Digital Commons Network^™

Generalized And Transferable Patient Language Representation For Phenotyping With Limited Data, Yuqi Si, Elmer V Bernstam, Kirk Roberts

Faculty, Staff and Student Publications

The paradigm of representation learning through transfer learning has the potential to greatly enhance clinical natural language processing. In this work, we propose a multi-task pre-training and fine-tuning approach for learning generalized and transferable patient representations from medical language. The model is first pre-trained with different but related high-prevalence phenotypes and further fine-tuned on downstream target tasks. Our main contribution focuses on the impact this technique can have on low-prevalence phenotypes, a challenging task due to the dearth of data. We validate the representation from pre-training, and fine-tune the multi-task pre-trained models on low-prevalence phenotypes including 38 circulatory diseases, 23 …

Preventing Physician Suicide., Jennifer L Middleton

Ambulatory and Primary Care Articles

No abstract provided.

Successful Distancing: Telemedicine In Gastroenterology And Hepatology During The Covid-19 Pandemic., Abhilash Perisetti M.B.B.S, M.D., Hemant Goyal

Other Specialties

Telemedicine involves delivering healthcare and preventative care services to patients without the need for in-person encounters. Traditionally, telemedicine has been used for acute events (e.g., stroke, used to relay essential information to the emergency department) and chronic disease management (e.g., diabetes and chronic kidney disease management). Though the utilization of telemedicine in gastroenterology and hepatology has been modest at best, especially for inflammatory bowel diseases and chronic liver disease management, since the onset of coronavirus disease 2019 (COVID-19) pandemic, utilization of telemedicine in gastroenterology increased by 4000% in the first two weeks, equivalent to the last six years of growth …

Meal-Induced Symptoms In Children With Dyspepsia-Relationships To Sex And The Presence Of Gastroparesis, Liz Febo-Rodriguez, Bruno P Chumpitazi, Salma Musaad, Andrew C Sher, Robert J Shulman

Children’s Nutrition Research Center Staff Publications

Objectives: To test the hypothesis that in children with dyspepsia, prospective symptom severity following ingestion of a meal would correlate with percent gastric retention, and those ultimately diagnosed with gastroparesis would report worse symptoms.

Study design: Prospective, single-center study with 104 children with dyspepsia completing a prospective dyspepsia symptom questionnaire before and after eating a standardized Tougas meal during gastric emptying scintigraphy. Main outcomes included correlation between gastric retention and symptoms and comparison of symptom severity between those with and without gastroparesis.

Results: Fifty-two children (50%) had gastroparesis (gastroparesis: 12.5 ± 2.9 years, 65% female; nongastroparesis: 13.0 ± 2.9 years, …

Cell Signaling Regulation In Salivary Gland Development, Akiko Suzuki, Kenichi Ogata, Junichi Iwata

Faculty, Staff and Student Publications

The mammalian salivary gland develops as a highly branched structure designed to produce and secrete saliva. This review focuses on research conducted on mammalian salivary gland development, particularly on the differentiation of acinar, ductal, and myoepithelial cells. We discuss recent studies that provide conceptual advances in the understanding of the molecular mechanisms of salivary gland development. In addition, we describe the organogenesis of submandibular glands (SMGs), model systems used for the study of SMG development, and the key signaling pathways as well as cellular processes involved in salivary gland development. The findings from the recent studies elucidating the identity of …

Uterine Contractions In Rodent Models And Humans, Manasi Malik, Michelle Roh, Sarah K England

2020-Current year OA Pubs

Aberrant uterine contractions can lead to preterm birth and other labour complications and are a significant cause of maternal morbidity and mortality. To investigate the mechanisms underlying dysfunctional uterine contractions, researchers have used experimentally tractable small animal models. However, biological differences between humans and rodents change how researchers select their animal model and interpret their results. Here, we provide a general review of studies of uterine excitation and contractions in mice, rats, guinea pigs, and humans, in an effort to introduce new researchers to the field and help in the design and interpretation of experiments in rodent models.

Automated Software-Assisted Diagnosis Of Esophageal Squamous Cell Neoplasia Using High-Resolution Microendoscopy, Mimi C Tan, Sheena Bhushan, Timothy Quang, Richard Schwarz, Kalpesh H Patel, Xinying Yu, Zhengqi Li, Guiqi Wang, Fan Zhang, Xueshan Wang, Hong Xu, Rebecca R Richards-Kortum, Sharmila Anandasabapathy

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: High-resolution microendoscopy (HRME) is an optical biopsy technology that provides subcellular imaging of esophageal mucosa but requires expert interpretation of these histopathology-like images. We compared endoscopists with an automated software algorithm for detection of esophageal squamous cell neoplasia (ESCN) and evaluated the endoscopists' accuracy with and without input from the software algorithm.

METHODS: Thirteen endoscopists (6 experts, 7 novices) were trained and tested on 218 post-hoc HRME images from 130 consecutive patients undergoing ESCN screening/surveillance. The automated software algorithm interpreted all images as neoplastic (high-grade dysplasia, ESCN) or non-neoplastic. All endoscopists provided their interpretation (neoplastic or non-neoplastic) …

Three-Year Outcomes From The Liberty 360 Study Of Endovascular Interventions For Peripheral Artery Disease Stratified By Rutherford Category., Stefanos Giannopoulos, Jihad Mustapha, William A Gray, Gary Ansel, George Adams, Eric A Secemsky, Ehrin J Armstrong

Heart and Vascular Articles

PURPOSE: To report the 3-year results of the LIBERTY 360 study, which investigated outcomes of endovascular treatment of symptomatic peripheral artery disease (PAD).

MATERIALS AND METHODS: The LIBERTY trial (

RESULTS: The 36-month KM survival rates were 86.0% in RC 2-3, 79.8% in RC 4-5, and 62.0% in RC 6 groups. The KM estimates of freedom from major amputation at 36 months were 98.5% in RC 2-3, 94.0% in RC 4-5, and 79.9% in RC 6. The 36-month KM estimates for freedom from TVR/TLR were 71.1% in RC 2-3, 64.2% in RC 4-5 and 61.9% in RC 6 groups. Patients …

Efficacy, Pharmacokinetics, And Safety Over 48 Weeks With Ibalizumab-Based Therapy In Treatment-Experienced Adults Infected With Hiv-1: A Phase 2a Study, Joseph C Gathe, Robin L Hardwicke, Fernando Garcia, Steven Weinheimer, Stanley T Lewis, Robert Brandon Cash

Faculty, Staff and Student Publications

Ibalizumab, a humanized monoclonal antibody targeting CD4, blocks HIV-1 entry into cells and is the first Food and Drug Adminstration-approved long-acting agent for HIV-1 treatment. In this phase 2a study, 82 HIV-infected adults failing antiretroviral therapy were assigned an individually optimized background regimen (OBR) and randomized 1:1:1 to arm A (15 mg/kg ibalizumab q2wk), arm B (10 mg/kg weekly for 9 weeks, then q2wk), or placebo. Subjects with an inadequate response at week 16 were permitted to cross over to a new OBR plus 15 mg/kg ibalizumab q2wk. At week 16, viral load (VL) reduction was significantly greater than placebo …

Discovery And Fine-Mapping Of Height Loci Via High-Density Imputation Of Gwass In Individuals Of African Ancestry, Mariaelisa Graff, Anne E Justice, Kristin L Young, Eirini Marouli, Xinruo Zhang, Rebecca S Fine, Elise Lim, Victoria Buchanan, Kristin Rand, Mary F Feitosa, Mary K Wojczynski, Lisa R Yanek, Yaming Shao, Rebecca Rohde, Adebowale A Adeyemo, Melinda C Aldrich, Matthew A Allison, Christine B Ambrosone, Stefan Ambs, Christopher Amos, Donna K Arnett, Larry Atwood, Elisa V Bandera, Traci Bartz, Diane M Becker, Sonja I Berndt, Leslie Bernstein, Lawrence F Bielak, William J Blot, Erwin P Bottinger, Donald W Bowden, Jonathan P Bradfield, Jennifer A Brody, Ulrich Broeckel, Gregory Burke, Brian E Cade, Qiuyin Cai, Neil Caporaso, Chris Carlson, John Carpten, Graham Casey, Stephen J Chanock, Guanjie Chen, Minhui Chen, Yii-Der I Chen, Wei-Min Chen, Alessandra Chesi, Charleston W K Chiang, Lisa Chu, Gerry A Coetzee, David V Conti, Richard S Cooper, Mary Cushman, Ellen Demerath, Sandra L Deming, Latchezar Dimitrov, Jingzhong Ding, W Ryan Diver, Qing Duan, Michele K Evans, Adeyinka G Falusi, Jessica D Faul, Myriam Fornage, Caroline Fox, Barry I Freedman, Melissa Garcia, Elizabeth M Gillanders, Phyllis Goodman, Omri Gottesman, Struan F A Grant, Xiuqing Guo, Hakon Hakonarson, Talin Haritunians, Tamara B Harris, Curtis C Harris, Brian E Henderson, Anselm Hennis, Dena G Hernandez, Joel N Hirschhorn, Lorna Haughton Mcneill, Timothy D Howard, Barbara Howard, Ann W Hsing, Yu-Han H Hsu, Jennifer J Hu, Chad D Huff, Dezheng Huo, Sue A Ingles, Marguerite R Irvin, Esther M John, Karen C Johnson, Joanne M Jordan, Edmond K Kabagambe, Sun J Kang, Sharon L Kardia, Brendan J Keating, Rick A Kittles, Eric A Klein, Suzanne Kolb, Laurence N Kolonel, Charles Kooperberg, Lewis Kuller, Abdullah Kutlar, Leslie Lange, Carl D Langefeld, Loic Le Marchand, Hampton Leonard, Guillaume Lettre, Albert M Levin, Yun Li, Jin Li, Yongmei Liu, Youfang Liu, Simin Liu, Kurt Lohman, Vaneet Lotay, Yingchang Lu, William Maixner, Joann E Manson, Barbara Mcknight, Yan Meng, Keri L Monda, Kris Monroe, Jason H Moore, Thomas H Mosley, Poorva Mudgal, Adam B Murphy, Rajiv Nadukuru, Mike A Nalls, Katherine L Nathanson, Uma Nayak, Amidou N'Diaye, Barbara Nemesure, Christine Neslund-Dudas, Marian L Neuhouser, Sarah Nyante, Heather Ochs-Balcom, Temidayo O Ogundiran, Adesola Ogunniyi, Oladosu Ojengbede, Hayrettin Okut, Olufunmilayo I Olopade, Andrew Olshan, Badri Padhukasahasram, Julie Palmer, Cameron D Palmer, Nicholette D Palmer, George Papanicolaou, Sanjay R Patel, Curtis A Pettaway, Patricia A Peyser, Michael F Press, D C Rao, Laura J Rasmussen-Torvik, Susan Redline, Alex P Reiner, Suhn K Rhie, Jorge L Rodriguez-Gil, Charles N Rotimi, Jerome I Rotter, Edward A Ruiz-Narvaez, Benjamin A Rybicki, Babatunde Salako, Michele M Sale, Maureen Sanderson, Eric Schadt, Pamela J Schreiner, Claudia Schurmann, Ann G Schwartz, Daniel A Shriner, Lisa B Signorello, Andrew B Singleton, David S Siscovick, Jennifer A Smith, Shad Smith, Elizabeth Speliotes, Margaret Spitz, Janet L Stanford, Victoria L Stevens, Alex Stram, Sara S Strom, Lara Sucheston, Yan V Sun, Salman M Tajuddin, Herman Taylor, Kira Taylor, Bamidele O Tayo, Michael J Thun, Margaret A Tucker, Dhananjay Vaidya, David J Van Den Berg, Sailaja Vedantam, Mara Vitolins, Zhaoming Wang, Erin B Ware, Sylvia Wassertheil-Smoller, David R Weir, John K Wiencke, Scott M Williams, L Keoki Williams, James G Wilson, John S Witte, Margaret Wrensch, Xifeng Wu, Jie Yao, Neil Zakai, Krista Zanetti, Babette S Zemel, Wei Zhao, Jing Hua Zhao, Wei Zheng, Degui Zhi, Jie Zhou, Xiaofeng Zhu, Regina G Ziegler, Joe Zmuda, Alan B Zonderman, Bruce M Psaty, Ingrid B Borecki, L Adrienne Cupples, Ching-Ti Liu, Christopher A Haiman, Ruth Loos, Maggie C Y Ng, Kari E North

Faculty, Staff and Student Publications

Although many loci have been associated with height in European ancestry populations, very few have been identified in African ancestry individuals. Furthermore, many of the known loci have yet to be generalized to and fine-mapped within a large-scale African ancestry sample. We performed sex-combined and sex-stratified meta-analyses in up to 52,764 individuals with height and genome-wide genotyping data from the African Ancestry Anthropometry Genetics Consortium (AAAGC). We additionally combined our African ancestry meta-analysis results with published European genome-wide association study (GWAS) data. In the African ancestry analyses, we identified three novel loci (SLC4A3, NCOA2, ECD/FAM149B1) in sex-combined results and two …

Value Of Emergent Neurovascular Imaging For "Seat Belt Injury": A Multi-Institutional Study, F G Sherbaf, B Chen, T Pomeranz, M Shahriari, M E Adin, S Mirbagheri, E Beheshtian, R Jalilianhasanpour, J Pakpoor, J W Lazor, A Kamali, D M Yousem

Faculty, Staff and Student Publications

BACKGROUND AND PURPOSE: Screening for blunt cerebrovascular injury in patients after motor vehicle collision (MVC) solely based on the presence of cervical seat belt sign has been debated in the literature without consensus. Our aim was to assess the value of emergent neurovascular imaging in patients after an MVC who present with a seat belt sign through a large-scale multi-institutional study.

MATERIALS AND METHODS: The electronic medical records of patients admitted to the emergency department with CTA/MRAs performed with an indication of seat belt injury of the neck were retrospectively reviewed at 5 participating institutions. Logistic regression analysis was used …

A Phase Ii Study Of Autologous Mesenchymal Stromal Cells And C-Kit Positive Cardiac Cells, Alone Or In Combination, In Patients With Ischaemic Heart Failure: The Cctrn Concert-Hf Trial, Roberto Bolli, Raul D Mitrani, Joshua M Hare, Carl J Pepine, Emerson C Perin, James T Willerson, Jay H Traverse, Timothy D Henry, Phillip C Yang, Michael P Murphy, Keith L March, Ivonne H Schulman, Sohail Ikram, David P Lee, Connor O'Brien, Joao A Lima, Mohammad R Ostovaneh, Bharath Ambale-Venkatesh, Gregory Lewis, Aisha Khan, Ketty Bacallao, Krystalenia Valasaki, Bangon Longsomboon, Adrian P Gee, Sara Richman, Doris A Taylor, Dejian Lai, Shelly L Sayre, Judy Bettencourt, Rachel W Vojvodic, Michelle L Cohen, Lara Simpson, David Aguilar, Catalin Loghin, Lem Moyé, Ray F Ebert, Barry R Davis, Robert D Simari

Faculty, Staff and Student Publications

AIMS: CONCERT-HF is an NHLBI-sponsored, double-blind, placebo-controlled, Phase II trial designed to determine whether treatment with autologous bone marrow-derived mesenchymal stromal cells (MSCs) and c-kit positive cardiac cells (CPCs), given alone or in combination, is feasible, safe, and beneficial in patients with heart failure (HF) caused by ischaemic cardiomyopathy.

METHODS AND RESULTS: Patients were randomized (1:1:1:1) to transendocardial injection of MSCs combined with CPCs, MSCs alone, CPCs alone, or placebo, and followed for 12 months. Seven centres enrolled 125 participants with left ventricular ejection fraction of 28.6 ± 6.1% and scar size 19.4 ± 5.8%, in New York Heart Association …

Hypoxia-Inducible Factor–1Α–Dependent Induction Of Mir122 Enhances Hepatic Ischemia Tolerance, Cynthia Ju, Meng Wang, Eunyoung Tak, Boyun Kim, Christoph Emontzpohl, Yang Yang, Xiaoyi Yuan, Huban Kutay, Yafen Liang, David R Hall, Wasim A Dar, J Steve Bynon, Peter Carmeliet, Kalpana Ghoshal, Holger K Eltzschig

Faculty, Staff and Student Publications

Hepatic ischemia and reperfusion (IR) injury contributes to the morbidity and mortality associated with liver transplantation. microRNAs (miRNAs) constitute a family of noncoding RNAs that regulate gene expression at the posttranslational level through the repression of specific target genes. Here, we hypothesized that miRNAs could be targeted to enhance hepatic ischemia tolerance. A miRNA screen in a murine model of hepatic IR injury pointed us toward the liver-specific miRNA miR122. Subsequent studies in mice with hepatocyte-specific deletion of miR122 (miR122loxP/loxP Alb-Cre+ mice) during hepatic ischemia and reperfusion revealed exacerbated liver injury. Transcriptional studies implicated hypoxia-inducible factor-1α (HIF1α) in the induction …

Hypoxia-Inducible Factor-Dependent Induction Of Myeloid-Derived Netrin-1 Attenuates Natural Killer Cell Infiltration During Endotoxin-Induced Lung Injury, Nathaniel K Berg, Jiwen Li, Boyun Kim, Tingting Mills, Guangsheng Pei, Zhongming Zhao, Xiangyun Li, Xu Zhang, Wei Ruan, Holger K Eltzschig, Xiaoyi Yuan

Faculty, Staff and Student Publications

Sepsis and sepsis-associated lung inflammation significantly contribute to the morbidity and mortality of critical illness. Here, we examined the hypothesis that neuronal guidance proteins could orchestrate inflammatory events during endotoxin-induced lung injury. Through a targeted array, we identified netrin-1 as the top upregulated neuronal guidance protein in macrophages treated with lipopolysaccharide (LPS). Furthermore, we found that netrin-1 is highly enriched in infiltrating myeloid cells, particularly in macrophages during LPS-induced lung injury. Transcriptional studies implicate hypoxia-inducible factor HIF-1α in the transcriptional induction of netrin-1 during LPS treatment. Subsequently, the deletion of netrin-1 in the myeloid compartment (Ntn1

The Human In The Middle: Artificial Intelligence In Health Care Summary Proceedings Symposium Presentation And Reactor Panel Of Experts Thomas Jefferson University December 10, 2019., Janice L. Clarke, Alexandria Skoufalos, Steven Klasko, Md, Mba

College of Population Health Faculty Papers

No abstract provided.

Rev-Erb In Gabaergic Neurons Controls Diurnal Hepatic Insulin Sensitivity, Guolian Ding, Xin Li, Xinguo Hou, Wenjun Zhou, Yingyun Gong, Fuqiang Liu, Yanlin He, Jia Song, Jing Wang, Paul Basil, Wenbo Li, Sichong Qian, Pradip Saha, Jinbang Wang, Chen Cui, Tingting Yang, Kexin Zou, Younghun Han, Christopher I Amos, Yong Xu, Li Chen, Zheng Sun

Faculty, Staff and Students Publications

Systemic insulin sensitivity shows diurnal rhythm with a peak at wakening1,2. The molecular mechanism underlying such a temporal pattern is unclear. Here we demonstrate that nuclear receptors Rev-erbα/β in the GABAergic neurons in the suprachiasmatic nucleus (SCNGABA) control the diurnal rhythm of insulin-mediated suppression of hepatic glucose production in mice, without affecting diurnal eating or locomotor behaviors under the regular light-dark cycles. Rev-erb regulates the rhythmic expression of genes involved in neurotransmission in the SCN and modulates the oscillatory firing activity of SCNGABA neurons. Chemogenetic stimulation of SCNGABA neurons at wakening causes glucose intolerance, while restoration …

A Millifluidic Perfusion Cassette For Studying The Pathogenesis Of Enteric Infections Using Ex-Vivo Organoids, Reid L Wilson, Sarah A Hewes, Anubama Rajan, Shih-Ching Lin, Carolyn Bomidi, Takanori Iida, Mary K Estes, Anthony W Maresso, K Jane Grande-Allen

Faculty, Staff and Students Publications

To generate physiologically-relevant experimental models, the study of enteric diarrheal diseases is turning increasingly to advanced in vitro models that combine ex vivo, stem cell-derived "organoid" cell lines with bioengineered culture environments that expose them to mechanical stimuli, such as fluid flow. However, such approaches require considerable technical expertise with both microfabrication and organoid culture, and are, therefore, inaccessible to many researchers. For this reason, we have developed a perfusion system that is simple to fabricate, operate, and maintain. Its dimensions approximate the volume and cell culture area of traditional 96-well plates and allow the incorporation of fastidious primary, stem …

Thrombotic Microangiopathy Following Onasemnogene Abeparvovec For Spinal Muscular Atrophy: A Case Series, Deepa H Chand, Craig Zaidman, Kapil Arya, Rachel Millner, Michelle A Farrar, Fiona E Mackie, Natalie L Goedeker, Vikas R Dharnidharka, Raja Dandamudi, Sandra P Reyna

2020-Current year OA Pubs

Spinal muscular atrophy is treated with onasemnogene abeparvovec, which replaces the missing survival motor neuron 1 gene via an adeno-associated virus vector. As of July 1, 2020, we had identified 3 infants who developed thrombotic microangiopathy following onasemnogene abeparvovec. Early recognition and treatment of drug-induced thrombotic microangiopathy may lessen mortality and morbidity.

Single-Cell Transcriptomics Identifies Limbal Stem Cell Population And Cell Types Mapping Its Differentiation Trajectory In Limbal Basal Epithelium Of Human Cornea, De-Quan Li, Sangbae Kim, Jin-Miao Li, Qianmiao Gao, Jongsu Choi, Fang Bian, Jiaoyue Hu, Yun Zhang, Jin Li, Rong Lu, Yumei Li, Stephen C Pflugfelder, Hongyu Miao, Rui Chen

Faculty, Staff and Students Publications

PURPOSE: This study aimed to uncover novel cell types in heterogenous basal limbus of human cornea for identifying LSC at single cell resolution.

METHODS: Single cells of human limbal basal epithelium were isolated from young donor corneas. Single-cell RNA-Sequencing was performed using 10x Genomics platform, followed by clustering cell types through the graph-based visualization method UMAP and unbiased computational informatic analysis. Tissue RNA in situ hybridization with RNAscope, immunofluorescent staining and multiple functional assays were performed using human corneas and limbal epithelial culture models.

RESULTS: Single-cell transcriptomics of 16,360 limbal basal cells revealed 12 cell clusters belonging to three lineages. …

The Impact Of Covid-19 On Kidney Transplantation And The Kidney Transplant Recipient – One Year Into The Pandemic, Pascale Khairallah, Nidhi Aggarwal, Ahmed A Awan, Chandan Vangala, Medha Airy, Jenny S Pan, Bhamidipati V R Murthy, Wolfgang C Winkelmayer, Venkat Ramanathan

Faculty, Staff and Students Publications

The COVID‐19 pandemic has significantly changed the landscape of kidney transplantation in the United States and worldwide. In addition to adversely impacting allograft and patient survival in postkidney transplant recipients, the current pandemic has affected all aspects of transplant care, including transplant referrals and listing, organ donation rates, organ procurement and shipping, and waitlist mortality. Critical decisions were made during this period by transplant centers and individual transplant physicians taking into consideration patient safety and resource utilization. As countries have begun administering the COVID vaccines, new and important considerations pertinent to our transplant population have arisen. This comprehensive review focuses …

Mechanisms, Diagnosis, Prevention And Management Of Perioperative Opioid-Induced Hyperalgesia, Sylvia H Wilson, Kevin M Hellman, Dominika James, Adam C Adler, Arvind Chandrakantan

Faculty, Staff and Students Publications

Opioid-induced hyperalgesia (OIH) occurs when opioids paradoxically enhance the pain they are prescribed to ameliorate. To address a lack of perioperative awareness, we present an educational review of clinically relevant aspects of the disorder. Although the mechanisms of OIH are thought to primarily involve medullary descending pathways, it is likely multifactorial with several relevant therapeutic targets. We provide a suggested clinical definition and directions for clinical differentiation of OIH from other diagnoses, as this may be confusing but is germane to appropriate management. Finally, we discuss prevention including patient education and analgesic management choices. As prevention may serve as the …

Quantitative Endophenotypes As An Alternative Approach To Understanding Genetic Risk In Neurodegenerative Diseases, Fabiana H G Farias, Bruno A Benitez, Carlos Cruchaga

2020-Current year OA Pubs

Endophenotypes, as measurable intermediate features of human diseases, reflect underlying molecular mechanisms. The use of quantitative endophenotypes in genetic studies has improved our understanding of pathophysiological changes associated with diseases. The main advantage of the quantitative endophenotypes approach to study human diseases over a classic case-control study design is the inferred biological context that can enable the development of effective disease-modifying treatments. Here, we summarize recent progress on biomarkers for neurodegenerative diseases, including cerebrospinal fluid and blood-based, neuroimaging, neuropathological, and clinical studies. This review focuses on how endophenotypic studies have successfully linked genetic modifiers to disease risk, disease onset, or …

Momentum: Momelotinib Vs Danazol In Patients With Myelofibrosis Previously Treated With Jaki Who Are Symptomatic And Anemic, Srdan Verstovsek, Stephen T Oh, Et Al

2020-Current year OA Pubs

Hallmark features of myelofibrosis (MF) are cytopenias, constitutional symptoms and splenomegaly. Anemia and transfusion dependency are among the most important negative prognostic factors and are exacerbated by many JAK inhibitors (JAKi). Momelotinib (MMB) has been investigated in over 820 patients with MF and possesses a pharmacological and clinical profile differentiated from other JAKi by inhibition of JAK1, JAK2 and ACVR1. MMB is designed to address the complex drivers of iron-restricted anemia and chronic inflammation in MF and should improve constitutional symptoms and splenomegaly while maintaining or improving hemoglobin in JAKi-naive and previously JAKi-treated patients. The MOMENTUM Phase III study is …

Publication Rate And Consistency Of Registered Trials Of Motor-Based Stroke Rehabilitation, Raabeae Aryan, David Jagroop, Cynthia J Danells, Gabriela Rozanski, Janelle Unger, Andrew H Huntley, Avril Mansfield

Physical Therapy Publications

OBJECTIVE: To determine the publication rate of motor-rehabilitation trials poststroke and the consistency between registry records and their corresponding main publications in trial design, primary objectives and outcomes, eligibility criteria, and sample size.

METHODS: We searched 18 clinical trial registries to identify randomized controlled trials of motor-based stroke rehabilitation registered after July 2005 and completed before April 2017. Eligible trials included adults with stroke, with at least one outcome measure related to motor function. Information in the registry records was compared with that of their main publications, if any.

RESULTS: Three hundred twenty-three trials met our eligibility criteria; we were …

Growth And Differentiation Factor 15 And Nf-Κb Expression In Benign Prostatic Biopsies And Risk Of Subsequent Prostate Cancer Detection, Benjamin A. Rybicki, Sudha M. Sadasivan, Yalei Chen, Oleksandr Kravtsov, Watchareepohn Palangmonthip, Kanika Arora, Nilesh S. Gupta, Sean R. Williamson, Kevin R. Bobbit, Dhananjay A. Chitale, Deliang Tang, Andrew G. Rundle, Kenneth A. Iczkowski

Public Health Sciences Articles

Growth and differentiation factor 15 (GDF-15), also known as macrophage inhibitory cytokine 1 (MIC-1), may act as both a tumor suppressor and promotor and, by regulating NF-κB and macrophage signaling, promote early prostate carcinogenesis. To determine whether expression of these two inflammation-related proteins affect prostate cancer susceptibility, dual immunostaining of benign prostate biopsies for GDF-15 and NF-κB was done in a study of 503 case-control pairs matched on date, age, and race, nested within a historical cohort of 10,478 men. GDF-15 and NF-κB expression levels were positively correlated (r = 0.39; p < 0.0001), and both were significantly lower in African American (AA) compared with White men. In adjusted models that included both markers, the odds ratio (OR) for NF-κB expression was statistically significant, OR =0.87; p = 0.03; 95% confidence interval (CI) =0.77-0.99, while GDF-15 expression was associated with a nominally increased risk, OR =1.06; p = 0.27; 95% CI =0.96-1.17. When modeling expression levels by quartiles, the highest quartile of NF-κB expression was associated with almost a fifty percent reduction in prostate cancer risk (OR =0.51; p = 0.03; 95% CI =0.29-0.92). In stratified models, NF-κB had the strongest negative association with prostate cancer in non-aggressive cases (p = 0.03), older men (p = 0.03), and in case-control pairs with longer follow-up (p = 0.02). Risk associated with GDF-15 expression was best fit using nonlinear regression modeling where both first (p = 0.02) and second (p = 0.03) order GDF-15 risk terms were associated with significantly increased risk. This modeling approach also revealed significantly increased risk associated with GDF-15 expression for subsamples defined by AA race, aggressive disease, younger age, and in case-control pairs with longer follow-up. Therefore, although positively correlated in benign prostatic biopsies, NF-κB and GDF-15 expression appear to exert opposite effects on risk of prostate tumor development.

Myocardial T1 And T2 Mapping By Magnetic Resonance In Patients With Immune Checkpoint Inhibitor-Associated Myocarditis., Paaladinesh Thavendiranathan, Lili Zhang, Amna Zafar, Zsofia D Drobni, Syed S Mahmood, Marcella Cabral, Magid Awadalla, Anju Nohria, Daniel A Zlotoff, Franck Thuny, Lucie M Heinzerling, Ana Barac, Ryan J Sullivan, Carol L Chen, Dipti Gupta, Michael C Kirchberger, Sarah E Hartmann, Jonathan W Weinsaft, Hannah K Gilman, Muhammad A. Rizvi Md, Bojan Kovacina, Caroline Michel, Gagan Sahni, Ana González-Mansilla, Antonio Calles, Francisco Fernández-Avilés, Michael Mahmoudi, Kerry L Reynolds, Sarju Ganatra, Juan José Gavira, Nahikari Salterain González, Manuel García De Yébenes Castro, Raymond Y Kwong, Michael Jerosch-Herold, Otavio R Coelho-Filho, Jonathan Afilalo, Eduardo Zataraín-Nicolás, A John Baksi, Bernd J Wintersperger, Oscar Calvillo-Arguelles, Stephane Ederhy, Eric H Yang, Alexander R Lyon, Michael G Fradley, Tomas G Neilan

Hematology-Medical Oncology Division

BACKGROUND: Myocarditis is a potentially fatal complication of immune checkpoint inhibitor (ICI) therapy. Data on the utility of cardiovascular magnetic resonance (CMR) T1 and T2 mapping in ICI myocarditis are limited.

OBJECTIVES: This study sought to assess the value of CMR T1 and T2 mapping in patients with ICI myocarditis.

METHODS: In this retrospective study from an international registry of patients with ICI myocarditis, clinical and CMR findings (including T1 and T2 maps) were collected. Abnormal T1 and T2 were defined as 2 SD above site (vendor/field strength specific) reference values and a z-score was calculated for each patient. Major …

Progression Of Pediatric Celiac Disease From Potential Celiac Disease To Celiac Disease: A Retrospective Cohort Study, Shruti Sakhuja, Lori R Holtz

2020-Current year OA Pubs

BACKGROUND: A subset of patients with serology suggesting celiac disease have an initially negative biopsy but subsequently develop histopathologic celiac disease. Here we characterize patients with potential celiac disease who progress to celiac disease.

METHODS: We performed a retrospective analysis of children (0-18 years of age) with biopsy-confirmed celiac disease seen at St. Louis Children's Hospital between 2013 and 2018.

RESULTS: Three hundred sixteen of 327 (96%) children with biopsy-confirmed celiac disease were diagnosed on initial biopsy. The 11 children with potential celiac disease who progressed to celiac disease had lower anti-tissue transglutaminase (anti-TTG IgA) concentrations (2.4 (1.6-5) X upper …

An Inactivated Bacterium (Paraprobiotic) Expressing Bacillus Thuringiensis Cry5b As A Therapeutic For Ascaris And Parascaris Spp. Infections In Large Animals, Joseph F. Urban, Martin K. Nielsen, David Gazzola, Yue Xie, Ethiopia Beshah, Yan Hu, Hanchen Li, Florentina Rus, Kelly Flanagan, Austin Draper, Sridhar Vakalapudi, Robert W. Li, Gary R. Ostroff, Raffi V. Aroian

Maxwell H. Gluck Equine Research Center Faculty Publications

Ascaris and Parascaris are important parasites in the family Ascarididae, large, ubiquitous intestinal-dwelling nematodes infecting all classes of vertebrates. Parasitic nematode drug resistance in veterinary medicine and drug recalcitrance in human medicine are increasing worldwide, with few if any new therapeutic classes on the horizon. Some of these parasites are zoonotic, e.g., Ascaris is passed from humans to pigs and vice versa. The development of new therapies against this family of parasites would have major implications for both human and livestock health. Here we tested the therapeutic ability of a paraprobiotic or dead probiotic that expresses the Bacillus …

Loss Of Bone Morphogenetic Protein-Binding Endothelial Regulator Causes Insulin Resistance, Hua Mao, Luge Li, Qiying Fan, Aude Angelini, Pradip K Saha, Huaizhu Wu, Christie M Ballantyne, Sean M Hartig, Liang Xie, Xinchun Pi

Faculty, Staff and Students Publications

Accumulating evidence suggests that chronic inflammation of metabolic tissues plays a causal role in obesity-induced insulin resistance. Yet, how specific endothelial factors impact metabolic tissues remains undefined. Bone morphogenetic protein (BMP)–binding endothelial regulator (BMPER) adapts endothelial cells to inflammatory stress in diverse organ microenvironments. Here, we demonstrate that BMPER is a driver of insulin sensitivity. Both global and endothelial cell-specific inducible knockout of BMPER cause hyperinsulinemia, glucose intolerance and insulin resistance without increasing inflammation in metabolic tissues in mice. BMPER can directly activate insulin signaling, which requires its internalization and interaction with Niemann-Pick C1 (NPC1), an integral membrane protein that …

Inactivated Rabies Virus Vectored Sars-Cov-2 Vaccine Prevents Disease In A Syrian Hamster Model., Drishya Kurup, Delphine C Malherbe, Christoph Wirblich, Rachael Lambert, Adam J Ronk, Leila Zabihi Diba, Alexander Bukreyev, Matthias J. Schnell

Department of Microbiology and Immunology Faculty Papers

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emergent coronavirus that has caused a worldwide pandemic. Although human disease is often asymptomatic, some develop severe illnesses such as pneumonia, respiratory failure, and death. There is an urgent need for a vaccine to prevent its rapid spread as asymptomatic infections accounting for up to 40% of transmission events. Here we further evaluated an inactivated rabies vectored SARS-CoV-2 S1 vaccine CORAVAX in a Syrian hamster model. CORAVAX adjuvanted with MPLA-AddaVax, a TRL4 agonist, induced high levels of neutralizing antibodies and generated a strong Th1-biased immune response. Vaccinated hamsters were protected from …