Medical Specialties Commons^™

Parental Diabetes Distress Is A Stronger Predictor Of Child Hba1c Than Diabetes Device Use In School-Age Children With Type 1 Diabetes., Susana R. Patton, Nicole Kahhan, Jessica S. Pierce, Matthew Benson, Larry A. Fox, Mark A. Clements

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: Diabetes distress (DD) describes the unrelenting emotional and behavioral challenges of living with, and caring for someone living with, type 1 diabetes (T1D). We investigated associations between parent-reported and child-reported DD, T1D device use, and child glycated hemoglobin (HbA1c) in 157 families of school-age children.

RESEARCH DESIGN AND METHODS: Parents completed the Parent Problem Areas in Diabetes-Child (PPAID-C) and children completed the Problem Areas in Diabetes-Child (PAID-C) to assess for DD levels. Parents also completed a demographic form where they reported current insulin pump or continuous glucose monitor (CGM) use (ie, user/non-user). We measured child HbA1c using a valid …

Differentiating Urgent From Elective Cases Matters In Minority Populations: Developing An Ordinal "Desirability Of Outcome Ranking" To Increase Granularity And Sensitivity Of Surgical Outcomes Assessment, Michael A Jacobs, Susanne Schmidt, Daniel E Hall, Karyn B Stitzenberg, Lillian S Kao, Chen-Pin Wang, Laura S Manuel, Paula K Shireman

Faculty, Staff and Student Publications

BACKGROUND: Surgical analyses often focus on single or binary outcomes; we developed an ordinal Desirability of Outcome Ranking (DOOR) for surgery to increase granularity and sensitivity of surgical outcome assessments. Many studies also combine elective and urgent procedures for risk adjustment. We used DOOR to examine complex associations of race/ethnicity and presentation acuity.

STUDY DESIGN: NSQIP (2013 to 2019) cohort study assessing DOOR outcomes across race/ethnicity groups risk-adjusted for frailty, operative stress, preoperative acute serious conditions, and elective, urgent, and emergent cases.

RESULTS: The cohort included 1,597,199 elective, 340,350 urgent, and 185,073 emergent cases with patient mean age of 60.0 …

Atopic Dermatitis And The Risk Of Myocardial Infarction And All-Cause Mortality: A Nationwide Population-Based Cohort Study, Yu Ri Woo, Minah Cho, Kyung Do Han, Sang Hyun Cho, Ji Hyun Lee

Faculty, Staff and Student Publications

PURPOSE: Atopic dermatitis (AD) is a chronic inflammatory skin disorder associated with various comorbidities. However, inconsistent results on the risk of myocardial infarction (MI) and mortality have been reported in patients with AD. This study was aimed to evaluate the risk of MI and all-cause mortality in patients with AD.

METHODS: This nationwide population-based retrospective cohort study enrolled 56,205 adults ≥ 20 years of age with AD and 3,825,609 controls without AD from the Korean National Health Service (NHIS) database from 2009 to 2016.

RESULTS: The risk of MI (adjusted hazard ratio [aHR], 1.111, 95% confidence interval [CI], 1.050-1.176) was …

The Effects Of Equine-Assisted Activities On Execution Function In Children Aged 7–8 Years: A Randomized Controlled Trial, Xiaodong Cheng, Kexin Zhen, Yongzhao Fan, Qian Tang, Hao Wu

Faculty, Staff and Student Publications

BACKGROUND: This study examines the effects of equine-assisted activity (EAA) training on executive functioning (EF) (inhibitory control, working memory, and cognitive flexibility) in children aged 7-8 years.

METHODS: Twenty-Four healthy children aged 7-8 years with a 1:1 ratio of boys to girls were randomly divided into EAA group (EAAG) or control group (CG). The subjects in EAAG were trained for 12 weeks, and CG participated in normal daily activities. All subjects conducted the Flanker, 1-Back, and More-odd shifting tasks at rest and recorded the average reaction times (RTs) and accuracy data of each task.

RESULTS: After 12 weeks of EAA …

Lymphocytic Choriomeningitis Virus In Person Living With Hiv, Connecticut, Usa, 2021, Jonathan Dyal, Shiv Gandhi, Caitlin M Cossaboom, Austin Leach, Ketan Patel, Marjorie Golden, Joseph Canterino, Marie-Louise Landry, Debi Cannon, Mary Choi, Inna Krapiunaya, John D Klena, Trevor Shoemaker

Faculty, Staff and Student Publications

Lymphocytic choriomeningitis virus is an underreported cause of miscarriage and neurologic disease. Surveillance remains challenging because of nonspecific symptomatology, inconsistent case reporting, and difficulties with diagnostic testing. We describe a case of acute lymphocytic choriomeningitis virus disease in a person living with HIV in Connecticut, USA, identified by using quantitative reverse transcription PCR.

Feasibility And Clinical Acceptability Of Automation-Assisted 3d Conformal Radiotherapy Planning For Patients With Cervical Cancer In A Resource-Constrained Setting, Sikudhani Muya, Jerry Ndumbalo, Sarah Kutika Nyagabona, Shaid Yusuf, Dong Joo Rhee, Beatrice Paul Mushi, Benjamin Li, Li Zhang, Surbhi Grover, Mary Feng, I-Chow Hsu, Elia Mmbaga, Katherine Van Loon, Laurence Court, Melody Xu

Faculty, Staff and Student Publications

Purpose: The Ocean Road Cancer Institute (ORCI) in Tanzania began offering 3D conformal radiation therapy (3DCRT) in 2018. Steep learning curves, high patient volume, and a limited workforce resulted in long radiation therapy (RT) planning workflows. We aimed to establish the feasibility of implementing an automation-assisted cervical cancer 3DCRT planning system.

Materials and methods: We performed chart abstractions on 30 patients with cervical cancer treated with 3DCRT at ORCI. The Radiation Planning Assistant (RPA) generated a new automated set of contours and plans on the basis of anonymized computed tomography images. Each were assessed for edit time requirements, dose-volume safety …

Evaluation Of The Prognostic Role Of Liver Metastases On Patient Outcomes: Systematic Review And Meta-Analysis, Jessica J Waninger, Vincent T Ma, Zoey Chopra, Ashley N Pearson, Michael D Green

Faculty, Staff and Student Publications

The liver is a common site of metastasis for many primary malignancies, but the quantitative impact on survival is unknown. We performed a systematic review and meta-analysis of 83 studies (604,853 patients) assessing the overall hazard associated with liver metastases by primary tumor type and treatment regimen. The pooled overall survival hazard ratio (HR) for all included studies was 1.77 (95% confidence interval [CI], 1.62-1.93). Patients with breast cancer primaries fared the worst (HR, 2.37; 95% CI, 1.64-3.44), as did patients treated with immunotherapies (HR, 1.86; 95% CI, 1.42-2.42). Liver metastases negatively impact survival, necessitating new approaches to disease management.

Immune Checkpoint Inhibitors Suppress Hepatitis C Virus Replication In Infected Patients With Solid Tumors, Marcel Yibirin, Khalis Mustafayev, Jeff Hosry, Pooja Pundhir, Joseph Klingen, Eduardo Yepez Guevara, Bruno P Granwehr, Ahmed Kaseb, Aung Naing, Sapna Patel, Amishi Y Shah, Ferdinandos Skoulidis, Hussein A Tawbi, Lan Wang, Ethan Miller, Hao Chi Zhang, Amado Zurita-Saavedra, Harrys A Torres

Faculty, Staff and Student Publications

Introduction: Data are scarce regarding the virologic impact and safety of immune checkpoint inhibitors (ICI) in patients with chronic hepatitis C virus (HCV) infection. We examined the virologic impact of ICI in HCV-infected patients with solid tumors and their safety.

Methods: HCV-infected patients with solid tumor treated with ICI at our institution between April 26, 2016, and January 5, 2022, were enrolled in a prospective observational study. The primary outcomes were ICI-induced changes in HCV viremia (HCV inhibition and HCV reactivation) and safety of ICI.

Results: We enrolled 52 consecutive patients with solid tumors treated with ICI. Most were men …

Fetal Echocardiographic Z Score Pilot Project: Study Design And Impact Of Gestational Age And Variable Type On Reproducibility Of Measurements Within And Across Investigators, Anita J Moon-Grady, Hyejung Lee, Leo Lopez, Oluwatosin Fatusin, Lindsay R Freud, Whitnee Hogan, Anita Krishnan, Carol Mcfarland, L Luann Minich, Shaine A Morris, Nelangi Pinto, Angela P Presson, Theresa A Tacy, Mary T Donofrio

Faculty, Staff and Students Publications

Background: Fetal echocardiography is widely available, but normative data are not robust. In this pilot study, the authors evaluated (1) the feasibility of prespecified measurements in a normal fetal echocardiogram to inform study design and (2) measurement variability to assign thresholds of clinical significance and guide analyses in larger fetal echocardiographic Z score initiatives.

Methods: Images from predefined gestational age groups (16-20, >20-24, >24-28, and >28-32 weeks) were retrospectively analyzed. Fetal echocardiography expert raters attended online group training and then independently analyzed 73 fetal studies (18 per age group) in a fully crossed design of 53 variables; each observer repeated …

Maternal Metabolism Influences Neural Tube Closure, Rachel A Keuls, Richard H Finnell, Ronald J Parchem

Faculty, Staff and Students Publications

Changes in maternal nutrient availability due to diet or disease significantly increase the risk of neural tube defects (NTDs). Because the incidence of metabolic disease continues to rise, it is urgent that we better understand how altered maternal nutrient levels can influence embryonic neural tube development. Furthermore, primary neurulation occurs before placental function during a period of histiotrophic nutrient exchange. In this review we detail how maternal metabolites are transported by the yolk sac to the developing embryo. We discuss recent advances in understanding how altered maternal levels of essential nutrients disrupt development of the neuroepithelium, and identify points of …

Loss Of The Maternal Effect Gene Nlrp2 Alters The Transcriptome Of Ovulated Mouse Oocytes And Impacts Expression Of Histone Demethylase Kdm1b, Zahra Anvar, Imen Chakchouk, Momal Sharif, Sangeetha Mahadevan, Eleni Theodora Nasiotis, Li Su, Zhandong Liu, Ying-Wooi Wan, Ignatia B Van Den Veyver

Faculty, Staff and Students Publications

The subcortical maternal complex (SCMC) is a multiprotein complex in oocytes and preimplantation embryos that is encoded by maternal effect genes. The SCMC is essential for zygote-to-embryo transition, early embryogenesis, and critical zygotic cellular processes, including spindle positioning and symmetric division. Maternal deletion of Nlrp2, which encodes an SCMC protein, results in increased early embryonic loss and abnormal DNA methylation in embryos. We performed RNA sequencing on pools of meiosis II (MII) oocytes from wild-type and Nlrp2-null female mice that were isolated from cumulus-oocyte complexes (COCs) after ovarian stimulation. Using a mouse reference genome-based analysis, we found 231 …

Age Differences In Core Symptoms And Symptom Relationships In Patients With Irritable Bowel Syndrome: A Network Analysis, Pei-Lin Yang, Kendra J Kamp, Robert L Burr, Hsin-Yi Jean Tang, Adrian Dobra, Robert J Shulman, Margaret M Heitkemper

Faculty, Staff and Students Publications

INTRODUCTION: Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction, characterized by symptoms of abdominal pain and changes in bowel habits. It often co-occurs with extraintestinal somatic and psychological symptoms. However, the nature of the interrelationships among these symptoms is unclear. Although previous studies have noted age differences in IBS prevalence and specific symptom severity, it remains unknown whether specific symptoms and symptom relationships may differ by age.

METHODS: Symptom data were collected in 355 adults with IBS (mean age 41.4 years, 86.2% female). Network analysis was used to examine the interrelationships among 28 symptoms and to identify …

Loss Of Growth Differentiation Factor 15 Exacerbates Lung Injury In Neonatal Mice, Faeq Al-Mudares, Manuel Cantu Gutierrez, Abiud Cantu, Weiwu Jiang, Lihua Wang, Xiaoyu Dong, Bhagavatula Moorthy, Eniko Sajti, Krithika Lingappan

Faculty, Staff and Students Publications

Growth differentiation factor 15 (GDF15) is a divergent member of the transforming growth factor-β (TGF-β) superfamily, and its expression increases under various stress conditions, including inflammation, hyperoxia, and senescence. GDF15 expression is increased in neonatal murine bronchopulmonary dysplasia (BPD) models, and GDF15 loss exacerbates oxidative stress and decreases cellular viability in vitro. Our overall hypothesis is that the loss of GDF15 will exacerbate hyperoxic lung injury in the neonatal lung in vivo. We exposed neonatal

Examining Whether Genetic Variants Moderate The Skeletal Effects Of Selective Serotonin Reuptake Inhibitors In Older Adolescents And Young Adults, Ifeoma Ezenwabachili, Emira Deumic Shultz, James A Mills, Vicki Ellingrod, Chadi A Calarge

Faculty, Staff and Students Publications

Objective: To examine whether serotonin (5-HT) related genetic variants moderate the effects of selective serotonin reuptake inhibitors (SSRIs) on skeletal outcomes. Methods: Trabecular bone mineral density (BMD) at the radius, lumbar spine (LS) BMD, total body less head (TBLH) bone mineral content (BMC) and markers of bone metabolism (osteocalcin, C-terminal telopeptide of type I collagen [CTX-1], and bone specific alkaline phosphatase to CTX-1 ratio) were examined in an observational study, enrolling 15- to 20-year-old participants, unmedicated or within a month of SSRI initiation. Variants in HTR1A (rs6295), HTR1B (rs6296), HTR1D (rs6300), HTR2A (rs6311 and rs6314), HTR2B (rs6736017), and the serotonin …

Global Sumoylation In Mouse Oocytes Maintains Oocyte Identity And Regulates Chromatin Remodeling And Transcriptional Silencing At The End Of Folliculogenesis, Shawn M Briley, Avery A Ahmed, Tessa E Steenwinkel, Peixin Jiang, Sean M Hartig, Karen Schindler, Stephanie A Pangas

Faculty, Staff and Students Publications

Meiotically competent oocytes in mammals undergo cyclic development during folliculogenesis. Oocytes within ovarian follicles are transcriptionally active, producing and storing transcripts required for oocyte growth, somatic cell communication and early embryogenesis. Transcription ceases as oocytes transition from growth to maturation and does not resume until zygotic genome activation. Although SUMOylation, a post-translational modification, plays multifaceted roles in transcriptional regulation, its involvement during oocyte development remains poorly understood. In this study, we generated an oocyte-specific knockout of Ube2i, encoding the SUMO E2 enzyme UBE2I, using Zp3-cre+ to determine how loss of oocyte SUMOylation during folliculogenesis affects oocyte development. Ube2i Zp3-cre+ female …

Revision Tracheotomy Complicated By History Of Follicular B-Cell Lymphoma, Sarah Ustrell, Jordan K Simmons, Garrett Henkle, Adam R Szymanowski

Faculty, Staff and Students Publications

This case report presents a 65-year-old woman with multiple complications during a revision tracheotomy including subcutaneous emphysema and a pneumothorax. Management of her airway was complicated by a history of recurrent follicular B-cell lymphoma associated with extensive cervical lymphadenopathy. We detail the importance of heightened clinical awareness and the use of intraoperative safety adjuncts when performing revision tracheostomies.

Intravenous Aviptadil And Remdesivir For Treatment Of Covid-19-Associated Hypoxaemic Respiratory Failure In The Usa (Tesico): A Randomised, Placebo-Controlled Trial, Samuel M Brown, Christina E Barkauskas, Birgit Grund, Shweta Sharma, Andrew N Phillips, Lindsay Leither, Ithan D Peltan, Michael Lanspa, Daniel L Gilstrap, Ahmad Mourad, Kathleen Lane, Jeremy R Beitler, Alexis L Serra, Ivan Garcia, Eyad Almasri, Mohamed Fayed, Kinsley Hubel, Estelle S Harris, Elizabeth A Middleton, Macy A G Barrios, Kusum S Mathews, Neha N Goel, Samuel Acquah, Jarrod Mosier, Cameron Hypes, Elizabeth Salvagio Campbell, Akram Khan, Catherine L Hough, Jennifer G Wilson, Joseph E Levitt, Abhijit Duggal, Siddharth Dugar, Andrew J Goodwin, Charles Terry, Peter Chen, Sam Torbati, Nithya Iyer, Uriel S Sandkovsky, Nicholas J Johnson, Bryce R H Robinson, Michael A Matthay, Neil R Aggarwal, Ivor S Douglas, Jonathan D Casey, Manuel Hache-Marliere, J Georges Youssef, William Nkemdirim, Brad Leshnower, Omar Awan, Sonal Pannu, Darragh Shane O'Mahony, Prasad Manian, J W Awori Hayanga, Glenn W Wortmann, Bruno M Tomazini, Robert F Miller, Jens-Ulrik Jensen, Daniel D Murray, Nina A Bickell, Jigna Zatakia, Sarah Burris, Elizabeth S Higgs, Ven Natarajan, Robin L Dewar, Adam Schechner, Nayon Kang, Alejandro Arenas-Pinto, Fleur Hudson, Adit A Ginde, Wesley H Self, Angela J Rogers, Cathryn F Oldmixon, Haley Morin, Adriana Sanchez, Amy C Weintrob, Alexandre Biasi Cavalcanti, Anne Davis-Karim, Nicole Engen, Eileen Denning, B Taylor Thompson, Annetine C Gelijns, Virginia Kan, Victoria J Davey, Jens D Lundgren, Abdel G Babiker, James D Neaton, H Clifford Lane

Faculty, Staff and Student Publications

BACKGROUND: There is a clinical need for therapeutics for COVID-19 patients with acute hypoxemic respiratory failure whose 60-day mortality remains at 30-50%. Aviptadil, a lung-protective neuropeptide, and remdesivir, a nucleotide prodrug of an adenosine analog, were compared with placebo among patients with COVID-19 acute hypoxaemic respiratory failure.

METHODS: TESICO was a randomised trial of aviptadil and remdesivir versus placebo at 28 sites in the USA. Hospitalised adult patients were eligible for the study if they had acute hypoxaemic respiratory failure due to confirmed SARS-CoV-2 infection and were within 4 days of the onset of respiratory failure. Participants could be randomly …

Greater Male Variability In Daily Energy Expenditure Develops Through Puberty, Lewis G Halsey, Vincent Careau, Philip N Ainslie, Heliodoro Alemán-Mateo, Lene F Andersen, Liam J Anderson, Leonore Arab, Issad Baddou, Linda Bandini, Kweku Bedu-Addo, Ellen E Blaak, Stephane Blanc, Alberto G Bonomi, Carlijn V C Bouten, Pascal Bovet, Soren Brage, Maciej S Buchowski, Nancy Butte, Stephan G Camps, Regian Casper, Graeme L Close, Lisa H Colbert, Jamie A Cooper, Richard Cooper, Prasangi Dabare, Sai Krupa Das, Peter S W Davies, Sanjoy Deb, Christine Delisle Nyström, William Dietz, Lara R Dugas, Simon Eaton, Ulf Ekelund, Asmaa El Hamdouchi, Sonja Entringer, Terrence Forrester, Barry W Fudge, Melanie Gillingham, Annelies H Goris, Michael Gurven, Hinke Haisma, Catherine Hambly, Daniel Hoffman, Marije B Hoos, Sumei Hu, Noorjehan Joonas, Annemiek Joosen, Peter Katzmarzyk, Kitty P Kempen, Misaka Kimura, William E Kraus, Wantanee Kriengsinyos, Rebecca Kuriyan, Robert F Kushner, Estelle V Lambert, Pulani Lanerolle, Christel L Larsson, Nader Lessan, Marie Löf, Corby Martin, Eric Matsiko, Gerwin A Meijer, James C Morehen, James P Morton, Aviva Must, Marian Neuhouser, Theresa A Nicklas, Robert M Ojiambo, Kirsi H Pietilainen, Yannis P Pitsiladis, Jacob Plange-Rhule, Guy Plasqui, Ross L Prentice, Roberto Rabinovich, Susan B Racette, David A Raichen, Eric Ravussin, Leanne Redman, John J Reilly, Rebecca Reynolds, Susan Roberts, Jennifer C Rood, Dulani Samaranayake, Luís B Sardinha, Albertine J Scuitt, Analiza M Silva, Srishti Sinha, Anders M Sjödin, Eric Stice, Albert Stunkard, Samuel S Urlacher, Mauro Eduardo Valencia, Giulio Valenti, Ludo M Van Etten, Edgar A Van Mil, Jeanine A Verbunt, Jonathan C K Wells, George Wilson, Brian Wood, Tsukasa Yoshida, Xueying Zhang, Alexia Murphy-Alford, Cornelia Loechl, Amy Luke, Herman Pontzer, Jennifer Rood, Hiroyuki Sagayama, Klaas R Westerterp, William W Wong, Yosuke Yamada, John R Speakman

Faculty, Staff and Student Publications

There is considerably greater variation in metabolic rates between men than between women, in terms of basal, activity and total (daily) energy expenditure (EE). One possible explanation is that EE is associated with male sexual characteristics (which are known to vary more than other traits) such as musculature and athletic capacity. Such traits might be predicted to be most prominent during periods of adolescence and young adulthood, when sexual behaviour develops and peaks. We tested this hypothesis on a large dataset by comparing the amount of male variation and female variation in total EE, activity EE and basal EE, at …

Breastfeeding Initiation And Duration Among People With Mild Chronic Hypertension: A Secondary Analysis Of The Chronic Hypertension And Pregnancy Trial, Alison N Goulding, Leah Antoniewicz, Justin M Leach, Kim Boggess, Lorraine Dugoff, Baha Sibai, Kirsten Lawrence, Brenna L Hughes, Joseph Bell, Rodney K Edwards, Kelly Gibson, David M Haas, Lauren Plante, Torri D Metz, Brian Casey, Sean Esplin, Sherri Longo, Matthew Hoffman, George R Saade, Kara K Hoppe, Janelle Foroutan, Methodius Tuuli, Michelle Y Owens, Hyagriv N Simhan, Heather Frey, Todd Rosen, Anna Palatnik, Susan Baker, Uma M Reddy, Wendy Kinzler, Emily Su, Iris Krishna, Nicki Nguyen, Mary E Norton, Daniel Skupski, Yasser Y El-Sayed, Dotun Ogunyemi, Lorie M Harper, Namasivayam Ambalavanan, Suzanne Oparil, Jeff M Szychowski, Alan T Tita

Faculty, Staff and Students Publications

BACKGROUND: Increased duration of breastfeeding improves maternal cardiovascular health and may be especially beneficial in high-risk populations, such as those with chronic hypertension. Others have shown that individuals with hypertension are less likely to breastfeed, and there has been limited research aimed at supporting breastfeeding goals in this population. The impact of perinatal blood pressure control on breastfeeding outcomes among people with chronic hypertension is unknown.

OBJECTIVE: This study aimed to evaluate whether breastfeeding initiation and short-term duration assessed at the postpartum clinic visit differed according to perinatal blood pressure treatment strategy (targeting blood pressure <140/90 mm Hg vs reserving antihypertensive treatment for blood pressure ≥160/105 mm Hg).

STUDY DESIGN: We performed a …

Lipid Dysfunction And Adrenomedullin Expression In Omental Versus Subcutaneous Adipose Tissues In Diabetic Pregnancies, Mary Duarte Thibault, Luyun Chen, Markus Huebner, John O Delancey, Carolyn W Swenson

Faculty, Staff and Students Publications

INTRODUCTION AND HYPOTHESIS: We sought to 1) test the hypothesis that young women (≤45 years) with pelvic organ prolapse have a higher prevalence of major levator ani muscle (LAM) defects than old women (≥70 years) with prolapse and 2) compare level II/III measurements between young and old women with prolapse and age-matched controls to evaluate age-related mechanistic differences in the disease process.

METHODS: A secondary analysis examined four groups of parous women: young prolapse (YPOP, n = 17); old prolapse (OPOP, n = 17); young controls (YC, n = 15); old controls, (OC, n = 13). Prolapse was defined as …

Archival Single-Cell Genomics Reveals Persistent Subclones During Dcis Progression, Kaile Wang, Tapsi Kumar, Junke Wang, Darlan Conterno Minussi, Emi Sei, Jianzhuo Li, Tuan M Tran, Aatish Thennavan, Min Hu, Anna K Casasent, Zhenna Xiao, Shanshan Bai, Lei Yang, Lorraine M King, Vandna Shah, Petra Kristel, Carolien L Van Der Borden, Jeffrey R Marks, Yuehui Zhao, Amado J Zurita, Ana Aparicio, Brian Chapin, Jie Ye, Jianjun Zhang, Don L Gibbons, Ellinor Sawyer, Alastair M Thompson, Andrew Futreal, E Shelley Hwang, Jelle Wesseling, Esther H Lips, Nicholas E Navin

Faculty, Staff and Student Publications

Ductal carcinoma in situ (DCIS) is a common precursor of invasive breast cancer. Our understanding of its genomic progression to recurrent disease remains poor, partly due to challenges associated with the genomic profiling of formalin-fixed paraffin-embedded (FFPE) materials. Here, we developed Arc-well, a high-throughput single-cell DNA-sequencing method that is compatible with FFPE materials. We validated our method by profiling 40,330 single cells from cell lines, a frozen tissue, and 27 FFPE samples from breast, lung, and prostate tumors stored for 3-31 years. Analysis of 10 patients with matched DCIS and cancers that recurred 2-16 years later show that many primary …

Sex-Specific Associations Between Adipokine Profiles And Carotid-Intima Media Thickness In The Cameron County Hispanic Cohort (Cchc), Daeeun Kim, Aylin Memili, Hung-Hsin Chen, Heather M Highland, Hannah G Polikowsky, Mohammad Yaser Anwar, Susan T Laing, Miryoung Lee, Joseph B Mccormick, Susan P Fisher-Hoch, Jennifer E Below, Kari E North, Absalon D Gutierrez

Faculty, Staff and Student Publications

Background: Adipokines are hormones secreted from adipose tissue and are associated with cardiometabolic diseases (CMD). Functional differences between adipokines (leptin, adiponectin, and resistin) are known, but inconsistently reported associations with CMD and lack of studies in Hispanic populations are research gaps. We investigated the relationship between subclinical atherosclerosis and multiple adipokine measures.

Methods: Cross-sectional data from the Cameron County Hispanic Cohort (N = 624; mean age = 50; Female = 70.8%) were utilized to assess associations between adipokines [continuous measures of adiponectin, leptin, resistin, leptin-to-adiponectin ratio (LAR), and adiponectin-resistin index (ARI)] and early atherosclerosis [carotid-intima media thickness (cIMT)]. We adjusted …

Sexually Dimorphic Extracellular Vesicle Responses After Chronic Spinal Cord Injury Are Associated With Neuroinflammation And Neurodegeneration In The Aged Brain, Yun Li, Niaz Khan, Rodney M Ritzel, Zhuofan Lei, Samantha Allen, Alan I Faden, Junfang Wu

Faculty, Staff and Student Publications

Background

Medical advances have made it increasingly possible for spinal cord injury (SCI) survivors to survive decades after the insult. But how SCI affects aging changes and aging impacts the injury process have received limited attention. Extracellular vesicles (EVs) are recognized as critical mediators of neuroinflammation after CNS injury, including at a distance from the lesion site. We have previously shown that SCI in young male mice leads to robust changes in plasma EV count and microRNA (miR) content. Here, our goal was to investigate the impact of biological sex and aging on EVs and brain after SCI.

Methods

Young …

Flavonoids Quercetin And Kaempferol Are Nr4a1 Antagonists And Suppress Endometriosis In Female Mice, Lei Zhang, Kumaravel Mohankumar, Gregory Martin, Fuada Mariyam, Yuri Park, Sang Jun Han, Stephen Safe

Faculty, Staff and Students Publications

Nuclear receptor 4A1 (NR4A1) plays an important role in endometriosis progression; levels of NR4A1 in endometriotic lesions are higher than in normal endometrium, and substituted bis-indole analogs (NR4A1) antagonists suppress endometriosis progression in mice with endometriosis. In addition, the flavonoids kaempferol and quercetin are natural products that directly bind NR4A1 and significantly repress the intrinsic NR4A1-dependent transcriptional activity in human endometriotic epithelial and stromal cells and Ishikawa endometrial cancer cells. NR4A1 knockdown and inhibition of NR4A1 by kaempferol and quercetin suppressed proliferation of human endometriotic epithelial cells and Ishikawa cells by inhibiting epidermal growth factor receptor/c-Myc/survivin-mediated growth-promoting and survival pathways, …

The Histone Chaperone Function Of Daxx Is Dispensable For Embryonic Development, Chang Sun, Yuan Qi, Natalie Fowlkes, Nina Lazic, Xiaoping Su, Guillermina Lozano, Amanda R Wasylishen

Faculty, Staff and Student Publications

Daxx functions as a histone chaperone for the histone H3 variant, H3.3, and is essential for embryonic development. Daxx interacts with Atrx to form a protein complex that deposits H3.3 into heterochromatic regions of the genome, including centromeres, telomeres, and repeat loci. To advance our understanding of histone chaperone activity in vivo, we developed two Daxx mutant alleles in the mouse germline, which abolish the interactions between Daxx and Atrx (DaxxY130A), and Daxx and H3.3 (DaxxS226A). We found that the interaction between Daxx and Atrx is dispensable for viability; mice are born at the …

Immunotherapy Targeting Different Immune Compartments In Combination With Radiation Therapy Induces Regression Of Resistant Tumors, Nils-Petter Rudqvist, Maud Charpentier, Claire Lhuillier, Erik Wennerberg, Sheila Spada, Caroline Sheridan, Xi Kathy Zhou, Tuo Zhang, Silvia C Formenti, Jennifer S Sims, Alicia Alonso, Sandra Demaria

Faculty, Staff and Student Publications

Radiation therapy (RT) increases tumor response to CTLA-4 inhibition (CTLA4i) in mice and in some patients, yet deep responses are rare. To identify rational combinations of immunotherapy to improve responses we use models of triple negative breast cancer highly resistant to immunotherapy in female mice. We find that CTLA4i promotes the expansion of CD4+ T helper cells, whereas RT enhances T cell clonality and enriches for CD8+ T cells with an exhausted phenotype. Combination therapy decreases regulatory CD4+ T cells and increases effector memory, early activation and precursor exhausted CD8+ T cells. A combined gene signature comprising these three CD8+ …

Bioaccumulation Of Non-Essential Trace Elements Detected In Women's Follicular Fluid, Urine, And Plasma Is Associated With Poor Reproductive Outcomes Following Single Euploid Embryo Transfer: A Pilot Study, Andrea Palomar, Roberto Gonzalez-Martin, Alicia Quiñonero, Nuria Pellicer, Rocio Fernandez-Saavedra, Isabel Rucandio, Rodolfo Fernandez-Martinez, Estefania Conde-Vilda, Alberto J. Quejido, Caroline Zuckerman, Christine Whitehead, Richard T. Scott, Francisco Dominguez

Department of Obstetrics and Gynecology Faculty Papers

This study aims to determine the association of non-essential trace elements present in follicular fluid, plasma, and urine with reproductive outcomes of women undergoing intracytoplasmic sperm injection (ICSI), preimplantation genetic testing for aneuploidies (PGT-A) and single frozen euploid embryo transfer (SET/FET). This single-center, prospective cohort study included sixty women undergoing ICSI with PGT-A and SET/FET between 2018 and 2019. Urine, plasma and follicular fluid samples were collected on the vaginal oocyte retrieval day to simultaneously quantify ten non-essential trace elements (i.e., Ba, Sr, Rb, Sn, Ti, Pb, Cd, Hg, Sb, and As). We found several associations between the levels of …

Building A Predictive Model Of Low Birth Weight In Low- And Middle-Income Countries: A Prospective Cohort Study, Jackie K. Patterson, Vanessa R Thorsten, Barry Eggleston, Tracy Nolen, Adrien Lokangaka, Antoinette Tshefu, Shivaprasad S. Goudar, Richard J. Derman, Elwyn Chomba, Waldemar A. Carlo, Manolo Mazariegos, Nancy F. Krebs, Sarah Saleem, Robert L. Goldenberg, Archana Patel, Patricia L. Hibberd, Fabian Esamai, Edward A. Liechty, Rashidul Haque, Bill Petri, Marion Koso-Thomas, Elizabeth M. Mcclure, Carl L. Bose, Melissa Bauserman

Global Health Articles

BACKGROUND: Low birth weight (LBW, < 2500 g) infants are at significant risk for death and disability. Improving outcomes for LBW infants requires access to advanced neonatal care, which is a limited resource in low- and middle-income countries (LMICs). Predictive modeling might be useful in LMICs to identify mothers at high-risk of delivering a LBW infant to facilitate referral to centers capable of treating these infants.

METHODS: We developed predictive models for LBW using the NICHD Global Network for Women's and Children's Health Research Maternal and Newborn Health Registry. This registry enrolled pregnant women from research sites in the Democratic Republic of the Congo, Zambia, Kenya, Guatemala, India (2 sites: Belagavi, Nagpur), Pakistan, and Bangladesh between January 2017 - December 2020. We tested five predictive models: decision tree, random forest, logistic regression, K-nearest neighbor and support vector machine.

RESULTS: We report a rate of LBW of 13.8% among the eight Global Network sites from 2017-2020, with a range of 3.8% (Kenya) …

Identification Of Usp9x As A Leukemia Susceptibility Gene, Saumya Dushyant Sisoudiya, Pamela Mishra, He Li, Jeremy M Schraw, Michael E Scheurer, Sejal Salvi, Harsha Doddapaneni, Donna Muzny, Danielle Mitchell, Olga Taylor, Aniko Sabo, Philip J Lupo, Sharon E Plon

Faculty, Staff and Students Publications

We recently reported that children with multiple birth defects have a significantly higher risk of childhood cancer. We performed whole-genome sequencing on a cohort of probands from this study with birth defects and cancer and their parents. Structural variant analysis identified a novel 5 kb de novo heterozygous inframe deletion overlapping the catalytic domain of USP9X in a female proband with multiple birth defects, developmental delay, and B-cell acute lymphoblastic leukemia (B-ALL). Her phenotype was consistent with female-restricted X-linked syndromic intellectual developmental disorder-99 (MRXS99F). Genotype-phenotype analysis including previously reported female probands (n = 42) demonstrated that MRXS99F probands with B-ALL …

Identifying The Reactive Metabolites Of Tyrosine Kinase Inhibitor Pexidartinib In Vitro Using Lc-Ms-Based Metabolomic Approaches, Xuan Qin, Yong Wang, Kevin R Mackenzie, John M Hakenjos, Si Chen, Saleh M Khalil, Sung Yun Jung, Damian W Young, Lei Guo, Feng Li

Faculty, Staff and Students Publications

Pexidartinib (PEX, TURALIO), a selective and potent inhibitor of the macrophage colony-stimulating factor-1 receptor, has been approved for the treatment of tenosynovial giant cell tumor. However, frequent and severe adverse effects have been reported in the clinic, resulting in a boxed warning on PEX for its risk of liver injury. The mechanisms underlying PEX-related hepatotoxicity, particularly metabolism-related toxicity, remain unknown. In the current study, the metabolic activation of PEX was investigated in human/mouse liver microsomes (HLM/MLM) and primary human hepatocytes (PHH) using glutathione (GSH) and methoxyamine (NH2OMe) as trapping reagents. A total of 11 PEX-GSH and 7 PEX-NH2OMe adducts were …