Biology subjects

Chen, D. Y.

Publications and source records attributed to Chen, D. Y..

6 recordsLinked to original sources

bioRxiv2025

Peak Anteroposterior Heel Slip Acceleration Predicts Lateral Trunk Flexion During Unexpected Slip Perturbations

Slip-induced falls are a major contributor to hip fractures and injury, particularly during sideways falls where lateral trunk flexion drives impact to the hip. While past studies have focused on sagittal-plane slip mechanics, the mechanisms of inducing frontal-plane trunk excursion remain poorly understood. This study investigated which slip foot kinematic variables predict lateral trunk flexion during unexpected slips. Twenty-six healthy young adults experienced an unexpected slip while walking in a laboratory setting. Peak anteroposterior (AP) heel slip distance, velocity, and acceleration, as well as mediolateral (ML) slip distance, velocity, and acceleration, were measured using three-dimensional motion capture. A stepwise multiple linear regression identified peak AP heel slip acceleration as the sole significant predictor of lateral trunk flexion (p = .026, R2 = 0.19). One-way repeated measures ANOVA and one-tailed paired t-tests further revealed that peak heel acceleration occurred significantly earlier than both peak heel velocity (p = .012) and the onset of lateral trunk flexion (p < .001), supporting its role as an early destabilizing mechanism. In contrast, neither velocity nor slip distance predicted lateral trunk flexion magnitude. These findings suggest that peak AP heel acceleration is associated with inducing lateral trunk flexion movements that likely precede lateral falls. Reducing heel acceleration through slip-resistant flooring or footwear, or enhancing compensatory strategies such as reactive arm movements, may reduce the likelihood of losing sideways balance. This work highlights the need for balance training interventions that emphasize rapid responses to early-phase slip dynamics. HighlightsO_LIEvery 1000 cm/s2 increase in AP heel acceleration leads to 6 degrees more lateral trunk flexion C_LIO_LIHeel acceleration occurs significantly earlier than heel velocity or the onset of lateral trunk flexion C_LIO_LIFindings highlight the importance in reducing forward heel acceleration to reduce sideways loss of balance C_LI

bioengineering↗

bioRxiv2024

Mapping single-cell developmental potential in health and disease with interpretable deep learning

Single-cell RNA sequencing (scRNA-seq) has transformed our understanding of cell fate in developmental systems. However, identifying the molecular hallmarks of potency - the capacity of a cell to differentiate into other cell types - has remained challenging. Here, we introduce CytoTRACE 2, an interpretable deep learning framework for characterizing potency and differentiation states on an absolute scale from scRNA-seq data. Across 31 human and mouse scRNA-seq datasets encompassing 28 tissue types, CytoTRACE 2 outperformed existing methods for recovering experimentally determined potency levels and differentiation states covering the entire range of cellular ontogeny. Moreover, it reconstructed the temporal hierarchy of mouse embryogenesis across 62 timepoints; identified pan-tissue expression programs that discriminate major potency levels; and facilitated discovery of cellular phenotypes in cancer linked to survival and immunotherapy resistance. Our results illuminate a fundamental feature of cell biology and provide a broadly applicable platform for delineating single-cell differentiation landscapes in health and disease.

genomics↗

bioRxiv2024

Brain activation during the N-back working memory task in individuals with spinal cord injury: a functional near-infrared spectroscopy study

Cognitive impairments have frequently been reported in individuals with spinal cord injury (SCI) across different domains such as working memory, attention, and executive function. The mechanism of cognitive impairment after SCI is not well understood due to the heterogeneity of SCI sample populations, and may possibly be due to factors such as cardiovascular dysfunction, concomitant traumatic brain injury (TBI), hypoxia, sleep disorders, and body temperature dysregulation. In this study, we implement the Neuropsychiatric Unit Cognitive Assessment Tool (NUCOG) to assess cognitive differences between individuals with SCI and age-matched able-bodied (AB) controls. We then use an N-back working memory task and functional near-infrared spectroscopy (fNIRS) to elucidate the neurovascular correlates of cognitive function in individuals with SCI. We observed significant differences between the SCI and AB groups on measures of executive function on the NUCOG test. On the N-back task, across the three levels of difficulty: 0-back, 2-back, and 3-back, no significant differences were observed between the SCI and AB group; however, both groups performed worse as the level of difficulty increased. Although there were no significant differences in N-back performance scores between the two groups, functional brain hemodynamic activity differences were observed between the SCI and AB groups, with the SCI group exhibiting higher maximum oxygenated hemoglobin concentration in the right inferior parietal lobe. These findings support the use of fNIRS to study cognitive function in individuals with SCI and may provide a useful tool during rehabilitation to obtain quantitative functional brain activity metrics.

neuroscience↗

bioRxiv2023

The Significance and Limited Influence of Cerebrovascular Reactivity on Age and Sex Effects in Task- and Resting-State Brain Activity

Functional MRI (fMRI) measures the blood-oxygen-level dependent (BOLD) signals, which provide an indirect measure of neural activity mediated by neurovascular responses. Cerebrovascular reactivity affects both task-induced and resting-state BOLD activity and may confound inter-individual effects observed in BOLD-based measures, such as those related to aging and biological sex. To investigate this, we examined a large open-access fMRI dataset containing a breath-holding task, checkerboard task, and resting-state scans. We used the breath-holding task to measure cerebrovascular reactivity, used the checkerboard task to obtain task-based activations, and from the resting-state data, we quantified the resting-state amplitude of low-frequency fluctuations (ALFF), and resting-state regional homogeneity (ReHo). We hypothesized that cerebrovascular reactivity would be correlated with BOLD measures and that accounting for these correlations would result in better estimates of age and sex effects. Our analysis showed that cerebrovascular reactivity was correlated with checkerboard task activations in the visual cortex and with ALFF and ReHo in widespread fronto-parietal regions, as well as regions with large vessels. We also found significant age and sex effects in cerebrovascular reactivity, some of which overlapped with those observed in ALFF and ReHo scores. Finally, we demonstrated that correcting for the effects of cerebrovascular reactivity had very limited influence on the estimates of age and sex. Our results highlight the limitations of accounting for cerebrovascular reactivity with the current breath-holding task.

neuroscience↗

bioRxiv2023

Neurovascular reactivity increases across development in the visual and frontal pole networks as revealed by a breath-holding task: a longitudinal fMRI study

Functional magnetic resonance imaging (fMRI) has been widely used to understand the neurodevelopmental changes that occur in cognition and behavior across childhood. The blood-oxygen-level-dependent (BOLD) signal obtained from fMRI is understood to be comprised of both neuronal and vascular information. However, it is unclear whether the vascular response is altered across age in studies investigating development in children. Since the breath-hold task is commonly used to understand cerebrovascular reactivity in fMRI studies, it can be used to account for developmental differences in vascular response. This study examines how the cerebrovascular response changes over age in a longitudinal childrens breath-hold dataset from the Nathan Kline Institute (NKI) Rockland Sample (ages 6 to 18 years old at enrollment). A general linear model (GLM) approach was applied to derive cerebrovascular reactivity from breath-hold data. To model both the longitudinal and cross-sectional effects of age on breath-hold response, we used mixed effects modeling with the following terms: linear, quadratic, logarithmic, and quadratic-logarithmic, to find the best-fitting model. We observed increased breath-hold BOLD signal in multiple networks across age, in which linear and logarithmic mixed effects models provided the best fit with the lowest Akaike Information Criterion (AIC) scores. This shows that the cerebrovascular response increases across development in a brain network-specific manner. Therefore, fMRI studies investigating the developmental period should account for cerebrovascular changes which occur with age.

neuroscience↗

bioRxiv2018

Mutation detection in thousands of acute myeloid leukemia cells using single cell RNA-sequencing

Virtually all tumors are genetically heterogeneous, containing subclonal populations of cells that are defined by distinct mutations1. Subclones can have unique phenotypes that influence disease progression2, but these phenotypes are difficult to characterize: subclones usually cannot be physically purified, and bulk gene expression measurements obscure interclonal differences. Single-cell RNA-sequencing has revealed transcriptional heterogeneity within a variety of tumor types, but it is unclear how this expression heterogeneity relates to subclonal genetic events - for example, whether particular expression clusters correspond to mutationally defined subclones3,4,5,6-9. To address this question, we developed an approach that integrates enhanced whole genome sequencing (eWGS) with the 10x Genomics Chromium Single Cell 5 Gene Expression workflow (scRNA-seq) to directly link expressed mutations with transcriptional profiles at single cell resolution. Using bone marrow samples from five cases of primary human Acute Myeloid Leukemia (AML), we generated WGS and scRNA-seq data for each case. Duplicate single cell libraries representing a median of 20,474 cells per case were generated from the bone marrow of each patient. Although the libraries were 5 biased, we detected expressed mutations in cDNAs at distances up to 10 kbp from the 5 ends of well-expressed genes, allowing us to identify hundreds to thousands of cells with AML-specific somatic mutations in every case. This data made it possible to distinguish AML cells (including normal-karyotype AML cells) from surrounding normal cells, to study tumor differentiation and intratumoral expression heterogeneity, to identify expression signatures associated with subclonal mutations, and to find cell surface markers that could be used to purify subclones for further study. The data also revealed transcriptional heterogeneity that occurred independently of subclonal mutations, suggesting that additional factors drive epigenetic heterogeneity. This integrative approach for connecting genotype to phenotype in AML cells is broadly applicable for analysis of any sample that is phenotypically and genetically heterogeneous.

cancer biology↗