Digital Commons Network^™

Plasma Growth Hormone Is A Potential Biomarker Of Response To Atezolizumab And Bevacizumab In Advanced Hepatocellular Carcinoma Patients, Yehia I Mohamed, Dan G Duda, Muhammad O Awiwi, Sunyoung S Lee, Lina Altameemi, Lianchun Xiao, Jeffrey S Morris, Robert A Wolff, Khaled M Elsayes, Rikita I Hatia, Aliya Qayyum, Shadi M Chamseddine, Asif Rashid, James C Yao, Armeen Mahvash, Manal M Hassan, Hesham M Amin, Ahmed Omar Kaseb

Faculty, Staff and Student Publications

INTRODUCTION: Hepatocellular carcinoma (HCC) has limited systemic therapy options when discovered at an advanced stage. Thus, there is a need for accessible and minimally invasive biomarkers of response to guide the selection of patients for treatment. This study investigated the biomarker value of plasma growth hormone (GH) level as a potential biomarker to predict outcome in unresectable HCC patients treated with current standard therapy, atezolizumab plus bevacizumab (Atezo/Bev).

MATERIALS AND METHODS: Study included unresectable HCC patients scheduled to receive Atezo/Bev. Patients were followed to determine progression-free survival (PFS) and overall survival (OS). Plasma GH levels were measured by ELISA and …

Tele-Medicine Based And Self-Administered Interactive Exercise Program (Tele-Exergame) To Improve Cognition In Older Adults With Mild Cognitive Impairment Or Dementia: A Feasibility, Acceptability, And Proof-Of-Concept Study, Catherine Park, Ram Kinker Mishra, Michele K York, Ana Enriquez, Abigail Lindsay, Gregory Barchard, Ashkan Vaziri, Bijan Najafi

Center on Aging Staff Publications

Improved life expectancy is increasing the number of older adults who suffer from motor-cognitive decline. Unfortunately, conventional balance exercise programs are not tailored to patients with cognitive impairments, and exercise adherence is often poor due to unsupervised settings. This study describes the acceptability and feasibility of a sensor-based in-home interactive exercise system, called tele-Exergame, used by older adults with mild cognitive impairment (MCI) or dementia. Our tele-Exergame is specifically designed to improve balance and cognition during distractive conditioning while a telemedicine interface remotely supervises the exercise, and its exercises are gamified balance tasks with explicit augmented visual feedback. Fourteen adults …

The Prevalence Of Sars-Cov-2 Antibodies Within The Community Of A Private Tertiary University In The Philippines: A Serial Cross Sectional Study, Lourdes S. Tanchanco, Jenica Clarisse Y. Sy, Angel Belle C. Dy, Myla D. Levantino, Arianna Maever L. Amit, John Wong, Kirsten Angeles, John Paul Vergara

Ateneo School of Medicine and Public Health Publications

The COVID-19 pandemic has caused a public health emergency in all sectors of society, including universities and other academic institutions. This study determined the seroprevalence of SARS-CoV-2 antibodies among administrators, faculty, staff, and students of a private tertiary academic institution in the Philippines over a 7 month period. It employed a serial cross-sectional method using qualitative and quantitative COVID-19 antibody test kits. A total of 1,318 participants were tested, showing 47.80% of the study population yielding IgG antibodies to SARS-CoV-2 virus. A general increase in seroprevalence was observed from June to December 2021, which coincided with the vaccine roll-out of …

A Cross-Sectional Study Of The Prevalence Of Anal Dysplasia Among Women With High-Grade Cervical, Vaginal, And Vulvar Dysplasia Or Cancer: The Panda Study, Samantha Batman, Craig A Messick, Andrea Milbourne, Ming Guo, Mark F Munsell, Joel Fokom-Domgue, Mila Salcedo, Ashish Deshmukh, Kristina R Dahlstrom, Mallory Ogburn, Anthony Price, Nicole D Fleming, Jolyn Taylor, Aaron Shafer, Lauren Cobb, Keith Sigel, Erich M Sturgis, Elizabeth Y Chiao, Kathleen M Schmeler

Faculty, Staff and Students Publications

BACKGROUND: High-risk human papillomavirus (HR-HPV) infection is a risk factor for anal cancer, yet no anal cancer screening guidelines exist for women with lower genital tract HPV-related disease. We sought to describe the prevalence of anal HR-HPV or cytologic abnormalities in such women.

METHODS: This cross-sectional study was performed between October 2018 and December 2021. Inclusion criteria were ≥21 years of age and a prior diagnosis of high-grade dysplasia/cancer of the cervix, vagina, or vulva. Participants underwent anal cytology and anal/cervicovaginal HR-HPV testing. Women with abnormal anal cytology were referred for high-resolution anoscopy (HRA).

RESULTS: 324 evaluable women were enrolled. …

Efficacy And Safety Of Pacritinib Vs Placebo For Patients With Severe Covid-19: A Phase 2 Randomized Clinical Trial, John Cafardi, Carole Miller, Howard Terebelo, Chad Tewell, Sadia Benzaquen, David Park, Pamela Egan, Daniel Lebovic, Kristen Pettit, Eric Whitman, Douglas Tremblay, Jonathan Feld, Sarah Buckley, Karisse Roman-Torres, Jennifer Smith, Adam Craig, John Mascarenhas

Einstein Health Papers

IMPORTANCE: The morbidity and mortality associated with COVID-19 remain high despite advances in standard of care therapy, and the role of anti-inflammatory agents that inhibit the interleukin 6/JAK2 pathway is still being elucidated.

OBJECTIVE: To evaluate the efficacy and safety of the oral JAK2/IRAK1 inhibitor pacritinib vs placebo in the treatment of adults with severe COVID-19.

DESIGN, SETTING, AND PARTICIPANTS: This phase 2, double-blind, placebo-controlled, randomized clinical trial enrolled hospitalized adult patients with severe COVID-19 at 21 centers across the US between June 2020 and February 2021, with approximately 1.5 months of safety follow-up per patient. Data analysis was performed …

Executive Summary Of The American Radium Society Appropriate Use Criteria For Management Of Uterine Clear Cell And Serous Carcinomas, Tracy Sherertz, Anuja Jhingran, Matthew Biagioli, David Gaffney, Mohamed Elshaikh, Robert L Coleman, Matthew Harkenrider, Elizabeth A Kidd, Shruti Jolly, Catheryn Yashar, Lorraine Portelance, Andrew Wahl, Aradhana Venkatesan, Linna Li, William Small, American Radium Society

Faculty, Staff and Student Publications

Background: Uterine clear cell and serous carcinomas have a high propensity for locoregional and distant spread, tend to be more advanced at presentation, and carry a higher risk of recurrence and death than endometrioid cancers. Limited prospective data exist to guide evidence-based management of these rare malignancies.

Objective: The American Radium Society sought to summarize evidence-based guidelines developed by a multidisciplinary expert panel that help to guide the management of uterine clear cell and serous carcinomas.

Methods: The American Radium Society Appropriate Use Criteria presented in this manuscript were developed by a multidisciplinary expert panel using an extensive analysis of …

Human Papillomavirus Vaccine Administration Trends Among Commercially Insured Us Adults Aged 27-45 Years Before And After Advisory Committee On Immunization Practices Recommendation Change, 2007-2020, Ryan Suk, Kaiping Liao, Cici X Bauer, Catherine Basil, Meng Li

Faculty, Staff and Student Publications

IMPORTANCE: In 2019, the Advisory Committee on Immunization Practices (ACIP) recommended patient-clinician shared decision-making for human papillomavirus (HPV) vaccination in adults aged 27 to 45 years. Less is known about the HPV vaccine administration trends in this age group before and after this recommendation update.

OBJECTIVE: to examine the association between the ACIP recommendation update and the HPV vaccine administration among US adults aged 27 to 45 years.

DESIGN, SETTING, AND PARTICIPANTS: This large commercial claim-based retrospective cohort study used the Optum Clinformatics database for validated claims from January 1, 2007, through December 31, 2020. A total of 22 600 …

Interview With Lucia Manzano, Kristen Laga

Immigrant Leaders

An interview with Lucia Manzano, a community organizer from New Jersey Communities United and Latino Action Network. The interview covers life before immigrating, arrival and integration, and political participation.

Research Note: Association Of Single Nucleotide Polymorphism Of Akt3 With Egg Production Traits In White Muscovy Ducks (Cairina Moschata)., Semiu Folaniyi Bello, Haiping Xu, Kan Li, Lijin Guo, Siyu Zhang, Ridwan Olawale Ahmed, Endashaw Jebessa Bekele, Ming Zheng, Mingjian Xian, Bahareldin Ali Abdalla, Adeniyi Charles Adeola, Adeyinka Abiola Adetula, Raman Akinyanju Lawal, Weijian Zhu, Dexiang Zhang, Xiquan Zhang, Congliang Ji, Qinghua Nie

Faculty Research 2022

Prior studies on transcriptomes of hypothalamus and ovary revealed that AKT3 is one of the candidate genes that might affect egg production in White Muscovy ducks. The role of AKT3 in the uterus during reproductive processes cannot be overemphasized. However, functional role of this gene in the tissues and on egg production traits of Muscovy ducks remains unknown. To identify the relationship between AKT3 and egg production traits in ducks, relative expression profile was first examined prior to identifying the variants within AKT3 that may underscore egg production traits [age at first egg (AFE), number of eggs at 300 d …

Metformin Is Associated With Reduced Covid-19 Severity In Patients With Prediabetes., Lauren E Chan, Elena Casiraghi, Bryan Laraway, Ben D Coleman, Hannah Blau, Adnin Zaman, Nomi L Harris, Kenneth Wilkins, Blessy Antony, Michael Gargano, Giorgio Valentini, David Sahner, Melissa Haendel, Peter N Robinson, Carolyn Bramante, Justin Reese

Faculty Research 2022

AIMS: Studies suggest that metformin is associated with reduced COVID-19 severity in individuals with diabetes compared to other antihyperglycemics. We assessed if metformin is associated with reduced incidence of severe COVID-19 for patients with prediabetes or polycystic ovary syndrome (PCOS), common diseases that increase the risk of severe COVID-19.

METHODS: This observational, retrospective study utilized EHR data from 52 hospitals for COVID-19 patients with PCOS or prediabetes treated with metformin or levothyroxine/ondansetron (controls). After balancing via inverse probability score weighting, associations with COVID-19 severity were assessed by logistic regression.

RESULTS: In the prediabetes cohort, when compared to levothyroxine, metformin was …

Expression And Localization Of Nrf2/Keap1 Signalling Pathway Genes In Mouse Preimplantation Embryos Exposed To Free Fatty Acids., Grace Dionne, Michele D. Calder, Dean H Betts, Basim Abu Rafea, Andrew J Watson

Obstetrics & Gynaecology Publications

Obese women experience greater incidence of infertility, with reproductive tracts exposing preimplantation embryos to elevated free fatty acids (FFA) such as palmitic acid (PA) and oleic acid (OA). PA treatment impairs mouse preimplantation development in vitro, while OA co-treatment rescues blastocyst development of PA treated embryos. In the present study, we investigated the effects of PA and OA treatment on NRF2/Keap1 localization, and relative antioxidant enzyme (Glutathione peroxidase; Gpx1, Catalase; Cat, Superoxide dismutase; Sod1 and γ-Glutamylcysteine ligase catalytic unit; Gclc) mRNA levels, during in vitro mouse preimplantation embryo development. Female mice were superovulated, mated, and embryos cultured in the presence …

Lifespan Benefits For The Combination Of Rapamycin Plus Acarbose And For Captopril In Genetically Heterogeneous Mice., Randy Strong, Richard A Miller, Catherine J Cheng, James F Nelson, Jonathan Gelfond, Shailaja Kesaraju Allani, Vivian Diaz, Angela Olsen Dorigatti, Jonathan Dorigatti, Elizabeth Fernandez, Andrzej Galecki, Brett Ginsburg, Karyn L Hamilton, Martin A Javors, Kerry Kornfeld, Matt Kaeberlein, Suja Kumar, David B Lombard, Marisa Lopez-Cruzan, Benjamin F Miller, Peter Rabinovitch, Peter C. Reifsnyder, Nadia Rosenthal, Molly A. Bogue, Adam B Salmon, Yousin Suh, Eric Verdin, Herbert Weissbach, John Newman, Francesca Maccchiarini, David E. Harrison

Faculty Research 2022

Mice bred in 2017 and entered into the C2017 cohort were tested for possible lifespan benefits of (R/S)-1,3-butanediol (BD), captopril (Capt), leucine (Leu), the Nrf2-activating botanical mixture PB125, sulindac, syringaresinol, or the combination of rapamycin and acarbose started at 9 or 16 months of age (RaAc9, RaAc16). In male mice, the combination of Rapa and Aca started at 9 months and led to a longer lifespan than in either of the two prior cohorts of mice treated with Rapa only, suggesting that this drug combination was more potent than either of its components used alone. In females, lifespan in mice …

Myocardial Infarction With Nonobstructive Coronary Arteries In New-Onset Inflammatory Bowel Disease, Benjamin B. Claxton, George Sun, Ritu Nahar, Christopher Henry

Division of Gastroenterology and Hepatology Faculty Papers

No abstract provided.

Agent-Based Modeling Predicts Rac1 Is Critical For Ovarian Cancer Metastasis, Melanie Rivera, Leslie Toledo-Jacobo, Elsa Romero, Tudor I. Oprea, Melanie E. Moses, Laurie G. Hudson, Angela Wandinger-Ness, Martha M. Grimes

Pathology Research and Scholarship

Experimental and computational studies pinpoint rate-limiting step(s) in metastasis governed by Rac1. Using ovarian cancer cell and animal models, Rac1 expression was manipulated, and quantitative measurements of cell-cell and cell-substrate adhesion, cell invasion, mesothelial clearance, and peritoneal tumor growth discriminated the tumor behaviors most highly influenced by Rac1. The experimental data were used to parameterize an agent-based computational model simulating peritoneal niche colonization, intravasation, and hematogenous metastasis to distant organs. Increased ovarian cancer cell survival afforded by the more rapid adhesion and intravasation upon Rac1 overexpression is predicted to increase the numbers of and the rates at which tumor cells …

Low-Molecular-Weight Cyclin E Deregulates Dna Replication And Damage Repair To Promote Genomic Instability In Breast Cancer, Mi Li, Spiridon Tsavachidis, Fuchenchu Wang, Tuyen Bui, Tuyen Duong Thanh Nguyen, Linjie Luo, Asha S Multani, Melissa L Bondy, Kelly K Hunt, Khandan Keyomarsi

Faculty, Staff and Student Publications

Low-molecular-weight cyclin E (LMW-E) is an N-terminus deleted (40 amino acid) form of cyclin E detected in breast cancer, but not in normal cells or tissues. LMW-E overexpression predicts poor survival in breast cancer patients independent of tumor proliferation rate, but the oncogenic mechanism of LMW-E and its unique function(s) independent of full-length cyclin E (FL-cycE) remain unclear. In the current study, we found LMW-E was associated with genomic instability in early-stage breast tumors (n = 725) and promoted genomic instability in human mammary epithelial cells (hMECs). Mechanistically, FL-cycE overexpression inhibited the proliferation of hMECs by replication stress and DNA …

Civil Rights Law—Preserving Female Athletics: Arkansas’S Fairness In Women’S Sports Act, Chandler Little Bray

University of Arkansas at Little Rock Law Review

No abstract provided.

Associations Of Neighborhood Opportunity And Social Vulnerability With Trajectories Of Childhood Body Mass Index And Obesity Among Us Children, Izzuddin M. Aris, Wei Perng, Dana Dabelea, Amy M. Padula, Akram Alshawabkeh, Carmen M. Vélez-Vega, Judy L. Aschner, Carlos A. Camargo, Tamara J. Sussman, Anne L. Dunlop, Amy J. Elliott, Assiamira Ferrara, Yeyi Zhu, Christine L. M. Joseph, Anne M. Singh, Tina Hartert, Ferdinand Cacho, Margaret R. Karagas, Tiffany North-Reid, Barry M. Lester, Nichole R. Kelly, Jody M. Ganiban, Su H. Chu, Thomas G. O'Connor, Rebecca C. Fry, Gwendolyn Norman, Leonardo Trasande, Bibiana Restrepo, Peter James, Emily Oken

Public Health Sciences Articles

IMPORTANCE: Physical and social neighborhood attributes may have implications for children's growth and development patterns. The extent to which these attributes are associated with body mass index (BMI) trajectories and obesity risk from childhood to adolescence remains understudied.

OBJECTIVE: To examine associations of neighborhood-level measures of opportunity and social vulnerability with trajectories of BMI and obesity risk from birth to adolescence.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from 54 cohorts (20 677 children) participating in the Environmental Influences on Child Health Outcomes (ECHO) program from January 1, 1995, to January 1, 2022. Participant inclusion required at least …

Chronic Kidney Disease In Public Renal Practices In Queensland, Australia, 2011–2018, Wendy E Hoy, Zaimin Wang, Jianzhen Zhang, Vishal Diwan, Anne Cameron, Sree K Venuthurupalli, Robert G Fassett, Samuel Chan, Helen G Healy, Ken-Soon Tan, Richard Baer, Andrew J Mallett, Nicholas Gray, Murty Mantha, Roy Cherian, Clyson Mutatiri, Krishan Madhan, George Kan, Geoffrey Mitchell, Shahadat Hossain, Danielle Wu, Thin Han, Adrian Kark, Thomas Titus, Dwarakanatan Ranganathan, Ann Bonner, Sridevi Govindarajulu, Nhmrc Ckd.Cre And The Ckd.Qld Collaborative

Faculty, Staff and Student Publications

AIM: To describe adults with (non-dialysis) chronic kidney disease (CKD) in nine public renal practice sites in the Australian state of Queensland.

METHODS: 7,060 persons were recruited to a CKD Registry in May 2011 and until start of kidney replacement therapy (KRT), death without KRT or June 2018, for a median period of 3.4 years.

RESULTS: The cohort comprised 7,060 persons, 52% males, with a median age of 68 yr; 85% had CKD stages 3A to 5, 45.4% were diabetic, 24.6% had diabetic nephropathy, and 51.7% were obese. Younger persons mostly had glomerulonephritis or genetic renal disease, while older persons …

Biobehavioral Factors Predict An Exosome Biomarker Of Ovarian Carcinoma Disease Progression, Susan K Lutgendorf, Premal H Thaker, Michael J Goodheart, Jesusa M G Arevalo, Mamur A Chowdhury, Alyssa E Noble, Laila Dahmoush, George M Slavich, Frank J Penedo, Anil K Sood, Steven W Cole

Faculty, Staff and Student Publications

BACKGROUND: Biobehavioral factors such as social isolation and depression have been associated with disease progression in ovarian and other cancers. Here, the authors developed a noninvasive, exosomal RNA profile for predicting ovarian cancer disease progression and subsequently tested whether it increased in association with biobehavioral risk factors.

METHODS: Exosomes were isolated from plasma samples from 100 women taken before primary surgical resection or neoadjuvant (NACT) treatment of ovarian carcinoma and 6 and 12 months later. Biobehavioral measures were sampled at all time points. Plasma from 76 patients was allocated to discovery analyses in which morning presurgical/NACT exosomal RNA profiles were …

Adjuvant Therapy In Women With Early Stage Uterine Serous Carcinoma: A Multi-Institutional Study, Katherine C Kurnit, Silvana Pedra Nobre, Bryan M Fellman, David A Iglesias, Kristina Lindemann, Anuja Jhingran, Ane Gerda Z Eriksson, Beyhan Ataseven, Gretchen E Glaser, Jennifer J Mueller, Shannon N Westin, Pamela T Soliman

Faculty, Staff and Student Publications

OBJECTIVE: Uterine serous carcinoma is a rare but aggressive subtype of endometrial adenocarcinoma. Our objective was to compare adjuvant treatment strategies for patients with early stage uterine serous carcinoma.

METHODS: This multi-institutional, retrospective cohort study evaluated patients with early stage uterine serous carcinoma. Patients with FIGO Stage IA-II disease after surgery, whose tumors had serous or any mixed serous/non-serous histology were included. Patients with carcinosarcoma were excluded. Clinical data were abstracted from local medical records. Summary statistics, Fisher's exact, and Kruskal-Wallis tests were used to analyze demographic and clinical characteristics. Univariable and multivariable analyses were performed for recurrence-free and overall …

Targeting The Pi3k Pathway In Gynecologic Malignancies, Monica Avila, Michaela Onstad Grinsfelder, Melissa Pham, Shannon N Westin

Faculty, Staff and Student Publications

Purpose of review: This review explores the PI3K pathway aberrations common in gynecologic malignancies, the relevant therapeutic targets that have been explored to date particularly given their success in endometrial cancers, and predictive biomarkers of response to therapy.

Recent findings: Landmark trials have been noted involving this pathway, particularly in endometrial cancers. One phase II trial of the potent orally bioavailable mTOR inhibitor, everolimus, in combination with letrozole demonstrated an unprecedented clinical benefit rate (CBR) of 40% and high objective response rate (RR) of 32% in hormone agnostic endometrial cancers. This was followed by GOG 3007 that compared everolimus and …

A Randomized, Phase Iii Trial To Evaluate Rucaparib Monotherapy As Maintenance Treatment In Patients With Newly Diagnosed Ovarian Cancer (Athena-Mono/Gog-3020/Engot-Ov45), Bradley J Monk, Christine Parkinson, Myong Cheol Lim, David M O'Malley, Ana Oaknin, Michelle K Wilson, Robert L Coleman, Domenica Lorusso, Paul Bessette, Sharad Ghamande, Athina Christopoulou, Diane Provencher, Emily Prendergast, Fuat Demirkiran, Olga Mikheeva, Oladapo Yeku, Anita Chudecka-Glaz, Michael Schenker, Ramey D Littell, Tamar Safra, Hung-Hsueh Chou, Mark A Morgan, Vít Drochýtek, Joyce N Barlin, Toon Van Gorp, Fred Ueland, Gabriel Lindahl, Charles Anderson, Dearbhaile C Collins, Kathleen Moore, Frederik Marme, Shannon N Westin, Iain A Mcneish, Danny Shih, Kevin K Lin, Sandra Goble, Stephanie Hume, Keiichi Fujiwara, Rebecca S Kristeleit

Faculty, Staff and Student Publications

PURPOSE: ATHENA (ClinicalTrials.gov identifier: NCT03522246) was designed to evaluate rucaparib first-line maintenance treatment in a broad patient population, including those without BRCA1 or BRCA2 (BRCA) mutations or other evidence of homologous recombination deficiency (HRD), or high-risk clinical characteristics such as residual disease. We report the results from the ATHENA–MONO comparison of rucaparib versus placebo.

METHODS: Patients with stage III-IV high-grade ovarian cancer undergoing surgical cytoreduction (R0/complete resection permitted) and responding to first-line platinum-doublet chemotherapy were randomly assigned 4:1 to oral rucaparib 600 mg twice a day or placebo. Stratification factors were HRD test status, residual disease after chemotherapy, and …

Soy Isoflavones Decrease Fibroglandular Breast Tissue Measured By Magnetic Resonance Imaging In Premenopausal Women: A 2-Year Randomized Double-Blind Placebo Controlled Clinical Trial, Lee-Jane W Lu, Nai-Wei Chen, Donald G Brunder, Fatima Nayeem, Manubai Nagamani, Thomas K Nishino, Karl E Anderson, Tuenchit Khamapirad

Faculty, Staff and Student Publications

BACKGROUND & AIMS: Populations consuming soy have reduced risk for breast cancer, but the mechanisms are unclear. We tested the hypothesis that soy isoflavones, which have ovarian hormone-like effects, can reduce fibroglandular breast tissue (FGBT, 'breast density'), a strong risk marker for breast cancer.

METHODS: Premenopausal women (age 30-42 years) were randomized to consume isoflavones (136.6 mg as aglycone equivalents, n = 99) or placebo (n = 98) for 5 days per week up to 2 years, and changes in breast composition measured by magnetic resonance imaging at baseline and yearly intervals were compared after square root transformation using linear …

Cell-Free Dna Screening Positive For Monosomy X: Clinical Evaluation And Management Of Suspected Maternal Or Fetal Turner Syndrome, Tazim Dowlut-Mcelroy, Shanlee Davis, Susan Howell, Iris Gutmark-Little, Vaneeta Bamba, Siddharth Prakash, Sheetal Patel, Doris Fadoju, Nandini Vijayakanthi, Mary Haag, Deborrah Hennerich, Lorraine Dugoff, Roopa Kanakatti Shankar

Faculty, Staff and Student Publications

Initially provided as an alternative to evaluation of serum analytes and nuchal translucency for the assessment of pregnancies at high risk of trisomy 21, cell-free DNA screening for fetal aneuploidy, also referred to as noninvasive prenatal screening, can now also screen for fetal sex chromosome anomalies such as monosomy X as early as 9 to 10 weeks of gestation. Early identification of Turner syndrome, a sex chromosome anomaly resulting from the complete or partial absence of the second X chromosome, allows medical interventions such as optimizing obstetrical outcomes, hormone replacement therapy, fertility preservation and support, and improved neurocognitive outcomes. However, …

Clinical And Economic Evaluation Of A Proteomic Biomarker Preterm Birth Risk Predictor: Cost-Effectiveness Modeling Of Prenatal Interventions Applied To Predicted Higher-Risk Pregnancies Within A Large And Diverse Cohort, Julja Burchard, Glenn R Markenson, George R Saade, Louise C Laurent, Kent D Heyborne, Dean V Coonrod, Corina N Schoen, Jason K. Baxter, David M Haas, Sherri A Longo, Scott A Sullivan, Sarahn M Wheeler, Leonardo M Pereira, Kim A Boggess, Angela F Hawk, Amy H Crockett, Ryan Treacy, Angela C Fox, Ashoka D Polpitiya, Tracey C Fleischer, Thomas J Garite, J Jay Boniface, John A F Zupancic, Gregory C Critchfield, Paul E Kearney

Department of Obstetrics and Gynecology Faculty Papers

Objectives: Preterm birth occurs in more than 10% of U.S. births and is the leading cause of U.S. neonatal deaths, with estimated annual costs exceeding $25 billion USD. Using real-world data, we modeled the potential clinical and economic utility of a prematurity-reduction program comprising screening in a racially and ethnically diverse population with a validated proteomic biomarker risk predictor, followed by case management with or without pharmacological treatment.

Methods: The ACCORDANT microsimulation model used individual patient data from a prespecified, randomly selected sub-cohort (N = 847) of a multicenter, observational study of U.S. subjects receiving standard obstetric care with …

Human Loss-Of-Function Variants In The Serotonin 2c Receptor Associated With Obesity And Maladaptive Behavior, Yang He, Bas Brouwers, Hesong Liu, Hailan Liu, Katherine Lawler, Edson Mendes De Oliveira, Dong-Kee Lee, Yongjie Yang, Aaron R Cox, Julia M Keogh, Elana Henning, Rebecca Bounds, Aliki Perdikari, Vikram Ayinampudi, Chunmei Wang, Meng Yu, Longlong Tu, Nan Zhang, Na Yin, Junying Han, Nikolas A Scarcelli, Zili Yan, Kristine M Conde, Camille Potts, Jonathan C Bean, Mengjie Wang, Sean M Hartig, Lan Liao, Jianming Xu, Inês Barroso, Jacek Mokrosinski, Yong Xu, I Sadaf Farooqi

Children’s Nutrition Research Center Staff Publications

Serotonin reuptake inhibitors and receptor agonists are used to treat obesity, anxiety and depression. Here we studied the role of the serotonin 2C receptor (5-HT2CR) in weight regulation and behavior. Using exome sequencing of 2,548 people with severe obesity and 1,117 control individuals without obesity, we identified 13 rare variants in the gene encoding 5-HT2CR (HTR2C) in 19 unrelated people (3 males and 16 females). Eleven variants caused a loss of function in HEK293 cells. All people who carried variants had hyperphagia and some degree of maladaptive behavior. Knock-in male mice harboring a human loss-of-function HTR2C variant developed …

Clinical And Demographic Factors Contributing To Asparaginase-Associated Toxicities In Children With Acute Lymphoblastic Leukemia, Priyadarshani Dharia, Michael D Swartz, M Brooke Bernhardt, Han Chen, M Monica Gramatges, Philip J Lupo, Austin L Brown, Michael E Scheurer

Center for Medical Ethics and Health Policy Staff Publications

A total of 548 patients (age range: 1-22 years, 60.4% Hispanic, 55.8% male) diagnosed with acute lymphoblastic leukemia were reviewed for pegaspargase-associated hypersensitivity (14.8%), hyperbilirubinemia (9.7%), venous thromboembolism (VTE, 9.7%), and pancreatitis (5.3%). Odds ratios (OR) and 95% confidence intervals (CI) evaluated associations between clinical factors and each toxicity, cumulative number of toxicities, and toxicity clusters identified using k-mode analysis. Most (68.9%) did not experience any toxicity, 24.6% experienced one toxicity, and 6.3% two or more. Age >10 years was associated with hyperbilirubinemia (OR = 3.83; 95% CI: 1.64-8.95), pancreatitis (OR = 3.72; 95% CI: 1.29-10.68), VTE (OR = 4.65; …

Prenatal Phenotyping Of Fetal Tubulinopathies: A Multicenter Retrospective Case Series, Bobby K Brar, Marisa Gilstrop Thompson, Neeta L Vora, Kelly Gilmore, Karin Blakemore, Kristen A Miller, Jessica Giordano, Andreas Dufke, Beatrix Wong, Samantha Stover, Billie Lianoglou, Ignatia Van Den Veyver, Esther Dempsey, Mara Rosner, Karen Chong, David Chitayat, Teresa N Sparks, Mary E Norton, Ronald Wapner, Kristin Baranano, Angie C Jelin, Fetal Sequencing Consortium

Center for Medical Ethics and Health Policy Staff Publications

Objective: Tubulinopathies refer to conditions caused by genetic variants in isotypes of tubulin resulting in defective neuronal migration. Historically, diagnosis was primarily via postnatal imaging. Our objective was to establish the prenatal phenotype/genotype correlations of tubulinopathies identified by fetal imaging.

Methods: A large, multicenter retrospective case series was performed across nine institutions in the Fetal Sequencing Consortium. Demographics, fetal imaging reports, genetic screening and diagnostic testing results, delivery reports, and neonatal imaging reports were extracted for pregnancies with a confirmed molecular diagnosis of a tubulinopathy.

Results: Nineteen pregnancies with a fetal tubulinopathy were identified. The most common prenatal imaging findings …

Effect Of Problem-Solving Treatment On Self-Reported Disability Among Veterans With Gulf War Illness: A Randomized Clinical Trial, Lisa M Mcandrew, Karen S Quigley, Shou-En Lu, David Litke, Joseph F Rath, Gudrun Lange, Susan L Santos, Nicole Anastasides, Beth Ann Petrakis, Lauren Greenberg, Drew A Helmer, Wilfred R Pigeon

Center for Medical Ethics and Health Policy Staff Publications

Importance: Few evidence-based treatments are available for Gulf War illness (GWI). Behavioral treatments that target factors known to maintain the disability from GWI, such as problem-solving impairment, may be beneficial. Problem-solving treatment (PST) targets problem-solving impairment and is an evidence-based treatment for other conditions.

Objective: To examine the efficacy of PST to reduce disability, problem-solving impairment, and physical symptoms in GWI.

Design, setting, and participants: This multicenter randomized clinical trial conducted in the US Department of Veterans Affairs compared PST with health education in a volunteer sample of 511 Gulf War veterans with GWI and disability (January 1, 2015, to …

Dietary And Complementary Feeding Practices Of Us Infants, 6 To 12 Months: A Narrative Review Of The Federal Nutrition Monitoring Data, Regan L Bailey, Jaime S Stang, Teresa A Davis, Timothy S Naimi, Barbara O Schneeman, Kathryn G Dewey, Sharon M Donovan, Rachel Novotny, Ronald E Kleinman, Elsie M Taveras, Lydia Bazzano, Linda G Snetselaar, Janet De Jesus, Kellie O Casavale, Eve E Stoody, Joseph D Goldman, Alanna J Moshfegh, Donna G Rhodes, Kirsten A Herrick, Kristin Koegel, Cria G Perrine, Tusarebecca Pannucci

Children’s Nutrition Research Center Staff Publications

Complementary foods and beverages (CFBs) are key components of an infant’s diet in the second 6 months of life. This article summarizes nutrition and feeding practices examined by the 2020 Dietary Guidelines Advisory Committees during the CFB life stage. Breastfeeding initiation is high (84%), but exclusive breastfeeding at 6 months (26%) is below the Healthy People 2030 goal (42%). Most infants (51%) are introduced to CFBs sometime before 6 months. The primary mode of feeding (ie, human milk fed [HMF]; infant formula or mixed formula and human milk fed [FMF]) at the initiation of CFBs is associated with the timing …