Medical Specialties Commons^™

Transcriptome-Wide Identification Of Rna-Binding Protein Binding Sites Using Seclip-Seq, Steven M Blue, Brian A Yee, Gabriel A Pratt, Jasmine R Mueller, Samuel S Park, Alexander A Shishkin, Anne C Starner, Eric L Van Nostrand, Gene W Yeo

Faculty, Staff and Students Publications

Discovery of interaction sites between RNA-binding proteins (RBPs) and their RNA targets plays a critical role in enabling our understanding of how these RBPs control RNA processing and regulation. Cross-linking and immunoprecipitation (CLIP) provides a generalizable, transcriptome-wide method by which RBP/RNA complexes are purified and sequenced to identify sites of intermolecular contact. By simplifying technical challenges in prior CLIP methods and incorporating the generation of and quantitative comparison against size-matched input controls, the single-end enhanced CLIP (seCLIP) protocol allows for the profiling of these interactions with high resolution, efficiency and scalability. Here, we present a step-by-step guide to the seCLIP …

Evaluating Eosinophilic Colitis As A Unique Disease Using Colonic Molecular Profiles: A Multi-Site Study, Tetsuo Shoda, Margaret H Collins, Mark Rochman, Ting Wen, Julie M Caldwell, Lydia E Mack, Garrett A Osswald, John A Besse, Yael Haberman, Seema S Aceves, Nicoleta C Arva, Kelley E Capocelli, Mirna Chehade, Carla M Davis, Evan S Dellon, Gary W Falk, Nirmala Gonsalves, Sandeep K Gupta, Ikuo Hirano, Paneez Khoury, Amy Klion, Calies Menard-Katcher, John Leung, Vincent A Mukkada, Philip E Putnam, Jonathan M Spergel, Joshua B Wechsler, Guang-Yu Yang, Glenn T Furuta, Lee A Denson, Marc E Rothenberg, Consortium Of Eosinophilic Gastrointestinal Diseases Researchers (Cegir)

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Colonic eosinophilia, an enigmatic finding often referred to as eosinophilic colitis (EoC), is a poorly understood condition. Whether EoC is a distinct disease or a colonic manifestation of eosinophilic gastrointestinal diseases (EGIDs) or inflammatory bowel disease (IBD) is undetermined.

METHODS: Subjects with EoC (n = 27) and controls (normal [NL, n = 20], Crohn's disease [CD, n = 14]) were enrolled across sites associated with the Consortium of Eosinophilic Gastrointestinal Disease Researchers. EoC was diagnosed as colonic eosinophilia (ascending ≥100, descending ≥85, sigmoid ≥65 eosinophils/high-power field) with related symptoms. Colon biopsies were subjected to RNA sequencing. Associations …

Internal Medicine Residents' Perceptions Of Virtual Morning Report: A Multicenter Survey, Tyler J Albert, Joel Bradley, Helene Starks, Jeff Redinger, Cherinne Arundel, Albertine Beard, Laura Caputo, Jonathan Chun, Craig G Gunderson, Dan Heppe, Anand Jagannath, Kyle Kent, Michael Krug, James Laudate, Vignesh Palaniappan, Amanda Pensiero, Zaven Sargsyan, Emily Sladek, Matthew Tuck, Paul B Cornia

Faculty, Staff and Students Publications

IMPORTANCE: The COVID-19 pandemic disrupted graduate medical education, compelling training programs to abruptly transition to virtual educational formats despite minimal experience or proficiency. We surveyed residents from a national sample of internal medicine (IM) residency programs to describe their experiences with the transition to virtual morning report (MR), a highly valued core educational conference.

OBJECTIVE: Assess resident views about virtual MR content and teaching strategies during the COVID-19 pandemic.

DESIGN: Anonymous, web-based survey.

PARTICIPANTS: Residents from 14 academically affiliated IM residency programs.

MAIN MEASURES: The 25-item survey on virtual MR included questions on demographics; frequency and reason for attending; opinions …

Inflammatory Links Between Hypertriglyceridemia And Atherogenesis, Xueying Peng, Huaizhu Wu

Faculty, Staff and Students Publications

Purpose of Review

Recent studies indicate an association between hypertriglyceridemia (HTG) and atherosclerotic cardiovascular disease (ASCVD). The purpose of this review is to discuss the potential mechanism connecting HTG and ASCVD risk and the potential efficacy of HTG-targeting therapies in ASCVD prevention.

Recent Findings

HTG, with elevations in triglyceride-rich lipoproteins (TGRL) and their remnants, are causal ASCVD risk factors. The mechanisms whereby HTG increases ASCVD risk are not well understood but may include multiple factors. Inflammation plays a crucial role in atherosclerosis. TGRL compared to low-density lipoproteins (LDL) correlate better with inflammation. TGRL remnants can penetrate endothelium and interact with …

Heightened Levels Of Plasma Growth Differentiation Factor 15 In Men Living With Hiv, Neeti Agarwal, Claudia E Ramirez Bustamante, Huaizhu Wu, Reina Armamento-Villareal, Jordan E Lake, Ashok Balasubramanyam, Sean M Hartig

Faculty, Staff and Students Publications

Plasma biomarkers that reflect energy balance disorders in people living with HIV (PLWH) remain limited. Growth differentiation factor 15 (GDF15) abundance in plasma of mice and humans induces negative energy balance but also becomes highly elevated in obesity and other metabolic diseases. We sought to compare plasma GDF15 levels in PLWH and HIV-negative persons and mouse models expressing the HIV accessory protein Vpr (that recapitulate HIV-associated metabolic disorders) and determine their relationship to metabolic parameters. We measured liver Gdf15 mRNA levels and plasma GDF15 levels in male Vpr mice and littermate controls. In parallel, we analyzed plasma GDF15 levels in …

Circadian Regulation Of Gene Expression And Metabolism In The Liver, Dongyin Guan, Mitchell A Lazar

Faculty, Staff and Students Publications

Circadian rhythms are approximately 24-hour cycles of variation in physiological processes, gene expression, and behavior. They result from the interplay of internal biological clocks with daily environmental rhythms, including light/dark and feeding/fasting. Note that 24-hour rhythms of liver metabolic processes have been known for almost 100 years. Modern studies reveal that, like metabolism, hepatic gene expression is highly rhythmic. Genetic or environmental changes can disrupt the circadian rhythms of the liver, leading to metabolic disorders and hepatocellular carcinoma. In this review, we summarize the current understanding of mechanisms regulating rhythmic gene expression in the liver, highlighting the roles of transcription …

Signal-To-Noise Analysis Can Inform The Likelihood That Incidentally Identified Variants In Sarcomeric Genes Are Associated With Pediatric Cardiomyopathy, Leonie M Kurzlechner, Edward G Jones, Amy M Berkman, Hanna J Tadros, Jill A Rosenfeld, Yaping Yang, Hari Tunuguntla, Hugh D Allen, Jeffrey J Kim, Andrew P Landstrom

Faculty, Staff and Students Publications

Background: Hypertrophic cardiomyopathy (HCM) is the most common heritable cardiomyopathy and can predispose individuals to sudden death. Most pediatric HCM patients host a known pathogenic variant in a sarcomeric gene. With the increase in exome sequencing (ES) in clinical settings, incidental variants in HCM-associated genes are being identified more frequently. Diagnostic interpretation of incidental variants is crucial to enhance clinical patient management. We sought to use amino acid-level signal-to-noise (S:N) analysis to establish pathogenic hotspots in sarcomeric HCM-associated genes as well as to refine the 2015 American College of Medical Genetics (ACMG) criteria to predict incidental variant pathogenicity.

Methods and …

The Covid-19 Pandemic: Early Ripple Effects In Pediatric Palliative Care, Linda Marisol Bustamante, Regina Okhuysen-Cawley, Julia Downing, Stephen R Connor, Mary Ann Muckaden, Marianne Phillips, Andrea Icaza, Nicole Garzon, Yuriko Nakashima, Kelsi Morgan, David Mauser, Michelle Grunauer

Faculty, Staff and Students Publications

Palliative care, which aims to provide comprehensive, interdisciplinary, holistic care to children, adolescents and adults with life-threatening, and ultimately life-limiting conditions, is a discipline that has emerged as an integral component of healthcare systems throughout the world. Although the value of life-affirming palliative care (PC) has been shown across many domains, funding and acceptance of palliative care teams have been variable: some hospital systems have free-standing, dedicated interdisciplinary teams while, in many instances, palliative care services are provided "pro bono" by individuals with a special interest in the discipline, who provide PC in addition to other responsibilities. In this article, …

Donor-Derived Multiple Leukemia Antigen-Specific T-Cell Therapy To Prevent Relapse After Transplant In Patients With All, Swati Naik, Spyridoula Vasileiou, Ifigeneia Tzannou, Manik Kuvalekar, Ayumi Watanabe, Catherine Robertson, Natalia Lapteva, Wang Tao, Mengfen Wu, Bambi Grilley, George Carrum, Rammurti T Kamble, Laquisa Hill, Robert A Krance, Caridad Martinez, Priti Tewari, Bilal Omer, Stephen Gottschalk, Helen E Heslop, Malcom K Brenner, Cliona M Rooney, Juan F Vera, Ann M Leen, Premal D Lulla

Faculty, Staff and Students Publications

Hematopoietic stem cell transplant (HSCT) is a curative option for patients with high-risk acute lymphoblastic leukemia (ALL), but relapse remains a major cause of treatment failure. To prevent disease relapse, we prepared and infused donor-derived multiple leukemia antigen-specific T cells (mLSTs) targeting PRAME, WT1, and survivin, which are leukemia-associated antigens frequently expressed in B- and T-ALL. Our goal was to maximize the graft-versus-leukemia effect while minimizing the risk of graft-versus-host disease (GVHD). We administered mLSTs (dose range, 0.5 × 107 to 2 × 107 cells per square meter) to 11 patients with ALL (8 pediatric, 3 adult), and observed no …

Perceived Roles, Benefits And Barriers Of Virtual Global Health Partnership Initiatives: A Cross-Sectional Exploratory Study, Lisa Umphrey, George Paasi, William Windsor, Grace Abongo, Jessica Evert, Heather Haq, Elizabeth M Keating, Suet Kam Lam, Megan S Mchenry, Carolyne Ndila, Charles Nwobu, Amy Rule, Reena P Tam, Daniel Olson, Peter Olupot-Olupot

Faculty, Staff and Students Publications

BACKGROUND: Virtual global health partnership initiatives (VGHPIs) evolved rapidly during the COVID-19 pandemic to ensure partnership continuity. However the current landscape for VGHPI use and preference is unknown. This study aimed to increase understanding of GH partners' perspectives on VGHPIs.

METHODS: From 15 October to 30 November 2020, An online, international survey was conducted using snowball sampling to document pandemic-related changes in partnership activities, preferences for VGHPIs, and perceived acceptability and barriers. The survey underwent iterative development within a diverse author group, representing academic and clinical institutions, and the non-profit sector. Participants from their professional global health networks were invited, …

Antiviral Activity Of Olanexidine-Containing Hand Rub Against Human Noroviruses, Khalil Ettayebi, Wilhelm Salmen, Kaoru Imai, Akifumi Hagi, Frederick H Neill, Robert L Atmar, B V Venkataram Prasad, Mary K Estes

Faculty, Staff and Students Publications

Human norovirus (HuNoV) is the leading cause of epidemic and sporadic acute gastroenteritis worldwide. HuNoV transmission occurs predominantly by direct person-to-person contact, and its health burden is associated with poor hand hygiene and a lack of effective antiseptics and disinfectants. Specific therapies and methods to prevent and control HuNoV spread previously were difficult to evaluate because of the lack of a cell culture system to propagate infectious virus. This barrier has been overcome with the successful cultivation of HuNoV in nontransformed human intestinal enteroids (HIEs). Here, we report using the HIE cultivation system to evaluate the virucidal efficacy of an …

Genetic Susceptibility To Patient-Reported Xerostomia Among Long-Term Oropharyngeal Cancer Survivors, Puja Aggarwal, Katherine A Hutcheson, Robert Yu, Jian Wang, Clifton D Fuller, Adam S Garden, Ryan P Goepfert, Jillian Rigert, Frank E Mott, Charles Lu, Stephen Y Lai, G Brandon Gunn, Mark S Chambers, Guojun Li, Chih-Chieh Wu, Ehab Y Hanna, Erich M Sturgis, Sanjay Shete

Faculty, Staff and Students Publications

Genetic susceptibility for xerostomia, a common sequela of radiotherapy and chemoradiotherapy for head and neck cancer, is unknown. Therefore, to identify genetic variants associated with moderate to severe xerostomia, we conducted a GWAS of 359 long-term oropharyngeal cancer (OPC) survivors using 579,956 autosomal SNPs. Patient-reported cancer treatment-related xerostomia was assessed using the MD Anderson Symptom Inventory. Patient response was dichotomized as moderate to severe or none to mild symptoms. In our study, 39.2% of OPC survivors reported moderate to severe xerostomia. Our GWAS identified eight SNPs suggestively associated with higher risk of moderate to severe xerostomia in six genomic regions …

Safety And Efficacy Of Systemic Anti-Scg3 Therapy To Treat Oxygen-Induced Retinopathy, Chang Dai, Hong Tian, Amit Bhatt, Guanfang Su, Keith A Webster, Wei Li

Faculty, Staff and Students Publications

BACKGROUND: To circumvent possible systemic side effects, anti-angiogenic drugs targeting vascular endothelial growth factor (VEGF) for ocular neovascular diseases in adults are approved only for intravitreal administration. However, intravitreal injection itself can elicit injection-related adverse effects, and premature eyes of infants with retinopathy of prematurity (ROP) may be particularly susceptible to intravitreal injection. Therefore, an unmet clinical need is to develop safe systemic anti-angiogenic therapies for ROP. We recently reported that secretogranin III (Scg3) is a disease-restricted angiogenic factor and that systemic anti-Scg3 mAb alleviates ROP in animal models with minimal side effects on developing eyes and organs. The aim …

Temporal Trends In Outcomes In Patients With Adrenocortical Carcinoma: A Multidisciplinary Referral-Center Experience, Marilyne Daher, Jeena Varghese, Stephen K Gruschkus, Camilo Jimenez, Steven G Waguespack, Sara Bedrose, Lina Altameemi, Hadil Bazerbashi, Aung Naing, Vivek Subaiah, Matthew T Campbell, Amishi Y Shah, Miao Zhang, Rahul A Sheth, Jose A Karam, Christopher G Wood, Nancy D Perrier, Paul H Graham, Jeffery E Lee, Mouhammed Amir Habra

Faculty, Staff and Students Publications

CONTEXT: Reporting temporal trends in adrenocortical carcinoma (ACC) helps guide management strategies.

OBJECTIVE: This work aimed to report the trends in disease burden and clinical outcomes over time that cannot be adequately captured from individual clinical trials.

METHODS: A retrospective study was held of ACC patients seen at a referral cancer center between February 1998 and August 2019. Clinical outcomes were compared between an early cohort (February 1998-June 2007) and a late cohort (July 2007-August 2019).

RESULTS: A total of 621 patients included with a median age at diagnosis of 49.3 years (range, 0.5-86.6 years). There were 285 (45.9%) patients …

Safety And Efficacy Of Systemic Anti-Scg3 Therapy To Treat Oxygen-Induced Retinopathy, Chang Dai, Hong Tian, Amit Bhatt, Guanfang Su, Keith A Webster, Wei Li

Faculty, Staff and Students Publications

BACKGROUND: To circumvent possible systemic side effects, anti-angiogenic drugs targeting vascular endothelial growth factor (VEGF) for ocular neovascular diseases in adults are approved only for intravitreal administration. However, intravitreal injection itself can elicit injection-related adverse effects, and premature eyes of infants with retinopathy of prematurity (ROP) may be particularly susceptible to intravitreal injection. Therefore, an unmet clinical need is to develop safe systemic anti-angiogenic therapies for ROP. We recently reported that secretogranin III (Scg3) is a disease-restricted angiogenic factor and that systemic anti-Scg3 mAb alleviates ROP in animal models with minimal side effects on developing eyes and organs. The aim …

Hyperactivation Is Sufficient To Release Porcine Sperm From Immobilized Oviduct Glycans, Momal Sharif, Vincent Hickl, Gabriel Juarez, Xingjian Di, Karl Kerns, Peter Sutovsky, Nicolai Bovin, David J Miller

Faculty, Staff and Students Publications

Fertilizing sperm are retained by adhesion to specific glycans on the epithelium of the oviduct forming a reservoir before sperm are released from the reservoir so fertilization can ensue. Capacitated sperm lose affinity for the oviduct epithelium but the components of capacitation that are important for sperm release are uncertain. One important correlate of capacitation is the development of hyperactivated motility. Hyperactivation is characterized by asymmetrical flagellar beating with high beat amplitude. We tested whether the development of full-type asymmetrical motility was sufficient to release sperm from immobilized oviduct glycans. Sperm hyperactivation was induced by four different compounds, a cell-permeable …

Emergency Department Antimicrobial Use In A Low-Resource Setting: Results From A Retrospective Observational Study At A Referral Hospital In Liberia, Sojung Yi, Anu Ramachandran, Lane Epps, Alex Mayah, Taylor W Burkholder, Michael Senyu Jaung, Ahson Haider, Paul Whesseh, John Shakpeh, Kayla Enriquez, Corey Bills

Faculty, Staff and Students Publications

OBJECTIVE: Data on antimicrobial use in low-income and middle-income countries (LMICs) remain limited. In Liberia, the absence of local data impedes surveillance and may lead to suboptimal treatment, injudicious use and resistance against antimicrobials. This study aims to examine antimicrobial prescribing patterns for patients in the emergency department (ED) of a large Liberian public hospital. Secondarily, this prescribing was compared with WHO prescribing indicators.

DESIGN: Retrospective observational study.

SETTING: An adult ED of a large public hospital in Monrovia, Liberia.

PARTICIPANTS: A total of 1082 adult patients (>18 years of age) were recorded in the ED, from 1 January …

A Photography-Based, Social Media Walking Intervention Targeting Autonomous Motivations For Physical Activity: Semistructured Interviews With Older Women, Michael C Robertson, Maria Chang Swartz, Ursela Christopherson, Jason R Bentley, Karen M Basen-Engquist, Debbe Thompson, Elena Volpi, Elizabeth J Lyons

Faculty, Staff and Students Publications

BACKGROUND: Older adult women are at risk for negative health outcomes that engaging in sustained physical activity can help prevent. However, promoting long-term maintenance of physical activity in this population has proven to be a challenge. Increasing autonomous motivations (ie, intrinsic, integrated, and identified regulations) for physical activity may facilitate enduring behavior change. Digitally delivered games for health that take a celebratory technology approach, that is, using technology to create new ways to experience valued behaviors and express valued beliefs, may be a useful way to target autonomous motivations for physical activity. Formative research with the target population is needed …

Neurofibromatosis Type 1 Has A Wide Spectrum Of Growth Hormone Excess, Fady Hannah-Shmouni, Giampaolo Trivellin, Pablo Beckers, Lefkothea P Karaviti, Maya Lodish, Christina Tatsi, Adekunle M Adesina, Fotini Adamidou, Gesthimani Mintziori, Jami L Josefson, Martha Quezado, Constantine A Stratakis

Faculty, Staff and Students Publications

Overgrowth due to growth hormone (GH) excess affects approximately 10% of patients with neurofibromatosis type 1 (NF1) and optic pathway glioma (OPG). Our aim is to describe the clinical, biochemical, pathological, and genetic features of GH excess in a retrospective case series of 10 children and adults with NF1 referred to a tertiary care clinical research center. Six children (median age = 4 years, range of 3−5 years), one 14-year-old adolescent, and three adults (median age = 42 years, range of 29−52 years) were diagnosed with NF1 and GH excess. GH excess was confirmed by the failure to suppress GH …

Variability Of Care And Access To Transplantation For Children With Biliary Atresia Who Need A Liver Replacement, Jean De Ville De Goyet, Toni Illhardt, Christophe Chardot, Peace N Dike, Ulrich Baumann, Katherine Brandt, Barbara E Wildhaber, Mikko Pakarinen, Fabrizio Di Francesco, Ekkehard Sturm, Marianna Cornet, Caroline Lemoine, Eva Doreen Pfister, Ana M Calinescu, Maria Hukkinen, Sanjiv Harpavat, Fabio Tuzzolino, Riccardo Superina

Faculty, Staff and Students Publications

Background & Aims: Biliary atresia (BA) is the commonest single etiology indication for liver replacement in children. As timely access to liver transplantation (LT) remains challenging for small BA children (with prolonged waiting time being associated with clinical deterioration leading to both preventable pre- and post-transplant morbidity and mortality), the care pathway of BA children in need of LT was analyzed—from diagnosis to LT—with particular attention to referral patterns, timing of referral, waiting list dynamics and need for medical assistance before LT. Methods: International multicentric retrospective study. Intent-to-transplant study analyzing BA children who had indication for LT early in life …

Human Pancreatic Microenvironment Promotes Β-Cell Differentiation Via Non-Canonical Wnt5a/Jnk And Bmp Signaling, Jolanta Chmielowiec, Wojciech J Szlachcic, Diane Yang, Marissa A Scavuzzo, Katrina Wamble, Alejandro Sarrion-Perdigones, Omaima M Sabek, Koen J T Venken, Malgorzata Borowiak

Faculty, Staff and Students Publications

In vitro derivation of pancreatic β-cells from human pluripotent stem cells holds promise as diabetes treatment. Despite recent progress, efforts to generate physiologically competent β-cells are still hindered by incomplete understanding of the microenvironment's role in β-cell development and maturation. Here, we analyze the human mesenchymal and endothelial primary cells from weeks 9-20 fetal pancreas and identify a time point-specific microenvironment that permits β-cell differentiation. Further, we uncover unique factors that guide in vitro development of endocrine progenitors, with WNT5A markedly improving human β-cell differentiation. WNT5A initially acts through the non-canonical (JNK/c-JUN) WNT signaling and cooperates with Gremlin1 to inhibit …

An Imaging Biomarker Of Tumor-Infiltrating Lymphocytes To Risk-Stratify Patients With Hpv-Associated Oropharyngeal Cancer, Germán Corredor, Paula Toro, Can Koyuncu, Cheng Lu, Christina Buzzy, Kaustav Bera, Pingfu Fu, Mitra Mehrad, Kim A Ely, Mojgan Mokhtari, Kailin Yang, Deborah Chute, David J Adelstein, Lester D R Thompson, Justin A Bishop, Farhoud Faraji, Wade Thorstad, Patricia Castro, Vlad Sandulache, Shlomo A Koyfman, James S Lewis, Anant Madabhushi

Faculty, Staff and Students Publications

BACKGROUND: Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) has excellent control rates compared to nonvirally associated OPSCC. Multiple trials are actively testing whether de-escalation of treatment intensity for these patients can maintain oncologic equipoise while reducing treatment-related toxicity. We have developed OP-TIL, a biomarker that characterizes the spatial interplay between tumor-infiltrating lymphocytes (TILs) and surrounding cells in histology images. Herein, we sought to test whether OP-TIL can segregate stage I HPV-associated OPSCC patients into low-risk and high-risk groups and aid in patient selection for de-escalation clinical trials.

METHODS: Association between OP-TIL and patient outcome was explored on whole slide …

Racial Disparities In Prostate Cancer: A Complex Interplay Between Socioeconomic Inequities And Genomics, Dallin Lowder, Kinza Rizwan, Collin Mccoll, Alyssa Paparella, Michael Ittmann, Nicholas Mitsiades, Salma Kaochar

Faculty, Staff and Students Publications

The largest US cancer health disparity exists in prostate cancer, with Black men having more than a two-fold increased risk of dying from prostate cancer compared to all other races. This disparity is a result of a complex network of factors including socioeconomic status (SES), environmental exposures, and genetics/biology. Inequity in the US healthcare system has emerged as a major driver of disparity in prostate cancer outcomes and has raised concerns that the actual incidence rates may be higher than current estimates. However, emerging studies argue that equalizing healthcare access will not fully eliminate racial health disparities and highlight the …

Envisioning Future Urinary Tract Infection Diagnostics, Robin Patel, Christopher R Polage, Jennifer Dien Bard, Larissa May, Francesca M Lee, Valeria Fabre, Mary K Hayden, Sarah D B Doernberg, David A Haake, Barbara W Trautner, Larissa Grigoryan, Ephraim L Tsalik, Kimberly E Hanson

Faculty, Staff and Students Publications

Urinary tract infections (UTIs) are among the most common bacterial infections in the United States and are a major driver of antibiotic use, both appropriate and inappropriate, across healthcare settings. Novel UTI diagnostics are a strategy that might enable better UTI treatment. Members of the Antibacterial Resistance Leadership Group Laboratory Center and the Infectious Diseases Society of America Diagnostics Committee convened to envision ideal future UTI diagnostics, with a view towards improving delivery of healthcare, patient outcomes and experiences, and antibiotic use, addressing which types of UTI diagnostics are needed and how companies might approach development of novel UTI diagnostics.

Demographic And Regional Trends Of Mortality In Patients With Aortic Dissection In The United States, 1999 To 2019, Salik Nazir, Robert W Ariss, Abdul Mannan Khan Minhas, Rochell Issa, Erin D Michos, Yochai Birnbaum, George V Moukarbel, P Kasi Ramanathan, Hani Jneid

Faculty, Staff and Students Publications

Background Aortic dissection (AoD) is associated with high morbidity and mortality. However, the burden of AoD mortality is not well characterized, and contemporary data and mortality trends in different demographic and geographic subgroups have not been described. Methods and Results Trends in AoD mortality were assessed using a cross-sectional analysis of the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database. Crude and age-adjusted mortality rates (AAMR) per 1 million people with associated annual percent changes were determined. Joinpoint regression was used to assess trends in the overall sample and different demographic (sex, race and ethnicity, …

Perceptions Of Weight Status And Energy Balance Behaviors Among Patients With Non-Alcoholic Fatty Liver Disease, Natalia I Heredia, Ruchi Gaba, Yan Liu, Shilpa Jain, Manasi Rungta, Manav Rungta, Hashem B El-Serag, Fasiha Kanwal, Aaron P Thrift, Maya Balakrishnan

Faculty, Staff and Students Publications

Weight loss through behavioral modification is central to treating non-alcoholic fatty liver disease (NAFLD). To achieve this, patients need to accurately self-perceive their health behaviors. We aimed to identify predictors of concordance between self-perception and objective measures of body weight, physical activity (PA) and dietary behaviors. We used data from the Harris County NAFLD Cohort, an ongoing prospective study in a regional safety-net healthcare system. Patients completed self-administered baseline questionnaires on demographics, diet, PA, and self-perceptions. We assessed concordance between actual and self-perceived body weight and energy-balance behaviors. Multivariable logistic regression identified predictors of concordance. Patients (n = 458; average …

Methylation Quantitative Trait Loci Are Largely Consistent Across Disease States In Crohn’S Disease, Suresh Venkateswaran, Hari K Somineni, Varun Kilaru, Seyma Katrinli, Jarod Prince, David T Okou, Jeffrey S Hyams, Lee A Denson, Richard Kellermayer, Greg Gibson, David J Cutler, Alicia K Smith, Subra Kugathasan, Karen N Conneely

Faculty, Staff and Students Publications

Recently, we identified 1,189 CpG sites whose DNA methylation level in blood associated with Crohn's disease. Here, we examined associations between DNA methylation and genetic variants to identify methylation quantitative trait loci across disease states in (1) 402 blood samples from 164 newly diagnosed pediatric Crohn's disease patients taken at 2 time points (diagnosis and follow-up), and 74 non-inflammatory bowel disease controls, (2) 780 blood samples from a non-Crohn's disease adult population, and (3) 40 ileal biopsies (17 Crohn's disease cases and 23 non-inflammatory bowel disease controls) from group (1). Genome-wide DNAm profiling and genotyping were performed using the Illumina …

Two-Dimensional Titanium Dioxide-Surfactant Photoactive Supramolecular Networks: Synthesis, Properties, And Applications For The Conversion Of Light Energy, Harold Lozano, Sindy Devis, Juan Aliaga, Matías Alegría, Hernán Guzmán, Roberto Villarroel, Eglantina Benavente, Guillermo González

Faculty, Staff and Students Publications

The desire to harness solar energy to address current global environmental problems led us to investigate two-dimensional (2D) core–shell hybrid photocatalysts in the form of a 2D-TiO2–surfactant, mainly composed of fatty acids. The bulk products, prepared by two slightly different methods, consist of stacked host–guest hybrid sheets held together by van der Waals forces between alkyl carboxylate moieties, favoring the synergistic conjugation of the photophysical properties of the core and the hydrophobicity of the self-assembled surfactant monolayer of the shell. X-ray diffraction and the vibrational characteristics of the products revealed the influence of synthesis strategies on two types of supramolecular …

Spata7 Is Required For Maintenance Of The Retinal Connecting Cilium, Jiaxiong Lu, Kaitlyn Xiong, Xinye Qian, Jongsu Choi, Yoon-Kyung Shim, Jacob Burnett, Graeme Mardon, Rui Chen

Faculty, Staff and Students Publications

SPATA7, an early onset LCA3 retinal disease gene, encodes a putative scaffold protein that is essential for the proper assembly of the connecting cilium (CC) complex in photoreceptors. Previous studies have shown that SPATA7 interacts with other photoreceptor-specific ciliary proteins, such as RPGR and RPGRIP1, and maintains the integrity of CC integrity. However, although it is known that Spata7 is required for early formation of the CC, it is unclear if Spata7 is also required for the maintenance of the CC. To investigate Spata7 function in the retina at the adult stage, loss of function was induced in the …

Derivation And Validation Of A Novel Risk Assessment Tool To Identify Children Aged 2–59 Months At Risk Of Hospitalised Pneumonia-Related Mortality In 20 Countries, Chris A Rees, Tim Colbourn, Shubhada Hooli, Carina King, Norman Lufesi, Eric D Mccollum, Charles Mwansambo, Clare Cutland, Shabir Ahmed Madhi, Marta Nunes, Joseph L Matthew, Emmanuel Addo-Yobo, Noel Chisaka, Mumtaz Hassan, Patricia L Hibberd, Prakash M Jeena, Juan M Lozano, William B Macleod, Archana Patel, Donald M Thea, Ngoc Tuong Vy Nguyen, Cissy B Kartasasmita, Marilla Lucero, Shally Awasthi, Ashish Bavdekar, Monidarin Chou, Pagbajabyn Nymadawa, Jean-William Pape, Glaucia Paranhos-Baccala, Valentina S Picot, Mala Rakoto-Andrianarivelo, Vanessa Rouzier, Graciela Russomando, Mariam Sylla, Philippe Vanhems, Jianwei Wang, Rai Asghar, Salem Banajeh, Imran Iqbal, Irene Maulen-Radovan, Greta Mino-Leon, Samir K Saha, Mathuram Santosham, Sunit Singhi, Sudha Basnet, Tor A Strand, Shinjini Bhatnagar, Nitya Wadhwa, Rakesh Lodha, Satinder Aneja, Alexey W Clara, Harry Campbell, Harish Nair, Jennifer Falconer, Shamim A Qazi, Yasir B Nisar, Mark I Neuman, World Health Organization Prepare Study Group

Faculty, Staff and Students Publications

INTRODUCTION: Existing risk assessment tools to identify children at risk of hospitalised pneumonia-related mortality have shown suboptimal discriminatory value during external validation. Our objective was to derive and validate a novel risk assessment tool to identify children aged 2-59 months at risk of hospitalised pneumonia-related mortality across various settings.

METHODS: We used primary, baseline, patient-level data from 11 studies, including children evaluated for pneumonia in 20 low-income and middle-income countries. Patients with complete data were included in a logistic regression model to assess the association of candidate variables with the outcome hospitalised pneumonia-related mortality. Adjusted log coefficients were calculated for …