Digital Commons Network^™

Effective Connectivity In The Default Mode Network After Paediatric Traumatic Brain Injury, Linda Ewing-Cobbs

Faculty, Staff and Student Publications

Children who experience a traumatic brain injury (TBI) are at elevated risk for a range of negative cognitive and neuropsychological outcomes. Identifying which children are at greatest risk for negative outcomes can be difficult due to the heterogeneity of TBI. To address this barrier, the current study applied a novel method of characterizing brain connectivity networks, Bayesian multi-subject vector autoregressive modelling (BVAR-connect), which used white matter integrity as priors to evaluate effective connectivity-the time-dependent relationship in functional magnetic resonance imaging (fMRI) activity between two brain regions-within the default mode network (DMN). In a prospective longitudinal study, children ages 8-15 years …

Enhancing Mesenchymal Stromal Cell Potency: Inflammatory Licensing Via Mechanotransduction, Charles S Cox

Faculty, Staff and Student Publications

Mesenchymal stromal cells (MSC) undergo functional maturation upon their migration from bone marrow and introduction to a site of injury. This inflammatory licensing leads to heightened immune regulation via cell-to-cell interaction and the secretion of immunomodulatory molecules, such as anti-inflammatory mediators and antioxidants. Pro-inflammatory cytokines are a recognized catalyst of inflammatory licensing; however, biomechanical forces, such as fluid shear stress, are a second, distinct class of stimuli that incite functional maturation. Here we show mechanotransduction, achieved by exposing MSC to various grades of wall shear stress (WSS) within a scalable conditioning platform, enhances the immunomodulatory potential of MSC independent of …

Career Transitions: Reflections Of Former Chairs And Academic Health Center Leaders, Fred Sanfilippo

Faculty, Staff and Student Publications

The 2022 Association of Pathology Chairs Annual Meeting included a live discussion session and a pre-meeting recorded panel webinar sponsored by the Senior Fellows Group (former chairs of academic departments of pathology who have remained active in the Association of Pathology Chairs). The presentation was focused on transition planning for academic health center leaders. Each of the discussion group panelists had served as a pathology department chair as well as in more senior leadership positions, and they provided perspectives based upon their personal experiences. It was noted that such positions are often "at will" appointments of indeterminate length and that …

Radiographic Findings And Association With Clinical Severity And Outcomes In Critically Ill Patients With Covid-19, Kevin I Duan, Daniel S Hippe, Gautham Reddy, Sudhakar Pipavath

Faculty, Staff and Student Publications

PURPOSE: To describe evolution and severity of radiographic findings and assess association with disease severity and outcomes in critically ill COVID-19 patients.

MATERIALS AND METHODS: This retrospective study included 62 COVID-19 patients admitted to the intensive care unit (ICU). Clinical data was obtained from electronic medical records. A total of 270 chest radiographs were reviewed and qualitatively scored (CXR score) using a severity scale of 0-30. Radiographic findings were correlated with clinical severity and outcome.

RESULTS: The CXR score increases from a median initial score of 10 at hospital presentation to the median peak CXR score of 18 within a …

Autologous Cellular Therapy For Cerebral Palsy: A Randomized, Crossover Trial, Nivedita Thakur, Margaret Jackson, Akshita Kumar, Benjamin Aertker, Henry Caplan, Fabio Triolo, Sean I Savitz

Faculty, Staff and Student Publications

We examined an autologous mononuclear-cell-therapy-based approach to treat cerebral palsy using autologous umbilical cord blood or bone-marrow-derived mononuclear cells. The primary objective was to determine if autologous cells are safe to administer in children with cerebral palsy. The secondary objectives were to determine if there was improvement in motor function of patients 12 months after infusion using the Gross Motor Function Measure and to evaluate impact of treatment on corticospinal tract microstructure as determined by radial diffusivity measurement. This Phase 1/2a trial was a randomized, blinded, placebo-controlled, crossover study in children aged 2–10 years of age with cerebral palsy enrolled …

Characterization Of The Blood Oxygen Level Dependent Hemodynamic Response Function In Human Subcortical Regions With High Spatiotemporal Resolution, Klaus Scheffler

Faculty, Staff and Student Publications

Subcortical brain regions are absolutely essential for normal human function. These phylogenetically early brain regions play critical roles in human behaviors such as the orientation of attention, arousal, and the modulation of sensory signals to cerebral cortex. Despite the critical health importance of subcortical brain regions, there has been a dearth of research on their neurovascular responses. Blood oxygen level dependent (BOLD) functional MRI (fMRI) experiments can help fill this gap in our understanding. The BOLD hemodynamic response function (HRF) evoked by brief (<4 >s) neural activation is crucial for the interpretation of fMRI results because linear analysis between neural …

Renal Disease And The Heart

Faculty, Staff and Student Publications

No abstract provided.

Complete Corpus Callosotomy Using A Frameless Navigation Probe Through A Minicraniotomy In Children With Medically Refractory Epilepsy: A Case Series And Technical Note, John C Mosher, Rajan Patel

Faculty, Staff and Student Publications

BACKGROUND: Medically refractory epilepsy constitutes up to one-third of the epilepsy pediatric patients. Corpus callosotomy (CC) has been used for the treatment of medically refractory epilepsy in children with atonic seizures and generalized tonic-clonic (GTC) seizures. In this case series study, we are describing a novel technique for CC using the frameless navigation probe through a minicraniotomy.

METHODS: Thirteen pediatric patients with the diagnosis of medically refractory epilepsy predominantly GTC with drop attack who underwent extensive Phase I. An L-shape was done, then through a 4 × 3 cm craniotomy, we were able to open the interhemispheric fissure until the …

Catalytic Asymmetric Synthesis Of Carbocyclic C-Nucleosides

Faculty, Staff and Student Publications

Access to carbocyclic C-nucleosides (CC-Ns) is currently restricted. The few methods available to make CC-Ns suffer from long syntheses and poor modularity, hindering the examination of potentially important chemical space. Here we report an approach to CC-Ns which uses an asymmetric Suzuki-Miyaura type reaction as the key C-C bond forming step. After coupling the densely functionalized racemic bicyclic allyl chloride and heterocyclic boronic acids, the trisubstituted cyclopentenyl core is elaborated to RNA analogues via a hydroborylation-homologation-oxidation sequence. We demonstrate that the approach can be used to produce a variety of enantiomerically enriched CC-Ns, including a carbocyclic derivative of Showdomycin.

A Tapered Cuff Tracheal Tube Decreases The Need For Cuff Pressure Adjustment After Surgical Retraction During Anterior Cervical Spine Surgery: A Randomized Controlled, Double-Blind Trial, Shiang-Suo Huang, Ya-Chun Chu

Faculty, Staff and Student Publications

Background: Surgical retraction to expose the vertebrae during anterior cervical spine surgery increases tracheal tube cuff pressure and may worsen postoperative sore throat and dysphonia. This randomized double-blind study investigated the effect of cuff shape on intraoperative cuff pressure and postoperative sore throat and dysphonia.

Methods: Eighty patients were randomized to tracheal intubation with a tapered cuff or a conventional cylindrical high-volume low-pressure cuff (control) during anesthesia. Intraoperative cuff pressures were compared. The primary outcome was the incidence of pressure adjustment needed when the cuff pressure increased to > 25 mm Hg after surgical retraction. The secondary outcome was the incidence …

Use Of Modeling To Inform Decision Making In North Carolina During The Covid-19 Pandemic: A Qualitative Study, Paul Delamater, Mehul D Patel

Faculty, Staff and Student Publications

Background. The COVID-19 pandemic has popularized computer-based decision-support models, which are commonly used to inform decision making amidst complexity. Understanding what organizational decision makers prefer from these models is needed to inform model development during this and future crises. Methods. We recruited and interviewed decision makers from North Carolina across 9 sectors to understand organizational decision-making processes during the first year of the COVID-19 pandemic (N = 44). For this study, we identified and analyzed a subset of responses from interviewees (n = 19) who reported using modeling to inform decision making. We used conventional content analysis to …

Case Report: Novel Pathogenic Variant In Nfix In Two Sisters With Malan Syndrome Due To Germline Mosaicism

Faculty, Staff and Student Publications

Malan syndrome is an autosomal dominant disorder caused by pathogenic variants in NFIX with less than 100 cases reported thus far. NFIX is important for stem cell proliferation, quiescence, and differentiation during development and its protein plays a role in replication, signal transduction, and transcription. As a result of pathogenic variants, symptoms of Malan syndrome include overgrowth, intellectual disability, speech delay, and dysmorphic features. Currently, the recurrence risk for this disorder is indicated at less than 1%, standard for de novo autosomal dominant disorders. Herein, we report an additional set of sisters with the same novel pathogenic variant in NFIX …

Multi-Center, Single-Blind Randomized Controlled Trial Comparing Functional Electrical Stimulation Therapy To Conventional Therapy In Incomplete Tetraplegia, James R Wilson, Lehana Thabane

Faculty, Staff and Student Publications

BACKGROUND: Loss of upper extremity function after tetraplegia results in significant disability. Emerging evidence from pilot studies suggests that functional electrical stimulation (FES) therapy may enhance recovery of upper extremity function after tetraplegia. The aim of this trial was to determine the effectiveness of FES therapy delivered by the Myndmove stimulator in people with tetraplegia.

METHODS: A multi-center

RESULTS: Between June 2019 to August 2021, 51 participants were randomized to FES (

CONCLUSION: Forty sessions of FES therapy delivered by the MyndMove stimulator are as effective as conventional therapy in producing meaningful functional improvements that persist after therapy is completed. …

Stat6 Suppression Prevents Bleomycin-Induced Dermal Fibrosis, Yi-Dong Li, Martin J Citardi, David B Corry, Amber U Luong, John Morgan Knight

Faculty, Staff and Student Publications

Unified airway disease, including concurrent asthma and chronic rhinosinusitis (CRS), is a common, but poorly understood disorder with no curative treatment options. To establish a murine model of chronic unified eosinophilic airway inflammation, mice were challenged with Aspergillus niger, and sinonasal mucosa and lung tissue were evaluated by immunohistochemistry, flow cytometry, and gene expression. Inhalation of A niger conidia resulted in a Th2-biased lung and sinus inflammation that typifies allergic asthma and CRS. Gene network and pathway analysis correlated with human disease with upregulation of not only the JAK-STAT and helper T-cell pathways, but also less expected pathways governing …

Digital Rehabilitation For Hand And Wrist Pain: A Single-Arm Prospective Longitudinal Cohort Study, Jorge Lains, Steven P Cohen, Fernando Dias Correia

Faculty, Staff and Student Publications

Introduction: Wrist and hand represent the third most common body part in work-related injuries, being associated with long-term absenteeism. Telerehabilitation can promote access to treatment, patient adherence, and engagement, while reducing health care-related costs.

Objective: Report the results of a fully remote digital care program (DCP) for wrist and hand pain (WP).

Methods: A single-arm interventional study was conducted on individuals with WP applying for a DCP. Primary outcome was the mean change in the Numerical Pain Rating Scale after 8 weeks (considering a minimum clinically important change of 30%). Secondary outcomes were: disability (Quick Disabilities of the Arm, Shoulder, …

Trending Tubes: A Social Media Analysis Of Tympanostomy Tubes In Children, Luis D Neve, Harold S Pine

Faculty, Staff and Student Publications

OBJECTIVE: To investigate the popular social media platforms Instagram and Facebook for public posts related to tympanostomy tubes in children, to discern attitudes and perceptions surrounding tympanostomy tubes, and to evaluate the content of social media posts related to tympanostomy tubes.

STUDY DESIGN: Qualitative study.

SETTING: Instagram and Facebook social media platforms.

METHODS: Instagram and Facebook were searched for public posts from 2018 and 2019 including the search terms "ear tubes,""ear tube surgery,""tympanostomy," and "myringotomy." Posts were excluded if they were unrelated to pediatric tympanostomy tubes or written in a non-English language. Relevant posts underwent subgroup analysis based on 6 …

Dysregulated Hypothalamic-Pituitary-Adrenal Axis Is Associated With Increased Inflammation And Worse Outcomes After Ischemic Stroke In Diabetic Mice

Faculty, Staff and Student Publications

Diabetic patients have larger infarcts, worse neurological deficits, and higher mortality rate after an ischemic stroke. Evidence shows that in diabetes, the hypothalamic-pituitary-adrenal (HPA) axis was dysregulated and levels of cortisol increased. Based on the role of the HPA axis in immunity, we hypothesized that diabetes-dysregulated stress response exacerbates stroke outcomes via regulation of inflammation. To test this hypothesis, we assessed the regulation of the HPA axis in diabetic mice before and after stroke and determined its relevance in the regulation of post-stroke injury and inflammation. Diabetes was induced in C57BL/6 mice by feeding a high-fat diet and intraperitoneal injection …

Dysphagia Is Associated With Worse Clinical Outcomes In Geriatric Trauma Patients, Michael W Wandling, Lillian S Kao, Thaddeus J Puzio

Faculty, Staff and Student Publications

INTRODUCTION: Dysphagia is associated with increased morbidity, mortality, and resource utilization in hospitalized patients, but studies on outcomes in geriatric trauma patients with dysphagia are limited. We hypothesized that geriatric trauma patients with dysphagia would have worse clinical outcomes compared with those without dysphagia.

METHODS: Patients with and without dysphagia were compared in a single-center retrospective cohort study of trauma patients aged ≥65 years admitted in 2019. The primary outcome was mortality. Secondary outcomes included intensive care unit (ICU) length of stay (LOS), hospital LOS, discharge destination, and unplanned ICU admission. Multivariable regression analyses and Bayesian analyses adjusted for age, …

Occurrence, Toxicity And Adsorptive Removal Of The Chloramphenicol Antibiotic In Water: A Review, Duyen Thi Cam Nguyen

Faculty, Staff and Student Publications

Chloramphenicol is a broad-spectrum bacterial antibiotic used against conjunctivitis, meningitis, plague, cholera, and typhoid fever. As a consequence, chloramphenicol ends up polluting the aquatic environment, wastewater treatment plants, and hospital wastewaters, thus disrupting ecosystems and inducing microbial resistance. Here, we review the occurrence, toxicity, and removal of chloramphenicol with emphasis on adsorption techniques. We present the adsorption performance of adsorbents such as biochar, activated carbon, porous carbon, metal-organic framework, composites, zeolites, minerals, molecularly imprinted polymers, and multi-walled carbon nanotubes. The effect of dose, pH, temperature, initial concentration, and contact time is discussed. Adsorption is controlled by π-π interactions, donor-acceptor interactions, …

Pain Management And Telemedicine: A Look At The Covid Experience And Beyond

Faculty, Staff and Student Publications

COVID-19 caused a drastic change in clinical medicine around the globe. In the United States, telemedicine was rapidly adopted on a wide scale to minimize direct patient interaction and to reduce the spread of the COVID-19 virus. Telemedicine also went hand in hand with the rapid movement of working remotely. This has provided several challenges to chronic pain management clinics along with other subspecialties. Telemedicine has also opened opportunities for providing valuable care for patients with significant barriers to healthcare professionals. Given the benefits and downfalls of telemedicine, it is ultimately up to the provider who has an established patient-physician …

Formation, Antimicrobial Activity, And Biomedical Performance Of Plant-Based Nanoparticles: A Review, Duyen Thi Cam Nguyen

Faculty, Staff and Student Publications

Because many engineered nanoparticles are toxic, there is a need for methods to fabricate safe nanoparticles such as plant-based nanoparticles. Indeed, plant extracts contain flavonoids, amino acids, proteins, polysaccharides, enzymes, polyphenols, steroids, and reducing sugars that facilitate the reduction, formation, and stabilization of nanoparticles. Moreover, synthesizing nanoparticles from plant extracts is fast, safe, and cost-effective because it does not consume much energy, and non-toxic derivatives are generated. These nanoparticles have diverse and unique properties of interest for applications in many fields. Here, we review the synthesis of metal/metal oxide nanoparticles with plant extracts. These nanoparticles display antibacterial, antifungal, anticancer, and …

Dat3m: A Data Tracker For Multi-Faceted Management Of Multi-Site Clinical Research Data Submission, Curation, Master Inventorying, And Sharing, Guo-Qiang Zhang

Faculty, Staff and Student Publications

Managing research data is an important and challenging aspect of clinical studies, especially for multi-site collaboratives. To address this challenge, we designed, developed and deployed a multi-faceted, multi-level interactive data tracker (DaT3M) for multi-site clinical research data submission, curation, master inventorying, and sharing. Components of DaT3M include data overview, data portal, data status panel, data query engine, and data downloader. DaT3M managed clinical research data for the Center for SUDEP Research (CSR). The CSR instance of DaT3M includes 2,743 subjects from seven data contributing institutions, 7 data modalities and 10,678 data components: 3,398 Epilepsy Monitoring Unit reports, 3,440 electroencephalography recordings, …

Temporal Cohort Logic

Faculty, Staff and Student Publications

We introduce a new logic, called Temporal Cohort Logic (TCL), for cohort specification and discovery in clinical and population health research. TCL is created to fill a conceptual gap in formalizing temporal reasoning in biomedicine, in a similar role that temporal logics play for computer science and its applications. We provide formal syntax and semantics for TCL and illustrate the various logical constructs using examples related to human health. Relationships and distinctions with existing temporal logical frameworks are discussed. Applications in electronic health record (EHR) and in neurophysiological data resource are provided. Our approach differs from existing temporal logics, in …

Causal Inference Of Genetic Variants And Genes In Amyotrophic Lateral Sclerosis, Yulin Dai, Yin-Ying Wang, Peilin Jia, Fan Liu

Faculty, Staff and Student Publications

Amyotrophic lateral sclerosis (ALS) is a fatal progressive multisystem disorder with limited therapeutic options. Although genome-wide association studies (GWASs) have revealed multiple ALS susceptibility loci, the exact identities of causal variants, genes, cell types, tissues, and their functional roles in the development of ALS remain largely unknown. Here, we reported a comprehensive post-GWAS analysis of the recent large ALS GWAS (n = 80,610), including functional mapping and annotation (FUMA), transcriptome-wide association study (TWAS), colocalization (COLOC), and summary data-based Mendelian randomization analyses (SMR) in extensive multi-omics datasets. Gene property analysis highlighted inhibitory neuron 6, oligodendrocytes, and GABAergic neurons (Gad1/Gad2) as …

An Ensemble-Based Deep Convolutional Neural Network For Computer-Aided Polyps Identification From Colonoscopy, Kunio Kasugai, Zhongming Zhao

Faculty, Staff and Student Publications

Colorectal cancer (CRC) is the third leading cause of cancer death globally. Early detection and removal of precancerous polyps can significantly reduce the chance of CRC patient death. Currently, the polyp detection rate mainly depends on the skill and expertise of gastroenterologists. Over time, unidentified polyps can develop into cancer. Machine learning has recently emerged as a powerful method in assisting clinical diagnosis. Several classification models have been proposed to identify polyps, but their performance has not been comparable to an expert endoscopist yet. Here, we propose a multiple classifier consultation strategy to create an effective and powerful classifier for …

A Deep Learning-Based Framework For Supporting Clinical Diagnosis Of Glioblastoma Subtypes, Zhongming Zhao

Faculty, Staff and Student Publications

Understanding molecular features that facilitate aggressive phenotypes in glioblastoma multiforme (GBM) remains a major clinical challenge. Accurate diagnosis of GBM subtypes, namely classical, proneural, and mesenchymal, and identification of specific molecular features are crucial for clinicians for systematic treatment. We develop a biologically interpretable and highly efficient deep learning framework based on a convolutional neural network for subtype identification. The classifiers were generated from high-throughput data of different molecular levels, i.e., transcriptome and methylome. Furthermore, an integrated subsystem of transcriptome and methylome data was also used to build the biologically relevant model. Our results show that deep learning model outperforms …

Crucial Roles Of Microrna-16-5p And Microrna-27b-3p In Ameloblast Differentiation Through Regulation Of Genes Associated With Amelogenesis Imperfecta, Naina Singh, Thanh Le, Zhongming Zhao, Junichi Iwata

Faculty, Staff and Student Publications

Amelogenesis imperfecta is a congenital disorder within a heterogeneous group of conditions characterized by enamel hypoplasia. Patients suffer from early tooth loss, social embarrassment, eating difficulties, and pain due to an abnormally thin, soft, fragile, and discolored enamel with poor aesthetics and functionality. The etiology of amelogenesis imperfecta is complicated by genetic interactions. To identify mouse amelogenesis imperfecta-related genes (mAIGenes) and their respective phenotypes, we conducted a systematic literature review and database search and found and curated 70 mAIGenes across all of the databases. Our pathway enrichment analysis indicated that these genes were enriched in tooth development-associated pathways, forming four …

Dimensionality Reduction And Louvain Agglomerative Hierarchical Clustering For Cluster-Specified Frequent Biomarker Discovery In Single-Cell Sequencing Data

Faculty, Staff and Student Publications

The major interest domains of single-cell RNA sequential analysis are identification of existing and novel types of cells, depiction of cells, cell fate prediction, classification of several types of tumor, and investigation of heterogeneity in different cells. Single-cell clustering plays an important role to solve the aforementioned questions of interest. Cluster identification in high dimensional single-cell sequencing data faces some challenges due to its nature. Dimensionality reduction models can solve the problem. Here, we introduce a potential cluster specified frequent biomarkers discovery framework using dimensionality reduction and hierarchical agglomerative clustering Louvain for single-cell RNA sequencing data analysis. First, we pre-filtered …

Explanation-Driven Deep Learning Model For Prediction Of Brain Tumour Status Using Mri Image Data, Zhongming Zhao

Faculty, Staff and Student Publications

Cancer research has seen explosive development exploring deep learning (DL) techniques for analysing magnetic resonance imaging (MRI) images for predicting brain tumours. We have observed a substantial gap in explanation, interpretability, and high accuracy for DL models. Consequently, we propose an explanation-driven DL model by utilising a convolutional neural network (CNN), local interpretable model-agnostic explanation (LIME), and Shapley additive explanation (SHAP) for the prediction of discrete subtypes of brain tumours (meningioma, glioma, and pituitary) using an MRI image dataset. Unlike previous models, our model used a dual-input CNN approach to prevail over the classification challenge with images of inferior quality …

Breast Cancer Detection: Shallow Convolutional Neural Network Against Deep Convolutional Neural Networks Based Approach, Kangkana Bora, Zhongming Zhao

Faculty, Staff and Student Publications

Introduction: Of all the cancers that afflict women, breast cancer (BC) has the second-highest mortality rate, and it is also believed to be the primary cause of the high death rate. Breast cancer is the most common cancer that affects women globally. There are two types of breast tumors: benign (less harmful and unlikely to become breast cancer) and malignant (which are very dangerous and might result in aberrant cells that could result in cancer).

Methods: To find breast abnormalities like masses and micro-calcifications, competent and educated radiologists often examine mammographic images. This study focuses on computer-aided diagnosis to help …