Digital Commons Network^™

Experiences With Menses In Transgender And Gender Nonbinary Adolescents., Beth I. Schwartz, Arielle Effron, Benjamin Bear, Vanessa L Short, Julia Eisenberg, Sarah Felleman, Anne E Kazak

Department of Obstetrics and Gynecology Faculty Papers

STUDY OBJECTIVE: To describe menstrual history, associated dysphoria, and desire for menstrual management in transgender male and gender diverse adolescents who were assigned female at birth

DESIGN: Retrospective chart review

SETTING: Tertiary care children's hospital

PARTICIPANTS: All patients seen in a multidisciplinary pediatric gender program from March 2015 through December 2020 who were assigned female at birth, identified as transgender male or gender nonbinary, and had achieved menarche

INTERVENTION: None

MAIN OUTCOME MEASURES: Patient demographics, menstrual history, interest in and prior experiences with menstrual management, parental support, and concerns about menstrual management

RESULTS: Of the 129 included patients, 116 (90%) …

The Association Between Lung Cancer Stigma And Race: A Descriptive Correlational Study, Karen Kane Mcdonnell, Lisa A. Webb, Swann A. Adams Ph.D., Ms, Face, Tisha M. Felder Phd, Msw, Rachel E. Davis Ph.D.

Publications

BACKGROUND:

Stigma is a formidable burden for survivors of lung cancer that can reduce the quality of life (QOL), resulting in physical, social and psychological challenges. This study investigates associations between stigma and depression, QOL and demographic and health-related characteristics, including race.

DESIGN:

An adapted conceptual model derived from the Cataldo Lung Cancer Stigma Scale guided this descriptive correlation study assessing stigma in African American and Caucasian survivors of lung cancer. Self-reported, written surveys measuring depression, QOL, lung cancer stigma and demographics were administered. Statistical analysis was conducted to assess associations between stigma and depression, stigma and QOL and stigma …

A Genome-Wide Association Study Of Obstructive Heart Defects Among Participants In The National Birth Defects Prevention Study, Sara R Rashkin, Mario Cleves, Gary M Shaw, Wendy N Nembhard, Eirini Nestoridi, Mary M Jenkins, Paul A Romitti, Xiang-Yang Lou, Marilyn L Browne, Laura E Mitchell, Andrew F Olshan, Kevin Lomangino, Sudeepa Bhattacharyya, John S Witte, Charlotte A Hobbs

Faculty, Staff and Student Publications

Obstructive heart defects (OHDs) share common structural lesions in arteries and cardiac valves, accounting for ~25% of all congenital heart defects. OHDs are highly heritable, resulting from interplay among maternal exposures, genetic susceptibilities, and epigenetic phenomena. A genome-wide association study was conducted in National Birth Defects Prevention Study participants (N

Insights From A Large-Scale Whole-Genome Sequencing Study Of Systolic Blood Pressure, Diastolic Blood Pressure, And Hypertension, Tanika N Kelly, Xiao Sun, Karen Y He, Michael R Brown, Sarah A Gagliano Taliun, Jacklyn N Hellwege, Marguerite R Irvin, Xuenan Mi, Jennifer A Brody, Nora Franceschini, Xiuqing Guo, Shih-Jen Hwang, Paul S De Vries, Yan Gao, Arden Moscati, Girish N Nadkarni, Lisa R Yanek, Tali Elfassy, Jennifer A Smith, Ren-Hua Chung, Amber L Beitelshees, Amit Patki, Stella Aslibekyan, Brandon M Blobner, Juan M Peralta, Themistocles L Assimes, Walter R Palmas, Chunyu Liu, Adam P Bress, Zhijie Huang, Lewis C Becker, Chii-Min Hwa, Jeffrey R O'Connell, Jenna C Carlson, Helen R Warren, Sayantan Das, Ayush Giri, Lisa W Martin, W Craig Johnson, Ervin R Fox, Erwin P Bottinger, Alexander C Razavi, Dhananjay Vaidya, Lee-Ming Chuang, Yen-Pei C Chang, Take Naseri, Deepti Jain, Hyun Min Kang, Adriana M Hung, Vinodh Srinivasasainagendra, Beverly M Snively, Dongfeng Gu, May E Montasser, Muagututi'a Sefuiva Reupena, Benjamin D Heavner, Jonathon Lefaive, James E Hixson, Kenneth M Rice, Fei Fei Wang, Jonas B Nielsen, Jianfeng Huang, Alyna T Khan, Wei Zhou, Jovia L Nierenberg, Cathy C Laurie, Nicole D Armstrong, Mengyao Shi, Yang Pan, Adrienne M Stilp, Leslie Emery, Quenna Wong, Nicola L Hawley, Ryan L Minster, Joanne E Curran, Patricia B Munroe, Daniel E Weeks, Kari E North, Russell P Tracy, Eimear E Kenny, Daichi Shimbo, Aravinda Chakravarti, Stephen S Rich, Alex P Reiner, John Blangero, Susan Redline, Braxton D Mitchell, Dabeeru C Rao, Yii-Der Ida Chen, Sharon L R Kardia, Robert C Kaplan, Rasika A Mathias, Jiang He, Bruce M Psaty, Myriam Fornage, Ruth J F Loos, Adolfo Correa, Eric Boerwinkle, Jerome I Rotter, Charles Kooperberg, Todd L Edwards, Gonçalo R Abecasis, Xiaofeng Zhu, Daniel Levy, Donna K Arnett, Alanna C Morrison, Samoan Obesity, Lifestyle, And Genetic Adaptations Study (Olaga) Group,‡ Nhlbi Trans-Omics For Precision Medicine Topmed) Consortium

Faculty, Staff and Student Publications

BACKGROUND: The availability of whole-genome sequencing data in large studies has enabled the assessment of coding and noncoding variants across the allele frequency spectrum for their associations with blood pressure.

METHODS: We conducted a multiancestry whole-genome sequencing analysis of blood pressure among 51 456 Trans-Omics for Precision Medicine and Centers for Common Disease Genomics program participants (stage-1). Stage-2 analyses leveraged array data from UK Biobank (N=383 145), Million Veteran Program (N=318 891), and Reasons for Geographic and Racial Differences in Stroke (N=10 643) participants, along with whole-exome sequencing data from UK Biobank (N=199 631) participants.

RESULTS: Two blood pressure signals …

Use Of Active Video Games With Or Without Videoconferencing On Health Outcomes In Adolescent And Young Adult Cancer Survivors: A Systematic Review, Ursela Christopherson, Stephanie J Wells, Nathan Parker, Elizabeth J Lyons, Michael D Swartz, Anna Blozinski, Karen Basen-Engquist, Susan Peterson, Maria C Swartz

Faculty, Staff and Student Publications

PURPOSE: Adolescent and young adult (AYA) cancer survivors experience greater functional deficits compared to non-cancer peers or older survivors with a similar diagnosis. Physical activity (PA) is a key strategy for mitigating functional decline, and motivation and peer support are critical PA facilitators in AYA cancer survivors. Active video games (AVGs) may be a "gateway" method to promote PA. Further, integrating AVGs into group videoconferencing, a medium used by AYAs to socialize, can capitalize on peer support needed for PA motivation. Thus, we examined the use of AVGs and/or videoconferencing in PA interventions that included AYA survivors and the effect …

Racial And Ethnic Disparities In The Refusal Of Surgical Treatment In Women 40 Years And Older With Breast Cancer In The Usa Between 2010 And 2017, Pierre Fwelo, Zenab I Yusuf, Abigail Adjei, Gabriel Huynh, Xianglin L Du

Faculty, Staff and Student Publications

PURPOSE: Although surgical resection is the main modality of treatment for breast cancer, some patients elect to refuse the recommended surgery. We assessed racial and ethnic differences in women 40 years and older who received or refused to receive surgical treatment for breast cancer in the USA and whether racial disparities in mortality were affected by their differences in the prevalence of refusal for surgical treatment.

METHODS: We studied 277,127 women with breast cancer using the Surveillance, Epidemiology, and End Results (SEER) data and performed multivariable logistic regressions to investigate the association between surgery status of breast cancer and race/ethnicity. …

A Systematic Review Up To 2018 Of Hiv And Associated Factors Among Criminal Justice-Involved (Cji) Black Sexual And Gender Minority Populations In The United States (Us), Russell Brewer, Santhoshini L Ramani, Aditya Khanna, Kayo Fujimoto, John A Schneider, Anna Hotton, Leo Wilton, Tania Escobedo, Nina T Harawa

Faculty, Staff and Student Publications

Black men who have sex with men (BMSM) and Black transgender women (BTW) are impacted by dual epidemics of HIV and incarceration. We advanced understanding of the relationship between criminal justice involvement, HIV, and other key HIV-related characteristics among these key populations in the US. We conducted a systematic review up to 2018 and 47 articles met the inclusion criteria of scientific publications involving quantitative findings of US-based HIV-related studies focused on criminal justice-involved (CJI) BMSM and BTW. Overall, there was a dearth of studies focused specifically on BTW. Criminal justice involvement was relatively high among BMSM and BTW and …

Mortality Among Patients With Covid-19 And Different Interstitial Lung Disease Subtypes: A Multicenter Cohort Study., Joy Zhao, Brandon Metra, Gautam George, Jesse Roman, Joseph Mallon, Baskaran Sundaram, Michael Li, Ross Summer

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

No abstract provided.

Gene Therapy For Fibrodysplasia Ossificans Progressiva: Feasibility And Obstacles, Elisabeth M W Eekhoff, Ruben D De Ruiter, Bernard J Smilde, Ton Schoenmaker, Teun J De Vries, Coen Netelenbos, Edward C Hsiao, Christiaan Scott, Nobuhiko Haga, Zvi Grunwald, Carmen L De Cunto, Maja Di Rocco, Patricia L R Delai, Robert J Diecidue, Vrisha Madhuri, Tae-Joon Cho, Rolf Morhart, Clive S Friedman, Michael Zasloff, Gerard Pals, Jae-Hyuck Shim, Guangping Gao, Frederick Kaplan, Robert J Pignolo, Dimitra Micha

Department of Anesthesiology Faculty Papers

Fibrodysplasia ossificans progressiva (FOP) is a rare and devastating genetic disease, in which soft connective tissue is converted into heterotopic bone through an endochondral ossification process. Patients succumb early as they gradually become trapped in a second skeleton of heterotopic bone. Although the underlying genetic defect is long known, the inherent complexity of the disease has hindered the discovery of effective preventions and treatments. New developments in the gene therapy field have motivated its consideration as an attractive therapeutic option for FOP. However, the immune system's role in FOP activation and the as-yet unknown primary causative cell, are crucial issues …

Prediction Of Breast Cancer-Related Lymphedema By Dermal Backflow Detected With Near-Infrared Fluorescence Lymphatic Imaging, Melissa B Aldrich, John C Rasmussen, Sarah M Desnyder, Wendy A Woodward, Wenyaw Chan, Eva M Sevick-Muraca, Elizabeth A Mittendorf, Benjamin D Smith, Michael C Stauder, Eric A Strom, George H Perkins, Karen E Hoffman, Melissa P Mitchell, Carlos H Barcenas, Lynn E Isales, Simona F Shaitelman

Faculty, Staff and Student Publications

PURPOSE: Mild breast cancer-related lymphedema (BCRL) is clinically diagnosed as a 5%-10% increase in arm volume, typically measured no earlier than 3-6 months after locoregional treatment. Early BCRL treatment is associated with better outcomes, yet amid increasing evidence that lymphedema exists in a latent form, treatment is typically delayed until arm swelling is obvious. In this study, we investigated whether near-infrared fluorescence lymphatic imaging (NIRF-LI) surveillance could characterize early onset of peripheral lymphatic dysfunction as a predictor of BCRL.

METHODS: In a prospective, longitudinal cohort/observational study (NCT02949726), subjects with locally advanced breast cancer who received axillary lymph node dissection and …

Perceived Discrimination And Injury At Work: A Cross-Sectional Study Among Latino Day Laborers, Lynn N Ibekwe, John S Atkinson, Rosalia Guerrero-Luera, Yesmel A King, Maria L Rangel, Maria Eugenia Fernández-Esquer

Faculty, Staff and Student Publications

BACKGROUND: Given the stigma of their undocumented status and their high prevalence of workplace injury, understanding the impact of discrimination on Latino day laborers (LDLs) is a critical public health issue.

METHODS: We surveyed LDLs (N = 149) and assessed their sociodemographics, experiences of and perceived reasons for discrimination, and work-related injury. A logistic regression examined the association between discrimination and injury, adjusting for sociodemographics. Next, Chi-square tests identified perceived reasons for discrimination associated with injury which were then included in a second logistic regression to test their association with injury, adjusting for discrimination and sociodemographics.

RESULTS: Participants reported a …

Perceived Discrimination And Injury At Work: A Cross-Sectional Study Among Latino Day Laborers, Lynn N Ibekwe, John S Atkinson, Rosalia Guerrero-Luera, Yesmel A King, Maria L Rangel, Maria Eugenia Fernández-Esquer

Faculty, Staff and Student Publications

BACKGROUND: Given the stigma of their undocumented status and their high prevalence of workplace injury, understanding the impact of discrimination on Latino day laborers (LDLs) is a critical public health issue.

METHODS: We surveyed LDLs (N = 149) and assessed their sociodemographics, experiences of and perceived reasons for discrimination, and work-related injury. A logistic regression examined the association between discrimination and injury, adjusting for sociodemographics. Next, Chi-square tests identified perceived reasons for discrimination associated with injury which were then included in a second logistic regression to test their association with injury, adjusting for discrimination and sociodemographics.

RESULTS: Participants reported a …

Association Of Disease Outcomes With Physical Activity In Multiple Sclerosis: A Cross-Sectional Study, Trinh L T Huynh, Stephanie L Silveira, Brenda Jeng, Robert W Motl

Faculty, Staff and Student Publications

Purpose/Objective Research: This study examined combinations of disease outcomes (i.e., walking, cognition, and symptoms) as correlates of physical activity subgroups (insufficiently active vs. sufficiently active) in persons with multiple sclerosis (MS).

RESEARCH METHOD/DESIGN: This study included 213 participants who completed walking and cognitive function tests and self-report measures of symptoms and physical activity. Multivariate analysis of variance and discriminant function analysis identified combinations of MS outcomes associated with physical activity.

RESULTS: The sample had a mean age of 49.6 years (

CONCLUSION/IMPLICATIONS: The findings identified walking endurance and limitations, processing speed, depression, and fatigue as primary correlates of physical activity …

Patients With Lung Cancer Of Different Racial Backgrounds Harbor Distinct Immune Cell Profiles, Yitian Xu, Licheng Zhang, Jose Thaiparambil, Sunny Mai, Dimuthu Nuwan Perera, Jilu Zhang, Ping-Ying Pan, Cristian Coarfa, Kenneth Ramos, Shu-Hsia Chen, Randa El-Zein

Faculty, Staff and Students Publications

UNLABELLED: Tumors accumulated with infiltrated immune cells (hot tumors) have a higher response rate to immune checkpoint blockade, when compared with those with minimal T-cell infiltration (cold tumors). We report here that patients with lung cancer with different racial backgrounds harbored distinct immune cell profiles in the tumor microenvironment. Compared with African Americans (AA), Caucasian Americans (CA) exhibited increased immune cell infiltration and vasculature, and increased survival. Changes of survival and immune profile were most pronounced among active smokers and nonsmokers, compared with former smokers and total patients. Neighborhood analysis showed that immune cells accumulated around cancer cells in CAs …

Exome Sequencing Identifies Genetic Variants In Anophthalmia And Microphthalmia, Jingjing Li, Wei Yang, Yuejun Jessie Wang, Chen Ma, Cynthia J Curry, Daniel Mcgoldrick, Deborah A Nickerson, Jessica X Chong, Elizabeth E Blue, James C Mullikin, Jennita Reefhuis, Wendy N Nembhard, Paul A Romitti, Martha M Werler, Marilyn L Browne, Andrew F Olshan, Richard H Finnell, Marcia L Feldkamp, Faith Pangilinan, Lynn M Almli, Mike J Bamshad, Lawrence C Brody, Mary M Jenkins, Gary M Shaw, University Of Washington Center For Mendelian Genomics, Nisc Comparative Sequencing Program, National Birth Defects Prevention Study

Faculty, Staff and Students Publications

Anophthalmia and microphthalmia (A/M) are rare birth defects affecting up to 2 per 10,000 live births. These conditions are manifested by the absence of an eye or reduced eye volumes within the orbit leading to vision loss. Although clinical case series suggest a strong genetic component in A/M, few systematic investigations have been conducted on potential genetic contributions owing to low population prevalence. To overcome this challenge, we utilized DNA samples and data collected as part of the National Birth Defects Prevention Study (NBDPS). The NBDPS employed multi-center ascertainment of infants affected by A/M. We performed exome sequencing on 67 …

Conventional And Advanced Mr Imaging Findings In A Cohort Of Pathology-Proven Dermoid Cysts Of The Pediatric Scalp And Skull, Bettina L Serrallach, Gunes Orman, M John Hicks, Nilesh Desai, Stephen Kralik, Thierry Agm Huisman

Faculty, Staff and Students Publications

BACKGROUND: In the pediatric population, dermoid cysts are among the most frequent lesions of the scalp and skull. Imaging plays a key role in characterizing scalp and skull lesions in order to narrow the differential diagnoses. In general, dermoids are described as heterogeneous T1-/T2-hypo- to hyperintense lesions on magnetic resonance imaging.

METHODS: The goal of this retrospective study is to evaluate the diffusion weighted imaging findings while reviewing the conventional T1-/T2-/T1+C-weighted MR characteristics in a pathology-proven series of 14 dermoids of the pediatric scalp and skull.

RESULTS: In our pediatric cohort (eight boys, six girls, age range 3-95 months), half …

Immune Phenotype Of The Cd4+ T Cells In The Aged Lymphoid Organs And Lacrimal Glands, Claudia M Trujillo-Vargas, Kelsey E Mauk, Humberto Hernandez, Rodrigo G De Souza, Zhiyuan Yu, Jeremias G Galletti, Jana Dietrich, Friedrich Paulsen, Cintia S De Paiva

Faculty, Staff and Students Publications

Aging is associated with a massive infiltration of T lymphocytes in the lacrimal gland. Here, we aimed to characterize the immune phenotype of aged CD4+ T cells in this tissue as compared with lymphoid organs. To perform this, we sorted regulatory T cells (Tregs, CD4+CD25+GITR+) and non-Tregs (CD4+CD25negGITRneg) in lymphoid organs from female C57BL/6J mice and subjected these cells to an immunology NanoString® panel. These results were confirmed by flow cytometry, live imaging, and tissue immunostaining in the lacrimal gland. Importantly, effector T helper 1 (Th1) genes were highly upregulated on aged Tregs, including the master regulator Tbx21. Among …

Oropharyngeal Cancer Outcomes Correlate With P16 Status, Multinucleation And Immune Infiltration, David C Wilde, Patricia D Castro, Kaustav Bera, Syeling Lai, Anant Madabhushi, German Corredor, Can Koyuncu, James S Lewis, Cheng Lu, Mitchell J Frederick, Allan M Frederick, Avery E Haugen, Jose P Zevallos, Erich M Sturgis, Justin Shi, Andrew T Huang, David J Hernandez, Heath D Skinner, Jan O Kemnade, Wendong Yu, Andrew G Sikora, Vlad C Sandulache

Faculty, Staff and Students Publications

Oropharyngeal squamous cell carcinoma (OPSCC), largely fueled by the human papillomavirus (HPV), has a complex biological and immunologic phenotype. Although HPV/p16 status can be used to stratify OPSCC patients as a function of survival, it remains unclear what drives an improved treatment response in HPV-associated OPSCC and whether targetable biomarkers exist that can inform a precision oncology approach. We analyzed OPSCC patients treated between 2000 and 2016 and correlated locoregional control (LRC), disease-free survival (DFS) and overall survival (OS) with conventional clinical parameters, risk parameters generated using deep-learning algorithms trained to quantify tumor-infiltrating lymphocytes (TILs) (OP-TIL) and multinucleated tumor cells …

Factors Associated With Parental Acceptance Of Covid-19 Vaccination: A Multicenter Pediatric Emergency Department Cross-Sectional Analysis, Brigitte M Baumann, Robert M Rodriguez, Amy M Delaroche, David Rayburn, Stephanie A Eucker, Nicole L Nadeau, Lisa A Drago, Danielle Cullen, Sarah Dennis Meskill, Suzanne Bialeck, Michael Gillman

Faculty, Staff and Students Publications

STUDY OBJECTIVE: During the delta surge of the COVID-19 pandemic in 2021, we sought to identify characteristics and beliefs associated with COVID-19 vaccination acceptance in parents of pediatric emergency department (ED) patients.

METHODS: We conducted a cross-sectional survey-based study of the parents of children aged 3 to 16 years presenting to 1 of 9 pediatric EDs from June to August 2021 to assess the parental acceptance of COVID-19 vaccines. Using multiple variable regression, we ascertained which factors were associated with parental and pediatric COVID-19 vaccination acceptance.

RESULTS: Of 1,491 parents approached, 1,298 (87%) participated, of whom 50% of the parents …

Randomized Placebo-Controlled Trial Of Losartan For Pediatric Nafld, Miriam B Vos, Mark L Van Natta, Niviann M Blondet, Srinivasan Dasarathy, Mark Fishbein, Paula Hertel, Ajay K Jain, Saul J Karpen, Joel E Lavine, Saeed Mohammad, Laura A Miriel, Jean P Molleston, Marialena Mouzaki, Arun Sanyal, Emily P Sharkey, Jeffrey B Schwimmer, James Tonascia, Laura A Wilson, Stavra A Xanthakos, Nash Clinical Research Network

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: To date, no pharmacotherapy exists for pediatric NAFLD. Losartan, an angiotensin II receptor blocker, has been proposed as a treatment due to its antifibrotic effects.

APPROACH AND RESULTS: The Nonalcoholic Steatohepatitis Clinical Research Network conducted a multicenter, double-masked, placebo-controlled, randomized clinical trial in children with histologically confirmed NAFLD at 10 sites (September 2018 to April 2020). Inclusion criteria were age 8-17 years, histologic NAFLD activity score ≥ 3, and serum alanine aminotransferase (ALT) ≥ 50 U/l. Children received 100 mg of losartan or placebo orally once daily for 24 weeks. The primary outcome was change in ALT …

Roles And Responsibilities Of Medicine Subinternship Directors : Medicine Subinternship Director Roles, Nicholas S Duca, Cindy J Lai, Temple A Ratcliffe, Irene Alexandraki, Nadia Ismail, Michael Kisielewski, Jackcy Jacob, Katherine Walsh, Diane L Levine, Karen Szauter, Harish Jasti, Amber T Pincavage, Jeffrey Larochelle, Susan A Glod

Faculty, Staff and Students Publications

BACKGROUND: The internal medicine (IM) subinternship (also referred to as acting internship) plays a crucial part in preparing medical students for residency. The roles, responsibilities, and support provided to subinternship directors have not been described.

OBJECTIVE: We sought to describe the current role of IM subinternship directors with respect to their responsibilities, salary support, and reporting structure.

DESIGN: Nationally representative, annually recurring thematic survey of IM core clerkship directors with membership in an academic professional association as of September 2017.

PARTICIPANTS: A total of 129 core clinical medicine clerkship directors at Liaison Committee on Medical Education fully accredited U.S./U.S.-territory-based medical …

Integrated Multi-Omic Characterization Of Congenital Heart Disease, Matthew C Hill, Zachary A Kadow, Hali Long, Yuka Morikawa, Thomas J Martin, Emma J Birks, Kenneth S Campbell, Jeanne Nerbonne, Kory Lavine, Lalita Wadhwa, Jun Wang, Diwakar Turaga, Iki Adachi, James F Martin

Faculty, Staff and Students Publications

The heart, the first organ to develop in the embryo, undergoes complex morphogenesis that when defective results in congenital heart disease (CHD). With current therapies, more than 90% of patients with CHD survive into adulthood, but many suffer premature death from heart failure and non-cardiac causes1. Here, to gain insight into this disease progression, we performed single-nucleus RNA sequencing on 157,273 nuclei from control hearts and hearts from patients with CHD, including those with hypoplastic left heart syndrome (HLHS) and tetralogy of Fallot, two common forms of cyanotic CHD lesions, as well as dilated and hypertrophic cardiomyopathies. We …

A Large-Scale Genome-Wide Gene-Gene Interaction Study Of Lung Cancer Susceptibility In Europeans With A Trans-Ethnic Validation In Asians, Ruyang Zhang, Sipeng Shen, Yongyue Wei, Ying Zhu, Yi Li, Jiajin Chen, Jinxing Guan, Zoucheng Pan, Yuzhuo Wang, Meng Zhu, Junxing Xie, Xiangjun Xiao, Dakai Zhu, Yafang Li, Demetrios Albanes, Maria Teresa Landi, Neil E Caporaso, Stephen Lam, Adonina Tardon, Chu Chen, Stig E Bojesen, Mattias Johansson, Angela Risch, Heike Bickeböller, H-Erich Wichmann, Gadi Rennert, Susanne Arnold, Paul Brennan, James D Mckay, John K Field, Sanjay S Shete, Loic Le Marchand, Geoffrey Liu, Angeline S Andrew, Lambertus A Kiemeney, Shan Zienolddiny-Narui, Annelie Behndig, Mikael Johansson, Angela Cox, Philip Lazarus, Matthew B Schabath, Melinda C Aldrich, Juncheng Dai, Hongxia Ma, Yang Zhao, Zhibin Hu, Rayjean J Hung, Christopher I Amos, Hongbing Shen, Feng Chen, David C Christiani

Faculty, Staff and Students Publications

INTRODUCTION: Although genome-wide association studies have been conducted to investigate genetic variation of lung tumorigenesis, little is known about gene-gene (G × G) interactions that may influence the risk of non-small cell lung cancer (NSCLC).

METHODS: Leveraging a total of 445,221 European-descent participants from the International Lung Cancer Consortium OncoArray project, Transdisciplinary Research in Cancer of the Lung and UK Biobank, we performed a large-scale genome-wide G × G interaction study on European NSCLC risk by a series of analyses. First, we used BiForce to evaluate and rank more than 58 billion G × G interactions from 340,958 single-nucleotide polymorphisms …

Cross-Ancestry Genome-Wide Meta-Analysis Of 61,047 Cases And 947,237 Controls Identifies New Susceptibility Loci Contributing To Lung Cancer, Jinyoung Byun, Younghun Han, Yafang Li, Jun Xia, Erping Long, Jiyeon Choi, Xiangjun Xiao, Meng Zhu, Wen Zhou, Ryan Sun, Yohan Bossé, Zhuoyi Song, Ann Schwartz, Christine Lusk, Thorunn Rafnar, Kari Stefansson, Tongwu Zhang, Wei Zhao, Rowland W Pettit, Yanhong Liu, Xihao Li, Hufeng Zhou, Kyle M Walsh, Ivan Gorlov, Olga Gorlova, Dakai Zhu, Susan M Rosenberg, Susan Pinney, Joan E Bailey-Wilson, Diptasri Mandal, Mariza De Andrade, Colette Gaba, James C Willey, Ming You, Marshall Anderson, John K Wiencke, Demetrius Albanes, Stephan Lam, Adonina Tardon, Chu Chen, Gary Goodman, Stig Bojeson, Hermann Brenner, Maria Teresa Landi, Stephen J Chanock, Mattias Johansson, Thomas Muley, Angela Risch, H-Erich Wichmann, Heike Bickeböller, David C Christiani, Gad Rennert, Susanne Arnold, John K Field, Sanjay Shete, Loic Le Marchand, Olle Melander, Hans Brunnstrom, Geoffrey Liu, Angeline S Andrew, Lambertus A Kiemeney, Hongbing Shen, Shanbeh Zienolddiny, Kjell Grankvist, Mikael Johansson, Neil Caporaso, Angela Cox, Yun-Chul Hong, Jian-Min Yuan, Philip Lazarus, Matthew B Schabath, Melinda C Aldrich, Alpa Patel, Qing Lan, Nathaniel Rothman, Fiona Taylor, Linda Kachuri, John S Witte, Lori C Sakoda, Margaret Spitz, Paul Brennan, Xihong Lin, James Mckay, Rayjean J Hung, Christopher I Amos

Faculty, Staff and Students Publications

To identify new susceptibility loci to lung cancer among diverse populations, we performed cross-ancestry genome-wide association studies in European, East Asian and African populations and discovered five loci that have not been previously reported. We replicated 26 signals and identified 10 new lead associations from previously reported loci. Rare-variant associations tended to be specific to populations, but even common-variant associations influencing smoking behavior, such as those with CHRNA5 and CYP2A6, showed population specificity. Fine-mapping and expression quantitative trait locus colocalization nominated several candidate variants and susceptibility genes such as IRF4 and FUBP1. DNA damage assays of prioritized genes in lung …

Chronic Granulomatous Disease-Like Presentation Of A Child With Autosomal Recessive Pkcδ Deficiency, Anna-Lena Neehus, Karen Tuano, Tom Le Voyer, Sarada L Nandiwada, Kruthi Murthy, Anne Puel, Jean-Laurent Casanova, Javier Chinen, Jacinta Bustamante

Faculty, Staff and Students Publications

BACKGROUND: Autosomal recessive (AR) PKCδ deficiency is a rare inborn error of immunity (IEI) characterized by autoimmunity and susceptibility to bacterial, fungal, and viral infections. PKCδ is involved in the intracellular production of reactive oxidative species (ROS).

MATERIAL AND METHODS: We studied a 5-year old girl presenting with a history of Burkholderia cepacia infection. She had no history of autoimmunity, lymphocyte counts were normal, and no auto-antibodies were detected in her plasma. We performed a targeted panel analysis of 407 immunity-related genes and immunological investigations of the underlying genetic condition in this patient.

RESULTS: Consistent with a history suggestive of …

Early Growth Response 1 Transcription Factor Is Essential For The Pathogenic Properties Of Human Endometriotic Epithelial Cells, Vineet K Maurya, Maria M Szwarc, Rodrigo Fernandez-Valdivia, David M Lonard, Song Yong, Niraj Joshi, Asgerally T Fazleabas, John P Lydon

Faculty, Staff and Students Publications

Although a non-malignant gynecological disorder, endometriosis displays some pathogenic features of malignancy, such as cell proliferation, migration, invasion and adaptation to hypoxia. Current treatments of endometriosis include pharmacotherapy and/or surgery, which are of limited efficacy and often associated with adverse side effects. Therefore, to develop more effective therapies to treat this disease, a broader understanding of the underlying molecular mechanisms that underpin endometriosis needs to be attained. Using immortalized human endometriotic epithelial and stromal cell lines, we demonstrate that the early growth response 1 (EGR1) transcription factor is essential for cell proliferation, migration and invasion, which represent some of the …

The Geriatric Nutritional Risk Index As A Predictor Of Complications In Geriatric Trauma Patients: Author Reply In Response To: “The Admission Serum Level Of Albumin Cannot Thoroughly Represent The Nutritional Status Of Trauma Patients”, Heather R Kregel, Patrick B Murphy, Mina Attia, David E Meyer, Rachel S Morris, Ezenwa C Onyema, Sasha D Adams, Charles E Wade, John A Harvin, Lillian S Kao, Thaddeus J Puzio

Faculty, Staff and Student Publications

BACKGROUND: Malnutrition is associated with increased morbidity and mortality after trauma. The Geriatric Nutritional Risk Index (GNRI) is a validated scoring system used to predict the risk of complications related to malnutrition in nontrauma patients. We hypothesized that GNRI is predictive of worse outcomes in geriatric trauma patients.

METHODS: This was a single-center retrospective study of trauma patients 65 years or older admitted in 2019. Geriatric Nutritional Risk Index was calculated based on admission albumin level and ratio of actual body weight to ideal body weight. Groups were defined as major risk (GNRI98). The primary outcome was mortality. Secondary outcomes …

Elucidating The Role Of Cerebellar Synaptic Dysfunction In C9orf72-Als/Ftd - A Systematic Review And Meta-Analysis, Aleksandra Kaliszewska, Joseph Allison, Tarik-Tarkan Col, Christopher Shaw, Natalia Arias

Faculty, Staff and Student Publications

A hexanucleotide repeat expansion in the C9orf72 gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) with synaptic dysfunction identified as an early pathological hallmark. Although TDP-43 pathology and overt neurodegeneration are largely absent from the cerebellum, the pathological hallmarks of RNA foci and dipeptide repeat protein (DPR) inclusions are most abundant. Here, we present a systematic literature search in the databases of PubMed, Scopus, Embase, Web of Science and Science Direct up until March 5, 2021, which yielded 19,515 publications. Following the exclusion criteria, 72 articles were included having referred to C9orf72 …

Strategy For Generating Blinded Evidence For Single-Arm Trials With External Controls Using Expert Review Of Home Video, Bharti Manwani, Carson Finger, Lynda Lisabeth

Faculty, Staff and Student Publications

Stroke risk and prevalence increase with advanced age and women tend to be older than men at the time of their first stroke. Advanced age in women confers unique stroke risks that are beyond reproductive factors. Previous reviews and guidelines have largely focused on risk factors specific to women, with a predominant focus on reproductive factors and, therefore, younger to middle-aged women. This review aims to specifically describe stroke risk factors in elderly women, the population of women where the majority of strokes occur, with a focus on atrial fibrillation, hormone therapy, psychosocial risk factors, and cognitive impairment. Our review …

Glucose Uptake By Glut1 In Photoreceptors Is Essential For Outer Segment Renewal And Rod Photoreceptor Survival, Lauren L. Daniele, John Y.S. Han, Ivy S Samuels, Ravikiran Komirisetty, Nikhil Mehta, Jessica L Mccord, Minzhong Yu, Yekai Wang, Kathleen Boesze-Battaglia, Brent A Bell, Jianhai Du, Neal S Peachey, Nancy J. Philp

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Photoreceptors consume glucose supplied by the choriocapillaris to support phototransduction and outer segment (OS) renewal. Reduced glucose supply underlies photoreceptor cell death in inherited retinal degeneration and age-related retinal disease. We have previously shown that restricting glucose transport into the outer retina by conditional deletion of Slc2a1 encoding GLUT1 resulted in photoreceptor loss and impaired OS renewal. However, retinal neurons, glia, and the retinal pigment epithelium play specialized, synergistic roles in metabolite supply and exchange, and the cell-specific map of glucose uptake and utilization in the retina is incomplete. In these studies, we conditionally deleted Slc2a1 in a pan-retinal or …