Medical Specialties Commons^™

Super-Enhancer Hijacking Drives Ectopic Expression Of Hedgehog Pathway Ligands In Meningiomas, Mark W Youngblood, Zeynep Erson-Omay, Chang Li, Hinda Najem, Süleyman Coșkun, Evgeniya Tyrtova, Julio D Montejo, Danielle F Miyagishima, Tanyeri Barak, Sayoko Nishimura, Akdes Serin Harmancı, Victoria E Clark, Daniel Duran, Anita Huttner, Timuçin Avşar, Yasar Bayri, Johannes Schramm, Julien Boetto, Matthieu Peyre, Maximilien Riche, Roland Goldbrunner, Nduka Amankulor, Angeliki Louvi, Kaya Bilgüvar, M Necmettin Pamir, Koray Özduman, Türker Kilic, James R Knight, Matthias Simon, Craig Horbinski, Michel Kalamarides, Marco Timmer, Amy B Heimberger, Ketu Mishra-Gorur, Jennifer Moliterno, Katsuhito Yasuno, Murat Günel

Faculty, Staff and Students Publications

Hedgehog signaling mediates embryologic development of the central nervous system and other tissues and is frequently hijacked by neoplasia to facilitate uncontrolled cellular proliferation. Meningiomas, the most common primary brain tumor, exhibit Hedgehog signaling activation in 6.5% of cases, triggered by recurrent mutations in pathway mediators such as SMO. In this study, we find 35.6% of meningiomas that lack previously known drivers acquired various types of somatic structural variations affecting chromosomes 2q35 and 7q36.3. These cases exhibit ectopic expression of Hedgehog ligands, IHH and SHH, respectively, resulting in Hedgehog signaling activation. Recurrent tandem duplications involving IHH permit de novo chromatin …

Early Season Monitoring Of Tarnished Plant Bug, Lygus Lineolaris, In Wild Hosts Using Pheromone Traps, Justin George, James P Glover, Gadi V P Reddy, Chris Johnson, David R Hall

Faculty, Staff and Student Publications

Simple Summary

The tarnished plant bug, Lygus lineolaris (Hemiptera: Miridae), is a polyphagous pest and causes severe economic damage to cotton crops. Managing the weedy field edges is important in preventing early-season infestations of L. lineolaris in cotton to prevent damage to the squares and other fruiting structures. Scouting fields for L. lineolaris is time- and labor-intensive, and end-user variability associated with field sampling can lead to inaccuracies. Insect traps that combine visual cues and pheromones are more accurate, sustainable, and economically feasible in contrast to traditional insect detection methods. In this study, we investigated the application of red or …

Stabilizing Peri-Stent Restenosis Using A Novel Therapeutic Carrier, Maria P Blasco Conesa, Frank W Blixt, Pedram Peesh, Romeesa Khan, Janelle Korf, Juneyoung Lee, Gayathri Jagadeesan, Alexander Andersohn, Tushar K Das, Chunfeng Tan, Claudia Di Gesu, Gabriela Delevati Colpo, Jose Félix Moruno-Manchón, Louise D Mccullough, Robert Bryan, Bhanu P Ganesh

Faculty, Staff and Student Publications

Stroke is the most common cause of long-term disability and places a high economic burden on the global healthcare system. Functional outcomes from stroke are largely determined by the extent of ischemic injury, however, there is growing recognition that systemic inflammatory responses also contribute to outcomes. Mast cells (MCs) rapidly respond to injury and release histamine (HA), a pro-inflammatory neurotransmitter that enhances inflammation. The gut serves as a major reservoir of HA. We hypothesized that cromolyn, a mast cell stabilizer that prevents the release of inflammatory mediators, would decrease peripheral and central inflammation, reduce MC trafficking to the brain, and …

The Gut Microbiome As A Biomarker And Therapeutic Target In Hepatocellular Carcinoma, Betul Gok Yavuz, Saumil Datar, Shadi Chamseddine, Yehia I Mohamed, Michael Lapelusa, Sunyoung S Lee, Zishuo Ian Hu, Eugene J Koay, Hop S Tran Cao, Prasun Kumar Jalal, Carrie Daniel-Macdougall, Manal Hassan, Dan G Duda, Hesham M Amin, Ahmed O Kaseb

Faculty, Staff and Student Publications

The microbiome is pivotal in maintaining health and influencing disease by modulating essential inflammatory and immune responses. Hepatocellular carcinoma (HCC), ranking as the third most common cause of cancer-related fatalities globally, is influenced by the gut microbiome through bidirectional interactions between the gut and liver, as evidenced in both mouse models and human studies. Consequently, biomarkers based on gut microbiota represent promising non-invasive tools for the early detection of HCC. There is a growing body of evidence suggesting that the composition of the gut microbiota may play a role in the efficacy of immunotherapy in different types of cancer; thus, …

Inpatient Palliative Care Utilization In Sickle Cell Disease: Temporal Trends And Factors Associated With Usage, Lois C. Akpati

Research Colloquium

Background: Sickle cell disease (SCD) is a highly morbid condition notable for recurrent hospitalizations due to vaso-occlusive crises and complications of end-organ damage. Palliative care (PC) aims to provide holistic care to patients with serious chronic illnesses. Little is known about the use of inpatient palliative care services in adult patients with SCD.

Methods: We conducted a retrospective cross-sectional study utilizing data from the National Inpatient Sample (NIS) from 2008-2017. Patients >18 years old hospitalized with a primary or secondary ICD-9-CM and ICD-10-CM diagnosis of SCD were included. Outcome of interest was PC service utilization using ICD-9-CM and ICD-10-CM diagnosis …

Catheter-Associated Urinary Tract Infections: Patient Characteristics, Treatment, And Clinical Outcomes In One South Texas Acute Care Hospital, Kimberly A. Ambrosini, Jose Campo Maldonado

Research Colloquium

Background: Catheter-associated urinary tract infections (CA-UTIs) account for 40 percent of nosocomial infections worldwide. Their elimination is at the forefront of quality improvement in one South Texas acute care hospital.

Methods: Over a period of 6 months, five CA-UTIs occurred in one South Texas acute care hospital. These cases were identified via regular surveillance by Infection Prevention staff and the Laboratory Department of the hospital. This research reviews patient age, sex, length of stay, bacteria contracted, appropriate antibiotic use, patient characteristics, and overall outcomes.

Results: Between the months of July and December 2021, 5 CAUTIs were contracted. Patients ranged in …

Rotator Cuff Injury In The Pediatric Population: A Systematic Review Of Patient Characteristics, Treatment, And Outcomes, Kevin J. Orellana, Kathleen L. Harwood, John G. Horneff 3rd, Joseph J. King, Brendan A. Williams

Research Colloquium

Background: Rotator cuff injuries (RCIs), traditionally thought to be an adult-type pathology, have been reported in the pediatric population, but there remains limited evidence regarding this injury pattern in pediatric patients. The purpose of this study was to systematically review the literature to characterize the epidemiology, injury patterns, treatment modalities, and outcomes for pediatric patients with RCIs.

Methods: A systematic review was performed in accordance with Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines reviewing Pubmed, Embase, Cochrane, and CINAHL databases. Studies reporting imaging confirmed RCIs and treatment outcomes in patientsdemographics, mechanism, injury type and injury location were …

Penile Calciphylaxis In An End Stage Renal Disease Patient., Juan Enrique Garcia Lopez, Alain Velazquez Blanco, Aileen Aguilar, Sareena Siyas, Daniel Ibarias Paz, Mays Abdulazeez, Jesus Garza-Tamez, Desmond Adamu

Research Colloquium

Background: Penile Calciphylaxis occurs in about 1–4% of hemodialysis patients worldwide. Associated mortality rates are very high, and hyperparathyroidism is the second most frequently associated disorder. Addressing the resulting metabolic imbalance, and surgical intervention guided by findings of radiological studies may improve quality of life. The pathogenesis is thought to be mediated by vascular smooth muscle cells which differentiate into osteoblast-like cells. Decrease in vascular calcification inhibitory proteins fetuin-A and matrix Gla is found in patients on dialysis causing systemic medial calcification of arterioles, leading to epidermal ischemia, tissue infarction, and ulceration.

Case presentation: 47-year-old male with history of coronary …

Improving Pharmacist-Led Pediatric Patient Education On Oral Chemotherapy At Home, Anika Patel, Christopher M. Nguyen, Kristin Willins, Elsabella Y. Wang, Grace Magedman, Sun Yang

Pharmacy Faculty Articles and Research

Oral chemotherapy (OC) has been increasingly used in pediatric patients diagnosed with cancer, which is primarily managed in the outpatient setting. Different from adults, pediatric patients face unique challenges in administering these hazardous medications at home. Because of the complexity of pediatric pharmaceutical care and the hazardous nature of chemotherapy agents, comprehensive patient education is imperative to mitigate the potential safety risks associated with OC administration at home. Pharmacists play a vital role in patient education and medication consultations. However, the lack of practice guidelines and limited resources supporting OC counseling are noted. Additional barriers include insufficient knowledge and training …

Medical Imaging Applications Of Federated Learning, Sukhveer Singh Sandhu, Hamed Taheri Gorji, Pantea Tavakolian, Kouhyar Tavakolian, Alireza Akhbardeh

Faculty, Staff and Student Publications

Since its introduction in 2016, researchers have applied the idea of Federated Learning (FL) to several domains ranging from edge computing to banking. The technique's inherent security benefits, privacy-preserving capabilities, ease of scalability, and ability to transcend data biases have motivated researchers to use this tool on healthcare datasets. While several reviews exist detailing FL and its applications, this review focuses solely on the different applications of FL to medical imaging datasets, grouping applications by diseases, modality, and/or part of the body. This Systematic Literature review was conducted by querying and consolidating results from ArXiv, IEEE Xplorer, and PubMed. Furthermore, …

Multiphoton In Vivo Microscopy Of Embryonic Thrombopoiesis Reveals The Generation Of Platelets Through Budding, Huan Liu, Hellen Ishikawa-Ankerhold, Julia Winterhalter, Michael Lorenz, Mykhailo Vladymyrov, Steffen Massberg, Christian Schulz, Mathias Orban

Faculty, Staff and Student Publications

Platelets are generated by specialized cells called megakaryocytes (MKs). However, MK's origin and platelet release mode have remained incompletely understood. Here, we established direct visualization of embryonic thrombopoiesis in vivo by combining multiphoton intravital microscopy (MP-IVM) with a fluorescence switch reporter mouse model under control of the platelet factor 4 promoter (Pf4CreRosa26mTmG). Using this microscopy tool, we discovered that fetal liver MKs provide higher thrombopoietic activity than yolk sac MKs. Mechanistically, fetal platelets were released from MKs either by membrane buds or the formation of proplatelets, with the former constituting the key process. In E14.5 c-Myb-deficient …

High-Fat Diet, But Not Duration Of Lactation, Increases Mammary Gland Lymphatic Vessel Function And Subsequent Growth Of Inflammatory Breast Cancer Cells, Wintana Balema, Janelle Morton, Richard A Larson, Li Li, Fred Christian Velasquez, Natalie W Fowlkes, Savitri Krishnamurthy, Bisrat G Debeb, Eva Sevick-Muraca, Wendy A Woodward

Faculty, Staff and Student Publications

Inflammatory breast cancer (IBC) presents as rapid-onset swelling and breast skin changes caused by tumor emboli in the breast and breast skin lymphatics. IBC has been linked with obesity and duration of breastfeeding, but how these factors affect IBC tumor progression is not clear. We modeled the simultaneous effects of diet and weaning in mice on in vivo lymphatic function; on IBC tumor growth; and on aspects of the mammary gland microenvironment before and after IBC (SUM149) xenograft inoculation. We hypothesized that weaning status and diet would have synergistic effects on lymphatic function and the breast microenvironment to enhance IBC …

Epigenomic Signature Of Major Congenital Heart Defects In Newborns With Down Syndrome, Julia S Mouat, Shaobo Li, Swe Swe Myint, Benjamin I Laufer, Philip J Lupo, Jeremy M Schraw, John P Woodhouse, Adam J De Smith, Janine M Lasalle

Faculty, Staff and Students Publications

BACKGROUND: Congenital heart defects (CHDs) affect approximately half of individuals with Down syndrome (DS), but the molecular reasons for incomplete penetrance are unknown. Previous studies have largely focused on identifying genetic risk factors associated with CHDs in individuals with DS, but comprehensive studies of the contribution of epigenetic marks are lacking. We aimed to identify and characterize DNA methylation differences from newborn dried blood spots (NDBS) of DS individuals with major CHDs compared to DS individuals without CHDs.

METHODS: We used the Illumina EPIC array and whole-genome bisulfite sequencing (WGBS) to quantitate DNA methylation for 86 NDBS samples from the …

E-Cigarette Or Vaping Use-Associated Lung Injury (Evali) In A Hispanic Male During The Covid-19 Pandemic, Juan C. Naranjo, Muhammad Jamal, Aramide Tijani, Fatimah Bello

Research Colloquium

Background: Electronic cigarette or vaping product use–associated lung injury established the relationship between vaping products and lung injury. Overlapping clinical manifestations may mimic those of other respiratory conditions including COVID-19. Multiple radiographic findings including diffuse, bilateral, ground-glass infiltrates with lower-lobe predominance, eosinophilic pneumonia, and diffuse alveolar damage have been described. It is important to consider this as an alternative diagnosis, particularly in patients with respiratory symptoms and a history of vaping in the last 90 days due to increased risk of COVID-19 infection and worse outcomes.

Case presentation: A 25-year-old male with a history of polysubstance abuse and frequent E-cigarette …

A Simple Case Of Viral Myopericarditis Or A Complication Of Monoclonal Antibody Infusion?, Jose A. Rivera, Michael Menowsky

Research Colloquium

Background: Myocarditis has been a rare, but well-documented side effect of the mRNA-based vaccines against SARS-CoV-2 as well as a complication of viral infections including SARS-CoV-2. However, myopericarditis as a complication of monoclonal antibody infusion or as complication of allergic reaction to antibody infusions might be and underreported.

Case presentation: In this case, we report a 30-year-old man with a previous diagnosis of COVID infection 1 week prior to presentation, unvaccinated for SARS-CoV-2 who was referred from a monoclonal infusion center where he received casirivimab and imdevimab and 15 minutes after infusion began to complain of chills, chest pain, shortness …

Trauma Center Designation Effects On Clinical Outcomes In Pediatric Dog Bites: A Retrospective Study, Jessy Feng, Sabrina Orta, Alejandro Aquino, Lori Berry, Demba Fofana, Paul Berry

Research Colloquium

Introduction: Clinical outcomes associated with the American College of Surgeons (ACS) trauma center designation have been examined for many conditions. However, we sought to analyze the association between ACS pediatric trauma center designation and outcomes following pediatric dog bite trauma cases, which has rarely been studied.

Methods: The National Trauma Data Bank was queried to identify pediatric (0-19y) dog bite trauma patients admitted to ACS pediatric level I or II trauma centers from 2007-2016. Chi-Squared and Odds Ratio statistical analyses were used to compare the outcomes.

Results:We identified 6,196 pediatric dog bite trauma patients treated at ACS level …

Covid-19 As A Second Hit For Anti-Phospholipid Syndrome, Himabindu Kolli, Pooja Maknoor, Celin Rajan, Nevin Varghese

Research Colloquium

Background: Anti-phospholipid syndrome (APS) is an autoimmune disorder characterized by venous and arterial thrombosis, usually in setting of underlying autoimmune disorders. Here, we present a case of anti-phospholipid syndrome post covid infection.

Case Presentation: 41-year-old lady presented to the ER with complaints of left sided facial droop for 3-day duration. On further evaluation, she was found to have subacute ischemic stroke and was managed with anticoagulation and supportive treatment. Past medical history is significant for a recent diagnosis of Covid infection and for subsequent development of lower extremity deep vein thrombosis (DVT). She was started on anticoagulation with rivaroxaban for …

Autoimmune Encephalitis Of Unknown Etiology, Elizabeth Cook, Giselle Ricoy

Research Colloquium

Encephalitis is the inflammation of the brain which can come about through various etiologies. Autoimmune encephalitis is a rare form that is most common among women and children. The clinical presentation can vary between patients with a constellation of symptoms including deficits in memory, cognition, seizures, abnormal movement, psychosis, and coma. Because of the variation in clinical presentation and the lack of specificity in imaging and laboratory findings, diagnosis and intervention are often delayed for months to years. These delays in diagnosis can have long term ramifications on patients especially pediatric patients whose neural pathways are still developing. In pediatric …

Appropriateness Of Inpatient Transthoracic Echocardiography In A Community Hospital With A New Cardiology Fellowship Program, Christian D. Avalos, Y. Wady Aude

Research Colloquium

Background: The 2011 Appropriate Use Criteria (AUC) for echocardiography was developed to guide in the rational use of high quality cardiovascular imaging. Transthoracic echocardiography (TTE) orders with seemingly inappropriate indications were repeatedly identified at our hospital. Our goals were to identify the percentage of inappropriate TTEs, find a correlation between ordering physicians and appropriateness of TTEs, and reduce the inappropriate use of TTEs in the inpatient setting.

Methods: After implementing a required free-text indication for TTE orders, the indications of 100 random TTEs were retrospectively categorized as appropriate, inappropriate, and uncertain based on the AUC. TTEs for cardiac evaluation prior …

Subacute Stroke In Young Hispanic Male With Vertebrobasilar Dolichoectasia, Ashika A. Chacko, Nevin A. Varghese

Research Colloquium

Background: Vertebrobasilar dolichoectasia (VBD) is a rare clinical entity characterized by dilatation, elongation, and tortuosity of the vertebrobasilar arteries. Patients with VBD can present varying symptoms from ischemia, compression of blood vessels, or rarely subarachnoid hemorrhage.

Case presentation: A 29-year-old Hispanic man with history of hypertension presented to emergency department with progressive left upper extremity weakness, dizziness, slurry speech, and diplopia of one-week duration. On arrival, the patient was afebrile, heart rate 75 bpm and blood pressure 193/107 mmHg. He was alert and oriented x3. Neurological exam demonstrated decreased strength (4/5) on left upper extremity and left arm pronator drift. …

Müllerian-Type Clear Cell Carcinoma Of Donor Origin In A Male Patient With A Kidney Transplant: Ascertained By Molecular Testing, J Bryan Iorgulescu, Leah K Shaw, Asif Rashid, Priya Rao, Sreedhar Mandayam, Keyur P Patel, Kathleen M Schmeler, Richard K Yang, Pavlos Msaouel

Faculty, Staff and Student Publications

Clear cell carcinomas of Müllerian origin have a strong female predominance and only extremely rarely will arise within the kidney, presumably due to ectopic Müllerian embryogenesis. Herein, we report a unique case of metastatic Müllerian type clear cell carcinoma in a 37-year-old patient who had previously received a transplanted kidney from his father at age 11 (due to severe bilateral vesicoureteral reflux) and remained on chronic immunosuppression. The tumor was highly aggressive and demonstrated somatic mutations in NF2 and SETD2. Imaging of the transplanted kidney did not reveal any clear evidence of malignancy. However, targeted multigene sequencing and short tandem …

Rare Variants In Long Non-Coding Rnas Are Associated With Blood Lipid Levels In The Topmed Whole-Genome Sequencing Study, Yuxuan Wang, Margaret Sunitha Selvaraj, Xihao Li, Zilin Li, Jacob A Holdcraft, Donna K Arnett, Joshua C Bis, John Blangero, Eric Boerwinkle, Donald W Bowden, Brian E Cade, Jenna C Carlson, April P Carson, Yii-Der Ida Chen, Joanne E Curran, Paul S De Vries, Susan K Dutcher, Patrick T Ellinor, James S Floyd, Myriam Fornage, Barry I Freedman, Stacey Gabriel, Soren Germer, Richard A Gibbs, Xiuqing Guo, Jiang He, Nancy Heard-Costa, Bertha Hildalgo, Lifang Hou, Marguerite R Irvin, Roby Joehanes, Robert C Kaplan, Sharon Lr Kardia, Tanika N Kelly, Ryan Kim, Charles Kooperberg, Brian G Kral, Daniel Levy, Changwei Li, Chunyu Liu, Don Lloyd-Jone, Ruth Jf Loos, Michael C Mahaney, Lisa W Martin, Rasika A Mathias, Ryan L Minster, Braxton D Mitchell, May E Montasser, Alanna C Morrison, Joanne M Murabito, Take Naseri, Jeffrey R O'Connell, Nicholette D Palmer, Michael H Preuss, Bruce M Psaty, Laura M Raffield, Dabeeru C Rao, Susan Redline, Alexander P Reiner, Stephen S Rich, Muagututi'a Sefuiva Ruepena, Wayne H-H Sheu, Jennifer A Smith, Albert Smith, Hemant K Tiwari, Michael Y Tsai, Karine A Viaud-Martinez, Zhe Wang, Lisa R Yanek, Wei Zhao, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium, Jerome I Rotter, Xihong Lin, Pradeep Natarajan, Gina M Peloso

Faculty, Staff and Student Publications

Long non-coding RNAs (lncRNAs) are known to perform important regulatory functions in lipid metabolism. Large-scale whole-genome sequencing (WGS) studies and new statistical methods for variant set tests now provide an opportunity to assess more associations between rare variants in lncRNA genes and complex traits across the genome. In this study, we used high-coverage WGS from 66,329 participants of diverse ancestries with measurement of blood lipids and lipoproteins (LDL-C, HDL-C, TC, and TG) in the National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) program to investigate the role of lncRNAs in lipid variability. We aggregated rare variants …

Pls3 Missense Variants Affecting The Actin-Binding Domains Cause X-Linked Congenital Diaphragmatic Hernia And Body-Wall Defects, Florence Petit, Mauro Longoni, Julie Wells, Richard S Maser, Eric L Bogenschutz, Matthew J Dysart, Hannah T M Contreras, Frederic Frénois, Barbara R Pober, Robin D Clark, Philip F Giampietro, Hilger H Ropers, Hao Hu, Maria Loscertales, Richard Wagner, Xingbin Ai, Harrison Brand, Anne-Sophie Jourdain, Marie-Ange Delrue, Brigitte Gilbert-Dussardier, Louise Devisme, Boris Keren, David J Mcculley, Lu Qiao, Rebecca Hernan, Julia Wynn, Tiana M Scott, Daniel G Calame, Zeynep Coban-Akdemir, Patricia Hernandez, Andres Hernandez-Garcia, Hagith Yonath, James R Lupski, Yufeng Shen, Wendy K Chung, Daryl A Scott, Carol J Bult, Patricia K Donahoe, Frances A High

Faculty, Staff and Student Publications

Congenital diaphragmatic hernia (CDH) is a relatively common and genetically heterogeneous structural birth defect associated with high mortality and morbidity. We describe eight unrelated families with an X-linked condition characterized by diaphragm defects, variable anterior body-wall anomalies, and/or facial dysmorphism. Using linkage analysis and exome or genome sequencing, we found that missense variants in plastin 3 (PLS3), a gene encoding an actin bundling protein, co-segregate with disease in all families. Loss-of-function variants in PLS3 have been previously associated with X-linked osteoporosis (MIM: 300910), so we used in silico protein modeling and a mouse model to address these seemingly disparate clinical …

Literature-Based Predictions Of Mendelian Disease Therapies, Cole A Deisseroth, Won-Seok Lee, Jiyoen Kim, Hyun-Hwan Jeong, Ryan S Dhindsa, Julia Wang, Huda Y Zoghbi, Zhandong Liu

Faculty, Staff and Students Publications

In the effort to treat Mendelian disorders, correcting the underlying molecular imbalance may be more effective than symptomatic treatment. Identifying treatments that might accomplish this goal requires extensive and up-to-date knowledge of molecular pathways-including drug-gene and gene-gene relationships. To address this challenge, we present "parsing modifiers via article annotations" (PARMESAN), a computational tool that searches PubMed and PubMed Central for information to assemble these relationships into a central knowledge base. PARMESAN then predicts putatively novel drug-gene relationships, assigning an evidence-based score to each prediction. We compare PARMESAN's drug-gene predictions to all of the drug-gene relationships displayed by the Drug-Gene Interaction …

An Intrinsically Disordered Region Controlling Condensation Of A Circadian Clock Component And Rhythmic Transcription In The Liver, Kun Zhu, Isaac J Celwyn, Dongyin Guan, Yang Xiao, Xiang Wang, Wenxiang Hu, Chunjie Jiang, Lan Cheng, Rafael Casellas, Mitchell A Lazar

Faculty, Staff and Students Publications

Circadian gene transcription is fundamental to metabolic physiology. Here we report that the nuclear receptor REV-ERBα, a repressive component of the molecular clock, forms circadian condensates in the nuclei of mouse liver. These condensates are dictated by an intrinsically disordered region (IDR) located in the protein's hinge region which specifically concentrates nuclear receptor corepressor 1 (NCOR1) at the genome. IDR deletion diminishes the recruitment of NCOR1 and disrupts rhythmic gene transcription in vivo. REV-ERBα condensates are located at high-order transcriptional repressive hubs in the liver genome that are highly correlated with circadian gene repression. Deletion of the IDR disrupts transcriptional …

Utility And Precision Evidence Of Technology In The Treatment Of Type 1 Diabetes: A Systematic Review, Laura M Jacobsen, Jennifer L Sherr, Elizabeth Considine, Angela Chen, Sarah M Peeling, Margo Hulsmans, Sara Charleer, Marzhan Urazbayeva, Mustafa Tosur, Selma Alamarie, Maria J Redondo, Korey K Hood, Peter A Gottlieb, Pieter Gillard, Jessie J Wong, Irl B Hirsch, Richard E Pratley, Lori M Laffel, Chantal Mathieu

Faculty, Staff and Students Publications

BACKGROUND: The greatest change in the treatment of people living with type 1 diabetes in the last decade has been the explosion of technology assisting in all aspects of diabetes therapy, from glucose monitoring to insulin delivery and decision making. As such, the aim of our systematic review was to assess the utility of these technologies as well as identify any precision medicine-directed findings to personalize care.

METHODS: Screening of 835 peer-reviewed articles was followed by systematic review of 70 of them (focusing on randomized trials and extension studies with ≥50 participants from the past 10 years).

RESULTS: We find …

Disease-Modifying Therapies And Features Linked To Treatment Response In Type 1 Diabetes Prevention: A Systematic Review, Jamie L Felton, Kurt J Griffin, Richard A Oram, Cate Speake, S Alice Long, Suna Onengut-Gumuscu, Stephen S Rich, Gabriela S F Monaco, Carmella Evans-Molina, Linda A Dimeglio, Heba M Ismail, Andrea K Steck, Dana Dabelea, Randi K Johnson, Marzhan Urazbayeva, Stephen Gitelman, John M Wentworth, Maria J Redondo, Emily K Sims, Ada/Easd Pmdi

Faculty, Staff and Students Publications

BACKGROUND: Type 1 diabetes (T1D) results from immune-mediated destruction of insulin-producing beta cells. Prevention efforts have focused on immune modulation and supporting beta cell health before or around diagnosis; however, heterogeneity in disease progression and therapy response has limited translation to clinical practice, highlighting the need for precision medicine approaches to T1D disease modification.

METHODS: To understand the state of knowledge in this area, we performed a systematic review of randomized-controlled trials with ≥50 participants cataloged in PubMed or Embase from the past 25 years testing T1D disease-modifying therapies and/or identifying features linked to treatment response, analyzing bias using a …

Genomic Variant Benchmark: If You Cannot Measure It, You Cannot Improve It, Sina Majidian, Daniel Paiva Agustinho, Chen-Shan Chin, Fritz J Sedlazeck, Medhat Mahmoud

Faculty, Staff and Students Publications

Genomic benchmark datasets are essential to driving the field of genomics and bioinformatics. They provide a snapshot of the performances of sequencing technologies and analytical methods and highlight future challenges. However, they depend on sequencing technology, reference genome, and available benchmarking methods. Thus, creating a genomic benchmark dataset is laborious and highly challenging, often involving multiple sequencing technologies, different variant calling tools, and laborious manual curation. In this review, we discuss the available benchmark datasets and their utility. Additionally, we focus on the most recent benchmark of genes with medical relevance and challenging genomic complexity.

Global Effect Of Modifiable Risk Factors On Cardiovascular Disease And Mortality, Global Cardiovascular Risk Consortium, Christina Magnussen, Francisco M Ojeda, Darryl P Leong, Jesus Alegre-Diaz, Philippe Amouyel, Larissa Aviles-Santa, Dirk De Bacquer, Christie M Ballantyne, Antonio Bernabé-Ortiz, Martin Bobak, Hermann Brenner, Rodrigo M Carrillo-Larco, James De Lemos, Annette Dobson, Marcus Dörr, Chiara Donfrancesco, Wojciech Drygas, Robin P Dullaart, Gunnar Engström, Marco M Ferrario, Jean Ferrières, Giovanni De Gaetano, Uri Goldbourt, Clicerio Gonzalez, Guido Grassi, Allison M Hodge, Kristian Hveem, Licia Iacoviello, M Kamran Ikram, Vilma Irazola, Modou Jobe, Pekka Jousilahti, Pontiano Kaleebu, Maryam Kavousi, Frank Kee, Davood Khalili, Wolfgang Koenig, Anna Kontsevaya, Kari Kuulasmaa, Karl J Lackner, David M Leistner, Lars Lind, Allan Linneberg, Thiess Lorenz, Magnus Nakrem Lyngbakken, Reza Malekzadeh, Sofia Malyutina, Ellisiv B Mathiesen, Olle Melander, Andres Metspalu, J Jaime Miranda, Marie Moitry, Joseph Mugisha, Mahdi Nalini, Vijay Nambi, Toshiharu Ninomiya, Karen Oppermann, Eleonora D'Orsi, Andrzej Pająk, Luigi Palmieri, Demosthenes Panagiotakos, Arokiasamy Perianayagam, Annette Peters, Hossein Poustchi, Andrew M Prentice, Eva Prescott, Ulf Risérus, Veikko Salomaa, Susana Sans, Satoko Sakata, Ben Schöttker, Aletta E Schutte, Sadaf G Sepanlou, Sanjib Kumar Sharma, Jonathan E Shaw, Leon A Simons, Stefan Söderberg, Abdonas Tamosiunas, Barbara Thorand, Hugh Tunstall-Pedoe, Raphael Twerenbold, Diego Vanuzzo, Giovanni Veronesi, Julia Waibel, S Goya Wannamethee, Masafumi Watanabe, Philipp S Wild, Yao Yao, Yi Zeng, Andreas Ziegler, Stefan Blankenberg

Faculty, Staff and Students Publications

BACKGROUND: Five modifiable risk factors are associated with cardiovascular disease (CVD) and all-cause mortality. The regional and sex-specific prevalence of these modifiable risk factors and their impact on CVD and all-cause mortality have not been evaluated using individual-level data.

METHODS: The Global Cardiovascular Risk Consortium harmonized individual-level data from 112 cohort studies conducted in 34 countries and 8 geographic regions. Associations between body-mass index, systolic blood pressure, non-high-density lipoprotein cholesterol, smoking, and diabetes with incident CVD and all-cause mortality were examined using Cox regression analyses and stratified by geographic region, age and sex. Population-attributable fractions were estimated for 10-year incident …

Analysis And Prediction Of Liver Volume Change Maps Derived From Computational Tomography Scans Acquired Pre- And Post-Radiation Therapy, Guillaume Cazoulat, Aashish C Gupta, Mais M Al Taie, Eugene J Koay, Kristy K Brock

Faculty, Staff and Student Publications

External beam radiation therapy (EBRT) of liver cancers can cause local liver atrophy as a result of tissue damage or hypertrophy as a result of liver regeneration. Predicting those volumetric changes would enable new strategies for liver function preservation during treatment planning. However, understanding of the spatial dose/volume relationship is still limited. This study leverages the use of deep learning-based segmentation and biomechanical deformable image registration (DIR) to analyze and predict this relationship. Pre- and Post-EBRT imaging data were collected for 100 patients treated for hepatocellular carcinomas, cholangiocarcinoma or CRC with intensity-modulated radiotherapy (IMRT) with prescription doses ranging from 50 …