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Biology subjects

Wood, R. W.

Publications and source records attributed to Wood, R. W..

3 recordsLinked to original sources

Automated Joint Space Detection Improves Bone Segmentation Accuracy

Quantitative description of complex anatomical structures remains challenging due to the expertise necessary for manual segmentation, labor, and interobserver variability. To overcome this, automated detection of specific landmarks can be provided by digital image analysis techniques including deep learning (DL) models. To this end, we undertook supervised automated analysis of micro-computed tomography (micro-CT) datasets of murine hindpaws and forepaws (30-33 bones). Advancing beyond previously published semi-automated (SA) marker-based watershed algorithms, we added structure enhancement, tensor voting, and output dilation to identify joint spaces. Segmentation was enhanced by the use of a DL joint space prediction model (3D U-Net architecture, ResNet-18 backbone) using wild-type (WT) hindpaw labels as ground truth. Prediction was then extended to hindpaws (52.4% in test group) and forepaws from WT and tumor necrosis factor transgenic (TNF-Tg) mice with inflammatory-erosive arthritis of both sexes across age. Segmentation accuracy improved dramatically using the DL methodology (WT male: SA 79.39{+/-}5.73% vs DL 98.16{+/-}1.47%, p<0.0001; WT female: SA 79.16{+/-}4.84% vs DL 99.19{+/-}1.63%, p<0.0001). Accuracy declined with increased disease severity and age in TNF-Tg mice (TNF-Tg male 93.54{+/-}4.73%, female 91.81{+/-}2.80%, p[&le;]0.01). Subsequent testing in forepaws also displayed progressive reduction in accuracy with increasing arthritic severity (i.e., WT 87.29{+/-}2.07%, TNF-Tg male 72.65{+/-}11.70%, p<0.0001). Overall, this supervised automated model outperforms recent SA approaches in healthy joints to enhance investigation of complex bone anatomy. Although flexible application to novel and disease-modified datasets demonstrates deprecated performance, utilization may nonetheless catalyze structure-specific segmentation model development.

pathology↗

Multi-omics Analysis Identifies IgG2b Class-Switching with ALCAM-CD6 Co-Stimulation in Lymph Nodes During Advanced Inflammatory-Erosive Arthritis

Defective lymphatic drainage and B-cell translocation into joint-draining lymph node sinuses are pathogenic phenomena in patients with severe rheumatoid arthritis (RA). However, the molecular mechanisms underlying this lymphatic dysfunction remain poorly understood. Here, by utilizing spatial and single-cell transcriptomics in tumor necrosis factor transgenic (TNF-Tg) mice, we characterized functional genomic changes in popliteal lymph nodes (PLNs) of "Early" and "Advanced" RA to determine the mechanisms orchestrating B-cell differentiation. We first show that Ighg2b expression localized to Marco+ sinuses and negatively correlated with bone volumes in ipsilateral joints. We further reveal that Advanced PLNs exhibited a concomitant accumulation of iron-laden macrophages and T-cells. Mechanistically, crosstalk between ALCAM+ macrophages and CD6+ T-cells was identified as a co-stimulatory pathway promoting IgG2b class-switching. These findings were validated by immunohistochemistry, flow cytometry, ELISPOT, and clinical correlates. Collectively, we propose that ALCAM-CD6 co-stimulation activates T cells, initiating IgG2b class-switching and plasma cell differentiation in RA flare.

immunology↗

Spike protein multiorgan tropism suppressed by antibodies targeting SARS-CoV-2

While there is clinical evidence of severe acute respiratory syndrome coronavirus 2 multiorgan tropism in severely infected coronavirus 19 patients, its unclear if there is differential multiorgan biodistribution and organ uptake in healthy young individuals, a group that usually has asymptomatic to moderate coronavirus 19 symptoms. In addition, for antibody therapies and vaccines that target the spike protein, its unclear if these reduce severe acute respiratory syndrome coronavirus 2 or spike protein multiorgan tropism equally. We used fluorescently labeled spike protein near infrared fluorescence to study viral behavior, using an in vivo dynamic imaging system, in young mice. We found a spike protein body-wide biodistribution followed by a slow regional elimination, except for the liver, which showed an accumulation. Spike protein uptake was highest for the lungs, and this was followed by kidney, heart and liver, but, unlike the choroid plexus, it was not detected in the brain parenchyma or cerebrospinal fluid. Thus, the brain vascular barriers were effective in restricting the entry of spike protein into brain parenchyma in young healthy mice. While both anti-angiotensin converting enzyme 2 and anti-spike protein antibodies suppressed spike protein biodistribution and organ uptake, anti-spike protein antibody was more effective. By extension, our data support the efficacy of these antibodies on severe acute respiratory syndrome coronavirus 2 biodistribution kinetics and multiorgan tropism that could determine coronavirus 19 organ-specific outcomes.

neuroscience↗