Medical Specialties Commons^™

Hospital Change To Mixed Lipid Emulsion From Soybean Oil-Based Lipid Emulsion For Parenteral Nutrition In Hospitalized And Critically Ill Adults Improves Outcomes: A Pre–Post-Comparative Study, Krista L Haines, Tetsu Ohnuma, Charles Trujillo, Obanor Osamudiamen, Vijay Krishnamoorthy, Karthik Raghunathan, Paul E Wischmeyer

Faculty, Staff and Student Publications

INTRODUCTION: Early data suggest use of a mixed lipid emulsion (LE) with a soybean oil reduction strategy in parenteral nutrition (PN) may improve clinical outcomes. Duke University Hospital made a full switch to a Soybean oil/MCT/Olive/Fish Oil lipid (4-OLE) from pure soybean oil-based LE (Intralipid, Baxter Inc) in May 2017. Since 4-OLE has limited evidence related to its effects on clinical outcome parameters in US hospitals, evidence for clinical benefits of switching to 4-OLE is needed. Therefore, we examined the clinical utility of a hospital-wide switch to 4-OLE and its effect on patient outcomes.

METHODS: We conducted a single-center retrospective …

Elevated Nras Expression During Dcis Is A Potential Driver For Progression To Basal-Like Properties And Local Invasiveness, Ze-Yi Zheng, Hanan Elsarraj, Jonathan T Lei, Yan Hong, Meenakshi Anurag, Long Feng, Hilda Kennedy, Yichao Shen, Flora Lo, Zifan Zhao, Bing Zhang, Xiang H-F Zhang, Ossama W Tawfik, Fariba Behbod, Eric C Chang

Faculty, Staff and Students Publications

BACKGROUND: Ductal carcinoma in situ (DCIS) is the most common type of in situ premalignant breast cancers. What drives DCIS to invasive breast cancer is unclear. Basal-like invasive breast cancers are aggressive. We have previously shown that NRAS is highly expressed selectively in basal-like subtypes of invasive breast cancers and can promote their growth and progression. In this study, we investigated whether NRAS expression at the DCIS stage can control transition from luminal DCIS to basal-like invasive breast cancers.

METHODS: Wilcoxon rank-sum test was performed to assess expression of NRAS in DCIS compared to invasive breast tumors in patients. NRAS …

Intensive Blood Pressure Lowering In Patients With Malignant Left Ventricular Hypertrophy, Simon B Ascher, James A De Lemos, Minjae Lee, Elaine Wu, Elsayed Z Soliman, Ian J Neeland, Dalane W Kitzman, Christie M Ballantyne, Vijay Nambi, Anthony A Killeen, Joachim H Ix, Michael G Shlipak, Jarett D Berry

Faculty, Staff and Students Publications

Background: Left ventricular hypertrophy (LVH) combined with elevations in cardiac biomarkers reflecting myocardial injury and neurohormonal stress (malignant LVH) is associated with a high risk for heart failure and death.

Objectives: The aim of this study was to determine the impact of intensive systolic blood pressure (SBP) control on the prevention of malignant LVH and its consequences.

Methods: A total of 8,820 participants in SPRINT (Systolic Blood Pressure Intervention Trial) were classified into groups based on the presence or absence of LVH assessed by 12-lead ECG, and elevations in biomarker levels (high-sensitivity cardiac troponin T ≥14 ng/L or N-terminal pro-B-type …

The Decision I Never Thought I Would Have To Make, Mary Nixon

Clinical Research in Practice: The Journal of Team Hippocrates

A brief essay on how the COVID pandemic has changed how we think about medicine and our patients.

Chemical Relaxers And Hair-Straightening Products: Potential Targets For Hormone-Related Cancer Prevention And Control, Adana A. M. Llanos, Jasmine A. Mcdonald, Dede K. Teteh, Traci N. Bethea

Health Sciences and Kinesiology Faculty Articles

"Emerging data show that use of permanent hair dyes, chemical relaxers, and straightening products might contribute to increased risk of hormone-related cancers (1-5) and potentially breast tumors with features indicative of more aggressive phenotypes (6). Given the wide use of these products globally, they are an important source of exposure to potentially harmful chemicals, including endocrine-disrupting chemicals—to which we are ubiquitously exposed (7)—and mutagenic and/or genotoxic compounds. The unequal burden of exposure across populations plausibly contributes to cancer inequities as the groups with the greatest exposure also experience poorer cancer outcomes (8). …

The Mechanisms Of Action Of Tumor Treating Fields, Justin C Moser, Ellaine Salvador, Karina Deniz, Kenneth Swanson, Jack Tuszynski, Kristen W Carlson, Narasimha Kumar Karanam, Chirag B Patel, Michael Story, Emil Lou, Carsten Hagemann

Faculty, Staff and Student Publications

Tumor treating fields (TTFields), a new modality of cancer treatment, are electric fields transmitted transdermally to tumors. The FDA has approved TTFields for the treatment of glioblastoma multiforme and mesothelioma, and they are currently under study in many other cancer types. While antimitotic effects were the first recognized biological anticancer activity of TTFields, data have shown that tumor treating fields achieve their anticancer effects through multiple mechanisms of action. TTFields therefore have the ability to be useful for many cancer types in combination with many different treatment modalities. Here, we review the current understanding of TTFields and their mechanisms of …

Two Cases Of Autoimmune Syndrome Induced By Adjuvants (Asia): A Multifaceted Condition Calling For A Multidisciplinary Approach, Christine E. Loftis, Aidee Nunez, Mauricio De La Garza, Emilia C. Dulgheru

School of Medicine Publications

Silicone implants have been used for cosmetic enhancement and reconstructive purposes for over 60 years. Despite assiduous efforts to ensure safety, there is continuous evidence that they are not as biologically inert as previously postulated. We present two cases of autoimmune syndrome induced by adjuvants (ASIA) in Hispanic women. The first patient developed biopsy-proven immune-mediated necrotizing myopathy that was successfully treated with the combination of silicone explantation along with immunosuppressive therapy. Findings after implant removal demonstrated rupture and leakage of silicone from gluteal implants. The second patient developed autoimmune hemolytic anemia in the setting of a ruptured silicone breast implant. …

Gastric Perforation From A Migrating Ventriculoperitoneal Shunt: A Case Report And Review Of Literature, Alessio Scarascia, Elias Atallah, Maria De Abreu Pineda, Robert H. Rosenwasswer, Kevin Judy

Department of Neurosurgery Faculty Papers

Ventriculoperitoneal (VP) shunts represent a surgical option for patients affected by increased intracranial hypertension when medical management fails or is contraindicated. Complications following implantation include shunt obstruction, infection, over and under drainage, migration or disconnection of the tube, formation of a pseudocyst, and allergy to the silicone tube. We report the case of a 31-year-old woman who presented to the emergency room with nausea and generalized malaise, found to have the distal segment of the VP catheter perforating her gastric wall into the stomach lumen which required surgical intervention. In this report, we describe a rare complication associated with the …

Serological Evidence Of Severe Fever With Thrombocytopenia Syndrome Virus And Igm Positivity Were Identified In Healthy Residents In Vietnam, Xuan Chuong Tran, Sung Hye Kim, Jeong-Eun Lee, So-Hee Kim, Su Yeon Kang, Nguyen D Binh, Pham V Duc, Phan T K Phuong, Nguyen T P Thao, Wonwoo Lee, Joon-Yong Bae, Man-Seong Park, Misun Kim, Jeong Rae Yoo, Sang Taek Heo, Kyeong Ho An, Jung Mogg Kim, Nam-Hyuk Cho, Sun-Ho Kee, Keun Hwa Lee

Faculty, Staff and Student Publications

Severe fever with thrombocytopenia syndrome (SFTS), an emerging tick-borne viral disease, is prevalent in East Asia and has also been reported in Southeast Asia since 2019. SFTS patients in Vietnam were first reported in 2019. However, the seroprevalence of severe fever with thrombocytopenia syndrome virus (SFTSV) in Vietnam has not been reported. To investigate the seroprevalence of SFTSV in Vietnam, we collected serum samples from 714 healthy residents in Thua Thien Hue and Quang Nam Province, Vietnam, and the seroprevalence of SFTSV was assessed using immunofluorescence antibody assay (IFA), Enzyme-Linked Immunosorbent Assays (ELISAs) and the 50% focus reduction neutralization test …

Tumor Microenvironment: Barrier Or Opportunity Towards Effective Cancer Therapy, Aadhya Tiwari, Rakesh Trivedi, Shiaw-Yih Lin

Faculty, Staff and Student Publications

Tumor microenvironment (TME) is a specialized ecosystem of host components, designed by tumor cells for successful development and metastasis of tumor. With the advent of 3D culture and advanced bioinformatic methodologies, it is now possible to study TME's individual components and their interplay at higher resolution. Deeper understanding of the immune cell's diversity, stromal constituents, repertoire profiling, neoantigen prediction of TMEs has provided the opportunity to explore the spatial and temporal regulation of immune therapeutic interventions. The variation of TME composition among patients plays an important role in determining responders and non-responders towards cancer immunotherapy. Therefore, there could be a …

Tachyarrhythmias During Hospitalization For Covid-19 Or Multisystem Inflammatory Syndrome In Children And Adolescents, Audrey Dionne, Kevin G. Friedman, Cameron C. Young, Margaret M. Newhams, Suden Kucukak, Ashley M. Jackson, Julie C. Fitzgerald, Laura S. Smallcomb, Sabrina Heidemann, Gwenn E. Mclaughlin, Katherine Irby, Tamara T. Bradford, Steven M. Horwitz, Laura L. Loftis, Vijaya L. Soma, Courtney M. Rowan, Michele Kong, Natasha B. Halasa, Keiko M. Tarquinio, Adam J. Schwarz, Janet R. Hume, Shira J. Gertz, Katharine N. Clouser, Christopher L. Carroll, Kari Wellnitz, Melissa L. Cullimore, Sule Doymaz, Emily R. Levy

School of Medicine Faculty Publications

BACKGROUND: Cardiac complications related to COVID-19 in children and adolescents include ventricular dysfunction, myocarditis, coronary artery aneurysm, and bradyarrhythmias, but tachyarrhythmias are less understood. The goal of this study was to evaluate the frequency, characteristics, and outcomes of children and adolescents experiencing tachyarrhythmias while hospitalized for acute severe COVID-19 or multisystem inflammatory syndrome in children. METHODS AND RESULTS: This study involved a case series of 63 patients with tachyarrhythmias reported in a public health surveillance registry of patients aged 15, 2020, to December 31, 2021, at 63 US hospitals. Patients with tachyarrhythmias were compared with patients with severe COVID-19–related complications …

Serum High Mobility Group Box-1 Levels Associated With Cardiovascular Events After Lower Extremity Revascularization: A Prospective Study Of A Diabetic Population, Maria Margherita Rando, Federico Biscetti, Andrea Leonardo Cecchini, Elisabetta Nardella, Maria Anna Nicolazzi, Flavia Angelini, Roberto Iezzi, Luis H. Eraso, Paul J Dimuzio, Dario Pitocco, Antonio Gasbarrini, Massimo Massetti, Andrea Flex

Department of Surgery Faculty Papers

Background: Peripheral arterial disease (PAD) is one of the most disabling cardiovascular complications of type 2 diabetes mellitus and is indeed associated with a high risk of cardiovascular and limb adverse events. High mobility group box-1 (HMGB-1) is a nuclear protein involved in the inflammatory response that acts as a pro-inflammatory cytokine when released into the extracellular space. HMBG-1 is associated with PAD in diabetic patients. The aim of this study was to evaluate the association between serum HMGB-1 levels and major adverse cardiovascular events (MACE) and major adverse limb events (MALE) after lower-extremity endovascular revascularization (LER) in a group …

Cost-Benefit Analysis Of The Cope Program For Persons Living With Dementia: Toward A Payment Model, Laura T Pizzi, Eric Jutkowitz, Katherine M Prioli, Ember Yiwei Lu, Zachary Babcock, Heather Mcabee-Sevick, Dorothy B Wakefield, Julie Robison, Sheila Molony, Catherine V. Piersol, Laura N Gitlin, Richard H Fortinsky

Department of Occupational Therapy Faculty Papers

Background and objectives: There is a critical need for effective interventions to support quality of life for persons living with dementia and their caregivers. Growing evidence supports nonpharmacologic programs that provide care management, disease education, skills training, and support. This cost-benefit analysis examined whether the Care of Persons with Dementia in their Environments (COPE) program achieves cost savings when incorporated into Connecticut's home- and community-based services (HCBS), which are state- and Medicaid-funded.

Research design and methods: Findings are based on a pragmatic trial where persons living with dementia and their caregiver dyads were randomly assigned to COPE with HCBS, or …

Poliovirus Immunity Among Children Aged 6-11 And 36-48 Months In 14 Polio High-Risk Provinces Of Afghanistan: A Health-Facility-Based Study, Sajid Bashir Soofi, Maureen Martinez, Noha H. Farag, William S. Hendley, Derek Ehrhardt, Imran Ahmed, Imtiaz Hussain, William Weldon, Ahmed M. Kassem

Department of Paediatrics and Child Health

Afghanistan is one of two countries where wild poliovirus (WPV) type 1 remains endemic. We conducted a facility-based cross-sectional survey of antipoliovirus antibodies in children in 14 provinces of Afghanistan. The provinces were selected based on programmatic priorities for polio eradication. Children aged 6-11 and 36-48 months attending outpatient clinics were enrolled in the study. We collected venous blood, isolated serum, and conducted neutralization assays to detect poliovirus neutralizing antibodies. A total of 2086 children from the 14 provinces were enrolled. Among the enrolled children, 44.3% were girls; the median age in the 6-11-month group was 9.4 months, and in …

Cronkhite-Canada Syndrome: First Case Report From Egypt And North Africa, Ahmed Elsayed Alzamzamy, Ashraf Aboubakr, Hussein H Okasha, Abeer Abdellatef, Shaimaa Elkholy, Mahmoudd Wahba, Mohamed Alboraie, Hussein Elsayed, Mohamed O Othman

Faculty, Staff and Students Publications

Background: Gastrointestinal (GI) polyposis is a rare condition in GI diseases. To date about 500 cases of Cronkhite-Canada syndrome (CCS) have been reported worldwide.

Case summary: We report a 60-year-old female patient who presented with dyspepsia, abdominal pain, and weight loss of 1-year duration. Her physical examination showed alopecia and onychodystrophy. Upper endoscopy revealed diffuse markedly thickened gastric mucosa involving the whole stomach with thickened gastric rugae and numerous polypoidal lesions. Histopathological examination showed marked hyperplasia of the foveolar glands with inflammatory cell infiltration. Endoscopic ultrasound showed a significantly hypertrophic mucosa and muscularis mucosa, while the submucosa and the muscularis …

Central Nervous System (Cns) Inflammatory Demyelinating Diseases (Idds) Associated With Covid-19: A Case Series And Review, Parissa Feizi, Kanika Sharma, Shreya R Pasham, Lalit Nirwan, Joe Joseph, Shruti Jaiswal, Shitiz Sriwastava

Faculty, Staff and Student Publications

BACKGROUND: Over the past two years, SARS-CoV-2 has frequently been documented with various post and para-infectious complications, including cerebrovascular, neuromuscular, and some demyelinating conditions such as acute disseminated encephalomyelitis (ADEM). We report two rare neurological manifestations post-COVID-19 infection; multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Further, we reviewed other CNS inflammatory demyelinating diseases (IDDs) associated with SARS-CoV-2, including optic neuritis (ON) and neuromyelitis optica spectrum disorders (NMOSD).

METHODS: A descriptive analysis and literature search of Google Scholar and PubMed was conducted by two independent reviewers from December 1st, 2019, to March 30th, 2022, and included all the …

Proteômica Plasmática Quantitativa De Pacientes Sobreviventes E Não Sobreviventes De Covid-19 Internados No Hospital Revela Potenciais Biomarcadores Prognósticos E Alvos Terapêuticos, D C. Flora, A D. Valle, H Abs Pereira, T F. Garbieri, L. T. Grizzo, T J. Dionisio, A L. Leite, D Mc Rosa, C F. Santos, M Ar Buzalaf

Nebraska Center for Virology: Faculty Publications

O desenvolvimento de novas abordagens que permitam a avaliação precoce de quais casos de COVID-19 provavelmente se tornarão críticos e a descoberta de novos alvos terapêuticos são importantes. Neste estudo de coorte, foi avaliado o perfil proteômico e laboratorial do plasma de 163 pacientes internados no Hospital Estadual de Bauru (Bauru, SP, Brasil) entre 4 de maio e 4 de julho de 2020, que foram diagnosticados com COVID-19 por RT-PCR a partir de amostras de swab nasofaríngeo amostras. Amostras de plasma foram coletadas na admissão para análises laboratoriais de rotina e análise proteôomica quantitativa shotgun livre de marcadores. De acordo …

Residency Program Directors Meeting, Sandor Shoichet

Conference Presentation Abstracts

No abstract provided.

Sars-Cov-2 Immunization/Therapeutics, Matthew Sims

Conference Presentation Abstracts

No abstract provided.

External Cephalic Version For A Malpresenting First Twin Before Labor: A Prospective Case Series, Laura Felder, Rebekah Jo Mccurdy, Vincenzo Berghella

Department of Obstetrics and Gynecology Faculty Papers

Background: In twin pregnancies where the presenting twin is not cephalic, cesarean delivery is the standard of care. External cephalic version (ECV) has been used for malpresenting singleton pregnancies with low risk of complications. ECV in twin pregnancies is poorly studied.

Objective: To assess feasibility and report any complications of ECV of a malpresenting twin before labor.

Study design: This is a prospective cohort of twin pregnancies with malpresenting first twin. Inclusion criteria included English or Spanish speaking women. Exclusions included cases where there was a contraindication to vaginal delivery. ECV was performed according to the institutional singleton protocol. Fetal …

How Can We Optimise Health Technology Assessment And Reimbursement Decisions To Accelerate Access To New Cardiovascular Medicines?, Martin R Cowie, Biykem Bozkurt, Javed Butler, Andrew Briggs, Maria Kubin, Adrian Jonas, Amanda I Adler, Bray Patrick-Lake, Faiez Zannad

Faculty, Staff and Students Publications

Regulatory approvals of, and subsequent access to, innovative cardiovascular medications have declined. How much of this decline relates to the final step of gaining reimbursement for new treatments is unknown. Payers and health technology assessment (HTA) bodies look beyond efficacy and safety to assess whether a new drug improves patient outcomes, quality of life, or satisfaction at a cost that is affordable compared to existing treatments. HTA bodies work within a limited healthcare budget, and this is one of the reasons why only half of newly approved drugs are accepted for reimbursement, or receive restricted or "optimised" recommendations from HTA …

Comparison Of Longitudinal Skeletal Thigh Muscle Findings With Magnetic Resonance Imaging In Patients With Peripheral Artery Disease With-Versus-Without Diabetes Mellitus, Olga A Gimnich, Carlos B Ortiz, Eric Y Yang, Changyi Chen, Salim S Virani, Panos Kougias, Alan B Lumsden, Joel D Morrisett, Christie M Ballantyne, Vijay Nambi, Gerd Brunner

Faculty, Staff and Students Publications

The aim of this secondary analysis of The Effect of Lipid Modification on Peripheral Artery Disease after Endovascular Intervention Trial (ELIMIT) was to determine longitudinal changes over 24-months in skeletal thigh muscle volumes and individual muscle compartments in peripheral artery disease (PAD) patients with and without diabetes. A total of 48 patients with available magnetic resonance imaging (MRI) of the distal superficial femoral artery (SFA) at baseline and 2-years were included in this analysis. Muscle volumes and SFA wall, lumen, and total vessel volumes were quantified. Intra-reader reproducibility of muscle tracings was assessed with the intraclass correlation coefficient (ICC) using …

Presentation And Predictors Of Metastatic Testicular Cancer: A Contemporary Population-Based Analysis, Yash Shah, Hanan Goldberg, Thenappan Chandrasekar

Student Papers, Posters & Projects

Introduction

• Testicular cancer (TC) is the most common solid malignancy in males aged 14-44, with incidence rising globally, although there are few established risk factors besides cryptorchidism.
• While 70% of men present with localized TC, 18% have regional spread and 12% have metastases. Moreover, one-third of patients diagnosed with Stage I TC actually have occult metastases.

The Use Of Virtual Tools In Narrowing The Impact Of Health Disparities In Neurology., Jean-Baptist Lepichon, Stephanie Horton, Omar Abdelmoity, Mark A. Hoffman, Emily Cramer, Nirmeen Kishk, Salah Hamada, Ahmed Abdelmoity

Manuscripts, Articles, Book Chapters and Other Papers

The concept of Epilepsy Treatment Gap (ETG) refers to the proportion of people with epilepsy who are not being appropriately treated. The ETG in the USA approaches 10%, with historically underserved populations and rural populations disproportionately affected. The ETG in Low-and Middle-Income Countries (LMIC) is reported to be 5-10 times higher than in high-income countries. The growing availability of reliable internet access offers a unique opportunity to provide better care to children and adults with epilepsy. In this paper we explore various telehealth (TH) initiatives that have leveraged the availability of easy and free access to an internet connection in …

Cognitive Functioning And Prevalence Of Seizures Among Older Persons In Uganda: A Hospital-Based, Cross-Sectional Study, Martha Sajatovic

Faculty Scholarship

There is limited data on the prevalence of seizures and dementia among older persons in Uganda. We evaluated cognitive functioning, and the prevalence and factors associated with seizures among older persons attending an outpatient medical clinic in Uganda. We randomly selected older adults (60 years and above) attending Kiruddu National Referral Hospital medical outpatient clinics between October 2020 and March 2021. We excluded individuals with a history of head injury, brain tumors, mental retardation, co-morbidity with HIV and patients who have had recent brain surgery. Cognitive functioning was assessed using the Identification for Dementia in Elderly Africans (IDEA) tool. We …

Machine Learning On Syngeneic Mouse Tumor Profiles To Model Clinical Immunotherapy Response, Zexian Zeng, Shengqing Stan Gu, Cheryl J Wong, Lin Yang, Nofal Ouardaoui, Dian Li, Wubing Zhang, Myles Brown, X Shirley Liu

Faculty, Staff and Student Publications

Most patients with cancer are refractory to immune checkpoint blockade (ICB) therapy, and proper patient stratification remains an open question. Primary patient data suffer from high heterogeneity, low accessibility, and lack of proper controls. In contrast, syngeneic mouse tumor models enable controlled experiments with ICB treatments. Using transcriptomic and experimental variables from >700 ICB-treated/control syngeneic mouse tumors, we developed a machine learning framework to model tumor immunity and identify factors influencing ICB response. Projected on human immunotherapy trial data, we found that the model can predict clinical ICB response. We further applied the model to predicting ICB-responsive/resistant cancer types in …

Radiologist Versus Non-Radiologist Detection Of Lymph Node Metastasis In Papillary Thyroid Carcinoma By Ultrasound: A Meta-Analysis, Peter P. Issa, Lauren Mueller, Mohammad Hussein, Aaron Albuck, Mohamed Shama, Eman Toraih, Emad Kandil

School of Medicine Faculty Publications

Papillary thyroid carcinoma (PTC) is the most common thyroid cancer worldwide and is known to spread to adjacent neck lymphatics. Lymph node metastasis (LNM) is a known predictor of disease recurrence and is an indicator for aggressive resection. Our study aims to determine if ultrasound sonographers’ degree of training influences overall LNM detection. PubMed, Embase, and Scopus articles were searched and screened for relevant articles. Two investigators independently screened and extracted the data. Diagnostic test parameters were determined for all studies, studies reported by radiologists, and studies reported by non-radiologists. The total sample size amounted to 5768 patients and 10,030 …

Advances In Retinopathy Of Prematurity Imaging, Taku Wakabayashi, Samir N. Patel, J. P. Campbell, Emmanuel Y. Chang, Eric D. Nudleman, Yoshihiro Yonekawa

Wills Eye Hospital Papers

Retinopathy of prematurity (ROP) remains the leading cause of childhood blindness worldwide. Recent advances in ROP imaging have significantly improved our understanding of the pathogenesis and pathophysiological course of ROP including the acute phase, regression, reactivation, and late complications, known as adult ROP. Recent progress includes various contact and noncontact wide-field imaging devices for fundus imaging, smartphone-based fundus photography, wide-field fluorescein angiography, handheld optical coherence tomography (OCT) devices for wide-field en face OCT images, and OCT angiography. Images taken by those devices were incorporated in the recently updated guidelines of ROP, the International Classification of Retinopathy of Prematurity, Third Edition …

Combined Trip13 And Aurora Kinase Inhibition Induces Apoptosis In Human Papillomavirus-Driven Cancers, Soma Ghosh, Tuhina Mazumdar, Wei Xu, Reid T Powell, Clifford Stephan, Li Shen, Pooja A Shah, Curtis R Pickering, Jeffery N Myers, Jing Wang, Mitchell J Frederick, Faye M Johnson

Faculty, Staff and Student Publications

PURPOSE: Human papillomavirus (HPV) causes >5% of cancers, but no therapies uniquely target HPV-driven cancers.

EXPERIMENTAL DESIGN: We tested the cytotoxic effect of 864 drugs in 16 HPV-positive and 17 HPV-negative human squamous cancer cell lines. We confirmed apoptosis in vitro and in vivo using patient-derived xenografts. Mitotic pathway components were manipulated with drugs, knockdown, and overexpression.

RESULTS: Aurora kinase inhibitors were more effective in vitro and in vivo in HPV-positive than in HPV-negative models. We hypothesized that the mechanism of sensitivity involves retinoblastoma (Rb) expression because the viral oncoprotein E7 leads to Rb protein degradation, and basal Rb protein …

Human Nop2/Nsun1 Regulates Ribosome Biogenesis Through Non-Catalytic Complex Formation With Box C/D Snornps, Han Liao, Anushri Gaur, Hunter Mcconie, Amirtha Shekar, Karen Wang, Jeffrey T Chang, Ghislain Breton, Catherine Denicourt

Faculty, Staff and Student Publications

5-Methylcytosine (m5C) is a base modification broadly found on various RNAs in the human transcriptome. In eukaryotes, m5C is catalyzed by enzymes of the NSUN family composed of seven human members (NSUN1-7). NOP2/NSUN1 has been primarily characterized in budding yeast as an essential ribosome biogenesis factor required for the deposition of m5C on the 25S ribosomal RNA (rRNA). Although human NOP2/NSUN1 has been known to be an oncogene overexpressed in several types of cancer, its functions and substrates remain poorly characterized. Here, we used a miCLIP-seq approach to identify human NOP2/NSUN1 RNA substrates. Our analysis revealed that NOP2/NSUN1 catalyzes the …