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http://dx.doi.org/10.1186/s13567-025-01498-9 | DOI Listing |
Biom J
October 2025
Novella Clinical Full Service, IQVIA, Melbourne, Australia.
Phase I dose escalation trials in oncology generally aim to find the maximum tolerated dose. However, with the advent of molecular-targeted therapies and antibody drug conjugates, dose-limiting toxicities are less frequently observed, giving rise to the concept of optimal biological dose (OBD), which considers both efficacy and toxicity. The estimand framework presented in the addendum of the ICH E9(R1) guidelines strengthens the dialogue between different stakeholders by bringing in greater clarity in the clinical trial objectives and by providing alignment between the targeted estimand under consideration and the statistical analysis methods.
View Article and Find Full Text PDFBr J Cancer
September 2025
Department of Genetics, Institut Curie, PSL Research University, Paris, France.
Background: Identifying molecular alterations specific to advanced lung adenocarcinomas could provide insights into tumour progression and dissemination mechanisms.
Method: We analysed tumour samples, either from locoregional lesions or distant metastases, from patients with advanced lung adenocarcinoma from the SAFIR02-Lung trial by targeted sequencing of 45 cancer genes and comparative genomic hybridisation array and compared them to early tumours samples from The Cancer Genome Atlas.
Results: Differences in copy-number alterations frequencies suggest the involvement in tumour progression of LAMB3, TNN/KIAA0040/TNR, KRAS, DAB2, MYC, EPHA3 and VIPR2, and in metastatic dissemination of AREG, ZNF503, PAX8, MMP13, JAM3, and MTURN.
Genes Dev
September 2025
Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, New York 10027, USA;
For neurons to establish the correct connections in animal nervous systems, interactions between cell adhesion molecules (CAMs), expressed presynaptically and postsynaptically, are thought to guide neurons to their targets. Here, we assess the role that affinity between two cognate CAMs-DIP-α and Dpr10-plays in establishing the leg neuromuscular system in If affinity decreases or, surprisingly, increases past certain thresholds, motor neuron (MN) terminal branches fail to be maintained. Live imaging during development shows that when affinities are aberrant, MN filopodia are unable to productively engage their muscle targets.
View Article and Find Full Text PDFClin Exp Optom
September 2025
School of Optometry and Vision Science, University of New South Wales, Sydney, Australia.
Clinical Relevance: Good vision is critical for childhood development and education. Pre-school vision screening is important for early detection and treatment of visual problems, and prevention of life-long vision loss.
Background: The aim of this study was to determine the prevalence of vision impairment (VI) and refractive error (RE) in rural Nepalese children under five years of age.
J Safety Res
September 2025
Department of Civil Engineering, Kırıkkale University, 71450 Yahşihan, Kırıkkale, Turkiye. Electronic address:
Introduction: Roundabouts are increasingly being used to improve traffic flow and reduce conflict points compared to traditional intersections. While previous studies have generally shown that roundabouts reduce vehicle collisions and improve traffic conditions, their impact on pedestrian safety, particularly in urban areas with high pedestrian traffic, has not been adequately studied. Despite the potential of roundabouts to reduce the overall severity of collisions, recent studies also point to specific safety challenges for pedestrians, including the difficulties faced by slow-moving people, changes in pedestrian behavior when avoiding roundabouts, and problems with disabled pedestrians are faced with.
View Article and Find Full Text PDF