Bempegaldesleukin Plus Nivolumab Versus Sunitinib or Cabozantinib in Previously Untreated Advanced Clear Cell Renal Cell Carcinoma: A Phase III Randomized Study (PIVOT-09).

Purpose: Bempegaldesleukin (BEMPEG) is a pegylated interleukin (IL)-2 cytokine prodrug engineered to provide controlled and sustained activation of the clinically validated IL-2 pathway, with the goal of preferentially activating and expanding effector CD8 T cells and natural killer cells over immunosuppressive regulator T cells in the tumor microenvironment. The open-label, phase III randomized controlled PIVOT-09 trial investigated the efficacy and safety of BEMPEG plus nivolumab (NIVO) as first-line treatment for advanced/metastatic clear cell renal cell carcinoma (ccRCC) with intermediate-/poor-risk disease.

Methods: Patients with previously untreated advanced/metastatic ccRCC were randomly assigned (1:1) to BEMPEG plus NIVO, or investigator's choice of tyrosine kinase inhibitor (TKI; sunitinib or cabozantinib).

Enhancing drug-drug Interaction Prediction by Integrating Physiologically-Based Pharmacokinetic Model with Fraction Metabolized by CYP3A4.

Background: Enhancing the precision of drug-drug interaction (DDI) prediction is essential for improving drug safety and efficacy. The aim is to identify the most effective fraction metabolized by CY3A4 () for improving DDI prediction using physiologically based pharmacokinetic (PBPK) models.

Research Design And Methods: The values were determined for 33 approved drugs using a human liver microsome for measurements and the ADMET Predictor software for in silico predictions.

Large-scale calibration and simulation of COVID-19 epidemiologic scenarios to support healthcare planning.

The COVID-19 pandemic has provided stiff challenges for planning and resourcing in health services in the UK and worldwide. Epidemiological models can provide simulations of how infectious disease might progress in a population given certain parameters. We adapted an agent-based model of COVID-19 to inform planning and decision-making within a healthcare setting, and created a software framework that automates processes for calibrating the model parameters to health data and allows the model to be run at national population scale on National Health Service (NHS) infrastructure.

Bempegaldesleukin plus Nivolumab in First-line Metastatic Urothelial Carcinoma: Results from PIVOT-02.

Background: Despite recent changes in the treatment landscape, there remains an unmet need for effective, tolerable, chemotherapy-free treatments for patients with advanced/metastatic urothelial carcinoma (mUC), especially cisplatin-ineligible patients.

Objective: To evaluate the immunostimulatory interleukin-2 cytokine prodrug bempegaldesleukin (BEMPEG) plus nivolumab in patients with advanced/mUC from the phase 2 multicenter PIVOT-02 study.

Design, Setting, And Participants: This open-label, multicohort phase 1/2 study enrolled patients with previously untreated locally advanced/surgically unresectable or mUC (N = 41).

Bempegaldesleukin plus nivolumab in first-line renal cell carcinoma: results from the PIVOT-02 study.

Background: Immune checkpoint inhibitor-based combinations have expanded the treatment options for patients with renal cell carcinoma (RCC); however, tolerability remains challenging. The aim of this study was to evaluate the safety and efficacy of the immunostimulatory interleukin-2 cytokine prodrug bempegaldesleukin (BEMPEG) plus nivolumab (NIVO) as first-line therapy in patients with advanced clear-cell RCC.

Methods: This was an open-label multicohort, multicenter, single-arm phase 1/2 study; here, we report results from the phase 1/2 first-line RCC cohort (N=49).

Predicting the Drug-Drug Interaction Mediated by CYP3A4 Inhibition: Method Development and Performance Evaluation.

The prediction of drug-drug interactions (DDIs) plays critical roles for the estimation of DDI risk caused by inhibition of CYP3A4. The aim of this paper is to develop a physiologically based pharmacokinetic (PBPK)-DDI model for prediction of the DDI co-administrated with ketoconazole in humans and evaluate the predictive performance of the model. The pharmacokinetic and biopharmaceutical properties of 35 approved drugs, as victims, were collected for the development of a PBPK model, which were linked to the PBPK model of ketoconazole for the DDI prediction.

Characterization of B-Genome Specific High Copy hAT MITE Families in Genome.

Miniature inverted-repeat transposable elements (MITEs) are non-autonomous class II transposons which have been shown to influence genome evolution. L. (B-genome) is one of three diploids cultivated primarily as an oil crop, which harbors novel alleles important for breeding.

A high-contiguity Brassica nigra genome localizes active centromeres and defines the ancestral Brassica genome.

It is only recently, with the advent of long-read sequencing technologies, that we are beginning to uncover previously uncharted regions of complex and inherently recursive plant genomes. To comprehensively study and exploit the genome of the neglected oilseed Brassica nigra, we generated two high-quality nanopore de novo genome assemblies. The N50 contig lengths for the two assemblies were 17.

Assessing Diversity in the Genus Provides Insights into the Genome Structure of .

(L.) Crantz an oilseed crop of the Brassicaceae family is gaining attention due to its potential as a source of high value oil for food, feed or fuel. The hexaploid domesticated has limited genetic diversity, encouraging the exploration of related species for novel allelic variation for traits of interest.

Mid-infrared spectroscopy is a fast screening method for selecting Arabidopsis genotypes with altered leaf cuticular wax.

Arabidopsis eceriferum (cer) mutants with unique alterations in their rosette leaf cuticular wax accumulation and composition established by gas chromatography have been investigated using attenuated total reflection (ATR)-Fourier transform infrared (FTIR) spectroscopy in combination with univariate and multivariate analysis. Objectives of this study were to evaluate the utility of ATR-FTIR for detection of chemical diversity in leaf cuticles, obtain spectral profiles of cer mutants in comparison with the wild type, and identify changes in leaf cuticles caused by drought stress. FTIR spectra revealed both genotype- and treatment-dependent differences in the chemical make-up of Arabidopsis leaf cuticles.

Effectiveness of a life story work program on older adults with intellectual disabilities.

Objective: This study examines the effectiveness of a life story work program (LSWp) in older adults with mild-to-moderate levels of intellectual disability (ID).

Methods: Using a quasiexperimental design, this study assigned 60 older adults who were between 50-90 years old with mild-to-moderate levels of ID to receive either the LSWp (intervention group, N=32) or usual activities (control group, N=28) during a period of 6 months. Evaluation was made based on the outcomes assessed by the Mood Interest and Pleasure Questionnaire, the Vineland Adaptive Behavior Scales, and the Personal Wellbeing Index - ID.

An archived activation tagged population of Arabidopsis thaliana to facilitate forward genetics approaches.

Background: Functional genomics tools provide researchers with the ability to apply high-throughput techniques to determine the function and interaction of a diverse range of genes. Mutagenized plant populations are one such resource that facilitate gene characterisation. They allow complex physiological responses to be correlated with the expression of single genes in planta, through either reverse genetics where target genes are mutagenized to assay the affect, or through forward genetics where populations of mutant lines are screened to identify those whose phenotype diverges from wild type for a particular trait.

A rapid two dot filter assay for the detection of E. coli O157 in water samples.

E. coli O157:H7 is an enterohemorrhagic bacteria that cause deadly water-borne infections implicated in outbreaks of a wide spectrum of human gastrointestinal diseases. It is therefore important to have a rapid convenient, simple and sensitive range of detection of E.

Pilot study of temporal variations in lead bioaccessibility and chemical fractionation in some Chinese soils.

The effect of ageing, following the addition of approximately 400mgkg(-1) lead (Pb) as Pb(NO(3))(2), on Pb bioaccessibility was examined in five typical Chinese soils using a physiologically based extraction test. Sequential extraction was employed to identify the source fraction(s) of bioaccessible Pb in the soils. Pb bioaccessibility decreased exponentially to nearly steady levels in mildly acidic or alkali (pH 6.

Diffusion-weighted imaging distinguishes recurrent epidermoid neoplasm from postoperative arachnoid cyst in the lumbosacral spine.

Diffusion-weighted imaging can be used to distinguish epidermoid tumor from arachnoid cyst in the intracranial compartment. We report the use of diffusion-weighted imaging in a postoperative spine to successfully distinguish a recurrent epidermoid tumor from arachnoid cyst in a noninvasive manner. Our case illustrates the value of this readily available sequence presently not generally used in the clinical evaluation of spinal pathology.

The effect of ageing on the bioaccessibility and fractionation of cadmium in some typical soils of China.

Ingestion of contaminated soil has been recognized as an important exposure pathway of cadmium (Cd) for humans, especially for children through outdoor hand-to-mouth activities. The effect of ageing process following the input of Cd into soil on the bioaccessibility of Cd in five typical soils of China was investigated using physiologically based in vitro test in this study. A sequential extraction procedure was employed with attempt to identify the bioaccessible fraction(s) of Cd in soils.

Assessment of the bioaccessibility of polycyclic aromatic hydrocarbons in soils from Beijing using an in vitro test.

As an important human exposure pathway of contaminants, soil ingestion is of increasing concern for assessing health risk from polycyclic aromatic hydrocarbons (PAHs) in soils. A wide range of total PAH concentrations ranging from 0.112 microg g(-1) to 27.

Contamination of polycyclic aromatic hydrocarbons (PAHs) in urban soils in Beijing, China.

Soil contamination with polycyclic aromatic hydrocarbons (PAHs) is an increasing problem in many countries, including China. An extensive and systematic survey has been undertaken to evaluate the contamination with PAHs of urban soils in Beijing, China. Soil samples were collected from campuses of universities, schools and kindergartens, public squares, fallow land and roadsides, and were analyzed for 16 PAHs by GC-MS.