Digital Commons Network^™

Distinct Cortical Systems Reinstate The Content And Context Of Episodic Memories., James E. Kragel, Youssef Ezzyat, Bradley C. Lega, Michael R. Sperling, Gregory A. Worrell, Robert E. Gross, Barbara C. Jobst, Sameer A. Sheth, Kareem A. Zaghloul, Joel M. Stein, Michael J. Kahana

Department of Neurology Faculty Papers

Episodic recall depends upon the reinstatement of cortical activity present during the formation of a memory. Evidence from functional neuroimaging and invasive recordings in humans suggest that reinstatement organizes our memories by time or content, yet the neural systems involved in reinstating these unique types of information remain unclear. Here, combining computational modeling and intracranial recordings from 69 epilepsy patients, we show that two cortical systems uniquely reinstate the semantic content and temporal context of previously studied items during free recall. Examining either the posterior medial or anterior temporal networks, we find that forward encoding models trained on the brain's …

Retinoids As Chemo-Preventive And Molecular-Targeted Anti-Cancer Therapies., Victoria O. Hunsu, Caroline O.B. Facey, Jeremy Z. Fields, Bruce M. Boman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Retinoic acid (RA) agents possess anti‐tumor activity through their ability to induce cellular differentiation. However, retinoids have not yet been translated into effective systemic treatments for most solid tumors. RA signaling is mediated by the following two nuclear retinoic receptor subtypes: the retinoic acid receptor (RAR) and the retinoic X receptor (RXR), and their isoforms. The identification of mutations in retinoid receptors and other RA signaling pathway genes in human cancers offers opportunities for target discovery, drug design, and personalized medicine for distinct molecular retinoid subtypes. For example, chromosomal translocation involving RARA occurs in acute promyelocytic leukemia (APL), and all‐trans …

Lysmd3: A Mammalian Pattern Recognition Receptor For Chitin, Xin He, Brad A. Howard, Yang Liu, Aaron K. Neumann, Liwu Li, Nidhi Menon, Tiffany Roach, Shiv D. Kale, David C. Samuels, Hongyan Li, Trenton Kite, Hirohito Kita, Tony Y. Hu, Mengyao Luo, Caroline N. Jones, Uju Joy Okaa, Diane L. Squillace, Bruce S. Klein, Christopher B. Lawrence

Pathology Research and Scholarship

Chitin, a major component of fungal cell walls, has been associated with allergic disorders such as asthma. However, it is unclear how mammals recognize chitin and the principal receptor(s) on epithelial cells that sense chitin remain to be determined. In this study, we show that LYSMD3 is expressed on the surface of human airway epithelial cells and demonstrate that LYSMD3 is able to bind chitin, as well as β-glucan, on the cell walls of fungi. Knockdown or knockout of LYSMD3 also sharply blunts the production of inflammatory cytokines by epithelial cells in response to chitin and fungal spores. Competitive inhibition …

Spoken Word Learning In Children With Developmental Language Disorder Or Dyslexia, Suzanne M. Adlof, Lauren S. Baron, Bethany A. Bell, Joanna Scoggins

Faculty Publications

Purpose Word learning difficulties have been documented in multiple studies involving children with dyslexia and developmental language disorder (DLD; see also specific language impairment). However, no previous studies have directly contrasted word learning in these two frequently co-occurring disorders. We examined word learning in second-grade students with DLD-only and dyslexia-only as compared to each other, peers with both disorders (DLD + dyslexia), and peers with typical development. We hypothesized that children with dyslexia-only and DLD-only would show differences in word learning due to differences in their core language strengths and weaknesses. Method Children ( = 244) were taught eight novel …

Reducing Covid-19 Quarantine With Sars-Cov-2 Testing: A Simulation Study, Bo Peng, Wen Zhou, Rowland W Pettit, Patrick Yu, Peter G Matos, Alexander L Greninger, Julie Mccashin, Christopher I Amos

Faculty, Staff and Students Publications

OBJECTIVE: To evaluate the effectiveness of SARS-CoV-2 testing on shortening the duration of quarantines for COVID-19 and to identify the most effective choices of testing schedules.

DESIGN: We performed extensive simulations to evaluate the performance of quarantine strategies when one or more SARS-CoV-2 tests were administered during the quarantine. Simulations were based on statistical models for the transmissibility and viral loads of SARS-CoV-2 infections and the sensitivities of available testing methods. Sensitivity analyses were performed to evaluate the impact of perturbations in model assumptions on the outcomes of optimal strategies.

RESULTS: We found that SARS-CoV-2 testing can effectively reduce the …

Significant Regional Differences In Antibiotic Use Across 576 Us Hospitals And 11 701 326 Adult Admissions, 2016-2017, Katherine E Goodman, Sara E Cosgrove, Lisa Pineles, Laurence S Magder, Deverick J Anderson, Elizabeth Dodds Ashley, Ronald E Polk, Hude Quan, William E Trick, Keith F Woeltje, Surbhi Leekha, Anthony D Harris

2020-Current year OA Pubs

BACKGROUND: Quantifying the amount and diversity of antibiotic use in United States hospitals assists antibiotic stewardship efforts but is hampered by limited national surveillance. Our study aimed to address this knowledge gap by examining adult antibiotic use across 576 hospitals and nearly 12 million encounters in 2016-2017.

METHODS: We conducted a retrospective study of patients aged ≥ 18 years discharged from hospitals in the Premier Healthcare Database between 1 January 2016 and 31 December 2017. Using daily antibiotic charge data, we mapped antibiotics to mutually exclusive classes and to spectrum of activity categories. We evaluated relationships between facility and case-mix …

Coding And Noncoding Variants In Ebf3 Are Involved In Hadds And Simplex Autism, Evin M Padhi, Jeffrey K Ng, Elvisa Mehinovic, Tychele N Turner, Et Al.

2020-Current year OA Pubs

BACKGROUND: Previous research in autism and other neurodevelopmental disorders (NDDs) has indicated an important contribution of protein-coding (coding) de novo variants (DNVs) within specific genes. The role of de novo noncoding variation has been observable as a general increase in genetic burden but has yet to be resolved to individual functional elements. In this study, we assessed whole-genome sequencing data in 2671 families with autism (discovery cohort of 516 families, replication cohort of 2155 families). We focused on DNVs in enhancers with characterized in vivo activity in the brain and identified an excess of DNVs in an enhancer named hs737. …

Systematic Analysis Of Sars-Cov-2 Infection Of An Ace2-Negative Human Airway Cell, Maritza Puray-Chavez, Kyle M Lapak, Jennifer L Elliott, Dhaval P Bhatt, Ria Jasuja, Dana Q Lawson, Keanu Davis, Paul W Rothlauf, Zhuoming Liu, Nakyung Lee, Kasyap Tenneti, Jenna E Eschbach, Christian Shema Mugisha, Hung R Vuong, Laura A Vanblargan, Adam L Bailey, Michael S Diamond, Sean P J Whelan, Amjad Horani, Steven L Brody, Dennis Goldfarb, M Ben Major, Sebla B Kutluay, Et Al

Open Access Publications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) variants govern transmissibility, responsiveness to vaccination, and disease severity. In a screen for new models of SARS-CoV-2 infection, we identify human H522 lung adenocarcinoma cells as naturally permissive to SARS-CoV-2 infection despite complete absence of angiotensin-converting enzyme 2 (ACE2) expression. Remarkably, H522 infection requires the E484D S variant; viruses expressing wild-type S are not infectious. Anti-S monoclonal antibodies differentially neutralize SARS-CoV-2 E484D S in H522 cells as compared to ACE2-expressing cells. Sera from vaccinated individuals block this alternative entry mechanism, whereas convalescent sera are less effective. Although the H522 receptor remains …

Later Sleep Timing Predicts Accelerated Summer Weight Gain Among Elementary School Children: A Prospective Observational Study, Jennette P Moreno, Javad Razjouyan, Houston Lester, Hafza Dadabhoy, Mona Amirmazaheri, Layton Reesor-Oyer, Teresia M O'Connor, Daphne C Hernandez, Bijan Najafi, Candice A Alfano, Stephanie J Crowley, Debbe Thompson, Tom Baranowski

Children’s Nutrition Research Center Staff Publications

Objectives and background: Social demands of the school-year and summer environment may affect children's sleep patterns and circadian rhythms during these periods. The current study examined differences in children's sleep and circadian-related behaviors during the school-year and summer and explored the association between sleep and circadian parameters and change in body mass index (BMI) during these time periods.

Methods: This was a prospective observational study with 119 children ages 5 to 8 years with three sequential BMI assessments: early school-year (fall), late school-year (spring), and beginning of the following school-year in Houston, Texas, USA. Sleep midpoint, sleep duration, variability of …

Homozygous Mtap Deletion In Primary Human Glioblastoma Is Not Associated With Elevation Of Methylthioadenosine, Yasaman Barekatain, Jeffrey J. Ackroyd, Victoria C. Yan, Sunada Khadka, Lin Wang, Ko-Chien Chen, Anton H. Poral, Theresa Tran, Dimitra K. Georgiou, Kenisha Arthur, Yu-Hsi Lin, Nikunj Satani, Elliot S. Ballato, Eliot I. Behr, Ana C. De Carvalho, Roel G.W. Verhaak, John De Groot, Jason T. Huse, John M. Asara, Raghu Kalluri, Florian L. Muller

Neurosurgery Articles

Homozygous deletion of methylthioadenosine phosphorylase (MTAP) in cancers such as glioblastoma represents a potentially targetable vulnerability. Homozygous MTAP-deleted cell lines in culture show elevation of MTAP's substrate metabolite, methylthioadenosine (MTA). High levels of MTA inhibit protein arginine methyltransferase 5 (PRMT5), which sensitizes MTAP-deleted cells to PRMT5 and methionine adenosyltransferase 2A (MAT2A) inhibition. While this concept has been extensively corroborated in vitro, the clinical relevance relies on exhibiting significant MTA accumulation in human glioblastoma. In this work, using comprehensive metabolomic profiling, we show that MTA secreted by MTAP-deleted cells in vitro results in high levels of extracellular MTA. We further demonstrate …

Therapeutic Efficacy Of A Potent Anti-Venezuelan Equine Encephalitis Virus Antibody Is Contingent On Fc Effector Function, Vanja Krneta-Stankic, Mark E Corkins, Adriana Paulucci-Holthauzen, Malgorzata Kloc, Andrew B Gladden, Rachel K Miller

Faculty, Staff and Student Publications

E-cadherin junctions facilitate assembly and disassembly of cell contacts that drive development and homeostasis of epithelial tissues. In this study, using Xenopus embryonic kidney and Madin-Darby canine kidney (MDCK) cells, we investigate the role of the Wnt/planar cell polarity (PCP) formin Daam1 (Dishevelled-associated activator of morphogenesis 1) in regulating E-cadherin-based intercellular adhesion. Using live imaging, we show that Daam1 localizes to newly formed cell contacts in the developing nephron. Furthermore, analyses of junctional filamentous actin (F-actin) upon Daam1 depletion indicate decreased microfilament localization and slowed turnover. We also show that Daam1 is necessary for efficient and timely localization of junctional …

Association Of Nonacute Opioid Use And Cardiovascular Diseases: A Scoping Review Of The Literature, Jade H. Singleton, Erin L. Abner, Peter D. Akpunonu, Anna M. Kucharska-Newton

Epidemiology and Environmental Health Faculty Publications

BACKGROUND

In this scoping review, we identified and reviewed 23 original articles from the PubMed database that investigated the relationship between nonacute opioid use (NOU) and cardiovascular outcomes.

METHODS AND RESULTS

We defined NOU to include both long-term opioid therapy and opioid use disorder. We summarized the association between NOU and 5 classes of cardiovascular disease, including infective endocarditis, coronary heart disease (including myocardial infarction), congestive heart failure, cardiac arrythmia (including cardiac arrest), and stroke. The most commonly studied outcomes were coronary heart disease and infective endocarditis. There was generally consistent evidence of a positive association between community prevalence of …

Long Non-Coding Rnas And Their Targets As Potential Biomarkers In Breast Cancer., Maryam Khalid, Rehan Zafar Paracha, Maryum Nisar, Sumaira Malik, Salma Tariq, Iqra Arshad, Amnah Siddiqa, Zamir Hussain, Jamil Ahmad, Amjad Ali

Faculty Research 2021

Breast cancer is among the lethal types of cancer with a high mortality rate, globally. Its high prevalence can be controlled through improved analysis and identification of disease-specific biomarkers. Recently, long non-coding RNAs (lncRNAs) have been reported as key contributors of carcinogenesis and regulate various cellular pathways through post-transcriptional regulatory mechanisms. The specific aim of this study was to identify the novel interactions of aberrantly expressed genetic components in breast cancer by applying integrative analysis of publicly available expression profiles of both lncRNAs and mRNAs. Differential expression patterns were identified by comparing the breast cancer expression profiles of samples with …

Clinical, Immunophenotypic And Genomic Findings Of Nk Lymphoblastic Leukemia: A Study From The Bone Marrow Pathology Group, Olga K. Weinberg, Karen M. Chisholm, Chi Young Ok, Yuri Fedoriw, Bartosz Grzywacz, Jason H. Kurzer, Emily F. Mason, Karen A. Moser, Siddharth Bhattacharya, Mina Xu, Daniel Babu, Kathryn Foucar, Wayne Tam, Adam Bagg, Attilio Orazi, Tracy I. George, Wei Wang, Sa A. Wang, Daniel A. Arber, Robert P. Hasserjian

Pathology Research and Scholarship

Natural killer (NK) cells are lymphocytes of the native immune system that play a pivotal role in host defense and immune surveillance. While the conceptual view of NK-neoplasms is evolving, little is known about the rare NK lymphoblastic leukemia (NK-LL), which remains as a provisional entity in the 2016 WHO Classification. The goal of this study is to characterize NK-LL cases and compare with other CD56 co-expressing acute leukemias. We identified 105 cases, diagnosed as NK-LL (6), CD56+ acute undifferentiated leukemia (AUL) (6), CD56+ T-lymphoblastic leukemia (T-LL) (51), and CD56+ acute myeloid leukemia (AML) (42). Compared to AUL patients, NK-LL …

Rabies Postexposure Prophylaxis In The United States: Opportunities To Improve Access, Coordination, And Delivery, Gavin T. Howington, Huy-Binh Nguyen, P Brandon Bookstaver, Peter Akpunonu, Joshua T. Swan

Faculty Publications

No abstract provided.

Active Surveillance Of Metastatic Renal Cell Carcinoma: Results From A Prospective Observational Study (Marcc), Michael R Harrison, Russell K Pachynski, Et Al.

2020-Current year OA Pubs

BACKGROUND: Systemic therapy (ST) can be deferred in patients who have metastatic renal cell carcinoma (mRCC) and slow-growing metastases. Currently, this subset of patients managed with active surveillance (AS) is not well described in the literature.

METHODS: This was a prospective observational study of patients with mRCC across 46 US community and academic centers. The objective was to describe baseline characteristics and demographics of patients with mRCC initially managed by AS, reasons for AS, and patient outcomes. Descriptive statistics were used to characterize demographics, baseline characteristics, and patient-related outcomes. Wilcoxon 2-sample rank-sum tests and χ

RESULTS: Of 504 patients, mRCC …

Riociguat: Clinical Research And Evolving Role In Therapy, James R Klinger, Murali M Chakinala, David Langleben, Stephan Rosenkranz, Olivier Sitbon

2020-Current year OA Pubs

Riociguat is a first-in-class soluble guanylate cyclase stimulator, approved for the treatment of adults with pulmonary arterial hypertension (PAH), inoperable chronic thromboembolic pulmonary hypertension (CTEPH), or persistent or recurrent CTEPH after pulmonary endarterectomy. Approval was based on the results of the phase III PATENT-1 (PAH) and CHEST-1 (CTEPH) studies, with significant improvements in the primary endpoint of 6-minute walk distance vs placebo of +36 m and +46 m, respectively, as well as improvements in secondary endpoints such as pulmonary vascular resistance and World Health Organization functional class. Riociguat acts as a stimulator of cyclic guanosine monophosphate synthesis rather than as …

Body Composition Changes In Children During Treatment For Moderate Acute Malnutrition: Findings From A 4-Arm Cluster-Randomized Trial In Sierra Leone, Devika J Suri, Isabel Potani, Akriti Singh, Stacy Griswold, William W Wong, Breanne Langlois, Ye Shen, Kwan Ho Kenneth Chui, Irwin H Rosenberg, Patrick Webb, Beatrice L Rogers

Children’s Nutrition Research Center Staff Publications

Background: Measures that better describe "healthy" and sustainable recovery during nutritional treatment of children with moderate acute malnutrition (MAM) are needed.

Objectives: We compared changes to body composition among children receiving 1 of 4 specialized nutritious food (SNFs) during treatment of MAM and by recovery and relapse outcomes.

Methods: The study was nested within a prospective, cluster-randomized, community-based, cost-effectiveness trial assessing 4 SNFs to treat children aged 6-59 mo with MAM [midupper arm circumference (MUAC) ≥11.5 cm and <12.5 cm without bipedal edema] in Sierra Leone. Biweekly SNF rations (1 of 3 fortified-blended foods or a lipid-based nutrient supplement) were given until children recovered (MUAC ≥12.5 cm), or up to 7 rations (∼12 wk). Deuterium dilution was used to estimate fat-free mass (FFM) and fat mass (FM) at enrollment and after 4 wk of treatment to ensure similar treatment exposure among the participants. Another MUAC measurement was performed among recovered children 4 wk after program exit to determine whether recovery was sustained. ANOVA, paired t tests, and linear regression models were used to determine significant differences in changes from baseline to 4 wk.

Results: Among 312 analyzed participants, mean baseline weight comprised ∼80% FFM; mean weight gained after 4 wk comprised ∼82% FFM. Changes in …

Reciprocal Control Of Obesity And Anxiety-Depressive Disorder Via A Gaba And Serotonin Neural Circuit, Guobin Xia, Yong Han, Fantao Meng, Yanlin He, Dollada Srisai, Monica Farias, Minghao Dang, Richard D Palmiter, Yong Xu, Qi Wu

Children’s Nutrition Research Center Staff Publications

The high comorbidity between obesity and mental disorders, such as depression and anxiety, often exacerbates metabolic and neurological symptoms significantly. However, neural mechanisms that underlie reciprocal control of feeding and mental states are largely elusive. Here we report that melanocortin 4 receptor (MC4R) neurons located in the dorsal bed nucleus of the stria terminus (dBNST) engage in the regulation of mentally associated weight gain by receiving GABAergic projections from hypothalamic AgRP neurons onto α5-containing GABA

Predicting The Environmental Suitability For Onchocerciasis In Africa As An Aid To Elimination Planning, Elizabeth A. Cromwell, Ziyad Al-Aly, Et Al

Open Access Publications

Recent evidence suggests that, in some foci, elimination of onchocerciasis from Africa may be feasible with mass drug administration (MDA) of ivermectin. To achieve continental elimination of transmission, mapping surveys will need to be conducted across all implementation units (IUs) for which endemicity status is currently unknown. Using boosted regression tree models with optimised hyperparameter selection, we estimated environmental suitability for onchocerciasis at the 5 × 5-km resolution across Africa. In order to classify IUs that include locations that are environmentally suitable, we used receiver operating characteristic (ROC) analysis to identify an optimal threshold for suitability concordant with locations where …

Cardiovascular Outcomes In Patients With Mitochondrial Disease In The United States: A Propensity Score Analysis, Tran Nguyen, Talal Alzahrani, Joseph Krepp, Gurusher Panjrath

The Texas Heart Institute Journal

Mitochondrial disease comprises a wide range of genetic disorders caused by mitochondrial dysfunction. Its rarity, however, has limited the ability to assess its effects on clinical outcomes. To evaluate this relationship, we collected data from the 2016 National Inpatient Sample, which includes data from >7 million hospital stays. We identified 705 patients (mean age, 22 ± 20.7 yr; 54.2% female; 67.4% white) whose records included the ICD-10-CM code E88.4. We also identified a propensity-matched cohort of 705 patients without mitochondrial disease to examine the effect of mitochondrial disease on major adverse cardiovascular events, including all-cause in-hospital death, cardiac arrest, and …

Central And Peripheral Arterial Diseases In Chronic Kidney Disease: Conclusions From A Kidney Disease: Improving Global Outcomes (Kdigo) Controversies Conference, Kirsten L Johansen, Pranav S Garimella, Caitlin W Hicks, Philip A Kalra, Dearbhla M Kelly, Sven Martens, Kunihiro Matsushita, Pantelis Sarafidis, Manish M Sood, Charles A Herzog, Michael Cheung, Michel Jadoul, Wolfgang C Winkelmayer, Holger Reinecke, Conference Participants

Faculty, Staff and Students Publications

Chronic kidney disease (CKD) affects about 10% of all populations worldwide, with about 2 million people requiring dialysis. Although patients with CKD are at high risk of cardiovascular disease and events, they are often underrepresented or excluded in clinical trials, leading to important knowledge gaps about how to treat these patients. KDIGO (Kidney Disease: Improving Global Outcomes) convened the fourth clinical Controversies Conference on the heart, kidney and vasculature in Dublin, Ireland, in February 2020, entitled Central and Peripheral Arterial Diseases in Chronic Kidney Disease. A global panel of multidisciplinary experts from the fields of nephrology, cardiology, neurology, surgery, radiology, …

High Burden Of Subclinical And Cardiovascular Disease Risk In Adults With Metabolically Healthy Obesity: The Atherosclerosis Risk In Communities (Aric) Study, Yvonne Commodore-Mensah, Mariana Lazo, Olive Tang, Justin B Echouffo-Tcheugui, Chiadi E Ndumele, Vijay Nambi, Dan Wang, Christie Ballantyne, Elizabeth Selvin

Faculty, Staff and Students Publications

OBJECTIVE: It is controversial whether adults who are obese but "metabolically healthy" have cardiovascular disease (CVD) risk comparable with that of normal-weight adults. High-sensitivity cardiac troponin T (hs-cTnT), a biomarker of myocardial damage, is useful in characterizing subclinical CVD. We categorized obesity phenotypes and studied their associations with subclinical and clinical CVD and CVD subtypes, including heart failure (HF).

RESEARCH DESIGN AND METHODS: We conducted cross-sectional and prospective analyses of 9,477 adults in the Atherosclerosis Risk in Communities (ARIC) study. We used the Adult Treatment Panel III criteria and BMI to define obesity phenotypes as follows: metabolically healthy normal weight, …

Sex-Related Disparities In Cardiovascular Health Care Among Patients With Premature Atherosclerotic Cardiovascular Disease, Michelle T Lee, Dhruv Mahtta, David J Ramsey, Jing Liu, Arunima Misra, Khurram Nasir, Zainab Samad, Dipti Itchhaporia, Safi U Khan, Richard S Schofield, Christie M Ballantyne, Laura A Petersen, Salim S Virani

Faculty, Staff and Students Publications

IMPORTANCE: There is a paucity of data regarding secondary prevention care disparities in women with premature and extremely premature atherosclerotic cardiovascular disease (ASCVD), defined as an ASCVD event at 55 years or younger and 40 years or younger, respectively.

OBJECTIVE: To evaluate sex-based differences in antiplatelet agents, any statin, high-intensity statin (HIS) therapy, and statin adherence in patients with premature and extremely premature ASCVD.

DESIGN, SETTING, AND PARTICIPANTS: This was a cross-sectional, multicenter, nationwide VA health care system-based study with patients enrolled in the Veterans With Premature Atherosclerosis (VITAL) registry. The study assessed patients who had at least 1 primary …

Socio-Demographic And Trauma-Related Predictors Of Ptsd Within 8 Weeks Of A Motor Vehicle Collision In The Aurora Study, Ronald C Kessler, Kerry J Ressler, Stacey L House, Francesca L Beaudoin, Xinming An, Jennifer S Stevens, Donglin Zeng, Thomas C Neylan, Sarah D Linnstaedt, Laura T Germine, Paul I Musey, Phyllis L Hendry, Sophia Sheikh, Alan B Storrow, Christopher W Jones, Brittany E Punches, Elizabeth M Datner, Kamran Mohiuddin, Nina T Gentile, Meghan E Mcgrath, Sanne J Van Rooij, Lauren A Hudak, John P Haran, David A Peak, Robert M Domeier, Claire Pearson, Leon D Sanchez, Niels K Rathlev, William F Peacock, Steven E Bruce, Mark W Miller, Jutta Joormann, Deanna M Barch, Diego A Pizzagalli, John F Sheridan, Jordan W Smoller, Thaddeus W W Pace, Steven E Harte, James M Elliott, Nathaniel G Harnett, Lauren A M Lebois, Irving Hwang, Nancy A Sampson, Karestan C Koenen, Samuel A Mclean

Faculty, Staff and Students Publications

This is the initial report of results from the AURORA multisite longitudinal study of adverse post-traumatic neuropsychiatric sequelae (APNS) among participants seeking emergency department (ED) treatment in the aftermath of a traumatic life experience. We focus on n = 666 participants presenting to EDs following a motor vehicle collision (MVC) and examine associations of participant socio-demographic and participant-reported MVC characteristics with 8-week posttraumatic stress disorder (PTSD) adjusting for pre-MVC PTSD and mediated by peritraumatic symptoms and 2-week acute stress disorder (ASD). Peritraumatic Symptoms, ASD, and PTSD were assessed with self-report scales. Eight-week PTSD prevalence was relatively high (42.0%) and positively …

Administrative Coding In Electronic Health Care Record-Based Research Of Nafld: An Expert Panel Consensus Statement, Hannes Hagström, Leon A Adams, Alina M Allen, Christopher D Byrne, Yoosoo Chang, Henning Grønbaek, Mona Ismail, Peter Jepsen, Fasiha Kanwal, Jennifer Kramer, Jeffrey V Lazarus, Michelle T Long, Rohit Loomba, Philip N Newsome, Ian A Rowe, Seungho Ryu, Jörn M Schattenberg, Marina Serper, Nick Sheron, Tracey G Simon, Elliot B Tapper, Sarah Wild, Vincent Wai-Sun Wong, Yusuf Yilmaz, Shira Zelber-Sagi, Fredrik Åberg

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Electronic health record (EHR)-based research allows the capture of large amounts of data, which is necessary in NAFLD, where the risk of clinical liver outcomes is generally low. The lack of consensus on which International Classification of Diseases (ICD) codes should be used as exposures and outcomes limits comparability and generalizability of results across studies. We aimed to establish consensus among a panel of experts on ICD codes that could become the reference standard and provide guidance around common methodological issues.

APPROACH AND RESULTS: Researchers with an interest in EHR-based NAFLD research were invited to collectively define …

Factors Associated With Access To And Receipt Of Liver Transplantation In Veterans With End-Stage Liver Disease, Fasiha Kanwal, Ruben Hernaez, Yan Liu, Thomas J Taylor, Abbas Rana, Jennifer R Kramer, Aanand D Naik, Donna Smith, Tamar Taddei, Steven M Asch

Faculty, Staff and Students Publications

IMPORTANCE: Organ scarcity means few patients with advanced liver disease undergo a transplant, making equitable distribution all the more crucial. Disparities may arise at any stage in the complex process leading up to this curative therapy.

OBJECTIVE: To examine the rate of and factors associated with referral, wait-listing, and receipt of liver allografts.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used linked data from comprehensive electronic medical records and the United Network of Organ Sharing. Adult patients with cirrhosis and a Model for End-Stage Liver Disease with addition of sodium score of at least 15 points between October 1, …

Cd8+ T Cells Inhibit Metastasis And Cxcl4 Regulates Its Function, Robiya Joseph, Rama Soundararajan, Suhas Vasaikar, Fei Yang, Kendra L Allton, Lin Tian, Petra Den Hollander, Sevinj Isgandarova, Monika Haemmerle, Barbara Mino, Tieling Zhou, Crystal Shin, Melisa Martinez-Paniagua, Aysegul A Sahin, Jaime Rodriguez-Canales, Juri Gelovani, Jeffrey T Chang, Ghanashyam Acharya, Anil K Sood, Ignacio I Wistuba, Don L Gibbons, Luisa M Solis, Michelle C Barton, Navin Varadarajan, Jeffrey M Rosen, Xiang H Zhang, Sendurai A Mani

Faculty, Staff and Students Publications

Background

The mechanism by which immune cells regulate metastasis is unclear. Understanding the role of immune cells in metastasis will guide the development of treatments improving patient survival.

Methods

We used syngeneic orthotopic mouse tumour models (wild-type, NOD/scid and Nude), employed knockout (CD8 and CD4) models and administered CXCL4. Tumours and lungs were analysed for cancer cells by bioluminescence, and circulating tumour cells were isolated from blood. Immunohistochemistry on the mouse tumours was performed to confirm cell type, and on a tissue microarray with 180 TNBCs for human relevance. TCGA data from over 10,000 patients were analysed as …

Intermittent Hypoxia And Effects On Early Learning/Memory: Exploring The Hippocampal Cellular Effects Of Pediatric Obstructive Sleep Apnea, Arvind Chandrakantan, Adam C Adler, Mehmet Tohsun, Farrah Kheradamand, Russell S Ray, Steven Roth

Faculty, Staff and Students Publications

This review provides an update on the neurocognitive phenotype of pediatric obstructive sleep apnea (OSA). Pediatric OSA is associated with neurocognitive deficits involving memory, learning, and executive functioning. Adenotonsillectomy (AT) is presently accepted as the first-line surgical treatment for pediatric OSA, but the executive function deficits do not resolve postsurgery, and the timeline for recovery remains unknown. This finding suggests that pediatric OSA potentially causes irreversible damage to multiple areas of the brain. The focus of this review is the hippocampus, 1 of the 2 major sites of postnatal neurogenesis, where new neurons are formed and integrated into existing circuitry …

Epigenetic Regulation During Human Cortical Development: Seq-Ing Answers From The Brain To The Organoid, Emily M A Lewis, Komal Kaushik, Luke A Sandoval, Irene Antony, Sabine Dietmann, Kristen L Kroll

2020-Current year OA Pubs

Epigenetic regulation plays an important role in controlling gene expression during complex processes, such as development of the human brain. Mutations in genes encoding chromatin modifying proteins and in the non-protein coding sequences of the genome can potentially alter transcription factor binding or chromatin accessibility. Such mutations can frequently cause neurodevelopmental disorders, therefore understanding how epigenetic regulation shapes brain development is of particular interest. While epigenetic regulation of neural development has been extensively studied in murine models, significant species-specific differences in both the genome sequence and in brain development necessitate human models. However, access to human fetal material is limited …