Background And Objectives: Morris screening sensitivity analysis (MSM) comes forth as the method needing the minimum number of model simulations to qualify the impact of input parameter variations on outputs of complex, nonlinear and overparametrized models. However, the reliability of MSM indices (mean and standard deviation) and the reproducibility of their results are rarely explored despite the input parameter tuning/identification needs. In fact, these models, such those used in medical applications as digital twins, often lie in this category and need efficient and robust tools to assess both sensitivity and reliability of the outputs to numerous input model parameters.
Methods: In this study, a new Robust Morris Screening Method (RMSM) is proposed and based on new indices: the absolute median (χ) and the median absolute deviation (ρ). The proposed RMSM approach is evaluated on a complex multi-scales neuromuscular electrophysiological model simulating HD-sEMG (high density surface electromyography) signals at the skin surface. The reliability and stability of new RMSM indicators are evaluated at different trajectories within the parameter space and compared to classical MSM results. For this purpose, We propose a new methodology for parameter screening based on the ratio ρ/χ as a graphic indicator of (non)linearity and (non)monotonicity of parameter effects.
Results: Firstly, the results demonstrated that the computed elementary effects (EE) of inputs are not normally distributed using MSM indices contrary to the proposed RMSM indices. Secondly, the ranking stability of RMSM indices was earlier obtained from 20 trajectories (T=20), while MSM ranking remained unstable until T = 100. Thirdly, The screening separation between influential and negligible input model parameters was more distinct and interpretable with RMSM than MSM.
Conclusion: The proposed RMSM approach ensures a fast, reliable and stable ranking of parameters for complex and overparametrized models compared to classical MSM. this allows a more precise exploration of the model parameter influence space for future application in parameter tuning and identification.
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http://dx.doi.org/10.1016/j.cmpb.2023.107368 | DOI Listing |
J Appl Physiol (1985)
January 2025
University of Kansas Alzheimerșs Disease Research Center, University of Kansas Medical Center, Fairway, KS, USA.
Impaired glycemic control increases the risk for type 2 diabetes (T2D) and Alzheimer's Disease (AD). Heat therapy (HT), via hot water immersion (HWI), has shown promise in improving shared mechanisms implicated in both T2D and AD, like blood glucose regulation, insulin sensitivity, and inflammation. The potential for HT to improve brain health in individuals at risk for AD has not been examined.
View Article and Find Full Text PDFAsia Pac J Clin Oncol
January 2025
Department of Medical Oncology, Gosford Hospital, Gosford, New South Wales, Australia.
Introduction: Despite the increased demand for medical cannabis (MC), MASCC guidelines state that there is insufficient evidence of its efficacy and safety. Although research has explored medical professionals' perceptions of MC, there is to our knowledge minimal research exploring patients' perceptions, particularly in an Australian cancer setting.
Methods: A survey of Australian cancer patients attending oncology outpatient clinics was performed.
J Pathol
January 2025
MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
Mucosal melanoma is a rare melanoma subtype associated with a poor prognosis and limited existing therapeutic interventions, in part due to a lack of actionable targets and translational animal models for preclinical trials. Comprehensive data on this tumour type are scarce, and existing data often overlooks the importance of the anatomical site of origin. We evaluated human and canine oronasal mucosal melanoma (OMM) to determine whether the common canine disease could inform the rare human equivalent.
View Article and Find Full Text PDFComput Biol Chem
January 2025
Drug Discovery and Development Laboratory (DDD Lab), Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India. Electronic address:
Multiple myeloma (MM) is the second most frequently diagnosed hematological malignancy, presenting limited treatment options with no curative potential and significant drug resistance. Recent studies involving genetic knockdown established the crucial role of GRK6 in upholding the viability of MM cells, emphasizing the need to identify potential inhibitors. Computational exploration of GRK6 inhibitors has not been attempted previously.
View Article and Find Full Text PDFCureus
December 2024
Geriatric and Memory Center, Broadlawns Medical Center, Des Moines, USA.
The novel amyloid-beta, p-Tau, and neurofilament light chain (ATN) classification scheme has become a promising system for clinically detecting and diagnosing Alzheimer's disease (AD). In addition to its utility in Alzheimer's diagnosis and treatment, the ATN framework may also have clinical relevance in identifying non-Alzheimer's pathologies. In this study conducted at Broadlawns Geriatric and Memory Center, 92 amyloid-negative profiles out of 182 patients with an ATN framework were categorized into subjective cognitive impairment (SCI), non-amnestic mild cognitive impairment (non-amnestic MCI), amnestic MCI, Alzheimer's dementia, vascular dementia, mixed dementia, unspecified dementia, or other memory changes based on diagnoses written in the chart.
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