Peckcox8588

In lifetime data, like cancer studies, there may be long term survivors, which lead to heavy censoring at the end of the follow-up period. Since a standard survival model is not appropriate to handle these data, a cure model is needed. In the literature, covariate hypothesis tests for cure models are limited to parametric and semiparametric methods. We fill this important gap by proposing a nonparametric covariate hypothesis test for the probability of cure in mixture cure models. A bootstrap method is proposed to approximate the null distribution of the test statistic. The procedure can be applied to any type of covariate, and could be extended to the multivariate setting. Its efficiency is evaluated in a Monte Carlo simulation study. Finally, the method is applied to a colorectal cancer dataset.Tyrosinase is a type 3 copper enzyme responsible for skin pigmentation disorders, skin cancer, and enzymatic browning of vegetables and fruits. Cisplatinum concentration In the present article, 12 small molecules of benzylidene-hydrazinecarbothioamide were designed, synthesized and evaluated for their anti-tyrosinase activities followed by molecular docking and pharmacophore-based screening. Among synthesized thiosemicarbazone derivatives, 3d is the strongest inhibitor of mushroom tyrosinase with IC 50 of 0.05 µM which demonstrated a 128 fold increase in potency compared to the positive control. Kinetic studies also revealed mix type inhibition by 3d . Docking studies confirmed the complete fitting of the synthesized compounds into the tyrosinase active site. The results underline the potential of benzylidene hydrazinecarbothioamides as potent pharmacophore to extend the tyrosinase inhibition in drug discovery.Background Application of fish skin collagen has received increasing attention due to mammalian derived diseases and religious limitations. Collagen fibril gel could be formed in vitro through the self-assembly process. The present study investigated the effect of pH on the self-assembly in vitro of acid-solubilized collagen (ASC) from golden pompano skin by determining the turbidity, rheological viscoelasticity, network structure, gel strength, and thermal stability of collagen fibril gel. Results The isoelectric point of ASC was pH 5.27. The turbidity-time and rheological viscoelasticity results indicate that the collagen self-assembly rate in vitro at pH 7.0 was the slowest. The rate was accelerated by increasing or decreasing the pH. Scanning electron microscopy images show that the fibril diameters of the collagen fibril gels and the collagenous fibril number in the collagen fiber increased with the pH. The gel strength of the collagen fibril gel prepared at pH 5.0 was 22.06 g and increased up to 220.46 g when pH increased to 8.0. No obvious peaks were observed in the differential scanning calorimetry curves of the collagen fibril gels prepared at pH 5.0, whereas high endothermic peak temperature (Tm ) and enthalpy change (ΔH) were found in the collagen fibril gels prepared at pH 6.0-8.0. Conclusion It is concluded that the physical properties of ASC fibril gels can be improved by increasing the fibril diameter controlled by pH. © 2020 Society of Chemical Industry.Background and aim Acute-on-chronic liver failure (ACLF) as a sinister prognosis and there is a need for accurate biomarkers and scoring systems to better characterize ACLF patients and predict prognosis. Systemic inflammation and renal failure are hallmarks in ACLF disease development and progression. We hypothesized that the combination of specific inflammatory markers in combination with clinical scores are better predictors of survival than the originally developed CLIF-C acute decompensation (AD) and CLIF-C ACLF scores. Methods We re-evaluated all previously measured inflammatory markers in 522 patients from the CANONIC study, 342 without and 180 with ACLF. We used the Harrell's C-index to determine the best marker alone or in combination with the original scores and calculated new scores for prediction of mortality in the original CANONIC cohort. Results The best markers to predict 90-day mortality in patients without ACLF were the plasma macrophage activation markers soluble (s)CD163 and mannose receptor (sMR). Urinary neutrophil gelatinase associated lipocalin (UNGAL) and sCD163 were predictors for 28-day mortality in patients with ACLF. The new developed CLIF-C AD+sMR score in patients without ACLF improved 90-days mortality prediction compared to the original CLIF-C AD score (C-index 0.82(0.78-0.86) vs. 0.74(0.70-0.78, P=0.004). Further, the new CLIF-C ACLF+sCD163+UNGAL improved the original CLIF-C ACLF score for 28-days mortality (0.85(0.79-0.91) vs. 0.75(0.70-0.80), P=0.039). Conclusions The capability of these inflammatory markers to improve the original prognostic scores in cirrhosis patients without and with ACLF points to a key role of macrophage activation and inflammation in the development and progression of AD and ACLF.Background Inappropriate disposal of herb residues in China has caused major problems for the immediate environment and to human safety. Here, three herb residues, compound Kushen injection (CKI), Qizhi Tongluo capsule (QTC), and Shenbai Shuxin capsule (SSC), were applied as substrates to corncob at various ratios (3060, 4545, and 6030) for the propagation of the mushroom Pleurotus ostreatus. The effects of supplementation using herb residues on yield, biodegradation ability, bioactive compounds, antioxidant properties, and safety of P. ostreatus were assessed. Results Different spawn running times were observed using growth medium, whereas 45CKI, 60QTC, and 30SSC media were determined as optimal-performing substrate combinations, resulting in yields of 843 g kg-1 , 828 g kg-1 , and 715 g kg-1 respectively. Biodegradation analysis of consumed substrates revealed a significant decrease in cellulose and hemicellulose levels compared with lignin. Furthermore, chemical analysis of fruiting bodies revealed that the 45CKI and 60QTC substrates resulted in higher total phenol, flavonoid, terpenoid, and vitamin C levels, but significantly reduced water-soluble polysaccharides compared with the corncob medium. The methanol extract of fruiting bodies grown on substrates containing herb residues exhibited higher antioxidant properties than the control, as it was more effective in scavenging 2,2-diphenyl-1-picrylhydrazyl radicals, had greater reducing power, and more strongly inhibiting lipid peroxidation. Furthermore, high-performance liquid chromatography studies indicated that fruiting bodies did not generate matrine (a specific toxin produced in Kushen) when cultivated using the CKI substrate. Conclusions P. ostreatus cultivation on substrates mixed with herb residues facilitates herb residue management as well as bioactivity-rich and non-toxic fruit body formation. © 2020 Society of Chemical Industry.