Medicine and Health Sciences Commons^™

Role Of Metabolism In Bone Development And Homeostasis, Akiko Suzuki, Mina Minamide, Chihiro Iwaya, Kenichi Ogata, Junichi Iwata

Faculty, Staff and Student Publications

Carbohydrates, fats, and proteins are the underlying energy sources for animals and are catabolized through specific biochemical cascades involving numerous enzymes. The catabolites and metabolites in these metabolic pathways are crucial for many cellular functions; therefore, an imbalance and/or dysregulation of these pathways causes cellular dysfunction, resulting in various metabolic diseases. Bone, a highly mineralized organ that serves as a skeleton of the body, undergoes continuous active turnover, which is required for the maintenance of healthy bony components through the deposition and resorption of bone matrix and minerals. This highly coordinated event is regulated throughout life by bone cells such …

Security And Privacy When Applying Fair Principles To Genomic Information, Jaime Delgado, Silvia Llorente

Faculty, Staff and Student Publications

Making data Findable, Accessible, Interoperable and Reusable (FAIR) is a good approach when data needs to be shared. However, security and privacy are still critical aspects. In the FAIRification process, there is a need both for de-identification of data and for license attribution. The paper analyses some of the issues related to this process when the objective is sharing genomic information. The main results are the identification of the already existing standards that could be used for this purpose and how to combine them. Nevertheless, the area is quickly evolving and more specific standards could be specified.

Social And Leisure Activities Predict Transitions In Cognitive Functioning In Older Mexican Adults: A Latent Transition Analysis Of The Mexican Health And Aging Study, Heather Mary Brown, Stephen A Murray, Hope Northrup, Kit Sing Au, Lee A Niswander

Faculty, Staff and Student Publications

Disruptions in neural tube (NT) closure result in neural tube defects (NTDs). To understand the molecular processes required for mammalian NT closure, we investigated the role of Snx3, a sorting nexin gene. Snx3−/− mutant mouse embryos display a fully-penetrant cranial NTD. In vivo, we observed decreased canonical WNT target gene expression in the cranial neural epithelium of the Snx3−/− embryos and a defect in convergent extension of the neural epithelium. Snx3−/− cells show decreased WNT secretion, and live cell imaging reveals aberrant recycling of the WNT ligand-binding protein WLS and mis-trafficking to the lysosome for degradation. The importance …

Impact Of Diabetes On The Gut And Salivary Iga Microbiomes, Eric L Brown, Heather T Essigmann, Kristi L Hoffman, Noah W Palm, Sarah M Gunter, Joel M Sederstrom, Joseph F Petrosino, Goo Jun, David Aguilar, William B Perkison, Craig L Hanis, Herbert L Dupont

Faculty, Staff and Student Publications

Mucosal surfaces like those present in the lung, gut, and mouth interface with distinct external environments. These mucosal gateways are not only portals of entry for potential pathogens but also homes to microbial communities that impact host health. Secretory immunoglobulin A (SIgA) is the single most abundant acquired immune component secreted onto mucosal surfaces and, via the process of immune exclusion, shapes the architecture of these microbiomes. Not all microorganisms at mucosal surfaces are targeted by SIgA; therefore, a better understanding of the SIgA-coated fraction may identify the microbial constituents that stimulate host immune responses in the context of health …

Lung Nodule In A Patient With Multiple Myeloma, William C Harding, Mathieu Marcoux, Roberto F Casal, Lara Bashoura, John Stewart, Hans C Lee, Saadia A Faiz

Faculty, Staff and Student Publications

No abstract provided.

A Genome-Wide Association Study Discovers 46 Loci Of The Human Metabolome In The Hispanic Community Health Study/Study Of Latinos, Elena V Feofanova, Han Chen, Yulin Dai, Peilin Jia, Megan L Grove, Alanna C Morrison, Qibin Qi, Martha Daviglus, Jianwen Cai, Kari E North, Cathy C Laurie, Robert C Kaplan, Eric Boerwinkle, Bing Yu

Faculty, Staff and Student Publications

Variation in levels of the human metabolome reflect changes in homeostasis, providing a window into health and disease. The genetic impact on circulating metabolites in Hispanics, a population with high cardiometabolic disease burden, is largely unknown. We conducted genome-wide association analyses on 640 circulating metabolites in 3,926 Hispanic Community Health Study/Study of Latinos participants. The estimated heritability for 640 metabolites ranged between 0%-54% with a median at 2.5%. We discovered 46 variant-metabolite pairs (p value < 1.2 × 10

Allogeneic Mesenchymal Cell Therapy In Anthracycline-Induced Cardiomyopathy Heart Failure Patients: The Cctrn Seneca Trial, Roberto Bolli, Emerson C Perin, James T Willerson, Phillip C Yang, Jay H Traverse, Timothy D Henry, Carl J Pepine, Raul D Mitrani, Joshua M Hare, Michael P Murphy, Keith L March, Sohail Ikram, David P Lee, Connor O'Brien, Jean-Bernard Durand, Kathy Miller, Joao A Lima, Mohammad R Ostovaneh, Bharath Ambale-Venkatesh, Adrian P Gee, Sara Richman, Doris A Taylor, Shelly L Sayre, Judy Bettencourt, Rachel W Vojvodic, Michelle L Cohen, Lara M Simpson, Dejian Lai, David Aguilar, Catalin Loghin, Lem Moyé, Ray F Ebert, Barry R Davis, Robert D Simari

Faculty, Staff and Student Publications

BACKGROUND: Anthracycline-induced cardiomyopathy (AIC) may be irreversible with a poor prognosis, disproportionately affecting women and young adults. Administration of allogeneic bone marrow-derived mesenchymal stromal cells (allo-MSCs) is a promising approach to heart failure (HF) treatment.

OBJECTIVES: SENECA (Stem Cell Injection in Cancer Survivors) was a phase 1 study of allo-MSCs in AIC.

METHODS: Cancer survivors with chronic AIC (mean age 56.6 years; 68% women; NT-proBNP 1,426 pg/ml; 6 enrolled in an open-label, lead-in phase and 31 subjects randomized 1:1) received 1 × 10

RESULTS: A total of 97% of subjects underwent successful study product injections; all allo-MSC-assigned subjects received the …

Prenatal Depression And Risk Of Short Interpregnancy Interval In A Predominantly Puerto Rican Population, Sami Backley, Alex Knee, Penelope Pekow, Glenn Markenson, Katharine O White, Corina Schoen, Lisa Chasan-Taber

Faculty, Staff and Student Publications

Background: Short interpregnancy interval (IPI) is associated with risk of adverse pregnancy outcomes; however, few studies have evaluated the role of depression as a risk factor for short IPI. Puerto Rican women in the United States experience disparities in adverse birth outcomes and have the highest birth rates.

Methods: We analyzed the association between prenatal depressive symptoms and IPI in Proyecto Buena Salud, a prospective cohort of predominantly Puerto Rican women in Western Massachusetts (2006–2011). Depression was measured using the Edinburgh Postnatal Depression Scale (EPDS) in early, mid, and late pregnancy. We calculated follow-up time as the difference between the …

Aerosol Generation With Common Rhinologic Devices: Cadaveric Study Conducted In A Surgical Suite, Bailey Leconte, Garren M I Low, Martin J Citardi, William C Yao, Arturo A Eguia, Amber U Luong

Faculty, Staff and Student Publications

No abstract provided.

Variable Expression Of Msh6 In Endometrial Carcinomas With Intact Mismatch Repair And With Mlh1 Loss Due To Mlh1 Methylation, Nidhi Tandon, Courtney Hudgens, Bryan Fellman, Michael T Tetzlaff, Russell R Broaddus

Faculty, Staff and Student Publications

Immunohistochemistry for mismatch repair proteins MLH1, MSH2, MSH6, and PMS2 is an effective screen to detect individuals at risk for Lynch syndrome. College of American Pathologists guidelines stipulate that protein expression should be reported as present versus absent, as most patients with germline mutations in a mismatch repair gene have complete loss of protein expression in tumor cells. A similar approach is employed to screen for cancer patients eligible for immune checkpoint blockade. This "all or none" interpretive approach ignores substantial evidence that mismatch repair may be more finely regulated by other mechanisms. We have observed clinically that MSH6 expression …

Identification Of Novel Candidate Risk Genes For Myelomeningocele Within The Glucose Homeostasis/Oxidative Stress And Folate/One-Carbon Metabolism Networks, Paul Hillman, Craig Baker, Luke Hebert, Michael Brown, James Hixson, Allison Ashley-Koch, Alanna C Morrison, Hope Northrup, Kit Sing Au

Faculty, Staff and Student Publications

BACKGROUND: Neural tube defects (NTDs) are the second most common complex birth defect, yet, our understanding of the genetic contribution to their development remains incomplete. Two environmental factors associated with NTDs are Folate and One Carbon Metabolism (FOCM) and Glucose Homeostasis and Oxidative Stress (GHOS). Utilizing next-generation sequencing of a large patient cohort, we identify novel candidate genes in these two networks to provide insights into NTD mechanisms.

METHODS: Exome sequencing (ES) was performed in 511 patients, born with myelomeningocele, divided between European American and Mexican American ethnicities. Healthy control data from the Genome Aggregation database were ethnically matched and …

Outcomes After In Utero Myelomeningocele Repair Based On Delivery Location, Eric P Bergh, Kuojen Tsao, Mary T Austin, Stephen A Fletcher, Suzanne M Lopez, Kenneth J Moise, Anthony Johnson, Ramesha Papanna

Faculty, Staff and Student Publications

Maternal and pediatric delivery outcomes may vary in patients who underwent open fetal myelomeningocele repair and elected to deliver at the fetal center where their fetal intervention was performed versus at the referring physician’s hospital. A prospective cohort study of 88 patients were evaluated following in utero open fetal myelomeningocele repair at a single fetal center between the years 2011–2019. Exclusion criteria included patients that delivered within two weeks of the procedure (n = 6), or if a patient was lost to follow-up (n = 1). Of 82 patients meeting inclusion criteria, 36 (44%) patients were delivered at …

Outcomes After In Utero Myelomeningocele Repair Based On Delivery Location, Eric P Bergh, Kuojen Tsao, Mary T Austin, Stephen A Fletcher, Suzanne M Lopez, Kenneth J Moise, Anthony Johnson, Ramesha Papanna

Faculty, Staff and Student Publications

Maternal and pediatric delivery outcomes may vary in patients who underwent open fetal myelomeningocele repair and elected to deliver at the fetal center where their fetal intervention was performed versus at the referring physician’s hospital. A prospective cohort study of 88 patients were evaluated following in utero open fetal myelomeningocele repair at a single fetal center between the years 2011–2019. Exclusion criteria included patients that delivered within two weeks of the procedure (n = 6), or if a patient was lost to follow-up (n = 1). Of 82 patients meeting inclusion criteria, 36 (44%) patients were delivered at …

Povidone-Iodine Solution As Sars-Cov-2 Prophylaxis For Procedures Of The Upper Aerodigestive Tract A Theoretical Framework, Syed H S Naqvi, Martin J Citardi, Davide Cattano, Luis Ostrosky-Zeichner, Mark I Knackstedt, Ron J Karni

Faculty, Staff and Student Publications

BACKGROUND: The COVID-19 pandemic has raised concerns of inadvertent SARS-CoV-2 transmission to healthcare workers during routine procedures of the aerodigestive tract in asymptomatic COVID-19 patients. Current efforts to mitigate this risk focus on Personal Protective Equipment, including high-efficiency filtration as well as other measures. Because the reservoir for SARS-CoV-2 shedding is in the nasopharynx and nasal and oral cavities, the application of viricidal agents to these surfaces may reduce virus burden. Numerous studies have confirmed that povidone-iodine inactivates many common respiratory viruses, including SARS-CoV-1. Povidone-iodine also has good profile for mucosal tolerance. Thus, we propose a prophylactic treatment protocol for …

Cd123 As A Biomarker In Hematolymphoid Malignancies: Principles Of Detection And Targeted Therapies, Hanadi El Achi, Edouard Dupont, Shilpa Paul, Joseph D Khoury

Faculty, Staff and Student Publications

CD123, the α chain of the interleukin 3 receptor, is a cytokine receptor that is overexpressed in multiple hematolymphoid neoplasms, including acute myeloid leukemia, blastic plasmacytoid dendritic cell neoplasm, acute lymphoblastic leukemia, hairy cell leukemia, and systemic mastocytosis. Importantly, CD123 expression is upregulated in leukemic stem cells relative to non-neoplastic hematopoietic stem cells, which makes it a useful diagnostic and therapeutic biomarker in hematologic malignancies. Varying levels of evidence have shown that CD123-targeted therapy represents a promising therapeutic approach in several cancers. Tagraxofusp, an anti-CD123 antibody conjugated to a diphtheria toxin, has been approved for use in patients with blastic …

Association Of Visceral Adipose Tissue And Subclinical Atherosclerosis In Us-Born Mexican Americans But Not First Generation Immigrants, Clarence Gill, Miryoung Lee, Kristina P Vatcheva, Nahid Rianon, Beverly Smulevitz, David D Mcpherson, Joseph B Mccormick, Susan P Fisher-Hoch, Susan T Laing

Faculty, Staff and Student Publications

Background Excess visceral adipose tissue (VAT) is a primary driver for the cardiometabolic complications of obesity; VAT-associated cardiovascular disease risk varies by race, but most studies have been done on Non-Hispanics. This study aimed to evaluate the clinical and metabolic correlates of VAT, its association with subclinical atherosclerosis, and the factors affecting this association in Mexican Americans. Methods and Results Participants (n=527) were drawn from the Cameron County Hispanic Cohort (CCHC), on whom a carotid ultrasound to assess carotid intima media thickness and a dual-energy X-ray absorptiometry scan to assess for VAT were obtained. Those in the highest quartiles of …

Potential Scenarios And Hazards In The Work Of The Future: A Systematic Review Of The Peer-Reviewed And Gray Literatures, Paul A Schulte, Jessica M K Streit, Fatima Sheriff, George Delclos, Sarah A Felknor, Sara L Tamers, Sherry Fendinger, James Grosch, Robert Sala

Faculty, Staff and Student Publications

It would be useful for researchers, practitioners, and decision-makers to anticipate the hazards that workers will face in the future. The focus of this study is a systematic review of published information to identify and characterize scenarios and hazards in the future of work. Eleven bibliographic databases were systematically searched for papers and reports published from 1999 to 2019 that described future of work scenarios or identified future work-related hazards. to compile a comprehensive collection of views of the future, supplemental and ad hoc searches were also performed. After screening all search records against a set of predetermined criteria, the …

Feasibility And Potential Efficacy Of Commercial Mhealth/Ehealth Tools For Weight Loss In African American Breast Cancer Survivors: Pilot Randomized Controlled Trial, Jeanne M Ferrante, Katie A Devine, Alicja Bator, Ashley Rodgers, Pamela A Ohman-Strickland, Elisa V Bandera, Kevin O Hwang

Faculty, Staff and Student Publications

Weight management after breast cancer (BC) treatment in African American (AA) women is crucial to reduce comorbid conditions and health disparities. We examined feasibility and potential efficacy of commercial eHealth/mHealth tools for weight management in AA BC survivors in New Jersey. Participants (N = 35) were randomized to an intervention (SparkPeople) plus activity tracker, Fitbit Charge (n = 18), or wait-list active control group (Fitbit only, n = 17). Anthropometric, behavioral, and quality of life (QOL) outcomes were collected at baseline, 3, 6, and 12 months. Differences in outcomes were assessed using intent-to-treat analysis. Retention was 97.1%. Both groups lost …

Predoctoral Periodontal Education And Covid-19: Challenges, Actions, And Learned Lessons, Karo Parsegian, Srinivas Ayilavarapu, Amity L Gardner, Nikola Angelov

Faculty, Staff and Student Publications

No abstract provided.

The Multiple Waves Of Covid-19 In Patients With Inflammatory Bowel Disease: A Temporal Trend Analysis, Elizabeth R Volkmann, Donald P Tashkin, Michael D Roth, Ning Li, Julio Charles, Maureen Mayes, Grace Kim, Jonathan Goldin, Lila Pourzand, Philip J Clements, Daniel E Furst, Dinesh Khanna, Robert M Elashoff, Shervin Assassi

Faculty, Staff and Student Publications

OBJECTIVE: To investigate the prevalence of the MUC5B promoter variant rs35705950 in patients with systemic sclerosis-interstitial lung disease (SSc-ILD) and whether its presence predicts response to immunosuppression with cyclophosphamide (CYC) and mycophenolate (MMF).

METHODS: SSc-ILD patients who participated in Scleroderma Lung Study (SLS) II (MMF versus CYC) were included in this study (N = 142). TaqMan Genotyping Assays were used to determine the MUC5B rs35705950 single nucleotide polymorphism. Joint models were created to examine how the presence of this variant affected the course of the forced vital capacity (FVC) over 2 years. Linear regression models were used to investigate the …

Representation Of Ehr Data For Predictive Modeling: A Comparison Between Umls And Other Terminologies, Laila Rasmy, Firat Tiryaki, Yujia Zhou, Yang Xiang, Cui Tao, Hua Xu, Degui Zhi

Faculty, Staff and Student Publications

OBJECTIVE: Predictive disease modeling using electronic health record data is a growing field. Although clinical data in their raw form can be used directly for predictive modeling, it is a common practice to map data to standard terminologies to facilitate data aggregation and reuse. There is, however, a lack of systematic investigation of how different representations could affect the performance of predictive models, especially in the context of machine learning and deep learning.

MATERIALS AND METHODS: We projected the input diagnoses data in the Cerner HealthFacts database to Unified Medical Language System (UMLS) and 5 other terminologies, including CCS, CCSR, …

Evidence For Craniofacial Enhancer Variation Underlying Nonsyndromic Cleft Lip And Palate, Vershanna E Morris, S Shahrukh Hashmi, Lisha Zhu, Lorena Maili, Christian Urbina, Steven Blackwell, Matthew R Greives, Edward P Buchanan, John B Mulliken, Susan H Blanton, W Jim Zheng, Jacqueline T Hecht, Ariadne Letra

Faculty, Staff and Student Publications

Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common birth defect for which only ~ 20% of the underlying genetic variation has been identified. Variants in noncoding regions have been increasingly suggested to contribute to the missing heritability. In this study, we investigated whether variation in craniofacial enhancers contributes to NSCLP. Candidate enhancers were identified using VISTA Enhancer Browser and previous publications. Prioritization was based on patterning defects in knockout mice, deletion/duplication of craniofacial genes in animal models and results of whole exome/whole genome sequencing studies. This resulted in 20 craniofacial enhancers to be investigated. Custom amplicon-based …

The Post Hurricane Harvey Respiratory Protection Training Program, Yiyao Li, Christine Bakos-Block, Amal Rammah, Rotem Magal, Joel Adekanye, Shari Esquenazi, Michelle R Mcdaniel, Kai Zhang, Elaine Symanski, William B Perkison

Faculty, Staff and Student Publications

OBJECTIVES: This study evaluated the effectiveness of an outreach program which included safety training and the distribution of personal protection kits in the Houston area in the aftermath of Hurricane Harvey.

METHODS: Outreach: 71 volunteers conducted training sessions at 19 different sites and distributed a total of 1187 kits. Follow-up study: We conducted telephonic interviews to collect data on respiratory symptoms and obtain perceptions of the quality of the safety training provided among 83 participants.

RESULTS: Participants reported an increase in airway symptoms four weeks after Hurricane Harvey. Outreach efforts were felt to be effective by a majority of participants. …

Social Determinants Of Health-Related Needs During Covid-19 Among Low-Income Households With Children, Shreela V Sharma, Ru-Jye Chuang, Melinda Rushing, Brittni Naylor, Nalini Ranjit, Mike Pomeroy, Christine Markham

Faculty, Staff and Student Publications

INTRODUCTION: Little is known about the social needs of low-income households with children during the coronavirus-2019 (COVID-19) pandemic. Our objective was to conduct a cross-sectional quantitative and qualitative descriptive analysis of a rapid-response survey among low-income households with children on social needs, COVID-19-related concerns, and diet-related behaviors.

METHODS: We distributed an electronic survey in April 2020 to 16,435 families in 4 geographic areas, and 1,048 responded. The survey asked families enrolled in a coordinated school-based nutrition program about their social needs, COVID-19-related concerns, food insecurity, and diet-related behaviors during the pandemic. An open-ended question asked about their greatest concern. We …

Targeted Fgfr Blockade For The Treatment Of Tumor-Induced Osteomalacia, Iris R Hartley, Carole B Miller, Georgios Z Papadakis, Clemens Bergwitz, Jaydira Del Rivero, Jenny E Blau, Pablo Florenzano, Jason A Berglund, Jing Tassone, Kelly L Roszko, Susan Moran, Rachel I Gafni, Randi Isaacs, Michael T Collins

Faculty, Staff and Student Publications

No abstract provided.

Sirolimus For Kaposiform Hemangioendothelioma And Kasabach-Merritt Phenomenon In A Neonate, Trevor B Cabrera, Allison L Speer, Matthew R Greives, Donna A Goff, Neethu M Menon, Eric W Reynolds

Faculty, Staff and Student Publications

We present a case of a neonate born with kaposiform hemangioendothelioma (KHE), complicated by Kasabach-Merritt phenomenon (KMP) and other serious conditions, who was successfully treated with sirolimus. In addition to complications from thrombocytopenia and fluid overload, during the course of therapy, our patient experienced supratherapeutic drug levels at the commonly accepted starting dose of sirolimus. Patients with KHE and KMP should be closely monitored for potential complications of both the initial disease and unexpected side effects of treatments.

Anesthetic Drugs And Cancer Progression, Juan P Cata, Anil K Sood, Holger K Eltzschig

Faculty, Staff and Student Publications

No abstract provided.

Canakinumab To Reduce Deterioration Of Cardiac And Respiratory Function In Sars-Cov-2 Associated Myocardial Injury With Heightened Inflammation (Canakinumab In Covid-19 Cardiac Injury: The Three C Study), Calvin C Sheng, Debasis Sahoo, Siddharth Dugar, Robier Aguillon Prada, Tom Kai Ming Wang, Ossama K Abou Hassan, Danielle Brennan, Daniel A Culver, Prabalini Rajendram, Abhijit Duggal, A Michael Lincoff, Steven E Nissen, Venu Menon, Paul C Cremer

Faculty, Staff and Student Publications

BACKGROUND: In patients with Covid-19, myocardial injury and increased inflammation are associated with morbidity and mortality. We designed a proof-of-concept randomized controlled trial to evaluate whether treatment with canakinumab prevents progressive respiratory failure and worsening cardiac dysfunction in patients with SARS-CoV2 infection, myocardial injury, and high levels of inflammation.

HYPOTHESIS: The primary hypothesis is that canakiumab will shorten time to recovery.

METHODS: The three C study (canakinumab in Covid-19 Cardiac Injury, NCT04365153) is a double-blind, randomized controlled trial comparing canakinumab 300 mg IV, 600 mg IV, or placebo in a 1:1:1 ratio in hospitalized Covid-19 patients with elevations in troponin …

Yebc Regulates Variable Surface Antigen Vlse Expression And Is Required For Host Immune Evasion In Borrelia Burgdorferi, Yan Zhang, Tong Chen, Sajith Raghunandanan, Xuwu Xiang, Jing Yang, Qiang Liu, Diane G Edmondson, Steven J Norris, X Frank Yang, Yongliang Lou

Faculty, Staff and Student Publications

Borrelia burgdorferi, the Lyme disease pathogen causes persistent infection by evading the host immune response. Differential expression of the surface-exposed lipoprotein VlsE that undergoes antigenic variation is a key immune evasion strategy employed by B. burgdorferi. Most studies focused on the mechanism of VlsE antigen variation, but little is known about VlsE regulation and factor(s) that regulates differential vlsE expression. In this study, we investigated BB0025, a putative YebC family transcriptional regulator (and hence designated BB0025 as YebC of B. burgdorferi herein). We constructed yebC mutant and complemented strain in an infectious strain of B. burgdorferi. The yebC mutant could …

Representation Of Ehr Data For Predictive Modeling: A Comparison Between Umls And Other Terminologies, Laila Rasmy, Firat Tiryaki, Yujia Zhou, Yang Xiang, Cui Tao, Hua Xu, Degui Zhi

Faculty, Staff and Student Publications

OBJECTIVE: Predictive disease modeling using electronic health record data is a growing field. Although clinical data in their raw form can be used directly for predictive modeling, it is a common practice to map data to standard terminologies to facilitate data aggregation and reuse. There is, however, a lack of systematic investigation of how different representations could affect the performance of predictive models, especially in the context of machine learning and deep learning.

MATERIALS AND METHODS: We projected the input diagnoses data in the Cerner HealthFacts database to Unified Medical Language System (UMLS) and 5 other terminologies, including CCS, CCSR, …