Medicine and Health Sciences Commons^™

Detection Of Cancers Three Years Prior To Diagnosis Using Plasma Cell-Free Dna, Yuxuan Wang, Corinne E Joshu, Samuel D Curtis, Christopher Douville, Vernon A Burk, Meng Ru, Maria Popoli, Janine Ptak, Lisa Dobbyn, Natalie Silliman, Josef Coresh, Eric Boerwinkle, Anna Prizment, Chetan Bettegowda, Kenneth W Kinzler, Nickolas Papadopoulos, Elizabeth A Platz, Bert Vogelstein

Faculty, Staff and Student Publications

To explore how early can cancers be detected prior to clinical signs or symptoms, we assessed prospectively collected serial plasma samples from the Atherosclerosis Risk in Communities (ARIC) study, including 26 participants diagnosed with cancer and 26 matched controls. At the index time point, eight of these 52 participants scored positively with a multicancer early detection (MCED) test. All eight participants were diagnosed with cancer within 4 months after blood collection. In six of these 8 participants, we were able to assess an earlier plasma sample collected 3.1 to 3.5 years prior to clinical diagnosis. In four of these six …

Risk Of Clonal Hematopoiesis In Families Exposed To Radiation Following The Chornobyl Accident, Mitchell J Machiela, Irenaeus Chan, Kelly Bolton, Et Al.

2020-Current year OA Pubs

Radiation exposure is a well-established risk factor for leukemia. Clonal hematopoiesis (CH), the expansion of mutated hematopoietic cells, is also associated with increased leukemia risk and its frequency is higher in cancer patients following radiotherapy and chemotherapy. We investigated whether low to moderate environmental ionizing radiation determined by state-of-the-art dosimetric analysis was associated with CH in the Chornobyl Family Study (CFS). Our study conducted targeted high-depth sequencing and array genotyping to identify and characterize clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) in 882 participants from 292 CFS families. Fathers had mean bone marrow radiation doses of …

Social Determinants Of Health In Lesbian, Gay, Bisexual, Transgender, Queer, And Other Sexual And Gender Minority (Lgbtq+) Older Adults: Impact Of Socioeconomic Disadvantage On Inpatient Hospitalizations, Jennifer T. May Phd, Rn, Anp-Bc, Devon Noonan, Susan G. Silva

Publications

Introduction

Little is known about the impact of socioeconomic disadvantage on lesbian, gay, bisexual, transgender, queer, and other sexual and gender minority (LGBTQ+) older adults (≥50 years). The aim of this study is to determine whether the distribution of LGBTQ+ inpatient hospitalizations are related to structural socioeconomic factors.

Methods

A secondary analysis of retrospective electronic health record data for LGBTQ+ older adults hospitalized from 2018 to 2022 was conducted at one large health system. The average county area deprivation index where the patient resided was calculated.

Results

The analysis included 2270 LGBTQ+ older adult inpatient hospitalizations, with 1508 (66.4%) from …

Intronic Fgf14 Gaa Repeat Expansions Impact Progression And Survival In Multiple System Atrophy., Viorica Chelban, David Pellerin, Nirosen Vijiaratnam, Hamin Lee, Yen Yee Goh, Lauren Brown, Sara Sambin, Danielle Seilhean, Stephane Lehericy, Pablo Iruzubieta, Rahema Mohammad, Eleanor Self, Annarita Scardamaglia, Cameron Lee, Miriama Ostrozovicova, Marie-Josée Dicaire, Christine Girges, Emil K. Gustavsson, David Murphy, Toby Curless, Joshua Laß, Joanne Trinh, Timothy Rittman, James B. Rowe, Marios Hadjivassiliou, Neil Archibald, Matt C. Danzi, Catherine Ashton, Virginie Roth, Marion Wandzel, Warren A. Cheung, Djordje O. Gveric, Bart De Vil, Jordan Follett, P Nigel Leigh, Lukas Beichert, Tomi Pastinen, Céline Bonnet, Mathilde Renaud, Wassilios G. Meissner, Anne Sieben, David Crosiers, Patrick Cras, Stephan Zuchner, Jean-Christophe Corvol, Matthew J. Farrer, Matthis Synofzik, Bernard Brais, Tom Warner, Huw R. Morris, Zane Jaunmuktane, Tom Foltynie, Henry Houlden

Manuscripts, Articles, Book Chapters and Other Papers

Partial phenotypic overlap has been suggested between multiple system atrophy and spinocerebellar ataxia 27B, the autosomal dominant ataxia caused by an intronic GAA•TTC repeat expansion in FGF14. In this study, we investigated the frequency of FGF14 GAA•TTC repeat expansion in clinically diagnosed and pathologically confirmed multiple system atrophy cases. We screened 657 multiple system atrophy cases (193 clinically diagnosed and 464 pathologically confirmed) and 1003 controls. The FGF14 repeat locus was genotyped using long-range PCR and bidirectional repeat-primed PCRs, and expansions were confirmed with targeted long-read Oxford Nanopore Technologies sequencing. We identified 19 multiple system atrophy cases carrying an FGF14 …

Periprocedural Results And Right Ventricular Outcomes Of Computer Assisted Vacuum Thrombectomy Treatment Of Acute Pulmonary Embolism: Interim Analysis Of 300 Patients From The Strike-Pe Study, John M. Moriarty, Brian J. Schiro, Suhail Y. Dohad, Houman Tamaddon, Hugh C. Davis, David M. Shavelle, George S. Chrysant, Elias A. Iliadis, David J. Dexter, Juan J. Ciampi Dopazo, Andrew Holden, Frances M. West, Brent Keeling, Andrew S. P. Sharp, Ido Weinberg

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

BACKGROUND: Pulmonary embolism (PE) can be a life-threatening condition. Endovascular treatment is emerging as a promising treatment to restore hemodynamic stability and reverse right ventricular (RV) dysfunction in PE; however, more studies are needed to elucidate the effects on the right ventricle after endovascular treatment. This analysis reports the effects of computer assisted vacuum thrombectomy on RV function.

METHODS: Eligible patients for the single-arm, prospective, international, multicenter STRIKE-PE (A Prospective, Multicenter Study of the Indigo Aspiration System Seeking to Evaluate the Long-Term Safety and Outcomes of Treating Pulmonary Embolism) cohort study are adults with acute PE with symptoms for ≤14 …

Transcutaneous Spinal Stimulation Paired With Visual Feedback Facilitates Retention Of Improved Weight Transfer Toward The Affected Side In People Post-Stroke, Hyunje Park, Beom-Chan Lee, Dimitry Sayenko, Sheng Li, Seoung Hoon Park

The Brown Foundation: Institute of Molecular Medicine

Background: Many individuals with hemiparesis after stroke are reluctant to transfer their body weight toward the affected side and rely more heavily on the unaffected leg while walking. Although visual feedback (VF) has been utilized to improve their weight transfer during walking, the effects of transcutaneous spinal stimulation (TSS) paired with VF during locomotor training in people post-stroke remain largely unexplored. The purpose of this study, therefore, was to determine whether phasic TSS paired with VF regarding weight shifting to the affected leg during treadmill walking would enhance weight transfer toward the affected side.

Methods: Eleven individuals post-stroke participated in …

Scenario Projections Of Covid-19 Burden In The Us, 2024-2025, Sara L Loo, Sung-Mok Jung, Lucie Contamin, Emily Howerton, Samantha J Bents, Harry Hochheiser, Michael C Runge, Claire P Smith, Erica C Carcelén, Katie Yan, Joseph C Lemaitre, Emily Przykucki, Clifton D Mckee, Koji Sato, Allison L Hill, Matteo Chinazzi, Jessica T Davis, Clara Bay, Alessandro Vespignani, Shi Chen, Rajib Paul, Daniel Janies, Jean-Claude Thill, Sean M Moore, T Alex Perkins, Ajitesh Srivastava, Majd Al Aawar, Kaiming Bi, Shraddha Ramdas Bandekar, Anass Bouchnita, Spencer J Fox, Lauren Ancel Meyers, Przemyslaw Porebski, Srinivasan Venkatramanan, Bryan Lewis, Jiangzhuo Chen, Madhav Marathe, Michal Ben-Nun, James Turtle, Pete Riley, Katriona Shea, Cécile Viboud, Justin Lessler, Shaun Truelove

Faculty, Staff and Student Publications

Importance: COVID-19 remains a disease with high burden in the US, prompting continued debate about optimal targets for annual vaccination.

Objective: To project COVID-19 burden in the US for April 2024 to April 2025 under 6 scenarios of immune escape (20% and 50% per year) and levels of vaccine recommendation (no recommendation, vaccination for individuals at high risk only, vaccination for all eligible groups) and to assess the potential benefit of vaccine recommendations in reducing disease burden.

Design, setting, and participants: For this decision analytical model, the US Scenario Modeling Hub, a collaborative modeling effort, convened 9 teams to provide …

Optimal Medical Care And Coronary Flow Capacity-Guided Myocardial Revascularization Vs Usual Care For Chronic Coronary Artery Disease: The Century Trial, K Lance Gould, Nils P Johnson, Amanda E Roby, Richard Kirkeeide, Mary Haynie, Tung Nguyen, Linh Bui, Monica B Patel, Danai Kitkungvan, Patricia Mendoza, Dejian Lai, Ruosha Li, Stefano Sdringola, David Mcpherson, Jagat Narula

Faculty, Staff and Student Publications

Background and aims: The randomized CENTURY trial tested the hypothesis that a comprehensive strategy integrating intense lifestyle modification and aggressive medical management to goals with revascularization reserved for severely reduced coronary flow capacity (CFC) by positron emission tomography (PET) would reduce risk factors, subsequent revascularization, death and myocardial infarction (MI) compared with standard of care in chronic stable coronary artery disease (CAD).

Methods: Participants were randomly assigned to standard or comprehensive care groups. Rest-stress PET quantified CFC for physiological CAD severity at baseline, 2, 5, and up to 11 years. The comprehensive care group reviewed PET results with frequent clinic …

Functional Connectivity Predicting Transdiagnostic Treatment Outcomes In Internalizing Psychopathologies, Kai Zhang, Heide Klumpp, Jagan Jimmy, K Luan Phan, Mohammed R Milad, Zhenfu Wen

Faculty, Staff and Student Publications

Importance: Predicting treatment outcomes for internalizing psychopathologies (IPs), such as depression and anxiety, holds promise for advancing precision medicine. The extent to which whole-brain functional connectivity (FC) can predict treatment responses for patients with IPs across different therapeutic modalities remains unclear.

Objective: To examine whether pretreatment FC patterns predict multidimensional treatment outcomes in patients with IPs and whether predictive performance generalizes across diagnoses and treatment modalities.

Design, setting, and participants: This prognostic study analyzed baseline neuroimaging and clinical data from patients with IPs enrolled in 1 of 2 randomized clinical trials (conducted from December 2013 to February 2018 and September …

Targeting The Il-36 Receptor With Spesolimab Mitigates Residual Inflammation And Prevents Generalized Pustular Psoriasis Flares, James G. Krueger, Milan J. Anadkat, Et Al.

2020-Current year OA Pubs

People with generalized pustular psoriasis experience underlying skin inflammation, even in the absence of flares. Spesolimab treatment helps control the inflammation and prevent future flares.

Surgery Versus Surveillance: A Quality-Of-Life Analysis Of Patients With Moderately Dilated Aortic Root Or Ascending Aorta, Ming Hao Guo, Puja Kachroo, Et Al.

2020-Current year OA Pubs

OBJECTIVES: The impact of diagnosis and management of ascending thoracic aortic aneurysm (ATAA) on patients' quality of life (QoL) is not well characterized. This study aims to compare QoL with surgery versus surveillance in patients with moderate ATAAs.

METHODS: Treatment In Thoracic Aortic aNeurysm: Surgery versus Surveillance is a multicentre randomized trial for patients with ATAA between 5.0 and 5.4 cm and includes a registry of patients who underwent either surgery or surveillance. From May 2019 to December 2022, 157 patients from 15 centres were enrolled in the surveillance (n = 105) or surgery (n = 52) registry and completed …

Genome-Wide Insights Into The Genes And Pathways Shaping Human Foveal Development: Redefining The Genetic Landscape Of Foveal Hypoplasia, Callum Hunt, Ha-Jun Yoon, Alvin Lirio, Kayesha Coley, Jun Wang, Nick Shrine, Jianming Shao, Gail D E Maconachie, Zhanhan Tu, Jonathan H Zippin, Pirro G Hysi, Christopher J Hammond, Omar A Mahroo, Mariya Moosajee, Michel Michaelides, Andrew R Webster, Ala Moshiri, Rui Chen, Martin D Tobin, Chiara Batini, Mervyn G Thomas, Uk Biobank Eye And Vision Consortium

Faculty, Staff and Students Publications

Purpose: To define the genetic architecture of foveal morphology and explore its relevance to foveal hypoplasia (FH), a hallmark of developmental macular disorders.

Methods: We applied deep-learning algorithms to quantify foveal pit depth from central optical coherence tomography (OCT) B-scans in 61,269 UK Biobank participants. A genome-wide association study (GWAS) was conducted using REGENIE, adjusting for age, sex, height, and ancestry. Rare coding variants (frequency < 1%) were analyzed in an exome-wide rare-variant association study (RVAS). Candidate genes were prioritized using integrative mapping; pathway, cross-ancestry, and genetic-correlation analyses were exploratory.

Results: GWAS identified 126 sentinel variants, including 47 novel associations. Integrative mapping prioritized 129 putative causal genes, with 64 not previously implicated in foveal biology. Enriched pathways included retinoic acid metabolism (e.g., CYP26A1), photoreceptor differentiation …

Neoadjuvant Bms-813160, Nivolumab, Gemcitabine, And Nab-Paclitaxel For Patients With Pancreatic Cancer, Patrick M Grierson, Crystal Wolf, Rama Suresh, Andrea Wang-Gillam, Benjamin R Tan, Lee Ratner, Peter Oppelt, Olivia Aranha, Ashley Frith, Katrina S Pedersen, Jennifer Spann, Nicholas Boice, Amberly Brown, John M Baer, Emily G Butka, Faiz Ahmad, Yifei Xu, Jingxia Liu, David G Denardo, Kian-Huat Lim

2020-Current year OA Pubs

PURPOSE: Targeting tumor-associated macrophages through C-C chemokine receptor type 2 (CCR) in pancreatic ductal adenocarcinoma (PDAC) improves the efficacy of chemotherapy and restores T-cell immunity in preclinical models.

PATIENTS AND METHODS: We conducted a phase I/II single-institution study (NCT03496662) combining chemotherapy gemcitabine and nab-paclitaxel (GnP), CCR2/5 inhibitor BMS-813160, and nivolumab for four 28-day cycles for patients with borderline resectable (BR) or locally advanced (LA) PDAC. The recommended phase II dose of BMS-813160 was established in the 3 + 3 design. Primary endpoints were safety and objective response rate (ORR). Secondary endpoints included resection rate, median progression-free survival, and median overall …

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 …

A Metabolomics Study Of Cardiac Dysfunction In Hyperglycemia: Findings From The Atherosclerosis Risk In Communities (Aric) Study And The Hispanic Community Health Study/Study Of Latinos (Hchs/Sol), Yilin Yoshida, Ngoc Quynh Nguyen, Eun Hye Moon, Casey Rebholz, Hicham Skali, Victoria Arthur, Justin B Echouffo-Tcheugui, Christie Ballantyne, Elizabeth Selvin, Amil Shah, Robert Kaplan, Carlos J Rodriguez, Qibin Qi, Susan Cheng, Bing Yu

Faculty, Staff and Student Publications

Objective: Hyperglycemic states (prediabetes and diabetes) are associated with heart failure (HF) risk. We aimed to identify distinct metabolites for subclinical cardiac dysfunction, a precursor of HF, in hyperglycemic or euglycemic individuals.

Research design and methods: We conducted cross-sectional and prospective analyses of 2,492 HF-free participants from the Atherosclerosis Risk in Communities (ARIC) study visit 5, 2011-2013. A total of 1,297 participants were hyperglycemic (assessed on the basis of hemoglobin A1c >5.7%, fasting glucose >100 mg/dL, use of diabetes medication, or diagnosis), and 1,195 were euglycemic. We used logistic regression for analysis of association between 790 metabolites and cardiac dysfunction, …

The Ethics Of Clinical Ethics, Matthew Shea

Center for Medical Ethics and Health Policy Staff Publications

The concept ethics defines health care ethics as a professional practice. Yet the meaning of "ethics" is often unclear in the theory and practice of clinical ethics. Clarity on this matter is crucial for understanding the nature of clinical ethics and for debates about the professional identity and proper role of ethicists, the sort of training and skills they should possess, and whether they have ethics expertise. This article examines two different ways the ethics of clinical ethics can be understood: Real Ethics, which consists of objective moral norms grounded in moral truth; and Conventional Ethics, which consists of conventional …

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 …

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 …

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 …

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 …

A Prospective, Randomized, Controlled Clinical Trial Of High-Frequency Electromagnetic Coupling Powered Permanent Peripheral Nerve Stimulator For The Treatment Of Chronic Craniofacial Pain, Salim M Hayek, Nameer Haider, Ashwin Viswanathan, Mehul Desai, Jeffrey Rosenberg, Niek E Vanquathem

Faculty, Staff and Students Publications

than one-fifth of the US population. While various medications and conservative treatment modalities are available for this condition, many patients have refractory symptoms. These patients suffer from social impairment, reduced quality of life, and increased financial burdens.

Objective: The objective of this study was to examine the clinical outcomes of patients receiving a permanent, high-frequency electromagnetic coupling (HF-EMC) powered peripheral nerve stimulator (PNS) system for the treatment of chronic craniofacial neuropathic pain.

Study design: This study was a multicenter, randomized, controlled clinical trial conducted under an investigational device exemption (IDE).

Setting: This study was conducted in 7 clinical sites in …

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 …

Mucinous Cystic Neoplasms Of The Pancreas And Liver Share A Similar Dna Methylation Profile With Mucinous Ovarian Tumors, Zoe Leoni, Teodor G Calina, Tobias Janik, Elena Grafenhorst, Eliane T Taube, Christopher Cm Neumann, Baoqing Chen, Elena I Braicu, Jalid Sehouli, Thomas Malinka, Wenzel Schöning, Johann Pratschke, George A Calin, David S Klimstra, Jamal K Benhamida, Irene Esposito, Markus Möbs, David Horst, Simon Schallenberg, David Capper, Mihnea P Dragomir

Faculty, Staff and Student Publications

The origin of mucinous cystic neoplasms (MCNs) remains a major challenge in hepato-pancreato-biliary pathology. These cystic tumors are defined by their mucinous epithelium and ovarian-like stroma, with an estimated 10% risk of progression to invasive carcinoma. The origin of the ovarian-like stroma remains a subject of debate. In this study, we conducted immunohistochemical profiling, targeted DNA sequencing, and genome-wide DNA methylation analysis on a cohort of 15 pancreatic MCNs (MCN-P) and six hepatic MCNs (MCN-L). Using immunohistochemistry and targeted DNA sequencing, we unequivocally established the diagnosis of MCN. Unsupervised DNA methylation profile analysis of reference classes of pancreatic neoplasms (11 …

Does Stem Design Affect Primary Stability Of Splined Tapered Fluted Stems? A Biomechanical Cadaver Study, Shuyang Han, Daniel C Mascarenhas, Camryn A Pletka, Jonathan E Gold, Sabir K Ismaily, Matthew Cao, Matthew W Brewer, Robert Frangie, Philip C Noble, David Rodriguez-Quintana

Faculty, Staff and Student Publications

Background: Tapered fluted stems are an excellent solution for revision hip arthroplasty following periprosthetic fractures. However, existing implant designs differ in terms of the number of splines, taper angle, and cross-sectional design, and there is a lack of knowledge on the biomechanical effect of these design variations. Therefore, the objective of this study was to compare the primary stability of two representative stem designs and the extent and distribution of stem-bone contact in a periprosthetic fracture model. It was hypothesized that a greater number of splines would lead to greater stability.

Methods: There were six pairs of cadaver femora included …

Trop2 Expression In Salivary Gland Adenoidcystic Carcinoma (Acc) According To Histologic Subtype: Therapeutic Implications, Juliana Mota Siqueira, Yoshitsugu Mitani, Mario L Marques-Piubelli, Camilla Oliveira Hoff, Flavia Bonini, Luana Guimaraes De Sousa, Mutsumi Mitani, Giovanna Lopes Carvalho, Fabio Daumas Nunes, Leandro Luongo Matos, Shiaw-Yih Lin, Michael T Spiotto, Ehab Y Hanna, Daniel J Mcgrail, Adel K El-Naggar, Renata Ferrarotto

Faculty, Staff and Student Publications

Background: Adenoid cystic carcinoma (ACC) is a common salivary gland carcinoma with high recurrence and distant metastasis rates. Currently, there is no standard systemic treatment available. TROP2 is a transmembrane glycoprotein involved in the oncogenesis of several tumors that can be therapeutically targeted by a TROP2-antibody-drug conjugate (ADC). We aimed to characterize TROP2 expression in ACC and assess TROP2 as a potential therapeutic target.

Methods: TROP2 immunohistochemistry was performed in a tissue microarray including 165 ACC of salivary gland. The tumors were grouped according to the histological pattern as non-solid, solid + non-solid, or solid. TROP2 protein expression in ACC …

One-Year Outcomes From The Pivotal Trial Of A Four-Branch Off-The-Shelf Solution To Treat Pararenal And Extent Iv Thoracoabdominal Aortic Aneurysms, Mark A Farber, Sukgu Han, Michel S Makaroun, Jon S Matsumura, Bernardo C Mendes, Gustavo S Oderich, Luis A Sanchez, Bjoern D Suckow, Carlos H Timaran

Faculty, Staff and Students Publications

Objective: To report 1-year primary-arm outcomes of the GORE EXCLUDER Thoracoabdominal Branch Endoprosthesis pivotal trial.

Methods: The multicenter, nonrandomized, prospective study included patients with extent IV thoracoabdominal aortic aneurysms (TAAAs) and pararenal aortic aneurysms (PRAAs). All-cause and adjudicated lesion-related mortality were assessed at 12 months. Core-lab-reported, imaging-dependent outcomes included aneurysm size, endoleaks assessed through 1-year follow-up window, and target vessel instability (defined as occlusion, stenosis, type Ic/IIIc endoleak, or reintervention) at 1 year.

Results: One hundred two patients were treated; 59 patients had an extent IV TAAA and 43 had a PRAA. The mean maximum aneurysm diameter was 59.4 ± …

Auricular Point Acupressure For Older Adults With Chronic Low Back Pain: A Randomized Controlled Trial, Jennifer Kawi, Chao Hsing Yeh, Nada Lukkahatai, Hulin Wu, Natalia E Morone, Ronald Glick, Elizabeth A Schlenk, Claudia Campbell, Johannes Thrul, Xinran Huang, Hongyu Wang, Hejingzi Monica Jia, Paul Christo, Constance Johnson

Faculty, Staff and Student Publications

Objective: Efficacious modalities are limited in chronic low back pain (cLBP). We determined the efficacy of auricular point acupressure (APA) in older adults with cLBP.

Design: 3-arm randomized controlled trial.

Setting: Baltimore, Maryland.

Participants: Participants, ≥60 years with cLBP, were randomized (1:1:1) to APA with ear points targeted to cLBP (T-APA, n = 92), points nontargeted to cLBP (NT-APA, n = 91), or waitlist education control (n = 89), and followed up to 6 months (6M). Participants in the APA groups received 4 weekly APA sessions; the education control group received 4 weekly educational sessions.

Intervention: APA.

Main outcomes and …