Digital Commons Network^™

Sex Differences In Fatigability And Recovery Following A 5 Km Running Time Trial In Recreationally Active Adults, Maria Solleiro Pons, Sandra K. Hunter, Paul Ansdell

Exercise Science Faculty Research and Publications

Females demonstrate greater fatigue resistance compared to males in tasks ranging from single-limb contractions to whole-body exercise, including running. Many of the studies investigating sex differences in fatigability following running, however, occur after long duration, low-intensity tasks and it is unknown whether there is a sex difference in fatigability following high-intensity running. This study compared fatigability and recovery following a 5 km running time trial in young males and females. Sixteen recreationally active participants (8 males, 8 females, age: 23 ± 4 years) completed a familiarisation and experimental trial. Knee-extensor maximal voluntary contractions (MVCs) were performed before and up to …

Apoe Genotype And Alzheimer Disease Risk Across Age, Sex, And Population Ancestry, Michael E Belloy, Shea J Andrews, Yann Le Guen, Michael Cuccaro, Lindsay A Farrer, Valerio Napolioni, Michael D Greicius

2020-Current year OA Pubs

IMPORTANCE: Apolipoprotein E (APOE)*2 and APOE*4 are, respectively, the strongest protective and risk-increasing, common genetic variants for late-onset Alzheimer disease (AD), making APOE status highly relevant toward clinical trial design and AD research broadly. The associations of APOE genotypes with AD are modulated by age, sex, race and ethnicity, and ancestry, but these associations remain unclear, particularly among racial and ethnic groups understudied in the AD and genetics research fields.

OBJECTIVE: To assess the stratified associations of APOE genotypes with AD risk across sex, age, race and ethnicity, and global population ancestry.

DESIGN, SETTING, PARTICIPANTS: This genetic association study included …

Nonsense Variant Prdm16-Q187x Causes Impaired Myocardial Development And Tgf-Β Signaling Resulting In Noncompaction Cardiomyopathy In Humans And Mice, Bo Sun, Omid M T Rouzbehani, Ryan J Kramer, Rajeshwary Ghosh, Robin M Perelli, Sage Atkins, Amir Nima Fatahian, Kathryn Davis, Marta W Szulik, Michael A Goodman, Marissa A Hathaway, Ellenor Chi, Tarah A Word, Hari Tunuguntla, Susan W Denfield, Xander H T Wehrens, Kevin J Whitehead, Hala Y Abdelnasser, Junco S Warren, Mingfu Wu, Sarah Franklin, Sihem Boudina, Andrew P Landstrom

Faculty, Staff and Students Publications

BACKGROUND: PRDM16 plays a role in myocardial development through TGF-β (transforming growth factor-beta) signaling. Recent evidence suggests that loss of PRDM16 expression is associated with cardiomyopathy development in mice, although its role in human cardiomyopathy development is unclear. This study aims to determine the impact of PRDM16 loss-of-function variants on cardiomyopathy in humans.

METHODS: Individuals with PRDM16 variants were identified and consented. Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) were generated from a proband hosting a Q187X nonsense variant as an in vitro model and underwent proliferative and transcriptional analyses. CRISPR-mediated knock-in mouse model hosting the Prdm16Q187X allele was generated …

Exposure To Agent Orange And Hepatocellular Carcinoma Among Us Military Personnel, Jihane N Benhammou, Mei Leng, Shailja C Shah, George Cholankeril, Tien S Dong, Arpan A Patel, Myron J Tong

Faculty, Staff and Students Publications

IMPORTANCE: Hepatocellular carcinoma (HCC) and its mortality are on the rise. Viral hepatitis and alcohol are leading risk factors; however, other risk factors among veterans are less defined, including Agent Orange (AO), an herbicide linked to several cancers.

OBJECTIVE: To assess the association of AO exposure and HCC in a national cohort of Vietnam veterans.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included Vietnam veterans who served between 1966 and 1975, were male, were older than 18 years at the time of deployment, and had established follow-up in the Veterans Affairs (VA) between 2000 and 2019. Veterans with AO …

Nurse Care Management For Opioid Use Disorder Treatment: The Proud Cluster Randomized Clinical Trial, Paige D Wartko, Jennifer F Bobb, Denise M Boudreau, Abigail G Matthews, Jennifer Mccormack, Amy K Lee, Hongxiang Qiu, Onchee Yu, Noorie Hyun, Abisola E Idu, Cynthia I Campbell, Andrew J Saxon, David S Liu, Andrea Altschuler, Jeffrey H Samet, Colleen T Labelle, Mohammad Zare-Mehrjerdi, Angela L Stotts, Jordan M Braciszewski, Mark T Murphy, Douglas Dryden, Julia H Arnsten, Chinazo O Cunningham, Viviana E Horigian, José Szapocznik, Joseph E Glass, Ryan M Caldeiro, Rebecca C Phillips, Mary Shea, Gavin Bart, Robert P Schwartz, Jennifer Mcneely, Jane M Liebschutz, Judith I Tsui, Joseph O Merrill, Gwen T Lapham, Megan Addis, Katharine A Bradley, Proud Trial Collaborators, Megan M Ghiroli, Leah K Hamilton, Yong Hu, Jennifer S Lahue, Amy M Loree, Sean M Murphy, Thomas F Northrup, Dikla Shmueli-Blumberg, Angela J Silva, Zoe M Weinstein, Mark Tinfook Wong, Rachael P Burganowski

Faculty, Staff and Student Publications

Importance: Few primary care (PC) practices treat patients with medications for opioid use disorder (OUD) despite availability of effective treatments.

Objective: To assess whether implementation of the Massachusetts model of nurse care management for OUD in PC increases OUD treatment with buprenorphine or extended-release injectable naltrexone and secondarily decreases acute care utilization.

Design, setting, and participants: The Primary Care Opioid Use Disorders Treatment (PROUD) trial was a mixed-methods, implementation-effectiveness cluster randomized clinical trial conducted in 6 diverse health systems across 5 US states (New York, Florida, Michigan, Texas, and Washington). Two PC clinics in each system were randomized to intervention …

Incidence And Risk Factors For Neutropenia After Intra-Arterial Chemotherapy For Retinoblastoma, Debora H Lee, Richard Donkor, Matthew N Parvus, Mark J Dannenbaum, Amy C Schefler

Faculty, Staff and Student Publications

Importance: Intra-arterial chemotherapy (IAC) has quickly gained popularity as a mainstay of treatment for retinoblastoma. Intra-arterial chemotherapy has been described as having several advantages over systemic chemotherapy, including reducing systemic toxicity and neutropenia; however, studies on the risk of neutropenia after IAC remain limited.

Objective: To estimate the incidence of neutropenia after IAC, as well as identify risk factors associated with the development of neutropenia.

Design, setting, and participants: This case series included pediatric patients with unilateral or bilateral retinoblastoma who were treated with IAC at a single quaternary care center from July 13, 2013, to January 6, 2023.

Exposure: …

Oral Glucose Tolerance Test In Pregnancy And Subsequent Maternal Hypertension, Maged M Costantine, Madeline Murguia Rice, Mark B Landon, Michael W Varner, Brian M Casey, Uma M Reddy, Ronald J Wapner, Dwight J Rouse, Alan T N Tita, John M Thorp, Edward K Chien, Alan M Peaceman, Sean C Blackwell

Faculty, Staff and Student Publications

Objective: The aim of the study is to evaluate whether values and the shape of the glucose curve during the oral glucose tolerance test (OGTT) in pregnancy identify women at risk of developing hypertension (HTN) later in life.

Study design: This category includes the secondary analysis of a follow-up from a mild gestational diabetes mellitus (GDM) study that included a treatment trial for mild GDM (n = 458) and an observational cohort of participants with abnormal 1-hour glucose loading test only (normal OGTT, n = 430). Participants were assessed at a median of 7 (IQR 6-8) years after their …

Characterizing Prostate Cancer Risk Through Multi-Ancestry Genome-Wide Discovery Of 187 Novel Risk Variants, Anqi Wang, Jiayi Shen, Alex A Rodriguez, Edward J Saunders, Fei Chen, Rohini Janivara, Burcu F Darst, Xin Sheng, Yili Xu, Alisha J Chou, Sara Benlloch, Tokhir Dadaev, Mark N Brook, Anna Plym, Ali Sahimi, Thomas J Hoffman, Atushi Takahashi, Koichi Matsuda, Yukihide Momozawa, Masashi Fujita, Triin Laisk, Jéssica Figuerêdo, Kenneth Muir, Shuji Ito, Xiaoxi Liu, Yuji Uchio, Michiaki Kubo, Yoichiro Kamatani, Artitaya Lophatananon, Peggy Wan, Caroline Andrews, Adriana Lori, Parichoy P Choudhury, Johanna Schleutker, Teuvo L J Tammela, Csilla Sipeky, Anssi Auvinen, Graham G Giles, Melissa C Southey, Robert J Macinnis, Cezary Cybulski, Dominika Wokolorczyk, Jan Lubinski, Christopher T Rentsch, Kelly Cho, Benjamin H Mcmahon, David E Neal, Jenny L Donovan, Freddie C Hamdy, Richard M Martin, Borge G Nordestgaard, Sune F Nielsen, Maren Weischer, Stig E Bojesen, Andreas Røder, Hein V Stroomberg, Jyotsna Batra, Suzanne Chambers, Lisa Horvath, Judith A Clements, Wayne Tilly, Gail P Risbridger, Henrik Gronberg, Markus Aly, Robert Szulkin, Martin Eklund, Tobias Nordstrom, Nora Pashayan, Alison M Dunning, Maya Ghoussaini, Ruth C Travis, Tim J Key, Elio Riboli, Jong Y Park, Thomas A Sellers, Hui-Yi Lin, Demetrius Albanes, Stephanie Weinstein, Michael B Cook, Lorelei A Mucci, Edward Giovannucci, Sara Lindstrom, Peter Kraft, David J Hunter, Kathryn L Penney, Constance Turman, Catherine M Tangen, Phyllis J Goodman, Ian M Thompson, Robert J Hamilton, Neil E Fleshner, Antonio Finelli, Marie-Élise Parent, Janet L Stanford, Elaine A Ostrander, Stella Koutros, Laura E Beane Freeman, Meir Stampfer, Alicja Wolk, Niclas Håkansson, Gerald L Andriole, Robert N Hoover, Mitchell J Machiela, Karina Dalsgaard Sørensen, Michael Borre, William J Blot, Wei Zheng, Edward D Yeboah, James E Mensah, Yong-Jie Lu, Hong-Wei Zhang, Ninghan Feng, Xueying Mao, Yudong Wu, Shan-Chao Zhao, Zan Sun, Stephen N Thibodeau, Shannon K Mcdonnell, Daniel J Schaid, Catharine M L West, Gill Barnett, Christiane Maier, Thomas Schnoeller, Manuel Luedeke, Adam S Kibel, Bettina F Drake, Olivier Cussenot, Geraldine Cancel-Tassin, Florence Menegaux, Thérèse Truong, Yves Akoli Koudou, Esther M John, Eli Marie Grindedal, Lovise Maehle, Kay-Tee Khaw, Sue A Ingles, Mariana C Stern, Ana Vega, Antonio Gómez-Caamaño, Laura Fachal, Barry S Rosenstein, Sarah L Kerns, Harry Ostrer, Manuel R Teixeira, Paula Paulo, Andreia Brandão, Stephen Watya, Alexander Lubwama, Jeannette T Bensen, Ebonee N Butler, James L Mohler, Jack A Taylor, Manolis Kogevinas, Trinidad Dierssen-Sotos, Gemma Castaño-Vinyals, Lisa Cannon-Albright, Craig C Teerlink, Chad D Huff, Patrick Pilie, Yao Yu, Ryan J Bohlender, Jian Gu, Sara S Strom, Luc Multigner, Pascal Blanchet, Laurent Brureau, Radka Kaneva, Chavdar Slavov, Vanio Mitev, Robin J Leach, Hermann Brenner, Xuechen Chen, Bernd Holleczek, Ben Schöttker, Eric A Klein, Ann W Hsing, Rick A Kittles, Adam B Murphy, Christopher J Logothetis, Jeri Kim, Susan L Neuhausen, Linda Steele, Yuan Chun Ding, William B Isaacs, Barbara Nemesure, Anselm J M Hennis, John Carpten, Hardev Pandha, Agnieszka Michael, Kim De Ruyck, Gert De Meerleer, Piet Ost, Jianfeng Xu, Azad Razack, Jasmine Lim, Soo-Hwang Teo, Lisa F Newcomb, Daniel W Lin, Jay H Fowke, Christine M Neslund-Dudas, Benjamin A Rybicki, Marija Gamulin, Davor Lessel, Tomislav Kulis, Nawaid Usmani, Aswin Abraham, Sandeep Singhal, Matthew Parliament, Frank Claessens, Steven Joniau, Thomas Van Den Broeck, Manuela Gago-Dominguez, Jose Esteban Castelao, Maria Elena Martinez, Samantha Larkin, Paul A Townsend, Claire Aukim-Hastie, William S Bush, Melinda C Aldrich, Dana C Crawford, Shiv Srivastava, Jennifer Cullen, Gyorgy Petrovics, Graham Casey, Ying Wang, Yao Tettey, Joseph Lachance, Wei Tang, Richard B Biritwum, Andrew A Adjei, Evelyn Tay, Ann Truelove, Shelley Niwa, Kosj Yamoah, Koveela Govindasami, Anand P Chokkalingam, Jacob M Keaton, Jacklyn N Hellwege, Peter E Clark, Mohamed Jalloh, Serigne M Gueye, Lamine Niang, Olufemi Ogunbiyi, Olayiwola Shittu, Olukemi Amodu, Akindele O Adebiyi, Oseremen I Aisuodionoe-Shadrach, Hafees O Ajibola, Mustapha A Jamda, Olabode P Oluwole, Maxwell Nwegbu, Ben Adusei, Sunny Mante, Afua Darkwa-Abrahams, Halimatou Diop, Susan M Gundell, Monique J Roobol, Guido Jenster, Ron H N Van Schaik, Jennifer J Hu, Maureen Sanderson, Linda Kachuri, Rohit Varma, Roberta Mckean-Cowdin, Mina Torres, Michael H Preuss, Ruth J F Loos, Matthew Zawistowski, Sebastian Zöllner, Zeyun Lu, Stephen K Van Den Eeden, Douglas F Easton, Stefan Ambs, Todd L Edwards, Reedik Mägi, Timothy R Rebbeck, Lars Fritsche, Stephen J Chanock, Sonja I Berndt, Fredrik Wiklund, Hidewaki Nakagawa, John S Witte, J Michael Gaziano, Amy C Justice, Nick Mancuso, Chikashi Terao, Rosalind A Eeles, Zsofia Kote-Jarai, Ravi K Madduri, David V Conti, Christopher A Haiman

Faculty, Staff and Student Publications

The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in …

Comparison Of Male And Female Ultramarathon Runners, Kelsey Klug

UNLV Theses, Dissertations, Professional Papers, and Capstones

This research study investigates how specific running variables and demographic characteristics impact performance, or speed, for ultramarathon runners. These variables and characteristics include biological sex, cadence, age range, total distance of the race, duration of the race, years of running experience, total number of ultramarathon races ever completed, and number of races completed in the last twelve months. An ultramarathon is any running distance over a standard marathon or 42.2 kilometers. Participation in ultramarathons has increased by 345% since 2010, with females making up 23% of participants. No in-person data collection was necessary for this study. Participants were asked to …

Qt Interval And Short-Term Outcome In Acute Heart Failure, Òscar Miró, Oriol Aguiló, Joan Carles Trullàs, Víctor Gil, Begoña Espinosa, Javier Jacob, Pablo Herrero-Puente, Josep Tost, María Luísa López-Grima, Pere Comas, Carlos Bibiano, Lluís Llauger, Enrique Martin Mojarro, María Pilar López-Díez, Julio Núñez, Zubaid Rafique, Kelly R Keene, Frank Peacock, Pedro Lopez-Ayala, Christian Mueller, Manuel Montero Pérez-Barquero, Lluís Mont, Pere Llorens

Faculty, Staff and Students Publications

Objective: To investigate the association of corrected QT (QTc) interval duration and short-term outcomes in patients with acute heart failure (AHF).

Methods: We analyzed AHF patients enrolled in 11 Spanish emergency departments (ED) for whom an ECG with QTc measurement was available. Patients with pace-maker rhythm were excluded. Primary outcome was 30-day all-cause mortality and secondary outcomes were need of hospitalization, in-hospital mortality and prolonged hospitalization (> 7 days). Association between QTc and outcomes was explored by restricted cubic spline (RCS) curves. Results were expressed as odds ratios (OR) and 95%CI adjusted by patients baseline and decompensation characteristics, using a …

Enlarged Perivascular Spaces In Infancy And Autism Diagnosis, Cerebrospinal Fluid Volume, And Later Sleep Problems, Dea Garic, Robert C Mckinstry, Kelly N Botteron, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Perivascular spaces (PVS) and cerebrospinal fluid (CSF) are essential components of the glymphatic system, regulating brain homeostasis and clearing neural waste throughout the lifespan. Enlarged PVS have been implicated in neurological disorders and sleep problems in adults, and excessive CSF volume has been reported in infants who develop autism. Enlarged PVS have not been sufficiently studied longitudinally in infancy or in relation to autism outcomes or CSF volume.

OBJECTIVE: To examine whether enlarged PVS are more prevalent in infants who develop autism compared with controls and whether they are associated with trajectories of extra-axial CSF volume (EA-CSF) and sleep …

Longitudinal Lipidomic Profiles During Pregnancy And Associations With Neonatal Anthropometry: Findings From A Multiracial Cohort, Yiqing Song, Ruijin Lu, Guoqi Yu, Mohammad L Rahman, Liwei Chen, Yeiyi Zhu, Michael Y Tsai, Oliver Fiehn, Zhen Chen, Cuilin Zhang

2020-Current year OA Pubs

BACKGROUND: Maternal lipidomic profiling offers promise for characterizing lipid metabolites during pregnancy, but longitudinal data are limited. This study aimed to examine associations of longitudinal lipidomic profiles during pregnancy with multiple neonatal anthropometry using data from a multiracial cohort.

METHODS: We measured untargeted plasma lipidome profiles among 321 pregnant women from the NICHD Fetal Growth Study-Singletons using plasma samples collected longitudinally during four study visits at gestational weeks (GW) 10-14, 15-26, 23-31, and 33-39, respectively. We evaluated individual lipidomic metabolites at each study visit in association with neonatal anthropometry. We also evaluated the associations longitudinally by constructing lipid networks using …

Autogenous Reproduction By Ornithodoros Turicata (Ixodida: Argasidae) Females And Vertical Transmission Of The Tick-Borne Pathogen Borrelia Turicatae (Spirochaetales: Borreliaceae), Serhii Filatov, Aparna Krishnavajhala, Job E Lopez

Faculty, Staff and Students Publications

Ornithodoros turicata is a vector of relapsing fever spirochetes in North America and transmits Borrelia turicatae to a variety of vertebrate hosts. The remarkably long lifespan of O. turicata and its ability to maintain spirochetes horizontally (between life stages) and vertically (to progeny) promote the perpetuation of B. turicatae in nature. Nevertheless, the reproductive biology of O. turicata is poorly understood. In this report, we collected ticks from a park within a neighborhood of Austin, TX. They were reared to adulthood, and male ticks were individually housed with females. We observed autogenous reproduction, which is the ability to produce eggs …

Early And Empirical High-Dose Cryoprecipitate For Hemorrhage After Traumatic Injury: The Cryostat-2 Randomized Clinical Trial, Ross Davenport, Nicola Curry, Erin E Fox, Helen Thomas, Joanne Lucas, Amy Evans, Shaminie Shanmugaranjan, Rupa Sharma, Alison Deary, Antoinette Edwards, Laura Green, Charles E Wade, Jonathan R Benger, Bryan A Cotton, Simon J Stanworth, Karim Brohi, Cryostat-2 Principal Investigators

Faculty, Staff and Student Publications

IMPORTANCE: Critical bleeding is associated with a high mortality rate in patients with trauma. Hemorrhage is exacerbated by a complex derangement of coagulation, including an acute fibrinogen deficiency. Management is fibrinogen replacement with cryoprecipitate transfusions or fibrinogen concentrate, usually administered relatively late during hemorrhage.

OBJECTIVE: To assess whether survival could be improved by administering an early and empirical high dose of cryoprecipitate to all patients with trauma and bleeding that required activation of a major hemorrhage protocol.

DESIGN, SETTING, AND PARTICIPANTS: CRYOSTAT-2 was an interventional, randomized, open-label, parallel-group controlled, international, multicenter study. Patients were enrolled at 26 UK and US …

A Novel Tailed Primer Nucleic Acid Test For Detection Of Hpv 16, 18 And 45 Dna At The Point Of Care, Megan M Chang, Ariel Ma, Emilie Newsham Novak, Maria Barra, Kathryn A Kundrod, Jane Richards Montealegre, Michael E Scheurer, Philip E Castle, Kathleen Schmeler, Rebecca Richards-Kortum

Center for Medical Ethics and Health Policy Staff Publications

Cervical cancer is a leading cause of death for women in low-resource settings despite being preventable through human papillomavirus (HPV) vaccination, early detection, and treatment of precancerous lesions. The World Health Organization recommends high-risk HPV (hrHPV) as the preferred cervical cancer screening strategy, which is difficult to implement in low-resource settings due to high costs, reliance on centralized laboratory infrastructure, and long sample-to-answer times. To help meet the need for rapid, low-cost, and decentralized cervical cancer screening, we developed tailed primer isothermal amplification and lateral flow detection assays for HPV16, HPV18, and HPV45 DNA. We translated these assays into a …

Vaginal Microbial Dynamics And Pathogen Colonization In A Humanized Microbiota Mouse Model, Marlyd E Mejia, Vicki Mercado-Evans, Jacob J Zulk, Samantha Ottinger, Korinna Ruiz, Mallory B Ballard, Stephanie W Fowler, Robert A Britton, Kathryn A Patras

Faculty, Staff and Students Publications

Vaginal microbial composition is associated with differential risk of urogenital infection. Although Lactobacillus spp. are thought to confer protection against infection, the lack of in vivo models resembling the human vaginal microbiota remains a prominent barrier to mechanistic discovery. Using 16S rRNA amplicon sequencing of C57BL/6J female mice, we found that vaginal microbial composition varies within and between colonies across three vivaria. Noting vaginal microbial plasticity in conventional mice, we assessed the vaginal microbiome of humanized microbiota mice (

Prediagnostic Selenium Status, Selenoprotein Gene Variants And Association With Breast Cancer Risk In A European Cohort Study, David J Hughes, Lutz Schomburg, Mazda Jenab, Carine Biessy, Catherine Méplan, Aurelie Moskal, Qian Sun, Kamil Demircan, Veronika Fedirko, Elisabete Weiderpass, Maryam Mukhtar, Anja Olsen, Anne Tjønneland, Kim Overvad, Matthias Schulze, Therese Haugdahl Nøst, Guri Skeie, Karina Standahl Olsen, Fulvio Ricceri, Sara Grioni, Domenico Palli, Giovanna Masala, Rosario Tumino, Fabrizio Pasanisi, Pilar Amiano, Sandra M Colorado Yohar, Antonio Agudo, Maria-Jose Sánchez, Eva Ardanaz, Malin Sund, Anne Andersson, Aurora Perez-Cornago, Ruth Travis, Alicia K Heath, Laure Dossus

Faculty, Staff and Student Publications

Selenium (Se) may help prevent breast cancer (BC) development. Owing to limited observational evidence, we investigated whether prediagnostic Se status and/or variants in the selenoprotein genes are associated with BC risk in a large European cohort. Se status was assessed by plasma measures of Se and its major circulating proteins, selenoprotein P (SELENOP) and glutathione peroxidase 3 (GPX3), in matched BC case-control pairs (2208 for SELENOP; 1785 for GPX3 and Se) nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). Single nucleotide polymorphisms (SNPs, n = 452) in 55 selenoprotein and Se metabolic pathway genes and an additional …

Efficacy Of Futibatinib, An Irreversible Fibroblast Growth Factor Receptor Inhibitor, In Fgfr-Altered Breast Cancer, Turcin Saridogan, Argun Akcakanat, Ming Zhao, Kurt W Evans, Erkan Yuca, Stephen Scott, Bryce P Kirby, Xiaofeng Zheng, Min Jin Ha, Huiqin Chen, Patrick K S Ng, Timothy P Diperi, Gordon B Mills, Jordi Rodon Ahnert, Senthil Damodaran, Funda Meric-Bernstam

Faculty, Staff and Student Publications

Several alterations in fibroblast growth factor receptor (FGFR) genes have been found in breast cancer; however, they have not been well characterized as therapeutic targets. Futibatinib (TAS-120; Taiho) is a novel, selective, pan-FGFR inhibitor that inhibits FGFR1-4 at nanomolar concentrations. We sought to determine futibatinib's efficacy in breast cancer models. Nine breast cancer patient-derived xenografts (PDXs) with various FGFR1-4 alterations and expression levels were treated with futibatinib. Antitumor efficacy was evaluated by change in tumor volume and time to tumor doubling. Alterations indicating sensitization to futibatinib in vivo were further characterized in vitro. FGFR gene expression between patient tumors and …

Gonadotropin-Secreting And Thyrotropin-Secreting Pituitary Adenomas: A Single-Center Experience, Manjiri Karlekar, Chakra Diwaker, Vijaya Sarathi, Anurag Lila, Anima Sharma, Saba Samad Memon, Virendra Patil, Tushar Bandgar

Faculty, Staff and Student Publications

OBJECTIVE: Data regarding rare FPAs from India, a resource limited setting, are limited. We describe a case series of rare FPAs from a single center in western India.

MATERIALS AND METHODS: This was a retrospective case record review of patients diagnosed between January 2010 and July 2022. The diagnosis was based on biochemical(inappropriately elevated serum FSH/LH) and pathologic (positive immunostaining for FSH/LH) features in patients with FGA, and elevated serum thyroid hormones and normal/elevated TSH in patients with TSHomas.

RESULTS: We identified 11 patients with a total of six FGAs (median age 43.5 years, five men, one FGA cosecreting TSH, …

Dissociable Effects Of Alzheimer's Disease-Related Cognitive Dysfunction And Aging On Functional Brain Network Segregation, Ziwei Zhang, Micaela Y Chan, Liang Han, Claudia A Carreno, Ezra Winter-Nelson, Gagan S Wig

Faculty, Staff and Student Publications

Alzheimer's disease (AD) is associated with changes in large-scale functional brain network organization. Individuals with AD exhibit less segregated resting-state brain networks compared with individuals without dementia. However, declines in brain network segregation are also evident as adult individuals grow older. Determining whether these observations reflect unique or overlapping alterations on the functional connectome of the brain is essential for understanding the impact of AD on network organization and incorporating measures of functional brain network organization toward AD characterization. Relationships between AD dementia severity and participant's age on resting-state brain system segregation were examined in 326 cognitively healthy and 275 …

Correlations Between Mental Health, Physical Activity, And Body Composition In American College Students After The Covid-19 Pandemic Lockdown, Luis Torres, Manuela C Caciula, Alin S Tomoiaga, Carmen Gugu-Gramatopol

Faculty, Staff and Student Publications

Restrictions associated with the COVID-19 pandemic had forced American college students to significantly reduce their daily energy expenditure and increase their sedentary behaviors, thus presumably increasing mental health symptoms, decreasing physical activity levels, and enhancing the promotion of unhealthy eating habits. This study aimed to explore the correlations between mental health symptoms, physical activity levels, and body composition in college students in the years following the pandemic, focusing on the lingering effects of lockdown measures. American college students completed pre-existing, well-validated surveys for both mental health (Hospital Anxiety and Depression Scale) and physical activity (International Physical Activity Questionnaire—Long Form). Body …

Height With Age Affects Body Mass Index (Bmi) Assessment Of Chronic Disease Risk, Peter R Holt, Osama Altayar, David H Alpers

2020-Current year OA Pubs

Body mass index (BMI) is a function of weight and height, but changing height has not been emphasized. Using the Framingham Heart Study with 5 decades of data on anthropomorphic measurements and disease states, changing height with age was extracted, and BMI was calculated using current and "young" height (calculated as height at age < 40 years). Decreased height began at age 40, with a mean loss from ages 40 to 80 of 4.8 cm for women and 3.6 cm for men. Using cutoff values of 25 and 30 for overweight and obesity, ~12.5% of women and ~10% of men were misclassified. Comparable figures for obesity classification were ~10 and 8%. At age 70, ~20% of women and ~15% of men were misclassified. Using the BMI corrected to "young" height, obese subjects had an increased risk for developing pre-diabetes and diabetes, with a higher risk for women than men. Using corrected BMI, obese subjects had a higher risk for developing hypertension, lower than for diabetes and higher for men than for women. These data do not establish whether the increased disease risk is clinically important but demonstrate that there is an advantage to using BMI corrected for "young" height when compared with BMI using current age-related height.

Association Between User Interaction And Treatment Response Of A Voice-Based Coach For Treating Depression And Anxiety: Secondary Analysis Of A Pilot Randomized Controlled Trial, Nan Lv, Thomas Kannampallil, Lan Xiao, Corina R Ronneberg, Vikas Kumar, Nancy E Wittels, Olusola A Ajilore, Joshua M Smyth, Jun Ma

2020-Current year OA Pubs

BACKGROUND: The quality of user interaction with therapeutic tools has been positively associated with treatment response; however, no studies have investigated these relationships for voice-based digital tools.

OBJECTIVE: This study evaluated the relationships between objective and subjective user interaction measures as well as treatment response on Lumen, a novel voice-based coach, delivering problem-solving treatment to patients with mild to moderate depression or anxiety or both.

METHODS: In a pilot trial, 42 adults with clinically significant depression (Patient Health Questionnaire-9 [PHQ-9]) or anxiety (7-item Generalized Anxiety Disorder Scale [GAD-7]) symptoms or both received Lumen, a voice-based coach delivering 8 problem-solving treatment …

Multimodal Analysis Of Secondary Cerebellar Alterations After Pediatric Traumatic Brain Injury, Finian Keleher, Hannah M Lindsey, Rebecca Kerestes, Houshang Amiri, Robert F Asarnow, Talin Babikian, Brenda Bartnik-Olson, Erin D Bigler, Karen Caeyenberghs, Carrie Esopenko, Linda Ewing-Cobbs, Christopher C Giza, Naomi J Goodrich-Hunsaker, Cooper B Hodges, Kristen R Hoskinson, Andrei Irimia, Marsh Königs, Jeffrey E Max, Mary R Newsome, Alexander Olsen, Nicholas P Ryan, Adam T Schmidt, Dan J Stein, Stacy J Suskauer, Ashley L Ware, Anne L Wheeler, Brandon A Zielinski, Paul M Thompson, Ian H Harding, David F Tate, Elisabeth A Wilde, Emily L Dennis

Faculty, Staff and Student Publications

Importance: Traumatic brain injury (TBI) is known to cause widespread neural disruption in the cerebrum. However, less is known about the association of TBI with cerebellar structure and how such changes may alter executive functioning.

Objective: To investigate alterations in subregional cerebellum volume and cerebral white matter microstructure after pediatric TBI and examine subsequent changes in executive function.

Design, setting, and participants: This retrospective cohort study combined 12 data sets (collected between 2006 and 2020) from 9 sites in the Enhancing Neuroimaging Genetics Through Meta-Analysis Consortium Pediatric TBI working group in a mega-analysis of cerebellar structure. Participants with TBI or …

Differences In The Circulating Proteome In Individuals With Versus Without Sickle Cell Trait, Yanwei Cai, Nora Franceschini, Aditya Surapaneni, Melanie E Garrett, Usman A Tahir, Li Hsu, Marilyn J Telen, Bing Yu, Hua Tang, Yun Li, Simin Liu, Robert E Gerszten, Josef Coresh, Joann E Manson, Genevieve L Wojcik, Charles Kooperberg, Paul L Auer, Matthew W Foster, Morgan E Grams, Allison E Ashley-Koch, Laura M Raffield, Alex P Reiner

Faculty, Staff and Student Publications

BACKGROUND: Sickle cell trait affects approximately 8% of Black individuals in the United States, along with many other individuals with ancestry from malaria-endemic regions worldwide. While traditionally considered a benign condition, recent evidence suggests that sickle cell trait is associated with lower eGFR and higher risk of kidney diseases, including kidney failure. The mechanisms underlying these associations remain poorly understood. We used proteomic profiling to gain insight into the pathobiology of sickle cell trait.

METHODS: We measured proteomics ( N =1285 proteins assayed by Olink Explore) using baseline plasma samples from 592 Black participants with sickle cell trait and 1:1 …

Correlations Between Elastic Modulus And Ultrashort Echo Time (Ute) Adiabatic T1Ρ Relaxation Time (Ute-Adiab-T1Ρ) In Achilles Tendons And Entheses, Saeed Jerban, Amir Masoud Afsahi, Yajun Ma, Dina Moazamian, Sheronda Statum, Alecio F Lombardi, Lena Kakos, Erik Dorthe, Daryll Dlima, Jiang Du, Christine B Chung, Eric Y Chang

Faculty, Staff and Students Publications

Patients with psoriatic arthritis commonly have abnormalities of their entheses, which are the connections between tendons and bone. There are shortcomings with the use of conventional magnetic resonance imaging (MRI) sequences for the evaluation of entheses and tendons, whereas ultrashort echo time (UTE) sequences are superior for the detection of high signals, and can also be used for non-invasive quantitative assessments of these structures. The combination of UTE-MRI with an adiabatic-T1ρ preparation (UTE-Adiab-T1ρ) allows for reliable assessment of entheses and tendons with decreased susceptibility to detrimental magic angle effects. This study aimed to investigate the relationship between quantitative UTE-MRI measures …

Geographic Variation In Late-Stage Cervical Cancer Diagnosis, Itunu O Sokale, Aaron P Thrift, Jane Montealegre, Victor Adekanmbi, Onyema G Chido-Amajuoyi, Ann Amuta, Lorraine R Reitzel, Abiodun O Oluyomi

Faculty, Staff and Students Publications

IMPORTANCE: There are stark disparities in cervical cancer burden in the United States, notably by race and ethnicity and geography. Late-stage diagnosis is an indicator of inadequate access to and utilization of screening.

OBJECTIVE: To identify geospatial clusters of late-stage cervical cancer at time of diagnosis in Texas.

DESIGN, SETTING, AND PARTICIPANTS: This population-based cross-sectional study used incident cervical cancer data from the Texas Cancer Registry from 2014 to 2018 of female patients aged 18 years or older. Late-stage cervical cancer cases were geocoded at the census tract level (n = 5265) using their residential coordinates (latitude and longitude) at …

Market Competition And Anemia Management In The United States Following Dialysis Payment Reform, Anshul Bhatnagar, Vishnupriyadevi Parvathareddy, Wolfgang C Winkelmayer, Glenn M Chertow, Kevin F Erickson

Faculty, Staff and Students Publications

BACKGROUND: Whether market competition influences health care provider responses to national reimbursement reforms is unknown.

OBJECTIVES: We examined whether changes in anemia management after the expansion of Medicare's dialysis payment bundle varied with market competition.

RESEARCH DESIGN: With data from the US dialysis registry, we used a difference-in-differences (DID) design to estimate the independent associations of market competition with changes in anemia management after dialysis reimbursement reform.

SUBJECTS: A total of 326,150 patients underwent in-center hemodialysis in 2009 and 2012, representing periods before and after reimbursement reform.

MEASURES: Outcomes were erythropoiesis-stimulating agent (ESA) and intravenous iron dosage, the probability of …

Obesity Dominates Early Effects On Cardiac Structure And Arterial Stiffness In People With Type 2 Diabetes, Layla A Abushamat, Daniel Enge, Takashi Fujiwara, Michal Schäfer, Ethan W Clark, Erin K Englund, Rebecca L Scalzo, Aspen Johnston, Deirdre Rafferty, Irene E Schauer, Mary O Whipple, Kendall Hunter, Amy G Huebschmann, Kristen J Nadeau, Kelly Jarvis, Alex J Barker, Judith G Regensteiner, Jane E B Reusch

Faculty, Staff and Students Publications

OBJECTIVE: Type 2 diabetes (T2D) and obesity are global epidemics leading to excess cardiovascular disease (CVD). This study investigates standard and novel cardiac MRI parameters to detect subclinical cardiac and central vascular dysfunction in inactive people with and without T2D.

METHODS: Physically inactive age and BMI-similar premenopausal women and men with ( n  = 22) and without [ n  = 34, controls with overweight/obesity (CWO)] uncomplicated T2D were compared to an age-similar and sex-similar reference control cohort ( n  = 20). Left ventricular (LV) structure, function, and aortic stiffness were assessed by MRI. Global arterial pulse wave velocity (PWV) was …

Molecular Diagnostic Yield Of Exome Sequencing In Patients With Congenital Hydrocephalus: A Systematic Review And Meta-Analysis, Ana B W Greenberg, Neel H Mehta, Garrett Allington, Sheng Chih Jin, Andrés Moreno-De-Luca, Kristopher T Kahle

2020-Current year OA Pubs

IMPORTANCE: Exome sequencing (ES) has been established as the preferred first line of diagnostic testing for certain neurodevelopmental disorders, such as global developmental delay and autism spectrum disorder; however, current recommendations are not specific to or inclusive of congenital hydrocephalus (CH).

OBJECTIVE: To determine the diagnostic yield of ES in CH and whether ES should be considered as a first line diagnostic test for CH.

DATA SOURCES: PubMed, Cochrane Library, and Google Scholar were used to identify studies published in English between January 1, 2010, and April 10, 2023. The following search terms were used to identify studies: congenital hydrocephalus, …