Early palliative care in metastatic uveal melanoma (early together): protocol of a prospective randomized Phase III trial.

Metastatic uveal melanoma (UM) patients often initially present with limited symptoms despite a poor prognosis, complicating communication with patients and caregivers. Early Together (NCT04728113) is a randomized Phase III trial that integrates early palliative care through systematic joint visits involving the palliative care team and the medical oncologist, compared with standard oncological care, in 162 metastatic UM patients beginning systemic treatment. This collaboration aims to enhance patient functioning, improve quality of life and facilitate coping mechanisms.

Negative gas adsorption transitions and pressure amplification phenomena in porous frameworks.

Nanoporous solids offer a wide range of functionalities for industrial, environmental, and energy applications. However, only a limited number of porous materials are responsive, the nanopore dynamically alters its size and shape in response to external stimuli such as temperature, pressure, light or the presence of specific molecular stimuli adsorbed inside the voids deforming the framework. Adsorption-induced structural deformation of porous solids can result in unique counterintuitive phenomena.

Nuclear calcium signaling in D1 receptor-expressing neurons of the nucleus accumbens regulates molecular, cellular and behavioral adaptations to cocaine.

Background: The persistence of cocaine-evoked adaptations relies on gene regulations within the reward circuit, especially in the ventral striatum (i.e., nucleus accumbens (NAc)).

Ferroptosis Transcriptional Regulation and Prognostic Impact in Medulloblastoma Subtypes Revealed by RNA-Seq.

Medulloblastoma (MB) is the most common malignant brain tumor in children, typically arising during infancy and childhood. Despite multimodal therapies achieving a response rate of 70% in children older than 3 years, treatment remains challenging. Ferroptosis, a form of regulated cell death, can be induced in medulloblastoma cells in vitro using erastin or RSL3.

Astrocyte-to-neuron HO signalling supports long-term memory formation in Drosophila and is impaired in an Alzheimer's disease model.

Astrocytes help protect neurons from potential damage caused by reactive oxygen species (ROS). While ROS can also exert beneficial effects, it remains unknown how neuronal ROS signalling is activated during memory formation, and whether astrocytes play a role in this process. Here we discover an astrocyte-to-neuron HO signalling cascade in Drosophila that is essential for long-term memory formation.

SMARCB1-deficient malignant melanocytic uveal tumours: a new neural crest-derived tumour entity with SMARCB1-related germline predisposition.

Rhabdoid tumours (RT) are an aggressive malignancy affecting <2-year-old infants, characterised by biallelic loss-of-function alterations in SWI/SNF-related BAF chromatin remodelling complex subunit B1 (SMARCB1) in nearly all cases. Germline SMARCB1 alterations are found in ~30% of patients and define the RT Predisposition Syndrome type 1 (RTPS1). Uveal melanoma (UVM), the most common primary intraocular cancer in adults, does not harbour SMARCB1 alterations.

Single-Cell RNA Sequencing Reveals LEF1-Driven Wnt Pathway Activation as a Shared Oncogenic Program in Hepatoblastoma and Medulloblastoma.

(1) Background: Hepatoblastoma and medulloblastoma are two types of pediatric tumors with embryonic origins. Both tumor types can exhibit genetic alterations that affect the β-catenin and Wnt pathways; (2) Materials and Methods: This study used bioinformatics and integrative analysis of multi-omics data at both the tumor and single-cell levels to investigate two distinct pediatric tumors: medulloblastoma and hepatoblastoma; (3) Results: The cross-transcriptome analysis revealed a commonly regulated expression signature between hepatoblastoma and medulloblastoma tumors. Among the commonly upregulated genes, the transcription factor LEF1 was significantly expressed in both tumor types.

Bone sarcomas and cancer predisposition syndromes.

Bone sarcomas, constituting less than 1% of malignant neoplasms across all age groups, are rare tumours possibly associated with genetic susceptibility syndromes. This review aims to provide recommendations for the detection of cancer predisposition syndromes associated with bone sarcomas and managing affected patients. Recommendations were formulated by a multidisciplinary working and reviewing group from GROUPOS and SFCE oncogenetic's group, including geneticists, oncologists, and radiologists.

Temporal and regional X-linked gene reactivation in the mouse germline reveals site-specific retention of epigenetic silencing.

Random X-chromosome inactivation is a hallmark of female mammalian somatic cells. This epigenetic mechanism, mediated by the long noncoding RNA Xist, occurs in the early embryo and is stably maintained throughout life, although inactivation is lost during primordial germ cell (PGC) development. Using a combination of single-cell allele-specific RNA sequencing and low-input chromatin profiling on developing mouse PGCs, we provide a detailed map of X-linked gene reactivation.

Cholesterol mobilization regulates dendritic cell maturation and the immunogenic response to cancer.

Maturation of conventional dendritic cells (cDCs) is crucial for maintaining tolerogenic safeguards against auto-immunity and for promoting immunogenic responses to pathogens and cancer. The subcellular mechanism for cDC maturation remains poorly defined. We show that cDCs mature by leveraging an internal reservoir of cholesterol (harnessed from extracellular cell debris and generated by de novo synthesis) to assemble lipid nanodomains on cell surfaces of maturing cDCs, enhance expression of maturation markers and stabilize immune receptor signaling.

Improving propulsive efficiency using bio-inspired intermittent locomotion.

Many swimmers, especially small- to medium-sized animals, use intermittent locomotion that differs from continuous swimming of large species. This type of locomotion, called burst and coast, is often associated with an energetic advantage. In this work, we investigate the intermittent locomotion inspired by fish locomotion but applied to a propeller.

Carbazole-Based Eu Complexes for Two-Photon Microscopy Imaging of Live Cells.

Lanthanide(III) complexes with two-photon absorbing antennas are attractive for microscopy imaging of live cells because they can be excited in the NIR. We describe the synthesis and luminescence and imaging properties of two Eu complexes, and , with (-carbazolyl)-aryl-alkynyl-picolinamide and (-carbazolyl)-aryl-picolinamide antennas, respectively, conjugated to the TAT cell-penetrating peptides. Contrary to what was previously observed with related Eu complexes with carbazole-based antennas in a mixture of water and organic solvents, these two complexes show very low emission quantum yield (Φ < 0.

Allostery and Evolution: A Molecular Journey Through the Structural and Dynamical Landscape of an Enzyme Super Family.

Allosteric regulation is a powerful mechanism for controlling the efficiency of enzymes. Deciphering the evolutionary mechanisms by which allosteric properties have been acquired in enzymes is of fundamental importance. We used the malate (MalDH) and lactate deydrogenases (LDHs) superfamily as model to elucidate this phenomenon.

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.

Automated tight Lyapunov analysis for first-order methods.

We present a methodology for establishing the existence of quadratic Lyapunov inequalities for a wide range of first-order methods used to solve convex optimization problems. In particular, we consider (i) classes of optimization problems of finite-sum form with (possibly strongly) convex and possibly smooth functional components, (ii) first-order methods that can be written as a linear system on state-space form in feedback interconnection with the subdifferentials of the functional components of the objective function, and (iii) quadratic Lyapunov inequalities that can be used to draw convergence conclusions. We present a necessary and sufficient condition for the existence of a quadratic Lyapunov inequality within a predefined class of Lyapunov inequalities, which amounts to solving a small-sized semidefinite program.

Dynamics of Persistent Submicroscopic and Microscopic in Pregnant Women Under Intermittent Preventive Treatment: A Study Cohort in Benin.

Background: Malaria infections in pregnancy are a major cause of maternal morbidity and neonatal mortality in sub-Saharan Africa. A high proportion of these infections are submicroscopic, which are usually asymptomatic and therefore untreated during pregnancy. Intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) aims to prevent and treat all potential infections whether submicroscopic or not.

Transcriptomic analysis reinforces the implication of spatacsin in neuroinflammation and neurodevelopment.

Hereditary spastic paraplegia (HSP) encompasses a group of rare genetic diseases primarily affecting motor neurons. Among these, spastic paraplegia type 11 (SPG11) represents a complex form of HSP caused by deleterious variants in the SPG11 gene, which encodes the spatacsin protein. Previous studies have described several potential roles for spatacsin, including its involvement in lysosome and autophagy mechanisms, neuronal and neurites development or mitochondria function.

Rationally designed universal passivator for high-performance single-junction and tandem perovskite solar cells.

Interfacial trap-assisted nonradiative recombination hampers the development of metal halide perovskite solar cells (PSCs). Herein, we report a rationally designed universal passivator to realize highly efficient and stable single junction and tandem PSCs. Multiple defects are simultaneously passivated by the synergistic effect of anion and cation.

Pogo transposons provide tools to restrict cancer growth.

Transposable elements provide material for novel gene formation. In particular, DNA transposons have contributed several essential genes involved in various physiological or pathological conditions. Here, we discuss recent findings by Tu et al.

Global regulators enable bacterial adaptation to a phenotypic trade-off.

Cellular fitness depends on multiple phenotypes that must be balanced during evolutionary adaptation. For instance, coordinating growth and motility is critical for microbial colonization and cancer invasiveness. In bacteria, these phenotypes are controlled by local regulators that target single operons, as well as by global regulators that impact hundreds of genes.

Predictive modelling of acute Promyelocytic leukaemia resistance to retinoic acid therapy.

Acute Promyelocytic Leukaemia (APL) arises from an aberrant chromosomal translocation involving the Retinoic Acid Receptor Alpha (RARA) gene, predominantly with the Promyelocytic Leukaemia (PML) or Promyelocytic Leukaemia Zinc Finger (PLZF) genes. The resulting oncoproteins block the haematopoietic differentiation program promoting aberrant proliferative promyelocytes. Retinoic Acid (RA) therapy is successful in most of the PML::RARA patients, while PLZF::RARA patients frequently become resistant and relapse.

Cardiovascular patches applied in congenital cardiac surgery: Current materials and prospects.

Congenital Heart Defects (CHDs) are the most common congenital anomalies, affecting between 4 and 75 per 1000 live births. Cardiovascular patches (CVPs) are frequently used as part of the surgical armamentarium to reconstruct cardiovascular structures to correct CHDs in pediatric patients. This review aims to evaluate the history of cardiovascular patches, currently available options, clinical applications, and important features of these patches.

Integration of clinical, pathological, radiological, and transcriptomic data improves prediction for first-line immunotherapy outcome in metastatic non-small cell lung cancer.

Immunotherapy is improving the survival of patients with metastatic non-small cell lung cancer (NSCLC), yet reliable biomarkers are needed to identify responders prospectively and optimize patient care. In this study, we explore the benefits of multimodal approaches to predict immunotherapy outcome using multiple machine learning algorithms and integration strategies. We analyze baseline multimodal data from a cohort of 317 metastatic NSCLC patients treated with first-line immunotherapy, including positron emission tomography images, digitized pathological slides, bulk transcriptomic profiles, and clinical information.