Digital Commons Network^™

Genomic Mapping Of Dna-Repair Reaction Intermediates In Living Cells With Engineered Dna Structure-Trap Proteins, Jingjing Liu, Qian Mei, Sadeieh Nimer, Devon M Fitzgerald, Susan M Rosenberg

Faculty, Staff and Students Publications

Diverse DNA structures occur as reaction intermediates in various DNA-damage and -repair mechanisms, most of which results from replication stress. We harness the power of proteins evolutionarily optimized to bind and "trap" specific DNA reaction-intermediate structures, to quantify the structures, and discern the mechanisms of their occurrence in cells. The engineered proteins also allow genomic mapping of sites at which specific DNA structures occur preferentially, using a structure-trapping protein and ChIP-seq- or Cut-and-Tag-like methods. Genome-wide identification of sites with recurrent DNA-damage intermediates has illuminated mechanisms implicated in genome instability, replication stress, and chromosome fragility. Here, we describe X-seq, for identifying …

Conduction Disorders In The Setting Of Acute Stemi, Kjell Nikus, Yochai Birnbaum, Miquel Fiol-Sala, Jani Rankinen, Antoni Bayés De Luna

Faculty, Staff and Students Publications

ST-elevation myocardial (STEMI) is frequently associated with conduction disorders. Regional myocardial ischemia or injury may affect the cardiac conduction system at various locations, and neural reflexes or changes in the balance of the autonomous nervous system may be involved. Sinoatrial and atrioventricular blocks are more frequent in inferior than anterior STEMI, while new left anterior fascicular block and right bundle branch block indicate proximal occlusion of the left anterior descending coronary artery. New left bundle branch block is associated with multi-vessel disease. Most conduction disorders associated with STEMI are reversible with reperfusion therapy, but they may still impair prognosis because …

Trace Element Concentrations In Blood And Scute Tissues From Wild And Captive Hawaiian Green Sea Turtles (Chelonia Mydas), Katherine R Shaw, Jennifer M Lynch, George H Balazs, T Todd Jones, Jeff Pawloski, Marc R Rice, Amanda D French, Jing Liu, George P Cobb, David M Klein

Faculty, Staff and Students Publications

Sea turtles are exposed to trace elements through water, sediment, and food. Exposure to these elements has been shown to decrease immune function, impair growth, and decrease reproductive output in wildlife. This study compares trace element concentrations in green turtles in captivity at Sea Life Park Hawaii (n = 6) to wild green turtles in Kapoho Bay, HI (n = 5 to 7). Blood and scute samples were collected and analyzed for eleven elements via inductively coupled plasma-mass spectrometry (ICP-MS). Selenium was significantly greater (p < 0.05) in the blood of captive turtles compared to wild turtles, while V, Ni, and Pb were significantly greater in the blood of wild turtles. In scute, V, Cu, Se, and Cr were significantly greater in captive turtles, while As was significantly greater in wild turtles. Pelleted food fed to the captive turtles and representative samples of the wild turtle diet were analyzed via ICP-MS to calculate trophic transfer factors and daily intake values. Wild turtles had greater estimated daily intake than captive turtles for all elements except Cu and Se. Because captive turtles are fed a diet very different from their wild counterparts, captive turtles do not represent control or reference samples for chemical exposure studies in wild turtles. No toxic thresholds are known for sea turtles, but rehabilitation and managed care facilities should monitor sea turtle elemental concentrations to ensure the animals’ health.

Patient-Perceived Versus Actual Risk Of Cardiovascular Disease And Associated Willingness To Consider And Use Prevention Therapy, Ann Marie Navar, Tracy Y Wang, Shuang Li, Xiaojuan Mi, Zhuokai Li, Jennifer G Robinson, Salim S Virani, Eric D Peterson

Faculty, Staff and Students Publications

BACKGROUND: Cardiovascular prevention guidelines use estimated 10-year atherosclerotic cardiovascular disease (CVD) risk based on the pooled cohort equations to guide treatment decisions and engage patients in shared decision-making. We sought to determine patient perceived versus actual risk of atherosclerotic CVD and associations with willingness for preventive therapy.

METHODS: We evaluated calculated and perceived CVD risk among 4187 patients across 124 sites in the Patient and Provider Assessment of Lipid Management Registry. Ten-year risk was assessed using the pooled cohort equations; risk relative-to-peers was determined based on age-, sex-, and race-based percentiles; and patient estimates of risk were assessed using patient …

Secretion Of Von Willebrand Factor And Suppression Of Adamts-13 Activity By Markedly High Concentration Of Ferritin, Dalia A Bashir, Qi Da, Subhashree Pradhan, Nitin Sekhar, Christian Valladolid, Fong Lam, Danielle Guffey, Jordana Goldman, Moreshwar S Desai, Miguel A Cruz, Carl Allen, Trung C Nguyen, K Vinod Vijayan

Faculty, Staff and Students Publications

Hyperferritinemia is associated with poor outcomes in critically ill patients with sepsis, hemophagocytic lymphohistiocytosis (HLH), macrophage activation syndromes (MAS) and coronavirus disease 19 (COVID-19). Autopsies of hyperferritinemic patients that succumbed to either sepsis, HLH, MAS or COVID-19 have revealed disseminated microvascular thromboses with von Willebrand factor (VWF)-, platelets-, and/or fibrin-rich microthrombi. It is unknown whether high plasma ferritin concentration actively promotes microvascular thrombosis, or merely serves as a prognostic biomarker in these patients. Here, we show that secretion of VWF from human umbilical vein endothelial cells (HUVEC) is significantly enhanced by 100,000 ng/ml of recombinant ferritin heavy chain protein (FHC). …

Hemoglobin A1c Threshold For Reduction In Bone Turnover In Men With Type 2 Diabetes Mellitus, Sabaa Joad, Elliot Ballato, Fnu Deepika, Giulia Gregori, Alcibiades Leonardo Fleires-Gutierrez, Georgia Colleluori, Lina Aguirre, Rui Chen, Vittoria Russo, Virginia Carolina Fuenmayor Lopez, Clifford Qualls, Dennis T Villareal, Reina Armamento-Villareal

Faculty, Staff and Students Publications

BACKGROUND: Emerging data suggest that type 2 diabetes mellitus (T2D) is associated with an increased risk for fractures despite relatively normal or increased bone mineral density (BMD). Although the mechanism for bone fragility in T2D patients is multifactorial, whether glycemic control is important in generating this impairment in bone metabolism remains unclear. The purpose of our study is to identify a hemoglobin A1c (A1c) threshold level by which reduction in bone turnover begins in men with T2D.

METHOD: A cross-sectional analysis of baseline data was obtained from 217 men, ages 35-65, regardless of the presence or absence of hypogonadism or …

Lrrtm4 Is A Member Of The Transsynaptic Complex Between Rod Photoreceptors And Bipolar Cells, Melina A Agosto, Theodore G Wensel

Faculty, Staff and Students Publications

Leucine rich repeat transmembrane (LRRTM) proteins are synaptic adhesion molecules with roles in synapse formation and signaling. LRRTM4 transcripts were previously shown to be enriched in rod bipolar cells (BCs), secondary neurons of the retina that form synapses with rod photoreceptors. Using two different antibodies, LRRTM4 was found to reside primarily at rod BC dendritic tips, where it colocalized with the transduction channel protein, TRPM1. LRRTM4 was not detected at dendritic tips of ON-cone BCs. Following somatic knockout of LRRTM4 in BCs by subretinal injection and electroporation of CRISPR/Cas9, LRRTM4 was abolished or reduced in the dendritic tips of transfected …

Women Of Color Faculty Reimagining Institutional Spaces During The Covid-19 Pandemic, Marie Lo, Patti Duncan, Reshmi Dutt-Ballerstadt

English Faculty Publications and Presentations

As women of color faculty who have experienced challenges associated with hostile work environments within predominantly white institutions, we consider the ways that working remotely during COVID-19 offers transformative possibilities for reimagining our relationship to the academy. We discuss our embodied responses to institutional spaces that often marginalize faculty of color; how university leadership may be reimagined through a blurring of gendered, racialized lines of “public” and “private” (or institutional and domestic) spaces; and the possibility of healing from the trauma associated with oppressive workplaces and institutional betrayals.

Book Review: Puritan Spirits In The Abolitionist Imagination, Elisabeth Ceppi

English Faculty Publications and Presentations

Book review; Puritan Spirits in the Abolitionist Imagination by Kenyon Gradert. Published by the University of Chicago Press, 2020

Is Digital Humanities Adjuncting Infrastructurally Significant?, Kathi Inman Berens

English Faculty Publications and Presentations

This essay examines the infrastructural causes of digital humanities adjunct invisibility and proposes two remedies: to motivate DH adjunct self-identification by convening DH adjunct-specific prizes and bursaries; and what I call "microbenefactions": small actions by senior faculty that extend opportunities to adjuncts that cost little effort and can give adjuncts access to payment, prize-worthy work opportunities, or other benefits. The unspoken assumption is that DH skills are so much in demand that people with these skills are protected from adjuncting. As I interviewed seven DH adjuncts, their heterogeneous responses to standard questions reminded me that happy families are all alike; …

Buprenorphine For Chronic Pain: A Safer Alternative To Traditional Opioids, Suhani Dalal, Ahish Chitneni, Amnon A Berger, Vwaire Orhurhu, Bilal Dar, Bennett Kramer, Anvinh Nguyen, John Pruit, Charles Halsted, Alan D Kaye, Jamal Hasoon

Faculty, Staff and Students Publications

With the ongoing public health crisis with prescription opioids, there is a need for safer alternatives for medication management in chronic pain patients. Buprenorphine is a partial mu-opioid agonist which is commonly utilized to treat patients with opioid-use disorders. The purpose of this review is to discuss the potential use of this medication for the treatment of chronic pain instead of resorting to more traditional Schedule II opioids. Buprenorphine offers a safer alternative for patients who require opioids to manage chronic pain, given the unique pharmacological properties that allow it to provide adequate analgesia with less abuse potential.

A New Aortic Arch Dissection Classification: The Fuwai Classification, Juntao Qiu, Xinjin Luo, Jinlin Wu, Wei Pan, Qian Chang, Xiangyang Qian, Xiaogang Sun, Bo Wei, Liang Zhang, Shen Liu, Wenxiang Jiang, Cuntao Yu

Faculty, Staff and Students Publications

Aims: We describe a new aortic arch dissection (AcD) classification, which we have called the Fuwai classification. We then compare the clinical characteristics and long-term prognoses of different classifications.

Methods: All AcD patients who underwent surgical procedures at Fuwai Hospital from 2010 to 2015 were included in the study. AcD procedures are divided into three types: Fuwai type Cp, Ct, and Cd. Type Cp is defined as the innominate artery or combined with the left carotid artery involved. Type Cd is defined as the left subclavian artery or combined with the left carotid artery involved. All other AcD surgeries are …

Prevalence And Factors Associated With Nafld Detected By Vibration Controlled Transient Elastography Among Us Adults: Results From Nhanes 2017–2018, Xiaotao Zhang, Natalia I Heredia, Maya Balakrishnan, Aaron P Thrift

Faculty, Staff and Students Publications

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is increasingly common in the adult population. In the United States, the overall burden of NAFLD is unknown due to challenges with population-level NAFLD detection. The purpose of this study was to estimate prevalence of NAFLD and significant NAFLD fibrosis and identify factors associated with them in the U.S.

METHODS: Data came from the 2017-2018 cycle of National Health and Nutrition Examination Survey. We defined NAFLD by controlled attenuation parameter (CAP) scores of ≥248 dB/m in absence of excessive alcohol use and viral hepatitis. We defined significant fibrosis as Vibration controlled transient elastography (VCTE) …

Alcohol Consumption And The Risk Of Gastric Intestinal Metaplasia In A Us Veterans Population, Hudson M Holmes, Andre G Jove, Mimi C Tan, Hashem B El-Serag, Aaron P Thrift

Faculty, Staff and Students Publications

BACKGROUND: Chronic alcohol use is a risk factor for non-cardia gastric adenocarcinoma. However, it is less well understood whether alcohol use is a risk factor for premalignant mucosal changes, namely gastric intestinal metaplasia. We examined the association between various parameters of alcohol use and risk of gastric intestinal metaplasia.

METHODS: We used data from 2084 participants (including 403 with gastric intestinal metaplasia) recruited between February 2008-August 2013 into a cross-sectional study at the Michael E. DeBakey Veterans Affairs Medical Center in Houston, Texas. All participants underwent a study upper endoscopy with systematic gastric mapping biopsies. Cases had intestinal metaplasia on …

Assessment Of The Impact Of Tardive Dyskinesia In Clinical Practice: Consensus Panel Recommendations, Richard Jackson, Matthew N Brams, Leslie Citrome, Amber R Hoberg, Stuart H Isaacson, John M Kane, Rajeev Kumar

Faculty, Staff and Students Publications

PURPOSE: Tardive dyskinesia (TD) is a hyperkinetic movement disorder in which patients experience abnormal involuntary movements that can have profound negative impacts on physical, cognitive, and psychosocial functioning. Use of measures to assess the functional impact of TD in routine clinical practice is lacking. To address this gap, an advisory panel of experts in psychiatry and movement disorder neurology was convened to develop consensus recommendations on assessment of the impact of TD on patients' functioning that can be used in clinical practice.

METHODS: An advisory panel provided recommendations using an iterative process, beginning with a narrative literature review regarding current …

Second Thoughts On Fda's Covid-Era Mental Health App Policy, Michael Mattioli

Articles by Maurer Faculty

As the coronavirus pandemic swept across the globe in April 2020, the US Food and Drug Administration (FDA) made an unusual decision. The agency announced that it would relax its enforcement of compliance rules for “digital therapeutics”—smartphone apps designed to address mental health disorders. The measure was a response to widely reported upticks in symptoms of anxiety, depression, and substance abuse brought on by the pandemic. As an added benefit, the agency explained, digital therapeutics could promote social distancing by removing patients’ need to visit health care providers.

This essay explores the possible lasting effects of the FDA’s temporary suspension …

The Legal Implications Of A Reservation Of Rights Defense Examined In The Context Of Recoupment Of Defense Costs And Tripartite Conflicts Of Interest, Johnny C. Parker, Tim J. Schaefer

Articles, Chapters in Books and Other Contributions to Scholarly Works

No abstract provided.

Edd Graduate Perspectives: Uplifting Our Own Voices, Staci B. Martin, Kara Gournaris, Zafreen Jaffery, Lisa Janie Hatfield, Su-Jin Sue Jung, Li Xiang, Ingrid Anderson, Micki M. Caskey

Education Faculty Publications and Presentations

The purpose of this essay is to share the voices of EdD graduates who are often underrepresented or missing in the literature. To begin, we invited EdD graduates to co-author this article about the connection among their EdD program experiences and interactions and their activism. We included our definition of activism and posed three open-ended questions. Six program graduates and one professor agreed to organize the graduates’ responses by the question topics and salient themes. We asked about our experiences in the EdD program and how these influence—positively and negatively—what we are doing now (post-program). We found (a) relationships with …

Case Report: Dupilumab Successfully Controls Severe Eczema In A Child With Elevated Ige Levels And Recurrent Skin Infections, Tejas P Joshi, Sara Anvari, Meera R Gupta, Carla M Davis, Joud Hajjar

Faculty, Staff and Students Publications

The efficacy of dupilumab in pediatric patients with severe eczema presenting in the setting of elevated immunoglobulin E (IgE) levels and recurrent bacterial skin infections is not well-understood. Here we present the case of a child with elevated IgE levels in whom dupilumab treatment led to remarkable control of his eczema and recurrent skin infections. We also review the use of dupilumab in other patients with molecularly proven cases of hyper IgE (HIGE) syndrome. Our case supports the notion that dupilumab may have a seminal application in treating severe eczema that occurs in the setting of elevated IgE levels and …

Novel Mutations In The Gtpbp3 Gene For Mitochondrial Disease And Characteristics Of Related Phenotypic Spectrum: The First Three Cases From China, Hui-Ming Yan, Zhi-Mei Liu, Bei Cao, Victor Wei Zhang, Yi-Duo He, Zheng-Jun Jia, Hui Xi, Jing Liu, Fang Fang, Hua Wang

Faculty, Staff and Students Publications

Combined Oxidative Phosphorylation Deficiency 23 (COXPD23) caused by mutations in GTPBP3 gene is a rare mitochondrial disease, and this disorder identified from the Chinese population has not been described thus far. Here, we report a case series of three patients with COXPD23 caused by GTPBP3 mutations, from a severe to a mild phenotype. The main clinical features of these patients include lactic acidosis, myocardial damage, and neurologic symptoms. Whole genome sequencing and targeted panels of candidate human mitochondrial genome revealed that patient 1 was a compound heterozygote with novel mutations c.413C > T (p. A138V) and c.509_510del (p. E170Gfs∗42) in GTPBP3 …

Effects Of Intensive Blood Pressure Treatment On Orthostatic Hypotension : A Systematic Review And Individual Participant-Based Meta-Analysis, Stephen P Juraschek, Jiun-Ruey Hu, Jennifer L Cluett, Anthony Ishak, Carol Mita, Lewis A Lipsitz, Lawrence J Appel, Nigel S Beckett, Ruth L Coleman, William C Cushman, Barry R Davis, Greg Grandits, Rury R Holman, Edgar R Miller, Ruth Peters, Jan A Staessen, Addison A Taylor, Lutgarde Thijs, Jackson T Wright, Kenneth J Mukamal

Faculty, Staff and Students Publications

BACKGROUND: Although intensive blood pressure (BP)-lowering treatment reduces risk for cardiovascular disease, there are concerns that it might cause orthostatic hypotension (OH).

PURPOSE: To examine the effects of intensive BP-lowering treatment on OH in hypertensive adults.

DATA SOURCES: MEDLINE, EMBASE, and Cochrane CENTRAL from inception through 7 October 2019, without language restrictions.

STUDY SELECTION: Randomized trials of BP pharmacologic treatment (more intensive BP goal or active agent) that involved more than 500 adults with hypertension or elevated BP and that were 6 months or longer in duration. Trial comparisons were groups assigned to either less intensive BP goals or placebo, …

Distribution Of Calcium Volume, Density, Number, And Type Of Coronary Vessel With Calcified Plaque In South Asians In The Us And Other Race/Ethnic Groups: The Masala And Mesa Studies, Mahmoud Al Rifai, Alka M Kanaya, Namratha R Kandula, Miguel Cainzos-Achirica, Jaideep Patel, Matthew Budoff, Michael H Criqui, Michael J Blaha, Salim S Virani

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: South Asians (SA) experience disproportionately higher rates of atherosclerotic cardiovascular disease (ASCVD) events than non-Hispanic whites (NHW) and several other Asian groups. The coronary artery calcium (CAC) Agatston score may not capture the unique characteristics of coronary plaque in SA. We therefore evaluated the prevalence and patterns of advanced CAC measures (specific coronary vessel involvement, CAC volume and density) in SA versus other race/ethnicities.

METHODS: We combined data from the Mediators of Atherosclerosis in South Asians Living in America (MASALA) and Multi-Ethnic Study of Atherosclerosis (MESA) cohorts. We used multivariable-adjusted linear regression models to compare advanced CAC …

How Do Red Blood Cells Die?, Perumal Thiagarajan, Charles J Parker, Josef T Prchal

Faculty, Staff and Students Publications

Normal human red blood cells have an average life span of about 120 days in the circulation after which they are engulfed by macrophages. This is an extremely efficient process as macrophages phagocytose about 5 million erythrocytes every second without any significant release of hemoglobin in the circulation. Despite large number of investigations, the precise molecular mechanism by which macrophages recognize senescent red blood cells for clearance remains elusive. Red cells undergo several physicochemical changes as they age in the circulation. Several of these changes have been proposed as a recognition tag for macrophages. Most prevalent hypotheses for red cell …

Identification Of Deep-Intronic Splice Mutations In A Large Cohort Of Patients With Inherited Retinal Diseases, Xinye Qian, Jun Wang, Meng Wang, Austin D Igelman, Kaylie D Jones, Yumei Li, Keqing Wang, Kerry E Goetz, David G Birch, Paul Yang, Mark E Pennesi, Rui Chen

Faculty, Staff and Students Publications

High throughput sequencing technologies have revolutionized the identification of mutations responsible for a diverse set of Mendelian disorders, including inherited retinal disorders (IRDs). However, the causal mutations remain elusive for a significant proportion of patients. This may be partially due to pathogenic mutations located in non-coding regions, which are largely missed by capture sequencing targeting the coding regions. The advent of whole-genome sequencing (WGS) allows us to systematically detect non-coding variations. However, the interpretation of these variations remains a significant bottleneck. In this study, we investigated the contribution of deep-intronic splice variants to IRDs. WGS was performed for a cohort …

The Bile Acid Induced Hepatokine Orosomucoid Suppresses Adipocyte Differentiation, Sung Ho Lee, Jong Min Choi, Sung Yun Jung, Aaron R Cox, Sean M Hartig, David D Moore, Kang Ho Kim

Faculty, Staff and Students Publications

Bile acids have recently emerged as key metabolic hormones with beneficial impacts in multiple metabolic diseases. We previously discovered that hepatic bile acid overload distally modulates glucose and fatty acid metabolism in adipose tissues to exert anti-obesity effects. However, the detailed mechanisms that explain the salutary effects of serum bile acid elevation remain unclear. Here, proteomic profiling identified a new hepatokine, Orosomucoid (ORM) that governs liver-adipose tissue crosstalk. Hepatic ORMs were highly induced by both genetic and dietary bile acid overload. To address the direct metabolic effects of ORM, purified ORM proteins were administered during adipogenic differentiation of 3T3-L1 cells …

Women Have A Lower Risk Of Nonalcoholic Fatty Liver Disease But A Higher Risk Of Progression Vs Men: A Systematic Review And Meta-Analysis, Maya Balakrishnan, Parth Patel, Sydney Dunn-Valadez, Cecilia Dao, Vinshi Khan, Hiba Ali, Laith El-Serag, Ruben Hernaez, Amy Sisson, Aaron P Thrift, Yan Liu, Hashem B El-Serag, Fasiha Kanwal

Library Staff Publications

BACKGROUND & AIMS: The risk of nonalcoholic fatty liver disease (NAFLD) and its progression may differ between men and women. We conducted a systematic review and meta-analysis to determine the relationship between sex and NAFLD, nonalcoholic steatohepatitis (NASH), and advanced NAFLD fibrosis.

METHODS: Studies reporting sex-stratified NAFLD prevalence among population-based samples and either NASH or advanced fibrosis among patients with biopsy-proven NAFLD were identified from MEDLINE, EMBASE, and Cochrane databases through December 2017. We calculated pooled relative risk ratios comparing women vs men for each outcome.

RESULTS: Our final analysis comprised 54 studies. Samples sizes were 62,239 for the NAFLD …

The Elastics Of Snap Removal: An Empirical Case Study Of Textualism, Thomas O. Main, Jeffrey W. Stempel, David Mcclure

Scholarly Works

This article reports the findings of an empirical study of textualism as applied by federal judges interpreting the statute that permits removal of diversity cases from state to federal court. The “snap removal” provision in the statute is particularly interesting because its application forces judges into one of two interpretive camps—which are fairly extreme versions of textualism and purposivism, respectively. We studied characteristics of cases and judges to find predictors of textualist outcomes. In this article we offer a narrative discussion of key variables and we detail the results of our logistic regression analysis. The most salient predictive variable was …

The People's Court: On The Intellectual Origins Of American Judicial Power, Ian C. Bartrum

Scholarly Works

This article enters into the modern debate between "constitutional departmentalists"-who contend that the executive and legislative branches share constitutional interpretive authority with the courts-and what are sometimes called "judicial supremacists." After exploring the relevant history of political ideas, I join the modern minority of voices in the latter camp.

This is an intellectual history of two evolving political ideas-popular sovereignty and the separation of powers-which merged in the making of American judicial power, and I argue we can only understand the structural function of judicial review by bringing these ideas together into an integrated whole. Or, put another way, we …

Talking Back In Court, M. Eve Hanan

Scholarly Works

No abstract provided.

Chevron’S Asylum: Judicial Deference In Refugee Cases, Michael Kagan

Scholarly Works

Chevron deference is at the height of its powers in refugee and asylum cases, with the highest possible human consequences. Why does the Supreme Court seem so comfortable with Chevron deference in asylum cases when it has been reluctant to defer to the government in other kinds of deportation cases? More to the point, is this deference justified? There are cogent arguments justifying more deference in asylum cases than in other kinds of deportation cases. These arguments rest to a great extent on the premise that greater political accountability is a good thing when interpreting a statute. Yet in a …