RANKL blockade inhibits cancer growth through reversing the tolerogenic profile of tumor-infiltrating (plasmacytoid) dendritic cells.

Background: Originally identified for its involvement in bone remodeling, accumulating data emerged in the past years indicating that receptor activator of nuclear factor κB ligand (RANKL) actually acts as a multifunctional soluble molecule that influences various physiological and pathological processes. Regarding its role in carcinogenesis, while direct effects on tumor cell behavior have been precisely characterized, the impact of the RANKL/RANK system (and its inhibition) on the intratumoral immune landscape remains unclear.

Methods: After various in silico/in situ/in vitro analyses, the immunotherapeutic efficacy of RANKL blockade (alone and in combination with immune checkpoint inhibitors (anti-programmed cell death protein-1 (PD-1)) or doxorubicin/paclitaxel-based chemotherapy) was investigated using different syngeneic mouse models of triple-negative breast cancer (4T1, 67NR and E0771).

High-Performance Polymer Blends: Manufacturing of Polyetherimide (PEI)-Polycarbonate (PC)-Based Filaments for 3D Printing.

The demand for high-performance polymers in 3D printing continues to grow due to their ability to produce intricate and complex structures. However, commercially available high-temperature 3D printing materials often exhibit limitations such as brittleness, warping, thermal sensitivity, and high costs, highlighting the need for advanced filament development. This study investigates the fabrication of polyetherimide (PEI) and polycarbonate (PC) blends via melt extrusion to enhance material properties for stable additive manufacturing.

Transfer Learning Approach to Multitarget QSRR Modeling in RPLC.

QSRR is a valuable technique for the retention time predictions of small molecules. This aims to bridge the gap between molecular structure and chromatographic behavior, offering invaluable insights for analytical chemistry. Given the challenge of simultaneous target prediction with variable experimental conditions and the scarcity of comprehensive data sets for such predictive modelings in chromatography, this study introduces a transfer learning-based multitarget QSRR approach to enhance retention time prediction.

Surface enhanced transmission Raman spectroscopy: Quantitative performances for impurity analysis in complex matrices.

A transmission detection mode was investigated with SERS analyses (SETRS). A comparison between backscattering and transmission detection modes was conducted to demonstrate the feasibility of performing SETRS analyses. The impact of various parameters on the SERS signal intensity such as sample volume, lens collection optic, laser beam size and laser power were then examined.

Optimisation of a Microwave Synthesis of Silver Nanoparticles by a Quality by Design Approach to Improve SERS Analytical Performances.

A major limitation preventing the use of surface-enhanced Raman scattering (SERS) in routine analyses is the signal variability due to the heterogeneity of metallic nanoparticles used as SERS substrates. This study aimed to robustly optimise a synthesis process of silver nanoparticles to improve the measured SERS signal repeatability and the protocol synthesis repeatability. The process is inspired by a chemical reduction method associated with microwave irradiation to guarantee better controlled and uniform heating.

Uncertainty management for In Silico screening of reversed-phase liquid chromatography methods for small compounds.

The process of developing new reversed-phase liquid chromatography methods can be both time-consuming and challenging. To meet this challenge, statistics-based strategies have emerged as cost-effective, efficient and flexible solutions. In the present study, we use a Bayesian response surface methodology, which takes advantage of the knowledge of the pKa values of the compounds present in the analyzed sample to model their retention behavior.

Understanding the determinants of sweet taste liking in the African and East Asian ancestry groups in the U.S.-A study protocol.

Background: The liking for sweet taste is a powerful driver for consuming added sugars, and therefore, understanding how sweet liking is formed is a critical step in devising strategies to lower added sugars consumption. However, current research on the influence of genetic and environmental factors on sweet liking is mostly based on research conducted with individuals of European ancestry. Whether these results can be generalized to people of other ancestry groups warrants investigation.

The benefits of validation of methods for toxicity testing outweigh its costs.

The 4th Annual Forum on Endocrine Disrupters organized by the European Commission brought together the authors of this article around the topic: “From bench to validated test guidelines: (pre)val­idation of test methods”. Validation activities are meant to demonstrate the relevance and reliability of methods and approaches used in regulatory safety testing. These activities are essential to facil­itate regulatory use, still they are largely underfunded and unattractive to the scientific community.

Comprehensive analysis of vitamin D impurities in oily drug products using supercritical fluid chromatography-mass spectrometry.

Vitamin D, an essential micronutrient, often requires supplementation via medicines or food supplements, which necessitate quality control (QC). This study presents the development of a method for detecting and quantifying seven impurities of vitamin D in oily drug products using supercritical fluid chromatography-mass spectrometry (SFC-MS). Targeted impurities include two esters of vitamin D and five non-esters including four that are isobaric to vitamin D.

Political affiliation as a moderator of the relationship between organizational climate and COVID-19 vaccine readiness.

Rationale: Organizations have a significant influence on their employees' behavior and attitudes across a wide range of areas. A framework to bundle these effects is organizational climate. Here, we argue that in a highly polarized society, such as the United States, many types of organizational climate revolve around issues that are divided along partisan lines (e.

Protective Effect of Ticagrelor Against Infective Endocarditis Induced by Virulent in Mice.

In addition to its potent antiplatelet activity, ticagrelor possesses antibacterial properties against gram-positive bacteria. We wondered whether the typical clinical dosage of ticagrelor could prevent the development of infective endocarditis caused by highly virulent . Ticagrelor prevented vegetation formation in a mouse model of inflammation-induced endocarditis.

Understanding the Determinants of Sweet Liking in the African and East Asian Ancestry Groups in the U.S. - A Study Protocol.

Background: The liking for sweet taste is a powerful driver for consuming added sugars, and therefore, understanding how sweet liking is formed is a critical step in devising strategies to lower added sugars consumption. However, current research on the influence of genetic and environmental factors on sweet liking is mostly based on research conducted with individuals of European ancestry. Whether these results can be generalized to people of other ancestry groups warrants investigation.

In-Field Implementation of Near-Infrared Quantitative Methods for Analysis of Medicines in Tropical Environments.

Near-infrared (NIR) spectroscopy is actually a well-established technique that demonstrates its performance in the frame of detection of poor-quality medicines. The use of low-cost handheld NIR spectrophotometers in low-resource contexts can allow an inexpensive and more rapid detection compared to laboratory methods. Considering these points, it was decided to develop, validate, and transfer methods for the quantification of ciprofloxacin and metronidazole tablet samples using a NIR handheld spectrophotometer in transmission mode (NIR-M-T1) coupled to chemometrics such as partial least squares regression (PLSR) algorithm.

A multi-target QSRR approach to model retention times of small molecules in RPLC.

Quantitative structure-retention relationship models (QSRR) have been utilized as an alternative to costly and time-consuming separation analyses and associated experiments for predicting retention time. However, achieving 100 % accuracy in retention prediction is unrealistic despite the existence of various tools and approaches. The limitations of vast data availability and time complexity hinder the use of most algorithms for retention prediction.

Usefulness of medicine screening tools in the frame of pharmaceutical post-marketing surveillance.

The negative consequences of Substandard and falsified (SF) medicines are widely documented nowadays and there is still an urgent need to find them in more efficient ways. Several screening tools have been developed for this purpose recently. In this study, three screening tools were used on 292 samples of ciprofloxacin and metronidazole collected in Cameroon.

Thermochemical and rheological characterization of highly reactive thermoset resins for liquid moulding.

Highly reactive thermosets are currently expanding the processability of high-performance structures for transportation industry. The short polymerization time makes it a suitable process to replace metallic structures with polymer matrix-based composite materials. The resin characterization is a fundamental step to obtain the properties and the associated constitutive models, which are required to design and optimize the manufacturing process parameters of composite materials.

Optimization of silver nanoparticles synthesis by chemical reduction to enhance SERS quantitative performances: Early characterization using the quality by design approach.

Surface-enhanced Raman scattering (SERS) is a vibrational widely used technique thanks to its multiple advantages such as its high specificity and sensitivity. The Raman signal exaltation comes from the use of metallic nanoparticles (Nps) acting as antennas by amplifying the Raman scattering. Controlling the Nps synthesis is a major point for the implementation of SERS in routine analysis and especially in quantitative applications.

Organizations affect their employees' vaccine readiness: A self-perception theory perspective.

Over the past 3 years, employees have constantly witnessed how their organizations have responded to the challenges posed by the COVID-19 pandemic. Here, we hypothesize that employees' perceptions of the COVID-19 safety climate of their organization positively affect their vaccine readiness. To examine the underlying mechanisms of this effect, we use a self-perception theory lens.

ReadEDTest: A tool to assess the readiness of in vitro test methods under development for identifying endocrine disruptors.

Growing evidence shows that endocrine disruptors (EDs), known to affect the reproductive system, may also disturb other hormone-regulated functions leading to cancers, neurodevelopmental defects, metabolic and immune diseases. To reduce exposure to EDs and limit their health effects, development of screening and mechanism-based assays to identify EDs is encouraged. Nevertheless, the crucial validation step of test methods by regulatory bodies is a time- and resource-consuming process.

Acute and Chronic Changes in Myocardial Work Parameters in Patients with Severe Primary Mitral Regurgitation Undergoing Transcatheter Edge-to-Edge Repair.

Background: The noninvasive assessment of myocardial work (MW) allows for the evaluation of left ventricular (LV) performance by considering the effect of LV afterload. This study aims to evaluate the acute and chronic impact of transcatheter edge-to-edge repair (TEER) on MW parameters and LV remodeling in patients with severe primary mitral regurgitation (PMR).

Methods: A total of 71 patients (age: 77 ± 9 years, females: 44%) with moderate-to-severe or severe PMR (effective regurgitant orifice: 0.

Quantitative Structure Retention-Relationship Modeling: Towards an Innovative General-Purpose Strategy.

Reversed-Phase Liquid Chromatography (RPLC) is a common liquid chromatographic mode used for the control of pharmaceutical compounds during their drug life cycle. Nevertheless, determining the optimal chromatographic conditions that enable this separation is time consuming and requires a lot of lab work. Quantitative Structure Retention Relationship models (QSRR) are helpful for doing this job with minimal time and cost expenditures by predicting retention times of known compounds without performing experiments.

Human papillomavirus E6/E7 oncoproteins promote radiotherapy-mediated tumor suppression by globally hijacking host DNA damage repair.

Whatever the mucosa primary infected, HPV-positive cancers are traditionally associated with a favorable outcome, attributable to a high sensitivity to radiation therapy. However, the direct impact of viral E6/E7 oncoproteins on the intrinsic cellular radiosensitivity (and, globally, on host DNA repair) remains mostly speculative. Using several isogenic cell models expressing HPV16 E6 and/or E7, the effect of viral oncoproteins on global DNA damage response was first investigated by approaches.

Prevalence of Poor Quality Ciprofloxacin and Metronidazole Tablets in Three Cities in Cameroon.

Quality is one of the essential components of medicines and needs to be ensured to preserve the population's health. This can be achieved through post-marketing quality control of medicines and is one of the most important duties of national regulatory authorities. In collaboration with the Cameroonian National Drug Quality Control and Valuation Laboratory, the decision was made to initiate a prevalence study to assess the quality of antiinfective medicines in Cameroon.

User-Driven Strategy for In Silico Screening of Reversed-Phase Liquid Chromatography Conditions for Known Pharmaceutical-Related Small Molecules.

In the pharmaceutical field, and more precisely in quality control laboratories, robust liquid chromatographic methods are needed to separate and analyze mixtures of compounds. The development of such chromatographic methods for new mixtures can result in a long and tedious process even while using the design of experiments methodology. However, developments could be accelerated with the help of in silico screening.