Digital Commons Network^™

The Bmal1/Hif2a Heterodimer Modulates Circadian Variations Of Myocardial Injury, Hui Li, Xinwei Kuang, Long Liang, Youqiong Ye, Yongchang Zhang, Jialu Li, Fangyu Ma, Juan Tao, Guang Lei, Shuang Zhao, Juan Su, Nong Yang, Cong Peng, Xiaowei Xu, Mien-Chie Hung, Leng Han, Hong Liu, Jing Liu, Xiang Chen

Faculty, Staff and Student Publications

Immune checkpoints blockades have shown promising clinical effects in various malignancies, but the overall response rate is low. Here, the immune features are comprehensively characterized in >10 000 cancer patients from The Cancer Genome Atlas and significantly positive correlations are observed between targets of Sunitinib and inhibitory immune checkpoints and suppressive immune cells. It is further confirmed that Sunitinib treatment increases the antitumor immunity in a phase III trial. Mechanistically, it is discovered that Sunitinib regulates the stability of tumor PD‐L1 via p62, that p62 can bind to PD‐L1 and specifically promote its translocation into autophagic lysosome for degradation. Preclinically, …

Pathologic Femur Fracture Through Osteoid Osteoma After Radiofrequency Ablation: Case Report And Review Of The Literature, Nathan B Rogers, Brennan P Roper, Alfred A Mansour

Faculty, Staff and Student Publications

This is a case report of a 4-year-old girl who sustained a femoral shaft fracture 2 weeks after radiofrequency ablation of an osteoid osteoma. The fracture occurred after a relatively low-energy impact, jumping off the second to last step of a staircase. The pathologic fracture was successfully treated with closed reduction and spica casting, with full return to activities. Cases have been reported in the literature of femoral shaft fractures in older patients after radiofrequency ablation, but all are farther out than 2 weeks and none in patients as young as 4 years.

Extensive Mycobacterium Abscessus Pneumonia In An Immunocompetent Infant With No Underlying Lung Pathology, Morouge M Alramadhan, James R Murphy, Michael L Chang

Faculty, Staff and Student Publications

Pulmonary infection due to Mycobacterium abscessus occurs in patients with cystic fibrosis, but rarely in immunocompetent children without underlying lung pathology. Treatment is complicated by frequent resistance to many antibiotics. We present a case report of a 4-month-old female infant with 2 months of cough, difficulty feeding, and failure to thrive, with extensive culture-confirmed M. abscessus pulmonary infection without identified immunodeficiency or underlying lung pathology following multidisciplinary evaluation. We describe our complete evaluation including immunodeficiency evaluation incorporating whole-exome sequencing, describe our antibiotic selection and treatment duration given complicated susceptibility pattern of the M. abscessus isolate, and review literature for nontuberculous …

Awareness And Preparedness Of Healthcare Workers Against The First Wave Of The Covid-19 Pandemic: A Cross-Sectional Survey Across 57 Countries, Nguyen Tien Huy, R Matthew Chico, Vuong Thanh Huan, Hosam Waleed Shaikhkhalil, Vuong Ngoc Thao Uyen, Ahmad Taysir Atieh Qarawi, Shamael Thabit Mohammed Alhady, Nguyen Lam Vuong, Le Van Truong, Mai Ngoc Luu, Shyam Prakash Dumre, Atsuko Imoto, Peter N Lee, Dao Ngoc Hien Tam, Sze Jia Ng, Mohammad Rashidul Hashan, Mitsuaki Matsui, Nguyen Tran Minh Duc, Sedighe Karimzadeh, Nut Koonrungsesomboon, Chris Smith, Sharon Cox, Kazuhiko Moji, Kenji Hirayama, Le Khac Linh, Kirellos Said Abbas, Tran Nu Thuy Dung, Tareq Mohammed Ali Al-Ahdal, Emmanuel Oluwadare Balogun, Nguyen The Duy, Mennatullah Mohamed Eltaras, Trang Huynh, Nguyen Thi Linh Hue, Bui Diem Khue, Abdelrahman Gad, Gehad Mohamed Tawfik, Kazumi Kubota, Hoang-Minh Nguyen, Dmytro Pavlenko, Vu Thi Thu Trang, Le Thuong Vu, Tran Hai Yen, Nguyen Thi Yen-Xuan, Luong Thi Trang, Vinh Dong, Akash Sharma, Vu Quoc Dat, Mohammed Soliman, Jeza Abdul Aziz, Jaffer Shah, Pham Dinh Long Hung, Yap Siang Jee, Dang Thuy Ha Phuong, Tran Thuy Huong Quynh, Hoang Thi Nam Giang, Vy Thi Nhat Huynh, Nguyen Anh Thi, Nacir Dhouibi, Truc Phan, Vincent Duru, Nguyen Hai Nam, Sherief Ghozy, Tmgh-Global Covid-19 Collaborative

Faculty, Staff and Student Publications

BACKGROUND: Since the COVID-19 pandemic began, there have been concerns related to the preparedness of healthcare workers (HCWs). This study aimed to describe the level of awareness and preparedness of hospital HCWs at the time of the first wave.

METHODS: This multinational, multicenter, cross-sectional survey was conducted among hospital HCWs from February to May 2020. We used a hierarchical logistic regression multivariate analysis to adjust the influence of variables based on awareness and preparedness. We then used association rule mining to identify relationships between HCW confidence in handling suspected COVID-19 patients and prior COVID-19 case-management training.

RESULTS: We surveyed 24,653 …

Pathologic Femur Fracture Through Osteoid Osteoma After Radiofrequency Ablation: Case Report And Review Of The Literature, Nathan B Rogers, Brennan P Roper, Alfred A Mansour

Faculty, Staff and Student Publications

This is a case report of a 4-year-old girl who sustained a femoral shaft fracture 2 weeks after radiofrequency ablation of an osteoid osteoma. The fracture occurred after a relatively low-energy impact, jumping off the second to last step of a staircase. The pathologic fracture was successfully treated with closed reduction and spica casting, with full return to activities. Cases have been reported in the literature of femoral shaft fractures in older patients after radiofrequency ablation, but all are farther out than 2 weeks and none in patients as young as 4 years.

N95 Respirator Reuse, Decontamination Methods, And Microbial Burden: A Randomized Controlled Trial, Zi Yang Jiang, Zhen Huang, Isaac Schmale, Eric L Brown, Michael C Lorenz, Scott J Patlovich, Karan Goswami, Hannah B Wilson, Jumah Ahmad, Ronda Alexander, William Bryan, Luke Burke, Martin J Citardi, Jose Elias, Tang Ho, Jack Jacob, Garren Low, Pedro Miramón, Aniruddha U Patki, William C Yao, Amber U Luong

Faculty, Staff and Student Publications

PURPOSE: To evaluate the effectiveness and ease of N95 respirator decontamination methods in a clinic setting and to identify the extent of microbial colonization on respirators associated with reuse.

METHODS: In a prospective fashion, N95 respirators (n = 15) were randomized to a decontamination process (time, dry heat, or ultraviolet C light [UVC]) in outpatient clinics. Each respirator was re-used up to 5 separate clinic sessions. Swabs on each respirator for SARS-CoV-2, bacteria, and fungi were obtained before clinic, after clinic and post-treatment. Mask integrity was checked after each treatment (n = 68). Statistical analyses were performed to determine factors …

N95 Respirator Reuse, Decontamination Methods, And Microbial Burden: A Randomized Controlled Trial, Zi Yang Jiang, Zhen Huang, Isaac Schmale, Eric L Brown, Michael C Lorenz, Scott J Patlovich, Karan Goswami, Hannah B Wilson, Jumah Ahmad, Ronda Alexander, William Bryan, Luke Burke, Martin J Citardi, Jose Elias, Tang Ho, Jack Jacob, Garren Low, Pedro Miramón, Aniruddha U Patki, William C Yao, Amber U Luong

Faculty, Staff and Student Publications

PURPOSE: To evaluate the effectiveness and ease of N95 respirator decontamination methods in a clinic setting and to identify the extent of microbial colonization on respirators associated with reuse.

METHODS: In a prospective fashion, N95 respirators (n = 15) were randomized to a decontamination process (time, dry heat, or ultraviolet C light [UVC]) in outpatient clinics. Each respirator was re-used up to 5 separate clinic sessions. Swabs on each respirator for SARS-CoV-2, bacteria, and fungi were obtained before clinic, after clinic and post-treatment. Mask integrity was checked after each treatment (n = 68). Statistical analyses were performed to determine factors …

Restoration Of Cardiac Function After Myocardial Infarction By Long-Term Activation Of The Cns Leptin-Melanocortin System, Fabio N Gava, Alexandre A Da Silva, Xuemei Dai, Romain Harmancey, Sadia Ashraf, Ana C M Omoto, Mateus C Salgado, Sydney P Moak, Xuan Li, John E Hall, Jussara M Do Carmo

Faculty, Staff and Student Publications

Heart failure has a high mortality rate, and current therapies offer limited benefits. The authors demonstrate that activation of the central nervous system leptin-melanocortin pathway confers remarkable protection against progressive heart failure following severe myocardial infarction. The beneficial cardiac-protective actions of leptin require activation of brain melanocortin-4 receptors and elicit improvements in cardiac substrate oxidation, cardiomyocyte contractility, Ca

Racial Disparities In Systemic Sclerosis: Short‐ And Long‐Term Outcomes Among African American Participants Of Sls I And Ii, Elizabeth R Volkmann, Virginia Steen, Ning Li, Michael D Roth, Philip J Clements, Daniel E Furst, Shervin Assassi, Dinesh Khanna, Grace-Hyun J Kim, Jonathan Goldin, Robert M Elashoff, Donald P Tashkin

Faculty, Staff and Student Publications

OBJECTIVE: To evaluate short- and long-term outcomes of African American (AA) participants of Scleroderma Lung Studies (SLS) I and II.

METHODS: SLS I randomized 158 participants with systemic sclerosis-interstitial lung disease (SSc-ILD) to 1 year of oral cyclophosphamide (CYC) versus placebo. SLS II randomized 142 participants with SSc-ILD to 1 year of oral CYC followed by 1 year of placebo versus 2 years of mycophenolate (MMF). Joint models compared the course of forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO) between AA and non-AA, and Cox proportional hazard models assessed long-term morbidity and mortality outcomes.

RESULTS: In …

Restoration Of Cardiac Function After Myocardial Infarction By Long-Term Activation Of The Cns Leptin-Melanocortin System, Fabio N Gava, Alexandre A Da Silva, Xuemei Dai, Romain Harmancey, Sadia Ashraf, Ana C M Omoto, Mateus C Salgado, Sydney P Moak, Xuan Li, John E Hall, Jussara M Do Carmo

Faculty, Staff and Student Publications

Heart failure has a high mortality rate, and current therapies offer limited benefits. The authors demonstrate that activation of the central nervous system leptin-melanocortin pathway confers remarkable protection against progressive heart failure following severe myocardial infarction. The beneficial cardiac-protective actions of leptin require activation of brain melanocortin-4 receptors and elicit improvements in cardiac substrate oxidation, cardiomyocyte contractility, Ca

Mir-9-1 Suppresses Cell Proliferation And Promotes Apoptosis By Targeting Uhrf1 In Lung Cancer, Cheng-You Jia, Wei Xiang, Ji-Bin Liu, Geng-Xi Jiang, Feng Sun, Jian-Jun Wu, Xiao-Li Yang, Rui Xin, Yi Shi, Dan-Dan Zhang, Wen Li, Zavuga Zuberi, Jie Zhang, Gai-Xia Lu, Hui-Min Wang, Pei-Yao Wang, Fei Yu, Zhong-Wei Lv, Yu-Shui Ma, Da Fu

Faculty, Staff and Student Publications

Lung cancer is listed as the most common reason for cancer-related death all over the world despite diagnostic improvements and the development of chemotherapy and targeted therapies. MicroRNAs control both physiological and pathological processes including development and cancer. A microRNA-9 to 1 (miR-9 to 1) overexpression model in lung cancer cell lines was established and miR-9 to 1 was found to significantly suppress the proliferation rate in lung cancer cell lines, colony formation in vitro, and tumorigenicity in nude mice of A549 cells. Ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) was then identified to direct target of miR-9 …

Stress Inoculation Training (Sit-Norcal), Part 1: The Development And Preliminary Evaluation Of A Psychological Performance Training Protocol, Sarah E Jackson, Matthew R Baity, Patrick R Thomas, Douglas Barba, Daniel Jacobson, Madeleine Goodkind, Diane Swick, A Sarah Ivey

Faculty, Staff and Student Publications

Background: Stress inoculation training (SIT) interventions have demonstrated promise within military contexts for human performance enhancement and psychological health applications. However, lack of manualized guidance on core content selection, delivery, and measurement processes has limited their use.

Purpose: The purpose of this study was to develop and evaluate a comprehensive SIT intervention protocol to enhance the performance and health of military personnel engaged in special warfare and first-response activities.

Methods: Multidisciplinary teams of subject matter experts (n = 19) were consulted in protocol generation. The performance improvement/human performance technology (HPT) model was used in the selection, refinement, and measurement of …

Helping Healthcare Teams Save Lives During Covid-19: Insights And Countermeasures From Team Science, Allison M Traylor, Scott I Tannenbaum, Eric J Thomas, Eduardo Salas

Faculty, Staff and Student Publications

As the COVID-19 pandemic has ravaged the United States, health care teams are on the frontlines of this global crisis, often navigating harrowing conditions at work, such as a lack of personal protective equipment and staffing shortages, and distractions at home, including worries about elderly relatives or making childcare arrangements. While the nature and severity of stressors impacting health care teams are in many ways unprecedented, decades of psychological research exploring teamwork in extreme contexts can provide insights to understand and improve outcomes for teams in a crisis. This review highlights the psychological principles that apply to teams in a …

Interscalene Block For Analgesia In Orthopedic Treatment Of Shoulder Trauma: Single-Dose Liposomal Bupivacaine Versus Perineural Catheter, Andrzej P Kwater, Nadia Hernandez, Carlos Artime, Johanna Blair De Haan

Faculty, Staff and Student Publications

BACKGROUND: Interscalene brachial plexus block is frequently utilized to provide perioperative analgesia to patients undergoing shoulder surgery to optimize recovery, minimize opioid consumption, and decrease overall hospital length of stay. The use of an indwelling perineural interscalene catheter provides extended analgesia and is efficacious in managing severe postoperative pain following major shoulder surgery. Currently, the only alternative to perineural catheters for extended analgesia with interscalene block involves the perineural infiltration of liposomal bupivacaine. However, there is limited published data regarding the overall analgesic effectiveness of using interscalene liposomal bupivacaine in the setting of shoulder surgery.

METHODS: We performed a retrospective …

Influenza Vaccination For The Prevention Of Cardiovascular Disease In The Americas: Consensus Document Of The Inter-American Society Of Cardiology And The Word Heart Federation, Álvaro Sosa Liprandi, María Inés Sosa Liprandi, Ezequiel José Zaidel, Gabriel M Aisenberg, Adrián Baranchuk, Eduardo Costa Duarte Barbosa, Gabriela Borrayo Sánchez, Bryce Alexander, Fernando Tomás Lanas Zanetti, Ricardo López Santi, Ana Girleza Múnera-Echeverri, Pablo Perel, Daniel Piskorz, Carlos Enrique Ruiz-Mori, Jorge Saucedo, Osiris Valdez, José Ramón González Juanatey, Daniel José Piñeiro, Fausto J Pinto, Fernando Stuardo Wyss Quintana

Faculty, Staff and Student Publications

BACKGROUND: Cardiovascular mortality is decreasing but remains the leading cause of death world-wide. Respiratory infections such as influenza significantly contribute to morbidity and mortality in patients with cardiovascular disease. Despite of proven benefits, influenza vaccination is not fully implemented, especially in Latin America.

OBJECTIVE: The aim was to develop a regional consensus with recommendations regarding influenza vaccination and cardiovascular disease.

METHODS: A multidisciplinary team composed by experts in the management and prevention of cardiovascular disease from the Americas, convened by the Inter-American Society of Cardiology (IASC) and the World Heart Federation (WHF), participated in the process and the formulation of …

A Developmental Stage-Specific Network Approach For Studying Dynamic Co-Regulation Of Transcription Factors And Micrornas During Craniofacial Development, Fangfang Yan, Peilin Jia, Hiroki Yoshioka, Akiko Suzuki, Junichi Iwata, Zhongming Zhao

Faculty, Staff and Student Publications

Craniofacial development is regulated through dynamic and complex mechanisms that involve various signaling cascades and gene regulations. Disruption of such regulations can result in craniofacial birth defects. Here, we propose the first developmental stage-specific network approach by integrating two crucial regulators, transcription factors (TFs) and microRNAs (miRNAs), to study their co-regulation during craniofacial development. Specifically, we used TFs, miRNAs and non-TF genes to form feed-forward loops (FFLs) using genomic data covering mouse embryonic days E10.5 to E14.5. We identified key novel regulators (TFs Foxm1, Hif1a, Zbtb16, Myog, Myod1 and Tcf7, and miRNAs miR-340-5p and miR-129-5p) and target genes (

The Cardiac Neural Crest Cells In Heart Development And Congenital Heart Defects, Eileen M Burd, Ahmed Babiker, Jessica K Fairley, Divya Bhamidipati, Laila E Woc-Colburn, Blaine A Mathison

Faculty, Staff and Student Publications

No abstract provided.

Clinical Prediction Of Coronavirus Disease-2019: How Accurate Can One Be?, Gabriel Aisenberg, Kevin O Hwang

Faculty, Staff and Student Publications

Background Some models based on clinical information have been reported to predict which patients have Coronavirus Disease-2019 (COVID-19) pneumonia but have failed so far to yield reliable results. We aimed to determine if physicians were able to accurately predict which patients, as described in clinical vignettes, had, or did not have this infection using their clinical acumen and epidemiological data. Methods Of 1177 patients under investigation for COVID-19 admitted, we selected 20 and presented them in a vignette form. We surveyed physicians from different levels of training (

Epilepsy Risk Prediction Model For Patients With Tuberous Sclerosis Complex, Laura S Farach, Melissa A Richard, Philip J Lupo, Mustafa Sahin, Darcy A Krueger, Joyce Y Wu, Elizabeth M Bebin, Kit Sing Au, Hope Northrup, Tacern Study Group

Faculty, Staff and Student Publications

BACKGROUND: Individuals with tuberous sclerosis complex are at increased risk of epilepsy. Early seizure control improves developmental outcomes, making identifying at-risk patients critically important. Despite several identified risk factors, it remains difficult to predict. The purpose of the study was to evaluate the combined risk prediction of previously identified risk factors for epilepsy in individuals with tuberous sclerosis complex.

METHODS: The study group (n = 333) consisted of individuals with tuberous sclerosis complex who were enrolled in the Tuberous Sclerosis Complex Autism Center of Excellence Research Network and UT TSC Biobank. The outcome was defined as having an epilepsy diagnosis. …

Tracheostomy While On Extracorporeal Membrane Oxygenation: A Comparison Of Percutaneous And Open Procedures, Ismael A Salas De Armas, Kha Dinh, Bindu Akkanti, Pushan Jani, Reshma Hussain, Lisa Janowiak, Kayla Kutilek, Manish K Patel, Mehmet H Akay, Rahat Hussain, Jayeshkumar Patel, Chandni Patel, Yafen Liang, John Zaki, Biswajit Kar, Igor D Gregoric

Faculty, Staff and Student Publications

Although the ideal timing of tracheostomy for critically ill patients is controversial, transitioning from an endotracheal tube can be beneficial. Concerns arise for patients under extracorporeal membrane oxygenation (ECMO) support. Studies have described percutaneous and open tracheostomy approaches for critically ill patients but, to our knowledge, have not compared the two specifically in ECMO patients. This study analyzed safety and aimed to identify if there was a difference in major bleeding or other tracheostomy-associated complications. A single-center retrospective cohort study of all patients who received tracheostomy while on ECMO from July 2013 to May 2019 was completed. The primary endpoint …

The Cortico-Limbo-Thalamo-Cortical Circuits: An Update To The Original Papez Circuit Of The Human Limbic System, Jochen Profit, Paul J Sharek, Xin Cui, Courtney C Nisbet, Eric J Thomas, Daniel S Tawfik, Henry C Lee, David Draper, J Bryan Sexton

Faculty, Staff and Student Publications

OBJECTIVES: Key validated clinical metrics are being used individually and in aggregate (Baby-MONITOR) to monitor the performance of neonatal intensive care units (NICUs). The degree to which perceptions of key components of safety culture, safety climate, and teamwork are related to aspects of NICU quality of care is poorly understood. The objective of this study was to test whether NICU performance on key clinical metrics correlates with caregiver perceptions of safety culture.

STUDY DESIGN: Cross-sectional study of 6253 very low-birth-weight infants in 44 NICUs. We measured clinical quality via the Baby-MONITOR and its nine risk-adjusted and standardized subcomponents (antenatal corticosteroids, …

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 …

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 …