Medical Specialties Commons^™

Targeting Neddylation And Sumoylation In Chemoresistant Triple Negative Breast Cancer, Wei Ruan, Jiwen Li, Seungwon Choi, Xinxin Ma, Yafen Liang, Ragini Nair, Xiaoyi Yuan, Tingting W Mills, Holger K Eltzschig

Faculty, Staff and Student Publications

Previous studies implicate extracellular adenosine signaling in attenuating myocardial ischemia and reperfusion injury (IRI). This extracellular adenosine signaling is terminated by its uptake into cells by equilibrative nucleoside transporters (ENTs). Thus, we hypothesized that targeting ENTs would function to increase cardiac adenosine signaling and concomitant cardioprotection against IRI. Mice were exposed to myocardial ischemia and reperfusion injury. Myocardial injury was attenuated in mice treated with the nonspecific ENT inhibitor dipyridamole. A comparison of mice with global Ent1 or Ent2 deletion showed cardioprotection only in Ent1-/- mice. Moreover, studies with tissue-specific Ent deletion revealed that mice with myocyte-specific Ent1 deletion (Ent1loxP/loxP …

Prediction Of Disease Progression To Upfront Pembrolizumab Monotherapy In Advanced Non-Small-Cell Lung Cancer With High Pd-L1 Expression Using Baseline Ct Disease Quantification And Smoking Pack Years, Ali Silver, Cheryl Ho, Qian Ye, Jianjun Zhang, Ian Janzen, Jessica Li, Montgomery Martin, Lang Wu, Ying Wang, Stephen Lam, Calum Macaulay, Barbara Melosky, Ren Yuan

Faculty, Staff and Student Publications

Health Canada approved pembrolizumab in the first-line setting for advanced non-small-cell lung cancer with PD-L1 ≥ 50% and no EGFR/ALK aberration. The keynote 024 trial showed 55% of such patients progress with pembrolizumab monotherapy. We propose that the combination of baseline CT and clinical factors can help identify those patients who may progress. In 138 eligible patients from our institution, we retrospectively collected their baseline variables, including baseline CT findings (primary lung tumor size and metastatic site), smoking pack years, performance status, tumor pathology, and demographics. The treatment response was assessed via RECIST 1.1 using the baseline and first follow-up …

Genome-Wide Analyses Characterize Shared Heritability Among Cancers And Identify Novel Cancer Susceptibility Regions, Sara Lindström, Lu Wang, Helian Feng, Arunabha Majumdar, Sijia Huo, James Macdonald, Tabitha Harrison, Constance Turman, Hongjie Chen, Nicholas Mancuso, Theo Bammler, Breast Cancer Association Consortium (Bcac), Steve Gallinger, Stephen B Gruber, Marc J Gunter, Loic Le Marchand, Victor Moreno, Kenneth Offit, Colorectal Transdisciplinary Study (Corect), Colon Cancer Family Registry Study (Ccfr), Genetics And Epidemiology Of Colorectal Cancer Consortium (Gecco), Immaculata De Vivo, Tracy A O'Mara, Amanda B Spurdle, Ian Tomlinson, Endometrial Cancer Association Consortium (Ecac), Rebecca Fitzgerald, Puya Gharahkhani, Ines Gockel, Janusz Jankowski, Stuart Macgregor, Johannes Schumacher, Jill Barnholtz-Sloan, Melissa L Bondy, Richard S Houlston, Robert B Jenkins, Beatrice Melin, Margaret Wrensch, Paul Brennan, David C Christiani, Mattias Johansson, James Mckay, Melinda C Aldrich, Christopher I Amos, Maria Teresa Landi, Adonina Tardon, International Lung Cancer Consortium (Ilcco), D Timothy Bishop, Florence Demenais, Alisa M Goldstein, Mark M Iles, Peter A Kanetsky, Matthew H Law, Ovarian Cancer Association Consortium (Ocac), Laufey T Amundadottir, Rachael Stolzenberg-Solomon, Brian M Wolpin, Pancreatic Cancer Cohort Consortium (Panscan), Alison Klein, Gloria Petersen, Harvey Risch, Pancreatic Cancer Case-Control Consortium (Panc4), The Practical Consortium, Stephen J Chanock, Mark P Purdue, Ghislaine Scelo, Paul Pharoah, Siddhartha Kar, Rayjean J Hung, Bogdan Pasaniuc, Peter Kraft

Faculty, Staff and Student Publications

BACKGROUND: The shared inherited genetic contribution to risk of different cancers is not fully known. In this study, we leverage results from 12 cancer genome-wide association studies (GWAS) to quantify pairwise genome-wide genetic correlations across cancers and identify novel cancer susceptibility loci.

METHODS: We collected GWAS summary statistics for 12 solid cancers based on 376 759 participants with cancer and 532 864 participants without cancer of European ancestry. The included cancer types were breast, colorectal, endometrial, esophageal, glioma, head and neck, lung, melanoma, ovarian, pancreatic, prostate, and renal cancers. We conducted cross-cancer GWAS and transcriptome-wide association studies to discover novel …

Bone Growth Induction In Mucopolysaccharidosis Iva Mouse, Estera Rintz, Angélica María Herreño-Pachón, Betul Celik, Fnu Nidhi, Shaukat Khan, Eliana Benincore-Flórez, Shunji Tomatsu

Department of Pediatrics Faculty Papers

Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is caused by a deficiency of the N-acetylgalactosamine-6-sulfate-sulfatase (GALNS) enzyme, leading to the accumulation of glycosaminoglycans (GAG), keratan sulfate (KS) and chondroitin-6-sulfate (C6S), mainly in cartilage and bone. This lysosomal storage disorder (LSD) is characterized by severe systemic skeletal dysplasia. To this date, none of the treatment options for the MPS IVA patients correct bone pathology. Enzyme replacement therapy with elosulfase alpha provides a limited impact on bone growth and skeletal lesions in MPS IVA patients. To improve bone pathology, we propose a novel gene therapy with a small peptide as a growth-promoting …

Germline Genetic Variants And Pediatric Rhabdomyosarcoma Outcomes: A Report From The Children’S Oncology Group, Bailey A Martin-Giacalone, Melissa A Richard, Michael E Scheurer, Javed Khan, Pagna Sok, Priya B Shetty, Stephen J Chanock, Shengchao Alfred Li, Meredith Yeager, Deborah A Marquez-Do, Donald A Barkauskas, David Hall, Matthew T Mcevoy, Austin L Brown, Aniko Sabo, Paul Scheet, Chad D Huff, Stephen X Skapek, Douglas S Hawkins, Rajkumar Venkatramani, Lisa Mirabello, Philip J Lupo

Faculty, Staff and Student Publications

BACKGROUND: Relative to other pediatric cancers, survival for rhabdomyosarcoma (RMS) has not improved in recent decades, suggesting the need to enhance risk stratification. Therefore, we conducted a genome-wide association study for event-free survival (EFS) and overall survival (OS) to identify genetic variants associated with outcomes in individuals with RMS.

METHODS: The study included 920 individuals with newly diagnosed RMS who were enrolled in Children's Oncology Group protocols. To assess the association of each single nucleotide polymorphism (SNP) with EFS and OS, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) using multivariable Cox proportional hazards models, adjusted for clinical …

A Review Of Isomirs In Colorectal Cancer, Molly A. Lausten, Bruce M. Boman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

As advancements in sequencing technology rapidly continue to develop, a new classification of microRNAs has occurred with the discovery of isomiRs, which are relatively common microRNAs with sequence variations compared to their established template microRNAs. This review article seeks to compile all known information about isomiRs in colorectal cancer (CRC), which has not, to our knowledge, been gathered previously to any great extent. A brief overview is given of the history of microRNAs, their implications in colon cancer, the canonical pathway of biogenesis and isomiR classification. This is followed by a comprehensive review of the literature that is available on …

Impact Of Social Media And Multimedia Platforms: View From The Jacc: Case Reports Some Editors, Estefania Oliveros, Yevgeniy Brailovsky, Alessandro Beneduce, Hooman Bakshi, Edoardo Zancanaro, Indah Sukmawati, Mrinali Shetty, Gina Lundberg

Division of Cardiology Faculty Papers

No abstract provided.

Contribution Of Contextual Factors And Neuropathology To Dementia, Monica E. Nelson

USF Tampa Graduate Theses and Dissertations

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that has extensive biological heterogeneity. It is not clear the extent to which this heterogeneity may be detected in participants without dementia, how it relates to incident AD dementia, and whether contextual factors may change how neuropathology relates to incident AD dementia. Therefore, this dissertation was completed using data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI; n = 1,703) and the Czech Brain Aging Study (CBAS; n = 385) to address the following aims: to assess biological heterogeneity in participants without dementia, to relate this heterogeneity to incident AD dementia, and to …

Establishment Of A Consensus Protocol To Explore The Brain Pathobiome In Patients With Mild Cognitive Impairment And Alzheimer's Disease: Research Outline And Call For Collaboration., Richard Lathe, Nikki M Schultek, Brian J. Balin, Garth D Ehrlich, Lavinia Alberi Auber, George Perry, Edward B Breitschwerdt, David B Corry, Richard L Doty, Robert A Rissman, Peter L Nara, Ruth Itzhaki, William A Eimer, Rudolph E Tanzi

PCOM Scholarly Works

Microbial infections of the brain can lead to dementia, and for many decades microbial infections have been implicated in Alzheimer's disease (AD) pathology. However, a causal role for infection in AD remains contentious, and the lack of standardized detection methodologies has led to inconsistent detection/identification of microbes in AD brains. There is a need for a consensus methodology; the Alzheimer's Pathobiome Initiative aims to perform comparative molecular analyses of microbes in post mortem brains versus cerebrospinal fluid, blood, olfactory neuroepithelium, oral/nasopharyngeal tissue, bronchoalveolar, urinary, and gut/stool samples. Diverse extraction methodologies, polymerase chain reaction and sequencing techniques, and bioinformatic tools will …

Plumbing Mysterious Rnas In “Dark Genome” For The Conquest Of Human Diseases, Lisa A Huang, Chunru Lin, Liuqing Yang

Faculty, Staff and Student Publications

Next-generation sequencing has revealed that less than 2% of transcribed genes are translated into proteins, with a large portion transcribed into noncoding RNAs (ncRNAs). Among these, long noncoding RNAs (lncRNAs) represent the largest group and are pervasively transcribed throughout the genome. Dysfunctions in lncRNAs have been found in various diseases, highlighting their potential as therapeutic, diagnostic, and prognostic targets. However, challenges, such as unknown molecular mechanisms and nonspecific immune responses, and issues of drug specificity and delivery present obstacles in translating lncRNAs into clinical applications. In this review, we summarize recent publications that have explored lncRNA functions in human diseases. …

Non-Melanoma Skin Cancer Detection In The Age Of Advanced Technology: A Review, Haleigh Stafford, Jane Buell, Elizabeth Chiang, Uma Ramesh, Michael Migden, Priyadharsini Nagarajan, Moran Amit, Dan Yaniv

Faculty, Staff and Student Publications

Skin cancer is the most common cancer diagnosis in the United States, with approximately one in five Americans expected to be diagnosed within their lifetime. Non-melanoma skin cancer is the most prevalent type of skin cancer, and as cases rise globally, physicians need reliable tools for early detection. Artificial intelligence has gained substantial interest as a decision support tool in medicine, particularly in image analysis, where deep learning has proven to be an effective tool. Because specialties such as dermatology rely primarily on visual diagnoses, deep learning could have many diagnostic applications, including the diagnosis of skin cancer. Furthermore, with …

Tebentafusp In Combination With Durvalumab And/Or Tremelimumab In Patients With Metastatic Cutaneous Melanoma: A Phase 1 Study, Omid Hamid, Jessica C. Hassel, Alexander N. Shoushtari, Friedegund Meier, Todd M. Bauer, April K.S. Salama, John M. Kirkwood, Paolo A. Ascierto, Paul C. Lorigan, Cornelia Mauch, Marlana Orloff, Thomas R. Jeffry Evans, Chris Holland, Ramakrishna Edukulla, Shaad E. Abedin, Mark R. Middleton

Department of Medical Oncology Faculty Papers

BACKGROUND: Immune checkpoint inhibitors have significantly improved outcomes in first line cutaneous melanoma. However, there is a high unmet need for patients who progress on these therapies and combination therapies are being explored to improve outcomes. Tebentafusp is a first-in-class gp100×CD3 ImmTAC bispecific that demonstrated overall survival (OS) benefit (HR 0.51) in metastatic uveal melanoma despite a modest overall response rate of 9%. This phase 1b trial evaluated the safety and initial efficacy of tebentafusp in combination with durvalumab (anti-programmed death ligand 1 (PDL1)) and/or tremelimumab (anti-cytotoxic T lymphocyte-associated antigen 4) in patients with metastatic cutaneous melanoma (mCM), the majority …

Decoding The Regulatory Roles Of Non-Coding Rnas In Cellular Metabolism And Disease, Yuru Zong, Xuliang Wang, Bing Cui, Xiaowei Xiong, Andrew Wu, Chunru Lin, Yaohua Zhang

Faculty, Staff and Student Publications

Non-coding RNAs, including long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), are being studied extensively in a variety of fields. Their roles in metabolism have received increasing attention in recent years but are not yet clear. The regulation of glucose, fatty acid, and amino acid metabolism is an imperative physiological process that occurs in living organisms and takes part in cancer and cardiovascular diseases. Here, we summarize the important roles played by non-coding RNAs in glucose metabolism, fatty acid metabolism, and amino acid metabolism, as well as the mechanisms involved. We also summarize the therapeutic advances for non-coding …

Noncoding Rnas: Hope And Hype At 30 Years, George A Calin

Faculty, Staff and Student Publications

No abstract provided.

Esophageal Lesion Reveals An Aortic Pseudoaneurysm In The Setting Of Actinomyces Odontolyticus Bacteremia, Anneliese Grewing, Harsha Jujjavarapu, Cameron Price, Lindsay F Eilers, Sloane Zimmerman, Nahid Hiermandi, Athar M Qureshi, Richard Kellermayer, Jolie J Britt

Faculty, Staff and Students Publications

A toddler presented with hematemesis a few weeks after ingesting a penny. Workup revealed an esophageal lesion communicating with an aortic pseudoaneurysm in the setting of Actinomyces odontolyticus bacteremia. A. odontolytica is an oropharyngeal bacteria known to cause fistulas when introduced into tissue planes. (Level of Difficulty: Intermediate.)

The Novel Uncompetitive Nmda Receptor Antagonist Esmethadone (Rel-1017) Has No Meaningful Abuse Potential In Recreational Drug Users, Megan J Shram, Jack E Henningfield, Glen Apseloff, Charles W Gorodetzky, Sara De Martin, Frank L Vocci, Frank L Sapienza, Thomas R Kosten, Jeff Huston, August Buchhalter, Judy Ashworth, Ryan Lanier, Franco Folli, Andrea Mattarei, Clotilde Guidetti, Stefano Comai, Cedric O'Gorman, Sergio Traversa, Charles E Inturrisi, Paolo L Manfredi, Marco Pappagallo

Faculty, Staff and Students Publications

Esmethadone (REL-1017) is the opioid-inactive dextro-isomer of methadone and a low-affinity, low-potency uncompetitive NMDA receptor antagonist. In a Phase 2, randomized, double-blind, placebo-controlled trial, esmethadone showed rapid, robust, and sustained antidepressant effects. Two studies were conducted to evaluate the abuse potential of esmethadone. Each study utilized a randomized, double-blind, active-, and placebo-controlled crossover design to assess esmethadone compared with oxycodone (Oxycodone Study) or ketamine (Ketamine Study) in healthy recreational drug users. Esmethadone 25 mg (proposed therapeutic daily dose), 75 mg (loading dose), and 150 mg (Maximum Tolerated Dose) were evaluated in each study. Positive controls were oral oxycodone 40 mg …

Comparison Of Medical Management Versus Parathyroidectomy In Patients With Mild Primary Hyperparathyroidism: A Meta-Analysis., Katherine A. Cironi, Peter P. Issa, Aaron L. Albuck, Christina Mccarthy, Leely Rezvani, Mohammad Hussein, Xinyi Luo, Mohamed Shama, Eman Toraih, Emad Kandil

School of Medicine Faculty Publications

Background: Parathyroidectomy is the definitive cure for patients with primary hyperparathyroidism (pHPT) and has an annual prevalence of 0.2–1% in the United States. Some patients with mild disease are medically managed effectively using calcium-lowering medications and drugs against complications such as osteoporosis; however, many maintain a persistently high calcium level that negatively impacts their skeletal, renal, and psychogenic systems over the long term. This meta-analysis aims to compare the outcomes of medical management versus parathyroidectomy in patients with mild pHPT. Study Design: This meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines …

Genetic Variants And Anterior Cruciate Ligament Rupture – Elastin Proteins Gene And Fibromodulin Gene Polymorphisms, Ewelina Lulińska, Joanna Żelazny, Agnieszka Lulińska, Elżbieta Grzywacz, Aleksandra Stroińska-Pluta, Marek Sawczuk, Magdalena Stanulewicz

Baltic Journal of Health and Physical Activity

Introduction: Anterior cruciate ligament (ACL) injuries are among the most common ligament injuries of the knee and often require reconstruction. The etiology of the molecular mechanisms of rupture of the anterior cruciate ligament (ACL) is poorly understood, and many external and internal factors have been associated with it, including genetics. This study aimed to investigate the association of sequence variants in the ELN and FMOD candidate genes with ACL ruptures based on the essential biological functions of these two proteoglycan-encoding genes in maintaining the structural integrity of tissues and regulating fibrillogenesis. Material and Methods: The partici-pants consisted of 229 (164 …

Acute Suppurative Thyroiditis Secondary To Gemella With Extensive Complications, Amber Champion

Department of Internal Medicine Faculty Research

A young woman developed thyroid storm secondary to acute suppurative thyroiditis, with Gemella morbillorum bacteremia. Her case was complicated by neck abscess, Lemierre syndrome (septic thrombophlebitis of the internal jugular vein), mediastinitis, and pleural effusion. She was treated for thyroid storm including steroids and antibiotics. The infectious complications required several surgical procedures and interventions and a prolonged hospital stay, but she ultimately made a full recovery. Complications from suppurative thyroiditis can be rapid and widespread; swift recognition and treatment by a multidisciplinary team can help to prevent complications.

A Nurse-Led Telehealth Program For Diabetes Foot Care: Feasibility And Usability Study, Hsiao-Hui Ju, Rashmi Momin, Stanley Cron, Jed Jularbal, Jeffery Alford, Constance Johnson

Faculty, Staff and Student Publications

BACKGROUND: Diabetes mellitus can lead to severe and debilitating foot complications, such as infections, ulcerations, and amputations. Despite substantial progress in diabetes care, foot disease remains a major challenge in managing this chronic condition that causes serious health complications worldwide.

OBJECTIVE: The primary aim of this study was to examine the feasibility and usability of a telehealth program focused on preventive diabetes foot care. A secondary aim was to descriptively measure self-reported changes in diabetes knowledge, self-care, and foot care behaviors before and after participating in the program.

METHODS: The study used a single-arm, pre-post design in 2 large family …

Achondroplasia Natural History Study (Clarity): 60-Year Experience In Orthopedic Surgery From Four Skeletal Dysplasia Centers, Nickolas J Nahm, W G Stuart Mackenzie, William G Mackenzie, Ethan Gough, S Shahrukh Hashmi, Jacqueline T Hecht, Janet M Legare, Mary Ellen Little, Peggy Modaff, Richard M Pauli, David F Rodriguez-Buritica, Maria Elena Serna, Cory J Smid, Julie Hoover-Fong, Michael B Bober

Faculty, Staff and Student Publications

BACKGROUND: The purpose of this study was to describe the frequency and risk factors for orthopedic surgery in patients with achondroplasia. CLARITY (The Achondroplasia Natural History Study) includes clinical data from achondroplasia patients receiving treatment at four skeletal dysplasia centers in the United States from 1957 to 2018. Data were entered and stored in a Research Electronic Data Capture (REDCap) database.

RESULTS: Information from one thousand three hundred and seventy-four patients with achondroplasia were included in this study. Four hundred and eight (29.7%) patients had at least one orthopedic surgery during their lifetime and 299 (21.8%) patients underwent multiple procedures. …

Effect Of Porosity In Activated Carbon Supports For Silicon-Based Lithium-Ion Batteries (Libs), Yun Jeong Choi, Jeong Bin Choi, Ji Sun Im, Ji Hong Kim

Faculty, Staff and Student Publications

Activated carbon supports for Si deposition with different porosities were prepared, and the effect of porosity on the electrochemical characteristics was investigated. The porosity of the support is a key parameter affecting the Si deposition mechanism and the stability of the electrode. In the Si deposition mechanism, as the porosity of activated carbon increases, the effect of particle size reduction due to the uniform dispersion of Si was confirmed. This implies that the porosity of activated carbon can affect the rate performance. However, excessively high porosity reduced the contact area between Si and activated carbon, resulting in poor electrode stability. …

Achondroplasia Natural History Study (Clarity): 60-Year Experience In Orthopedic Surgery From Four Skeletal Dysplasia Centers, Nickolas J Nahm, W G Stuart Mackenzie, William G Mackenzie, Ethan Gough, S Shahrukh Hashmi, Jacqueline T Hecht, Janet M Legare, Mary Ellen Little, Peggy Modaff, Richard M Pauli, David F Rodriguez-Buritica, Maria Elena Serna, Cory J Smid, Julie Hoover-Fong, Michael B Bober

Faculty, Staff and Student Publications

BACKGROUND: The purpose of this study was to describe the frequency and risk factors for orthopedic surgery in patients with achondroplasia. CLARITY (The Achondroplasia Natural History Study) includes clinical data from achondroplasia patients receiving treatment at four skeletal dysplasia centers in the United States from 1957 to 2018. Data were entered and stored in a Research Electronic Data Capture (REDCap) database.

RESULTS: Information from one thousand three hundred and seventy-four patients with achondroplasia were included in this study. Four hundred and eight (29.7%) patients had at least one orthopedic surgery during their lifetime and 299 (21.8%) patients underwent multiple procedures. …

Steroid Responsive Idiopathic Calcitriol Induced Hypercalcemia: A Case Report And Review Of The Literature, Omar El Fadel, Anshel Kenkare, Jingjing Zhang

Division of Internal Medicine Faculty Papers & Presentations

BACKGROUND: Idiopathic Calcitriol Induced Hypercalcemia is a rare cause of a common condition of hypercalcemia. Hypercalcemia is most commonly the result of hyperparathyroidism and together with hypercalcemia of malignancy accounts for over 95% of cases. Idiopathic Calcitriol Induced Hypercalcemia can mimic hypercalcemia secondary to granulomatous diseases like sarcoidosis, but with apparent absences of both imaging and physical exam findings consistent with the disease. We report here a 51-year-old man who presented with recurrent nephrolithiasis, hypercalcemia, and acute kidney injury.

CASE PRESENTATION: A 51-year-old man presented with severe back pain and mild hematuria. He had a history of recurrent nephrolithiasis over …

Targeting Cxcr4 Abrogates Resistance To Trastuzumab By Blocking Cell Cycle Progression And Synergizes With Docetaxel In Breast Cancer Treatment, Shuying Liu, Shelly M Xie, Wenbin Liu, Mihai Gagea, Ariella B Hanker, Nguyen Nguyen, Akshara Singareeka Raghavendra, Gloria Yang-Kolodji, Fuliang Chu, Sattva S Neelapu, Adriano Marchese, Samir Hanash, Johann Zimmermann, Carlos L Arteaga, Debasish Tripathy

Faculty, Staff and Student Publications

Background: Although trastuzumab and other HER2-targeted therapies have significantly improved survival in patients with HER2 overexpressed or amplified (HER2+) breast cancer, a significant proportion of patients do not respond or eventually develop clinical resistance. Strategies to reverse trastuzumab resistance remain a high clinical priority. We were the first to report the role of CXCR4 in trastuzumab resistance. The present study aims to explore the therapeutic potential of targeting CXCR4 and better understand the associated mechanisms.

Methods: Immunofluorescent staining, confocal microscopy analysis, and immunoblotting were used to analyze CXCR4 expression. BrdU incorporation assays and flow cytometry were used to analyze dynamic …

Achondroplasia Natural History Study (Clarity): 60-Year Experience In Orthopedic Surgery From Four Skeletal Dysplasia Centers, Nickolas J Nahm, W G Stuart Mackenzie, William G Mackenzie, Ethan Gough, S Shahrukh Hashmi, Jacqueline T Hecht, Janet M Legare, Mary Ellen Little, Peggy Modaff, Richard M Pauli, David F Rodriguez-Buritica, Maria Elena Serna, Cory J Smid, Julie Hoover-Fong, Michael B Bober

Faculty, Staff and Student Publications

BACKGROUND: The purpose of this study was to describe the frequency and risk factors for orthopedic surgery in patients with achondroplasia. CLARITY (The Achondroplasia Natural History Study) includes clinical data from achondroplasia patients receiving treatment at four skeletal dysplasia centers in the United States from 1957 to 2018. Data were entered and stored in a Research Electronic Data Capture (REDCap) database.

RESULTS: Information from one thousand three hundred and seventy-four patients with achondroplasia were included in this study. Four hundred and eight (29.7%) patients had at least one orthopedic surgery during their lifetime and 299 (21.8%) patients underwent multiple procedures. …

Achondroplasia Natural History Study (Clarity): 60-Year Experience In Orthopedic Surgery From Four Skeletal Dysplasia Centers, Nickolas J Nahm, W G Stuart Mackenzie, William G Mackenzie, Ethan Gough, S Shahrukh Hashmi, Jacqueline T Hecht, Janet M Legare, Mary Ellen Little, Peggy Modaff, Richard M Pauli, David F Rodriguez-Buritica, Maria Elena Serna, Cory J Smid, Julie Hoover-Fong, Michael B Bober

Faculty, Staff and Student Publications

BACKGROUND: The purpose of this study was to describe the frequency and risk factors for orthopedic surgery in patients with achondroplasia. CLARITY (The Achondroplasia Natural History Study) includes clinical data from achondroplasia patients receiving treatment at four skeletal dysplasia centers in the United States from 1957 to 2018. Data were entered and stored in a Research Electronic Data Capture (REDCap) database.

RESULTS: Information from one thousand three hundred and seventy-four patients with achondroplasia were included in this study. Four hundred and eight (29.7%) patients had at least one orthopedic surgery during their lifetime and 299 (21.8%) patients underwent multiple procedures. …

17Β-Estradiol Promotes Extracellular Vesicle Release And Selective Mirna Loading In Erα-Positive Breast Cancer, Rares Drula, Barbara Pardini, Xiao Fu, Mireia Cruz De Los Santos, Ancuta Jurj, Lan Pang, Sherien M El-Daly, Linda Fabris, Erik Knutsen, Mihnea P Dragomir, Recep Bayraktar, Yongfeng Li, Meng Chen, Filippo Del Vecchio, Léa Berland, Jessica Dae, Daniel Fan, Masayoshi Shimizu, Anh M Tran, Mercedes Barzi, Carlotta Pioppini, Angelica M Gutierrez, Cristina Ivan, Salyna Meas, Carolyn S Hall, Suresh K Alahari, Ioana Berindan-Neagoe, Muller Fabbri, Anthony Lucci, Banu Arun, Simone Anfossi, George A Calin

Faculty, Staff and Student Publications

The causes and consequences of abnormal biogenesis of extracellular vesicles (EVs) are not yet well understood in malignancies, including in breast cancers (BCs). Given the hormonal signaling dependence of estrogen receptor-positive (ER+) BC, we hypothesized that 17β-estradiol (estrogen) might influence EV production and microRNA (miRNA) loading. We report that physiological doses of 17β-estradiol promote EV secretion specifically from ER+ BC cells via inhibition of miR-149-5p, hindering its regulatory activity on SP1, a transcription factor that regulates the EV biogenesis factor nSMase2. Additionally, miR-149-5p downregulation promotes hnRNPA1 expression, responsible for the loading of let-7's miRNAs into EVs. In multiple patient cohorts, …

Non-Homologous End-Joining Pathway Genotypes Significantly Associated With Nasopharyngeal Carcinoma Susceptibility, Chia-Wen Tsai, Liang-Chun Shih, Wen-Shin Chang, Che-Lun Hsu, Jie-Long He, Te-Chun Hsia, Yun-Chi Wang, Jian Gu, Da-Tian Bau

Faculty, Staff and Student Publications

Defects in the non-homologous end-joining (NHEJ) DNA repair pathway lead to genomic instability and carcinogenesis. However, the roles of individual NHEJ genes in nasopharyngeal carcinoma (NPC) etiology are not well-understood. The aim of this study was to assess the contribution of NHEJ genotypes, including XRCC4 (rs6869366, rs3734091, rs28360071, rs28360317, rs1805377), XRCC5 (rs828907, rs11685387, rs9288518), XRCC6 (rs5751129, rs2267437, rs132770, rs132774), XRCC7 rs7003908, and Ligase4 rs1805388, to NPC risk, with 208 NPC patients and 416 controls. Genotype-phenotype correlations were also investigated by measuring mRNA and protein expression in adjacent normal tissues and assessing the NHEJ repair capacity in blood lymphocytes from 43 …

Genotype-Degree Of Hemolysis Correlation In Hereditary Spherocytosis, Yimeng Shi, Yuan Li, Xiawan Yang, Xiaoxia Li, Guangxin Peng, Xin Zhao, Xu Liu, Yufei Zhao, Jing Hu, Xiangrong Hu, Baohang Zhang, Kang Zhou, Yang Yang, Youzhen Xiong, Jianping Li, Huihui Fan, Wenrui Yang, Lei Ye, Liping Jing, Li Zhang, Fengkui Zhang

Faculty, Staff and Student Publications

BACKGROUND: Hereditary spherocytosis (HS) is a common inherited hemolytic anemia, caused by mutations in five genes that encode erythrocyte membrane skeleton proteins. The red blood cell (RBC) lifespan could directly reflect the degree of hemolysis. In the present cohort of 23 patients with HS, we performed next-generation sequencing (NGS) and Levitt's carbon monoxide (CO) breath test to investigate the potential genotype-degree of hemolysis correlation.

RESULTS: In the present cohort, we identified 8 ANK1,9 SPTB,5 SLC4A1 and 1 SPTA1 mutations in 23 patients with HS, and the median RBC lifespan was 14(8-48) days. The median RBC lifespan of patients with ANK1, …