Accelerating the Future of Oncology Drug Development: The Role of Consortia in the Delivery of Precision Oncology Early Phase Clinical Trials.

Purpose: Over the past 15 years, the landscape of early phase clinical trials (EPCTs) has undergone a remarkable expansion in both quantity and intricacy. The proliferation of sites, trials, sponsors, and contract research organizations has surged exponentially, marking a significant shift in research conduct. However, EPCT operations suffer from numerous inefficiencies, such as cumbersome start-up processes, which are particularly critical when drug safety and the recommended phase II dose need to be established in a timely manner.

Full Quantum Dynamics Study for H Atom Scattering from Graphen.

This study deals with the understanding of hydrogen atom scattering from graphene, a process critical for exploring C-H bond formation and energy transfer during atom surface collision. In our previous work [Shi, L.; 2023, 159, 194102], starting from a cell with 24 carbon atoms treated periodically, we have achieved quantum dynamics (QD) simulations with a reduced-dimensional model (15D) and a simulation in full dimensionality (75D).

Epigenetics in the modern era of crop improvements.

Epigenetic mechanisms are integral to plant growth, development, and adaptation to environmental stimuli. Over the past two decades, our comprehension of these complex regulatory processes has expanded remarkably, producing a substantial body of knowledge on both locus-specific mechanisms and genome-wide regulatory patterns. Studies initially grounded in the model plant Arabidopsis have been broadened to encompass a diverse array of crop species, revealing the multifaceted roles of epigenetics in physiological and agronomic traits.

Two-Step Reshaping of Acicular Gold Nanoparticles.

Anisometric plasmonic nanoparticles find applications in various fields, from photocatalysis to biosensing. However, exposure to heat or to specific chemical environments can induce their reshaping, leading to loss of function. Understanding this process is therefore relevant both for the fundamental understanding of such nano-objects and for their practical applications.

Do national cancer control plans address care and research for children, adolescents, and young adults? A review of status, priorities, and recommendations across 41 European countries.

Paediatric cancers, although rare, are the leading cause of disease-related mortality in European children above one year. A key pillar of the European Health Union, Europe's Beating Cancer Plan (EBCP) puts a spotlight on childhood cancer. National Cancer Control Plans (NCCPs) have a key role but did not address childhood cancers sufficiently previously.

Catalytic reduction of imines with silylformates: Formation of silyl carbamates through CO2 insertion.

Silylformates are emerging surrogates of hydrosilanes, able to reduce carbonyl groups in transfer hydrosilylation reactions, with the concomitant release of CO2. In this work, a new reactivity is revealed for silylformates, in the presence of imines. Using ruthenium catalysts, and lithium iodide as a co-catalyst, imines are shown to undergo hydrocarboxysilylation by formal insertion of CO2 to the N-Si bond of silyl amine to yield silyl carbamates in excellent yields.

Impacts of immersive 3D videos on students' surgical learning compared to 2D videos: a randomized controlled trial.

Background: Unlike other medical specialties, surgery is primarily learned through apprenticeship, by observing surgeons in action during operations. However, the increasing number of medical students and work-hour restrictions limit opportunities for learning in the operating room (OR). These circumstances call for novel technologies, such as immersive video.

PAK3 pathogenic variant associated with sleep-related hypermotor epilepsy in a family with parental mosaicism.

Protein-activated kinases mediate spine morphogenesis and synaptic plasticity. PAK3 is part of the p21-activated kinases (PAKs) family of Ras-signaling serine/threonine kinases. Pathogenic variants in the X-linked gene PAK3 have been described in patients with neurodevelopmental syndromes.

Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition.

The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, and signaling molecules that interact to promote tumor growth and therapeutic resistance. Elucidating the intricate interactions between cancer cells and the TME is crucial in understanding cancer progression and therapeutic challenges.

CRISPR/Cas9-editing of PRNP in Alpine goats.

Misfolding of the cellular PrP (PrP) protein causes prion disease, leading to neurodegenerative disorders in numerous mammalian species, including goats. A lack of PrP induces complete resistance to prion disease. The aim of this work was to engineer Alpine goats carrying knockout (KO) alleles of PRNP, the PrP-encoding gene, using CRISPR/Cas9-ribonucleoproteins and single-stranded donor oligonucleotides.

Genome-wide association study unravels mechanisms of brain glymphatic activity.

Brain glymphatic activity, as indicated by diffusion-tensor imaging analysis along the perivascular space (ALPS) index, is involved in developmental neuropsychiatric and neurodegenerative diseases, but its genetic architecture is poorly understood. Here, we identified 17 unique genome-wide significant loci and 161 candidate genes linked to the ALPS-indexes in a discovery sample of 31,021 individuals from the UK Biobank. Seven loci were replicated in two independent datasets.

[Recommendations for clinical practice: Prevention and management of varicella zoster virus (VZV) infection during pregnancy and the perinatal period (extended version)].

The Société de Pathologie Infectieuse de Langue Française released in 2024 a new national recommendation for clinical practice on the prevention and management of varicella zoster virus (VZV) infection during pregnancy and the perinatal period. The previous recommendation was issued in 1998, at a time of anti-VZV immunoglobulins shortage; it has hence become obsolete. This recommendation is a formalized expert consensus focusing on infectious diseases management; it is drawn up by a multidisciplinary working group (infectiologists, obstetricians, pediatricians, microbiologists, midwives, hygienists).

Medication Use in People Aged 90 Years and Older: A Nationwide Study.

Objective: We aimed to describe the medications prescribed to people aged ≥90 years.

Design: A cohort study was performed using data from the year 2022.

Setting And Participants: Using data from the French National Health Data System, people aged ≥90 years affiliated with the general insurance scheme were included.

Arctic soil carbon insulation averts large spring cooling from surface-atmosphere feedbacks.

The insulative properties of soil organic carbon (SOC) and surface organic layers (moss, lichens, litter) regulate surface-atmosphere energy exchanges in the Arctic through a coupling with soil temperatures. However, a physical description of this process is lacking in many climate models, potentially biasing their high-latitude climate predictions. Using a coupled surface-atmosphere model, we identified a strong feedback loop between soil insulation, surface air temperature, and snowfall.

Dialogue mechanisms between astrocytic and neuronal networks: A whole-brain modelling approach.

Astrocytes critically shape whole-brain structure and function by forming extensive gap junctional networks that intimately and actively interact with neurons. Despite their importance, existing computational models of whole-brain activity ignore the roles of astrocytes while primarily focusing on neurons. Addressing this oversight, we introduce a biophysical neural mass network model, designed to capture the dynamic interplay between astrocytes and neurons via glutamatergic and GABAergic transmission pathways.

Identification of novel genes responsible for a pollen killer present in local natural populations of Arabidopsis thaliana.

Gamete killers are genetic loci that distort segregation in the progeny of hybrids because the killer allele promotes the elimination of the gametes that carry the sensitive allele. They are widely distributed in eukaryotes and are important for understanding genome evolution and speciation. We had previously identified a pollen killer in hybrids between two distant natural accessions of Arabidopsis thaliana.

Dynamic Control of Weight-Update Linearity in Magneto-Ionic Synapses.

Multifunctional hardware technologies for neuromorphic computing are essential for replicating the complexity of biological neural systems, thereby improving the performance of artificial synapses and neurons. Integrating ionic and spintronic technologies offers new degrees of freedom to modulate synaptic potentiation and depression, introducing novel magnetic functionalities alongside the established ionic analogue behavior. We demonstrate that magneto-ionic devices can perform as synaptic elements with dynamically tunable depression linearity controlled by an external magnetic field, a functionality reminiscent of neuromodulation in biological systems.

Near-Surface Concentration Profile of Sheared Semidilute Polymer Solutions.

Controlling the structure of polymer solutions near a solid surface is crucial for many industrial processes as it significantly impacts solution flow and influences slip at the interface. To date, only a few techniques have been developed to experimentally investigate this type of interface at the nanometric scale of solid/liquid interactions. In this study, we probe the interface between a smooth sapphire surface and a semidilute polystyrene solution, using neutron reflectivity.

Five-Year Results With Patisiran for Hereditary Transthyretin Amyloidosis With Polyneuropathy: A Randomized Clinical Trial With Open-Label Extension.

Importance: There is a lack of long-term efficacy and safety data on hereditary transthyretin amyloidosis with polyneuropathy (hATTR-PN) and on RNA interference (RNAi) therapeutics in general. This study presents the longest-term data to date on patisiran for hATTR-PN.

Objective: To present the long-term efficacy and safety of patisiran in adults with hATTR-PN.

Safety and Efficacy of IV Onasemnogene Abeparvovec for Pediatric Patients With Spinal Muscular Atrophy: The Phase 3b SMART Study.

Background And Objectives: Safety and efficacy of IV onasemnogene abeparvovec has been demonstrated for patients with spinal muscular atrophy (SMA) weighing <8.5 kg. SMART was the first clinical trial to evaluate onasemnogene abeparvovec for participants weighing 8.

Comparison of the immunological and virological responses to cART between HIV-1/O and HIV-1/M patients followed up in France.

Background: Therapeutic outcomes for patients infected by genetically divergent HIV-1/O are not well-known due to scarce data and the lack of an appropriate comparison with patients infected by pandemic HIV-1/M. We aimed to compare the immunological and virological response to cART between HIV-1/O and HIV-1/M patients followed in France.

Methods: All naïve HIV-1/O subjects initiating cART in France in ANRS-ORIVAO study were compared to naïve HIV-1/M subjects initiating cART in ANRS-COPANA cohort.

Head and neck automatic multi-organ segmentation on Dual-Energy Computed Tomography.

Background And Purpose: Deep-learning-based automatic segmentation is widely used in radiation oncology to delineate organs-at-risk. Dual-energy CT (DECT) allows the reconstruction of enhanced contrast images that could help with manual and auto-delineation. This paper presents a performance evaluation of a commercial auto-segmentation software on image series generated by a DECT.