Publications by Year: 2025

PURPOSE: Compressed-sensing (CS) methods can decrease the acquisition time for T1-weighted (T1w) structural MRI images to 1-2 min. Rapid acquisitions reduce participant burden, reduce the risk of motion artifacts, and allow for repeat scans to be acquired within a session. This study investigated the tradeoffs of sparse sampling and CS image reconstruction for brain morphometric applications.

METHODS: Magnetization-Prepared Rapid Gradient Echo (MPRAGE) images were acquired at 1.0 mm spatial resolution. The effects of the acceleration factor (x2 to x8) and regularization factor were examined. Subcortical volumes and regional cortical thickness estimates of brain structure were obtained for all T1w images. Within-sequence agreement was evaluated by comparing estimates obtained using the same protocol in the same imaging session. Between-sequence agreement was evaluated by comparing estimates from a fully sampled MPRAGE protocol to the novel CS-accelerated MPRAGE protocols within the same session.

RESULTS: Higher acceleration lowered the SNR in white matter but not in gray matter. SNR could be further manipulated by the regularization parameter. Within-sequence agreement was comparable across all protocols. In fact, the spread in estimates from the 58-s CSx8 protocol was similar to those from the fully sampled protocol. Similarly, high agreement was found between estimates from the fully sampled and under-sampled protocols for all acceleration levels up to eight. Modifying the regularization factor had a quantifiable effect on image smoothness, however it had minimal impact on the agreement of morphometric estimates.

CONCLUSION: Accelerated CS imaging protocols show comparable performance to traditional longer protocols for morphometric brain estimates.

Gliomas engage in bidirectional communication with neurons, promoting hyperexcitable conditions that enable neural circuit infiltration and drive tumor growth. These neuron-glioma interactions create patterns of aberrant neural activity that can be detected using intracranial electrodes. While conventional clinical electrodes are limited by low spatiotemporal resolution and lack of single-unit precision, recent advances in neural engineering have introduced multiple types of high-density electrodes that provide orders of magnitude greater spatial resolution. Pairing these tools with emerging characterizations of novel, glioma-associated electrophysiological signatures offers new opportunities to understand disease progression and improve surgical and medical management for gliomas and glioma-related epilepsy. In this review, we begin by outlining foundational research in cancer neuroscience and neuron-glioma interactions through the lens of extracellular dynamics. We then discuss established and emerging methods for intraoperative evaluation of neural activity, what is known about glioma-associated oscillatory and aperiodic trends, and implications for future studies. Finally, we consider the therapeutic potential of neuromodulation for gliomas.

BACKGROUND: Microsatellite instability (MSI) is an important molecular biomarker in colorectal cancer (CRC), associated with favorable prognosis and response to immune checkpoint inhibitors. Conventional MSI testing, including immunohistochemistry (IHC) and polymerase chain reaction (PCR), is invasive, time-consuming, and resource-dependent, underscoring the need for non-invasive and automated alternatives. This study aimed to develop and evaluate an ensemble learning framework integrating pretreatment colonoscopy images and routine clinical data for non-invasive MSI prediction in CRC.

METHODS: In this retrospective study, patients with pathologically confirmed CRC and IHC-determined MSI status were included. Pretreatment colonoscopy images and routine clinical variables were collected. Five deep learning architectures (ResNet-50, EfficientNet, DenseNet, VGG-16, and Vision Transformer) were trained on image data, while four machine learning algorithms (Logistic Regression, Random Forest, Support Vector Machine, and Gradient Boosting) were trained on clinical data. The best-performing models from each modality were combined using a majority-voting ensemble. Model performance was assessed using accuracy, precision, recall, and area under the receiver operating characteristic curve (AUROC). Interpretability was evaluated using Gradient-weighted Class Activation Mapping (Grad-CAM) for image models and SHapley Additive exPlanations (SHAP) for clinical models.

RESULTS: Among 1,844 patients, VGG-16 achieved the best image-based performance (AUROC = 0.896, accuracy = 0.832, recall = 0.708). Logistic Regression outperformed other clinical models (AUROC = 0.898, accuracy = 0.825, recall = 0.828). The ensemble model integrating both modalities achieved AUROC = 0.886, precision = 0.920, and recall = 0.845, outperforming single-modality approaches.

CONCLUSION: The proposed ensemble learning framework provides a non-invasive, interpretable, and accurate method for MSI prediction, offering potential to improve preoperative precision diagnostics and clinical decision-making in colorectal cancer.

Cathelicidins are short cationic peptides with potent microbicidal activities and comprise an important arm of host innate immunity. Many cell types can produce cathelicidins, but they are mainly expressed by recruited immune cells and are induced in epithelial cells during infection. Although the mechanisms of bacterial killing by cathelicidins have been largely elucidated in vitro, those that regulate their activities in vivo are less well understood. Bacterial pathogens often co-opt host extracellular matrix (ECM) components and their functions to escape host defense; however, it is unclear whether such mechanisms exist against cathelicidins. Several studies have demonstrated that host heparan sulfate (HS) inhibits LL-37, the human cathelicidin, suggesting that bacteria might exploit HS to evade killing by cathelicidins. However, precisely how HS inhibits LL-37 and possibly other cathelicidins remains unknown, and the role of the HS-cathelicidin interaction in infectious disease has not been rigorously studied. Here, we found that deleting CRAMP, the murine cathelicidin, significantly increases the susceptibility of mice to Staphylococcus aureus corneal infection. We also determined that heparan compounds bind to CRAMP with low nanomolar affinity, the secondary structure of CRAMP is required for HS binding, and HS binding to CRAMP inhibits CRAMP binding to target bacterial cells. Furthermore, we found that heparan compounds inhibit the killing of S. aureus by cathelicidins derived from several mammalian species in a 2-O-sulfate-dependent manner. Additionally, we demonstrate for the first time that conditional deletion of HS2ST, the enzyme responsible for 2-O-sulfation of HS, in corneal epithelial cells significantly reduces the susceptibility of mice to corneal infection. Altogether, these data uncover an endogenous inhibition mechanism of cathelicidins where 2-O-sulfated epithelial HS tightly binds and neutralizes the antibacterial activity of cathelicidins.

PURPOSE: Corneal injury is a leading cause of vision loss and demands rapid, coordinated regeneration. Myeloid-derived suppressor cells (MDSC), innate immunoregulatory cells that aid repair in peripheral tissues, have not been evaluated in corneal healing. We tested whether MDSC promote epithelial closure and temper postinjury inflammation.

METHODS: For scratch assays, 1.0 × 105 human corneal epithelial cells were cocultured with 1.5 × 106 MDSC or CD11b+Gr-1- control cells, and wound areas at 18 and 24 hours were quantified in ImageJ. In vivo, corneal epithelial debridement was induced in BALB/c mice using an Algerbrush-II, followed by subconjunctival injection of MDSC or control cells (5 × 104 cells in 50 μL saline). Epithelial healing was assessed by fluorescein staining and slitlamp imaging at 6, 22, and 28 hours, with ImageJ analysis. At 28 hours, corneas were collected for real-time polymerase chain reaction and flow cytometry to assess inflammatory markers. On day 3, corneas were harvested for hematoxylin and eosin staining and histological analysis.

RESULTS: MDSC significantly enhanced human corneal epithelial cells migration in vitro versus controls. In vivo, MDSC delivery accelerated epithelial wound closure, reduced CD11b+Ly6G+ neutrophil infiltration, and lowered corneal tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) expression compared with saline or CD11b+Gr-1- control cells. Histology confirmed restoration of epithelial integrity in MDSC-treated eyes.

CONCLUSIONS: MDSC expedite corneal epithelial repair and attenuate acute inflammation after injury. These findings identify a previously unrecognized reparative function for MDSC in the cornea and support their development as a cell-based therapy for ocular surface injury.

BACKGROUND: Speech biomarkers have been used to assess motor dysfunction in people with Parkinson's disease (PD), but speech biomarkers for mild cognitive impairment in PD (PD-MCI) have not been well studied.

OBJECTIVE: To identify speech acoustic features associated with PD-MCI and evaluate the performance of a model to discriminate PD-MCI from participants with normal cognitive status (PD-NC).

METHODS: We analyzed speech samples from 42 participants with PD, diagnosed as either PD-MCI or PD-NC using the Movement disorders Society Task Force Tier II criteria as a gold-standard classification of MCI. A reading passage and a picture description task were analyzed for acoustic features, which were used to generate individual and then a final fused Gaussian mixture model (GMM) to discriminate PD-MCI and PD-NC participants.

RESULTS: The picture description task yielded a larger number of acoustic features that were highly associated with PD-MCI status compared to the reading task. Fusing the model outputs from the picture description task resulted in an AUC = 0.82 for discriminating PD-MCI from PD-NC participants. The acoustic features associated with PD-MCI stemmed from multiple speech subsystems.

CONCLUSION: PD-MCI has a distinct speech acoustic signature that may be harnessed to develop better tools to detect and monitor this complication.

BACKGROUND: Obesity is a cardiovascular risk factor and coronary artery calcium (CAC) is frequently used to assess coronary atherosclerosis burden. The purpose of this study was to evaluate body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) as predictors of CAC incidence.

METHODS: We analyzed ELSA-Brasil cohort participants with no cardiovascular disease who had an initial CAC score of zero and repeated the test. Multivariate logistic regression analyses were performed to assess BMI, WC, and WHtR as predictors of CAC incidence.

FINDINGS: A total of 2721 participants (mean age 48.1 ± 7.56 years, 62.6% females) self-reported as White (57%), Brown/mixed (22.8%), Black (15.4%), Asian (4%) or Native/Indigenous (0.9%) were analyzed. CAC incidence after a mean of 5.24 years was 15.5% (confidence interval [CI] 95%: 14.2-17%). In unadjusted analysis, BMI, WC, and WHtR were positively associated with CAC incidence with an odds ratio (OR) of 1.19 (CI 95%: 1.08-1.31), 1.37 (CI 95% 1.23-1.52) and 1.39 (CI 95%: 1.25-1.54) per standard deviation, respectively. In the fully adjusted model, WHtR was the only independent predictor of CAC incidence, OR: 1.18 (CI 95% 1.03-1.35) per standard deviation. This effect was mainly driven by individuals with BMI <30 kg/m2.

INTERPRETATION: WHtR was the only independent anthropometric measure predictor of atherosclerosis incidence assessed by coronary artery calcium score. This effect is particularly relevant in individuals with BMI <30 kg/m2.

FUNDING: National Council for Scientific and Technological Development (CNPq), Brazil.

Arthroscopy-assisted lower trapezius transfer is increasingly recognized as a standard approach for addressing irreparable posterosuperior rotator cuff tears. A posterior incision is made along the medial margin of the scapula to identify and dissect the lower trapezius. The Achilles allograft is arthroscopically fixed to the greater tuberosity with a knotless double-row "transosseous-equivalent" repair and to the trapezius using Pulver-Taft technique sutures. The arm should remain immobilized in abduction and neutral rotation for 6 weeks. This procedure enables a dynamic tendon transfer, restoring torque biomechanics and normalizing glenohumeral joint function.

Men who have sex with men (MSM) living with HIV who use substances often report internalized stigma associated with aspects of their identities and behaviors, which can negatively influence health behaviors including engagement in HIV care. Given the de-valuing nature of stigma, one's perception of their hierarchical rank in society may account for the relationships between internalized stigma and suboptimal engagement in HIV care. This study investigated relationships between internalized stigmas (i.e., linked to HIV-status, sexual orientation, and substance use), subjective social status in relation to one's community and the U.S., and missed HIV appointments among 143 MSM living with HIV who use substances. In bivariate regression models, internalized HIV stigma related to disclosure (OR = 1.46; confidence interval [CI]: 1.02, 2.09), and substance use stigma (OR = 1.07; CI:1.02, 1.12) were associated with greater odds of missing HIV appointments. Selfperception of higher social status in one's community (OR = 0.81; CI: 0.69, 0.96) and the U.S. (OR= 0.80; CI: 0.69, 0.94) were associated with lower odds of missing HIV appointments. Indirect effects models demonstrated that subjective social status in the U.S., but not in one's community, explained variance in the relationship between internalized HIV and sexual orientation stigmas and missing HIV appointments. Results suggest that perceptions of social status in the U.S. may partially account for the associations between internalized HIV and sexual orientation-related stigmas and sub-optimal engagement in HIV care, potentially related to the discriminatory policies and practices across the U.S., in contrast to more liberal states such as where this study took place. Efforts, including policies, are needed to stop the devaluation of people with stigmatized identities nationally, including those living with HIV and those who identify as sexual minorities, to improve the health and well-being of all people.