Pembrolizumab 400 mg every 6 weeks as first-line therapy for advanced melanoma (KEYNOTE-555): Results from cohort B of an open-label, phase 1 study.

Intravenous pembrolizumab 400 mg every 6 weeks was approved across tumor types based on pharmacokinetic modeling, which showed exposures consistent with previous standard dosing of 200 mg or 2 mg/kg every 3 weeks, and early results of cohort B of the phase 1 KEYNOTE-555 study. Results after ≥1 year of potential follow-up for all patients in cohort B of KEYNOTE-555 are presented. Patients aged ≥18 years with previously untreated stage III/IV melanoma received pembrolizumab 400 mg every 6 weeks for ≤18 cycles.

Histological ovarian features and hormonal determinations in assigned females at birth transgender individuals according to different testosterone preparations.

Introduction: Distinct androgen formulations have been used as gender-affirming hormone treatment, but little is known about the specific changes that may occur in the ovary depending on the testosterone preparation used. The study aims to evaluate the histological modifications of the ovarian tissue and the hormonal changes after gender-affirming surgery based on the testosterone preparation employed, such as testosterone cypionate or undecanoate.

Design: Unicenter transversal cohort study.

Evolution and Impact of Hepatitis A Epidemiology in Europe-Systematic Literature Review of the Last 20 Years.

While globally hepatitis A (hepA) infections occur in 150 million people annually, European high-income countries now have a low endemicity. However, this results in a more susceptible adult population which is prone to severe illness. To determine current epidemiological characteristics, we performed a systematic literature review to assess the severity of hepA disease in the past two decades in 11 European countries (i.

NpmC - a novel A1408 16S rRNA methyltransferase in the gut of humans and animals.

NpmA and NpmB are 16S rRNA methyltransferases that act on residue A1408 and confer high-level resistance to almost all aminoglycosides; however, these methyltransferases are rarely reported. A novel gene, npmC, was identified after analysisng all world-wide available metagenomic projects in a One Health context. This gene has a high level of similarity (91.

Sustainable Synthesis of New Antioxidants from Hydroxytyrosol by Direct Biocatalytic Esterification in Ionic Liquids.

Hydroxytyrosol (HT) is a nutraceutical compound, mainly found in the fruit, leaves and waste from the olive oil industry, known for exhibiting one of the highest antioxidant activities among molecules of natural origin. To harness this bioactivity in cosmetics, pharmaceuticals and the food industry, it is essential to modify the hydrophilicity of HT to enhance its compatibility with lipid-based mixtures. This chemical modification must be carried out with high selectivity to avoid compromising its radical scavenging activity.

Productive, Physiological, and Environmental Implications of Reducing Crude Protein Content in Swine Diets: A Review.

Pig production is one of the most important providers of high-quality proteins and amino acids (AAs) to human nutrition. In this sector, feeding has an important economic and environmental impact. A strategy to reduce production costs and negative sustainability effects is reducing dietary crude protein (CP) contents with or without AA supplementation.

Adjuvant Use of Pembrolizumab for Stage III Melanoma in a Real-World Setting in Europe.

Background: Although data on patients treated with pembrolizumab are available from clinical trials and single-country real-world reports, to our knowledge no multi-country real-world studies have investigated the use of pembrolizumab as an adjuvant treatment for stage III melanoma.

Methods: We used the European Melanoma Registry (EUMelaReg), a disease entity-based registry specific for melanoma, to examine treatment and outcomes for adult patients with stage III melanoma with lymph node involvement who had complete resection and received adjuvant treatment with pembrolizumab. The primary objectives were to describe the demographic and clinical characteristics of the included patients as well as time on adjuvant pembrolizumab treatment (TOT), real-world recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) from adjuvant pembrolizumab initiation.

Generalization of the Carothers equation for linear step growth polymers.

In the synthesis of linear step-growth polymers molecular weight control is accomplished through the addition of a controlled amount of monomer carrying the functional group B in excess (B-B or H-B types). The Carothers equation is used to calculate average chain lengths. This paper extends the analysis of chain lengths to include the effect of monofunctional monomers carrying the limiting group A (H-A), allowing the systematic analysis of complex systems containing both bifunctional and monofunctional species of any type (A-A, B-B, H-B and H-A).

Dinor-12-oxo-phytodienoic acid conjugation with amino acids inhibits its phytohormone bioactivity in Marchantia polymorpha.

Jasmonates (JAs) are important phytohormones that regulate plant tolerance to biotic and abiotic stresses, and developmental processes. Distinct JAs in different plant lineages activate a conserved signaling pathway that mediates these responses: dinor-12-oxo-phytodienoic acid (dn-OPDA) isomers in bryophytes and lycophytes, and JA-Ile in most vascular plants. In many cases, the final responses triggered by these phytohormones depend on the accumulation of specialized metabolites.

Aptamer-Hytac Chimeras for Targeted Degradation of SARS-CoV-2 Spike-1.

The development of novel tools to tackle viral processes has become a central focus in global health, during the COVID-19 pandemic. The spike protein is currently one of the main SARS-CoV-2 targets, owing to its key roles in infectivity and virion formation. In this context, exploring innovative strategies to block the activity of essential factors of SARS-CoV-2, such as spike proteins, will strengthen the capacity to respond to current and future threats.

Pharmacological characterization of prostaglandin E EP2 and EP4 receptors in male rat locus coeruleus neurons ex vivo.

The inflammatory mediator prostaglandin E (PGE) binds to G-coupled EP2 and EP4 receptors. These receptors are located in the locus coeruleus (LC), the principal noradrenergic nucleus in the brain, but their functional role remains unknown. In this study, the PGE EP2 and EP4 receptors in LC cells from male rat brain slices were pharmacologically characterized by single-unit extracellular electrophysiology.

QCD challenges from pp to AA collisions: 4th edition.

This paper is a write-up of the ideas that were presented, developed and discussed at the fourth International Workshop on QCD Challenges from pp to AA, which took place in February 2023 in Padua, Italy. The goal of the workshop was to focus on some of the open questions in the field of high-energy heavy-ion physics and to stimulate the formulation of concrete suggestions for making progresses on both the experimental and theoretical sides. The paper gives a brief introduction to each topic and then summarizes the primary results.

Embedding patient engagement in the R&D process of a life sciences company through co-creation with a patient expert R&D board: a case study.

Patient involvement is crucial in healthcare, a factor increasingly recognised by life sciences companies and research institutes. This article presents a case study on Servier, a life sciences company that founded a patient expert board, ahead of launching a new research and development (R&D) institute. The aim was to foster a patient-centric culture within the company.

New evidence on the spread in Catalonia of the invasive longhorn beetle, Xylotrechus chinensis, and the efficacy of abamectin control.

The invasive wasp-mimicking Tiger Longicorn Beetle, Xylotrechus chinensis, a potentially lethal pest of mulberry trees (Moraceae: Morus spp.), was first reported in Europe in 2018. In Catalonia its spread has been impressive: one district, four towns, 44 km in February 2018; four districts, 12 towns, 378 km in July 2020; seven districts, 65 towns, 1134 km in December 2023.

Effectiveness and safety of cannabis-based products for medical use in patients with fibromyalgia syndrome: A systematic review.

Background: There is a need to explore pharmacological options for syndrome (FMS), such as medical cannabis. The aim of this systematic review was to synthesize and analyze the available information about the effectiveness/efficacy and safety of cannabis-based products for medical use (CBPMs) and cannabis-based medicines (CBMs), in patients with FMS.

Methods: Interventional or observational studies, systematic reviews and meta-analysis regarding the effectiveness/efficacy and safety of CBPMs and CBMs in patients with FMS were retrieved from the PubMed/Medline database until April 2024.

Disentangling Neurodegeneration From Aging in Multiple Sclerosis Using Deep Learning: The Brain-Predicted Disease Duration Gap.

Background And Objectives: Disentangling brain aging from disease-related neurodegeneration in patients with multiple sclerosis (PwMS) is increasingly topical. The brain-age paradigm offers a window into this problem but may miss disease-specific effects. In this study, we investigated whether a disease-specific model might complement the brain-age gap (BAG) by capturing aspects unique to MS.

The mA-YTH regulatory system in plants: A status.

Plants use mRNA methylation to regulate gene expression. As in other eukaryotes, the only abundant methylated nucleotide in plant mRNA bodies is N6-methyladenosine (mA). The conserved core components of mA-based genetic control are a multi-subunit nuclear methyltransferase, and a set of nuclear and cytoplasmic RNA-binding proteins consisting of an mA recognition module, the YT521-B homology (YTH) domain, and long intrinsically disordered regions (IDRs).