Comparison of two strategies of glucocorticoid withdrawal in patients with rheumatoid arthritis in low disease activity (STAR): a randomised, placebo- controlled, double-blind trial.

Objectives: To compare two strategies-a hydrocortisone replacement strategy and a prednisone tapering strategy-for their success in glucocorticoid discontinuation in patients with rheumatoid arthritis (RA) with low disease activity (LDA).

Methods: The Strategies for glucocorticoid TApering in Rheumatoid arthritis (STAR) study was a double- blind, double-placebo randomised controlled trial including patients with RA receiving a stable dose of glucocorticoid 5 mg/day for ≥3 months and were in LDA for ≥3 months. Patients were randomly assigned in a 1:1 ratio to either replace prednisone with 20 mg/day of hydrocortisone for 3 months, then reduce to 10 mg/day for 3 months before discontinuation or to taper prednisone by 1 mg/day every month until complete discontinuation, contingent on maintaining LDA.

Nickel-Catalyzed Selective Reduction of Carbon Monoxide with Magnesium Alkyl Compounds.

Research on CO activation and homologation is pivotal for promoting sustainable chemistry and the construction of Cn molecular blocks. This work reports the nickel-catalyzed reduction of CO by magnesium alkyl compounds utilizing a bimetallic Mg/Ni synergistic strategy. The exposure of β-diketiminato ligand-supported magnesium monoalkyl compounds LMgR (L = [(DippNCMe)2CH]-, Dipp = 2,6-iPr2C6H3; R = nBu, CH3, C5H9) to 1 bar of CO in the presence of 10 mol% Ni(COD)2 (COD: 1,5-cyclooctadiene) selectively afforded the CO single-insertion product [LMg(CHO)C5H8], the dimerization product [(LMg)2(μ-C2O2)(CH3)2], and the linear trimerization product [(LMg)2(μ-C3O3)(nBu)2], respectively, depending on the R group.

Emoquine-1: A Hybrid Molecule Efficient against Multidrug-Resistant Parasites, Including the Artemisinin-Resistant Quiescent Stage, and Also Active In Vivo.

To challenge the multidrug resistance of malaria parasites, new hybrid compounds were synthesized and evaluated against laboratory strains and multidrug-resistant clinical isolates. Among these hybrids, emoquine-1 was the most active on proliferative , with IC values in the range of 20-55 nM and a high selectivity index with respect to mammalian cells. This drug retained its activity on several multiresistant field isolates from Cambodia and Guiana, exhibited no cross-resistance to artemisinin, and is also very active against the quiescent stage of the artemisinin-resistant parasites, three features that constitute the gold standard for new antimalarial drugs.

Lanternfish as bioindicator of microplastics in the deep sea: A spatiotemporal analysis using museum specimens.

We investigated MP ingestion in lanternfishes (Myctophidae), one of the most abundant vertebrates in the world, using archived specimens from museum collections from 1999 to 2017. Microplastics were detected in 55 % of the 1167 specimens analysed (0.95 ± 1.

Beyond the Dailey-Townes Model: Chemical Information from the Electric Field Gradient.

In this work, we reexamine the Dailey-Townes model by systematically investigating the electric field gradient (EFG) in various chlorine compounds, dihalogens, and the uranyl ion (). Through the use of relativistic molecular calculations and projection analysis, we decompose the EFG expectation value in terms of atomic reference orbitals. We show how the Dailey-Townes model can be seen as an approximation to our projection analysis.

On the need to better integrate the social environment in research on climate change and health: recommendations and thinking tools.

Social inequality impacts health, is aggravated by the consequences of climate change, and may be influenced by inappropriate policy responses. These interdependent effects create a self-perpetuating loop exacerbating the impact of climate dysregulation on health in an uncontrolled and poorly understood way. Holistic approaches to public health such as One Health, EcoHealth or Planetary Health are well suited to tackling the considerable and complex environmental and social issues underlying climate dysregulation.

Organoids, organs-on-chips, complex in vitro model: Definitions, applications, validation, ethics.

Over the past decade, new in vitro biological models have emerged which can reproduce certain characteristics of human physiology and pathologies. From organoids to organs-on-chips, these new technologies are currently revolutionizing the entire chain of research and development in pharmacology. All stakeholders are thus involved, from academic laboratories to pharmaceutical companies, start-ups, and assessment agencies.

The Omics-Driven Machine Learning Path to Cost-Effective Precision Medicine in Chronic Kidney Disease.

Chronic kidney disease (CKD) poses a significant and growing global health challenge, making early detection and slowing disease progression essential for improving patient outcomes. Traditional diagnostic methods such as glomerular filtration rate and proteinuria are insufficient to capture the complexity of CKD. In contrast, omics technologies have shed light on the molecular mechanisms of CKD, helping to identify biomarkers for disease assessment and management.

Operando Gravimetric and Energy Loss Analysis of NaV(PO)F Composite Films by Electrochemical Quartz Microbalance with Dissipation Monitoring.

The rising demand for energy storage calls for technological advancements to address the growing needs. In this context, sodium-ion (Na-ion) batteries have emerged as a potential complementary technology to lithium-ion batteries (Li-ion). Among other materials, NaV(PO)F (NVPF) is a promising cathode for Na-ion batteries due to its high operating voltage and good energy density.

Evaluation of rheumatoid arthritis-associated interstitial lung disease in patients treated with JAK inhibitors: a MAJIK-SFR cohort study.

Objective: To examine the course of interstitial lung disease associated with rheumatoid arthritis (RA-ILD) in France on treatment with Janus kinase inhibitors (JAKis) using the MAJIK-SFR registry.

Methods: Prospective national multicentre observational study identifying patients with RA-ILD from the MAJIK-SFR registry. Pulmonary assessment data were collected at JAKi initiation and follow-up visits (6 months, 12 months and a median of 21 months postinclusion), including chest high-resolution CT (HRCT), pulmonary function tests (forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO)), acute exacerbations of ILD, respiratory infections and lung cancers.

Four-electron reduction of benzene by a samarium(II)-alkyl without the addition of external reducing agents.

Benzene reduction by molecular complexes remains an important synthetic challenge, requiring harsh reaction conditions involving group I metals. Reductions of benzene, to date, typically result in a loss of aromaticity, although the benzene tetra-anion, a 10π-electron system, has been calculated to be stable and aromatic. Due to the lack of sufficiently potent reductants, four-electron reduction of benzene usually requires the use of group I metals.

Mechanical compressive forces increase PI3K output signaling in breast and pancreatic cancer cells.

Mechanical stresses, including compression, arise during cancer progression. In solid cancer, especially breast and pancreatic cancers, the rapid tumor growth and the environment remodeling explain their high intensity of compressive forces. However, the sensitivity of compressed cells to targeted therapies remains poorly known.

The multi-faceted roles of MYC in the prognosis of chronic lymphocytic leukemia.

In this review, we focus on the pro-oncogene MYC, the modes of deregulation in mouse and human B-cells, its undisputable importance in the evaluation of biological prognostication of patients, but also how it impacts on response to modern therapeutics, and how it should be targeted to improve the overall survival of chronic lymphocytic lymphoma (CLL) patients. After an overview of the current understanding of the molecular dysregulation of c-MYC, we will show how CLL, both in its indolent and transformed phases, has developed among other B-cell lymphomas a tight regulation of its expression through the chronic activation of B-Cell Receptors (among others). This is particularly important if one desires to understand the mechanisms at stake in the over-expression of c-MYC especially in the lymph nodes compartment.

Conservation of symbiotic signaling since the most recent common ancestor of land plants.

Plants have colonized lands 450 million years ago. This terrestrialization was facilitated by developmental and functional innovations. Recent evo-devo approaches have demonstrated that one of these innovations was the mutualistic arbuscular mycorrhizal symbiosis (AMS).

Lack of fibro-inflammatory response in human mammary adipose tissue in obesity.

Background: Understanding how obesity impacts human mammary adipose tissue (MAT) biology is crucial for deciphering its role in mammary epithelium during both physiological and pathophysiological processes, including breast cancer. Hypertrophic mammary adipocytes and Crown-Like Structures are present in MAT of patients with obesity but whether these changes initiate a fibro-inflammatory response at the tissue level remains insufficiently explored.

Objective: We investigated the markers of adipose tissue dysfunction (immune cell infiltration, secretion pattern and fibrosis) in tumor-free MAT of patients with obesity versus patients who are lean.

Nanopore Sequencing as a Cutting-Edge Technology for Medulloblastoma Classification.

Background: Medulloblastoma (MB) is one of the most prevalent embryonal malignant brain tumors. Current classification organizes these tumors into four molecular subgroups (WNT, SHH, Group 3, and Group 4 MB). Recently, a comprehensive classification has been established, identifying numerous subtypes, some of which exhibit a poor prognosis.

Fumagillin Shortage: How to Treat Microsporidiosis in Solid Organ Transplant Recipients in 2024?

Unlabelled: Intestinal microsporidiosis caused by is an opportunistic infection that especially affects solid organ transplant (SOT) recipients. Management revolves around tapering the immunosuppressive regimen and/or using a specific anti-microsporidia treatment, but only fumagillin has demonstrated efficacy for treatment of this infection. Since fumagillin has been commercially discontinued, nitazoxanide is increasingly being used in this indication.

Diverse polysaccharide production and biofilm formation abilities of clinical Klebsiella pneumoniae.

Klebsiella pneumoniae infections have become a growing threat for human health. The lack of understanding of the relationship between antibiotic resistance, mucoviscosity, and biofilm formation impedes our abilities to effectively predict K. pneumoniae infection outcomes.

Mass Spectrometry-Based Workflow for the Identification and Quantification of Alternative and Canonical Proteins in Pancreatic Cancer Cells.

The identification of small proteins and proteins produced from unannotated open reading frames (called alternative proteins or AltProts) has changed our vision of the proteome and has attracted more and more attention from the scientific community. Despite several studies investigating particular AltProts in diseases and demonstrating their importance in such context, we are still missing data on their expression and functions in many pathologies. Among these, pancreatic ductal adenocarcinoma (PDAC) is a particularly relevant case to study alternative proteins.

Reductive Activation of Artefenomel (OZ439) by Fe(II)-Heme, Related to Its Antimalarial Activity.

The 1,2,4-trioxolane antimalarial drug, OZ439 (artefenomel), exhibits cross-resistance to artemisinins with similar survival rates of artemisinin-resistant parasites after dihydroartemisinin or OZ439 exposure, suggesting that this drug shares some mechanisms of action with artemisinins. In this way, we investigated the reductive activation of OZ439 by heme in the presence of dithionite, demonstrating the formation of covalent heme-drug adducts. However, in the presence of the biologically abundant reductant glutathione instead of dithionite, heme-drug adducts were not detected, contrary to artemisinin that efficiently alkylates heme regardless of the reductant used.

Evidence of Epigenetic Oncogenesis: A Turning Point in Cancer Research.

In cancer research, the term epigenetics was used in the 1970s in its modern sense encompassing non-genetic events modifying the chromatin state, mainly to oppose the emerging oncogene paradigm. However, starting from the establishment of this prominent concept, the importance of these epigenetic phenomena in cancer rarely led to questioning the causal role of genetic alterations. Only in the last 10 years, the accumulation of problematic data, better experimental technologies, and some ambitious models pushed the idea that epigenetics could be at least as important as genetics in early oncogenesis.