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[This corrects the article DOI: 10.1371/journal.pone.0235234.].
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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 PDFPulm Ther
September 2025
Boehringer Ingelheim Pharma GmbH & Co. KG, Binger Straße 173, 55216, Ingelheim am Rhein, Germany.
Introduction: The modification of an inhaler's air flow resistance influences a patient's inhalation flow profile, thereby affecting the exit velocity of an aerosol leaving the Respimat® mouthpiece. A slower inhalation maneuver results in reduced plume velocity and thus a decreased oropharyngeal deposition due to reduced impaction. This could not only lead to fewer unwanted side effects associated with inhaled therapies, but also enhance lung deposition.
View Article and Find Full Text PDFClin Rheumatol
September 2025
Histocompatibility Department, Hedi Chaker UH, University of Sfax, Sfax, Tunisia.
Objective: Systemic sclerosis (SSc) is a complex autoimmune connective tissue disease. Genetic factors may play a pivotal role in determining susceptibility to these disorders. HLA associations with SSc, especially HLA class II, were investigated in different populations but not in Tunisia.
View Article and Find Full Text PDFMol Psychiatry
September 2025
Center for Gene Regulation in Health and Disease, Cleveland State University, Cleveland, OH, 44115, USA.
Dysregulated spine morphology is a common feature in the pathology of many neurodevelopmental and neuropsychiatric disorders. Overabundant immature dendritic spines in the hippocampus are causally related to cognitive deficits of Fragile X syndrome (FXS), the most common form of heritable intellectual disability. Recent findings from us and others indicate autophagy plays important roles in synaptic stability and morphology, and autophagy is downregulated in FXS neurons.
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.