Digital Commons Network^™

Effectiveness And Adherence To Closed Face Shields In The Prevention Of Covid-19 Transmission: A Non-Inferiority Randomized Controlled Trial In A Middle-Income Setting (Covproshield), Andrea Ramirez Varela, Alejandro Pacheco Gurruchaga, Silvia Restrepo Restrepo, Juan David Martin, Yessica Daniela Campaz Landazabal, Guillermo Tamayo-Cabeza, Sandra Contreras-Arrieta, Yuldor Caballero-Díaz, Luis Jorge Hernandez Florez, John Mario González, Juan Carlos Santos-Barbosa, José David Pinzón, Juan José Yepes-Nuñez, Rachid Laajaj, Giancarlo Buitrago Gutierrez, Martha Vives Florez, Janner Fuentes Castillo, Gianni Quinche Vargas, Andres Casas, Antonio Medina, Eduardo Behrentz, Covida Working Group

Faculty, Staff and Student Publications

BACKGROUND: The use of respiratory devices can mitigate the spread of diseases such as COVID-19 in community settings. We aimed to determine the effectiveness of closed face shields with surgical face masks to prevent SARS-CoV-2 transmission in working adults during the COVID-19 pandemic in Bogotá, Colombia.

METHODS: An open-label non-inferiority randomized controlled trial that randomly assigned participants to one of two groups: the intervention group was instructed to wear closed face shields with surgical face masks, and the active control group was instructed to wear only surgical face masks. The primary outcome was a positive reverse transcription polymerase chain reaction …

Food Insecurity Among Low-Income Households With Children Participating In A School-Based Fruit And Vegetable Co-Op, Allison N Marshall, Ru-Jye Chuang, Joanne Chow, Nalini Ranjit, Jayna M Dave, Mallika Mathur, Christine Markham, Shreela V Sharma

Faculty, Staff and Student Publications

The purpose of this study was to evaluate the impact of a nutrition intervention on food insecurity among low-income households with children. Data were collected from 371 parent−child dyads in a quasi-experimental evaluation study of a 1-year intervention (n = 6 intervention schools receiving Brighter Bites, n = 6 wait-list control schools), and longitudinal follow-up of the intervention group 2 years post-intervention in Houston, Texas. Data were collected at three timepoints: at baseline and 1 year for all participants, and at 2 year follow-up for the intervention group (the wait-list control group received the intervention during that time). At baseline, …

Investigation Of The Hydrogen Sulfide Signaling Pathway In Schwann Cells During Peripheral Nerve Degeneration: Multi-Omics Approaches, Yoo Lim Chun, Won-Joon Eom, Jun Hyung Lee, Thy N C Nguyen, Ki-Hoon Park, Hyung-Joo Chung, Han Seo, Youngbuhm Huh, Sang Hoon Kim, Seung Geun Yeo, Wonseok Park, Geul Bang, Jin Young Kim, Min-Sik Kim, Na Young Jeong, Junyang Jung

Faculty, Staff and Student Publications

No abstract provided.

Structure-Based Design Of Stapled Peptides That Bind Gabarap And Inhibit Autophagy, Hawley Brown, Mia Chung, Alina Üffing, Nefeli Batistatou, Tiffany Tsang, Samantha Doskocil, Weiqun Mao, Dieter Willbold, Robert C Bast, Zhen Lu, Oliver H Weiergräber, Joshua A Kritzer

Faculty, Staff and Student Publications

The LC3/GABARAP family of proteins is involved in nearly every stage of autophagy. Inhibition of LC3/GABARAP proteins is a promising approach to blocking autophagy, which sensitizes advanced cancers to DNA-damaging chemotherapy. Here, we report the structure-based design of stapled peptides that inhibit GABARAP with nanomolar affinities. Small changes in staple structure produced stapled peptides with very different binding modes and functional differences in LC3/GABARAP paralog selectivity, ranging from highly GABARAP-specific to broad inhibition of both subfamilies. The stapled peptides exhibited considerable cytosolic penetration and resistance to biological degradation. They also reduced autophagic flux in cultured ovarian cancer cells and sensitized …

Cross-Sector Decision Landscape In Response To Covid-19: A Qualitative Network Mapping Analysis Of North Carolina Decision-Makers, Caitlin B Biddell, Karl T Johnson, Mehul D Patel, Raymond L Smith, Hillary K Hecht, Julie L Swann, Maria E Mayorga, Kristen Hassmiller Lich

Faculty, Staff and Student Publications

INTRODUCTION: The COVID-19 pandemic response has demonstrated the interconnectedness of individuals, organizations, and other entities jointly contributing to the production of community health. This response has involved stakeholders from numerous sectors who have been faced with new decisions, objectives, and constraints. We examined the cross-sector organizational decision landscape that formed in response to the COVID-19 pandemic in North Carolina.

METHODS: We conducted virtual semi-structured interviews with 44 organizational decision-makers representing nine sectors in North Carolina between October 2020 and January 2021 to understand the decision-making landscape within the first year of the COVID-19 pandemic. In line with a complexity/systems thinking …

Accuracy Of Iol Power Calculation Formulas For Acrysof Sn60wf Versus Tecnis Zcb00 Intraocular Lenses, Cynthia C Jiang, Noah M Hodson, Daniel A Johnson, Ahmad Kheirkhah

Faculty, Staff and Student Publications

PURPOSE: To compare the accuracy of various intraocular lens power formulas for two monofocal hydrophobic foldable lenses, the AcrySof SN60WF and the Tecnis ZCB00.

METHODS: This retrospective study included 409 eyes from 409 patients who underwent uncomplicated cataract surgery (299 eyes with SN60WF and 110 eyes with ZCB00). Biometry was performed for all eyes with an IOLMaster 700. Predicted refraction from five different IOL power formulas (Barrett Universal II, Haigis, Hoffer-Q, Holladay 2, and SRK/T) was compared to postoperative refraction at one to three months for the following axial length strata: short eyes (

RESULTS: In patients with medium eyes, …

Good Scientific Practice In Eeg And Meg Research: Progress And Perspectives, Guiomar Niso, Laurens R Krol, Etienne Combrisson, A Sophie Dubarry, Madison A Elliott, Clément François, Yseult Héjja-Brichard, Sophie K Herbst, Karim Jerbi, Vanja Kovic, Katia Lehongre, Steven J Luck, Manuel Mercier, John C Mosher, Yuri G Pavlov, Aina Puce, Antonio Schettino, Daniele Schön, Walter Sinnott-Armstrong, Bertille Somon, Anđela Šoškić, Suzy J Styles, Roni Tibon, Martina G Vilas, Marijn Van Vliet, Maximilien Chaumon

Faculty, Staff and Student Publications

Good scientific practice (GSP) refers to both explicit and implicit rules, recommendations, and guidelines that help scientists to produce work that is of the highest quality at any given time, and to efficiently share that work with the community for further scrutiny or utilization. For experimental research using magneto- and electroencephalography (MEEG), GSP includes specific standards and guidelines for technical competence, which are periodically updated and adapted to new findings. However, GSP also needs to be regularly revisited in a broader light. At the LiveMEEG 2020 conference, a reflection on GSP was fostered that included explicitly documented guidelines and technical …

Mixed-Phenotype Acute Leukemia: Clinical Diagnosis And Therapeutic Strategies, Binsah S George, Binoy Yohannan, Anneliese Gonzalez, Adan Rios

Faculty, Staff and Student Publications

Mixed-phenotype acute leukemia (MPAL) comprises a heterogenous group of leukemias that are genetically, immunophenotypically, and clinically, diverse. Given the rarity of the disease, the diagnosis and treatment of MPAL is extremely challenging. Recent collaborative efforts have made significant progress in understanding the complex genomic landscape of MPAL. Some retrospective studies support starting ALL-type induction followed by an allogeneic stem cell transplant(allo-sct) in the first complete remission; however, due to the inherent bias of retrospective data and small case series, a prospective validation of AML- and ALL-based regimen, and the incorporation of targeted therapies based on genetics and immunophenotype are warranted. …

Relevance Of Medullary Vein Sign In Neurosarcoidosis, Richard Liberio, Emily Kramer, Anza B Memon, Ryan Reinbeau, Parissa Feizi, Joe Joseph, Janet Wu, Shitiz Sriwastava

Faculty, Staff and Student Publications

BACKGROUND: Central nervous system involvement is uncommon in patients with sarcoidosis. It remains a diagnostic challenge for clinicians, as there is a broad differential diagnosis that matches the presenting neurological signs. Often, the imaging findings also overlap with other disease entities. One understudied finding in patients with neurosarcoidosis is the presence of medullary vein engorgement on SWI imaging, termed the "medullary vein sign", which has been postulated to be a specific sign for neurosarcoidosis. This study aims to provide an understanding of the diagnostic potential of the medullary vein sign.

METHODS: Thirty-two patients who presented with neurologic signs concerning for …

Immunotherapy For Type 1 Diabetes Mellitus By Adjuvant-Free Schistosoma Japonicum-Egg Tip-Loaded Asymmetric Microneedle Patch (Stamp), Haoming Huang, Dian Hu, Zhuo Chen, Jiarong Xu, Rengui Xu, Yusheng Gong, Zhengming Fang, Ting Wang, Wei Chen

Faculty, Staff and Student Publications

BACKGROUND: Type 1 diabetes mellitus (T1DM) is an autoimmune disease mediated by autoreactive T cells and dominated by Th1 response polarization. Insulin replacement therapy faces great challenges to this autoimmune disease, requiring highly frequent daily administration. Intriguingly, the progression of T1DM has proven to be prevented or attenuated by helminth infection or worm antigens for a relatively long term. However, the inevitable problems of low safety and poor compliance arise from infection with live worms or direct injection of antigens. Microneedles would be a promising candidate for local delivery of intact antigens, thus providing an opportunity for the clinical immunotherapy …

Identification Of Missing Hierarchical Relations In The Vaccine Ontology Using Acquired Term Pairs, Warren Manuel, Rashmie Abeysinghe, Yongqun He, Cui Tao, Licong Cui

Faculty, Staff and Student Publications

Background

The Vaccine Ontology (VO) is a biomedical ontology that standardizes vaccine annotation. Errors in VO will affect a multitude of applications that it is being used in. Quality assurance of VO is imperative to ensure that it provides accurate domain knowledge to these downstream tasks. Manual review to identify and fix quality issues (such as missing hierarchical is-a relations) is challenging given the complexity of the ontology. Automated approaches are highly desirable to facilitate the quality assurance of VO.

Methods

We developed an automated lexical approach that identifies potentially missing is-a relations in VO. First, we construct two types …

Current Challenges In Image-Guided Magnetic Hyperthermia Therapy For Liver Cancer, Anirudh Sharma, Erik Cressman, Anilchandra Attaluri, Dara L Kraitchman, Robert Ivkov

Faculty, Staff and Student Publications

For patients diagnosed with advanced and unresectable hepatocellular carcinoma (HCC), liver transplantation remains the best option to extend life. Challenges with organ supply often preclude liver transplantation, making palliative non-surgical options the default front-line treatments for many patients. Even with imaging guidance, success following treatment remains inconsistent and below expectations, so new approaches are needed. Imaging-guided thermal therapy interventions have emerged as attractive procedures that offer individualized tumor targeting with the potential for the selective targeting of tumor nodules without impairing liver function. Furthermore, imaging-guided thermal therapy with added standard-of-care chemotherapies targeted to the liver tumor can directly reduce the …

Understanding Diagnostic Pathways In Systemic Sclerosis And Systemic Sclerosis-Associated Interstitial Lung Disease: A Retrospective Cohort Study, Shervin Assassi, Nan Shao, Ziwei Yin, Elizabeth R Volkmann, Donald F Zoz, Thomas B Leonard

Faculty, Staff and Student Publications

Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is usually detected in a patient known to have SSc but may be diagnosed prior to SSc. We probed an insurance database to investigate documentation of ILD prior to SSc. Using Optum's Clinformatics® Data Mart Database, we identified patients with an SSc index date between January 1, 2010, and September 30, 2015, based on International Classification of Diseases (ICD)-9-Clinical Modification (CM) codes, ≥2 medical claims associated with SSc on different dates within 1 year, and ≥3 years of continuous enrollment prior to SSc index date (ICD-9-CM cohort). We identified an ICD-10-CM cohort comprising patients …

A Comprehensive Search Of Non-Canonical Proteins In Non-Small Cell Lung Cancer And Their Impact On The Immune Response, Ehsan Irajizad, Johannes F Fahrmann, James P Long, Jody Vykoukal, Makoto Kobayashi, Michela Capello, Chuan-Yih Yu, Yining Cai, Fu Chung Hsiao, Nikul Patel, Soyoung Park, Qian Peng, Jennifer B Dennison, Taketo Kato, Mei Chee Tai, Ayumu Taguchi, Humam Kadara, Ignacio I Wistuba, Hiroyuki Katayama, Kim-Anh Do, Samir M Hanash, Edwin J Ostrin

Faculty, Staff and Student Publications

There is substantial interest in mining neoantigens for cancer applications. Non-canonical proteins resulting from frameshift mutations have been identified as neoantigens in cancer. We investigated the landscape of non-canonical proteins in non-small cell lung cancer (NSCLC) and their induced immune response in the form of autoantibodies. A database of cryptoproteins was computationally constructed and comprised all alternate open reading frames (altORFs) and ORFs identified in pseudogenes, noncoding RNAs, and untranslated regions of mRNAs that did not align with known canonical proteins. Proteomic profiles of seventeen lung adenocarcinoma (LUAD) cell lines were searched to evaluate the occurrence of cryptoproteins. To assess …

The Immune Response To Airway Mycosis, Wei Ruan, Xinxin Ma, In Hyuk Bang, Yafen Liang, Jochen Daniel Muehlschlegel, Kuang-Lei Tsai, Tingting W Mills, Xiaoyi Yuan, Holger K Eltzschig

Faculty, Staff and Student Publications

Despite increasing availability and more successful interventional approaches to restore coronary reperfusion, myocardial ischemia-reperfusion injury is a substantial cause of morbidity and mortality worldwide. During myocardial ischemia, the myocardium becomes profoundly hypoxic, thus causing stabilization of hypoxia-inducible transcription factors (HIF). Stabilization of HIF leads to a transcriptional program that promotes adaptation to hypoxia and cellular survival. Transcriptional consequences of HIF stabilization include increases in extracellular production and signaling effects of adenosine. Extracellular adenosine functions as a signaling molecule via the activation of adenosine receptors. Several studies implicated adenosine signaling in cardioprotection, particularly through the activation of the Adora2a and Adora2b …

A Differential Diagnosis Of Unusual Gastric Ulcer, Soo-Yoon Sung, Hyun Ho Choi, Kyung Jin Seo

Faculty, Staff and Student Publications

The endoscopic findings of diffuse large B cell lymphoma have various presentations. In our case, the patient had developed multiple elevated central ulceration lesions, and the peripheral elevated portion had a heaped-up margin. The margin had a sharp, smooth edge that was not infiltrative and could be confused with a simple gastric ulcer. Endoscopists should be aware of the possibility of multiple lymphoma ulcers with heaped-up margins. We present some unusual endoscopic features of lymphoma, which are easily misdiagnosed as gastric ulcers.

Increased Expression Of Interferon-Induced Transmembrane 3 (Ifitm3) In Stroke And Other Inflammatory Conditions In The Brain, Elisabeth Harmon, Andrea Doan, Jesus Bautista-Garrido, Joo Eun Jung, Sean P Marrelli, Gab Seok Kim

Faculty, Staff and Student Publications

Microglia, the resident innate immune cells of the brain, become more highly reactive with aging and diseased conditions. In collaboration with other cell types in brains, microglia can contribute both to worsened outcome following stroke or other neurodegenerative diseases and to the recovery process by changing their phenotype toward reparative microglia. Recently, IFITM3 (a member of the "interferon-inducible transmembrane" family) has been revealed as a molecular mediator between amyloid pathology and neuroinflammation. Expression of IFITM3 in glial cells, especially microglia following stroke, is not well described. Here, we present evidence that ischemic stroke causes an increase in IFITM3 expression along …

Miracle Of Microrna-Driven Cancer Nanotherapeutics, Goknur Kara, Banu Arun, George A Calin, Bulent Ozpolat

Faculty, Staff and Student Publications

MicroRNAs (miRNAs) are non-protein-coding RNA molecules 20-25 nucleotides in length that can suppress the expression of genes involved in numerous physiological processes in cells. Accumulating evidence has shown that dysregulation of miRNA expression is related to the pathogenesis of various human diseases and cancers. Thus, stragegies involving either restoring the expression of tumor suppressor miRNAs or inhibiting overexpressed oncogenic miRNAs hold potential for targeted cancer therapies. However, delivery of miRNAs to tumor tissues is a challenging task. Recent advances in nanotechnology have enabled successful tumor-targeted delivery of miRNA therapeutics through newly designed nanoparticle-based carrier systems. As a result, miRNA therapeutics …

Adaptation And Dosimetric Commissioning Of A Synchrotron-Based Proton Beamline For Flash Experiments, Ming Yang, Xiaochun Wang, Fada Guan, Uwe Titt, Kiminori Iga, Dadi Jiang, Takeshi Takaoka, Satoshi Tootake, Tadashi Katayose, Masumi Umezawa, Emil Schüler, Steven Frank, Steven H Lin, Narayan Sahoo, Albert C Koong, Radhe Mohan, X Ronald Zhu

Faculty, Staff and Student Publications

Objective. Irradiation with ultra-high dose rates (>40 Gy s^-1), also known as FLASH irradiation, has the potential to shift the paradigm of radiation therapy because of its reduced toxicity to normal tissues compared to that of conventional irradiations. The goal of this study was to (1) achieve FLASH irradiation conditions suitable for pre-clinicalin vitroandin vivobiology experiments using our synchrotron-based proton beamline and (2) commission the FLASH irradiation conditions achieved.

Approach. To achieve these suitable FLASH conditions, we made a series of adaptations to our proton beamline, including modifying the spill length …

A Multi-Layer Functional Genomic Analysis To Understand Noncoding Genetic Variation In Lipids, Shweta Ramdas, Jonathan Judd, Sarah E Graham, Stavroula Kanoni, Yuxuan Wang, Ida Surakka, Brandon Wenz, Shoa L Clarke, Alessandra Chesi, Andrew Wells, Konain Fatima Bhatti, Sailaja Vedantam, Thomas W Winkler, Adam E Locke, Eirini Marouli, Greg J M Zajac, Kuan-Han H Wu, Ioanna Ntalla, Qin Hui, Derek Klarin, Austin T Hilliard, Zeyuan Wang, Chao Xue, Gudmar Thorleifsson, Anna Helgadottir, Daniel F Gudbjartsson, Hilma Holm, Isleifur Olafsson, Mi Yeong Hwang, Sohee Han, Masato Akiyama, Saori Sakaue, Chikashi Terao, Masahiro Kanai, Wei Zhou, Ben M Brumpton, Humaira Rasheed, Aki S Havulinna, Yogasudha Veturi, Jennifer Allen Pacheco, Elisabeth A Rosenthal, Todd Lingren, Qiping Feng, Iftikhar J Kullo, Akira Narita, Jun Takayama, Hilary C Martin, Karen A Hunt, Bhavi Trivedi, Jeffrey Haessler, Franco Giulianini, Yuki Bradford, Jason E Miller, Archie Campbell, Kuang Lin, Iona Y Millwood, Asif Rasheed, George Hindy, Jessica D Faul, Wei Zhao, David R Weir, Constance Turman, Hongyan Huang, Mariaelisa Graff, Ananyo Choudhury, Dhriti Sengupta, Anubha Mahajan, Michael R Brown, Weihua Zhang, Ketian Yu, Ellen M Schmidt, Anita Pandit, Stefan Gustafsson, Xianyong Yin, Jian'an Luan, Jing-Hua Zhao, Fumihiko Matsuda, Hye-Mi Jang, Kyungheon Yoon, Carolina Medina-Gomez, Achilleas Pitsillides, Jouke Jan Hottenga, Andrew R Wood, Yingji Ji, Zishan Gao, Simon Haworth, Ruth E Mitchell, Jin Fang Chai, Mette Aadahl, Anne A Bjerregaard, Jie Yao, Ani Manichaikul, Wen-Jane Lee, Chao Agnes Hsiung, Helen R Warren, Julia Ramirez, Jette Bork-Jensen, Line L Kårhus, Anuj Goel, Maria Sabater-Lleal, Raymond Noordam, Pala Mauro, Floris Matteo, Aaron F Mcdaid, Pedro Marques-Vidal, Matthias Wielscher, Stella Trompet, Naveed Sattar, Line T Møllehave, Matthias Munz, Lingyao Zeng, Jianfeng Huang, Bin Yang, Alaitz Poveda, Azra Kurbasic, Sebastian Schönherr, Lukas Forer, Markus Scholz, Tessel E Galesloot, Jonathan P Bradfield, Sanni E Ruotsalainen, E Warwick Daw, Joseph M Zmuda, Jonathan S Mitchell, Christian Fuchsberger, Henry Christensen, Jennifer A Brody, Phuong Le, Mary F Feitosa, Mary K Wojczynski, Daiane Hemerich, Michael Preuss, Massimo Mangino, Paraskevi Christofidou, Niek Verweij, Jan W Benjamins, Jorgen Engmann, Tsao L Noah, Anurag Verma, Roderick C Slieker, Ken Sin Lo, Nuno R Zilhao, Marcus E Kleber, Graciela E Delgado, Shaofeng Huo, Daisuke D Ikeda, Hiroyuki Iha, Jian Yang, Jun Liu, Ayşe Demirkan, Hampton L Leonard, Jonathan Marten, Carina Emmel, Börge Schmidt, Laura J Smyth, Marisa Cañadas-Garre, Chaolong Wang, Masahiro Nakatochi, Andrew Wong, Nina Hutri-Kähönen, Xueling Sim, Rui Xia, Alicia Huerta-Chagoya, Juan Carlos Fernandez-Lopez, Valeriya Lyssenko, Suraj S Nongmaithem, Alagu Sankareswaran, Marguerite R Irvin, Christopher Oldmeadow, Han-Na Kim, Seungho Ryu, Paul R H J Timmers, Liubov Arbeeva, Rajkumar Dorajoo, Leslie A Lange, Gauri Prasad, Laura Lorés-Motta, Marc Pauper, Jirong Long, Xiaohui Li, Elizabeth Theusch, Fumihiko Takeuchi, Cassandra N Spracklen, Anu Loukola, Sailalitha Bollepalli, Sophie C Warner, Ya Xing Wang, Wen B Wei, Teresa Nutile, Daniela Ruggiero, Yun Ju Sung, Shufeng Chen, Fangchao Liu, Jingyun Yang, Katherine A Kentistou, Bernhard Banas, Anna Morgan, Karina Meidtner, Lawrence F Bielak, Jennifer A Smith, Prashantha Hebbar, Aliki-Eleni Farmaki, Edith Hofer, Maoxuan Lin, Maria Pina Concas, Simona Vaccargiu, Peter J Van Der Most, Niina Pitkänen, Brian E Cade, Sander W Van Der Laan, Kumaraswamy Naidu Chitrala, Stefan Weiss, Amy R Bentley, Ayo P Doumatey, Adebowale A Adeyemo, Jong Young Lee, Eva R B Petersen, Aneta A Nielsen, Hyeok Sun Choi, Maria Nethander, Sandra Freitag-Wolf, Lorraine Southam, Nigel W Rayner, Carol A Wang, Shih-Yi Lin, Jun-Sing Wang, Christian Couture, Leo-Pekka Lyytikäinen, Kjell Nikus, Gabriel Cuellar-Partida, Henrik Vestergaard, Bertha Hidalgo, Olga Giannakopoulou, Qiuyin Cai, Morgan O Obura, Jessica Van Setten, Karen Y He, Hua Tang, Natalie Terzikhan, Jae Hun Shin, Rebecca D Jackson, Alexander P Reiner, Lisa Warsinger Martin, Zhengming Chen, Liming Li, Takahisa Kawaguchi, Joachim Thiery, Joshua C Bis, Lenore J Launer, Huaixing Li, Mike A Nalls, Olli T Raitakari, Sahoko Ichihara, Sarah H Wild, Christopher P Nelson, Harry Campbell, Susanne Jäger, Toru Nabika, Fahd Al-Mulla, Harri Niinikoski, Peter S Braund, Ivana Kolcic, Peter Kovacs, Tota Giardoglou, Tomohiro Katsuya, Dominique De Kleijn, Gert J De Borst, Eung Kweon Kim, Hieab H H Adams, M Arfan Ikram, Xiaofeng Zhu, Folkert W Asselbergs, Adriaan O Kraaijeveld, Joline W J Beulens, Xiao-Ou Shu, Loukianos S Rallidis, Oluf Pedersen, Torben Hansen, Paul Mitchell, Alex W Hewitt, Mika Kähönen, Louis Pérusse, Claude Bouchard, Anke Tönjes, Yii-Der Ida Chen, Craig E Pennell, Trevor A Mori, Wolfgang Lieb, Andre Franke, Claes Ohlsson, Dan Mellström, Yoon Shin Cho, Hyejin Lee, Jian-Min Yuan, Woon-Puay Koh, Sang Youl Rhee, Jeong-Taek Woo, Iris M Heid, Klaus J Stark, Martina E Zimmermann, Henry Völzke, Georg Homuth, Michele K Evans, Alan B Zonderman, Ozren Polasek, Gerard Pasterkamp, Imo E Hoefer, Susan Redline, Katja Pahkala, Albertine J Oldehinkel, Harold Snieder, Ginevra Biino, Reinhold Schmidt, Helena Schmidt, Stefania Bandinelli, George Dedoussis, Thangavel Alphonse Thanaraj, Patricia A Peyser, Norihiro Kato, Matthias B Schulze, Giorgia Girotto, Carsten A Böger, Bettina Jung, Peter K Joshi, David A Bennett, Philip L De Jager, Xiangfeng Lu, Vasiliki Mamakou, Morris Brown, Mark J Caulfield, Patricia B Munroe, Xiuqing Guo, Marina Ciullo, Jost B Jonas, Nilesh J Samani, Jaakko Kaprio, Päivi Pajukanta, Teresa Tusié-Luna, Carlos A Aguilar-Salinas, Linda S Adair, Sonny Augustin Bechayda, H Janaka De Silva, Ananda R Wickremasinghe, Ronald M Krauss, Jer-Yuarn Wu, Wei Zheng, Anneke I Den Hollander, Dwaipayan Bharadwaj, Adolfo Correa, James G Wilson, Lars Lind, Chew-Kiat Heng, Amanda E Nelson, Yvonne M Golightly, James F Wilson, Brenda Penninx, Hyung-Lae Kim, John Attia, Rodney J Scott, D C Rao, Donna K Arnett, Mark Walker, Laura J Scott, Heikki A Koistinen, Giriraj R Chandak, Josep M Mercader, Clicerio Gonzalez Villalpando, Lorena Orozco, Myriam Fornage, E Shyong Tai, Rob M Van Dam, Terho Lehtimäki, Nish Chaturvedi, Mitsuhiro Yokota, Jianjun Liu, Dermot F Reilly, Amy Jayne Mcknight, Frank Kee, Karl-Heinz Jöckel, Mark I Mccarthy, Colin N A Palmer, Veronique Vitart, Caroline Hayward, Eleanor Simonsick, Cornelia M Van Duijn, Zi-Bing Jin, Fan Lu, Haretsugu Hishigaki, Xu Lin, Winfried März, Vilmundur Gudnason, Jean-Claude Tardif, Guillaume Lettre, Leen M T Hart, Petra J M Elders, Daniel J Rader, Scott M Damrauer, Meena Kumari, Mika Kivimaki, Pim Van Der Harst, Tim D Spector, Ruth J F Loos, Michael A Province, Esteban J Parra, Miguel Cruz, Bruce M Psaty, Ivan Brandslund, Peter P Pramstaller, Charles N Rotimi, Kaare Christensen, Samuli Ripatti, Elisabeth Widén, Hakon Hakonarson, Struan F A Grant, Lambertus Kiemeney, Jacqueline De Graaf, Markus Loeffler, Florian Kronenberg, Dongfeng Gu, Jeanette Erdmann, Heribert Schunkert, Paul W Franks, Allan Linneberg, J Wouter Jukema, Amit V Khera, Minna Männikkö, Marjo-Riitta Jarvelin, Zoltan Kutalik, Cucca Francesco, Dennis O Mook-Kanamori, Ko Willems Van Dijk, Hugh Watkins, David P Strachan, Niels Grarup, Peter Sever, Neil Poulter, Wayne Huey-Herng Sheu, Jerome I Rotter, Thomas M Dantoft, Fredrik Karpe, Matt J Neville, Nicholas J Timpson, Ching-Yu Cheng, Tien-Yin Wong, Chiea Chuen Khor, Hengtong Li, Charumathi Sabanayagam, Annette Peters, Christian Gieger, Andrew T Hattersley, Nancy L Pedersen, Patrik K E Magnusson, Dorret I Boomsma, Eco J C De Geus, L Adrienne Cupples, Joyce B J Van Meurs, Arfan Ikram, Mohsen Ghanbari, Penny Gordon-Larsen, Wei Huang, Young Jin Kim, Yasuharu Tabara, Nicholas J Wareham, Claudia Langenberg, Eleftheria Zeggini, Jaakko Tuomilehto, Johanna Kuusisto, Markku Laakso, Erik Ingelsson, Goncalo Abecasis, John C Chambers, Jaspal S Kooner, Paul S De Vries, Alanna C Morrison, Scott Hazelhurst, Michèle Ramsay, Kari E North, Martha Daviglus, Peter Kraft, Nicholas G Martin, John B Whitfield, Shahid Abbas, Danish Saleheen, Robin G Walters, Michael V Holmes, Corri Black, Blair H Smith, Aris Baras, Anne E Justice, Julie E Buring, Paul M Ridker, Daniel I Chasman, Charles Kooperberg, Gen Tamiya, Masayuki Yamamoto, David A Van Heel, Richard C Trembath, Wei-Qi Wei, Gail P Jarvik, Bahram Namjou, M Geoffrey Hayes, Marylyn D Ritchie, Pekka Jousilahti, Veikko Salomaa, Kristian Hveem, Bjørn Olav Åsvold, Michiaki Kubo, Yoichiro Kamatani, Yukinori Okada, Yoshinori Murakami, Bong-Jo Kim, Unnur Thorsteinsdottir, Kari Stefansson, Jifeng Zhang, Y Eugene Chen, Yuk-Lam Ho, Julie A Lynch, Philip S Tsao, Kyong-Mi Chang, Kelly Cho, Christopher J O'Donnell, John M Gaziano, Peter Wilson, Karen L Mohlke, Timothy M Frayling, Joel N Hirschhorn, Sekar Kathiresan, Michael Boehnke, Million Veterans Program, Global Lipids Genetics Consortium, Struan Grant, Pradeep Natarajan, Yan V Sun, Andrew P Morris, Panos Deloukas, Gina Peloso, Themistocles L Assimes, Cristen J Willer, Xiang Zhu, Christopher D Brown

Faculty, Staff and Student Publications

A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective …

Bioengineering Tools Applied To Dentistry: Validation Methods For In Vitro And In Silico Analysis, Jefferson David Melo De Matos, Daher Antonio Queiroz, Leonardo Jiro Nomura Nakano, Valdir Cabral Andrade, Nathália De Carvalho Ramos Ribeiro, Alexandre Luiz Souto Borges, Marco Antonio Bottino, Guilherme Da Rocha Scalzer Lopes

Faculty, Staff and Student Publications

This study aimed to evaluate the use of bioengineering tools, finite element analysis, strain gauge analysis, photoelastic analysis, and digital image correlation, in computational studies with greater validity and reproducibility. A bibliographic search was performed in the main health databases PUBMED and Scholar Google, in which different studies, among them, laboratory studies, case reports, systematic reviews, and literature reviews, which were developed in living individuals, were included. Therefore, articles that did not deal with the use of finite element analysis, strain gauge analysis, photoelastic analysis, and digital image correlation were excluded, as well as their use in computational studies with …

Tale Of Two Cities: Narrative Review Of Oxygen, Sung-Ho Ahn, Angela Burkett, Atzhiry Paz, Jude P Savarraj, Sarah Hinds, Georgene Hergenroeder, Aaron M Gusdon, Xuefeng Ren, Jeong-Ho Hong, Huimahn A Choi

Faculty, Staff and Student Publications

BACKGROUND: Cerebral edema (CE) at admission is a surrogate marker of 'early brain injury' (EBI) after subarachnoid hemorrhage (SAH). Only recently has the focus on the changes in CE after SAH such as delayed resolution or newly developed CE been examined. Among several factors, an early systemic inflammatory response has been shown to be associated with CE. We investigate inflammatory markers in subjects with early CE which does not resolve, i.e., persistent CE after SAH.

METHODS: Computed tomography scans of SAH patients were graded at admission and at 7 days after SAH for CE using the 0-4 'subarachnoid hemorrhage early …

Implant-Abutment Misfit After Cyclic Loading: An In Vitro Experimental Study, John Eversong Lucena De Vasconcelos, Jefferson David Melo De Matos, Daher Antonio Queiroz, Guilherme Da Rocha Scalzer Lopes, Bruna Caroline Gonçalves Vasconcelos De Lacerda, Marco Antonio Bottino, Cecilia Pedroso Turssi, Roberta Tarkany Basting, Flávia Lucisano Botelho Do Amaral, Fabiana Mantovani Gomes França

Faculty, Staff and Student Publications

This study aimed to evaluate the influence of thermomechanical cycling (TMC) and type of abutment on the misfit and compressive strength of the implant−abutment interface. Forty 3.75-mm external hexagon implants with 25° angled abutments were divided into four groups (N = 10). Group A: overcast plus TMC; Group B: overcast without TMC; Group C: completely cast plus TMC; Group D: completely cast without TMC. Abutments were fixed to the implants with 32-Ncm torque, and groups A and C specimens were cyclically loaded at 80 N with 2 Hz for 1 million cycles. The misfit on the implant−abutment interface was evaluated …

Robust And Efficient Assessment Of Potency (Reap) As A Quantitative Tool For Dose-Response Curve Estimation, Shouhao Zhou, Xinyi Liu, Xinying Fang, Vernon M Chinchilli, Michael Wang, Hong-Gang Wang, Nikolay V Dokholyan, Chan Shen, J Jack Lee

Faculty, Staff and Student Publications

The median-effect equation has been widely used to describe the dose-response relationship and identify compounds that activate or inhibit specific disease targets in contemporary drug discovery. However, the experimental data often contain extreme responses, which may significantly impair the estimation accuracy and impede valid quantitative assessment in the standard estimation procedure. To improve the quantitative estimation of the dose-response relationship, we introduce a novel approach based on robust beta regression. Substantive simulation studies under various scenarios demonstrate solid evidence that the proposed approach consistently provides robust estimation for the median-effect equation, particularly when there are extreme outcome observations. Moreover, simulation …

Dual Leucine Zipper Kinase Regulates Dscam Expression Through A Noncanonical Function Of The Cytoplasmic Poly(A)-Binding Protein, Monika Singh, Bing Ye, Jung Hwan Kim

Faculty, Staff and Student Publications

Dual leucine zipper kinase (DLK) plays a pivotal role in the development, degeneration, and regeneration of neurons. DLK can regulate gene expression post-transcriptionally, but the underlying mechanism remains poorly understood. The Drosophila DLK, Wallenda (Wnd), regulates the expression of Down syndrome cell adhesion molecule (Dscam) to control presynaptic arbor growth. This regulation is mediated by the 3′ untranslated region (3′UTR) of Dscam mRNA, which suggests that RNA binding proteins (RBPs) mediate DLK function. We performed a genome-wide cell-based RNAi screen of RBPs and identified the cytoplasmic poly(A)-binding protein, pAbp, as an RBP that mediates Wnd-induced increase in Dscam expression. Genetic …

Polygenic Risk, Midlife Life's Simple 7, And Lifetime Risk Of Stroke, Emy A Thomas, Nitesh Enduru, Adrienne Tin, Eric Boerwinkle, Michael E Griswold, Thomas H Mosley, Rebecca F Gottesman, Myriam Fornage

Faculty, Staff and Student Publications

Background

Recent genetic discoveries in stroke have unleashed the potential of using genetic information for risk prediction and health interventions aimed at disease prevention. We sought to estimate the lifetime risk of stroke (LTRS) by levels of genetic risk and to investigate whether optimal cardiovascular health can offset the negative impact of high genetic risk on lifetime risk of stroke.

Methods and Results

Study participants were 11 568 middle‐aged adults (56% women, 23% Black adults), who were free of stroke at baseline and were followed up for a median of 28 years. The remaining LTRS was estimated according to levels …

Knowledge Representation And Management: Notable Contributions In 2021, Licong Cui, Ferdinand Dhombres, Jean Charlet

Faculty, Staff and Student Publications

OBJECTIVES: To select, present, and summarize the best papers in the field of Knowledge Representation and Management (KRM) published in 2021.

METHODS: Following the International Medical Informatics Association (IMIA) Yearbook guidelines, a comprehensive and standardized review of the biomedical informatics literature was performed to select the best KRM papers published in 2021, based on PubMed queries.

RESULTS: A total of 1,231 publications were retrieved from PubMed. We nominated 15 candidate best papers, and four of them were finally selected as the best papers in the KRM section. The topics covered by these papers include knowledge graph, ontology development, ontology alignment, …

Risk Of Alzheimer’S Disease Following Influenza Vaccination: A Claims-Based Cohort Study Using Propensity Score Matching, Avram S Bukhbinder, Yaobin Ling, Omar Hasan, Xiaoqian Jiang, Yejin Kim, Kamal N Phelps, Rosemarie E Schmandt, Albert Amran, Ryan Coburn, Srivathsan Ramesh, Qian Xiao, Paul E Schulz

Faculty, Staff and Student Publications

BACKGROUND: Prior studies have found a reduced risk of dementia of any etiology following influenza vaccination in selected populations, including veterans and patients with serious chronic health conditions. However, the effect of influenza vaccination on Alzheimer's disease (AD) risk in a general cohort of older US adults has not been characterized.

OBJECTIVE: To compare the risk of incident AD between patients with and without prior influenza vaccination in a large US claims database.

METHODS: Deidentified claims data spanning September 1, 2009 through August 31, 2019 were used. Eligible patients were free of dementia during the 6-year look-back period and≥65 years …

Updated Estimates Of Sepsis Hospitalizations At United States Academic Medical Centers, Hei Kit Chan, Swapnil Khose, Summer Chavez, Bela Patel, Henry E Wang

Faculty, Staff and Student Publications

Objective: Sepsis is a major public health problem. Understanding the epidemiology of sepsis subtypes is important to quantify the magnitude of the problem and identify targets for system wide treatment strategies. We sought to describe the current national epidemiology of community-acquired (CAS), hospital-acquired (HAS) and healthcare-associated sepsis (HCAS) hospitalizations among academic medical centers in the United States using current discharge diagnosis taxonomies.

Methods: Retrospective analysis of patient discharge data from the Vizient Clinical Data Base/Resource Manager. We identified sepsis hospitalizations using four ICD-10 coding strategies: (1) "Martin" sepsis codes (21 ICD-10 codes), (2) "Angus" sepsis codes (ICD-10 infection + ICD-10 …

Integrated Regulation Of Pka By Fast And Slow Neurotransmission In The Nucleus Accumbens Controls Plasticity And Stress Responses, Rachel Thomas, Adan Hernandez, David R Benavides, Wei Li, Chunfeng Tan, Alan Umfress, Florian Plattner, Ayanabha Chakraborti, Lucas Pozzo-Miller, Susan S Taylor, James A Bibb

Faculty, Staff and Student Publications

Cortical glutamate and midbrain dopamine neurotransmission converge to mediate striatum-dependent behaviors, while maladaptations in striatal circuitry contribute to mental disorders. However, the crosstalk between glutamate and dopamine signaling has not been entirely elucidated. Here we uncover a molecular mechanism by which glutamatergic and dopaminergic signaling integrate to regulate cAMP-dependent protein kinase (PKA) via phosphorylation of the PKA regulatory subunit, RIIβ. Using a combination of biochemical, pharmacological, neurophysiological, and behavioral approaches, we find that glutamate-dependent reduction in cyclin-dependent kinase 5 (Cdk5)-dependent RIIβ phosphorylation alters the PKA holoenzyme autoinhibitory state to increase PKA signaling in response to dopamine. Furthermore, we show that …