Analytical, Diagnostic and Therapeutic Techniques and Equipment Commons^™

Implementation Of A Triage System For The Residents At A Residential Facility To Improve Triage Assessment Skills Of The Staff As Well As Improve The Level And Timeliness Of Care, Andrew J. Choi Rn, Neha Gopal Rn, Andres N. Padilla Rn, Dana Son

Master's Projects and Capstones

Triage is an integral part of the clinical process which involves assessing patients and determining their level of care in order to get them appropriate, timely treatment. Several countries utilize a standardized triage system with established criteria to aid staff in their decision-making during assessments (Peta et al., 2023). The Nursing and Residential Triage (NaRT) tool, from the Manchester Triage System (MTS), was shown to enhance staff clinical assessment skills and help avoid inappropriate ED transfers during a study among older adults in a residential facility (Markey et al., 2024). For this project, the main issue identified at the residential …

Updates In Contemporary Management Of Singleton Pregnancies Complicated By A Short Cervix, Moti Gulersen, Vincenzo Berghella, Eran Bornstein

Department of Obstetrics and Gynecology Faculty Papers

Singleton pregnancies complicated by a short cervical length (≤25 mm) are at significantly increased risk for spontaneous preterm birth. Several treatment strategies aimed at reducing this risk and improving perinatal outcomes have been evaluated, including vaginal progesterone, cervical cerclage, and cervical pessary. This review summarizes the latest evidence regarding the efficacy of these interventions. Vaginal progesterone and/or cervical cerclage have been identified as proven evidence-based practices for preterm birth prevention and improve neonatal outcomes. Vaginal progesterone reduces the risk of preterm birth < 35 weeks by 27% (relative risk 0.73, 95% confidence interval 0.58-0.90). Cervical cerclage has been shown to reduce the risk of preterm birth < 35 weeks by 30% (relative risk 0.70, 95% confidence interval 0.55-0.89) in patients with a short cervical length and prior preterm birth. In contrast, recent data suggest that cervical pessary should no longer be considered a management option for these patients. A continued focus on individualized, evidence-based approaches remains essential to optimizing outcomes in this high-risk population.

Comparison Of 10 Mv Flattening Filter And Flattening Filter-Free Volumetric Modulated Art Therapy (Vmat) Radiation Plans In Partial Breast Irradiation: Evaluating Dose Sparing To The Left Anterior Descending Coronary Artery, Jillian Beliew

Masters Projects

Importance Minimizing radiation dose to the heart, particularly the left anterior descending coronary artery (LAD), is essential in left-sided partial breast irradiation (PBI). Flattening filter-free (FFF) beam configurations may improve organ-at-risk (OAR) sparing and treatment efficiency.

Objective To compare dosimetric outcomes between 10 MV flattening filter (FF) and 10 MV flattening filter-free (FFF) VMAT plans in patients receiving accelerated partial breast irradiation (APBI), focusing on LAD dose sparing.

Design, Setting, and Participants This retrospective dosimetric study included 10 patients with early-stage, left-sided breast cancer. Each patient had two VMAT plans generated using identical geometry and constraints in Eclipse v16.01: one …

Nuak Kinases: Signaling Mechanisms And Therapeutic Applications, Nicole M. Cullen, Peter Rosston, Bakhtawar Tufail, Anne E. D'Armond, Ayushi Patel, Dara H. Khosravi, Bridgette M. Collins-Burow, Van T. Hoang, Elizabeth C. Martin, David H. Drewry, Matthew E. Burow, Suresh K. Alahari

School of Medicine Faculty Publications

The novel (nua) kinases 1 and 2 are two of 12 AMP-activated protein–related kinases whose signaling pathways are involved in cancer progression, as well as neurologic, fibrotic, and inflammatory diseases. Currently, there are 80 Food and Drug Administration-approved kinase inhibitors which target roughly 24 of the 500+ known human kinases, leaving most kinases underexplored, including NUAK1 and NUAK2. Thus, there is a critical need for selective inhibition of NUAK1 and NUAK2 signaling. Here, we review the protein structure, known upstream regulators and downstream targets, and expression profiles of NUAK1 and NUAK2 in cancerous compared to noncancerous tissue. We also delineate …

Exploring Hepatic Stellate Cell-Driven Fibrosis: Therapeutic Advances And Future Perspectives, Alka Singh, Ansab Akhtar, Prashant Shukla

School of Medicine Faculty Publications

BACKGROUND AND PURPOSE: Liver fibrosis, a progressive liver disease arising from viral or metabolic causes, poses a major global health challenge due to its potential progression to cirrhosis and hepatocellular carcinoma. Due to the complex aetiology and epidemiology of liver fibrosis, most therapies fail in the clinic, and very few drugs have been approved by the US FDA. APPROACH: This review highlights the pathophysiological features of liver fibrosis, with a focus on novel targets in hepatic stellate cells (HSCs), key players in the fibrogenesis process, to develop successful therapeutic approaches using both pharmacological agents and active targeting strategies. The review …

Case Report: Sarcina Ventriculi, A Masquerade Of Motility, Katherine Westbrook Cates, Catherine Hudson

School of Medicine Faculty Publications

Sarcina ventriculi is a rare bacterium that has the potential to cause severe disease in the gastric mucosa. According to our search, there are less than 100 prior published case reports. This case discusses a 69-year-old man who presented to the hospital with severe gastric distention noted on CT of the abdomen with intractable nausea and emesis, for which endoscopy was performed and ruled out gastric outlet obstruction, with biopsies resulting as S. ventriculi. This bacterium has previously been reported to cause gastric dysmotility, as well as severe side effects including gastric perforation.

Breast Cancer Survival Rates And Determinants In Ethiopia: A Systematic Review And Meta-Analysis Of Longitudinal Studies, Abenezer M. Tafese, Meseker T. Fentie, Beminate L. Seifu, Angwach A. Asnake, Bikiltu D. Dirbaba, Abdisa G. Jara, Elsabeth Tizazu Asare, Brandon George

College of Population Health Faculty Papers

BACKGROUND: Breast cancer is the most common cancer and the leading cause of cancer mortality among women in Ethiopia, accounting for 32% of new cancer cases and 17.6% of cancer deaths. Despite its growing burden, comprehensive data on survival rates and contributing factors remain limited. This systematic review and meta-analysis aimed to synthesize existing data on breast cancer survival in Ethiopia and identify key determinants influencing outcomes.

METHODS: A comprehensive systematic search was conducted in PubMed, Web of Science, Scopus, Embase, and CINAHL to identify studies on breast cancer survival in Ethiopia published between January 2014 and August 2024. Eligible …

Comparative Outcomes Of Coil Embolization And Surgical Clipping In Elderly Patients With Subarachnoid Hemorrhage: A Systematic Review And Meta-Analysis, Yohanna Idsabella Rossi, Gabriel Bolner, Jonathan Costa Dall'acqua, Fabiana Dolovitsch De Oliveira, Lucas V. Zacaria, Taís L. Denicol, Michel Frudit, Natália Vasconcellos De Oliveira Souza

Department of Neurology Faculty Papers

BACKGROUND AND OBJECTIVES: Elderly patients with subarachnoid hemorrhage (SAH) face a disproportionately high burden of morbidity and mortality. While endovascular coiling is often favored in this population, direct comparisons with surgical clipping are limited. We conducted a meta-analysis to compare outcomes of clipping versus coiling in SAH patients aged ≥ 60 years.

METHODS: A systematic search of PubMed, Embase, and Cochrane databases identified studies comparing the two treatments in this age group. The primary outcome was a composite of unfavorable outcomes (modified Rankin Scale [mRS] > 2 and mortality). Secondary outcomes included mortality, favorable outcome (mRS 0-2), rebleeding, and hospital length …

The Effect Of Hcv On Methadone Dose During Pregnancy, Sarah Boudova, Neel S. Iyer, Danielle M. Tholey, Jonathan M. Fenkel, Rupsa C. Boelig

Department of Obstetrics and Gynecology Faculty Papers

Pregnancy is a time of high patient motivation to initiate treatment for opioid use disorder (OUD). Hepatic drug metabolism can be altered by pregnancy and hepatitis C virus (HCV) infection. We aimed to examine the impact of HCV during pregnancy on methadone dosing. Retrospective chart review of all pregnant patients with OUD admitted for initiation of methadone from 1/2020-6/2022. Associations were examined using Student's T-tests, chi-squared tests, Fisher's exact tests and univariate and multivariate linear regression. We identified 191 pregnancies initiated on methadone, of which 188 were screened for HCV. 111 (59.0%) were HCV Antibody (Ab)+, of whom 108 were …

Evaluation Of The User Experience For A Point Of Care Molecular Test For Causes Of Vaginitis, Barbara Van Der Pol, Rebecca Lillis, Irving Nachamkin, Stephen Young, La Shonda Crane, Jacqueline Brown, R. Lamar Parker, Alice Weissfeld, Xiaohong Liu, Christina Huang, Aarthi Raman

School of Medicine Faculty Publications

Background: Vaginitis is a major cause of healthcare visits in the US, costing over $1.2 billion annually. Point-of-care (POC) nucleic acid amplification tests (NAATs) could improve accuracy of diagnosis and treatment during initial visit for vaginitis compared to send-out NAATs. Methods: A secondary analysis of data was collected from test operators at POC testing sites where the Xpert Xpress Multiplex Vaginal Panel test (“MVP test”) was performed. Users completed a survey assessing their experience with the instrument system and the PCR-based MVP test. Results: The MVP test demonstrated consistent performance, measured by positive and negative percent agreement, across all user …

Quantile Index Predictors Using R Package Hyper.Gam, Tingting Zhan, Misung Yi, Inna Chervoneva

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

MOTIVATION: Evaluation of single-cell protein expression from immunohistochemistry images is used increasingly in biomedical research. Many proteins are used solely for phenotyping cells in the tumor microenvironment. Other proteins with meaningfully quantitative expression levels provide so-called functional protein biomarkers. There is still a limited number of methods and software tools available for utilizing the entire distributions of single-cell expression levels.

RESULTS: We present the R package hyper.gam, providing a supervised learning framework for deriving biomarkers based on single-cell distribution quantiles. The single-cell data are first converted into sample quantile functions, which are then used as predictors in scalar-on-function regression models …

Efficacy Of Infliximab Versus Vedolizumab In The Management Of Immune Checkpoint Inhibitor-Induced Colitis: A Systematic Review And Meta-Analysis., Shreya Shambhavi, Harmanjeet Singh, Ganesh Ramaprasad, Murod Khikmatov, Varun Vankeshwaram, Kumar Ashish, Carlos Valladares, Tanushree Bhatt, Seth D Cohen

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Immune checkpoint inhibitors (ICIs) can cause severe gastrointestinal immune-related adverse events (irAEs), often leading to treatment interruption and increased morbidity. Immune-mediated colitis (IMC) ranges from mild diarrhea to life-threatening colitis, sometimes requiring urgent intervention. While corticosteroids are the first-line treatment, selective immunosuppressive therapy (SIT) with either infliximab or vedolizumab is used for steroid-refractory or dependent cases. However, standardized practices are lacking, and treatment decisions are largely left to provider discretion. This study compares infliximab and vedolizumab for IMC, focusing on remission rates, recurrence, SIT dosing, and systemic steroid exposure duration.

METHODS: We identified six retrospective cohort studies that compared …

Hardware And Software Design For A Portable Surgical Training Simulator, Victoria Nelson

Department of Mechanical and Materials Engineering: Dissertations, Theses, and Student Research

More than 51 million surgeries are performed on patients annually in the United States. That number grows to 310 million surgeries performed globally each year. Most surgeons go through a minimum of five years of residency – where they train and hone their surgical skills. It is important during this time, and throughout their careers, that they get plenty of practice. Surgical training is time intensive, expensive, and frequently under-resourced. There are finite amounts of surgical training modules for students to share at their facilities. The problem of getting adequate surgical training time continues to exist after surgeons begin their …

Advancing Point-Of-Care Diagnosis Of Joint Infection Using A Diffuse Reflectance Spectroscopy (Drs) System, Erin Elizabeth Drewke

Graduate Theses and Dissertations

Septic arthritis is a severe joint infection that can rapidly destroy cartilage and cause lifelong disability if not diagnosed and treated promptly. Faster, bedside diagnostic tools are needed to reduce delays and support timely treatment decisions while preserving standard laboratory workflows. A syringe-mounted diffuse reflectance spectroscopy (DRS) system was developed for rapid, sterile, point-of-care measurement of synovial fluid optical properties. Broadband light (400–650 nm) was delivered and collected through the syringe barrel without contaminating the sample. An empirical lookup table (LUT) and a boundary-aware Monte Carlo (MC) model were implemented to extract absorption (μₐ) and reduced scattering (μs′) coefficients from …

Applications Of Preclinical Magnetic Resonance Imaging In The Treatment Of Traumatic Brain Injury And Understanding Carotid Artery Atherosclerosis, Evan Timothy Curtis

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

Advances in magnetic resonance imaging (MRI) provide the opportunity to investigate research questions that have been left unanswered. In the cases of traumatic brain injury (TBI) and carotid artery atherosclerosis, MRI is a resource for non-invasively viewing the phenomena taking place. Additionally, potential interventions and treatments can be observed without harm to the subject. This dissertation expands the understanding of two preclinical applications of MRI: traumatic brain injury and carotid artery atherosclerosis in mouse models.

TBI is a leading cause of death and disability for individuals between 15–45 years of age and effective pharmaceutical interventions for treating the secondary damage …

Study Of Ai Applications In Biomedical Data Acquisition, Communication, And Analysis: Cest Mri Acceleration And Ecg Transmissions, Adarsha Bhattarai

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

This dissertation investigates the application of artificial intelligence in biomedical data acquisition, communication, and analysis to advance neurological research and to enable the early detection of cardiovascular conditions. Despite significant advances in imaging and physiological modalities, challenges persist. Imaging modalities, such as the chemical exchange saturation transfer magnetic resonance imaging (CEST MRI) technique are challenged by a prolonged data acquisition time and high operational costs. In addition, physiological modalities such as electrocardiogram (ECG) sensors face constraints in providing uninterrupted signal monitoring which is crucial for the timely detection of premature cardiac abnormalities. The primary goal of this work is to …

Chronic Pain After Traumatic Brain Injury: Treatment Experiences And Effects On Cognition And Functioning, Rachael L. Snyder

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

Traumatic brain injury (TBI) can contribute to changes in cognitive and emotional functioning, quality of life, and psychosocial reintegration. Chronic pain is a common consequence of TBI which can uniquely impact such outcomes. Still, the exact nature of the contribution of pain on post-TBI outcomes remains unclear, and there are few existing studies exploring the treatment journey for chronic pain and injury rehabilitation through qualitative methods, specifically individual interviews with TBI survivors. This study aimed to document these narratives and to identify precisely how the experiences of TBI survivors seeking treatments, rather than the treatments themselves, impact outcomes. It also …

Machine Learning Based Medical Ultrasound Image Classification And Grad-Cam Interpretation, Victoria C. Hemphill

All Theses

This work takes a step in creating a diagnostic tool for the classification decision process of Achilles tendinopathy using ultrasound images. An attention-based multiple instance learning model is developed to classify the images. Typically, doctors capture multiple ultrasound images of the Achilles tendon during a study to determine a complete diagnosis. Multiple instance models adopt this behavior by providing a single label for a set of instances (images). The images are grouped into ”bags” at the study level and passed into the model. The MIL model then uses its attention property to assign an importance score to each image to …

Impact Of S-Phase Kinase Protien 2 Blockades On Hematopoetic Stem Cell Metabolism, Nicole Elmaraghy

Electronic Theses, Projects, and Dissertations

Hematopoietic stem and progenitor cells (HSPCs) quiescence is vital for the success of bone marrow transplantation, as it preserves long term self- renewal and prevents premature exhaustion (Takubo et al., 2013; Wilson et al., 2008). However, bone marrow transplant (BMT) failure remains a clinical challenge, often due to lack of long-term engraftment and insufficient stress reliance. Both of these characteristics are tightly linked to disrupted stem cell quiescence and metabolic imbalance (Anso et al., 2017; Vannini et al., 2016). One key player is S-phase kinase protein (SKP2), an E3 ubiquitin ligase that targets cell cycle inhibitors, like p27, for proteosome …

Identifying Critical Evidence Gaps In Wound Closure And Incision Management After Total Hip Arthroplasty: Delphi Panel Insights, Margaret Ainslie-Garcia, Lucas Anderson, Benjamin Bloch, Tim N Board, Antonia Chen, Samantha Craigie, Walter Danker, Najmuddin Gunja, James Harty, Victor Hernandez, Kate Lebedeva, Mitchell Ng, Daniel Hameed, Michael Mont, Ryan Nunley, Javad Parvizi, Sean Sequeira, Carsten Perka, Nicolas Piuzzi, Ola Rolfson, Joshua Rychlik, Emilio Romanini, Pablo Sanz-Ruiz, Rafael Sierra, Linda Suleiman, Eleftherios Tsiridis, Pascal-André Vendittoli, Helge Wangen, Luigi Zagra

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: In total hip arthroplasty (THA), proper management of surgical incisions is essential for optimal wound healing and patient outcomes. Despite advances in surgical techniques, significant challenges remain in preventing complications and infections. This study aimed to identify evidence gaps in THA wound care, including presurgical preparation, intraoperative practices, and postsurgical complications.

METHODS: Using a modified Delphi method, 20 expert orthopedic surgeons from Europe and North America participated in a 3-phase consensus process from April 1 to September 30, 2023. This included a preliminary questionnaire, a remote conference, and a final online survey. The panel reviewed literature and achieved agreement …

Radiation Induced Vaporization Of Exoskeletal Droplets As Potential X-Ray Acoustic Contrast Agents, Mohamed E. Eldib, William N. Frantz, Mark A. Borden, Ryan Lanning, Moyed Miften, David H. Thomas

Department of Radiation Oncology Faculty Papers

BACKGROUND: In vivo dosimetry is a crucial component of ensuring accurate and safe radiation therapy (RT) delivery, but many existing techniques face challenges such as low signal-to-noise ratio (SNR), which can limit their clinical applicability.

PURPOSE: In this study, we investigate a novel contrast agent sensitive to megavoltage (MV) radiation in vitro, ultimately aiming for in vivo dosimetry.

METHODS: Vaporizable exoskeletal droplets were engineered to phase-change into ultrasound-responsive microbubbles upon exposure to MV photon radiation. These droplets comprised a hydrocarbon (HC) exoskeleton doped with gold nanoparticles (GNPs) surrounding a liquid fluorocarbon (FC) core. Radiation absorbed by the GNPs induced localized …

Gastric Sarcina Ventriculi: A Report On Two Cases, Yaomin Chen, Yu Liu, Zhiyan Fu

School of Medicine Faculty Publications

: Sarcina ventriculi is a rare Gram-positive coccus that thrives in acidic environments such as the human stomach. It has been increasingly identified in individuals with delayed gastric emptying and has been reported in association with various gastric disorders. However, its exact pathogenic role is not fully understood and remains controversial. : We present two cases of patients, one with a small bowel obstruction and the other with epigastric pain, both diagnosed with Sarcina ventriculi infection by histological examination of gastric biopsies. The patients were managed with a combination of antibiotics and a proton pump inhibitor, resulting in symptom resolution …

The Impact Of Mindfulness Therapy To Reduce Disruptive Behavior In High School, Wendy Peters

Electronic Theses and Dissertations

The aim of this project was to determine the impact and effectiveness of Gina Biegel’s mindfulness techniques for stressed teens method on adolescent anxiety and the disruptive symptoms that lead to high school adolescents being assigned to detention. This project described a quantitative correlational design research project that investigated a small adolescent sample size, with a goal of decreasing the number of local high school adolescent students who are repeat detention offenders, by implementing Gina Biegel’s mindfulness techniques for stressed teens method on those high school adolescents who were assigned to detention. This was achieved by collecting demographic data from …

Discordance Of Small Dense Ldl Cholesterol Beyond Ldl Cholesterol Or Non–Hdl Cholesterol And Carotid Plaque, Jinqi Wang, Xiaoyu Zhao, Yanchen Zhao, Rui Jin, Yunfei Li, Jiahe Wang, Yueruijing Liu, Zhiyuan Wu, Xiuhua Guo, Lixin Tao

Research outputs 2022 to 2026

Background: Different low-density lipoprotein (LDL) particles exhibit distinct proatherogenic properties. Objectives: This study sought to evaluate associations of small dense low-density lipoprotein cholesterol (sdLDL-C), large buoyant low-density lipoprotein cholesterol (lbLDL-C), sdLDL-C/LDL-C ratio, and sdLDL-C/lbLDL-C ratio with carotid plaque (CP) risk in the general population, and to perform discordance analyses to determine which biomarker better reflects CP risk beyond low-density lipoprotein cholesterol (LDL-C) and non–high-density lipoprotein cholesterol (non-HDL-C). Methods: This study enrolled 20,369 participants from Beijing Health Management Cohort. Discordant sdLDL-C, lbLDL-C, or ratio metrics (sdLDL-C/LDL-C and sdLDL-C/lbLDL-C) relative to LDL-C or non-HDL-C, and discordant ratio metrics relative to sdLDL-C, were …

Angioedema: Is Icu Admission Warranted? A Single Institution Assessment, Madeleine Brill-Edwards, W. Chase Hamilton, Erika J. Yoo, Jennifer Costello, George J. Koenig, Murray J. Cohen, Joshua A. Marks

Department of Surgery Faculty Papers

INTRODUCTION: Angioedema has potential for rapid airway decompensation requiring intervention. Patients are often admitted to an ICU for "airway watch." There is a lack of evidence to support which patients require this.

AIM: We aimed to characterize admission patterns and outcomes of angioedema patients at our institution to assess resource utilization and necessity of ICU use. We hypothesized that patients not requiring intubation upon presentation are safe to manage outside the ICU.

MATERIALS AND METHODS: Retrospective chart review of patients admitted to our urban academic quaternary referral institution with angioedema ICD-10 codes between 2017 and 2020. Charts reviewed for demographics, …

Unusual Wave Morphologies In Ulnar Neuropathy With Marinacci Anastomosis: A Case Report, Micaela Owens

Marshall Journal of Medicine

Marinacci anastomosis is a normal but rare anatomic variant of the median and ulnar nerves, consisting of an interconnection from the ulnar nerve to the median nerve within the proximal forearm. This is a case of Marinacci anastomosis occurring in the presence of both median and ulnar neuropathies, producing unusual waveform characteristics. Knowledge of normal anatomic variation can improve diagnostic accuracy in nerve conduction studies.

Effects Of Neoadjuvant Immunotherapy On Hearing In Patients With Head And Neck Squamous Cell Carcinoma, Bryce Hambach, Anhelina Bilokon, John Lee, L. Noelle Allemang, Jennifer Chisholm, Chris K. Zalewski, Julie Christensen, Carmen C. Brewer, James L. Gulley, Clint T. Allen, Lisa L. Cunningham, Katharine A. Fernandez

SKMC Student Presentations and Publications

Immune checkpoint blockade (ICB) is a commonly used treatment modality for cancer with a growing list of oncologic indications. Ototoxicity is a potential immune-related adverse event of ICB treatment, but the risk of hearing loss after ICB remains unknown. This retrospective chart review sought to identify individuals who received ICB and had available audiometric data before and after treatment in order to identify clinically meaningful changes in hearing. This single center, institutional chart review examined hearing function data in patients who underwent audiometry before and after ICB treatment. Measures included pure tone thresholds, distortion product otoacoustic emissions (DPOAEs), tympanometry, and …

Refinement Of Hyams Grading Criteria For Olfactory Neuroblastoma In An Endoscopic Sinus Surgery Predominant Cohort With Extended Follow-Up: Worth The Effort?, Stacey Gargano, Vincent Cracolici, Carl Snyderman, Eric Wang, Garret Choby, Aron Pollack, Paul Gardner, Diana Bell, Raja Seethala

Computational Medicine Center Faculty Papers

BACKGROUND: Hyams grading is considered prognostic in olfactory neuroblastoma (ONB), but grading criteria are subjective and predate modern classification and surgical approach. We evaluate the application of granular grading criteria to an endoscopic surgery predominant cohort with extended follow-up.

METHODS: 78 ONB patients were identified (1994-2019) with original diagnoses dating to 1979. Original Hyams grade, Modified Hyams grade incorporating more detailed criteria and other histologic features (i.e. divergent differentiation, clear cell/oncocytic change, and spindling) were assessed if feasible, evaluated for distribution by grade and correlated with outcomes.

RESULTS: Original Hyams grade (n = 43) distribution was: I: 4 (9%), II: …

Microneedle-Based Lc-Ms/Ms Profiling Of Dermal Interstitial Fluid Reveals Early Lipid Dysregulation Contributing To Painful Neuropathy In Prediabetic And Type 2 Diabetic Rats, Srinivasa Rao Gadam

Biomedical Sciences ETDs

Painful diabetic neuropathy (PDN), a complication of type 1 and type 2 diabetes, also occurs in obesity and prediabetes, with dyslipidemia as a modifiable risk factor. The distal-to-proximal neuropathy pattern and length-dependent intraepidermal nerve fiber loss suggest peripheral contributions. We hypothesized that elevated neurotoxic lipid intermediates—diacylglycerols (DAG), free fatty acids (FFA), and acylcarnitines (CARs)—in the dermal interstitial fluid (ISF) drive metabolism-associated hyperalgesia in prediabetic and diabetic rats. Using a microneedle array (MIA) with LC-MS/MS, we profiled ISF and serum lipids from high-fat diet (HFD) and HFD + streptozotocin (STZ) rat models alongside Hargreaves testing. ISF lipid changes appeared earlier (weeks …

Elevated Nr2f1 Underlies The Persistence Of Invasive Disease After Treatment Of Braf-Mutant Melanoma, Manoela Tiago, Timothy J. Purwin, Casey D. Stefanski, Renaira Oliveira Da Silva, Mitchell E. Fane, Yash Chhabra, Jelan I. Haj, Jessica L. F. Teh, Rama Kadamb, Weijia Cai, Sheera Rosenbaum, Vivian Chua, Nir Hacohen, Michael A. Davies, Jessie Villanueva, Inna Chervoneva, Ashani T. Weeraratna, Dan A. Erkes, Claudia Capparelli, Julio A. Aguirre-Ghiso, Andrew E. Aplin

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Despite the success of targeted inhibitors in cutaneous melanoma, therapeutic responses are limited by the aged tumor microenvironment and drug-tolerant residual cells. Given the similarities between drug tolerance and cellular dormancy, we studied the dormancy marker, nuclear receptor subfamily 2 group F member 1 (NR2F1), in response to BRAF-V600E inhibitors (BRAFi) plus MEK inhibitors (MEKi) in BRAF-mutant melanoma models. Transcriptomic analysis of melanoma patient samples treated with BRAFi + MEKi showed increased NR2F1. NR2F1 was highly expressed in the drug-tolerant invasive cell state of minimal residual disease in patient-derived and mouse-derived xenografts on BRAFi + MEKi. NR2F1 over-expression was sufficient …