Anatomy Commons^™

Metabolic Reprogramming Following Mitochondrial Transfer Between Idh2-Mutant Chondrosarcoma Cells And A Normal B-Cell Line, Caleb Wyckoff, Christopher Osgood, Ellen Jing, Michael Stacey

Bioelectrics Publications

Background/Objectives: Chondrosarcoma, glioblastoma, acute myeloid leukemia, chronic lymphocytic leukemia, and cholangiocarcinoma cancers all contain mutations in the gene isocitrate dehydrogenase 2 (IDH2). The mutant IDH2 enzyme metabolizes alpha-ketoglutarate (αKG) into the potent oncometabolite D-2-hydroxyglutarate (D2HG) in the mitochondria of these cancers, leading to altered cellular metabolism. Emerging evidence suggests that mitochondrial transfer between cancer and recipient cells represents an important form of intercellular communication that may influence cellular metabolism. The presence of intercellular TNTs between IDH2-mutant chondrosarcoma cells motivated an investigation into mitochondria-associated physiological changes occurring during an intercellular exchange with immune cells. A mitochondrial transfer is a two-way …

Establishment And Histopathological Characterization Of A Kyse-30 Subcutaneous Xenograft Model Of Esophageal Squamous Cell Carcinoma, Pavel A. Solopov, Alayna Enos, Mantas Silkunas, Giedre Silkuniene, Eleni Zivla, Andrei G. Pakhomov, Olga N. Pakhomova

Bioelectrics Publications

Background/Objectives: Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy with poor prognosis and limited treatment options, highlighting the need for reliable preclinical models for translational research. Although xenograft models are widely used in cancer biology, systematic characterization of subcutaneous ESCC models under defined implantation conditions remains limited. The objective of this study was to systematically compare implantation conditions and define histopathological and growth-related parameters that enable reproducible tumor establishment while maintaining a practical experimental window for therapeutic studies. Methods: We established and characterized a subcutaneous ESCC xenograft model using human ESCC cell line KYSE-30 implanted into immunodeficient J:NU mice. …

Influence Of Motion Artifacts On Instantaneous Frequency Based Heart Rate Variability Of Arterial Pulse Signals Measured By A Tactile Sensor: An Analytical Study, Mamun Hasan, Zhili Hao

Mechanical & Aerospace Engineering Faculty Publications

Objective: Heart rate variability (HRV), quantified via the instantaneous frequency (IF) of arterial pulse signals, is a key indicator of cardiovascular (CV) regulation. This study presents a theoretical and experimental investigation of how motion artifacts (MA) influence IF-and thus HRVmeasured with a tactile sensor, emphasizing underlying mechanisms rather than population-level validation. Approach: Building on a previously developed single-degree-of-freedom (SDOF) model of the tissue-contact-sensor (TCS) stack between the sensor and the artery, MA is represented as low-frequency baseline drift and time-varying system parameters (TVSP) of the TCS stack. Analytical expressions quantify the effect of MA on the IF of each harmonic …

Z Variant Heterozygosity In Alpha-1 Antitrypsin Deficiency: Disease Risk And Treatment Implications, Craig P. Hersh, Jeffrey H. Teckman, Pavel Strnad, Aaron Hakim, Tomás P. Carroll, Ian P. Hall, Auyon J. Ghosh, Igor Barjaktarevic, Noel G. Mcelvaney, Joseph E. Kaserman, David A. Lomas, Charlie Strange, M Bradley Drummond, Stephen I. Rennard, Kathi E. Hanna, Virginia C. Clark, Monica P. Goldklang, Peg Iverson, Andrew A. Wilson

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Individuals heterozygous for alpha-1 antitrypsin deficiency (AATD) have one copy of the normal "M" allele and one copy of an abnormal allele ("Z", "S", or another variant) in the SERPINA1 gene. Historically, evidence has been lacking to support the concept that heterozygotes are at increased risk for liver and/or lung complications compared to individuals homozygous for the M allele. However, growing evidence suggests that inheritance of a single Z allele increases the risk of disease in some individuals. The Alpha-1 Foundation convened a workshop on October 27, 2023, in Bethesda, Maryland that included stakeholders from the research, pharmaceutical, and …

The Relationship Between Phone Usage, Activity Participation, And Hand Strength, Debra Gibbs, Will Best, Raegan Adams, Amanda Finke, Rachel Pierce, Salem Swallows, Alisha Yoo

SPARK Symposium Presentations

Smartphone use among university students in the United States is steadily increasing. Longer duration of smartphone use has been associated with increased risk of smartphone addiction, reduced musculoskeletal strength, and engagement in meaningful activities. While prior research has examined these variables separately, limited evidence exists on the associations between smartphone use, hand grip and pinch strength, and extracurricular and leisure activities among U.S. university students. To address this gap, a correlational study was conducted using the Spearman rank correlation to analyze the relationship between phone use, activity participation, and hand strength. A Qualtrics survey including demographic information, phone usage, and …

Radial And Carotid Arterial Pulse Signals For Assessing Cardiovascular Function At Rest And During Post-Exercise Recovery In A Heart Transplant Patient: A Case Study, Md Mahfuzur Rahman, Mamun Hasan, Jennifer F. May, John M. Herre, Leryn Reynolds, Zhili Hao

Mechanical & Aerospace Engineering Faculty Publications

Aim: This study investigates the feasibility of using radial and carotid arterial pulse signals to assess cardiovascular (CV) function at rest and during post-exercise recovery in a heart transplant (HTx) patient. Method: Two micro-fabricated tactile sensors were used to simultaneously acquire arterial pulse signals at the radial artery (RA) and carotid artery (CA). Measurements were taken at rest and at multiple time points post-exercise on three subjects: an HTx patient, a percutaneous coronary intervention (PCI; coronary stent) patient and a healthy control. An SDOF-TF-based time-frequency analysis algorithm was applied to extract a comprehensive set of CV parameters, including heart rate …

Radial And Carotid Arterial Pulse Signals For Assessing Cardiovascular Function At Rest And During Post-Exercise Recovery In A Heart Transplant Patient: A Case Study, Md Mahfuzur Rahman, Mamun Hasan, Jennifer F. May, John M. Herre, Leryn Reynolds, Zhili Hao

Mechanical & Aerospace Engineering Faculty Publications

Aim: This study investigates the feasibility of using radial and carotid arterial pulse signals to assess cardiovascular (CV) function at rest and during post-exercise recovery in a heart transplant (HTx) patient. Method: Two micro-fabricated tactile sensors were used to simultaneously acquire arterial pulse signals at the radial artery (RA) and carotid artery (CA). Measurements were taken at rest and at multiple time points post-exercise on three subjects: an HTx patient, a percutaneous coronary intervention (PCI; coronary stent) patient and a healthy control. An SDOF-TF-based time-frequency analysis algorithm was applied to extract a comprehensive set of CV parameters, including heart rate …

What Does The Quality Of Life For Congenital Heart Defect Patients Look Like Across The Lifespan?, Kaylee F. Maynor

Undergraduate Honors Theses

Throughout history, birth defects have left a mark on patients and families across the world. From an infant's first few breaths to an elderly person's last breath, congenital heart birth defects play a major role in that person's life. There are many different types of birth defects that effect the heart. Each defect is unique and has different outcomes on the body. Some congenital heart diseases have multiple defects causing more than one complication. The treatment options for many of the common congenital heart birth defects have come a long way throughout decades of research. By diving into what heart …

Dose-Dependent Developmental Toxicity Of Cisplatin In Zebrafish Embryos, Reagan D. Sellers, Katherine T. Doucet, Jinhee Park, Andrea Florian

SPARK Symposium Presentations

Cisplatin is a widely used chemotherapy drug for treating various types of cancer. Although cisplatin is effective in killing cancer, it can also cause toxic side effects in normal tissues. Because cisplatin can cross the placental barrier, its use during pregnancy is generally avoided, particularly during early embryonic stages of fetal development. Exposure to cytotoxic drugs during embryogenesis may lead to developmental abnormalities, birth defects, or pregnancy complications. Understanding how cisplatin affects early development is therefore important.          
       Zebrafish (Danio rerio) are an established model for studying developmental toxicity due to their rapid external development, transparent embryos, and genetic similarity to …

Temporal Evolution Of Brain Inflammation In The Bilateral Common Carotid Artery Stenosis Model Of Chronic Cerebral Hypoperfusion, Makayla F. Cox, Jill M. Roberts, Ryan K. Shahidehpour, David L. Dornbos Iii, Adam D. Bachstetter

Neuroscience Faculty Publications

Chronic cerebral hypoperfusion is a major contributor to vascular cognitive impairment and dementia, primarily through its disruption of white matter integrity and promotion of neuroinflammatory cascades. The bilateral common carotid artery stenosis (BCAS) model has emerged as the predominant experimental approach for studying the effects of chronic cerebral hypoperfusion, particularly in aging-relevant contexts. This review synthesizes current knowledge of inflammatory responses in the BCAS model, with an emphasis on their temporal progression and functional consequences. We begin by outlining the clinical burden of hypoperfusion, the rationale for BCAS, and the hemodynamic phases it produces. We then examine early neurovascular unit …

Dim Light At Night Impacts Circadian Rhythms And Alzheimer’S Disease-Like Neuroinf Lammation And Neuropathology In Humanized App Saa Knock-In Mice, Marilyn J. Duncan, Margaret R. Hawkins, Leke Bytyqi, Haleigh R. Whitlock, Savannah M. Shepard, Makayla F. Cox, Esther G. Drinkard, Teresa Macheda, Kelly N. Roberts, Katharina Kohler, Mary-Claire Schmidt, Carrie E. Johnson, Sridhar Sunderam, Bruce F. O'Hara, Michael Paul Murphy, Adam D. Bachstetter

Neuroscience Faculty Publications

Artificial light at night (light pollution) is widespread but understudied in the context of Alzheimer’s disease (AD). Sleep and circadian disruption have been linked to amyloid-β (Aβ) accumulation and neuroinflammation, but whether dim light at night (dLAN) modifies these processes remains unclear. We tested whether chronic dLAN exposure (8 lux during the dark phase, 8 weeks) alters circadian rhythms, amyloid pathology, and neuroinflammation in 12–13 month-old humanized APP knock-in (KI) mice. hAPP^SAA KI mice, which develop plaques, were compared with hAPP^WT KI controls carrying only a humanized APP sequence. dLAN reduced circadian rhythm amplitude and stability while increasing …

Atrial Fibrillation Detection From At-Rest Ppg Signals Using An Sdof-Tf Method, Mamun Hasan, Zhili Hao

Mechanical & Aerospace Engineering Faculty Publications

At-rest PPG signals have been explored for detecting atrial fibrillation (AF), yet current signal-processing techniques do not achieve perfect accuracy even under low-motion artifact (MA) conditions. This study evaluates the effectiveness of a single-degree-of-freedom time–frequency (SDOF-TF) method in analyzing at-rest PPG signals for AF detection. The method leverages the influence of MA on the instant parameters of each harmonic, which is identified using an SDOF model in which the tissue–contact–sensor (TCS) stack is treated as an SDOF system. In this model, MA induces baseline drift and time-varying system parameters. The SDOF-TF method enables the quantification and removal of MA and …

Self-Assembly Of Anti-Inflammatory Peptide Amphiphiles For Mucosal Health, Maria José Gómara, Ignacio Pérez-Pomeda, Ramon Pons, Paul Ziprin, Carolina Herrera, Isabel Haro

CONRAD Publications

Broad spectrum anti-inflammatory peptide amphiphiles (AIF-PAs) have been developed as an innovative strategy for the treatment of chronic mucosal inflammation and the prevention of HIV transmission. Novel lipopeptides based on two linear sequences of anti-inflammatory peptides were obtained by solid-phase peptide chemistry. In a pilot study, ex vivo exposure of colorectal tissue explants from Crohn's disease patients to AIF-PAs induced a downregulation of the proinflammatory profile. Furthermore, the HIV inhibitory potency of AIF-PAs was evaluated ex vivo in colorectal tissue explants, obtaining sub-micromolar IC₅₀ values. Characterization of AIF-PAs self-aggregation in aqueous solution revealed that the net charge distribution within the …

Innovative Endovascular Stapling Technique Using The Aortoseal Device In Challenging Infrarenal Aortic Neck, Emidio Germano, Animesh Rathore, David J. Dexter

Department Surgery Faculty Publications

We report the use of the Aortoseal Endostapling system by Endoron in a 63-year-old man with infrarenal abdominal aortic aneurysm with high-risk neck features. Endovascular abdominal aneurysm repair was performed using a Medtronic Endurant IIs endograft with an adjunctive Aortoseal system as part of an international feasibility trial. The procedure was technically successful, with no endoleaks on completion angiography. Follow-up computed tomography angiography at 1 month confirmed a well-deployed AortoSeal system and complete aneurysm exclusion. This case highlights this innovative device and the technical considerations to enhance endograft proximal fixation with the potential to improve long-term outcomes in endovascular aneurysm …

Bayesian Reanalysis Of Early Remdesivir For The Treatment Of Covid-19 In Outpatients With High Risk Of Progression To Severe Disease, Mazin Abdelghany, Fang Yu, Stephen I. Rennard, Yeongjin Gwon

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Though Bayesian methods are flexible, intuitive, and readily incorporated into clinical decision-making, with particular utility when prior information is available, they remain underutilized in the analysis of clinical trials.

METHODS: In PINETREE, a Phase 3 randomized controlled trial (RCT) of remdesivir (RDV) for the treatment of outpatients with COVID-19 at high risk of severe disease, the primary outcome of COVID-19-related hospitalization or all-cause death was reanalyzed using a range of reference and data-driven priors. Posterior probability distributions were used to calculate the probability that the estimated hazard ratio (HR) was below a range of clinically meaningful specified thresholds and …

Bringing Awareness And Education To Rural Areas About The Role Occupational Therapy (Ot) Has In Infant Care, Makenzi Richwald

Occupational Therapy Doctorate Capstone Posters

This capstone project focused on education and advocacy. The aim of my capstone project was to provide education to parents of eastern Kentucky (KY) about what Occupational Therapy (OT) can address with infants aged 0-18 months. I saw a gap in knowledge in the eastern KY community about what OT could do for infants and wanted to address this. Through my research, consultation with my mentors, and collaboration with the occupational therapists at my site (BPT) I discerned 14 areas of development and/or common reasons of needed referral for OT services by this age group. These educational materials aimed to …

Peculiarities Of Phosphatidylserine Externalization By Nano- And Microsecond Electric Pulses, Mantas Silkunas, Alayna Enos, Iurii Semenov, Giedre Silkuniene, Eleni Zivla, Olga N. Pakhomova, Andrei G. Pakhomov

Bioelectrics Publications

Phosphatidylserine (PS) externalization is a hallmark of apoptosis but can also be triggered within seconds by pulsed electric fields (PEFs). Whether PS reaches the outer leaflet by lateral migration through electropores or indirectly through Ca²⁺-dependent signaling and scramblase activation remains debated. We used total internal reflection fluorescence (TIRF) microscopy with Annexin V-Alexa Fluor 568 and/or bovine lactadherin-FITC to resolve PS externalization in HEK293 cells placed on an indium tin oxide (ITO) transparent electrode. PEF exposures produced discrete PS-positive puncta ("freckles") within ~ 10 s after a 20-µs pulse (1.2-2.5 kV/cm) or with a ~ 1-min delay after a …

Non-Invasive Detection Of Intracranial Pressure, Andrei V. Nesterenko

Honors Undergraduate Theses

Intracranial pressure is a critical metric used when managing tumors, strokes, TBIs, hydrocephalus, and other operative conditions. Traditional methods for continuous ICP monitoring, intraparenchymal catheters, epidural transducers etc., are invasive and carry a high risk of infection. Previous attempts to create accurate, easy to use, and non-invasive ICP monitoring techniques have been unsuccessful. In this study, we investigated the utility of supraorbital and posterior auricular photoplethysmography to monitor changes in ICP during orthostatic tilt and hyperventilation, which increase and decrease ICP respectively.

Through a continuous 5-minute recording on a tilt-table we characterized SOA and PAA waveforms in 12 participants (ages …

Indirect Treatment Comparison Of Tezepelumab Versus Other Biologics In Severe Chronic Rhinosinusitis With Nasal Polyps: A Systematic Literature Review And Network Meta-Analysis, Joseph K. Han, Joaquim Mullol, Claire Hopkins, Oliver Pfaar, Martin Desrosiers, Jason Steenkamp, Danny Gibson, Santiago Zuluaga Sanchez, Andrew Foster, Christopher S. Ambrose

Department of Otolaryngology (ENT) Faculty Publications

Introduction

This study compared the efficacy of tezepelumab with other approved biologics and endoscopic sinus surgery (ESS) using indirect treatment comparisons (ITCs) in adults with severe, uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP).

Methods

Randomized controlled trials (RCTs) identified via a systematic literature review (SLR) were synthesized in a network meta-analysis (NMA). Outcomes included change from baseline in nasal polyp score (NPS), nasal congestion/obstruction score (NCS/NOS), difficulty with sense of smell (DSS), Sino-Nasal Outcome Test-22 (SNOT-22) score, Lund Mackay score (LMS), time to nasal polyposis (NP) surgery decision, proportions requiring NP surgery or systemic corticosteroids (SCS), time to SCS use, …

Severity And Duration-Dependent Aortic Stiffening In A Rabbit Coarctation Model Identifies Constitutive Material Parameters As Promising Regional Biomarkers For Hypertension Progression, Arash Ghorbannia, Jamasp Azarnoosh, John F. Ladisa Jr.

VMASC Publications

Coarctation of the aorta (CoA) alters hemodynamics and drives regional remodeling, yet the influence of severity and duration on constitutive properties is undefined. We quantified mechanical responses from CoA to identify constitutive parameters capturing stiffening across clinical severities and durations. Mild (≤ 12 mmHg), intermediate (13–20 mmHg), and severe (> 20 mmHg) CoA was created in rabbits for short, long, and prolonged durations (~ 1, 3, or 22 weeks, respectively). Stress–stretch curves from proximal and distal regions were fit with multiple constitutive models (Linear Elastic, Neo-Hookean, Yeoh, Ogden, Mooney–Rivlin, Holzapfel). Model performance was evaluated by normalized RMSE and R², with …