Pembrolizumab Plus Carboplatin and Paclitaxel as First-Line Therapy for Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (KEYNOTE-B10): A Single-Arm Phase IV Trial.

Purpose: Standard-of-care first-line treatment for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) is pembrolizumab plus platinum and fluorouracil (FU). However, FU is associated with potential challenges (continuous 4-day infusion, high administration costs, and cardiovascular and gastrointestinal toxicities), creating a clinical need for alternative chemotherapy combinations. We evaluated the efficacy and safety of first-line pembrolizumab plus carboplatin and paclitaxel for R/M HNSCC in the open-label, single-arm, phase IV KEYNOTE-B10 study (ClinicalTrials.

Temporal trend data (2005-2020) in density and biomass of 13 herbivorous fishes in the Gulf of California.

This dataset comes from a multi-institution compilation of monitoring information for 13 marine herbivorous fishes belonging to six genera of five families: Acanthuridae, Girellidae, Kyphosidae, Pomacentridae and Scaridae, gathered from 2005 to 2020 in the Gulf of California. The database presents a total of 884 records of biomass and density got from 15,542 visual censuses performed using scuba diving in 34 localities comprising 268 rocky and coral reef sites. The censuses consisted of belt transects (250 m, 100 m, and 60 m) laid parallel to the coastline, where expert monitors recorded the abundance of all observed adult individuals of the 13 target herbivorous species, and visually estimated the total length (cm) of each fish.

Dostarlimab or pembrolizumab plus chemotherapy in previously untreated metastatic non-squamous non-small cell lung cancer: the randomized PERLA phase II trial.

PERLA is a global, double-blind, parallel phase II trial (NCT04581824) comparing efficacy and safety of anti-PD-1 antibodies dostarlimab and pembrolizumab, plus chemotherapy (DCT and PCT, respectively) as first-line treatment in patients with metastatic non-squamous NSCLC without known targetable genomic aberrations. Patients stratified by PD-L1 tumor proportion score and smoking status were randomized 1:1, receiving ≤35 cycles 500 mg dostarlimab or 200 mg pembrolizumab, ≤35 cycles 500 mg/m pemetrexed and ≤4 cycles cisplatin (75 mg/m) or carboplatin (AUC 5 mg/ml/min) Q3W. Primary endpoint was overall response rate (ORR) (blinded independent central review).

Initial adhesion suppression of biofilm-forming and copper-tolerant bacterium Variovorax sp. on laser microtextured copper surfaces.

The growth of detrimental biofilms on metal surfaces affects their structural performance and lifespan. Microtopographic texturization has emerged as an approach to suppress biofilm growth by preventing the initial stages of bacterial adhesion. This work studies the effects of linear pattern copper texturization on the initial adhesion steps of the biofilm-forming and copper-resistant bacterium Variovorax sp.

Activation of P2X4 receptors induces an increase in the area of the extracellular region and a decrease in receptor mobility.

The P2X4 receptor (P2X4R) is an ATP-gated cation channel. Here, we used fast-scan atomic force microscopy (AFM) to visualize changes in the structure and mobility of individual P2X4Rs in response to activation. P2X4Rs were purified from detergent extracts of transfected cells and integrated into lipid bilayers.

Polydisperse molecular architecture of connexin 26/30 heteromeric hemichannels revealed by atomic force microscopy imaging.

Connexin (Cx) protein forms hemichannels and gap junctional channels, which play diverse and profound roles in human physiology and diseases. Gap junctions are arrays of intercellular channels formed by the docking of two hemichannels from adjacent cells. Each hexameric hemichannel contains the same or different Cx isoform.

Live endothelial cells on plasma-nitrided and oxidized titanium: An approach for evaluating biocompatibility.

We evaluated the effects of titanium plasma nitriding and oxidation on live endothelial cell viscoelasticity. For this, mechanically polished titanium surfaces and two surfaces treated by planar cathode discharge in nitriding (36N and 24H) and oxidant (36O and 24H). Surfaces were characterized regarding wettability, roughness and chemical composition.

Function of P2X4 Receptors Is Directly Modulated by a 1:1 Stoichiometric Interaction With 5-HTA Receptors.

Interacting receptors at the neuronal plasma membrane represent an additional regulatory mode for intracellular transduction pathways. P2X4 receptor triggers fast neurotransmission responses a transient increase in intracellular Ca levels. It has been proposed that the P2X4 receptor interacts with the 5-HTA receptor in hippocampal neurons, but their binding stoichiometry and the role of P2X4 receptor activation by ATP on this crosstalking system remains unknown.

Nanoscale Mobility of the Apo State and TARP Stoichiometry Dictate the Gating Behavior of Alternatively Spliced AMPA Receptors.

Neurotransmitter-gated ion channels are allosteric proteins that switch on and off in response to agonist binding. Most studies have focused on the agonist-bound, activated channel while assigning a lesser role to the apo or resting state. Here, we show that nanoscale mobility of resting α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type ionotropic glutamate receptors (AMPA receptors) predetermines responsiveness to neurotransmitter, allosteric anions and TARP auxiliary subunits.

An autocrine ATP release mechanism regulates basal ciliary activity in airway epithelium.

Key Points: Extracellular ATP, in association with [Ca ] regulation, is required to maintain basal ciliary beat frequency. Increasing extracellular ATP levels increases ciliary beating in airway epithelial cells, maintaining a sustained response by inducing the release of additional ATP. Extracellular ATP levels in the millimolar range, previously associated with pathophysiological conditions of the airway epithelium, produce a transient arrest of ciliary activity.