Using Four Machine Learning Methods to Analyze the Association Between Polycyclic Aromatic Hydrocarbons and Visual Impairment in American Adults: Evidence from NHANES.

The causes of visual impairment are complex and may be influenced by exposure to environmental pollutants. Using data from the 2003-2004 National Health and Nutrition Examination Survey (NHANES), we examined the association between exposure to ten polycyclic aromatic hydrocarbons (PAHs) and vision problems in 1149 U.S.

Evaluation of a non-nucleoside inhibitor of the RSV RNA-dependent RNA polymerase in translatable animals models.

Respiratory Syncytial Virus (RSV) causes severe respiratory infections and concomitant disease resulting in significant morbidity and mortality in infants, elderly, and immunocompromised adults. Vaccines, monoclonal antibodies, and small-molecule antivirals are now either available or in development to prevent and treat RSV infections. Although rodent and non-rodent preclinical animal models have been used to evaluate these emerging agents, there is still a need to improve our understanding of the pharmacokinetic (PK)-pharmacodynamic (PD) relationships within and between animal models to enable better design of human challenge studies and clinical trials.

Intracellular islatravir-triphosphate half-life supports extended dosing intervals.

Antiretroviral therapy has substantially reduced morbidity, mortality, and disease transmission in people living with HIV. Islatravir is a nucleoside reverse transcriptase translocation inhibitor that inhibits HIV-1 replication by multiple mechanisms of action, and it is in development for the treatment of HIV-1 infection. In preclinical and clinical studies, islatravir had a long half-life (t) of 3.

Nitrogen and phosphorus addition promote invasion success of invasive species via increased growth and nutrient accumulation under elevated CO2.

In the context of the resource allocation hypothesis regarding the trade-off between growth and defence, compared with native species, invasive species generally allocate more energy to growth and less energy to defence. However, it remains unclear how global change and nutrient enrichment will influence the competition between invasive species and co-occurring native species. Here, we tested whether nitrogen (N) and phosphorus (P) addition under elevated CO2 causes invasive species (Mikania micrantha and Chromolaena odorata) to produce greater biomass, higher growth-related compounds and lower defence-related compounds than native plants (Paederia scandens and Eupatorium chinense).

Physiologically-Based Modeling and Interspecies Prediction of Cisplatin Pharmacokinetics.

The goal of this work was to develop a physiologically-based pharmacokinetic (PBPK) modeling framework for cisplatin. The model was constructed based on 11 published data sets from rodents; and rabbit, dog, and human data were used to evaluate its utility in predicting plasma and tissue distribution of platinum in larger species, including humans. The model included biotransformation of cisplatin into mobile (k) and fixed (k) metabolites in all tissues, and subsequent conversion of fixed metabolites to mobile metabolites (k) due to protein degradation and turnover.

A Retrospective Analysis of Preclinical and Clinical Pharmacokinetics from Administration of Long-Acting Aqueous Suspensions.

Administration of long-acting injectable suspensions is an increasingly common approach to increasing patient compliance and improving therapeutic efficacy through less frequent dosing. While several long-acting suspensions have recently been marketed, parameters modulating drug absorption from suspension-based formulations are not well understood. Further, methods for predicting clinical pharmacokinetic data from preclinical studies are not well established.

Prediction and Construction of Energetic Materials Based on Machine Learning Methods.

Energetic materials (EMs) are the core materials of weapons and equipment. Achieving precise molecular design and efficient green synthesis of EMs has long been one of the primary concerns of researchers around the world. Traditionally, advanced materials were discovered through a trial-and-error processes, which required long research and development (R&D) cycles and high costs.

A Randomized, Double-Blind, Placebo-Controlled, Phase 1 Trial of Radiopaque Islatravir-Eluting Subdermal Implants for Pre-exposure Prophylaxis Against HIV-1 Infection.

Background: Islatravir (MK-8591) is a deoxyadenosine analog in development for the treatment and prevention of HIV-1 infection. An islatravir-eluting implant could provide an additional option for pre-exposure prophylaxis (PrEP).

Setting: Previous data support a threshold islatravir triphosphate concentration for PrEP of 0.

Effects of elevated CO2 concentration and nitrogen addition on the chemical compositions, construction cost and payback time of subtropical trees in Cd-contaminated mesocosm soil.

Rising atmospheric CO2 concentration ([CO2]) and nitrogen (N) deposition are changing plant growth, physiological characteristics and chemical compositions; however, few studies have explored such impacts in a heavy metal-contaminated environment. In this study, we conducted an open-top chamber experiment to explore the impacts of 2 years of elevated atmospheric [CO2] and N addition on the growth, physiological characteristics and chemical compositions of five subtropical tree species in a cadmium (Cd)-contaminated environment. Results showed that N addition significantly increased concentration of leaf N and protein in five tree species and also decreased payback time (PBT) and leaf carbon:nitrogen ratios and increased tree relative height growth rate (RGR-H) and basal diameter growth rate (RGR-B) in Liquidambar formosana Hance and Syzygium hainanense Chang et Miau.

Prediction of Individual Analgesic Response to Intravenous Lidocaine in Painful Diabetic Peripheral Neuropathy: A Randomized, Placebo-controlled, Crossover Trial.

Objectives: Intravenous lidocaine can alleviate painful diabetic peripheral neuropathy (DPN) in some patients. Whether quantitative sensory testing (QST) can identify treatment responders has not been prospectively tested.

Materials And Methods: This was a prospective, randomized, double-blind, crossover, placebo-controlled trial comparing intravenous lidocaine to normal saline (placebo) for painful DPN.

Effects of elevated CO concentration and nitrogen addition on foliar phosphorus fractions of Mikania micranatha and Chromolaena odorata under low phosphorus availability.

Invasive plants rapidly spread in habitats with low soil phosphorus (P) availability and have triggered a sharp decline in the diversity of native species. However, no studies have explored how widespread invasive species acclimate to low soil P availability via changing foliar P fractions, especially under elevated atmospheric CO concentrations ([CO ]) and nitrogen (N) deposition. Here, an open-top chamber experiment was conducted to explore the effect of nutrient addition and elevated [CO ] on leaf traits and foliar functional P fractions (i.

Administration in fed state but not controlled release in the colon increases oral bioavailability of DF030263, a promising drug candidate for chronic lymphocytic leukemia.

For treatment of chronic cancers, the oral administration route is preferred as it provides numerous advantages over other delivery routes. However, these benefits of oral chemotherapy can be limited due to unfavorable pharmacokinetics. Accordingly, pharmacokinetic development of chemotherapeutic agents is crucial to the improvement of cancer treatment.

Interspecies prediction of pharmacokinetics and tissue distribution of doxorubicin by physiologically-based pharmacokinetic modeling.

The aim of the study was to develop a physiologically-based pharmacokinetic (PBPK) model to describe and predict whole-body disposition of doxorubicin following intravenous administration. The PBPK model was established using previously published data in mice and included 10 tissue compartments: lungs, heart, brain, muscle, kidneys, pancreas, intestine, liver, spleen, adipose tissue, and plasma. Individual tissues were described by either perfusion-limited or permeability-limited models.

Effects of forest conversion on carbon-degrading enzyme activities in subtropical China.

The mineralization of soil organic carbon (SOC) is primarily mediated by carbon (C) degrading enzyme. In the current study, we determined how the activities of four soil C-degrading enzymes, the hydrolases β-glucosidase (BG) and cellobiohydrolase (CBH) and the oxidases polyphenol oxidase (PPO) and peroxidase (POD), responded to forest conversion of natural broadleaf forests (BF) to secondary forests (SF) and plantation forests (PF) in subtropical China. We also quantified SOC, dissolved organic C (DOC), permanganate oxidase organic C (PXC), recalcitrant C (RC), microbial biomass C (MBC), mineral-associated C (MOC), soil particle-sizes distribution, pH, and moisture content, and C: nitrogen (N) ratio.

Prevention of paclitaxel-induced neuropathy by formulation approach.

Chemotherapy-induced peripheral neuropathy (CIPN) is a major adverse effect of paclitaxel. Several liposome-based products have been approved and demonstrated superior efficacy and safety profiles for other drugs. The first objective of this work was to evaluate the effect of liposome formulation of paclitaxel (L-PTX) on neurotoxicity in-vitro and in-vivo in comparison to the standard Taxol® formulation.

Effects of elevated atmospheric CO and nitrogen deposition on leaf litter and soil carbon degrading enzyme activities in a Cd-contaminated environment: A mesocosm study.

Rising atmospheric CO concentration and nitrogen (N) deposition are changing terrestrial carbon (C) cycle; however, little has been known about such impacts in a heavy-metal-contaminated environment. This study conducted an open-top chamber experiment to explore the impacts of rising atmospheric CO concentration and N deposition on the leaf litter and soil C cycle in cadmium (Cd)-contaminated environment. The experiment include five treatments: control, Cd (30 g ha yr) addition, Cd addition under elevated CO (700 ppm CO), Cd and N(100 kg ha yr) additions, and Cd and N additions under elevated CO, with three replicates per treatment.

Physiologically-based modeling and interspecies prediction of paclitaxel pharmacokinetics.

The objective was to develop a physiologically-based pharmacokinetic (PBPK) model to characterize the whole-body disposition of paclitaxel (formulated in Cremophor EL and ethanol-Taxol) in mice and to evaluate the utility of this model for predicting pharmacokinetics in other species. Published studies that reported paclitaxel plasma and tissue concentration-time data following single intravenous bolus administration of Taxol to mice were used; and the PBPK model included plasma, liver, lungs, kidneys, spleen, heart, gastrointestinal tract, and remainder compartments. The final model resulted in a good description of the experimental plasma and tissues data in mice, where all tissues were represented by a single compartment, except the remainder that included two sub-compartments.

Quantitative analysis of lab-to-lab variability in Caco-2 permeability assays.

In this study, Caco-2 permeability results from different laboratories were compared. Six different sets of apparent permeability coefficient (P) values reported in the literature were compared to experimental P obtained in our laboratory. The differences were assessed by determining the root mean square error (RMSE) values between the datasets, which reached levels as high as 0.