Digital Commons Network^™

Needle Biopsy Accelerates Pro-Metastatic Changes And Systemic Dissemination In Breast Cancer: Implications For Mortality By Surgery Delay, Hiroyasu Kameyama, Priya Dondapati, Reese Simmons, Macall Leslie, John Langenheim, Yunguang Sun, Misung Yi, Aubrey Rottschaefer, Rashmi Pathak, Shreya Nuguri, Kar-Ming Fung, Shirng-Wern Tsaih, Inna Chervoneva, Hallgeir Rui, Takemi Tanaka

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

ncreased breast cancer (BC) mortality risk posed by delayed surgical resection of tumor after diagnosis is a growing concern, yet the underlying mechanisms remain unknown. Our cohort analyses of early-stage BC patients reveal the emergence of a significantly rising mortality risk when the biopsy-to-surgery interval was extended beyond 53 days. Additionally, histology of post-biopsy tumors shows prolonged retention of a metastasis-permissive wound stroma dominated by M2-like macrophages capable of promoting cancer cell epithelial-to-mesenchymal transition and angiogenesis. We show that needle biopsy promotes systemic dissemination of cancer cells through a mechanism of sustained activation of the COX-2/PGE₂/EP2 feedforward loop, …

Prmt Blockade Induces Defective Dna Replication Stress Response And Synergizes With Parp Inhibition, Yang Li, Lacey E Dobrolecki, Christina Sallas, Xudong Zhang, Travis D Kerr, Deepa Bisht, Yalong Wang, Sharad Awasthi, Babita Kaundal, Siqi Wu, Weiyi Peng, Marc L Mendillo, Yiling Lu, Collene R Jeter, Guang Peng, Jinsong Liu, Shannon N Westin, Anil K Sood, Michael T Lewis, Jishnu Das, S Stephen Yi, Mark T Bedford, Daniel J Mcgrail, Nidhi Sahni

Faculty, Staff and Student Publications

Multiple cancers exhibit aberrant protein arginine methylation by both type I arginine methyltransferases, predominately protein arginine methyltransferase 1 (PRMT1) and to a lesser extent PRMT4, and by type II PRMTs, predominately PRMT5. Here, we perform targeted proteomics following inhibition of PRMT1, PRMT4, and PRMT5 across 12 cancer cell lines. We find that inhibition of type I and II PRMTs suppresses phosphorylated and total ATR in cancer cells. Loss of ATR from PRMT inhibition results in defective DNA replication stress response activation, including from PARP inhibitors. Inhibition of type I and II PRMTs is synergistic with PARP inhibition regardless of homologous …

Life, The Genome And Everything, Susan M Rosenberg

Faculty, Staff and Students Publications

In this issue of the Journal of Bacteriology, N. J. Bonde, E. A. Wood, K. S. Myers, M. Place, J. L. Keck, and M. M. Cox (J Bacteriol 205:e00184-23, 2023, https://doi.org/10.1128/jb.00184-23) used an unbiased transposon-sequencing (Tn-seq) screen to identify proteins required for life when cells lose the RecG branched-DNA helicase (synthetic lethality). The proteins’ identities indicate pathways that prevent endogenous DNA damage, pathways that prevent its homology-directed repair (HDR) “strand-exchange” intermediates between sister chromosomes, and pathways that resolve those intermediates. All avoid intermediate pile-up, which blocks chromosome segregation, causing “death-by-recombination.” DNA damage is managed to regulate crucial but …

Rotavirus-Mediated Dgat1 Degradation: A Pathophysiological Mechanism Of Viral-Induced Malabsorptive Diarrhea, Zheng Liu, Hunter Smith, Jeanette M Criglar, Antonio J Valentin, Umesh Karandikar, Xi-Lei Zeng, Mary K Estes, Sue E Crawford

Faculty, Staff and Students Publications

Gastroenteritis is among the leading causes of mortality globally in infants and young children, with rotavirus (RV) causing ~258 million episodes of diarrhea and ~128,000 deaths annually in infants and children. RV-induced mechanisms that result in diarrhea are not completely understood, but malabsorption is a contributing factor. RV alters cellular lipid metabolism by inducing lipid droplet (LD) formation as a platform for replication factories named viroplasms. A link between LD formation and gastroenteritis has not been identified. We found that diacylglycerol O-acyltransferase 1 (DGAT1), the terminal step in triacylglycerol synthesis required for LD biogenesis, is degraded in RV-infected cells by …

Mirna-211 Maintains Metabolic Homeostasis In Medulloblastoma Through Its Target Gene Long-Chain Acyl-Coa Synthetase 4, Menglang Yuan, Iqbal Mahmud, Keisuke Katsushima, Kandarp Joshi, Olivier Saulnier, Rudramani Pokhrel, Bongyong Lee, Wathsala Liyanage, Haritha Kunhiraman, Stacie Stapleton, Ignacio Gonzalez-Gomez, Rangaramanujam M Kannan, Tanja Eisemann, Elayaraja Kolanthai, Sudipta Seal, Timothy J Garrett, Saed Abbasi, Kimberly Bockley, Justin Hanes, Prem Chapagain, George Jallo, Robert J Wechsler-Reya, Michael D Taylor, Charles G Eberhart, Animesh Ray, Ranjan J Perera

Faculty, Staff and Students Publications

The prognosis of childhood medulloblastoma (MB) is often poor, and it usually requires aggressive therapy that adversely affects quality of life. microRNA-211 (miR-211) was previously identified as an important regulator of cells that descend from neural cells. Since medulloblastomas primarily affect cells with similar ontogeny, we investigated the role and mechanism of miR-211 in MB. Here we showed that miR-211 expression was highly downregulated in cell lines, PDXs, and clinical samples of different MB subgroups (SHH, Group 3, and Group 4) compared to normal cerebellum. miR-211 gene was ectopically expressed in transgenic cells from MB subgroups, and they were subjected …

Nucleus Accumbens Core Single Cell Ensembles Bidirectionally Respond To Experienced Versus Observed Aversive Events, Oyku Dinckol, Noah Harris Wenger, Jennifer E Zachry, Munir Gunes Kutlu

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Fear learning is a critical feature of survival skills among mammals. In rodents, fear learning manifests itself through direct experience of the aversive event or social transmission of aversive stimuli such as observing and acting on conspecifics' distress. The neuronal network underlying the social transmission of information largely overlaps with the brain regions that mediate behavioral responses to aversive and rewarding stimuli. In this study, we recorded single cell activity patterns of nucleus accumbens (NAc) core neurons using in vivo optical imaging of calcium transients via miniature scopes. This cutting-edge imaging methodology not only allows us to record activity patterns …

Genetic And Epigenetic Features Of Bilateral Wilms Tumor Predisposition In Patients From The Children’S Oncology Group Aren18b5-Q, Andrew J Murphy, Changde Cheng, Justin Williams, Timothy I Shaw, Emilia M Pinto, Karissa Dieseldorff-Jones, Jack Brzezinski, Lindsay A Renfro, Brett Tornwall, Vicki Huff, Andrew L Hong, Elizabeth A Mullen, Brian Crompton, Jeffrey S Dome, Conrad V Fernandez, James I Geller, Peter F Ehrlich, Heather Mulder, Ninad Oak, Jamie Maciezsek, Carolyn M Jablonowski, Andrew M Fleming, Prahalathan Pichavaram, Christopher L Morton, John Easton, Kim E Nichols, Michael R Clay, Teresa Santiago, Jinghui Zhang, Jun Yang, Gerard P Zambetti, Zhaoming Wang, Andrew M Davidoff, Xiang Chen

Faculty, Staff and Student Publications

Developing synchronous bilateral Wilms tumor suggests an underlying (epi)genetic predisposition. Here, we evaluate this predisposition in 68 patients using whole exome or genome sequencing (n = 85 tumors from 61 patients with matched germline blood DNA), RNA-seq (n = 99 tumors), and DNA methylation analysis (n = 61 peripheral blood, n = 29 non-diseased kidney, n = 99 tumors). We determine the predominant events for bilateral Wilms tumor predisposition: 1)pre-zygotic germline genetic variants readily detectable in blood DNA [WT1 (14.8%), NYNRIN (6.6%), TRIM28 (5%), and BRCA-related genes (5%)] or 2)post-zygotic epigenetic hypermethylation at 11p15.5 H19/ICR1 that may require analysis of …

Pathway Centric Analysis For Single-Cell Rna-Seq And Spatial Transcriptomics Data With Gsdensity, Qingnan Liang, Yuefan Huang, Shan He, Ken Chen

Faculty, Staff and Student Publications

Advances in single-cell technology have enabled molecular dissection of heterogeneous biospecimens at unprecedented scales and resolutions. Cluster-centric approaches are widely applied in analyzing single-cell data, however they have limited power in dissecting and interpreting highly heterogenous, dynamically evolving data. Here, we present GSDensity, a graph-modeling approach that allows users to obtain pathway-centric interpretation and dissection of single-cell and spatial transcriptomics (ST) data without performing clustering. Using pathway gene sets, we show that GSDensity can accurately detect biologically distinct cells and reveal novel cell-pathway associations ignored by existing methods. Moreover, GSDensity, combined with trajectory analysis can identify curated pathways that are …

Lesion Detection In Women Breast’S Dynamic Contrast-Enhanced Magnetic Resonance Imaging Using Deep Learning, Sudarshan Saikia, Tapas Si, Darpan Deb, Kangkana Bora, Saurav Mallik, Ujjwal Maulik, Zhongming Zhao

Faculty, Staff and Student Publications

Breast cancer is one of the most common cancers in women and the second foremost cause of cancer death in women after lung cancer. Recent technological advances in breast cancer treatment offer hope to millions of women in the world. Segmentation of the breast's Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) is one of the necessary tasks in the diagnosis and detection of breast cancer. Currently, a popular deep learning model, U-Net is extensively used in biomedical image segmentation. This article aims to advance the state of the art and conduct a more in-depth analysis with a focus on the use …

Air-Jet Bioprinting Of Stem Cell-Encapsulated Alginate Micro-Droplets For Organoid Biomanufacturing, Mirabella B. Stump

Electronic Theses and Dissertations

Biomanufactured 3D-organoids show promise for modeling and treating various conditions, particularly insulin-dependent diabetes mellitus (type-1 diabetes). Pancreatic islet organoids serve as sustainable sources of insulin-producing β-cells, potentially restoring insulin regulation in patients and providing a long-term solution for diabetes. Hydrogel droplet printing is an emerging technique in regenerative medicine due to its advantageous tunability and biocompatibility; however, challenges of consistency, quality control, and scalability persist. To address these issues, we developed a novel air-jetting based droplet bioprinting system for the generation of monodispersed alginate micro-droplets. The objective of this project was to incorporate human induced pluripotent stem cells (hiPSCs) into …

The Effect Of Non-Immersive Virtual Reality Radiographic Positioning Simulation On First-Year Radiography Students' Image Evaluation Of Routine Positioning Errors, Ellie M. Miller

Theses & Dissertations

Optimal radiographic image quality is critical because it affects the accuracy of the radiologist’s interpretation. Radiologic technologists are obligated to obtain diagnostic images while minimizing patient radiation. However, repeated images due to technologist error have increased in recent years. This study aimed to evaluate the effectiveness of non-immersive virtual reality (VR) simulation on first-year students’ image evaluation of common positioning errors on routine knee and lumbar spine protocols. Research questions were 1) Does guided instruction using non-immersive radiographic positioning simulation software lead to improved image evaluation scores? 2) How well do participants describe evaluation of positioning errors after guided instruction …

The Impact Of An Educational Cooking Class On Inflammatory Potential Of Diet In Cancer Survivors, Mariah K. Jackson

Theses & Dissertations

Cancer survivors face long-term effects from cancer treatments, with cognitive dysfunction being an important, yet understudied, consequence of cancer treatment. Inflammation is a proposed mechanism for impaired cognition status. As research demonstrates diet is associated with both pro- and anti-inflammatory effects, diet may represent a novel strategy to mitigate cognitive decline in cancer survivors. The purpose of this study was to 1) quantify the impact of an educational cooking class on inflammatory potential of diet (measured by the Dietary Inflammatory Index (DII)) in cancer survivors and 2) determine the relationship between dietary changes and cognitive function in cancer survivors. Dietary …

Differences In Set-Based Tests For Sparse Alternatives When Testing Sets Of Outcomes Compared To Sets Of Explanatory Factors In Genetic Association Studies, Ryan Sun, Andy Shi, Xihong Lin

Faculty, Staff and Student Publications

Set-based association tests are widely popular in genetic association settings for their ability to aggregate weak signals and reduce multiple testing burdens. In particular, a class of set-based tests including the Higher Criticism, Berk-Jones, and other statistics have recently been popularized for reaching a so-called detection boundary when signals are rare and weak. Such tests have been applied in two subtly different settings: (a) associating a genetic variant set with a single phenotype and (b) associating a single genetic variant with a phenotype set. A significant issue in practice is the choice of test, especially when deciding between innovated and …

Bayesian Longitudinal Tensor Response Regression For Modeling Neuroplasticity, Suprateek Kundu, Alec Reinhardt, Serena Song, Joo Han, M Lawson Meadows, Bruce Crosson, Venkatagiri Krishnamurthy

Faculty, Staff and Student Publications

A major interest in longitudinal neuroimaging studies involves investigating voxel-level neuroplasticity due to treatment and other factors across visits. However, traditional voxel-wise methods are beset with several pitfalls, which can compromise the accuracy of these approaches. We propose a novel Bayesian tensor response regression approach for longitudinal imaging data, which pools information across spatially distributed voxels to infer significant changes while adjusting for covariates. The proposed method, which is implemented using Markov chain Monte Carlo (MCMC) sampling, utilizes low-rank decomposition to reduce dimensionality and preserve spatial configurations of voxels when estimating coefficients. It also enables feature selection via joint credible …

Utility Of T-Cell Immunosequencing In Distinguishing Mycosis Fungoides Progression From Treatment Related Cutaneous Adverse Events, Safiyyah Bhatti, Daniel Joffe, Lauren Banner, Sahithi Talasila, Jenna Mandel, Jason Lee, Pierluigi Porcu, Neda Nikbakht

Department of Dermatology and Cutaneous Biology Faculty Papers

Cutaneous adverse events of both topical and systemic drugs in patients with mycosis fungoides (MF) present a diagnostic challenge as it is often difficult to distinguish drug associated rash from disease progression in the skin. Mogamulizumab and mechlorethamine gel are approved treatments for MF, both of which can cause treatment related cutaneous adverse events. It can often be challenging to distinguish mogamulizumab associated rash (MAR) and mechlorethamine gel associated hypersensitivity dermatitis from MF progression both clinically and histologically. High-throughput sequencing (HTS) of the T-cell receptor (TCR), also known as immunosequencing, can be used to assess T-cell clonality to support a …

Combining The Tyrosine Kinase Inhibitor Cabozantinib And The Mtorc1/2 Inhibitor Sapanisertib Blocks Erk Pathway Activity And Suppresses Tumor Growth In Renal Cell Carcinoma, Yige Wu, Siqi Chen, Xiaolu Yang, Kazuhito Sato, Preet Lal, Yuefan Wang, Andrew T Shinkle, Michael C Wendl, Tina M Primeau, Yanyan Zhao, Alanna Gould, Hua Sun, Jacqueline L Mudd, Jeremy Hoog, R Jay Mashl, Matthew A Wyczalkowski, Chia-Kuei Mo, Ruiyang Liu, John M Herndon, Sherri R Davies, Di Liu, Xi Ding, Yvonne A Evrard, Bryan E Welm, David Lum, Mei Yee Koh, Alana L Welm, Jeffrey H Chuang, Jeffrey A Moscow, Funda Meric-Bernstam, Ramaswamy Govindan, Shunqiang Li, James Hsieh, Ryan C Fields, Kian-Huat Lim, Cynthia X Ma, Hui Zhang, Li Ding, Feng Chen

Faculty, Staff and Student Publications

Current treatment approaches for renal cell carcinoma (RCC) face challenges in achieving durable tumor responses due to tumor heterogeneity and drug resistance. Combination therapies that leverage tumor molecular profiles could offer an avenue for enhancing treatment efficacy and addressing the limitations of current therapies. To identify effective strategies for treating RCC, we selected ten drugs guided by tumor biology to test in six RCC patient-derived xenograft (PDX) models. The multitargeted tyrosine kinase inhibitor (TKI) cabozantinib and mTORC1/2 inhibitor sapanisertib emerged as the most effective drugs, particularly when combined. The combination demonstrated favorable tolerability and inhibited tumor growth or induced tumor …

Plants As Vectors For Environmental Prion Transmission, Christina M Carlson, Samuel Thomas, Matthew W Keating, Paulina Soto, Nicole M Gibbs, Haeyoon Chang, Jamie K Wiepz, Annabel G Austin, Jay R Schneider, Rodrigo Morales, Christopher J Johnson, Joel A Pedersen

Faculty, Staff and Student Publications

Prions cause fatal neurodegenerative diseases and exhibit remarkable durability, which engenders a wide array of potential exposure scenarios. In chronic wasting disease of deer, elk, moose, and reindeer and in scrapie of sheep and goats, prions are transmitted via environmental routes and the ability of plants to accumulate and subsequently transmit prions has been hypothesized, but not previously demonstrated. Here, we establish the ability of several crop and other plant species to take up prions via their roots and translocate them to above-ground tissues from various growth media including soils. We demonstrate that plants can accumulate prions in above-ground tissues …

Gatekeeping At Bio, Daniel A Gorelick

Faculty, Staff and Students Publications

No abstract provided.

Early Cellular And Molecular Signatures Correlate With Severity Of West Nile Virus Infection, Ho-Joon Lee, Yujiao Zhao, Ira Fleming, Sameet Mehta, Xiaomei Wang, Brent Vander Wyk, Shannon E Ronca, Heather Kang, Chih-Hung Chou, Benoit Fatou, Kinga K Smolen, Ofer Levy, Clary B Clish, Ramnik J Xavier, Hanno Steen, David A Hafler, J Christopher Love, Alex K Shalek, Leying Guan, Kristy O Murray, Steven H Kleinstein, Ruth R Montgomery

Faculty, Staff and Students Publications

Infection with West Nile virus (WNV) drives a wide range of responses, from asymptomatic to flu-like symptoms/fever or severe cases of encephalitis and death. To identify cellular and molecular signatures distinguishing WNV severity, we employed systems profiling of peripheral blood from asymptomatic and severely ill individuals infected with WNV. We interrogated immune responses longitudinally from acute infection through convalescence employing single-cell protein and transcriptional profiling complemented with matched serum proteomics and metabolomics as well as multi-omics analysis. At the acute time point, we detected both elevation of pro-inflammatory markers in innate immune cell types and reduction of regulatory T cell …

Enniatin A Inhibits The Chaperone Hsp90 And Unleashes The Immune System Against Triple-Negative Breast Cancer, Nada H Eisa, Vincent M Crowley, Asif Elahi, Vamsi Krishna Kommalapati, Michael A Serwetnyk, Taoufik Llbiyi, Sumin Lu, Kashish Kainth, Yasmeen Jilani, Daniela Marasco, Abdeljabar El Andaloussi, Sukyeong Lee, Francis T F Tsai, Paulo C Rodriguez, David Munn, Esteban Celis, Hasan Korkaya, Abdessamad Debbab, Brian Blagg, Ahmed Chadli

Faculty, Staff and Students Publications

Low response rates and immune-related adverse events limit the remarkable impact of cancer immunotherapy. To improve clinical outcomes, preclinical studies have shown that combining immunotherapies with N-terminal Hsp90 inhibitors resulted in improved efficacy, even though induction of an extensive heat shock response (HSR) and less than optimal dosing of these inhibitors limited their clinical efficacy as monotherapies. We discovered that the natural product Enniatin A (EnnA) targets Hsp90 and destabilizes its client oncoproteins without inducing an HSR. EnnA triggers immunogenic cell death in triple-negative breast cancer (TNBC) syngeneic mouse models and exhibits superior antitumor activity compared to Hsp90 N-terminal inhibitors. …

Targeting Eif4a Triggers An Interferon Response To Synergize With Chemotherapy And Suppress Triple-Negative Breast Cancer, Na Zhao, Elena B Kabotyanski, Alexander B Saltzman, Anna Malovannaya, Xueying Yuan, Lucas C Reineke, Nadia Lieu, Yang Gao, Diego A Pedroza, Sebastian J Calderon, Alex J Smith, Clark Hamor, Kazem Safari, Sara Savage, Bing Zhang, Jianling Zhou, Luisa M Solis, Susan G Hilsenbeck, Cheng Fan, Charles M Perou, Jeffrey M Rosen

Faculty, Staff and Students Publications

Protein synthesis is frequently dysregulated in cancer and selective inhibition of mRNA translation represents an attractive cancer therapy. Here, we show that therapeutically targeting the RNA helicase eIF4A with zotatifin, the first-in-class eIF4A inhibitor, exerts pleiotropic effects on both tumor cells and the tumor immune microenvironment in a diverse cohort of syngeneic triple-negative breast cancer (TNBC) mouse models. Zotatifin not only suppresses tumor cell proliferation but also directly repolarizes macrophages toward an M1-like phenotype and inhibits neutrophil infiltration, which sensitizes tumors to immune checkpoint blockade. Mechanistic studies revealed that zotatifin reprograms the tumor translational landscape, inhibits the translation of Sox4 …

Aspirin And Nonaspirin Nonsteroidal Antiinflammatory Drug Use And Occurrence Of Colorectal Adenoma In Black American Women, Lauren E Barber, Kimberly A Bertrand, Shanshan Sheehy, Laura F White, Hemant K Roy, Lynn Rosenberg, Julie R Palmer, Jessica L Petrick

Faculty, Staff and Students Publications

Evidence suggests that aspirin use reduces the occurrence of colorectal neoplasia. Few studies have investigated the association among Black Americans, who are disproportionately burdened by the disease. We assessed aspirin use in relation to colorectal adenoma among Black women. The Black Women's Health Study is a prospective cohort of self-identified Black American women established in 1995. Participants reported regular aspirin use on baseline and follow-up questionnaires. Beginning in 1999, participants reported undergoing a colonoscopy or sigmoidoscopy, the only procedures through which colorectal adenomas can be diagnosed. Multivariable logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals …

Timigp: An R Package To Depict The Tumor Microenvironment From Bulk Transcriptomics, Chenyang Li, Jianjun Zhang, Chao Cheng

Faculty, Staff and Students Publications

Exploring the clinical relevance of diverse immune cell types within the tumor microenvironment is pivotal for unraveling cancer intricacies and developing treatments. Here, we present a protocol for using tumor immune microenvironment illustration based on gene pairs, an R package to deduce cell-cell interactions, unveiling the association between immune cell relative abundance and patient prognoses from bulk gene expression and survival data. We describe steps for harnessing cell-type markers derived from single-cell RNA sequencing data to map the tumor immune microenvironment across a spectrum of cancer types. For complete details on the use and execution of this protocol, please refer …

Lilrb3 Modulates Acute Myeloid Leukemia Progression And Acts As An Effective Target For Car T-Cell Therapy, Sunny Mai, Alan Hodges, Hui-Ming Chen, Jilu Zhang, Yi-Ling Wang, Yongbin Liu, Fumiko Nakatsu, Xiaoxuan Wang, Jing Fang, Yitian Xu, Vitaliy Davidov, Kyeongah Kang, Sai Ravi Pingali, Siddhartha Ganguly, Masataka Suzuki, Marina Konopleva, Brooke Prinzing, Youli Zu, Stephen Gottschalk, Yong Lu, Shu-Hsia Chen, Ping-Ying Pan

Faculty, Staff and Students Publications

Identifying novel cell surface receptors that regulate leukemia cell differentiation and can be targeted to inhibit cellular proliferation is crucial to improve current treatment modalities in acute myeloid leukemia (AML), especially for relapsed or chemotherapy-refractory leukemia. Leukocyte immunoglobulin-like receptor type B (LILRB) is an immunomodulatory receptor originally found to be expressed in myeloid cells. In this study, we found that LILRB receptors can be induced under inflammatory stimuli and chemotherapy treatment conditions. Blockade of LILRB3 inhibited leukemia cell proliferation and leukemia progression. Additionally, treatment with LILRB3 blocking antibodies upregulated myeloid lineage differentiation transcription factors, including PU.1, C/EBP family, and IRF, …

In Memoriam: Prof. Dr. Rer. Nat. Jeanette Erdmann, Pashmina Wiqar Shah, Satwat Hashmi, Tobias Reinberger, Nadine Odenthal, Luis Eichelmann, Daria Kosenko, Ilyas Ahmad, Jaafar Al-Hasani, Till Joscha Demal, Zouhair Aherrahrou

Department of Biological & Biomedical Sciences

No abstract provided.

A Review Of Slipping Rib Syndrome: Diagnostic And Treatment Updates To A Rare And Challenging Problem, Isheeta Madeka, Sneha Alaparthi, Marisa Moreta, Shawn Peterson, Jeffrey Mojica, Johanes Roedl, Olugbenga Okusanya

Department of Surgery Faculty Papers

Slipping rib syndrome (SRS) is a disorder that occurs when one or more of the eighth through tenth ribs become abnormally mobile. SRS is a poorly understood condition leading to a significant delay in diagnosis and therapeutic management. History and a physical exam are usually sufficient for a diagnosis of SRS. The utility of dynamic ultrasounds has also been studied as a useful diagnostic tool. Multiple surgical techniques for SRS have been described within the literature. Cartilage rib excision (CRE) has been the most common technique utilized. However, the literature has shown a high rate of recurrence and associated risks …

Gap Junctions Or Hemichannel-Dependent And Independent Roles Of Connexins In Fibrosis, Epithelial-Mesenchymal Transitions, And Wound Healing, Yuting Li, Francisca M Acosta, Jean X Jiang

Faculty, Staff and Student Publications

Fibrosis initially appears as a normal response to damage, where activated fibroblasts produce large amounts of the extracellular matrix (ECM) during the wound healing process to assist in the repair of injured tissue. However, the excessive accumulation of the ECM, unresolved by remodeling mechanisms, leads to organ dysfunction. Connexins, a family of transmembrane channel proteins, are widely recognized for their major roles in fibrosis, the epithelial-mesenchymal transition (EMT), and wound healing. Efforts have been made in recent years to identify novel mediators and targets for this regulation. Connexins form gap junctions and hemichannels, mediating communications between neighboring cells and inside …

Recombination-Mediated Dissemination Of Methicillin-Resistant S Aureus Clonal Complex 1 In The Egyptian Health Care Settings, Salma W Elsayed, Reem A Elghaish, Eman Badr, Shaimaa F Mouftah, Nehal A Saif, Iman S Naga, Ahmed H Shata, Ben Pascoe, Samuel K Sheppard, Mohamed Elhadidy

Faculty, Staff and Student Publications

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a rapidly evolving pathogen that is frequently associated with outbreaks and sustained epidemics. This study investigated the population structure, resistome, virulome, and the correlation between antimicrobial resistance determinants with phenotypic resistance profiles of 36 representative hospital-acquired MRSA isolates recovered from hospital settings in Egypt.

Results: The community-acquired MRSA lineage, clonal complex 1 (CC1) was the most frequently detected clone, followed by three other globally disseminated clones, CC121, CC8, and CC22. Most isolates carried SCCmec type V and more than half of isolates demonstrated multi-drug resistant phenotypes. Resistance to linezolid, a last resort antibiotic for …

A Comprehensive Program Evaluation Of Colorectal Rescreening Initiatives In Rural Virginia, Sarah E. Stowell

Doctors of Nursing Practice (DNP) Final Projects, 2020-current

Background: Despite low-cost and effective screening tools, colorectal cancer (CRC) mortality remains high in the U.S., particularly in rural areas like Virginia’s Northern Shenandoah Valley, where screening rates are low. While literature highlights barriers to CRC screening in these communities and suggests improvement strategies, few studies focus on long-term adherence to screening in rural health clinics (RHCs).

Purpose: This program evaluation assessed the impact and effectiveness of the Rural Colorectal Cancer Rescreening Initiative (RCRI), a pilot program to increase colorectal cancer rescreening rates in a local RHC. It also offers recommendations for optimizing future RCRI efforts. Methods: The program evaluation …

Evaluation Of The Aggressive-Variant Prostate Cancer Molecular Signature In Clinical Laboratory Improvement Amendments (Clia) Environments, Paul V Viscuse, Rebecca S Slack-Tidwell, Miao Zhang, Prih Rohra, Keyi Zhu, F Anthony San Lucas, Eric Konnick, Patrick G Pilie, Bilal Siddiqui, Christopher J Logothetis, Paul Corn, Sumit K Subudhi, Colin C Pritchard, Rama Soundararajan, Ana Aparicio

Faculty, Staff and Student Publications

Aggressive-variant prostate cancers (AVPCs) are a subset of metastatic castrate-resistant prostate cancers (mCRPCs) characterized by defects in ≥ two of three of TP53, RB1, and PTEN (AVPCm), a profile linked to lineage plasticity, androgen indifference, and platinum sensitivity. Men with mCRPC undergoing biopsies for progression were assessed for AVPCm using immunohistochemistry (IHC), next-generation sequencing (NGS) of solid tumor DNA (stDNA), and NGS of circulating tumor DNA (ctDNA) assays in CLIA-certified labs. Biopsy characteristics, turnaround times, inter-reader concordance, and inter-assay concordance were assessed. AVPCm was detected in 13 (27%) patients via IHC, two (6%) based on stDNA, and seven …