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.

Analysis of partly bio-derived nonionic polyethylene glycol-based rheology modifiers by comprehensive two-dimensional liquid chromatography.

Rheology modifiers (RMs) are polymeric molecules providing rheological control of formulations, which are important in product application, shelf-life, and aesthetic perception. Bio-derived polyethylene glycol (PEG)-based RMs thicken formulations through nonionic-associative thickening where at least two hydrophobic end groups from a RM molecule interact with other hydrophobic groups of other RM molecules or ingredients in the formulation to form an associative network. We report a comprehensive two-dimensional liquid chromatography (2D-LC) separation of partly bio-derived PEG-based RMs in size exclusion chromatography (SEC) × reversed-phase liquid chromatography (RPLC) mode for the separation of RM components based on both molecular weight distribution and end group hydrophobe distribution.

Uncovering a new family of conserved virulence factors that promote the production of host-damaging outer membrane vesicles in gram-negative bacteria.

CprA is a short-chain dehydrogenase/reductase (SDR) that contributes to resistance against colistin and antimicrobial peptides. The cprA gene is conserved across Pseudomonas aeruginosa clades and its expression is directly regulated by the two-component system PmrAB. We have shown that cprA expression leads to the production of outer membrane vesicles (OMVs) that block autophagic flux and have a greater capacity to activate the non-canonical inflammasome pathway.

De novo and inherited dominant variants in U4 and U6 snRNAs cause retinitis pigmentosa.

The U4 small nuclear RNA (snRNA) forms a duplex with the U6 snRNA and, together with U5 and ∼30 proteins, is part of the U4/U6.U5 tri-snRNP complex, located at the core of the major spliceosome. Recently, recurrent variants in the U4 RNA, transcribed from the gene, and in at least two other genes were discovered to cause neurodevelopmental disorder.

Quantifying intratumoral biomarker heterogeneity in tubo-ovarian high-grade serous carcinoma to optimize clinical translation.

Intratumoral heterogeneity (ITH) is spatial, phenotypic, or molecular differences within the same tumor that have important implications for accurate tumor classification and assessment of predictive biomarkers. The Canadian Ovarian Experimental Unified Resource (COEUR) has created a cohort of 437 FFPE tissue specimens from 108 tubo-ovarian high-grade serous carcinoma (HGSC) patients to quantify ITH across the anatomical sites and between primary and recurrence. We quantified the ITH of six clinically used immunohistochemical diagnostic and prognostic biomarkers (WT1, p53, p16, PR, CD8, and Ki67).

Raman Signature of Stripe Domains in Monolayer WMoS Alloys.

We study the Raman signature of stripe domains in monolayer WMoS alloys, characterized using experimental techniques and density functional theory (DFT) calculations. These stripe domains were found in star-shaped monolayer WS exhibiting a high concentration of molybdenum (Mo) atoms in its central region, and unique Raman peaks that were not previously reported. We attribute these peaks to the splitting of the original doubly degenerate E modes, arising from the lower symmetry of the W-Mo stripe domains.

Development and pilot testing of INTERVENER, a web-based tool to match barriers to the cancer continuum organization to evidence-based interventions.

Background: Barriers to the cancer continuum organization and interventions to approach them have been identified; however, there is a lack of a tool matching them. Our aim was to develop a web-based tool to identify the main barriers to the process of the cancer continuum organization, and propose matched evidence-based interventions (EBI) to overcome them.

Methods: A questionnaire on barriers at six steps of the process of the cancer continuum organization was answered by collaborators.

Successful desensitization of donor-specific antibodies in a single cord blood transplant recipient.

Umbilical cord blood (UCB) represents a valuable graft source in the absence of a human leukocyte antigen (HLA)-matched donor for hematopoietic cell transplantation (HCT). Donor-specific anti-HLA antibodies (DSAs), targeting grafts with mismatched HLA antigens, pose a significant obstacle by increasing the risk of primary graft failure, delayed engraftment, and decreased survival. Existing literature on HLA desensitization has primarily focused on haploidentical transplants, and there is a lack of experience regarding the optimal strategy in UCB transplantation.

Particle emissions study from tire sample with nano-silver tracer from different steps of its life cycle. A new approach to trace emissions of tire microparticles.

Emissions due to tires retread/repair and incineration are a cause of concern owing to the presence of nanoparticles in the products. The assessment exposure to humans hereto related is a challenge in an environmental context. The first object of this work is to develop a method to characterize the emission sources using online (counting and sizing) and offline measurements.

Cyclin switch tailors a cell cycle variant to orchestrate multiciliogenesis.

Meiosis, endoreplication, and asynthetic fissions are variations of the canonical cell cycle where either replication or mitotic divisions are muted. Here, we identify a cell cycle variantconserved across organs and mammals, where both replication and mitosis are muted, and that orchestrates the differentiation of post-mitotic progenitors into multiciliated cells (MCCs). MCC progenitors reactivate most of the cell cycle transcriptional program but replace the temporal expression of cyclins E2 and A2 with non-canonical cyclins O and A1.

Cyclin O controls entry into the cell-cycle variant required for multiciliated cell differentiation.

Multiciliated cells (MCCs) ensure fluid circulation in various organs. Their differentiation is marked by the amplification of cilia-nucleating centrioles, driven by a genuine cell-cycle variant, which is characterized by wave-like expression of canonical and non-canonical cyclins such as Cyclin O (CCNO). Patients with CCNO mutations exhibit a subtype of primary ciliary dyskinesia called reduced generation of motile cilia (RGMC).

The walnut tree as a source of progesterone for reproductive control in goats.

Intravaginal sponges impregnated with the progesterone (P4) analogue fluorogestone acetate (FGA) induce synchronous oestrous behaviour and normal ovulatory cycle in goats. To explore alternatives using natural P4 from plants, we developed a method of ethanolic extraction and a specific enzyme immunoassay (EIA) to measure P4 in the different parts of the walnut tree Juglans regia. We found a very high concentration of P4, specifically in the leaves of the three most common French varieties (∼100 mg/kg of DM) but not in flowers, fruits, septa, husk, oil or cake.

Musical Experience and Speech Processing: The Case of Whistled Words.

In this paper, we explore the effect of musical expertise on whistled word perception by naive listeners. In whistled words of nontonal languages, vowels are transposed to relatively stable pitches, while consonants are translated into pitch movements or interruptions. Previous behavioral studies have demonstrated that naive listeners can categorize isolated consonants, vowels, and words well over chance.

Neuro-cognitive multilevel causal modeling: A framework that bridges the explanatory gap between neuronal activity and cognition.

Explaining how neuronal activity gives rise to cognition arguably remains the most significant challenge in cognitive neuroscience. We introduce neuro-cognitive multilevel causal modeling (NC-MCM), a framework that bridges the explanatory gap between neuronal activity and cognition by construing cognitive states as (behaviorally and dynamically) causally consistent abstractions of neuronal states. Multilevel causal modeling allows us to interchangeably reason about the neuronal- and cognitive causes of behavior while maintaining a physicalist (in contrast to a strong dualist) position.

Actin-based deformations of the nucleus control mouse multiciliated ependymal cell differentiation.

Ependymal cells (ECs) are multiciliated cells in the brain that contribute to cerebrospinal fluid flow. ECs are specified during embryonic stages but differentiate later in development. Their differentiation depends on genes such as GEMC1 and MCIDAS in conjunction with E2F4/5 as well as on cell-cycle-related factors.

Contrasting Approaches in the Implementation of GRADE Methodology in Guidelines for Haemophilia and Von Willebrand Disease.

Introduction: The 2024 ISTH clinical practice guideline (CPG) for treatment of congenital haemophilia, the NBDF-McMaster Guideline on Care Models for Haemophilia Management, and ASH ISTH NBDF WFH guidelines on the diagnosis and management of VWD all utilised GRADE methodology.

Aim: Discuss missed opportunities and the methodological approach of the ISTH Guideline in contrast to how GRADE was previously applied in rare diseases.

Methods: Critically analyse the methodology of each guideline along with best practices in the use of GRADE.

Towards promoting a legal framework for ending discrimination against cancer survivors. A human rights-centered approach.

The article explores the development of the right to be forgotten (RTBF) for cancer survivors, with a focus on preventing discrimination based on their medical history. It discusses legal progress in European Union (EU) countries, including national laws and EU initiatives such as Europe's Beating Cancer Plan and the Consumer Credits Directive, which aim to protect survivors from financial and social obstacles. These measures are designed to standardize protection across member states and ensure that cancer survivors are not unfairly treated due to their past illness.

International Society on Thrombosis and Haemostasis Clinical Practice Guideline for Treatment of Congenital Haemophilia-A Critical Appraisal.

Introduction: Evidence-based clinical practice guidelines drive optimal patient care and facilitate access to high-quality treatment. Creating guidelines for rare diseases such as haemophilia, where evidence does not often come from randomized controlled trials but from non-randomized and well-designed observational studies and real-world data, is challenging. The methodology used for assessing available evidence should consider this critical fact.

Long lasting argon neuroprotection in a non-human primate model of transient endovascular ischemic stroke.

In the past decade, noble gases have emerged as highly promising neuroprotective agents. Previous studies have demonstrated the efficacy of argon neuroprotection in rodent models of cerebral ischemia. The objective of the present pre-clinical study was to confirm the neuroprotective effect of argon in a non-human primate model of endovascular ischemic stroke.

Towards a liana plant functional type for vegetation models.

Lianas (woody climbers) are crucial components of tropical forests and they have been increasingly recognized to have profound effects on tropical forest carbon dynamics. Despite their importance, lianas' representation in vegetation models remains limited, partly due to the complexity of liana-tree dynamics and the diversity in liana life history strategies. This paper provides a comprehensive review of advances and challenges for mechanistically representing lianas in forest ecosystem models and a proposed path towards effectively representing lianas in these models.

Effects of temperature, salinity and CO concentration on growth and toxin production of the harmful algal bloom species Alexandrium pseudogonyaulax (Dinophyceae) from the Danish Limfjord.

The marine dinoflagellate Alexandrium pseudogonyaulax is a widely distributed Harmful Algal Bloom (HAB) species that produces the macrocyclic polyketide goniodomin A (GDA). Occurrences in northern European waters are increasing and a spreading of the species along a salinity gradient into the Baltic Sea has been observed. As GDA is suspected to lead to invertebrate mortality, the spreading is of concern for the environment and possibly human health.

The phenotypic spectrum of gene variants.

Introduction: Classically, Usher syndrome is characterized by the association of sensorineural hearing loss (SNHL), retinitis pigmentosa (RP) and possible vestibular dysfunction. Pathogenic bi-allelic variants in cause atypical autosomal recessive Usher syndrome, which is associated with SNHL and photoreceptors dysfunction without vestibular signs. To date, only 19 scattered descriptions have been reported.

Extensive macular atrophy with pseudodrusen-like appearance (EMAP) clinical characteristics, diagnostic criteria, and insights from allied inherited retinal diseases and age-related macular degeneration.

Extensive macular atrophy with pseudodrusen-like appearance (EMAP) was first described in France in 2009 as a symmetric and rapidly progressive form of macular atrophy primarily affecting middle-aged individuals. Despite the recent identification of a significant number of cases in Italy and worldwide, EMAP remains an underrecognized condition. The clinical triad typical of EMAP consists of vertically oriented macular atrophy with multilobular borders, pseudodrusen-like deposits across the posterior pole and mid-periphery, and peripheral pavingstone degeneration.