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We identified the most sensitive genotype-specific parameters (GSPs) and their contribution to the uncertainty of the MANIHOT simulation model. We applied a global sensitivity and uncertainty analysis (GSUA) of the GSPs to the simulation outputs for the cassava development, growth, and yield in contrasting environments. We compared enhanced Sampling for Uniformity, a qualitative screening method new to crop simulation modeling, and Sobol, a quantitative, variance-based method. About 80% of the GSPs contributed to most of the variation in maximum leaf area index (LAI), yield, and aboveground biomass at harvest. Relative importance of the GSPs varied between warm and cool temperatures but did not differ between rainfed and no water limitation conditions. Interactions between GSPs explained 20% of the variance in simulated outputs. Overall, the most important GSPs were individual node weight, radiation use efficiency, and maximum individual leaf area. Base temperature for leaf development was more important for cool compared to warm temperatures. Parameter uncertainty had a substantial impact on model predictions in MANIHOT simulations, with the uncertainty 2-5 times larger for warm compared to cool temperatures. Identification of important GSPs provides an objective way to determine the processes of a simulation model that are critical versus those that have little relevance.
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http://dx.doi.org/10.1016/j.eja.2020.126031 | DOI Listing |
Clin Orthop Relat Res
September 2025
Leni & Peter W. May Department of Orthopaedic Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Background: Peripheral nerve injury commonly results in pain and long-term disability for patients. Recovery after in-continuity stretch or crush injury remains inherently unpredictable. However, surgical intervention yields the most favorable outcomes when performed shortly after injury.
View Article and Find Full Text PDFCereb Cortex
August 2025
Aix-Marseille Université, Institut National de la Santé et de la Recherche Médicale, Institut de Neurosciences des Systèmes (INS) UMR1106, Marseille 13005, France.
Over three decades, statistical parametric mapping has transformed neuroimaging from descriptive mapping to causal inference, placing generative models at the core of causal explanations for brain function. It inspired to a large degree The Virtual Brain, which builds subject-specific digital twins from multimodal data, enabling brain simulations and exploration. Both frameworks converge at parameter estimation, where model and data meet, providing the mathematical manifestation of cause-effect in pathophysiology.
View Article and Find Full Text PDFPharmacoeconomics
September 2025
Department of Pharmacy, Uppsala University, Box 580, 751 23, Uppsala, Sweden.
Background: Immune checkpoint inhibitors (ICIs) are clinically beneficial but associated with high costs that represent a growing challenge for healthcare budgets and may affect affordability, especially in resource-limited settings. Moreover, the healthcare sector is a significant source of greenhouse gas emissions, and medication-related waste-such as that from vial-based therapies-has been identified as a contributing factor. Alternative dosing strategies could reduce the environmental and financial impact of ICI therapy while maintaining clinical safety and efficacy.
View Article and Find Full Text PDFMol Divers
September 2025
State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi, 830011, Xinjiang, China.
Aurora kinases are a group of serine/threonine kinases essential for cell mitosis, comprising Aurora A, B, and C. However, the Aurora B is overexpressed in multiple tumors and the aurone has been proved to exhibit potent inhibitory activity against Aurora B kinase by our group. The indolinone was considered as an aurone scaffold hopping analog, and the indolinone-based Aurora B inhibitor library (3577 molecules) was constructed by FBDD strategy.
View Article and Find Full Text PDFNaunyn Schmiedebergs Arch Pharmacol
September 2025
Department of Pharmacology, All India Institute of Medical Sciences (AIIMS), Bhubaneswar, India.
Clozapine, the only drug approved by the FDA for treatment-resistant schizophrenia, operates within a narrow therapeutic range (0.35-0.60 mg/mL) and requires titration from 12.
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