Medicine and Health Sciences Commons^™

Encapsulation Of Disease-Causing And Commensal Mitis Group Non-Pneumococcal Streptococci, Daniel M Musher, Mathias Müsken, M John Hicks, Lesley Mcgee, Bernard Beall

Faculty, Staff and Students Publications

Background: Mitis group non-pneumococcal streptococci (MGNPS), specifically Streptococcus mitis, Streptococcus infantis and Streptococcus oralis, have recently been shown to cause pneumonia and/or bacteremia. These organisms often have capsular (cps) operons resembling those in pneumococci, and some express cps-generated polysaccharides that antigenically cross-react with pneumococcal capsular serotypes. But, to date, a series of MGNPS isolates has not been studied by electron microscopy (EM) for the presence of a capsule.

Methods: We studied 21 MGNPS; 11 were isolated from sputum and determined to have caused pneumonia, 3 were isolated from blood, and 7 were commensal isolates cultured …

Ontology Accelerates Few-Shot Learning Capability Of Large Language Model: A Study In Extraction Of Drug Efficacy In A Rare Pediatric Epilepsy, Pedram Golnari, Katrina Prantzalos, Veronica Hood, Mary Anne Meskis, Lori L Isom, Karen Wilcox, Jack M Parent, Dennis Lal, Samden D Lhatoo, Howard P Goodkin, Elaine C Wirrell, Kelly G Knupp, Manisha Patel, Jeffrey A Loeb, Joseph E Sullivan, Lauren Harte-Hargrove, Brandy E Fureman, Jeffrey Buchhalter, Satya S Sahoo

Faculty, Staff and Student Publications

OBJECTIVE: Dravet Syndrome (DS) is a developmental and epileptic encephalopathy that is characterized by severe, prolonged motor seizures and high resistance to multiple antiseizure medications (ASMs) with multiple comorbidities. Evaluating the efficacy of new drugs in DS preclinical models and mapping them to human phenotypes of DS through analysis of published literature is an important goal for improving outcomes in this rare pediatric epilepsy.

MATERIALS AND METHODS: Large language models (LLM) have demonstrated great promise in parsing published literature; however, the performance of LLMs falls short in medical applications. In this study, we investigate the effectiveness of domain ontology developed …

Looking Beyond Hospital Discharge: One-Year Mortality Following Tracheostomy Creation In Traumatically Injured Older Adults, Heather R Kregel, Jan-Michael Van Gent, Fatimah Sunez, Michael W Wandling, Krislynn M Mueck, Bryan A Cotton, David E Meyer, Laura J Moore, Lillian S Kao, Thaddeus J Puzio

Faculty, Staff and Student Publications

Introduction: We aimed to evaluate long-term outcomes following tracheostomy in older trauma patients and hypothesized that 1-year survival decreases with older age.

Methods: This was a descriptive analysis of intensive care unit patients ≥65 y old who underwent tracheostomy from 2015 to 2020. The National Death Index was accessed to determine time from tracheostomy creation to death. Groups were categorized by age. The primary outcome was 1-year mortality. Survival by age strata was analyzed using the Kaplan-Meier method.

Results: Of 205 eligible patients, 125 (61%) were 65-74, 68 (33%) were 75-84, and 12 (6%) were >85 y old. Median injury …

Exploring Boundaries With Food, Substances, And People In Substance Use Recovery: A Qualitative Analysis, Tiffany Champagne-Langabeer, Audrey Sarah Cohen, Kriti Shrestha, Jie Zhu, Audrey Lopez, Alisha Campbell, Christine Bakos-Block

Faculty, Staff and Student Publications

Background: In the United States, over 47 million youth and adults live with a substance use disorder (SUD). These individuals are frequently malnourished and have metabolic dysregulation as a result. Nutrition interventions incorporating a mindfulness-based approach help recovery efforts that are physical and mental.

Objective: The objective of this study was to explore and analyze the perspectives and experiences of individuals with SUD regarding emotional regulation and nutrition. The study used a mixed methods approach to generate insights for improving recovery support and developing future interventions.

Design: In 2024, an exploratory mixed methods study was conducted based on a large …

Synthetic Zfta Fusions Pinpoint Disordered Protein Domain Acquisition As A Mechanism Of Brain Tumorigenesis, A Arabzade, H K Shirnekhi, S Varadharajan, S M Ippagunta, A H Phillips, N Laboe, D W Baggett, Wahiduzzaman, M Jo, T Zheng, R Pathak, D Gee, D Bhimsaria, H Wu, X Gao, J Liu, E Emanus, A Bland, A Kardian, A Hancock, B Holcomb, T Wright, T Bugbee, H Sun, M Zhai, E Caesar, M Park, S Tripathi, A Shirinifard, K Lowe, A Khalighifar, R A Petersen, S King, D Stabley, A Pitre, G E Campbell, C-G Park, W T Freyaldenhoven, B Chandra, Y Xia, E Bonten, A Achari, S Kandikonda, A Carisey, S B Pounds, J Xu, D W Ellison, B Deneen, K C Bertrand, R W Kriwacki, S C Mack

Children’s Nutrition Research Center Staff Publications

Over 95% of ependymomas that arise in the cortex are driven by a gene fusion involving the zinc finger translocation-associated (ZFTA) protein. Here, using super-resolution and lattice light-sheet microscopy, we demonstrate that the most frequent fusion variant, ZFTA-RELA (ZR), forms dynamic nuclear condensates that are required for oncogene expression and tumorigenesis. Mutagenesis studies of ZR reveal a key intrinsically disordered region (IDR) in RELA that governs condensate formation. Condensate-modulating IDR mutations introduced into ZR impaired its genomic occupancy at oncogenic loci and inhibited the recruitment of transcriptional effector proteins, such as MED1, BRD4 and RNA polymerase II. Using nuclear magnetic …

Randomized Trial: Peppermint Oil (Menthol) Pharmacokinetics In Children And Effects On Gut Motility In Children With Functional Abdominal Pain: 540 Mg Vs. 900 Mg Dose Comparison, Robert J Shulman, Bruno P Chumpitazi, Daniel Gonzalez, Uttam Garg, Salma Musaad, Jiali Wen, Gregory L Kearns

Children’s Nutrition Research Center Staff Publications

Aims: There is a paucity of information on the pharmacokinetics (PK) and pharmacodynamics (PD) of menthol, the active ingredient in peppermint oil (PMO). We studied the PK of menthol (540 and 900 mg) in children and measured their effects on gut transit/contractility.

Methods: Children 7-12 years of age with functional abdominal pain underwent wireless motility capsule (WMC) testing. One week later, they were randomized to 540 mg or 900 mg of oral enteric-coated PMO. Blood was sampled over 24 h to determine menthol PK. The WMC test was repeated while they took their respective dose (180 mg thrice or 180 …

Replication Of Blood Dna Methylomic Signatures Associated With Cerebrospinal Fluid Levels Of Ykl-40 And Nfl Biomarkers, Timo Kaleck, Rafael Campos-Martin, Amanda Cano, Maria Victoria Fernández, Pamela Martino-Adami, Luca Kleineidam, Victor M Andrade Fuentes, Kumar P Tripathi, Kayenat Parveen, Raquel Puerta, Itziar De Rojas, Kishore A Ravichandran, Oliver Peters, Julian Hellmann-Regen, Josef Priller, Maria Gemenetzi, Anja Schneider, Jens Wiltfang, Emrah Düzel, Katharina Buerger, Robert Perneczky, Stefan Teipel, Christoph Laske, Frederic Brosseron, Marta Marquié, Daniel La Van Den Hove, Mercè Boada, Michael T Heneka, Michael Wagner, Natalie Marchant, Jean-Charles Lambert, Ruth Frikke-Schmidt, Frank Jessen, Agustín Ruiz, Alfredo Ramirez

Faculty, Staff and Student Publications

No abstract provided.

Drivers Of Frequent Emergency Department Use In Socioeconomically Disadvantaged Older Adults: A Qualitative Study, Anita Chary, Annika Bhananker, Michelle Suh, David Leavitt, Elise Brickhouse, Shreya Tamma, Jose Ramirez, Mariana Rios, Aanand D Naik, Margaret Samuels-Kalow, Naomi George

Faculty, Staff and Student Publications

Background: The emergency department (ED) is the safety net for and a common point of healthcare access for socioeconomically disadvantaged older adults. Little is known about socioeconomically disadvantaged older ED patients' perspectives on their health, healthcare access, and ED use. Such insights could guide tailored interventions to address unmet clinical and health-related social needs (HRSN).

Methods: We performed a qualitative study with older adults in a single public safety net hospital ED. We interviewed patients age 60+ who had ≥ 4 ED 4 visits in the past year. Semi-structured interviews explored perceived health needs and motivations underlying ED visits. We …

Identifying Geographic Cold Spots Of Pcos Diagnosis In Texas: A Spatial Analysis Of Underdiagnosis And Rural Disparities, Ryan Ramphul, Geethika Yalavarthy, Jooyeon Lee

Faculty, Staff and Student Publications

Context: Polycystic ovary syndrome (PCOS) is a common yet underdiagnosed endocrine disorder with substantial reproductive and metabolic consequences. Although disparities in PCOS care have been documented, few studies have employed spatial methods to identify areas of potential underdiagnosis.

Objective: This study uses geospatial analysis to detect cold spots of PCOS clinical encounters across Texas and investigates neighborhood characteristics associated with these areas.

Methods: We analyzed inpatient and outpatient encounter data from the Texas Public Use Data File (PUDF) between 2018 and 2024 to identify PCOS-related visits (International Classification of Diseases, revision 10: E28.2). ZIP code tabulation area (ZCTA)-level PCOS encounter …

Do Medicaid Data Accurately Reflect The Expenditures And Outcomes For Extremely Premature Infants?, Elenir B C Avritscher, Jon E Tyson, Therese A Stukel, Youngran Kim, Cecilia Ganduglia Cazaban, Kanekal S Gautham, David Lynch, David C Goodman

Faculty, Staff and Student Publications

The accurate and meaningful assessment of Medicaid expenditures relative to survival rates among Medicaid-eligible extremely premature infants has received little scrutiny, despite its importance for improving outcomes. We have identified key problems that hindered such assessments using Texas Medicaid data, which may also be relevant to other states.

Maternal Sleep Disorders And Maternal And Birth Outcomes: A Retrospective Us Claims-Based Study, Anayeli Herrera Morales, Audrey C Choh, Cici X Bauer, Stefan A Czerwinski, Miryoung Lee

Faculty, Staff and Student Publications

Introduction: Sleep disturbances are commonly reported during pregnancy and have been associated with adverse maternal, fetal, and neonatal outcomes. However, self-reported sleep disturbances may not be accurately reflected in the prevalence of clinically diagnosed sleep disorders.

Methods: Using Optum's de-identified Clinformatics Data Mart Database, we conducted a cross-sectional study of 93,767 American women who were pregnant with singletons between January 1, 2015 and June 30, 2021, to (1) determine the prevalence of clinically diagnosed sleep disorders and breathing abnormalities; (2) examine their associations with maternal health outcomes; and (3) examine their associations with birth outcomes. Sleep disorders and breathing abnormalities …

Genome-Wide Association Study Provides Novel Insight Into The Genetic Architecture Of Severe Obesity, Mohanraj Krishnan, Mohammad Yaser Anwar, Anne E Justice, Geetha Chittoor, Hung-Hsin Chen, Rashedeh Roshani, Alyssa Scartozzi, Rachel R Dickerson, Roelof A J Smit, Michael H Preuss, Nathalie Chami, Benjamin S Hadad, Esteban J Parra, Miguel Cruz, Qin Hui, Peter W F Wilson, Yan V Sun, Xiaoyu Zhang, Gregorio V Linchangco, Sharon L R Kardia, Jessica D Faul, David R Weir, Lawrence F Bielak, Heather M Highland, Kristin L Young, Baiyu Qi, Yujie Wang, Myriam Fornage, Christopher Haiman, Iona Cheng, Ulrike Peters, Charles Kooperberg, Steven Buyske, Joseph B Mccormick, Susan P Fisher-Hoch, Frida Lona-Durazo, Jesus Peralta, Jamie Gomez-Zamudio, Stephen S Rich, Kendra R Ferrier, Ethan M Lange, Christopher R Gignoux, Eimear E Kenny, Genevieve L Wojcik, Kelly Cho, Michael J Gaziano, Luc Djousse, Shuwei Liu, Dhananjay Vaidya, Renée De Mutsert, Navya S Josyula, Christopher R Bauer, Wei Zhao, Ryan W Walker, Jennifer A Smith, Leslie A Lange, Mariah C Meyer, Ching-Ti Liu, Lisa R Yanek, Miryoung Lee, Laura M Raffield, Ruth J F Loos, Penny Gordon-Larsen, Jennifer E Below, Kari E North, Mariaelisa Graff

The Brown Foundation: Institute of Molecular Medicine

Severe obesity (SevO) is a primary driver of cardiovascular diseases (CVD), cardiometabolic diseases (CMD) and several cancers, with a disproportionate impact on marginalized populations. SevO is an understudied global health disease, limiting knowledge about its mechanisms and impacts. In genome-wide association study (GWAS) meta-analyses of the tail end of the BMI distribution (≥95th percentile BMI) and two SevO phenotypes [Obesity Class III BMI ≥ 40 kg/m2 and Obesity Class IV BMI ≥ 50 kg/m2] in 159,359 individuals across eleven ancestrally diverse population-based studies followed by replication in 480,897 individuals across six ancestrally diverse studies, we identified and replicated three novel …

Utilization Of Outpatient Mental Health Services During And 2 Years After The Covid-19 Pandemic, Michelle A Hayek, Hye-Chung Kum, Sulki Park, Robert Ohsfeldt, Mark A Lawley, Michelle J Bovin

The Brown Foundation: Institute of Molecular Medicine

Objective: Analyze the impact of COVID-19 on outpatient mental health (OP-MH) utilization patterns, particularly telehealth, across eight different MH conditions with a 2-year follow-up.

Methods: This population-based cohort study uses a 5% random sample of Medicare beneficiaries aged ≥18 and newly diagnosed with one of the eight MH disorders: psychotic, depressive, bipolar, anxiety, trauma-related, substance-use, other MH disorders, and two or more MH disorders. Monthly OP-MH utilization patterns were compared among patients in 2020-2021 newly diagnosed in 2019 to comparable prepandemic cohorts newly diagnosed in 2017. Multiple logistic regression models were conducted to examine differences in telehealth utilization across MH …

Preoperative Focused Echocardiography On Patients With Fractured Neck Of Femur. Echonof-Iii Trial: Study Protocol For A Multicenter Randomized Controlled Trial, Ximena Cid-Serra, Alistair Royse, Andrea Bowyer, David Canty, Daniel Sessler, Sandy Clarke-Errey, Andre Denault, Dina Logiudice, Guy Ludbrook, D-Yin Lin, Yang Yang, Kavi Haji, Lisa Zucherrelli, Andrew J Palmer, Benjamin Piper, Thar Nyan Lwin, Stefan Dieleman, David Eccleston, Alwin Chuan, Richard Cooper, Gregory Henderson, Colin Royse

Faculty, Staff and Student Publications

Background: Hip fractures are common in older people and are associated with high perioperative mortality. Prompt surgical intervention within the first 48 h of fraction reduces complications; however, surgical urgency often precludes a comprehensive preoperative cardiac evaluation. Preliminary data suggests that performing a focused cardiac ultrasound (FCU) before surgery may reduce postoperative complications. We therefore propose to test the primary hypothesis that FCU reduces a 30-day composite of mortality and serious complications.

Methods: We plan a definitive multicenter pragmatic randomized trial that will enroll 2000 adults with hip fractures. Participants will be randomized before surgery to either receive FCU as …

Polygenic Prediction Of Body Mass Index And Obesity Through The Life Course And Across Ancestries, Roelof A J Smit, Kaitlin H Wade, Qin Hui, Joshua D Arias, Xianyong Yin, Malene R Christiansen, Loic Yengo, Michael H Preuss, Mariam Nakabuye, Ghislain Rocheleau, Sarah E Graham, Victoria L Buchanan, Geetha Chittoor, Marielisa Graff, Marta Guindo-Martínez, Yingchang Lu, Eirini Marouli, Saori Sakaue, Cassandra N Spracklen, Sailaja Vedantam, Emma P Wilson, Shyh-Huei Chen, Teresa Ferreira, Yingjie Ji, Tugce Karaderi, Kreete Lüll, Moara Machado, Deborah E Malden, Carolina Medina-Gomez, Amy Moore, Sina Rüeger, Masato Akiyama, Matthew A Allison, Marcus Alvarez, Mette K Andersen, Vivek Appadurai, Liubov Arbeeva, Eric Bartell, Seema Bhaskar, Lawrence F Bielak, Joshua C Bis, Sailalitha Bollepalli, Jette Bork-Jensen, Jonathan P Bradfield, Yuki Bradford, Caroline Brandl, Peter S Braund, Jennifer A Brody, Ulrich Broeckel, Kristoffer S Burgdorf, Brian E Cade, Qiuyin Cai, Silvia Camarda, Archie Campbell, Marisa Cañadas-Garre, Jin-Fang Chai, Alessandra Chesi, Seung Hoan Choi, Paraskevi Christofidou, Christian Couture, Gabriel Cuellar-Partida, Rebecca Danning, Frauke Degenhardt, Graciela E Delgado, Alessandro Delitala, Ayşe Demirkan, Xuan Deng, Alexander Dietl, Maria Dimitriou, Latchezar Dimitrov, Rajkumar Dorajoo, Fabian Eichelmann, Anders U Eliasen, Jorgen E Engmann, Michael R Erdos, Zammy Fairhurst-Hunter, Aliki-Eleni Farmaki, Jessica D Faul, Juan-Carlos Fernandez-Lopez, Lukas Forer, Mirjam Frank, Sandra Freitag-Wolf, Lars G Fritsche, Christian Fuchsberger, Tessel E Galesloot, Yan Gao, Frank Geller, Olga Giannakopoulou, Franco Giulianini, Anette P Gjesing, Anuj Goel, Scott D Gordon, Mathias Gorski, Jakob Grove, Xiuqing Guo, Stefan Gustafsson, Jeffrey Haessler, Thomas F Hansen, Aki S Havulinna, Simon J Haworth, Nancy Heard-Costa, Daiane Hemerich, Heather M Highland, George Hindy, Yuk-Lam Ho, Edith Hofer, Elizabeth Holliday, Katrin Horn, Whitney E Hornsby, Jouke-Jan Hottenga, Hongyan Huang, Jie Huang, Alicia Huerta-Chagoya, Shaofeng Huo, Mi Yeong Hwang, Chii-Min Hwu, Hiroyuki Iha, Daisuke D Ikeda, Masato Isono, Anne U Jackson, Iris E Jansen, Yunxuan Jiang, Ingegerd Johansson, Anna Jonsson, Torben Jørgensen, Ioanna P Kalafati, Masahiro Kanai, Stavroula Kanoni, Line L Kårhus, Anuradhani Kasturiratne, Tomohiro Katsuya, Takahisa Kawaguchi, Rachel L Kember, Katherine A Kentistou, Daeeun Kim, Han-Na Kim, Young Jin Kim, Marcus E Kleber, Maria J Knol, Azra Kurbasic, Marie Lauzon, Phuong Le, Rodney Lea, Jong-Young Lee, Wen-Jane Lee, Hampton L Leonard, Hengtong Li, Shengchao A Li, Xiaohui Li, Xiaoyin Li, Jingjing Liang, Honghuang Lin, Kuang Lin, Jun Liu, Xueping Liu, Ken Sin Lo, Jirong Long, Laura Lores-Motta, Jian'an Luan, Valeriya Lyssenko, Leo-Pekka Lyytikäinen, Anubha Mahajan, Md Zubbair Malik, Vasiliki Mamakou, Massimo Mangino, Ani Manichaikul, Jonathan Marten, Manuel Mattheisen, Aaron F Mcdaid, Quanshun Mei, Heike Meiselbach, Tori L Melendez, Yuri Milaneschi, Jason E Miller, Iona Y Millwood, Pashupati P Mishra, Ruth E Mitchell, Line T Møllehave, Nina Mononen, Sören Mucha, Matthias Munz, Juha Mykkänen, Masahiro Nakatochi, Giuseppe Giovanni Nardone, Christopher P Nelson, Maria Nethander, Chu Won Nho, Aneta A Nielsen, Ilja M Nolte, Suraj S Nongmaithem, Raymond Noordam, Ioanna Ntalla, Teresa Nutile, Anita Pandit, Marc Pauper, Eva R B Petersen, Liselotte V Petersen, Francesco Piluso, Ozren Polašek, Alaitz Poveda, Saiju Pyarajan, Laura M Raffield, Hiromi Rakugi, Julia Ramirez, Asif Rasheed, Dennis Raven, Nigel W Rayner, Carlos Riveros, Rebecca Rohde, Daniela Ruggiero, Sanni E Ruotsalainen, Kathleen A Ryan, Maria Sabater-Lleal, Aurora Santin, Richa Saxena, Markus Scholz, Botong Shen, Jingchunzi Shi, Jae Hun Shin, Carlo Sidore, Julia Sidorenko, Xueling Sim, Roderick C Slieker, Albert V Smith, Jennifer A Smith, Laura J Smyth, Lorraine Southam, Valgerdur Steinthorsdottir, Liang Sun, Fumihiko Takeuchi, Kent D Taylor, Bamidele O Tayo, Catherine Tcheandjieu, Natalie Terzikhan, Paola Tesolin, Alexander Teumer, Elizabeth Theusch, Deborah J Thompson, Gudmar Thorleifsson, Paul R H J Timmers, Stella Trompet, Constance Turman, Simona Vaccargiu, Sander W Van Der Laan, Peter J Van Der Most, Jan B Van Klinken, Jessica Van Setten, Shefali S Verma, Niek Verweij, Yogasudha Veturi, Carol A Wang, Chaolong Wang, Jun-Sing Wang, Lihua Wang, Ya Xing Wang, Zhe Wang, Helen R Warren, Wen Bin Wei, Wanqing Wen, William A Wheeler, Ananda R Wickremasinghe, Matthias Wielscher, Bendik S Winsvold, Andrew Wong, Matthias Wuttke, Rui Xia, Ken Yamamoto, Jingyun Yang, Jie Yao, Hannah Young, Noha A Yousri, Lei Yu, Lingyao Zeng, Weihua Zhang, Xinyuan Zhang, Jing-Hua Zhao, Wei Zhao, Wei Zhou, Martina E Zimmermann, Magdalena Zoledziewska, Leen M 'T Hart, Linda S Adair, Hieab H H Adams, Carlos A Aguilar-Salinas, Fahd Al-Mulla, Donna K Arnett, Folkert W Asselbergs, Bjørn Olav Åsvold, John Attia, Bernhard Banas, Stefania Bandinelli, Lawrence J Beilin, David A Bennett, Tobias Bergler, Dwaipayan Bharadwaj, Ginevra Biino, Eric Boerwinkle, Carsten A Böger, Judith B Borja, Claude Bouchard, Donald W Bowden, Ivan Brandslund, Ben Brumpton, Julie E Buring, Mark J Caulfield, John C Chambers, Giriraj R Chandak, Stephen J Chanock, Nish Chaturvedi, Yii-Der Ida Chen, Zhengming Chen, Ching-Yu Cheng, Yoon Shin Cho, Kaare Christensen, Ingrid E Christophersen, Marina Ciullo, John W Cole, Francis S Collins, Maria Pina Concas, Richard S Cooper, Miguel Cruz, Francesco Cucca, Michael J Cutler, Scott M Damrauer, Thomas M Dantoft, Gert J De Borst, Eco J C De Geus, Lisette C P G M De Groot, Philip L De Jager, Dominique P V De Kleijn, H Janaka De Silva, George V Dedoussis, Anneke I Den Hollander, Shufa Du, Douglas F Easton, Kai-Uwe Eckardt, Petra J M Elders, A Heather Eliassen, Patrick T Ellinor, Sölve Elmståhl, Jeanette Erdmann, Michele K Evans, Diane Fatkin, Bjarke Feenstra, Mary F Feitosa, Luigi Ferrucci, Jose C Florez, Ian Ford, Myriam Fornage, Andre Franke, Paul W Franks, Barry I Freedman, Christian Gieger, Giorgia Girotto, Yvonne M Golightly, Clicerio Gonzalez-Villalpando, Penny Gordon-Larsen, Harald Grallert, Struan F A Grant, Niels Grarup, Lyn Griffiths, Vilmundur Gudnason, Christopher Haiman, Hakon Hakonarson, Torben Hansen, Catharina A Hartman, Andrew T Hattersley, Caroline Hayward, Iris M Heid, Chew-Kiat Heng, Christian Hengstenberg, Karl-Heinz Herzig, Alex W Hewitt, Haretsugu Hishigaki, David M Hougaard, Carel B Hoyng, Paul L Huang, Wei Huang, Wen-Yi Huang, Jennifer E Huffman, Steven C Hunt, Nina Hutri, Kristian Hveem, Elina Hyppönen, William G Iacono, Sahoko Ichihara, M Arfan Ikram, Carmen R Isasi, Marjo-Riitta Jarvelin, Zi-Bing Jin, Karl-Heinz Jöckel, Jost B Jonas, Peter K Joshi, Pekka Jousilahti, J Wouter Jukema, Mika Kähönen, Yoichiro Kamatani, Kui Dong Kang, Jaakko Kaprio, Sharon L R Kardia, Fredrik Karpe, Norihiro Kato, Maryam Kavousi, Frank Kee, Thorsten Kessler, Amit V Khera, Chiea Chuen Khor, Lambertus A L M Kiemeney, Bong-Jo Kim, Eung Kweon Kim, Hyung-Lae Kim, Paulus Kirchhof, Mika Kivimaki, Woon-Puay Koh, Heikki A Koistinen, Alexander Kokkinos, Jaspal S Kooner, Charles Kooperberg, Peter Kovacs, Adriaan Kraaijeveld, Peter Kraft, Ronald M Krauss, Meena Kumari, Zoltan Kutalik, Markku Laakso, Leslie A Lange, Claudia Langenberg, Lenore J Launer, Hyejin Lee, Nanette R Lee, Terho Lehtimäki, Rozenn N Lemaitre, Huaixing Li, Liming Li, Wolfgang Lieb, Xu Lin, Lars Lind, Allan Linneberg, Ching-Ti Liu, Jianjun Liu, Markus Loeffler, Barry London, Fan Lu, Steven A Lubitz, David A Mackey, Patrik K E Magnusson, Joann E Manson, Gregory M Marcus, Pedro Marques Vidal, Nicholas G Martin, Winfried März, Fumihiko Matsuda, Mark I Mccarthy, Robert W Mcgarrah, Matt Mcgue, Amy Jayne Mcknight, Sarah E Medland, Dan Mellström, Andres Metspalu, Braxton D Mitchell, Paul Mitchell, Dennis O Mook-Kanamori, Trevor A Mori, Andrew D Morris, Lorelei A Mucci, Patricia B Munroe, Mike A Nalls, Saman Nazarian, Amanda E Nelson, Matt J Neville, Christopher Newton-Cheh, Christopher S Nielsen, Harri Niinikoski, Kjell Nikus, Markus M Nöthen, Adesola Ogunniyi, Claes Ohlsson, Albertine J Oldehinkel, Lorena Orozco, Katja Pahkala, Päivi Pajukanta, Colin N A Palmer, Esteban J Parra, Cristian Pattaro, Oluf Pedersen, Craig E Pennell, Brenda W J H Penninx, Louis Perusse, Annette Peters, Patricia A Peyser, David J Porteous, Danielle Posthuma, Chris Power, Peter P Pramstaller, Michael A Province, Bruce M Psaty, Qibin Qi, Jia Qu, Daniel J Rader, Olli T Raitakari, Loukianos S Rallidis, Dabeeru C Rao, Susan Redline, Dermot F Reilly, Alexander P Reiner, Sang Youl Rhee, Paul M Ridker, Michiel Rienstra, Samuli Ripatti, Marylyn D Ritchie, Fernando Rivadeneira, Dan M Roden, Frits R Rosendaal, Jerome I Rotter, Igor Rudan, Femke Rutters, Seungho Ryu, Charumathi Sabanayagam, Babatunde Salako, Danish Saleheen, Veikko Salomaa, Nilesh J Samani, Dharambir K Sanghera, Naveed Sattar, Börge Schmidt, Helena Schmidt, Reinhold Schmidt, Matthias B Schulze, Heribert Schunkert, Laura J Scott, Rodney J Scott, Peter Sever, Wayne H H Sheu, M Benjamin Shoemaker, Xiao-Ou Shu, Eleanor M Simonsick, Mario Sims, Andrew B Singleton, Moritz F Sinner, J Gustav Smith, Harold Snieder, Tim D Spector, Beatrice Spedicati, Meir J Stampfer, Klaus J Stark, David P Strachan, Yasuharu Tabara, E Shyong Tai, Hua Tang, Jean-Claude Tardif, Thangavel A Thanaraj, Anke Tönjes, Tiinamaija Tuomi, Jaakko Tuomilehto, Maria-Teresa Tusié-Luna, Rob M Van Dam, Pim Van Der Harst, Nathalie Van Der Velde, Cornelia M Van Duijn, Natasja M Van Schoor, Veronique Vitart, Marie-Claude Vohl, Uwe Völker, Peter Vollenweider, Henry Völzke, Scott Vrieze, Niels H Wacher-Rodarte, Mark Walker, Gurpreet S Wander, Nicholas J Wareham, Richard M Watanabe, Hugh Watkins, David R Weir, Thomas M Werge, Elisabeth Widen, Gonneke Willemsen, Walter C Willett, James F Wilson, Peter W F Wilson, Tien Y Wong, Jeong-Taek Woo, Alan F Wright, Huichun Xu, Chittaranjan S Yajnik, Jian Yang, Mitsuhiro Yokota, Jian-Min Yuan, Eleftheria Zeggini, Babette S Zemel, Wei Zheng, Xiaofeng Zhu, M Carola Zillikens, Alan B Zonderman, John-Anker Zwart, Goncalo R Abecasis, Themistocles L Assimes, Adam Auton, Michael Boehnke, Daniel I Chasman, Tõnu Esko, Kari Stefansson, Guillaume Lettre, Cecilia M Lindgren, Maggie C Y Ng, Christopher J O'Donnell, Unnur Thorsteinsdottir, Peter M Visscher, Robin G Walters, Thomas W Winkler, Andrew R Wood, Panos Deloukas, Timothy M Frayling, Anne E Justice, Tuomas O Kilpeläinen, Adam E Locke, Karen L Mohlke, Kari E North, Yukinori Okada, Cristen J Willer, Kristin L Young, Segun Fatumo, Jeanne M Mccaffery, Nicholas J Timpson, Joel N Hirschhorn, Yan V Sun, Sonja I Berndt, Ruth J F Loos

Faculty, Staff and Student Publications

Polygenic scores (PGSs) for body mass index (BMI) may guide early prevention and targeted treatment of obesity. Using genetic data from up to 5.1 million people (4.6% African ancestry, 14.4% American ancestry, 8.4% East Asian ancestry, 71.1% European ancestry and 1.5% South Asian ancestry) from the GIANT consortium and 23andMe, Inc., we developed ancestry-specific and multi-ancestry PGSs. The multi-ancestry score explained 17.6% of BMI variation among UK Biobank participants of European ancestry. For other populations, this ranged from 16% in East Asian-Americans to 2.2% in rural Ugandans. In the ALSPAC study, children with higher PGSs showed accelerated BMI gain from …

Chest X-Ray Interpretation In The Epico Pediatric Covid-19 Study: Addressing Misconceptions, Luis Miguel Navarro-Ramirez, Pablo Vásquez-Hoyos, María Lucía Mesa-Rubio, Melisa Naranjo Vanegas, Daniela Duarte-Montero, Claudia Burgos, Laura Melissa Mendez, María Margarita Rodriguez, Arianna Martinez, Paola Sanchez, Carolina Tovar, Gabriela Friedrich, Gustavo Adolfo Triana-Rodriguez, Mónica Royero-Arias, Jessica Echeverry, Tamara Gamo, Luz Ángela Moreno, Olga Lucía Baquero, Luz Marina Mejía, Sonia Restrepo-Gualteros, Sergio Moreno-Lopez, Juan Gabriel Piñeros, Carlos Álvarez-Moreno, Alejandro Díaz-Díaz, Iván Felipe Gutierrez, Clara Galvis-Diaz, José Manuel Nieto, Irati Gastesi, Cinta Moraleda, Alfredo Tagarro García, Andrea Ramirez Varela, Epico‐Colombia And Epico‐Aep Working Groups

Faculty, Staff and Student Publications

No abstract provided.

Five-Year Change In Sleep Duration And Incident Alzheimer’S Disease And Related Dementias Among Lower-Income Older Adults, Hui Shi, Loren Lipworth, Qian Xiao, Xijing Han, Michael Mumma, Laura M Keohane, Danxia Yu, Corey J Bolton, Derek B Archer, Timothy J Hohman, Kelsie M Full

Faculty, Staff and Student Publications

Introduction: Little is known about change in sleep duration over time and Alzheimer's Disease and Related Dementias (ADRD) risk.

Methods: ADRD cases were identified among Southern Community Cohort Study participants enrolled in Medicare. Sleep duration was reported at enrollment and first study follow-up and categorized (short (< 7 hours), recommended (7-9) and long (> 9)), change was calculated between timepoints. Adjusted Cox proportional hazards regression was used to estimate hazard ratios (HRs, 95% CIs) for incident ADRD.

Results: We identified 2,093 ADRD cases among 17,945 participants. Compared to maintaining optimal sleep duration (7-9 hours) over 5 years, suboptimal changes were associated with 20-69% greater ADRD risk: adjusted …

Steroid Hormone Biosynthesis And Dietary Related Metabolites Associated With Excessive Daytime Sleepiness, Tariq Faquih, Kaitlin S Potts, Pavithra Nagarajan, Bing Yu, Robert Kaplan, Carmen R Isasi, Qibin Qi, Kent D Taylor, Peter Y Liu, Satu J Strausz, Hanna M Ollila, Tianyi Huang, Russell P Tracy, Craig Johnson, Stephen S Rich, Clary B Clish, Jerome I Rotter, Susan Redline, Tamar Sofer, Heming Wang

Faculty, Staff and Student Publications

Background: Excessive daytime sleepiness (EDS) is a complex sleep problem that affects approximately 33% of the United States population. Although EDS usually occurs in conjunction with insufficient sleep and other sleep and circadian disorders, recent studies have shown unique genetic markers and metabolic pathways underlying EDS. Here, we aimed to further elucidate the biological profile of EDS using large-scale single- and pathway-level metabolomics analyses.

Methods: Metabolomics data were available for 877 metabolites in 6071 individuals from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). EDS was assessed using the Epworth Sleepiness Scale (ESS) questionnaire. We performed linear regression for each …

Proximity-Dependent Proteomics And Network Analysis Of Adenylyl Cyclase Isoforms 5, 6, And 9 In Cardiomyocytess, Taeyeop Park, Yong Li, Neha Arora, Anibal Garza-Carbajal, Karen Colwill, Cassandra J Wong, Yong Zhou, Carmen W Dessauer

Faculty, Staff and Student Publications

cAMP influences multiple aspects of cardiac biology, including the regulation of contraction, relaxation, and overall stress responses. The functional outcomes of cAMP are driven by the spatial arrangement of enzymes that produce and degrade cAMP (adenylyl cyclase [AC] and phosphodiesterase, respectively), together with the downstream targets of cAMP. We performed proximity-dependent biotin identification (BioID) of near-neighbor interactions proteomics in cardiomyocytes to generate proximity maps for three cardiac AC isoforms. Processing and trafficking functions were the most common gene ontology terms for ACs, with AC5 and AC6 generating unique proximal protein sets compared to AC9. AC5/6 proximal proteins showed significant localization …

Buprenorphine Salivary Gland Accumulation Sustaining High Oral Fluid Exposure And Increasing The Risk Of Streptococcus Mutans Biofilm Formation, Zicong Zheng, Jie Chen, Songpol Srinual, Vesna Tumbas Šaponjac, Taijun Yin, Bing-Yan Wang, Rongjin Sun, Ming Hu

Faculty, Staff and Student Publications

Objectives: The US Food and Drug Administration (FDA) issued a warning about buprenorphine-induced dental caries of unknown mechanism in 2022. To investigate the potential mechanism, the association between local buprenorphine exposure and dental biofilm formation will be explored in this study.

Methods: Female F344 rats were dosed with sublingual buprenorphine film or intravenous injection to explore the oral cavity exposure of the buprenorphine. The buprenorphine distribution in salivary glands after the sublingual and intravenous administration was also evaluated. To investigate the effects of buprenorphine exposure on dental caries formation, buprenorphine's impact on the biofilm formation of S. mutans in vitro …

Mechanisms Underlying Treatment-Resistant Depression: Exploring Sex-Based Biological Differences, Francisco E R Da Silva, Atakan Yucel, Antonio P M Menezes, Ana C Ruiz, Marcela C Carbajal Tamez, Tatiana Barichello, Giselli Scaini, Joao Quevedo

Faculty, Staff and Student Publications

Treatment-resistant depression (TRD) represents a severe and complex subtype of major depressive disorder (MDD), affecting approximately 30% of patients who fail to respond adequately to multiple standard antidepressant therapies. While the pathophysiology of TRD remains incompletely understood, emerging evidence suggests that sex-based biological differences might influence its onset, progression, and treatment response. Women are disproportionately affected by depression and are more likely to experience residual symptoms and treatment resistance, potentially due to hormonal fluctuations, immune system differences, and variations in brain circuitry and neuroplasticity. This narrative explores the current literature on the mechanisms underlying TRD, with a particular emphasis on …

Variational Temporal Deconfounder Network For Individualized Treatment Effect Estimation With Longitudinal Observational Data, Hao Dai, Yu Huang, Yuxi Liu, Xing He, Jingchuan Guo, Mattia Prosperi, Jiang Bian

Faculty, Staff and Student Publications

Objective: By leveraging real-world electronic health record (EHR) data, this study set out to estimate individualized treatment effects (ITE) in longitudinal observational settings to advance personalized medicine, addressing key challenges that are often observed in real-world clinical scenarios and pose statistical challenges, including hidden confounding and dynamic treatment regimens.

Methods: We propose the Variational Temporal Deconfounder Network (VTDNet), a novel framework designed to account for time-varying hidden confounding using a variational recurrent transformer-based autoencoder. Specifically, VTDNet comprises three critical components: a temporal Encoder-Decoder structure to capture hidden representation, a Treatment Block that captures interdependencies among multiple treatments, and a Potential …

Sex Differences In The Treatment With Pcsk9 Monoclonal Antibodies- Real World Experience From A Dedicated Preventive Cardiology Clinic, Lital Hodeda, Alon Eisen, Aviad Rotholz, Ran Kornowski, Chen Gurevitz

Faculty, Staff and Student Publications

Purpose: Proprotein convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9 mAb) lower low-density lipoprotein cholesterol (LDL-C) levels and reduce atherosclerotic cardiovascular disease (ASCVD). Data regarding sex differences in PCSK9 mAb treatment remain lacking. This study examines sex differences in patients' characteristics, indications, efficacy, and safety of PCSK9 mAb treatment.

Methods: Retrospective study based on data from the Preventive Cardiology and Lipids Clinic in Rabin Medical Center on patients prescribed with PCSK9 mAb. Collected data included medical background, medications, indications and laboratory data, analyzed by sex.

Results: 246 patients were included (mean age 67y, ASCVD 78.8 %, mean baseline LDL-C 128.2 mg/dL). …

Role Of Exchange Proteins Directly Activated By Camp Signaling In Vascular Remodeling, Xiaodong Cheng, Hua Liu, Wenbo Zhang, Wenli Yang, Fang Mei

Faculty, Staff and Student Publications

Vascular remodeling is a complex process involving the coordinated actions of multiple cellular signaling pathways in various cell types, leading to structural and functional changes in blood vessels. These changes can be adaptive, as in wound healing, or maladaptive, as seen in chronic vascular diseases such as atherosclerosis, hypertension, and retinopathy. Exchange proteins directly activated by cAMP (EPACs) are key players in cAMP-mediated cell signaling, distinct from the more traditionally studied protein kinase A pathway. EPAC proteins are guanine nucleotide exchange factors for the small G proteins Rap1 and Rap2. Recent studies have also revealed noncanonical functions of EPAC1 involving …

Immune Impacts Of Fire Smoke Exposure, Mary M Johnson, Abhinav Kaushik, Olivia A Kline, Eric M Smith, Xiaoying Zhou, Yagiz Pat, Laura Buergi, Juan Aguilera, Shifaa Alkotob, Elisabeth M Simonin, Alberto Favaro, Miguel Couto, Oscar Bennett, R Sharon Chinthrajah, Ella Parsons, Mohamed Shamji, Marshall Burke, Melissa Bondy, Mubeccel Akdis, Cezmi A Akdis, Kari C Nadeau

Faculty, Staff and Student Publications

Fire smoke exposure has become a global health concern and is associated with increased morbidity and mortality. There is a lack of understanding of the specific immune mechanisms involved in smoke exposure with preventative and targeted interventions needed. After exposure to fire smoke, which includes PM2.5, toxic metals and per- and polyfluoroalkyl substances (PFAS), epidemiology-based studies demonstrate increases in respiratory (e.g. asthma exacerbations), cardiac (e.g. myocardial infarctions, arrhythmias), neurologic (e.g. stroke) and pregnancy-related (e.g. low birthweight, premature births) outcomes. However, mechanistic studies exploring how smoke exposure disrupts cellular homeostasis are lacking. Therefore, we collected blood from smoke-exposed individuals (n …

Outcomes In Systemic Sclerosis-Associated Interstitial Lung Disease Based On Serological Profiles With A Focus On Anticentromere And Anti-Rna Polymerase Iii Antibodies, Elizabeth R Volkmann, Shervin Assassi, Christopher P Denton, Rozeta Simonovska, Steven Sambevski, Margarida Alves, Elana J Bernstein

Faculty, Staff and Student Publications

Objective: We aimed to compare the progression of systemic sclerosis-associated interstitial lung disease (SSc-ILD) based on serological status.

Methods: In a posthoc analysis of the SENSCIS trial (nintedanib vs placebo in SSc-ILD; ClinicalTrials.gov: NCT02597933), we analyzed the rate of decline in forced vital capacity (FVC) over 52 weeks in 3 subsets: (1) positive for anticentromere antibody (ACA), (2) positive for anti-RNA polymerase III antibody (ARA), and (3) negative for ACA, ARA, and antitopoisomerase I antibody (ATA).

Results: Among study participants who underwent baseline serological evaluation, 32/549 (5.8%) were ACA positive, 98/528 (18.6%) were ARA positive, and 127/526 (24.1%) were …

Ixekizumab Improves Signs, Symptoms, And Quality Of Life In Patients With Axial Spondyloarthritis Irrespective Of Symptom Duration, Victoria Navarro-Compán, John D Reveille, Proton Rahman, José A Maldonado-Cocco, Marina Magrey, Rebecca Bolce, Tommaso Panni, Andris Kronbergs, Martin Rudwaleit

Faculty, Staff and Student Publications

Introduction: The objective of this study was to assess treatment response to ixekizumab, an interleukin-17A antagonist, by shorter versus longer symptom duration (< 5 years vs. ≥ 5 years) in patients with radiographic axial spondyloarthritis (r-axSpA) and non-radiographic axial spondyloarthritis (nr-axSpA) up to 52 weeks.

Methods: This post hoc analysis used data from three randomized, placebo-controlled trials including patients with r-axSpA from COAST-V [biologic disease-modifying anti-rheumatic drug (bDMARD)-naïve] and COAST-W (tumor necrosis factor inhibitor-experienced) and patients with nr-axSpA from COAST-X (bDMARD-naïve). Patients received ixekizumab (80 mg every 2 or 4 weeks) or placebo through Week 16 and ixekizumab to Week 52. Assessments included the Assessment in SpondyloArthritis international Society 40% improvement (ASAS40) and Axial Spondyloarthritis Disease Activity Score (ASDAS) low disease activity …

Intraoperative Pain Management Shared Decision Making With A Patient With A Complex Pain And Mental Health History: A Case Report, Aubrey Samost-Williams, Jerry Wang, Casey Horani, Eric J Thomas, Robert J Volk

Faculty, Staff and Student Publications

Shared decision making is where the patient and clinician come together to decide on the appropriate course of action in a patient's medical care based on their goals, preferences, and values. Typically, decision making in anesthesia remains more paternalistic, with clinicians making decisions for patients. However, there is a move towards embracing a shared decision making model. We present here a case report of using shared decision making principles to develop a pain and anxiety management plan in a patient with chronic pain and a complex mental health history. A 40-year-old female with a history of chronic pain, bipolar disorder, …

Code Telestroke: On The Necessity Of Formalizing Training In Telestroke For Future Vascular Neurologists, Amanda L Jagolino-Cole, Christina Mijalski, Amy Katherine Guzik

Faculty, Staff and Student Publications

No abstract provided.

Is Our Assessment Of Bias In Academics … Biased?, Sunil A Sheth, Ashutosh P Jadhav, Tudor G Jovin

Faculty, Staff and Student Publications

No abstract provided.