The prognostic impact of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio on patients with small cell lung cancer receiving first-line platinum-based chemotherapy: a systematic review and meta-analysis.

Background: The prognostic significance of Neutrophil-to-Lymphocyte Ratio (NLR) and Platelet-to-Lymphocyte Ratio (PLR) in Small Cell Lung Cancer (SCLC) patients receiving platinum-based chemotherapy is debated.

Methods: This study aims to elucidate their roles in survival outcomes. A systematic search across PubMed, Embase, Web of Science, and Cochrane Library identified relevant studies.

Data-assimilated crystal growth simulation for multiple crystalline phases.

To determine crystal structures from a powder x-ray diffraction (PXRD) pattern containing multiple unknown phases, a data-assimilated crystal growth (DACG) simulation method has been developed. The PXRD penalty function selectively stabilizes the structures in the experimental data, promoting their grain growth during simulated annealing. Since the PXRD pattern is calculated as the Fourier transform of the pair distribution function, the DACG simulation can be performed without prior determination of the lattice parameters.

Intermolecular correlations of liquid and glassy CS studied by synchrotron radiation x-ray diffraction.

How is the orientation of molecular liquids ordered on cooling? What are the basic structures of molecular glasses, e.g., close to the crystalline structure or some special structures such as icosahedral cluster? These are long-standing questions in liquid and glass physics.

Structural analysis and potential extraction from diffraction data of disordered systems by least-biased feature matching.

Determining the structure and underlying potential from the experiment data is an important task in the study of disordered systems such as liquids and glasses. In this article, a new approach to tackle this problem is proposed. This method can iteratively refine any interaction potential u with the form of a fixed potential ψ added by a dot product between adjustable parameter θ and some functions of atomic coordinates called features f (i.

An adiabatic method to train binarized artificial neural networks.

An artificial neural network consists of neurons and synapses. Neuron gives output based on its input according to non-linear activation functions such as the Sigmoid, Hyperbolic Tangent (Tanh), or Rectified Linear Unit (ReLU) functions, etc..

Effect of Phosphorus Modification on the Acidity, Nanostructure of the Active Phase, and Catalytic Performance of Residue Hydrodenitrogenation Catalysts.

A series of NiMoP()-Al catalysts with different phosphorus contents were prepared by the incipient wetness co-impregnation method. The effects of phosphorus modification on the acidity, active phase nanostructure, and catalytic properties of the residue hydrodenitrogenation catalysts were investigated to find the role of phosphorus in the catalytic mechanism. The results of temperature-programmed desorption of NH and pyridine IR spectroscopy of the catalysts indicate that phosphorus modification can increase the total acid and Brønsted acid.

Mass Spectrometry Imaging: Applications in Drug Distribution Studies.

In the past decade, mass spectrometry imaging (MSI) has received an increasing amount of attention due to its ability in displaying the spatial distribution of a wide range of molecules, including peptides, proteins, lipids, endogenous and exogenous metabolites, and xenobiotics in biological tissues. Information regarding drug localization within tissues provides a better understanding of pharmacokinetic behaviors and pharmacological and toxicological effects. This review presents an introduction to MSI, along with an in-depth analysis of its general process.

A Physiologically Based Pharmacokinetic Model of Amiodarone and its Metabolite Desethylamiodarone in Rats: Pooled Analysis of Published Data.

Background And Objective: Amiodarone (AMD) is one of the most effective drugs for rhythm control of atrial fibrillation. The use of AMD is also associated with adverse effects in multiple tissues. Both the parent compound and its major metabolite desethylamiodarone (DEA) contribute to the drug's therapeutic and toxic action.

Quantitative evaluation of drug-drug interaction potentials by in vivo information- guided prediction approach.

Drug-drug interaction (DDI) is one important topic in drug discovery, drug development and clinical practice. Recently, a novel approach, in vivo information-guided prediction (IVIP), was introduced for predicting the magnitude of pharmacokinetic DDIs which are caused by changes in cytochrome P450 (CYP) activity. This approach utilizes two parameters, i.

Are circulating metabolites important in pharmacokinetic drug-drug interactions? A retroanalysis of clinical data.

Pharmacokinetic (PK) drug-drug interactions (DDIs) give rise to adverse events and/or reduced efficacy. Comprehensive, systematic and mechanistic approaches have been applied in the evaluation, propagation and management of the interaction potential of a new drug during its development and clinical use. However, the role of drug metabolite(s) in DDIs was not extensively investigated.

Identification of known chemicals and their metabolites from Alpinia oxyphylla fruit extract in rat plasma using liquid chromatography/tandem mass spectrometry (LC-MS/MS) with selected reaction monitoring.

Alpinia oxyphylla (Yizhi) capsularfruits are commonly used in traditional medicine. Pharmacological studies have demonstrated that A. oxyphylla capsularfruits have some beneficial roles.

Different accumulation profiles of multiple components between pericarp and seed of Alpinia oxyphylla capsular fruit as determined by UFLC-MS/MS.

Plant secondary metabolites are known to not only play a key role in the adaptation of plants to their environment, but also represent an important source of active pharmaceuticals. Alpinia oxyphylla capsular fruits, made up of seeds and pericarps, are commonly used in traditional East Asian medicines. In clinical utilization of these capsular fruits, inconsistent processing approaches (i.

A physiologically based pharmacokinetic model of alvespimycin in mice and extrapolation to rats and humans.

Background And Purpose: Alvespimycin, a new generation of heat shock protein 90 (Hsp90) inhibitor in clinical trial, is a promising therapeutic agent for cancer. Pharmacokinetic models of alvespimycin would help in the understanding of drug disposition, predicting drug exposure and interpreting dose-response relationship. In the present study we aimed to develop a physiologically based pharmacokinetic (PBPK) model of alvespimycin in mice and evaluate the utility of the model for predicting alvespimycin disposition in other species.

Physiologically based pharmacokinetic modelling and in vivo [I]/K(i) accurately predict P-glycoprotein-mediated drug-drug interactions with dabigatran etexilate.

Background And Purpose: In vitro inhibitory potency (Ki )-based predictions of P-glycoprotein (P-gp)-mediated drug-drug interactions (DDIs) are hampered by the substantial variability in inhibitory potency. In this study, in vivo-based [I]/Ki values were used to predict the DDI risks of a P-gp substrate dabigatran etexilate (DABE) using physiologically based pharmacokinetic (PBPK) modelling.

Experimental Approach: A baseline PBPK model was established with digoxin, a known P-gp substrate.

Intestinal absorption and presystemic elimination of various chemical constituents present in GBE50 extract, a standardized extract of Ginkgo biloba leaves.

The nature and level of systemic exposure to the active herbal constituents will profoundly affect their effects at action sites, which is fundamental in understanding their roles in the overall beneficial effects of a herbal medicine. The objective of this study is to gain a full picture of the systemic exposure to various putatively active ginkgo constituents after p.o.

Dose-dependent association between UGT1A1*28 polymorphism and irinotecan-induced diarrhoea: a meta-analysis.

Life-threatening diarrhoea is observed in up to 25% of cancer patients receiving irinotecan. The associations between the UGT1A1*28 polymorphism and irinotecan-induced diarrhoea remains controversial because of conflicting data in the literature. Meta-analyses were performed on published data in terms of relationships between UGT1A1*28 and severe diarrhoea.

Sex-dependent differences in cytochrome P450 3A activity as assessed by midazolam disposition in humans: a meta-analysis.

Controversy exists concerning the sex-dependent differences in cytochrome P450 3A activity in humans. Meta-analysis of selected studies may address this question. Meta-analysis was performed on published or unpublished data in terms of sex-dependent differences in midazolam (MDZ) disposition in humans.

Endogenous cortisol 6 beta-hydroxylation clearance is not an accurate probe for overall cytochrome P450 3A phenotyping in humans.

Background: We determined if endogenous cortisol 6 beta-hydroxylation clearance [CL(m(6 beta))] could be used as a reliable index for in vivo CYP3A phenotyping (including both hepatic and intestinal CYP3A activities).

Methods: In this study, 16 healthy volunteers received a single 7.5 mg oral dose of midazolam (MDZ).