Biomedical subjects

Charles L Howe

Publications and source records attributed to Charles L Howe.

3 recordsLinked to original sources

PubMed2026

Instrumented Walkway Gait Analysis Predicts Fallers in Neurological Disorders: Identifying Digital Biomarkers for Balance Monitoring.

Assessing balance is crucial in neurological rehabilitation, yet while wearable sensors enable real-world monitoring, identifying reliable digital biomarkers remains challenging. This study utilized a high-fidelity instrumented walkway to determine which gait parameters best predict balance impairment, providing robust targets for future wearable applications. We analyzed 49 steady-state gait metrics from 140 individuals with diverse neurological conditions. Using statistical analysis and machine learning, we evaluated these parameters against objective force plate sway scores and clinical fall-history labels. Group analysis identified 16 parameters significantly distinguishing fallers from non-fallers, and a neural network classified fallers with an area under the curve of 0.75. Across all analytical approaches, overall gait variability, e.g., Stride Width S.D. and the Gait Variability Index, emerged as a universal predictor of balance impairment and fall risk. Furthermore, while traditional linear models emphasized spatial postural control, machine learning classification uniquely identified inter-limb asymmetry as a premier driver of fall prediction. These findings indicate that instrumented gait analysis effectively identifies digital biomarkers for balance deficits. Isolating these specific metrics provides a clear blueprint for meaningful metrics required for continuous objective monitoring and future development of personalized, adaptive rehabilitation strategies.

Humans↗

PubMed2026

Integration of biological avatars and digital twins for "ex vivo clinical trials".

Drug development is slow, costly, and prone to late-stage failure, in part because animal models poorly predict human responses. Two human-relevant technologies are maturing in parallel: biological avatars, defined as patient- or stem-cell-derived models such as organoids and organ-on-a-chip systems, and digital twins, defined as computational models that integrate a patient's molecular and clinical data to forecast treatment responses. We propose the ex vivo clinical trial concept, in which an avatar and a digital twin are coupled in an iterative loop so that laboratory measurements refine the computational prediction and the prediction guides the next experiment, allowing candidate therapies to be tested and prioritised before a patient is exposed. We review the platforms, their predictive performance in cancer, cystic fibrosis, and liver toxicity, the conditions under which they fail, and the qualification, turnaround, and standardisation requirements that must be met before such trials can inform drug development or clinical care.

Biological avatars↗

PubMed2025

Genomewide association study of a homogeneous multiple sclerosis cohort: Tumefactive demyelination.

BACKGROUND: Tumefactive demyelination (TD) is a rare variant of multiple sclerosis (MS) characterized by tumor-like lesions that often require aggressive management. Genome-wide association studies (GWAS) identified variants associated with MS; similar analyses in TD are lacking. OBJECTIVE: A GWAS was performed to identify variants associated with TD. METHODS: The case-control study included 142 TD cases and 293 controls. TD patients were required to have a demyelinating event and magnetic resonance imaging (MRI) showing one or more lesions. Controls were patients without a neurologic or systemic inflammatory disease or cancer. Logistic regression was used to compare cases versus controls for each variant; age, sex, and principal components were included as covariates. A p-value threshold of 5 × 10-8 was GWAS significant and 5 × 10-6 nominally significant. A polygenic risk score (PRS) was compared across TD and controls. RESULTS: Variants on chromosome 14 (rs117797734, p = 2.06 × 10-11, odds ratio (OR) = 13.14) and chromosome 6 (most significant rs6936540, p = 5.5 × 10-7, OR = 2.61) near DCBLD1 were significant. Seven non-MHC and two MHC variants associated with MS were associated with TD. The PRS was significantly higher in TD versus controls. CONCLUSION: We identified novel regions associated with TD, demonstrating the importance of performing GWAS in homogeneous subtypes of MS. Further validation and functional experiments are necessary.

Humans↗