Targeting the activated allosteric conformation of the endothelin receptor B in melanoma with an antibody-drug conjugate: mechanisms and therapeutic efficacy.

Background: Endothelin 1 receptors are one of the drivers of tumor progression in many cancers. Inhibition of their signaling pathways with antagonist drugs has been the subject of numerous clinical trials, but the results have not met expectations probably due to the high endothelin concentrations in the tumor microenvironment and their unusually high affinity for their receptors.

Methods: We previously reported the rendomab B49 antibody (RB49) exhibiting a preferential affinity for the activated conformation of human endothelin B receptor (ET), not displaced by high endothelin levels, and without any pharmacological properties that could inhibit the division of melanoma cells.

Management and outcomes of internal carotid artery, anterior cerebral artery, or middle cerebral artery injury during microsurgical approach of the anterior and middle cranial skull base: insights from a systematic review and a case series.

Injury of the internal carotid artery (ICA), anterior cerebral artery (ACA), and middle cerebral artery (MCA) are rare but devastating complications during microsurgery of the anterior and middle cranial skull base. We systematically reviewed the current knowledge on ICA, ACA, and MCA injury during skull base microsurgery and performed a multicentric data collection to refine their management. A systematic review of ICA, ACA, and MCA injuries during direct microsurgical approaches to the anterior and middle cranial skull base was performed, using PRISMA-IPD guidelines and using a multicentric case collection.

Formal guidelines from an expert panel: intensive care unit medical staffing, organisation and working hours to improve quality of life at work in France.

Background: Intensive care units (ICU) are characterized by high medical assistance costs and great complexity. Recommendations to determine the needs of medical staff are scarce, generating appreciable variability. The French Intensive Care Society (FICS) and the French National Council of Intensive Care Medicine (CNP MIR, Conseil National Professionel de Médecine Intensive Réanimation) have established a technical committee of experts, the purposes of which were to draft recommendations regarding staffing needs in ICUs and to propose optimal organisation of work hours, a key objective being improved workplace quality of life.

Trust in scientists and their role in society across 68 countries.

Science is crucial for evidence-based decision-making. Public trust in scientists can help decision makers act on the basis of the best available evidence, especially during crises. However, in recent years the epistemic authority of science has been challenged, causing concerns about low public trust in scientists.

Epigenetic regulation of HOXA2 expression affects tumor progression and predicts breast cancer patient survival.

Accumulating evidence suggests that genetic and epigenetic biomarkers hold potential for enhancing the early detection and monitoring of breast cancer (BC). Epigenetic alterations of the Homeobox A2 (HOXA2) gene have recently garnered significant attention in the clinical management of various malignancies. However, the precise role of HOXA2 in breast tumorigenesis has remained elusive.

Sex-modulated association between thyroid stimulating hormone and informant-perceived anxiety in non-depressed older adults: Prediction models and relevant cutoff value.

The aim of this study was to assess the association between thyroid function and perceived anxiety in non-depressed older adults. Non-depressed Alzheimer's Disease Neuroimaging Initiative (ADNI) participants with complete Thyroid Stimulating Hormone (TSH) and neuropsychiatric inventory (NPI/NPI-Q) were included. The association between anxiety and thyroid function was assessed by logistic regression and sex stratification.

Invariance of the speckle pattern of the transmitted wave in periodic waveguides.

We report on conditions of invariance of the transmitted pattern in the propagation through a periodic waveguide, the incident wave having no effect on the intensity pattern of the transmitted field. This phenomenon is reminiscent of that observed when illuminating a disordered medium in the regime of Anderson localization, as a consequence of the contribution of a single transmission eigenchannel to the transmitted wave. It is shown that the freezing of the transmitted wave is not intrinsically related to the disorder and that, whatever the frequency, it can also be observed in a regular, periodic system, provided that at most one Bloch mode is propagating.

Investigating canonical size phenomenon in drawing from memory task in different perceptual conditions among children.

The canonical size phenomenon refers to the mental representation of real-object size information: the objects larger in the physical world are represented as larger in mental spatial representations. This study tested this phenomenon in a drawing-from-memory task among children aged 5, 7, and 9 years. The participants were asked to draw objects whose actual sizes varied at eight size rank levels.

Perceptions of science, science communication, and climate change attitudes in 68 countries - the TISP dataset.

Science is integral to society because it can inform individual, government, corporate, and civil society decision-making on issues such as public health, new technologies or climate change. Yet, public distrust and populist sentiment challenge the relationship between science and society. To help researchers analyse the science-society nexus across different geographical and cultural contexts, we undertook a cross-sectional population survey resulting in a dataset of 71,922 participants in 68 countries.

Proximal tubule-on-chip as a model for predicting cation transport and drug transporter dynamics.

Deciphering the sources of variability in drug responses requires to understand the processes modulating drug pharmacokinetics. However, pharmacological research suffers from poor reproducibility across clinical, animal, and experimental models. Predictivity can be improved by using Organs-on-Chips, which are more physiological, human-oriented, micro-engineered devices that include microfluidics.

Centromere positioning orchestrates telomere bouquet formation and the initiation of meiotic differentiation.

Accurate gametogenesis requires the establishment of the telomere bouquet, an evolutionarily conserved, 3D chromosomal arrangement. In this spatial configuration, telomeres temporarily aggregate at the nuclear envelope during meiotic prophase, which facilitates chromosome pairing and recombination. The mechanisms governing the assembly of the telomere bouquet remain largely unexplored, primarily due to the challenges in visualizing and manipulating the bouquet.

Designing of an innovative conserved multiepitope subunit vaccine targeting SARS-CoV-2 glycoprotein and nucleoprotein through immunoinformatic.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has imposed substantial challenges on our society due to the COVID-19 pandemic. This virus relies heavily on its surface glycoprotein (S-glycoprotein) to facilitate attachment, fusion, and entry into host cells. While the nucleoprotein (N) in the ribonucleoprotein core binds to the viral RNA genome.

Brucella abortus impairs T lymphocyte responsiveness by mobilizing IL-1RA-secreting omental neutrophils.

Immune evasion strategies of Brucella, the etiologic agent of brucellosis, a global zoonosis, remain partially understood. The omentum, a tertiary lymphoid organ part of visceral adipose tissue, has never been explored as a Brucella reservoir. We report that B.

Unveiling pelagic-benthic coupling associated with the biological carbon pump in the Fram Strait (Arctic Ocean).

Settling aggregates transport organic matter from the ocean surface to the deep sea and seafloor. Though plankton communities impact carbon export, how specific organisms and their interactions affect export efficiency is unknown. Looking at 15 years of eDNA sequences (18S-V4) from settling and sedimented organic matter in the Fram Strait, here we observe that most phylogenetic groups were transferred from pelagic to benthic ecosystems.

Effectiveness of the ARTHE-e app for exercise adherence in people with knee osteoarthritis: protocol for a randomised controlled trial.

Introduction: Osteoarthritis, the most prevalent joint disease, poses a significant challenge due to its progressive nature and impact on the whole joint and periarticular structures. Although exercise is crucial for symptom improvement and progression slowdown, adherence to exercise programmes remains a concern. In response, we have developed a novel smartphone-based m-health application, ARTH-e, specifically designed to enhance adherence to adapted physical activity in individuals with knee osteoarthritis.

Effect of a multimodal analgesia strategy on remifentanil daily consumption in mechanically ventilated adult ICU patients: study protocol for a randomised, placebo-controlled, double-blind, parallel-group clinical trial.

Introduction: Intensive care unit (ICU) patients under mechanical ventilation experience mild-to-severe pain. International guidelines emphasise the importance and benefits of multimodal analgesia to minimise opioid consumption and its side effects. However, no recommendation about drugs or protocol has been formulated.

Residual sleepiness and impaired alertness in treated obstructive sleep apnoea: role of hypoxic burden and sleep fragmentation.

The pathophysiology of residual sleepiness in treated obstructive sleep apnoea (OSA) remains poorly understood. Animal models suggest that it may involve neuronal damage due to intermittent hypoxia and sleep fragmentation. In a cohort of 122 continuous positive airway pressure (CPAP) treated OSA patients referred for maintenance of wakefulness test, we explored the determinants of (objective) alertness and those of (subjective) sleepiness assessed by Epworth Sleepiness Scale.

Emulation of ARISTOTLE and ROCKET AF trials in real-world atrial fibrillation patients results in similar efficacy and safety as original landmark trials: insights from the GARFIELD-AF registry.

Aims: This study aimed to determine the robustness, reproducibility and representativeness of the landmark Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (AF) (ARISTOTLE) and Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in AF (ROCKET AF) randomised trials through replication in an observational AF patient registry.

Methods And Results: Patients from the Global Anticoagulant Registry in the FIELD (GARFIELD)-AF registry treated with apixaban, rivaroxaban or vitamin K antagonist (VKA) were assessed for eligibility for the ARISTOTLE and ROCKET AF trials. HRs of apixaban and rivaroxaban versus comparator for stroke/systemic embolism, major bleeding and all-cause mortality within 2 years follow-up were calculated using propensity score overlap-weighted Cox models.

Introducing the Caliber-Flow Status Scale (CFSS): a novel tool for assessing covered cortical branch status after flow diverter treatment of middle cerebral artery aneurysms.

Background: This study assessed caliber and flow changes of covered cortical middle cerebral artery (MCA) branches using the new Caliber-Flow Status Scale (CFSS), postoperative diffusion-weighted imaging (DWI) lesions, and clinical outcome following flow diverter (FD) treatment of MCA aneurysms.

Methods: This single-center retrospective study collected data from patients treated with FD between January 2016 and March 2024, including patient characteristics, aneurysm features, postoperative DWI lesions, and clinical outcomes. Vessel status was assessed using CFSS: 1a (normal caliber and flow), 1b (normal caliber, reduced flow), 2a (reduced caliber, normal flow), 2b (reduced caliber and flow), and 3 (occlusion).

High-throughput screening to identify endocrine disruptors: Contribution of low-resolution tandem MS and high-resolution MS.

Background: Considering the large diversity of chemicals present in the environment and the need to study their effects (alone or as mixtures), the development of high-throughput in vitro assays in line with the Replacement, Reduction, Refinement (3R) strategy is essential for chemical risk assessments.

Results: We developed a robust analytical workflow based on both low resolution tandem mass spectrometry (MS/MS) and high-resolution mass spectrometry (HRMS) to quantify 13 steroids in NCI-H295R cell culture medium, human plasma and serum. The workflow was validated by screening media from the NCI-H295R cell line exposed in dose-response experiments to 5 endocrine disruptors (EDs) such as bisphenol A, prochloraz, ketoconazole, atrazine and forskolin.

Entropy driven-based catalytic biosensors for bioanalysis: From construction to application-A review.

The rapid advancement of precision medicine and the continuous emergence of novel pathogens have presented new challenges for biosensors, necessitating higher requirements. Target amplification technology serves as the core component in biosensor construction. Enzyme-based amplification methods are often sensitive and selective but involve relatively complex operational steps, whereas enzyme-free amplification methods offer simplicity but frequently fail to meet both sensitivity and selectivity simultaneously.

Plasma transfusions in neonatal intensive care units: a prospective observational study.

Objective: Despite lack of evidence supporting efficacy, prophylactic fresh frozen plasma and Octaplas transfusions may be administered to very preterm infants to reduce bleeding risk. International variation in plasma transfusion practices in neonatal intensive care units (NICUs) is poorly understood, therefore, we aimed to describe neonatal plasma transfusion practice in Europe.

Design: Prospective observational study.

Outcomes of extremely preterm infants who participated in a randomised trial of dopamine for treatment of hypotension (the HIP trial) at 2 years corrected age.

Objective: To determine survival and neurodevelopmental outcomes in the Hypotension in Preterm (HIP) trial.

Design: Prospective follow-up of infants enrolled in randomised controlled trial.

Participants: 58 infants born before 28 weeks of gestation with low mean arterial blood pressure.

Importance, structure, cultivability, and resilience of the bacterial microbiota during infection of laboratory-grown Haematococcus spp. by the blastocladialean pathogen Paraphysoderma sedebokerense: evidence for a domesticated microbiota and its potential for biocontrol.

Industrial production of the unicellular green alga Haematococcus lacustris is compromised by outbreaks of the fungal pathogen Paraphysoderma sedebokerense (Blastocladiomycota). Here, using axenic algal and fungal cultures and antibiotic treatments, we show that the bacterial microbiota of H. lacustris is necessary for the infection by P.