Medical Specialties Commons^™

Dynamics Of Karyotype Evolution, Elena Kuzmin, Toby M Baker, Peter Van Loo, Leon Glass

Faculty, Staff and Student Publications

In the evolution of species, the karyotype changes with a timescale of tens to hundreds of thousand years. In the development of cancer, the karyotype often is modified in cancerous cells over the lifetime of an individual. Characterizing these changes and understanding the mechanisms leading to them has been of interest in a broad range of disciplines including evolution, cytogenetics, and cancer genetics. A central issue relates to the relative roles of random vs deterministic mechanisms in shaping the changes. Although it is possible that all changes result from random events followed by selection, many results point to other non-random …

Pet Imaging Of Metabolism, Perfusion, And Hypoxia: Fdg And Beyond, Austin R Pantel, Seong-Woo Bae, Elizabeth J Li, Sophia R O'Brien, H Charles Manning

Faculty, Staff and Student Publications

Imaging glucose metabolism with [18F]fluorodeoxyglucose positron emission tomography has transformed the diagnostic and treatment algorithms of numerous malignancies in clinical practice. The cancer phenotype, though, extends beyond dysregulation of this single pathway. Reprogramming of other pathways of metabolism, as well as altered perfusion and hypoxia, also typifies malignancy. These features provide other opportunities for imaging that have been developed and advanced into humans. In this review, we discuss imaging metabolism, perfusion, and hypoxia in cancer, focusing on the underlying biology to provide context. We conclude by highlighting the ability to image multiple facets of biology to better characterize cancer and …

Benefit Of Axicabtagene Ciloleucel Versus Chemoimmunotherapy In Older Patients And/Or Patients With Poor Ecog Performance Status With Relapsed Or Refractory Large B-Cell Lymphoma After 2 Or More Lines Of Prior Therapy, Matthew A Lunning, Hai-Lin Wang, Zhen-Huan Hu, Frederick L Locke, Tanya Siddiqi, Caron A Jacobson, Sairah Ahmed, David B Miklos, Yi Lin, Brian T Hill, Armin Ghobadi, Sattva S Neelapu, Jason Westin, Chrisopher Dieyi, Polly Field, Harry Miao, Shilpa A Shahani, Anik Patel, Clare Spooner, Christine Fu, David Muramoto, Hairong Xu, Marcelo C Pasquini

Faculty, Staff and Student Publications

Axicabtagene ciloleucel (axi-cel) in trials has demonstrated favorable efficacy compared with historical controls after ≥2 lines of therapy for the treatment of relapsed or refractory (R/R) large B cell lymphoma (LBCL). Herein, we compared the real-world effectiveness of axi-cel with efficacy and effectiveness of chemoimmunotherapy (CIT) in patients aged ≥65 years and patients with Eastern Cooperative Oncology Group performance status (ECOG PS) of 2. A total of 1146 patients treated with commercial axi-cel for R/R LBCL with ≥2 lines of prior therapy were included from the Center for International Blood and Marrow Transplantation Research prospective observational study, and 469 patients …

On The Optimal Diagnosis And The Evolving Role Of Pimavanserin In Parkinson's Disease Psychosis, Fernando L Pagan, Paul E Schulz, Yasar Torres-Yaghi, Gregory M Pontone

Faculty, Staff and Student Publications

Parkinson's disease (PD) is associated with the development of psychosis (PDP), including hallucinations and delusions, in more than half of the patient population. Optimal PD management must therefore involve considerations about both motor and non-motor symptoms. Often, clinicians fail to diagnosis psychosis in patients with PD and, when it is recognized, treat it suboptimally, despite the availability of multiple interventions. In this paper, we provide a summary of the current guidelines and clinical evidence for treating PDP with antipsychotics. We also provide recommendations for diagnosis and follow-up. Finally, an updated treatment algorithm for PDP that incorporates the use of pimavanserin, …

Artificial Intelligence-Powered Assessment Of Pathologic Response To Neoadjuvant Atezolizumab In Patients With Nsclc: Results From The Lcmc3 Study, Sanja Dacic, William D Travis, Jennifer M Giltnane, Filip Kos, John Abel, Stephanie Hilz, Junya Fujimoto, Lynette Sholl, Jon Ritter, Farah Khalil, Yi Liu, Amaro Taylor-Weiner, Murray Resnick, Hui Yu, Fred R Hirsch, Paul A Bunn, David P Carbone, Valerie Rusch, David J Kwiatkowski, Bruce E Johnson, Jay M Lee, Stephanie R Hennek, Ilan Wapinski, Alan Nicholas, Ann Johnson, Katja Schulze, Mark G Kris, Ignacio I Wistuba

Faculty, Staff and Student Publications

Introduction: Pathologic response (PathR) by histopathologic assessment of resected specimens may be an early clinical end point associated with long-term outcomes with neoadjuvant therapy. Digital pathology may improve the efficiency and precision of PathR assessment. LCMC3 (NCT02927301) evaluated neoadjuvant atezolizumab in patients with resectable NSCLC and reported a 20% major PathR rate.

Methods: We determined PathR in primary tumor resection specimens using guidelines-based visual techniques and developed a convolutional neural network model using the same criteria to digitally measure the percent viable tumor on whole-slide images. Concordance was evaluated between visual determination of percent viable tumor (n = …

Discovering Genetic Biomarkers For Targeted Cancer Therapeutics With Explainable Artificial Intelligence, Debaditya Chakraborty, Elizabeth Gutierrez-Chakraborty, Cristian Rodriguez-Aguayo, Hakan Başağaoğlu, Gabriel Lopez-Berestein, Paola Amero

Faculty, Staff and Student Publications

No abstract provided.

Survival Outcomes Of Patients With Her2/Neu-Positive Breast Cancer With Germline Brca Mutations, Fatma Nihan Akkoc Mustafayev, Mihir Amitabh Shukla, Amanda Lanier, Denái R Milton, Angelica M Gutierrez, Stephen K Gruschkus, John E Lewis, Rashmi K Murthy, Banu K Arun

Faculty, Staff and Student Publications

Background: Breast cancer (BC) with germline BRCA1/2 mutations and their association with triple-negative BC has been thoroughly investigated. However, some carriers of BRCA1/2 mutations have human epidermal growth factor receptor 2 (HER2/neu)-positive BC, which has a different targeted therapy approach, and data are scarce for this patient population. The authors sought to characterize the clinical characteristics and outcomes of patients with HER2/neu-positive BC who had germline BRCA1/2 mutations.

Methods: This was a retrospective analysis of data from 1099 patients diagnosed with HER2/neu-positive BC who were screened for germline BRCA mutations between 1996 and 2022. Clinicopathologic features and survival rates were …

A Novel Sik2 Inhibitor Sic-19 Exhibits Synthetic Lethality With Parp Inhibitors In Ovarian Cancer, Fang Wang, Xuejiao Yu, Jun Qian, Yumin Cao, Shunli Dong, Shenghua Zhan, Zhen Lu, Robert C Bast, Qingxia Song, Youguo Chen, Yi Zhang, Jinhua Zhou

Faculty, Staff and Student Publications

Purpose: Ovarian cancer patients with HR proficiency (HRP) have had limited benefits from PARP inhibitor treatment, highlighting the need for improved therapeutic strategies. In this study, we developed a novel SIK2 inhibitor, SIC-19, and investigated its potential to enhance the sensitivity and expand the clinical utility of PARP inhibitors in ovarian cancer.

Methods: The SIK2 protein was modeled using a Molecular Operating Environment (MOE), and the most favorable model was selected based on a GBVI/WSA dG scoring function. The Chembridge Compound Library was screened, and the top 20 candidate compounds were tested for their interaction with SIK2 and downstream substrates, …

Safety And Tolerability Of Online Adaptive High-Field Magnetic Resonance-Guided Radiotherapy, Jasmijn M Westerhoff, Lois A Daamen, John P Christodouleas, Erwin L A Blezer, Ananya Choudhury, Rosalyne L Westley, Beth A Erickson, Clifton D Fuller, Shaista Hafeez, Uulke A Van Der Heide, Martijn P W Intven, Anna M Kirby, Susan Lalondrelle, Bruce D Minsky, Stella Mook, Marlies E Nowee, Corrie A M Marijnen, Kristina M Orrling, Arjun Sahgal, Christopher J Schultz, Corinne Faivre-Finn, Robbert J H A Tersteeg, Alison C Tree, Chia-Lin Tseng, Tine Schytte, Dustin M Silk, Dave Eggert, Marco Luzzara, Jochem R N Van Der Voort Van Zyp, Helena M Verkooijen, William A Hall

Faculty, Staff and Student Publications

Importance: In 2018, the first online adaptive magnetic resonance (MR)-guided radiotherapy (MRgRT) system using a 1.5-T MR-equipped linear accelerator (1.5-T MR-Linac) was clinically introduced. This system enables online adaptive radiotherapy, in which the radiation plan is adapted to size and shape changes of targets at each treatment session based on daily MR-visualized anatomy.

Objective: To evaluate safety, tolerability, and technical feasibility of treatment with a 1.5-T MR-Linac, specifically focusing on the subset of patients treated with an online adaptive strategy (ie, the adapt-to-shape [ATS] approach).

Design, setting, and participants: This cohort study included adults with solid tumors treated with a …

Guidance For Assessment Of The Inflammation Etiologic Criterion For The Glim Diagnosis Of Malnutrition: A Modified Delphi Approach., Tommy Cederholm, Gordon L Jensen, Maria D Ballesteros-Pomar, Renee Blaauw, M Isabel T D Correia, Cristina Cuerda, David C Evans, Ryoji Fukushima, Juan Bernardo Ochoa Gautier, M Cristina Gonzalez, Andre Van Gossum, Leah Gramlich, Joseph Hartono, Steven B Heymsfield, Harriët Jager-Wittenaar, Renuka Jayatissa, Heather Keller, Ainsley Malone, William Manzanares, M Molly Mcmahon, Yolanda Mendez, Kris M Mogensen, Naoharu Mori, Maurizio Muscaritoli, Guillermo Contreras Nogales, Ibolya Nyulasi, Wendy Phillips, Matthias Pirlich, Veeradej Pisprasert, Elisabet Rothenberg, Marian De Van Der Schueren, Han Ping Shi, Alison Steiber, Marion F Winkler, Rocco Barazzoni, Charlene Compher

Ambulatory and Primary Care Articles

BACKGROUND & AIMS: The Global Leadership Initiative on Malnutrition (GLIM) approach to malnutrition diagnosis is based on assessment of three phenotypic (weight loss, low body mass index, and reduced skeletal muscle mass) and two etiologic (reduced food intake/assimilation and disease burden/inflammation) criteria, with diagnosis confirmed by fulfillment of any combination of at least one phenotypic and at least one etiologic criterion. The original GLIM description provided limited guidance regarding assessment of inflammation and this has been a factor impeding further implementation of the GLIM criteria. We now seek to provide practical guidance for assessment of inflammation in support of the …

The Impact Of Severe Obesity On Image Quality And Ventricular Function Assessment In Echocardiography And Cardiac Mri., Akash Goyal, Christopher D Crabtree, Bryan C Lee, Thura T Harfi, Saurabh Rajpal, Vedat O Yildiz, Orlando P Simonetti, Matthew S Tong

Heart and Vascular Articles

This study sought to evaluate the impact of severe obesity on image quality and ventricular function assessment in cardiovascular magnetic resonance (MRI) and trans-thoracic echocardiography (TTE). We studied 100 consecutive patients who underwent clinically indicated cardiac MRI and TTE studies within 12 months between July 2017 and December 2020; 50 (28 females and 22 males; 54.5 ± 18.7 years) with normal body mass index (BMI) (18.5-25 kg/m

Three-Year Outcomes Of The Abre Venous Self-Expanding Stent System In Patients With Symptomatic Iliofemoral Venous Outflow Obstruction., Stephen Black, Marc Sapoval, David J Dexter, Kathleen Gibson, Raghu Kolluri, Mahmood Razavi, Dorian J Defreitas, Hong Wang, Stephanie Brucato, Erin Murphy

Heart and Vascular Articles

PURPOSE: To report 36-month outcomes and subgroup analysis of the ABRE study evaluating the safety and effectiveness of the Abre venous self-expanding stent system for the treatment of symptomatic iliofemoral venous outflow obstruction disease.

METHODS: The ABRE study was a prospective, multicenter, nonrandomized study that enrolled and implanted Abre venous stents in 200 participants (mean age 51.5 years [SD ± 15.9], 66.5% women) with symptomatic iliofemoral venous outflow obstruction at 24 global sites. Outcomes assessed through 36 months included patency, major adverse events, stent migration, stent fracture, and quality-of-life changes. Adverse events and imaging studies were adjudicated by independent clinical …

Post-Covid Small Fiber Neuropathy, Implications Of Innate Immunity, And Challenges On Ivig Therapy, Marinos Dalakas

Department of Neurology Faculty Papers

No abstract provided.

Guidance For Assessment Of The Inflammation Etiologic Criterion For The Glim Diagnosis Of Malnutrition: A Modified Delphi Approach., Tommy Cederholm, Gordon L Jensen, Maria D Ballesteros-Pomar, Renee Blaauw, M Isabel T D Correia, Cristina Cuerda, David C Evans, Ryoji Fukushima, Juan Bernardo Ochoa Gautier, M Cristina Gonzalez, Andre Van Gossum, Leah Gramlich, Joseph Hartono, Steven B Heymsfield, Harriët Jager-Wittenaar, Renuka Jayatissa, Heather Keller, Ainsley Malone, William Manzanares, M Molly Mcmahon, Yolanda Mendez, Kris M Mogensen, Naoharu Mori, Maurizio Muscaritoli, Guillermo Contreras Nogales, Ibolya Nyulasi, Wendy Phillips, Matthias Pirlich, Veeradej Pisprasert, Elisabet Rothenberg, Marian De Van Der Schueren, Han Ping Shi, Alison Steiber, Marion F Winkler, Rocco Barazzoni, Charlene Compher

Ambulatory and Primary Care Articles

BACKGROUND & AIMS: The Global Leadership Initiative on Malnutrition (GLIM) approach to malnutrition diagnosis is based on assessment of three phenotypic (weight loss, low body mass index, and reduced skeletal muscle mass) and two etiologic (reduced food intake/assimilation and disease burden/inflammation) criteria, with diagnosis confirmed by fulfillment of any combination of at least one phenotypic and at least one etiologic criterion. The original GLIM description provided limited guidance regarding assessment of inflammation and this has been a factor impeding further implementation of the GLIM criteria. We now seek to provide practical guidance for assessment of inflammation in support of the …

Angiogenic Gene Therapy For Refractory Angina: Results Of The Exact Phase 2 Trial, Kenta Nakamura, Timothy D Henry, Jay H Traverse, David A Latter, Nahush A Mokadam, Geoffrey A Answini, Adam R Williams, Benjamin C Sun, Christopher R Burke, Faisal G Bakaeen, Marcelo F Dicarli, Bernard R Chaitman, Mark W Peterson, Dawn G Byrnes, E Magnus Ohman, Carl J Pepine, Ronald G Crystal, Todd K Rosengart, Elaine Kowalewski, Gary G Koch, Howard C Dittrich, Thomas J Povsic, Exact Trial Investigators

Faculty, Staff and Students Publications

Background: XC001 is a novel adenoviral-5 vector designed to express multiple isoforms of VEGF (vascular endothelial growth factor) and more safely and potently induce angiogenesis. The EXACT trial (Epicardial Delivery of XC001 Gene Therapy for Refractory Angina Coronary Treatment) assessed the safety and preliminary efficacy of XC001 in patients with no option refractory angina.

Methods: In this single-arm, multicenter, open-label trial, 32 patients with no option refractory angina received a single treatment of XC001 (1×1011 viral particles) via transepicardial delivery.

Results: There were no severe adverse events attributed to the study drug. Twenty expected severe adverse events in 13 patients …

Consensus Guidelines For The Diagnosis And Management Of Succinic Semialdehyde Dehydrogenase Deficiency, Itay Tokatly Latzer, Mariarita Bertoldi, Nenad Blau, Melissa L Dibacco, Sarah H Elsea, Àngels García-Cazorla, K Michael Gibson, Andrea L Gropman, Ellen Hanson, Carolyn Hoffman, Kathrin Jeltsch, Natalia Juliá-Palacios, Ina Knerr, Henry H C Lee, Patrizia Malaspina, Alice Mcconnell, Thomas Opladen, Mari Oppebøen, Alexander Rotenberg, Mark Walterfang, Lee Wang-Tso, Ron A Wevers, Jean-Baptiste Roullet, Phillip L Pearl

Faculty, Staff and Students Publications

Succinic semialdehyde dehydrogenase deficiency (SSADHD) (OMIM #271980) is a rare autosomal recessive metabolic disorder caused by pathogenic variants of ALDH5A1. Deficiency of SSADH results in accumulation of γ-aminobutyric acid (GABA) and other GABA-related metabolites. The clinical phenotype of SSADHD includes a broad spectrum of non-pathognomonic symptoms such as cognitive disabilities, communication and language deficits, movement disorders, epilepsy, sleep disturbances, attention problems, anxiety, and obsessive-compulsive traits. Current treatment options for SSADHD remain supportive, but there are ongoing attempts to develop targeted genetic therapies. This study aimed to create consensus guidelines for the diagnosis and management of SSADHD. Thirty relevant statements were …

Robotic-Assisted Single-Site Abdominal Cerclage In The Bicornuate Uterus Patient With Cervical Insufficiency, Nurul Farhanah Binte Abdul Latif, Zhenkun Guan, Sylvia Asare, Xiaoming Guan

Faculty, Staff and Students Publications

Objective: To demonstrate the surgical techniques for improving safety in robotic-assisted abdominal cerclage in patients with bicornuate uteri complicated by recurrent pregnancy loss and cervical insufficiency.

Design: Stepwise demonstration with narrated video footage.

Setting: An academic tertiary care hospital.

Patients: Our patient is a 22-year-old G2P0020 with a history of recurrent pregnancy loss. During her first pregnancy, she was asymptomatic until 19 weeks and delivered because of a preterm premature rupture of membranes. A transvaginal cerclage was performed for her second pregnancy at 14 weeks, which ended at 16 weeks because of preterm premature rupture of membranes. The final magnetic …

Social Determinants Of Health And Risk Of Stillbirth In The United States, April Adams, Deepa Dongarwar, Lena Shay, Mariana Baroni, Eunique Williams, Priscilla Ehieze, Rhanna Wilson, Alexia Awoseyi, Hamisu M Salihu

Faculty, Staff and Students Publications

Objective: Our aim was to evaluate the impact of social determinants of health (SDoH) risk factors on stillbirth among pregnancy-related hospitalizations in the United States.

Study design: We conducted a cross-sectional analysis of delivery-related hospital discharges using annualized data (2016-2017) from the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample. The International Classification of Diseases, 10th Revision ICD-10-CM codes were used to select women with singleton stillbirth. Z-codes were utilized to identify SDoH risk factors and their subtypes. The association between SDoH risk factors and stillbirth was assessed using survey logistic regression models.

Results: We analyzed 8,148,646 hospitalizations, out of …

Systematic Evaluation Of Machine Learning-Enhanced Trifocal Iol Power Selection For Axial Myopia Cataract Patients, Danmin Cao, Min Hu, Danlin Zhi, Jianheng Liang, Qian Tan, Qiong Lei, Maoyan Li, Hao Cheng, Li Wang, Weiwei Dai

Faculty, Staff and Students Publications

Purpose: This study aimed to evaluate and optimize intraocular lens (IOL) power selection for cataract patients with high axial myopia receiving trifocal IOLs.

Design: A multi-center, retrospective observational case series was conducted. Patients having an axial length ≥26 mm and undergoing cataract surgery with trifocal IOL implanted were studied.

Methods: Preoperative biometric and postoperative outcome data from 139 eyes were collected to train and test various machine learning (ML) models (support vector machine, linear regression, and stacking regressor) using five-fold cross-validation. The models' performance was further validated externally using data from 48 eyes enrolled from other hospitals. Performance of seven …

Voiding Phase Dysfunction In Multiple Sclerosis: Contemporary Review Of Terminology, Diagnosis, Management, And Future Directions, Catherine Frances Ingram, John A Lincoln, Rose Khavari

Faculty, Staff and Student Publications

Lower urinary tract symptoms (LUTS) are highly prevalent in individuals with multiple sclerosis (MS). However, assessment of these symptoms is often hindered by vague definitions or absence of screening in asymptomatic patients. It is crucial to exercise caution when applying the non-neurogenic definition of urinary retention in this population. For men with MS experiencing persistent and treatment-resistant LUTS, urodynamic studies should be used to identify the underlying causes of symptoms. Although numerous therapies are presently accessible for managing LUTS in MS, there is a need for further investigation into emerging treatments such as percutaneous tibial nerve, and noninvasive brain stimulation.

Immune Cell Pair Ratio Captured By Imaging Mass Cytometry Has Superior Predictive Value For Prognosis Of Non-Small Cell Lung Cancer Than Cell Fraction And Density, Jian-Rong Li, Chao Cheng

Faculty, Staff and Students Publications

No abstract provided.

Use Of Topical Methylene Blue To Image Nuclear Morphometry With A Low-Cost Scanning Darkfield Microendoscope, Huayu Hou, Jennifer Carns, Richard A Schwarz, Ann M Gillenwater, Sharmila Anandasabapathy, Rebecca R Richards-Kortum

Faculty, Staff and Students Publications

SIGNIFICANCE: Fiber-optic microendoscopy is a promising approach to noninvasively visualize epithelial nuclear morphometry for early cancer and precancer detection. However, the broader clinical application of this approach is limited by a lack of topical contrast agents available for

AIM: The aim of this study was to evaluate the ability to image nuclear morphometry in vivo with a novel fiber-optic microendoscope used together with topical application of methylene blue (MB), a dye with FDA approval for use in chromoendoscopy in the gastrointestinal tract.

APPROACH: The low-cost, high-resolution microendoscope implements scanning darkfield imaging without complex optomechanical components by leveraging programmable illumination and …

Natural History Of Cancer-Associated Splanchnic Vein Thrombosis, Hanqing Shang, Jun Y Jiang, Danielle Guffey, Francisco Novoa, Raka Bandyo, Shengling Ma, Ang Li

Faculty, Staff and Students Publications

Background: There is uncertainty in the management of cancer-associated isolated splanchnic vein thrombosis (SpVT).

Objectives: To describe the natural history of SpVT by cancer type and thrombus composition and to review anticoagulation (AC) practices and associated rates of usual-site venous thromboembolism (VTE), major and clinically relevant nonmajor bleeding (MB/CRNMB), recanalization/progression, and mortality.

Methods: We performed a retrospective cohort study in patients with SpVT at 2 cancer care centers in Houston, Texas. We estimated the incidence of usual-site VTE and MB/CRNMB at 6 months using competing risk methods and examined venous patency in a subset of patients with repeat imaging. We …

Using Workplace-Based Assessments In Undergraduate Medical Education, Arindam Sarkar

Faculty, Staff and Students Publications

No abstract provided.

Avoidant/Restrictive Food Intake Disorder Prevalence Is High In Children With Gastroparesis And Functional Dyspepsia, Isha Kaul, Helen Burton-Murray, Salma Musaad, Yiming Mirabile, Danita Czyzewski, Miranda A L Van Tilburg, Andrew C Sher, Bruno P Chumpitazi, Robert J Shulman

Children’s Nutrition Research Center Staff Publications

BACKGROUND: Avoidant/restrictive food intake disorder (ARFID) prevalence in children with gastroparesis (Gp) and/or functional dyspepsia (FD) is unknown. We aimed to identify ARFID prevalence and trajectory over 2 months in children with Gp, FD, and healthy children (HC) using two screening questionnaires. We also explored the frequency of a positive ARFID screen between those with/without delayed gastric emptying or abnormal fundic accommodation.

METHODS: In this prospective longitudinal study conducted at an urban tertiary care hospital, patients ages 10-17 years with Gp or FD and age- and gender-matched HC completed two validated ARFID screening tools at baseline and 2-month follow-up: the …

Genome-Wide Analysis In Over 1 Million Individuals Of European Ancestry Yields Improved Polygenic Risk Scores For Blood Pressure Traits, Jacob M Keaton, Zoha Kamali, Tian Xie, Ahmad Vaez, Ariel Williams, Slavina B Goleva, Alireza Ani, Evangelos Evangelou, Jacklyn N Hellwege, Loic Yengo, William J Young, Matthew Traylor, Ayush Giri, Zhili Zheng, Jian Zeng, Daniel I Chasman, Andrew P Morris, Mark J Caulfield, Shih-Jen Hwang, Jaspal S Kooner, David Conen, John R Attia, Alanna C Morrison, Ruth J F Loos, Kati Kristiansson, Reinhold Schmidt, Andrew A Hicks, Peter P Pramstaller, Christopher P Nelson, Nilesh J Samani, Lorenz Risch, Ulf Gyllensten, Olle Melander, Harriette Riese, James F Wilson, Harry Campbell, Stephen S Rich, Bruce M Psaty, Yingchang Lu, Jerome I Rotter, Xiuqing Guo, Kenneth M Rice, Peter Vollenweider, Johan Sundström, Claudia Langenberg, Martin D Tobin, Vilmantas Giedraitis, Jian'an Luan, Jaakko Tuomilehto, Zoltan Kutalik, Samuli Ripatti, Veikko Salomaa, Giorgia Girotto, Stella Trompet, J Wouter Jukema, Pim Van Der Harst, Paul M Ridker, Franco Giulianini, Veronique Vitart, Anuj Goel, Hugh Watkins, Sarah E Harris, Ian J Deary, Peter J Van Der Most, Albertine J Oldehinkel, Bernard D Keavney, Caroline Hayward, Archie Campbell, Michael Boehnke, Laura J Scott, Thibaud Boutin, Chrysovalanto Mamasoula, Marjo-Riitta Järvelin, Annette Peters, Christian Gieger, Edward G Lakatta, Francesco Cucca, Jennie Hui, Paul Knekt, Stefan Enroth, Martin H De Borst, Ozren Polašek, Maria Pina Concas, Eulalia Catamo, Massimiliano Cocca, Ruifang Li-Gao, Edith Hofer, Helena Schmidt, Beatrice Spedicati, Melanie Waldenberger, David P Strachan, Maris Laan, Alexander Teumer, Marcus Dörr, Vilmundur Gudnason, James P Cook, Daniela Ruggiero, Ivana Kolcic, Eric Boerwinkle, Michela Traglia, Terho Lehtimäki, Olli T Raitakari, Andrew D Johnson, Christopher Newton-Cheh, Morris J Brown, Anna F Dominiczak, Peter J Sever, Neil Poulter, John C Chambers, Roberto Elosua, David Siscovick, Tõnu Esko, Andres Metspalu, Rona J Strawbridge, Markku Laakso, Anders Hamsten, Jouke-Jan Hottenga, Eco De Geus, Andrew D Morris, Colin N A Palmer, Ilja M Nolte, Yuri Milaneschi, Jonathan Marten, Alan Wright, Eleftheria Zeggini, Joanna M M Howson, Christopher J O'Donnell, Tim Spector, Mike A Nalls, Eleanor M Simonsick, Yongmei Liu, Cornelia M Van Duijn, Adam S Butterworth, John N Danesh, Cristina Menni, Nicholas J Wareham, Kay-Tee Khaw, Yan V Sun, Peter W F Wilson, Kelly Cho, Peter M Visscher, Joshua C Denny, Million Veteran Program, Lifelines Cohort Study, Charge Consortium, Icbp Consortium, Daniel Levy, Todd L Edwards, Patricia B Munroe, Harold Snieder, Helen R Warren

Faculty, Staff and Student Publications

Hypertension affects more than one billion people worldwide. Here we identify 113 novel loci, reporting a total of 2,103 independent genetic signals (P < 5 × 10-8) from the largest single-stage blood pressure (BP) genome-wide association study to date (n = 1,028,980 European individuals). These associations explain more than 60% of single nucleotide polymorphism-based BP heritability. Comparing top versus bottom deciles of polygenic risk scores (PRSs) reveals clinically meaningful differences in BP (16.9 mmHg systolic BP, 95% CI, 15.5-18.2 mmHg, P = 2.22 × 10-126) and more than a sevenfold higher odds of hypertension risk (odds ratio, 7.33; 95% CI, 5.54-9.70; P = 4.13 × 10-44) in an independent dataset. Adding PRS into hypertension-prediction models increased the area under the receiver operating characteristic curve (AUROC) from 0.791 (95% CI, 0.781-0.801) to 0.826 (95% CI, 0.817-0.836, ∆AUROC, 0.035, P = 1.98 × 10-34). We compare the 2,103 loci results in non-European ancestries and show significant PRS associations in a large African-American sample. Secondary analyses implicate 500 genes previously unreported for BP. Our study highlights the role of increasingly large genomic studies for precision health research.

Targeted Accurate Rna Consensus Sequencing (Tarc-Seq) Reveals Mechanisms Of Replication Error Affecting Sars-Cov-2 Divergence, Catherine C Bradley, Chen Wang, Alasdair J E Gordon, Alice X Wen, Pamela N Luna, Matthew B Cooke, Brendan F Kohrn, Scott R Kennedy, Vasanthi Avadhanula, Pedro A Piedra, Olivier Lichtarge, Chad A Shaw, Shannon E Ronca, Christophe Herman

Duncan NRI Faculty and Staff Publications

RNA viruses, like SARS-CoV-2, depend on their RNA-dependent RNA polymerases (RdRp) for replication, which is error-prone. Monitoring replication errors is crucial for understanding the virus’s evolution. Current methods lack the precision to detect rare de novo RNA mutations, particularly in low-input samples such as those from patients. Here, we introduce a new targeted Accurate RNA Consensus sequencing method (tARC-seq) to accurately determine the mutation frequency and types in SARS-CoV-2, both in cell culture and clinical samples. Our findings show an average of 2.68×10−5 new errors per cycle with a C>T bias that cannot be solely attributed to APOBEC …

Family Accommodation In Children And Adolescents With Misophonia, Eric A Storch, Andrew G Guzick, Johann D'Souza, Jane Clinger, Daphne Ayton, Minjee Kook, Conor Rork, Eleanor E Smith, Isabel A Draper, Nasim Khalfe, Catherine E Rast, Nicholas Murphy, Marijn Lijfijjt, Wayne K Goodman, Matti Cervin

Center for Medical Ethics and Health Policy Staff Publications

Family accommodation (e.g., reassurance, modifying routines, assisting avoidance) has not been explored among youth with misophonia but may have important clinical and intervention implications. We examined family accommodation in 102 children and adolescents with interview-confirmed misophonia and compared its frequency and content to family accommodation in 95 children and adolescents with anxiety disorders. Findings showed that family accommodation was ubiquitous in pediatric misophonia and may be even more frequent than in youth with anxiety disorders. Assisting the child, participating in misophonia-related behaviors, and modifying family routines were endorsed by more than 70% of parents of children with misophonia. Further, compared …

Parent-Led Cognitive Behavioral Teletherapy For Anxiety In Autistic Youth: A Randomized Trial Comparing Two Levels Of Therapist Support, Andrew G Guzick, Sophie C Schneider, Minjee Kook, Julia Rose Iacono, Saira A Weinzimmer, Troy Quast, Sean M Olsen, Killian Rainey Hughes, Emily Jellinek-Russo, Amanda Perozo Garcia, Abigail Candelari, Leandra N Berry, Robin P Goin-Kochel, Wayne K Goodman, Eric A Storch

Center for Medical Ethics and Health Policy Staff Publications

Parent-led cognitive behavioral therapy (CBT) is an efficient, promising form of therapy that may be well suited for autistic youth with anxiety disorders, though to date it has been minimally tested. In this study, 87 autistic youth (7 to 13 years old) with anxiety disorders and their parents were randomized to two forms of parent-led CBT in which parents led their child through a guided CBT workbook across 12 weeks: one with low therapist contact (four 30-minute telehealth calls), and one with standard therapist contact (ten 60-minute telehealth calls). Anxiety, functional impairment, and autism features significantly declined across therapy, without …

Prospects For Leveraging The Microbiota As Medicine For Hypertension, David J Durgan, Jasenka Zubcevic, Matam Vijay-Kumar, Tao Yang, Ishan Manandhar, Sachin Aryal, Rikeish R Muralitharan, Hong-Bao Li, Ying Li, Justine M Abais-Battad, Jennifer L Pluznick, Dominik N Muller, Francine Z Marques, Bina Joe

Faculty, Staff and Students Publications

No abstract provided.