Digital Commons Network^™

Association Of Pediatric Buccal Epigenetic Age Acceleration With Adverse Neonatal Brain Growth And Neurodevelopmental Outcomes Among Children Born Very Preterm With A Neonatal Infection., Noha Gomaa, Chaini Konwar, Nicole Gladish, Stephanie H Au-Young, Ting Guo, Min Sheng, Sarah M Merrill, Edmond Kelly, Vann Chau, Helen M Branson, Linh G Ly, Emma G Duerden, Ruth E Grunau, Michael S Kobor, Steven P Miller

Department of Medicine Publications

IMPORTANCE: Very preterm neonates (24-32 weeks' gestation) remain at a higher risk of morbidity and neurodevelopmental adversity throughout their lifespan. Because the extent of prematurity alone does not fully explain the risk of adverse neonatal brain growth or neurodevelopmental outcomes, there is a need for neonatal biomarkers to help estimate these risks in this population.

OBJECTIVES: To characterize the pediatric buccal epigenetic (PedBE) clock-a recently developed tool to measure biological aging-among very preterm neonates and to assess its association with the extent of prematurity, neonatal comorbidities, neonatal brain growth, and neurodevelopmental outcomes at 18 months of age.

DESIGN, SETTING, AND …

Comparison Of Evaluations For Heart Transplant Before Durable Left Ventricular Assist Device And Subsequent Receipt Of Transplant At Transplant Vs Nontransplant Centers, Thomas M. Cascino, Jeffrey S. Mccullough, Xiaoting Wu, Michael J. Pienta, James W. Stewart, Robert B. Hawkins, Alexander A. Brescia, Ashraf Abou El Ala, Min Zhang, Pierre-Emmanuel Noly, Jonathan W. Haft, Jennifer A. Cowger, Monica Colvin, Keith D. Aaronson, Francis D. Pagani, Donald S. Likosky

Cardiology Articles

IMPORTANCE: In 2020, the Centers for Medicare & Medicaid Services revised its national coverage determination, removing the requirement to obtain review from a Medicare-approved heart transplant center to implant a durable left ventricular assist device (LVAD) for bridge-to-transplant (BTT) intent at an LVAD-only center. The association between center-level transplant availability and access to heart transplant, the gold-standard therapy for advanced heart failure (HF), is unknown.

OBJECTIVE: To investigate the association of center transplant availability with LVAD implant strategies and subsequent heart transplant following LVAD implant before the Centers for Medicare & Medicaid Services policy change.

DESIGN, SETTING, AND PARTICIPANTS: A …

Risk Factors For Community-Acquired Bacterial Infection Among Young Infants In South Asia: A Longitudinal Cohort Study With Nested Case-Control Analysis, Nicholas E Connor, Mohammad Shahidul Islam, Luke C Mullany, Nong Shang, Zulfiqar A Bhutta, Anita K M Zaidi, Sajid Soofi, Imran Nisar, Pinaki Panigrahi, Kalpana Panigrahi, Radhanath Satpathy, Anuradha Bose, Rita Isaac, Abdullah H Baqui, Dipak K Mitra, Qazi Sadeq-Ur Rahman, Tanvir Hossain, Stephanie J Schrag, Jonas M Winchell, Melissa L Arvay, Maureen H Diaz, Jessica L Waller, Martin W Weber, Davidson H Hamer, Patricia Hibberd, A S M Nawshad Uddin Ahmed, Maksuda Islam, Mohammad Belal Hossain, Shamim A Qazi, Shams El Arifeen, Gary L Darmstadt, Samir K Saha

Faculty, Staff and Student Publications

OBJECTIVE: Risk factors predisposing infants to community-acquired bacterial infections during the first 2 months of life are poorly understood in South Asia. Identifying risk factors for infection could lead to improved preventive measures and antibiotic stewardship.

METHODS: Five sites in Bangladesh, India and Pakistan enrolled mother-child pairs via population-based pregnancy surveillance by community health workers. Medical, sociodemographic and epidemiological risk factor data were collected. Young infants aged 0-59 days with signs of possible serious bacterial infection (pSBI) and age-matched controls provided blood and respiratory specimens that were analysed by blood culture and real-time PCR. These tests were used to build …

Investigation Of Murine Host Sex As A Biological Variable In Epithelial Barrier Function And Muscle Contractility In Human Intestinal Organoids, Brooke T Beanland, Eoin P Mcneill, David J Sequeira, Hasen Xue, Noah F Shroyer, Allison L Speer

Faculty, Staff and Student Publications

Intestinal failure (IF) occurs when intestinal surface area or function is not sufficient to support digestion and nutrient absorption. Human intestinal organoid (HIO)-derived tissue-engineered intestine is a potential cure for IF. Research to date has demonstrated successful HIO transplantation (tHIO) into mice with significant in vivo maturation. An area lacking in the literature is exploration of murine host sex as a biological variable (SABV) in tHIO function. In this study, we investigate murine host SABV in tHIO epithelial barrier function and muscle contractility. HIOs were generated in vitro and transplanted into nonobese diabetic, severe combined immunodeficiency gamma chain deficient male …

Trim-Nhl Protein, Nhl-2, Modulates Cell Fate Choices In The C. Elegans Germ Line, John L. Brenner, Erin M. Jyo, Ariz Mohammad, Paul Fox, Vovanti Jones, Elaine Mardis, Tim Schedl, Eleanor M. Maine

2020-Current year OA Pubs

Many tissues contain multipotent stem cells that are critical for maintaining tissue function. In Caenorhabditis elegans, germline stem cells allow gamete production to continue in adulthood. In the gonad, GLP-1/Notch signaling from the distal tip cell niche to neighboring germ cells activates a complex regulatory network to maintain a stem cell population. GLP-1/Notch signaling positively regulates production of LST-1 and SYGL-1 proteins that, in turn, interact with a set of PUF/FBF proteins to positively regulate the stem cell fate. We previously described sog (suppressor of glp-1 loss of function) and teg (tumorous enhancer of glp-1 gain of function) genes that …

Sex-Specific Role Of Myostatin Signaling In Neonatal Muscle Growth, Denervation Atrophy, And Neuromuscular Contractures., Marianne E Emmert, Parul Aggarwal, Kritton Shay-Winkler, Se-Jin Lee, Qingnian Goh, Roger Cornwall

Faculty Research 2023

Neonatal brachial plexus injury (NBPI) causes disabling and incurable muscle contractures that result from impaired longitudinal growth of denervated muscles. This deficit in muscle growth is driven by increased proteasome-mediated protein degradation, suggesting a dysregulation of muscle proteostasis. The myostatin (MSTN) pathway, a prominent muscle-specific regulator of proteostasis, is a putative signaling mechanism by which neonatal denervation could impair longitudinal muscle growth, and thus a potential target to prevent NBPI-induced contractures. Through a mouse model of NBPI, our present study revealed that pharmacologic inhibition of MSTN signaling induces hypertrophy, restores longitudinal growth, and prevents contractures in denervated muscles of female …

The Risks Of Birth Defects And Childhood Cancer With Conception By Assisted Reproductive Technology, Barbara Luke, Morton B Brown, Ethan Wantman, Maria J Schymura, Marilyn L Browne, Sarah C Fisher, Nina E Forestieri, Chandrika Rao, Hazel B Nichols, Mahsa M Yazdy, Susan T Gershman, Caitlin R Sacha, Melanie Williams, Mary K Ethen, Mark A Canfield, Kevin J Doody, Michael L Eisenberg, Valerie L Baker, Carrie Williams, Alastair G Sutcliffe, Melissa A Richard, Philip J Lupo

Center for Medical Ethics and Health Policy Staff Publications

Study question: Is there an association between fertility status, method of conception and the risks of birth defects and childhood cancer?

Summary answer: The risk of childhood cancer had two independent components: (i) method of conception and (ii) presence, type and number of birth defects.

What is known already: The rarity of the co-occurrence of birth defects, cancer and ART makes studying their association challenging. Prior studies have indicated that infertility and ART are associated with an increased risk of birth defects or cancer but have been limited by small sample size and inadequate statistical power, failure to adjust for …

Genetic Testing To Inform Epilepsy Treatment Management From An International Study Of Clinical Practice, Dianalee Mcknight, Ana Morales, Kathryn E. Hatchell, Sara L. Bristow, Joshua L. Bonkowsky, Michael Scott Perry, Anne T. Berg, Felippe Borlot, Edward D. Esplin, Chad Moretz, Katie Angione, Loreto Ríos-Pohl, Robert L. Nussbaum, Swaroop Aradhya, Chad R. Haldeman-Englert, Rebecca J. Levy, Venu G. Parachuri, Guillermo Lay-Son, David J. Dávila-Ortiz De Montellano, Miguel Angel Ramirez-Garcia, Edmar O. Benítez Alonso, Julie Ziobro, Adela Chirita-Emandi, Temis M. Felix, Dianne Kulasa-Luke, Andre Megarbane, Shefali Karkare, Sarah L. Chagnon, Jennifer B. Humberson, Melissa J. Assaf, Sebastian Silva, Katherine Zarroli, Oksana Boyarchuk, Gary R. Nelson, Rachel Palmquist, Katherine C. Hammond, Sean T. Hwang, Susan B. Boutlier, Melinda Nolan, Kaitlin Y. Batley, Devraj Chavda, Carlos Alberto Reyes-Silva, Oleksandr Miroshnikov, Britton Zuccarelli, Louise Amlie-Wolf, James W. Wheless, Syndi Seinfeld, Manoj Kanhangad, Jeremy L. Freeman, Susana Monroy-Santoyo, Natalia Rodriguez-Vazquez, Monique M. Ryan, Michelle Machie, Patricio Guerra, Muhammad Jawad Hassan, Meghan S. Candee, Caleb P. Bupp, Kristen L. Park, Eric Muller, Pamela Lupo, Robert C. Pedersen, Amir M. Arain, Andrea Murphy, Krista Schatz, Weiyi Mu, Paige M. Kalika, Lautaro Plaza, Marissa A. Kellogg, Evelyn G. Lora, Robert P. Carson, Victoria Svystilnyk, Viviana Venegas, Rebecca R. Luke, Huiyuan Jiang, Tetiana Stetsenko, Milagros M. Dueñas-Roque, Joseph Trasmonte, Rebecca J. Burke, Anna C. E. Hurst, Douglas M. Smith, Lauren J. Massingham, Laura Pisani, Carrie E. Costin, Betsy Ostrander, Francis M. Filloux, Amitha L. Ananth, Ismail S. Mohamed, Alla Nechai, Jasmin M. Dao, Michael C. Fahey, Ermal Aliu, Stephen Falchek, Craig A. Press, Lauren Treat, Krista Eschbach, Angela Starks, Ryan Kammeyer, Joshua J. Bear, Mona Jacobson, Veronika Chernuha, Bailey Meibos, Kristen Wong, Matthew T. Sweney, A. Chris Espinoza, Colin B. Van Orman, Arie Weinstock, Ashutosh Kumar, Claudia Soler-Alfonso, Danielle A. Nolan, Muhammad Raza, Miguel David Rojas Carrion, Geetha Chari, Eric D. Marsh, Yael Shiloh-Malawsky, Sumit Parikh, Ernesto Gonzalez-Giraldo, Stephen Fulton, Yoshimi Sogawa, Kaitlyn Burns, Myroslava Malets, Johnny David Montiel Blanco, Christa W. Habela, Carey A. Wilson, Guillermo G. Guzmán, Mariia Pavliuk

Department of Pediatrics Faculty Papers

IMPORTANCE: It is currently unknown how often and in which ways a genetic diagnosis given to a patient with epilepsy is associated with clinical management and outcomes.

OBJECTIVE: To evaluate how genetic diagnoses in patients with epilepsy are associated with clinical management and outcomes.

DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cross-sectional study of patients referred for multigene panel testing between March 18, 2016, and August 3, 2020, with outcomes reported between May and November 2020. The study setting included a commercial genetic testing laboratory and multicenter clinical practices. Patients with epilepsy, regardless of sociodemographic features, who received a …

A Cop1-Gata2 Axis Suppresses Ar Signaling And Prostate Cancer, Tao Shen, Bingning Dong, Yanling Meng, David D Moore, Feng Yang

Faculty, Staff and Students Publications

Androgen receptor (AR) signaling is crucial for driving prostate cancer (PCa), the most diagnosed and the second leading cause of death in male patients with cancer in the United States. Androgen deprivation therapy is initially effective in most instances of AR-positive advanced or metastatic PCa. However, patients inevitably develop lethal castration-resistant PCa (CRPC), which is also resistant to the next-generation AR signaling inhibitors. Most CRPCs maintain AR expression, and blocking AR signaling remains a main therapeutic approach. GATA2 is a pioneer transcription factor emerging as a key therapeutic target for PCa because it promotes AR expression and activation. While directly …

Sex Difference Leads To Differential Gene Expression Patterns And Therapeutic Efficacy In Mucopolysaccharidosis Iva Murine Model Receiving Aav8 Gene Therapy, Matthew Matthew Piechnik, Paige C. Amendum, Kazuki Sawamoto, Molly Stapleton, Shaukat Khan, Nidhi Fnu, Victor Álvarez, Angelica Maria Herreño Pachon, Olivier Danos, Joseph T. Bruder, Subha Karumuthil-Melethil, Shunji Tomatsu

Student Papers, Posters & Projects

Adeno-associated virus (AAV) vector-based therapies can effectively correct some disease pathology in murine models with mucopolysaccharidoses. However, immunogenicity can limit therapeutic effect as immune responses target capsid proteins, transduced cells, and gene therapy products, ultimately resulting in loss of enzyme activity. Inherent differences in male versus female immune response can significantly impact AAV gene transfer. We aim to investigate sex differences in the immune response to AAV gene therapies in mice with mucopolysaccharidosis IVA (MPS IVA). MPS IVA mice, treated with different AAV vectors expressing human N-acetylgalactosamine 6-sulfate sulfatase (GALNS), demonstrated a more robust antibody response in female mice resulting …

Loss Of Activity-Induced Mitochondrial Atp Production Underlies The Synaptic Defects In A Drosophila Model Of Als, Nicholas E Karagas, Richa Gupta, Elham Rastegari, Kai Li Tan, Ho Hang Leung, Hugo J Bellen, Kartik Venkatachalam, Ching-On Wong

Faculty, Staff and Students Publications

Mutations in the gene encoding vesicle-associated membrane protein B (VAPB) cause a familial form of amyotrophic lateral sclerosis (ALS). Expression of an ALS-related variant of vapb (vapb^P58S) in Drosophila motor neurons results in morphologic changes at the larval neuromuscular junction (NMJ) characterized by the appearance of fewer, but larger, presynaptic boutons. Although diminished microtubule stability is known to underlie these morphologic changes, a mechanism for the loss of presynaptic microtubules has been lacking. By studying flies of both sexes, we demonstrate the suppression of vapb^P58S-induced changes in NMJ morphology by either a loss of endoplasmic …

Maternal Gut Microbiota Mediate Intergenerational Effects Of High-Fat Diet On Descendant Social Behavior, Claudia M Di Gesù, Lisa M Matz, Ian J Bolding, Robert Fultz, Kristi L Hoffman, Antonella Marino Gammazza, Joseph F Petrosino, Shelly A Buffington

Faculty, Staff and Students Publications

Dysbiosis of the maternal gut microbiome during pregnancy is associated with adverse neurodevelopmental outcomes. We previously showed that maternal high-fat diet (MHFD) in mice induces gut dysbiosis, social dysfunction, and underlying synaptic plasticity deficits in male offspring (F1). Here, we reason that, if HFD-mediated changes in maternal gut microbiota drive offspring social deficits, then MHFD-induced dysbiosis in F1 female MHFD offspring would likewise impair F2 social behavior. Metataxonomic sequencing reveals reduced microbial richness among female F1 MHFD offspring. Despite recovery of microbial richness among MHFD-descendant F2 mice, they display social dysfunction. Post-weaning Limosilactobacillus reuteri treatment increases the abundance of short-chain …

Differential Patterns And Outcomes Of 20.6 Million Cardiovascular Emergency Department Encounters For Men And Women In The United States., Zahra Raisi-Estabragh, Ofer Kobo, Ayman Elbadawi, Poonam Velagapudi, Garima Sharma, Renee P Bullock-Palmer, Steffen E Petersen, Laxmi S Mehta, Waqas Ullah, Ariel Roguin, Louise Y Sun, Mamas A Mamas

Division of Cardiology Faculty Papers

Background We describe sex-differential disease patterns and outcomes of >20.6 million cardiovascular emergency department encounters in the United States. Methods and Results We analyzed primary cardiovascular encounters from the Nationwide Emergency Department Sample between 2016 and 2018. We grouped cardiovascular diagnoses into 15 disease categories. The sample included 48.7% women; median age was 67 (interquartile range, 54-78) years. Men had greater overall baseline comorbidity burden; however, women had higher rates of obesity, hypertension, and cerebrovascular disease. For women, the most common emergency department encounters were essential hypertension (16.0%), hypertensive heart or kidney disease (14.1%), and atrial fibrillation/flutter (10.2%). For men, …

Association Of Prediagnosis Obesity And Postdiagnosis Aspirin With Survival From Stage Iv Colorectal Cancer, Jennifer S Davis, Janelle C Chavez, Melissa Kok, Yazmin San Miguel, Hwa Young Lee, Henry Henderson, Michael J Overman, Van Morris, Bryan Kee, David Fogelman, Shailesh M Advani, Benny Johnson, Christine Parseghian, John Paul Shen, Arvind Dasari, Kenna R Shaw, Eduardo Vilar, Kanwal P Raghav, Imad Shureiqi, Robert A Wolff, Funda Meric-Bernstam, Dipen Maru, David G Menter, Scott Kopetz, Shine Chang

Faculty, Staff and Student Publications

IMPORTANCE: The potential relationship between obesity and colorectal cancer (CRC) outcome is poorly understood in patients with late-stage disease. Increased body mass index may negate aspirin use for cancer prevention, but its role as a factor on the effectiveness of postdiagnosis aspirin use is unclear.

OBJECTIVE: To evaluate how prediagnosis obesity and postdiagnosis aspirin use may be associated with overall survival in patients with late-stage colorectal cancer.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used self-reported data from patients with metastatic or treatment-refractory disease who consented to a clinical protocol at MD Anderson Cancer Center, a large US cancer treatment …

Synergistic Associations Of Pnpla3 I148m Variant, Alcohol Intake, And Obesity With Risk Of Cirrhosis, Hepatocellular Carcinoma, And Mortality, Hyun-Seok Kim, Xiangjun Xiao, Jinyoung Byun, Goo Jun, Stacia M Desantis, Han Chen, Aaron P Thrift, Hashem B El-Serag, Fasiha Kanwal, Christopher I Amos

Faculty, Staff and Student Publications

IMPORTANCE: Alcohol drinking and obesity are associated with an increased risk of cirrhosis and hepatocellular carcinoma (HCC), but the risk is not uniform among people with these risk factors. Genetic variants, such as I148M in the patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene, may play an important role in modulating cirrhosis and HCC risk.

OBJECTIVE: to investigate the joint associations of the PNPLA3 I148M variant, alcohol intake, and obesity with the risk of cirrhosis, HCC, and liver disease-related mortality.

DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study analyzed 414 209 participants enrolled in the UK Biobank study from March 2006 …

Percentage Of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy Vs Placebo In The Treatment Of Adult Patients With Alcohol Use Disorder: A Randomized Clinical Trial, Michael P. Bogenschutz, Stephen Ross, Snehal Bhatt, Tara Baron, Alyssa A. Forcehimes, Eugene Laska, Sarah E. Mennenga, Kelley O'Donnell, Lindsey T. Owens, Samantha Podrebarac, John Rotrosen, J Scott Tonigan, Lindsay Worth

Family and Community Medicine Research and Scholarship

IMPORTANCE: Although classic psychedelic medications have shown promise in the treatment of alcohol use disorder (AUD), the efficacy of psilocybin remains unknown.

OBJECTIVE: To evaluate whether 2 administrations of high-dose psilocybin improve the percentage of heavy drinking days in patients with AUD undergoing psychotherapy relative to outcomes observed with active placebo medication and psychotherapy.

DESIGN, SETTING, AND PARTICIPANTS: In this double-blind randomized clinical trial, participants were offered 12 weeks of manualized psychotherapy and were randomly assigned to receive psilocybin vs diphenhydramine during 2 day-long medication sessions at weeks 4 and 8. Outcomes were assessed over the 32-week double-blind period following …

A Randomized Controlled Trial Evaluating The Effects Of Social Networking On Chronic Disease Management In Rheumatoid Arthritis, Maria A Lopez-Olivo, Jessica T Foreman, Cheuk Leung, Heather Y Lin, Tiffany Westrich-Robertson, Catherine Hofstetter, Jude K A Des Bordes, Anne Lyddiatt, Amye Leong, Irmgard U Willcockson, Susan K Peterson, Maria E Suarez-Almazor

Faculty, Staff and Student Publications

OBJECTIVE: Social networking has been shown to improve health outcomes in certain patient populations. While patients with rheumatoid arthritis (RA) increasingly use social networking to communicate with peers, the effects of these interactions are largely unknown.

METHODS: In a randomized controlled trial, we compared RA patients who participated in a social networking group moderated by peer leaders and who had access to a static website offering RA materials with a control group, who only had access to the website. The primary outcomes were patients' RA knowledge, self-efficacy and empowerment. Secondary outcomes included participation in desired health behaviors, and satisfaction with …

Variability In Energy Expenditure Is Much Greater In Males Than Females, Lewis G Halsey, Vincent Careau, Herman Pontzer, Philip N Ainslie, Lene F Andersen, Liam J Anderson, Lenore Arab, Issad Baddou, Kweku Bedu-Addo, Ellen E Blaak, Stephane Blanc, Alberto G Bonomi, Carlijn V C Bouten, Pascal Bovet, Maciej S Buchowski, Nancy F Butte, Stefan G J A Camps, Graeme L Close, Jamie A Cooper, Sai Krupa Das, Richard Cooper, Lara R Dugas, Ulf Ekelund, Sonja Entringer, Terrence Forrester, Barry W Fudge, Annelies H Goris, Michael Gurven, Catherine Hambly, Asmaa El Hamdouchi, Marije B Hoos, Sumei Hu, Noorjehan Joonas, Annemiek M Joosen, Peter Katzmarzyk, Kitty P Kempen, Misaka Kimura, William E Kraus, Robert F Kushner, Estelle V Lambert, William R Leonard, Nader Lessan, Corby K Martin, Anine C Medin, Erwin P Meijer, James C Morehen, James P Morton, Marian L Neuhouser, Theresa A Nicklas, Robert M Ojiambo, Kirsi H Pietiläinen, Yannis P Pitsiladis, Jacob Plange-Rhule, Guy Plasqui, Ross L Prentice, Roberto A Rabinovich, Susan B Racette, David A Raichlen, Eric Ravussin, Rebecca M Reynolds, Susan B Roberts, Albertine J Schuit, Anders M Sjödin, Eric Stice, Samuel S Urlacher, Giulio Valenti, Ludo M Van Etten, Edgar A Van Mil, George Wilson, Brian M Wood, Jack Yanovski, Tsukasa Yoshida, Xueying Zhang, Alexia J Murphy-Alford, Cornelia U Loechl, Amy H Luke, Jennifer Rood, Hiroyuki Sagayama, Dale A Schoeller, Klaas R Westerterp, William W Wong, Yosuke Yamada, John R Speakman

Children’s Nutrition Research Center Staff Publications

In mammals, trait variation is often reported to be greater among males than females. However, to date, mainly only morphological traits have been studied. Energy expenditure represents the metabolic costs of multiple physical, physiological, and behavioral traits. Energy expenditure could exhibit particularly high greater male variation through a cumulative effect if those traits mostly exhibit greater male variation, or a lack of greater male variation if many of them do not. Sex differences in energy expenditure variation have been little explored. We analyzed a large database on energy expenditure in adult humans (1494 males and 3108 females) to investigate whether …

Influence Of Pregabalin Maintenance On Cannabis Effects And Related Behaviors In Daily Cannabis Users, Joshua A Lile, Joseph L Alcorn, Lon R Hays, Thomas H Kelly, William W Stoops, Michael J Wesley, Philip M Westgate

Faculty, Staff and Student Publications

No medications are approved for cannabis use disorder (CUD), though a small clinical trial demonstrated that the voltage-dependent calcium channel (VDCC) ligand gabapentin reduced cannabis use in treatment seekers. VDCCs are modulated by cannabinoid (CB) ligands, and there are shared effects between CB agonists and VDCC ligands. This overlapping neuropharmacology and the initial clinical results supported the evaluation of pregabalin, a "next-generation" VDCC ligand, as a CUD medication. Two separate placebo-controlled, double-blind, counterbalanced, within-subjects human laboratory studies tested placebo and 300 (N = 2 females, 11 males; Experiment [EXP] 1) or 450 (N = 3 females, 11 males; …

Association Of Puberty Stage And Weight Status With Cardiometabolic Risk In Children And Adolescents Living On The Texas-Mexico Border, Ee Vien Low, Miryoung Lee, Cici Bauer, Susan P Fisher-Hoch, Joseph B Mccormick, Susan Abughosh, Ekere J Essien, Jessica Rodriguez, Hua Chen

Faculty, Staff and Student Publications

Background: This retrospective cohort study aimed to examine the interaction effect between puberty stage and weight status on individual and clustering of cardiometabolic risk factors (CMRFs) among Mexican American children and adolescents. A total of 333 children and adolescents (aged 8-18 years) enrolled in the Cameron County Hispanic Cohort (CCHC) from 2014 to 2020 were included in the study.

Methods: CCHC is a longitudinal, randomly recruited cohort based on the United States Census tracts/blocks of Mexican Americans living on the Texas-Mexico border. Individual CMRFs, including high blood pressure, central obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol, and insulin resistance (IR) were …

223ra Induces Transient Functional Bone Marrow Toxicity, Maria Parlani, Francesco Boccalatte, Anna Yeaton, Feng Wang, Jianhua Zhang, Iannis Aifantis, Eleonora Dondossola

Faculty, Staff and Student Publications

223Ra is a bone-seeking, α-particle-emitting radionuclide approved for the treatment of patients with metastatic prostate cancer and is currently being tested in a variety of clinical trials for primary and metastatic cancers to bone. Clinical evaluation of 223Ra hematologic safety showed a significantly increased rate of neutropenia and thrombocytopenia in patients, hinting at myelosuppression as a side effect. Methods: In this study, we investigated the consequences of 223Ra treatment on bone marrow biology by combining flow cytometry, single-cell RNA sequencing, three-dimensional multiphoton microscopy and bone marrow transplantation analyses. Results: 223Ra accumulated in bones and induced zonal radiation damage confined to …

Characteristics Of Graft-Versus-Host Disease (Gvhd) After Post-Transplantation Cyclophosphamide Versus Conventional Gvhd Prophylaxis, Rima M Saliba, Amin M Alousi, Joseph Pidala, Mukta Arora, Stephen R Spellman, Michael T Hemmer, Tao Wang, Camille Abboud, Sairah Ahmed, Joseph H Antin, Amer Beitinjaneh, David Buchbinder, Michael Byrne, Jean-Yves Cahn, Hannah Choe, Rabi Hanna, Peiman Hematti, Rammurti T Kamble, Carrie L Kitko, Mary Laughlin, Lazaros Lekakis, Margaret L Macmillan, Rodrigo Martino, Parinda A Mehta, Taiga Nishihori, Sagar S Patel, Miguel-Angel Perales, Hemalatha G Rangarajan, Olov Ringdén, Joseph Rosenthal, Bipin N Savani, Kirk R Schultz, Sachiko Seo, Takanori Teshima, Marjolein Van Der Poel, Leo F Verdonck, Daniel Weisdorf, Baldeep Wirk, Jean A Yared, Jeffrey Schriber, Richard E Champlin, Stefan O Ciurea

Center for Medical Ethics and Health Policy Staff Publications

Post-transplantation cyclophosphamide (PTCy) has been shown to effectively control graft-versus-host disease (GvHD) in haploidentical (Haplo) transplantations. In this retrospective registry study, we compared GvHD organ distribution, severity, and outcomes in patients with GvHD occurring after Haplo transplantation with PTCy GvHD prophylaxis (Haplo/PTCy) versus HLA-matched unrelated donor transplantation with conventional prophylaxis (MUD/conventional). We evaluated 2 cohorts: patients with grade 2 to 4 acute GvHD (aGvHD) including 264 and 1163 recipients of Haplo and MUD transplants; and patients with any chronic GvHD (cGvHD) including 206 and 1018 recipients of Haplo and MUD transplants, respectively. In comparison with MUD/conventional transplantation ± antithymocyte globulin …

Sex-Specific Epigenetic Development In The Mouse Hypothalamic Arcuate Nucleus Pinpoints Human Genomic Regions Associated With Body Mass Index, Harry Mackay, Chathura J Gunasekara, Kit-Yi Yam, Dollada Srisai, Hari Krishna Yalamanchili, Yumei Li, Rui Chen, Cristian Coarfa, Robert A Waterland

Duncan NRI Faculty and Staff Publications

Recent genome-wide association studies corroborate classical research on developmental programming indicating that obesity is primarily a neurodevelopmental disease strongly influenced by nutrition during critical ontogenic windows. Epigenetic mechanisms regulate neurodevelopment; however, little is known about their role in establishing and maintaining the brain's energy balance circuitry. We generated neuron and glia methylomes and transcriptomes from male and female mouse hypothalamic arcuate nucleus, a key site for energy balance regulation, at time points spanning the closure of an established critical window for developmental programming of obesity risk. We find that postnatal epigenetic maturation is markedly cell type and sex specific and …

Identification Of An Early Survival Prognostic Gene Signature For Localized Osteosarcoma Patients, Harry Mackay, Chathura J Gunasekara, Kit-Yi Yam, Dollada Srisai, Hari Krishna Yalamanchili, Yumei Li, Rui Chen, Cristian Coarfa, Robert A Waterland

Faculty, Staff and Students Publications

Recent genome-wide association studies corroborate classical research on developmental programming indicating that obesity is primarily a neurodevelopmental disease strongly influenced by nutrition during critical ontogenic windows. Epigenetic mechanisms regulate neurodevelopment; however, little is known about their role in establishing and maintaining the brain's energy balance circuitry. We generated neuron and glia methylomes and transcriptomes from male and female mouse hypothalamic arcuate nucleus, a key site for energy balance regulation, at time points spanning the closure of an established critical window for developmental programming of obesity risk. We find that postnatal epigenetic maturation is markedly cell type and sex specific and …

Insular Cortical Circuits As An Executive Gateway To Decipher Threat Or Extinction Memory Via Distinct Subcortical Pathways, Qi Wang, Jia-Jie Zhu, Lizhao Wang, Yan-Peng Kan, Yan-Mei Liu, Yan-Jiao Wu, Xue Gu, Xin Yi, Ze-Jie Lin, Qin Wang, Jian-Fei Lu, Qin Jiang, Ying Li, Ming-Gang Liu, Nan-Jie Xu, Michael X Zhu, Lu-Yang Wang, Siyu Zhang, Wei-Guang Li, Tian-Le Xu

Faculty, Staff and Student Publications

Threat and extinction memories are crucial for organisms' survival in changing environments. These memories are believed to be encoded by separate ensembles of neurons in the brain, but their whereabouts remain elusive. Using an auditory fear-conditioning and extinction paradigm in male mice, here we discovered that two distinct projection neuron subpopulations in physical proximity within the insular cortex (IC), targeting the central amygdala (CeA) and nucleus accumbens (NAc), respectively, to encode fear and extinction memories. Reciprocal intracortical inhibition of these two IC subpopulations gates the emergence of either fear or extinction memory. Using rabies-virus-assisted tracing, we found IC-NAc projection neurons …

Single-Cell Rna Sequencing Reveals Molecular Features Of Heterogeneity In The Murine Retinal Pigment Epithelium., Ravi S Pandey, Mark P. Krebs, Mohan Bolisetty, Jeremy R. Charette, Juergen K. Naggert, Paul Robson, Patsy M. Nishina, Gregory W. Carter

Faculty Research 2022

Transcriptomic analysis of the mammalian retinal pigment epithelium (RPE) aims to identify cellular networks that influence ocular development, maintenance, function, and disease. However, available evidence points to RPE cell heterogeneity within native tissue, which adds complexity to global transcriptomic analysis. Here, to assess cell heterogeneity, we performed single-cell RNA sequencing of RPE cells from two young adult male C57BL/6J mice. Following quality control to ensure robust transcript identification limited to cell singlets, we detected 13,858 transcripts among 2667 and 2846 RPE cells. Dimensional reduction by principal component analysis and uniform manifold approximation and projection revealed six distinct cell populations. All …

Modelling Aggressive Prostate Cancers Of Young Men In Immune-Competent Mice, Driven By Isogenic Trp53 Alterations And Pten Loss, Javier Octavio Mejía-Hernández, Simon P Keam, Reem Saleh, Fenella Muntz, Stephen B Fox, David Byrne, Arielle Kogan, Lokman Pang, Jennifer Huynh, Cassandra Litchfield, Franco Caramia, Guillermina Lozano, Hua He, James M You, Shahneen Sandhu, Scott G Williams, Ygal Haupt, Sue Haupt

Faculty, Staff and Student Publications

Understanding prostate cancer onset and progression in order to rationally treat this disease has been critically limited by a dire lack of relevant pre-clinical animal models. We have generated a set of genetically engineered mice that mimic human prostate cancer, initiated from the gland epithelia. We chose driver gene mutations that are specifically relevant to cancers of young men, where aggressive disease poses accentuated survival risks. An outstanding advantage of our models are their intact repertoires of immune cells. These mice provide invaluable insight into the importance of immune responses in prostate cancer and offer scope for studying treatments, including …

Ablating Lgr5-Expressing Prostatic Stromal Cells Activates The Erk-Mediated Mechanosensory Signaling And Disrupts Prostate Tissue Homeostasis, Xing Wei, Li Zhang, Yiqun Zhang, Cody Cooper, Chris Brewer, Chia-Feng Tsai, Yi-Ting Wang, Micah Glaz, Hunter B Wessells, Jianwen Que, Mark A Titus, Vincenzino Cirulli, Adam Glaser, Tao Liu, Nicholas P Reder, Chad J Creighton, Li Xin

Faculty, Staff and Student Publications

Functional implication of stromal heterogeneity in the prostate remains incompletely understood. Using lineage tracing and light-sheet imaging, we show that some fibroblast cells at the mouse proximal prostatic ducts and prostatic urethra highly express Lgr5. Genetic ablation of these anatomically restricted stromal cells, but not nonselective ablation of prostatic stromal cells, rapidly induces prostate epithelial turnover and dedifferentiation that are reversed following spontaneous restoration of the Lgr5

Genomic Testing In Localized Prostate Cancer Can Identify Subsets Of African Americans With Aggressive Disease, Shivanshu Awasthi, G. Daniel Grass, Javier Torres-Roca, Peter A. S. Johnstone, Julio Pow-Sang, Jasreman Dhillon, Jong Park, Robert J. Rounbehler, Elai Davicioni, Alex Hakansson, Yang Liu, Angelina K. Fink, Amanda Derenzis, Jordan H. Creed, Michael Poch, Roger Li, Brandon Manley, Daniel Fernandez, Arash Naghavi, Kenneth Gage, Grace Lu-Yao, Evangelia Katsoulakis, Ryan J. Burri, Andrew Leone, Cesar E. Ercole, Joshua D. Palmer, Neha Vapiwala, Curtiland Deville, Timothy R. Rebbeck, Adam P. Dicker, William Kelly, Kosj Yamoah

Department of Medical Oncology Faculty Papers

BACKGROUND: Personalized genomic classifiers have transformed the management of prostate cancer (PCa) by identifying the most aggressive subsets of PCa. Nevertheless, the performance of genomic classifiers to risk classify African American men is thus far lacking in a prospective setting.

METHODS: This is a prospective study of the Decipher genomic classifier for National Comprehensive Cancer Network low- and intermediate-risk PCa. Study-eligible non-African American men were matched to African American men. Diagnostic biopsy specimens were processed to estimate Decipher scores. Samples accrued in NCT02723734, a prospective study, were interrogated to determine the genomic risk of reclassification (GrR) between conventional clinical risk …

Chd1 Promotes Sensitivity To Aurora Kinase Inhibitors By Suppressing Interaction Of Aurka With Its Coactivator Tpx2, Haoyan Li, Yin Wang, Kevin Lin, Varadha Balaji Venkadakrishnan, Martin Bakht, Wei Shi, Chenling Meng, Jie Zhang, Kaitlyn Tremble, Xin Liang, Jian H Song, Xu Feng, Vivien Van, Pingna Deng, Jared K Burks, Ana Aparicio, Khandan Keyomarsi, Junjie Chen, Yue Lu, Himisha Beltran, Di Zhao

Faculty, Staff and Student Publications

UNLABELLED: Clinical studies have shown that subsets of patients with cancer achieve a significant benefit from Aurora kinase inhibitors, suggesting an urgent need to identify biomarkers for predicting drug response. Chromodomain helicase DNA binding protein 1 (CHD1) is involved in chromatin remodeling, DNA repair, and transcriptional plasticity. Prior studies have demonstrated that CHD1 has distinct expression patterns in cancers with different molecular features, but its impact on drug responsiveness remains understudied. Here, we show that CHD1 promotes the susceptibility of prostate cancer cells to inhibitors targeting Aurora kinases, while depletion of CHD1 impairs their efficacy in vitro and in vivo. …