Cisplatin- or Carboplatin-Based Chemotherapy Plus Pembrolizumab in Advanced Urothelial Cancer: Exploratory Analysis From the Phase 3 KEYNOTE-361 Study.

Introduction: KEYNOTE-361 evaluated first-line pembrolizumab with and without platinum-based chemotherapy versus chemotherapy alone in advanced or metastatic urothelial carcinoma. The primary end points of progression-free survival (PFS) or overall survival (OS) were not met. Exploratory analysis of efficacy by platinum agent (cisplatin or carboplatin) is reported.

Outcomes by Retrospective Eligibility for Maintenance Therapy of Patients With Advanced Urothelial Carcinoma: Post Hoc Analysis of the Phase 3 KEYNOTE-361 Trial.

Introduction: The phase 3 KEYNOTE-361 trial of first-line pembrolizumab with or without chemotherapy versus chemotherapy alone in patients with locally advanced or metastatic urothelial carcinoma (la/mUC) completed enrollment before the approval of postchemotherapy maintenance avelumab for patients without progressive disease. This post hoc analysis evaluated the outcomes of patients who received chemotherapy alone in KEYNOTE-361 by retrospective eligibility for subsequent maintenance therapy.

Patients And Methods: Patients in the chemotherapy alone arm were retrospectively categorized as maintenance eligible (received ≥4 cycles of chemotherapy and did not die or experience disease progression within 10 weeks of chemotherapy completion), maintenance ineligible (received <4 cycles of chemotherapy or had progressive disease or died within 0-10 weeks after completion of ≥4 cycles of chemotherapy), and indeterminate eligibility for maintenance therapy (if neither maintenance eligible or ineligible).

Probing atomic-scale processes at the ferrihydrite-water interface with reactive molecular dynamics.

Interfacial processes involving metal (oxyhydr)oxide phases are important for the mobility and bioavailability of nutrients and contaminants in soils, sediments, and water. Consequently, these processes influence ecosystem health and functioning, and have shaped the biological and environmental co-evolution of Earth over geologic time. Here we employ reactive molecular dynamics simulations, supported by synchrotron X-ray spectroscopy to study the molecular-scale interfacial processes that influence surface complexation in ferrihydrite-water systems containing aqueous .

Exposure to microplastics contaminated with pharmaceuticals and personal care products: Histological effects on Ucides cordatus.

Pharmaceuticals and personal care products (PPCPs) are known to interact with microplastics (MPs) in aquatic environments, with substances such as the antimicrobial triclosan (TCS) and the synthetic hormone 17α-ethinylestradiol (EE2) being prevalent. These persistent contaminants are linked to toxic effects in aquatic organisms. This study aimed to investigate histological and morphometric changes in the gills of Ucides cordatus exposed to microplastics alone and microplastics contaminated with PPCPs.

Spermiogram, Kinetics, Flow Cytometric Characteristics and DNA Damage Degree in Boar Ejaculates: Summarization and Clustering.

Boar semen analysis includes sperm motility, concentration, morphology and other more complex analyses such as membrane integrity, DNA damage and seminal plasma components. This study aims to summarize these numerous data by linear combinations of them, to classify ejaculates in several categories (clusters) and to investigate the potential differences among clusters on fertility and prolificacy. Young Pietrain boars (23 ± 3.

Combined Li NMR, density functional theory and synchrotron X-ray powder diffraction to investigate a structural evolution of cathode material LiFeVO.

In our recent study, we demonstrated using Li solid-state Nuclear Magnetic Resonance (ssNMR) and single-crystal X-ray diffraction that the cathode LiFeVO possesses a defect associated with the positioning of vanadium atoms. We proposed that this defect could be the source of extra signals detected in the Li spectra. In this context, we now apply density functional theory (DFT) calculations to assign the experimental signals observed in Li NMR spectra of the pristine sample.

A novel means to generate high pressure.

Diamond anvil cells are the most popular means of generating pressures above 2 GPa. However, in many experiments, such as nuclear magnetic resonance and x-ray absorption, the metallic pressurizing gasket (which confines much of the sample) represents an occluding barrier that requires a low Z gasket material (e.g.

Microplastics and 17α Ethinylestradiol: How Do Different Aquatic Invertebrates Respond to This Combination of Contaminants?

The synthetic hormone 17α ethinyl estradiol (EE2) is a molecule widely used in female contraceptives and recognized as a contaminant of attention (Watch List) in the European Union due to its high consumption, endocrine effects and occurrence in aquatic environments. Its main source of introduction is domestic sewage where it can be associated with other contaminants such as microplastics (MPs). Due to their characteristics, they can combine with each other and exacerbate their isolated effects on biota.

Systemic effects of settleable atmospheric particulate matter (SePM) on swamp ghost crab Ucides cordatus.

Metallurgical activities are a significant source of settleable atmospheric particulate matter (SePM). The material is exposed to wind action, leading to its deposition throughout terrestrial and aquatic ecosystems, thus promoting contamination by metals and metalloids. However, knowledge of the impacts on biota is scarce.

CD3 aptamers promote expansion and persistence of tumor-reactive T cells for adoptive T cell therapy in cancer.

The CD3/T cell receptor (TCR) complex is responsible for antigen-specific pathogen recognition by T cells, and initiates the signaling cascade necessary for activation of effector functions. CD3 agonistic antibodies are commonly used to expand T lymphocytes in a wide range of clinical applications, including in adoptive T cell therapy for cancer patients. A major drawback of expanding T cell populations using CD3 agonistic antibodies is that they expand and activate T cells independent of their TCR antigen specificity.

Multidrug resistance in pathogenic isolates from urinary tract infections in dogs, Spain.

() is a pathogen frequently isolated in cases of urinary tract infections (UTIs) in both humans and dogs and evidence exists that dogs are reservoirs for human infections. In addition, is associated to increasing antimicrobial resistance rates. This study focuses on the analysis of antimicrobial resistance and the presence of selected virulence genes in isolates from a Spanish dog population suffering from UTI.

Identification of spp. in Slaughtered Sheep from Spain and Evaluation of Bradyzoite Viability after Freezing.

spp. are complex apicomplexan parasites that cause a substantial economic impact on livestock used for meat production. These parasites are present worldwide.

Sea water temperature and light intensity at high-Arctic subtidal shallows - 16 years perspective.

Manifestations of climate change in the Arctic include an increase in water temperatures and massive loss of sea ice enabling more light penetration. Yet to understand tempo and scale of these parameters change over time, constant monitoring is needed. We present 16-yr long-term datasets of sea water temperature and relative light intensity at two depth strata (8 and 14 ± 1 m) of two hard-bottom sites in southern Isfjorden proper (Spitsbergen, 78°N).

Differential regulation of innate immune system in frontal cortex and hippocampus in a "double-hit" neurodevelopmental model in rats.

Neurodevelopmental disorders (NDs) are neuropsychiatric conditions affecting central nervous system development, characterized by cognitive and behavioural alterations. Inflammation has been recently linked to NDs. Animal models are essential for understanding their pathophysiology and identifying therapeutic targets.

Transfluthrin diffusers do not protect two-person US military tents from mosquitoes in open field and canopy warm-temperate habitats.

Spatial repellents are volatile or volatilized chemicals that may repel arthropod vectors in free space, preventing bites and reducing the potential for pathogen transmission. In a 21-week field study, we investigated the efficacy of passive transfluthrin-impregnated diffusers placed in two-person United States (US) military tents located in canopy and open field habitats in north Florida to prevent mosquitoes from entering. Mosquito collections with US Centers for Disease Control and Prevention traps baited with light and carbon dioxide were conducted weekly for weeks 0-4, every two weeks for weeks 5-10, and monthly for weeks 11-21.

Diagnosis in Scrapie: Conventional Methods and New Biomarkers.

Scrapie, a naturally occurring prion disease affecting goats and sheep, comprises classical and atypical forms, with classical scrapie being the archetype of transmissible spongiform encephalopathies. This review explores the challenges of scrapie diagnosis and the utility of various biomarkers and their potential implications for human prion diseases. Understanding these biomarkers in the context of scrapie may enable earlier prion disease diagnosis in humans, which is crucial for effective intervention.

Mass spectrometry as a tool for the dereplication of specialised metabolites from DC.

genus comprises 26 species, half of them have been phytochemical investigations regarding the chemical composition, and coumarins have been considered the chemotaxonomic markers in the genus. Herein DC (Asteraceae), a native plant from Brazil, is investigated for the first time. Twenty-six compounds were isolated from aerial parts of DC.

A plain language summary exploring a new treatment combination for untreated locally advanced or metastatic urothelial cancer: enfortumab vedotin plus pembrolizumab.

What Is This Summary About?: This summary provides the results of a study of two treatments for cancer, enfortumab vedotin and pembrolizumab, that were studied together against locally advanced or metastatic urothelial cancer (la/mUC), a cancer that occurs most commonly in the bladder.

What Were The Results?: In the 45 patients studied, around 16% did have serious side effects, but most side effects were manageable. Twenty-four percent of patients, however, stopped the study treatment because of their side effects.

Plastic pellets make Excirolana armata more aggressive: Intraspecific interactions and isopod mortality differences between populations.

Plastic pellets represent a significant component of microplastic (< 5 mm) pollution. Impacts caused by plastic pellets involve physical harm and toxicity related to ingestion and non-ingestion (such as the release of chemicals in leachates). The latter is the main route of exposure for invertebrate macrobenthic populations.