development of irAEs were: C-reactive protein, neutrophil lymphocyte ratio (NLR), use of PD-1 inhibitor, high PD-L1 expression, an active or former smoking status, ground glass attenuation, and a better treatment response. CONCLUSION: The identified risk factors for the development of these irAEs are mostly related to the alteration of the immune system, proinflammatory states and loss of immunological self-tolerance. Patients identified as having a higher risk for irAEs should be monitored more closely.

Toxicity, uptake and metabolism of 4-n-nonylphenol in root cultures and intact plants under septic and aseptic conditions.

4-Nonylphenol, a compound with estrogenic activity, has been shown to occur in sewage sludges and effluents of sludge treatment. This, as well as its use in the formulation of pesticides, may result in the contamination of crop plants and may therefore have an impact on the quality of food or feedstuff. The toxicity, uptake and metabolism of 4-n-nonylphenol (4-n-NP) were investigated as(14)C-labeled 4-n-NP in root cultures under septical and aseptical conditions and with intact plants grown in containers with soil and aseptically grown in nutrient media. 4-n-NP was toxic to all plant systems tested. The presence of microorganisms and the developmental state of the plant material appeared to have an influence on the EC(50) values. 4-n-NP was taken up by the roots and a metabolism to polar compounds was observed in the cases where sufficiently high uptake rates. With intact plants a transport from roots to the shoots was evident. Metabolism in roots changed quantitatively in the presence of microorganisms. The mineralization of 4-n-NP to(14)CO(2) only occurred with microorganisms.

Synthesis of hydroxycinnamic acid esters of betacyanins via 1-O-acylglucosides of hydroxycinnamic acids by protein preparations from cell suspension cultures of Chenopodium rubrum and petals of Lampranthus sociorum.

Protein preparations from cell suspension cultures of Chenopodium rubrum L. and petals of Lampranthus sociorum (L.Bol.) N.E.Br. (Mes.C.L.Bol.) catalyzed the formation of acylated betacyanins, i.e. celosianin I and II (p-coumaroyl-and feruloylamaranthins) and lampranthin I and II (p-coumaroyl- and feruloylbetanins), from 1-O-(p-coumaroyl)-and 1-O-feruloyl-ß-glucoses as acyldonors and the respective acceptor molecules amaranthin (betanidin 5-O-sophorobiuronic acid = betanidin 5-O-ß-[1″→2']-glucuronosyl-ß-glucoside) and betanin (betanidin 5-O-ß-glucoside). The enzymes involved could generally be classified as 1-O-hydroxycinnamoyl-ß-glucose:betanidinglycoside O-hydroxycinnamoyltransferases (EC 2.3.1.-).

Accumulation of phenolic acid conjugates and betacyanins, and changes in the activities of enzymes involved in feruloylglucose metabolism in cell-suspension cultures of Chenopodium rubrum L.

Cell-suspension cultures of Chenopodium rubrum accumulate various soluble secondary phenolic metabolites such as the hydroxybenzoic acid glycosides 4-hydroxybenzoic acid-ß-glucoside, vanillic acid-ß-glucoside, the hydroxycinnamic acid acylglycosides 1-O-(4-coumaroyl)-ß-glucose, 1-O-feruloyl-ß-glucose, 1-O-sinapoyl-ß-glucose and 1-O-feruloyl-(ß-1,2-glucuronosyl)-ß-glucose, the hydroxycinnamic acid amide N-feruloylaspartate, and the betacyanins betanin, amaranthin and celosianin II. In addition, accumulation of the insoluble cell wall-bound hydroxycinnamic acids with ferulic acid as the major component occurs parallel to culture growth. The changes of three pivotal enzymatic activities, all O-transferases which are involved in the formation of the dominant ferulic acid conjugates, were determined. These are (i) uridine 5'-diphosphate(UDP)glucose-hydroxycinnamic acid O-glucosyltransferase (EC 2.4.1), (ii) UDP-glucuronic acid:1-O-hydroxycin-namoyl-ß-glucose O-glucuronosyltransferase (EC 2.4.1) and (iii) 1-O-hydroxycinnamoyl-ß-glucose:amaranthin O-hydroxycinnamoyltransferase (EC 2.3.1). The patterns of metabolite accumulation associated with these enzyme activities show that the hydroxycinnamic acid-glucose esters play a central role as metabolically active intermediates in the secondary metabolism of Ch. rubrum. Two cell lines of this culture (CH, CHN), differing in their betacyanin content, were compared with respect to this metabolism. A markedly higher total betacyanin content in the CHN line might possibly be the consequence of an increased supply of the key precursor for betalain biosynthesis, i.e. 3,4-dihydroxyphenylalanine (DOPA). In addition, the enhanced accumulation of celosianin II in the CHN line correlates well with a higher activity of the enzyme catalyzing the transfer of ferulic acid from 1-O-feruloyl-ß-glucose to amaranthin.

Compensated speckle imaging: theory and experimental results.

Previous analyses have predicted that improved power-spectrum estimation results from application of speckle-imaging postprocessing to compensated astronomical images. We report the first results, to our knowledge, of compensated-speckle-imaging experiments, conducted at a compensated telescope operated by the U.S. Air Force, that confirm these predictions. The power-spectrum signal-to-noise ratio is used as the metric for evaluating the performance. We report the results of power-spectrum estimation for a single star and three binary stars, and we reconstruct images of the binary stars using the bispectrum method to obtain the Fourier phase of the object. Compensated and uncompensated results are compared. A previously derived expression that expresses the power-spectrum signal-to-noise ratio in terms of the compensated optical transfer function statistics and object parameters is verified by experimental data.