Digital Commons Network^™

Fruquintinib In Less Pretreated Patients: Multivariate Profile-Matching Analysis Of Fresco-2 To Fresco, Arvind Dasari, Cathy Eng, Sara Lonardi, Rocio Garcia-Carbonero, Toshiki Masuishi, Chiara Cremolini, François Ghiringhelli, Joleen Hubbard, Tanios Bekaii-Saab, Jeremy Jones, Rui-Hua Xu, Lin Shen, Jianming Xu, Yuxian Bai, Yanhong Deng, Ying Yuan, Wei Wei, Jianchang Lin, Lucy Chen, Zhao Yang, William R Schelman, Shukui Qin, Jin Li

Faculty, Staff and Student Publications

Background: In the phase 3 FRESCO (NCT02314819) and FRESCO-2 (NCT04322539) studies, fruquintinib vs placebo, plus best supportive care, significantly improved overall survival (OS) in patients with metastatic colorectal cancer (mCRC). These studies were conducted in temporally and geographically diverse populations that received distinct prior therapies; FRESCO patients were less pretreated than FRESCO-2 patients. This analysis assessed the efficacy and safety of fruquintinib in a less pretreated global population than the FRESCO-2 intention-to-treat (ITT) population.

Methods: In FRESCO and FRESCO-2, patients were randomized 2:1 to receive oral fruquintinib 5 mg or matched placebo. Profile matching was undertaken …

Evaluation Of In Vivo Car Transgene Levels In Tisagenlecleucel-Treated Patients With Relapsed/Refractory B-All And Dlbcl., Rakesh Awasthi, Stephan A. Grupp, Edward R. Waldron, Gregory A. Yanik, Constantine S. Tam, Susana Rives, Joseph P. Mcguirk, Michael A. Pulsipher, Ulrich Jaeger, Douglas Myers, Peter Borchmann, Stephen J. Schuster, Heather E. Stefanski, Michael R. Bishop, Abhijit Chakraborty, Aisha Masood, André Baruchel, Edmund K. Waller

Manuscripts, Articles, Book Chapters and Other Papers

Tisagenlecleucel is a CD19-directed autologous chimeric antigen receptor (CAR) T-cell therapy. Quantitative polymerase chain reaction assays are highly sensitive in defining in vivo kinetics by measuring CAR transgene in peripheral blood. This study aimed to identify clinically meaningful CAR T-cell blood levels that correlated with response/relapse. In pediatric/young adult patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL), maximum CAR T-cell blood levels were higher in patients with ongoing complete remission and in patients with CD19- relapse relative to those with CD19+ relapse. In adult patients with R/R diffuse large B-cell lymphoma (DLBCL), no apparent association between in vivo kinetics …

Minimum Standards For Training In Colorectal Endoscopic Mucosal Resection Among Advanced Endoscopy Trainees, Dennis Yang, Ernesto Robalino Gonzaga, Muhammad Khalid Hasan, Arvind Julius Trindade, Mark Radlinski, Rebecca A Burbridge, Jeffrey Mosko, Pushpak Taunk, Salmaan Jawaid, Mohamed O Othman, David L Diehl, Harshit S Khara, Quin Liu, Srinivas Gaddam, Harry Aslanian, Shailendra S Chauhan, Amrita Sethi, John Poneros, Jason Samarasena, Ali M Ahmed, Uzma D Siddiqui, Dennis Chen, Moamen Gabr, Andrew Y Wang

Faculty, Staff and Students Publications

Background and study aims: Data on colorectal endoscopic mucosal resection (C-EMR) training during advanced endoscopy fellowship remain limited. We aimed to determine the number of procedures required by an "average" advanced endoscopy trainee (AET) to achieve competence in cognitive and technical C-EMR skills.

Methods: AETs from advanced endoscopy training programs (AETPs) were graded on every C-EMR using a standardized assessment tool. Cumulative sum (CUSUM) analysis was used to generate individual and aggregate learning curves to estimate the minimum number of cases required to achieve competence for overall, technical, and cognitive components of C-EMR. AETs completed a self-assessment questionnaire on C-EMR …

Computationally Resolved Neuroprogenitor Cell Biomarkers Associate With Human Disorders, Gerarda Cappuccio, William T Choi, Fatih Semerci, Jill A Rosenfeld, Toni Claire Tacorda, Guantong Qi, Anthony W Zoghbi, Yi Zhong, Hu Chen, Pengfei Liu, Zhandong Liu, Mirjana Maletić-Savatić

Duncan NRI Faculty and Staff Publications

Adult hippocampal neurogenesis, the process of generating new neurons, relies on a rare population of neural stem and progenitor cells (NPCs) within the dentate gyrus complex microenvironment. Discovering the specific genes that define these cells is vital yet challenging due to overlapping expression patterns, limiting detection of rare cell populations using traditional approaches. By employing the computational digital sorting algorithm (DSA) that deconvolves complex gene expression data based on pattern recognition, we identified 129 genes enriched in murine NPCs. We validated these genes against published single-cell RNA sequencing (scRNA-seq) data and discovered that 25 human orthologs were known to cause …

Increased Risk Of Postoperative Complications In Patients With Hypertension Undergoing Mohs Micrographic Surgery, Alexandra Elder, Henry Yang, Megan O'Donnell-Capelli, Jenna Mandel, Molly Wallace, Lauren Banner, Ramsay Hafer, Thomas Rohan, Neda Nikbakht

Department of Dermatology and Cutaneous Biology Faculty Papers

Hypertension has been previously associated with higher intraoperative bleeding risk in patients undergoing Mohs micrographic surgery. However, the risks of common postoperative Mohs micrographic surgery complications have not been substantiated by large studies. Our study aimed to assess the risks of common Mohs micrographic surgery complications for patients with hypertension utilizing the TriNetX database, a global health records database encompassing over 105 million patients' data, from January 2009 to January 2024. After 1:1 propensity score matching for age, sex, race, diabetes, nicotine dependence, obesity, and anticoagulant use, the final analysis included 80,739 patients in each cohort of patients with hypertension …

Results Of Tor001: An Open-Label Single Patient Study Using Targeted Bacteriophage Therapy For The Treatment Of A Chronic Urinary Tract Infection, Jonathan D Cook, Payton B Hooey, Keiko C Salazar, Justin R Clark, Umesh Jain, Carlos Fernando, Hanjeong Harvey, Alexander Cervantes, Stephanie Omagari, Udi Blankstein, Andrew M Kropinski, Alan R Davidson, Karen L Maxwell, Lori L Burrows, Austen L Terwilliger, Anthony W Maresso, Greg J German

Faculty, Staff and Students Publications

Chronic urinary tract infections are persistent bacterial infections with the potential to drive antibiotic resistance. Like other persistent bacterial infections, intracellular bacterial reservoirs and biofilm formation hinder the clearance of pathogens despite long courses of antibiotic therapy. New strategies for treatment of these persistent infections are needed. Here we describe the results of an open-label individual patient study using bacteriophage therapy to treat a chronic urinary tract infection in an immunocompetent 72-year-old woman without underlying urolithiasis or indwelling devices. We co-administered HP3.1, HP3, and ES19 bacteriophages with demonstrated in vitro activity via bladder instillation, orally, and as a topical formulation. …

Identification Of Cobra And Viper Bites In Southern India Using Enzyme-Linked Immunosorbent Assay, Tejeswara Rao Asuru, Raskin Erusan Rajagopal, Albert Rajendran, Gulistan Parveen, Anushka Das, Pabitha Devi, Swapan K Dasgupta, Shantaraman Kalyanaraman, Prasenjit Guchhait, Perumal Thiagarajan

Faculty, Staff and Students Publications

Introduction: Snakebite-related deaths are major concerns in populations worldwide that lack access to medical care. Current treatment of snakebites includes administration of polyspecific and polyvalent heterologous equine antiserum. Swift diagnosis of the species of snake responsible is essential to initiate a specific treatment.

Methods: We generated murine monoclonal and rabbit polyclonal antibodies against the venom of the 3 most common venomous snakes in southern India: the Russell viper, the saw-scaled viper, and the Indian cobra. We developed an enzyme-linked immunosorbent assay to distinguish the snake by analyzing the exudates from the snakebite wound.

Results: Monoclonal antibody EC3 reacts specifically with …

Reasons For Maintaining The Classification Of Esmethadone As An Investigational Uncompetitive Nmdar Antagonist Rapid Antidepressant: Reply To Ferré And Michaelides, Sara De Martin, Stefano Comai, Andrea Mattarei, Thomas R Kosten, Frank J Vocci, Charles W Gorodetzky, Marco Pappagallo, Paolo L Manfredi

Faculty, Staff and Students Publications

No abstract provided.

Co-Occurrence Of Congenital Anomalies And Childhood Brain Tumors In 22 Million Live Births, Thanh T Hoang, Jeremy M Schraw, Charles Shumate, Tania A Desrosiers, Wendy N Nembhard, Mahsa Yazdy, Eirini Nestoridi, Amanda E Janitz, Russell S Kirby, Jason L Salemi, Jean Paul Tanner, Tiffany M Chambers, Michael D Taylor, Chad D Huff, Sharon E Plon, Philip J Lupo, Michael E Scheurer

Faculty, Staff and Students Publications

Background: Children born with a congenital anomaly have a higher risk of developing a brain tumor during childhood or adolescence, but the co-occurrence between specific types of congenital anomalies and specific types of childhood brain tumors (CBTs) is not well described. This study characterized the associations between specific congenital anomalies and CBTs.

Methods: We leveraged a population-based registry linkage study of births (1990-2018), congenital anomalies, and cancer from 9 states (n = 22,599,099 births). Congenital anomalies were classified as major structural without a known chromosomal or genetic syndrome, chromosomal, neurofibromatosis, and/or tuberous sclerosis complex. CBT classification was based on the …

Integrative Analysis Of Lung Adenocarcinoma Across Diverse Ethnicities And Exposures, Shankha Satpathy, Natalie M Clark, Yi-Ju Chen, Noshad Hosseini, Ya-Hsuan Chang, Yi Hsiao, Jonathan T Lei, Francesca Petralia, Jin-Shing Chen, Yifat Geffen, David I Heiman, Indranil Paul, Hanbyul Cho, Michelle Hollenberg, Giacomo B Marino, Kuen-Tyng Lin, Rahul Mannan, C Jackson White, Joe Allen, Shayan C Avanessian, M Harry Kane, Ashley Wolfe, Miloni Kinarivala, Wenke Liu, Shankara Anand, Mong-Wei Lin, Moe Haines, Erik J Bergstrom, Grant Hussey, Ginny Xiaohe Li, Deepak C Mani, Hao Fang, Eric J Jaehnig, Hasmik Keshishian, Brecca Miller, Kang-Yi Su, Yi-Jing Hsiao, Hsao-Hsun Hsu, Min-Shu Hsieh, Kuo-Hsuan Hsu, Alexi Monovoukas, Simone Gohsman, John R Thorup, Yamei Deng, Yo Akiyama, Eden Deng, Eric Sheng-Wen Chen, Azra Krek, Rodrigo Espinoza, Weiping Ma, Daniel Charytonowicz, Robert Sebra, Jyun-Hong Lin, Yan-Si Chen, Yin-Chen Hsu, Ze-Shiang Lin, Kun-Chieh Chen, Chang-Wei Yeh, Yu-Tai Wang, Alexander J Lazar, Mehdi Mesri, Eunkyung An, Xu Zhang, Karl R Clauser, David Fenyö, Arul M Chinnaiyan, Bing Zhang, Li Ding, Kelly Ruggles, Chelsea Newton, Hui Zhang, Pei Wang, Galen Hostetter, Gilbert S Omenn, Chandan Kumar-Sinha, Mathangi Thiagarajan, Ramaswamy Govindan, Paul Paik, Abhijit Parolia, Qing K Li, Avi Ma'ayan, Gad A Getz, Saravana M Dhanasekaran, Ana I Robles, Gee-Chen Chang, Pan-Chyr Yang, Sung-Liang Yu, Hsuan-Yu Chen, Alexey I Nesvizhskii, Steven A Carr, D R Mani, Marcin P Cieslik, Yu-Ju Chen, Michael A Gillette, Taiwan Cancer Moonshot Program, Clinical Proteomic Tumor Analysis Consortium

Faculty, Staff and Students Publications

Lung adenocarcinomas (LUAD) are a pressing global health problem with enduring lethality and rapidly shifting epidemiology. Proteogenomic studies integrating proteomics and post-translational modifications with genomics can identify clinical strata and oncogenic mechanisms, but have been underpowered to examine effects of ethnicity, smoking and environmental exposures, or sex on this heterogeneous disease. This comprehensive proteogenomic analysis of LUAD tumors and matched normal adjacent tissues from 406 patients across diverse geographic and demographic backgrounds explores the impact of understudied driver mutations, prognostic role of chromosomal instability, patterns of immune signaling, differential and sex-specific effects of endogenous mutagens and environmental carcinogens, and pathobiology …

High Energy Consumption Characterizes Abnormal Brain State Transitions In Temporal Lobe Epilepsy, Sam S. Javidi, Qirui Zhang, Ankeeta Ankeeta, Michael R. Sperling, Joseph I. Tracy

Farber Institute for Neuroscience Faculty Papers

Temporal lobe epilepsy (TLE) patients experience shifts between non-seizing and seizing brain states, but the structural networks underlying these transitions remain undefined and poorly characterized. We detected dynamic brain states in resting-state fMRI and constructed linked structural networks utilizing multi-shell diffusion-weighted MR data. Leveraging network control theory, we interrogated the structural data for all possible brain state transitions, identifying those requiring abnormal levels of transition energy (low or high) in TLE compared to matched healthy participants (n's = 25). Results revealed three transitions requiring significantly higher energy in TLE; no abnormally low-energy transitions were observed. In HPs, transitions relied on …

Defining Breast Epithelial Cell Types In The Single-Cell Era, G Kenneth Gray, Eric G Carlson, Tatyana Lev, Bailey Marshall, Austin D Reed, Alex P Sánchez-Covarrubias, Alecia-Jane Twigger, Aleix Puig-Barbe, Aatish Thennavan, Ayodele Omotoso, Lyndsay M Murrow, Deeptiman Chatterjee, Siyuan He, Sara Pensa, Brian Aevermann, Norbert K Tavares, Natalie Chen, Jason A Hilton, Kerrigan Blake, Yunlong Liu, Kiet Phong, Zev J Gartner, Devon A Lawson, Alexander Swarbrick, Camila O Dos Santos, Sophia H L George, Joan S Brugge, Mark A Labarge, Harikrishna Nakshatri, Nicholas Navin, Kai Kessenbrock, Walid T Khaled

Faculty, Staff and Student Publications

Single-cell studies on breast tissue have contributed to a change in our understanding of breast epithelial diversity that has, in turn, precipitated a lack of consensus on breast cell types. The confusion surrounding this issue highlights a possible challenge for advancing breast atlas efforts. In this perspective, we present our consensus on the identities, properties, and naming conventions for breast epithelial cell types and propose goals for future atlas endeavors. Our proposals and their underlying thought processes aim to catalyze the adoption of a shared model for this tissue and to serve as guidance for other investigators facing similar challenges.

Author Correction: Functional Mechanisms Underlying Pleiotropic Risk Alleles At The 19p131 Breast-Ovarian Cancer Susceptibility Locus, Kate Lawrenson, Siddhartha Kar, Karen Mccue, Karoline Kuchenbaeker, Kyriaki Michailidou, Jonathan Tyrer, Jonathan Beesley, Susan J Ramus, Qiyuan Li, Melissa K Delgado, Janet M Lee, Kristiina Aittomäki, Irene L Andrulis, Hoda Anton-Culver, Volker Arndt, Banu K Arun, Brita Arver, Elisa V Bandera, Monica Barile, Rosa B Barkardottir, Daniel Barrowdale, Matthias W Beckmann, Javier Benitez, Andrew Berchuck, Maria Bisogna, Line Bjorge, Carl Blomqvist, William Blot, Natalia Bogdanova, Anders Bojesen, Stig E Bojesen, Manjeet K Bolla, Bernardo Bonanni, Anne-Lise Børresen-Dale, Hiltrud Brauch, Paul Brennan, Hermann Brenner, Fiona Bruinsma, Joan Brunet, Shaik Ahmad Buhari, Barbara Burwinkel, Ralf Butzow, Saundra S Buys, Qiuyin Cai, Trinidad Caldes, Ian Campbell, Rikki Cannioto, Jenny Chang-Claude, Jocelyne Chiquette, Ji-Yeob Choi, Kathleen B M Claes, Linda S Cook, Angela Cox, Daniel W Cramer, Simon S Cross, Cezary Cybulski, Kamila Czene, Mary B Daly, Francesca Damiola, Agnieszka Dansonka-Mieszkowska, Hatef Darabi, Joe Dennis, Peter Devilee, Orland Diez, Jennifer A Doherty, Susan M Domchek, Cecilia M Dorfling, Thilo Dörk, Martine Dumont, Hans Ehrencrona, Bent Ejlertsen, Steve Ellis, Christoph Engel, Eunjung Lee, D Gareth Evans, Peter A Fasching, Lidia Feliubadalo, Jonine Figueroa, Dieter Flesch-Janys, Olivia Fletcher, Henrik Flyger, Lenka Foretova, Florentia Fostira, William D Foulkes, Brooke L Fridley, Eitan Friedman, Debra Frost, Gaetana Gambino, Patricia A Ganz, Judy Garber, Montserrat García-Closas, Aleksandra Gentry-Maharaj, Maya Ghoussaini, Graham G Giles, Rosalind Glasspool, Andrew K Godwin, Mark S Goldberg, David E Goldgar, Anna González-Neira, Ellen L Goode, Marc T Goodman, Mark H Greene, Jacek Gronwald, Pascal Guénel, Christopher A Haiman, Per Hall, Emily Hallberg, Ute Hamann, Thomas V O Hansen, Patricia A Harrington, Mikael Hartman, Norhashimah Hassan, Sue Healey, Florian Heitz, Josef Herzog, Estrid Høgdall, Claus K Høgdall, Frans B L Hogervorst, Antoinette Hollestelle, John L Hopper, Peter J Hulick, Tomasz Huzarski, Evgeny N Imyanitov, Kconfab Investigators, Australian Ovarian Cancer Study Group, Claudine Isaacs, Hidemi Ito, Anna Jakubowska, Ramunas Janavicius, Allan Jensen, Esther M John, Nichola Johnson, Maria Kabisch, Daehee Kang, Miroslav Kapuscinski, Beth Y Karlan, Sofia Khan, Lambertus A Kiemeney, Susanne Kruger Kjaer, Julia A Knight, Irene Konstantopoulou, Veli-Matti Kosma, Vessela Kristensen, Jolanta Kupryjanczyk, Ava Kwong, Miguel De La Hoya, Yael Laitman, Diether Lambrechts, Nhu Le, Kim De Leeneer, Jenny Lester, Douglas A Levine, Jingmei Li, Annika Lindblom, Jirong Long, Artitaya Lophatananon, Jennifer T Loud, Karen Lu, Jan Lubinski, Arto Mannermaa, Siranoush Manoukian, Loic Le Marchand, Sara Margolin, Frederik Marme, Leon F A G Massuger, Keitaro Matsuo, Sylvie Mazoyer, Lesley Mcguffog, Catriona Mclean, Iain Mcneish, Alfons Meindl, Usha Menon, Arjen R Mensenkamp, Roger L Milne, Marco Montagna, Kirsten B Moysich, Kenneth Muir, Anna Marie Mulligan, Katherine L Nathanson, Roberta B Ness, Susan L Neuhausen, Heli Nevanlinna, Silje Nord, Robert L Nussbaum, Kunle Odunsi, Kenneth Offit, Edith Olah, Olufunmilayo I Olopade, Janet E Olson, Curtis Olswold, David O'Malley, Irene Orlow, Nick Orr, Ana Osorio, Sue Kyung Park, Celeste L Pearce, Tanja Pejovic, Paolo Peterlongo, Georg Pfeiler, Catherine M Phelan, Elizabeth M Poole, Katri Pylkäs, Paolo Radice, Johanna Rantala, Muhammad Usman Rashid, Gad Rennert, Valerie Rhenius, Kerstin Rhiem, Harvey A Risch, Gus Rodriguez, Mary Anne Rossing, Anja Rudolph, Helga B Salvesen, Suleeporn Sangrajrang, Elinor J Sawyer, Joellen M Schildkraut, Marjanka K Schmidt, Rita K Schmutzler, Thomas A Sellers, Caroline Seynaeve, Mitul Shah, Chen-Yang Shen, Xiao-Ou Shu, Weiva Sieh, Christian F Singer, Olga M Sinilnikova, Susan Slager, Honglin Song, Penny Soucy, Melissa C Southey, Marie Stenmark-Askmalm, Dominique Stoppa-Lyonnet, Christian Sutter, Anthony Swerdlow, Sandrine Tchatchou, Manuel R Teixeira, Soo H Teo, Kathryn L Terry, Mary Beth Terry, Mads Thomassen, Maria Grazia Tibiletti, Laima Tihomirova, Silvia Tognazzo, Amanda Ewart Toland, Ian Tomlinson, Diana Torres, Thérèse Truong, Chiu-Chen Tseng, Nadine Tung, Shelley S Tworoger, Celine Vachon, Ans M W Van Den Ouweland, Helena C Van Doorn, Elizabeth J Van Rensburg, Laura J Van't Veer, Adriaan Vanderstichele, Ignace Vergote, Joseph Vijai, Qin Wang, Shan Wang-Gohrke, Jeffrey N Weitzel, Nicolas Wentzensen, Alice S Whittemore, Hans Wildiers, Robert Winqvist, Anna H Wu, Drakoulis Yannoukakos, Sook-Yee Yoon, Jyh-Cherng Yu, Wei Zheng, Ying Zheng, Kum Kum Khanna, Jacques Simard, Alvaro N Monteiro, Juliet D French, Fergus J Couch, Matthew L Freedman, Douglas F Easton, Alison M Dunning, Paul D Pharoah, Stacey L Edwards, Georgia Chenevix-Trench, Antonis C Antoniou, Simon A Gayther

Faculty, Staff and Student Publications

No abstract provided.

Gene Context Drift Identifies Drug Targets To Mitigate Cancer Treatment Resistance, Amir Jassim, Birgit V Nimmervoll, Sabrina Terranova, Erica Nathan, Linda Hu, Jessica T Taylor, Katherine E Masih, Lisa Ruff, Matilde Duarte, Elizabeth Cooper, Gunjan Katyal, Melika Akhbari, Reuben J Gilbertson, Jennifer C Coleman, Joseph S Toker, Colton Terhune, Gabriel Balmus, Stephen P Jackson, Hailong Liu, Tao Jiang, Michael D Taylor, Kui Hua, Jean E Abraham, Mariella G Filbin, Anthony Hill, Anarita Patrizi, Neil Dani, Aviv Regev, Maria K Lehtinen, Richard J Gilbertson

Faculty, Staff and Students Publications

Cancer treatment often fails because combinations of different therapies evoke complex resistance mechanisms that are hard to predict. We introduce REsistance through COntext DRift (RECODR): a computational pipeline that combines co-expression graph networks of single-cell RNA sequencing profiles with a graph-embedding approach to measure changes in gene co-expression context during cancer treatment. RECODR is based on the idea that gene co-expression context, rather than expression level alone, reveals important information about treatment resistance. Analysis of tumors treated in preclinical and clinical trials using RECODR unmasked resistance mechanisms -invisible to existing computational approaches- enabling the design of highly effective combination treatments …

Intensive Telemedicine Transitions Of Care Clinic: A Prospective Feasibility Study Of A Novel Ambulatory Model Serving Appalachian Patients, Jessica Thayer, Brett Miller, Marcelino Mederos Liriano, Kathryn Hoffman, Gina Baugh, Jenna Sizemore

Journal of Appalachian Health

Introduction: Hospital discharge is a complex process plagued with medical errors and poor coordination. Disjointed discharges are detrimental to Appalachian patients with access barriers and multiple chronic diseases. Telehealth is a tool used to improve access within rural Appalachia. To address this high-risk transition period, an interprofessional team deployed telemedicine to improve post-hospital care for Appalachian patients.

Purpose: Patients with uncontrolled chronic medical conditions were enrolled into the Intensive Telemedicine Transition of Care Clinic (I-TTC) with a primary outcome of 30-day Emergency Department (ED) presentations and hospital readmissions. Secondary outcomes included improved control of chronic conditions and patient cost savings. …

Upper Gastrointestinal Symptoms And Gulf War Illness In A Clinical Cohort Of Us Veterans: A Retrospective, Cross-Sectional Study, Abdelrahman Yousef, Sarah T Ahmed, Theresa H Nguyen Wenker, Alice B S Nono-Djotsa, Stephen H Boyle, Elizabeth J Gifford, Deeksha Malhotra, Helena Chandler, Sandhya Bandi, Drew A Helmer

Faculty, Staff and Students Publications

Objective: Approximately 30% of the 700 000 US Gulf War Veterans (GWVs) report symptoms collectively termed Gulf War Illness (GWI), a multisymptom illness of uncertain pathophysiology. Prior studies in GWI focus on overlap with irritable bowel syndrome. This study examines the associations between upper gastrointestinal (UGI) symptoms, GWI and specialty GI care.

Methods: This cross-sectional study analysed GWVs referred to a Veterans Health Administration clinical War-Related Illness and Injury Study Center (2008-2020). Symptoms, demographics, military service and clinical history were obtained from self-reported intake packets. GWI was defined by the Centers for Disease Control and Prevention criteria requiring moderate-to-severe symptoms …

Establishing Best Practices Guidelines For Collaborative Research In Global Surgery: Developing A Delphi Survey, Ramitha Eshan Ruwanpathirana, Swati Deshpande, Sophia Abdulhai, Mathilde Djeneba Billau, Sumeja Catic, Theresa L Chin, Julia N Harrison, Pratyush Kumar, Maria Cecilia T Leyson, Helen W Li, Katayoun S Madani, Arthur Serumaga, Margaret Tarpley, Grayson Wright, Nia N Zalamea, Joshua S Ng-Kamstra

Faculty, Staff and Students Publications

Background: Collaborative research in global surgery has resulted in the rapid development of the field via knowledge creation and dissemination, research capacity building, and direct improvements in the delivery of clinical care. Yet the establishment and maintenance of trans-boundary collaborations carries significant risk to health systems, clinicians, patients, and researchers, particularly if such collaborations are not developed thoughtfully and with appropriate guardrails. In recent years, there has been significant growth in the literature on the pervasiveness and impact of neocolonialism on global health research.

Methods: To harness the benefits of global surgery research collaboration while mitigating these risks, we reviewed …

Advancing Ckd Diagnosis: Race-Free Egfr, Cystatin C, And Genetic Insights, Halah Tariq Albar

Saudi Toxicology Journal

Globally, the rates of chronic kidney disease (CKD) are increasing due to the increasing incidence of hypertension, obesity, and diabetes mellitus. Early detection and treatment of kidney disease are essential in improving health outcomes. Estimate glomerular filtration rate (eGFR) is used to diagnose, stage, and manage CKD. CKD biomarkers are broadly categorized into traditional (serum creatinine), emerging (cystatin C), and disease specific (Interleukin-6). The purpose of this narrative review is to synthesize the current evidence regarding the use of eGFR in diverse populations. The initial eGFR equations included race variables, which created a controversial debate about their relevancy and has …

Modeling The Impact Of Mmr Vaccination Strategies On Measles Outbreaks In Texas, Kaiming Bi, Thuy Nguyen, Boya Peng, Trudy Krause, Cecilia Ganduglia Cazaban, Janelle Rios, Cici Bauer, Catherine Troisi, Eric Boerwinkle, Aanand D Naik

Faculty, Staff and Student Publications

No abstract provided.

Association Between Body Mass Index And Uterotonic Use In Postpartum Hemorrhage: A Retrospective Cohort Study, Cece Cheng, Bryce T Munter, Michaela Y Lee, Claire D Sundjaja, Natasha D Paul, Margaret M Klausmeyer, Nastassia A Yammine, Patrick S Ramsey, John J Byrne

Faculty, Staff and Student Publications

Background/Objectives: Our primary objective was to determine whether patients with a higher body mass index (BMI) who experienced postpartum hemorrhage (PPH) required ≥2 uterotonics more often than those with lower BMI.

Methods: We conducted a retrospective cohort study that included all patients who experienced a PPH between 1 August 2020 and 31 July 2022. Extracted data included patient demographics, PPH risk factors, details regarding the labor course and hemorrhage management, and maternal and neonatal outcomes, such as mode of delivery, etiology of hemorrhage, need for nonpharmacological management, neonatal Apgar scores, requirement for phototherapy, neonatal intensive care unit (NICU) admission, and …

Identifying Bio-Behavioural Signatures Of Persistent Opioid Use Risk In Trauma Injury Patients: A Protocol For A Prospective Cohort Study, Joy M Schmitz, Jin Ho Yoon, Bruno Kluwe-Schiavon, John A Harvin, Preethi H Gunaratne, Darrion Mouton, Kandice Motley, Erin E Fox, Jessica Vincent, Megan Tarbet, Consuelo Walss-Bass

Faculty, Staff and Student Publications

Introduction: Exposure to prescription opioids following traumatic injury can increase the risk of developing tolerance, persistent opioid use and opioid use disorder. The mechanisms underlying opioid tolerance or dependence are not well understood, and no biomarkers predict risk. Opioid exposure causes epigenetic modifications, including alterations in microRNA (miRNA) expression. Several miRNAs, which regulate synaptic plasticity, are hypothesised to underlie substance use disorders and influence µ-opioid receptor levels, modulating opioid tolerance. This project aims to develop a bio-behavioural signature to predict persistent opioid use and chronic pain up to 6 months post-discharge.

Methods and analysis: The study will use a prospective …

Regulation Of Food Intake By Connexin43 Via Adipocyte-Sensory Neuron Electrical Synapses, Xi Chen, Xing Fang, Hong Zhou, Jieyi Meng, Yang He, Leon G Straub, Andrew Lemoff, Clair Crewe, Shangang Zhao, Yong Xu, Yi Zhu

Duncan NRI Faculty and Staff Publications

Background and objective: Connexin43 (Cx43), encoded by Gja1, forms gap junctions between adjacent cells. In adipose tissue, it is upregulated during adipose beiging while downregulated by high-fat-diet (HFD) feeding. Adipocyte-specific Gja1 overexpression enhances adipose tissue beiging in response to mild cold stress of room temperature. Moreover, those mice display a surprising decrease in food intake, but the mechanism remains unclear. This study investigates how adipocyte Cx43 influences feeding behavior.

Methods: Mice with adipose tissue-specific Gja1 overexpression (Adipoq-Cx43) were fed with HFD. Food intake, weight gain, substrate utilization, and serum lipolysis were assessed. RNA-seq, proteomics, and cytokine measurements were employed to …

Tet2-Mutant Myeloid Cells Mitigate Alzheimer’S Disease Progression Via Cns Infiltration And Enhanced Phagocytosis In Mice, Katie A Matatall, Trisha K Wathan, Minh Nguyen, Hu Chen, Alexandra Mcdonald, Guantong Qi, Julia A Belk, Marcus A Florez, Duy T Le, Temitope Olarinde, Caitlyn Vlasschaert, Marco M Buttigieg, Chih-Wei Fan, Saul Carcamo, Ruoqiong Cao, Daniel E Kennedy, Arushana A Maknojia, Apoorva Thatavarty, Josaura V Fernandez Sanchez, Hind Bouzid, Surabi Veeraragavan, Susan Crocker, Margaret A Goodell, Antony Rodriguez, Siddhartha Jaiswal, Michael J Rauh, Eirini P Papapetrou, Samuele G Marro, Katherine Y King

Faculty, Staff and Students Publications

No abstract provided.

Incidence And Risk Factors Of Developing A Dysrhythmia After Blunt Thoracic Trauma., Jessica Jowers, Kevin Van Derveer, Katherine Moore, Nathaniel Harshaw, Julie M Reichert, Hannah Karr, Urhum Khaliq, David J Cziperle, Lindsey L Perea

General Surgery Resident Research

Background/Objectives: The incidence of dysrhythmia after blunt thoracic trauma varies in the literature from 8-75%, and the complication rate from these dysrhythmias is not well studied. The aims of this study are to (1) identify the incidence of dysrhythmia following blunt thoracic trauma, (2) identify risk factors associated with developing a dysrhythmia, and (3) identify the incidence of cardiac intervention after developing a dysrhythmia. We hypothesize that blunt thoracic trauma may result in post-injury dysrhythmias. Methods: This is a retrospective review of trauma patients ≥ 18 years with a blunt mechanism of injury at a Level 1 Trauma …

Human Papillomavirus Integration Induces Oncogenic Host Gene Fusions In Oropharyngeal Cancers, Nusrat Khan, Keiko Akagi, Shiming Jiang, Joe Dan Dunn, Bo Jiang, Weihong Xiao, Madison P O'Hara, Li Shen, Qi Wang, Vakul Mohanty, Jing Wang, Sara Goodwin, Jamie L Hutchins, Kevin R Coombes, Jagannadha K Sastry, David E Symer, Maura L Gillison

Faculty, Staff and Student Publications

HPV integration disrupts host genomic structure and expression, but whether these alterations promote cancer development remains unclear. Multiple genomic analyses of oropharyngeal cancers identified several host fusion genes, including recurrent FGFR3-TACC3 fusions, expressed from rearranged genomic loci adjacent to HPV integration sites. Evolutionary modeling implicated integration of virus concatemers into the host genome as a common initiating event in fusion formation. Co-expression of HPV16 E6/E7 and FGFR3-TACC3, but neither alone, was sufficient for tumor development in both xenograft and syngeneic mouse models and led to unique transcriptional programs implicated in carcinogenesis. FGFR3-TACC3 expression decreased the ubiquitination and degradation of …

Dissecting Microbial Communities With Single-Cell Transcriptome Analysis, Andrew W Pountain, Itai Yanai

Faculty, Staff and Student Publications

Revealing insights into the function of microbial communities requires moving beyond measuring bulk taxonomic composition to detecting interactions between subpopulations. Following the transformative impact of single-cell gene expression profiling techniques on numerous fields of human biology, recent years have seen increased application to microbes. We review progress in the development of these techniques and discuss challenges in applying them to microbial communities. We highlight applications for dissecting the microbiome in human health and disease that reveal functional heterogeneity within gut communities, antibiotic responses, and the dynamics of mobile genetic elements. As single-cell gene expression technologies continue to develop, they are …

Lewy Body Dementia Promotion By Air Pollutants, Xiaodi Zhang, Haiqing Liu, Xiao Wu, Longgang Jia, Kundlik Gadhave, Lena Wang, Kevin Zhang, Hanyu Li, Rong Chen, Ramhari Kumbhar, Ning Wang, Chantelle E Terrillion, Bong Gu Kang, Bin Bai, Minhan Park, Ma Cristine Faye Denna, Shu Zhang, Wenqiang Zheng, Denghui Ye, Xiaoli Rong, Liu Yang, Lili Niu, Han Seok Ko, Weiyi Peng, Lingtao Jin, Mingyao Ying, Liana S Rosenthal, David W Nauen, Alex Pantelyat, Mahima Kaur, Kezia Irene, Liuhua Shi, Rahel Feleke, Sonia García-Ruiz, Mina Ryten, Valina L Dawson, Francesca Dominici, Rodney J Weber, Xuan Zhang, Pengfei Liu, Ted M Dawson, Shizhong Han, Xiaobo Mao

Faculty, Staff and Student Publications

Evidence links air pollution to dementia, yet its role in Lewy body dementia (LBD) remains unclear. Here we showed in a cohort of 56.5 million individuals across the U.S. that PM2.5 exposure raises LBD risk. Mechanistically, we found PM2.5 exposure led to brain atrophy in wild-type mice, an effect not seen in α-synuclein (αSyn)-deficient mice. PM2.5 exposure generated a highly pathogenic αSyn strain, PM-PFF, with enhanced proteinase K-resistance and neurotoxicity, resembling αSyn LBD strains. PM2.5 samples from China, the U.S., and Europe consistently induced proteinase-resistant αSyn strains and in vivo pathology. Transcriptomic analyses revealed shared responses between PM2.5-exposed mice and …

Detection Of Cancers Three Years Prior To Diagnosis Using Plasma Cell-Free Dna, Yuxuan Wang, Corinne E Joshu, Samuel D Curtis, Christopher Douville, Vernon A Burk, Meng Ru, Maria Popoli, Janine Ptak, Lisa Dobbyn, Natalie Silliman, Josef Coresh, Eric Boerwinkle, Anna Prizment, Chetan Bettegowda, Kenneth W Kinzler, Nickolas Papadopoulos, Elizabeth A Platz, Bert Vogelstein

Faculty, Staff and Student Publications

To explore how early can cancers be detected prior to clinical signs or symptoms, we assessed prospectively collected serial plasma samples from the Atherosclerosis Risk in Communities (ARIC) study, including 26 participants diagnosed with cancer and 26 matched controls. At the index time point, eight of these 52 participants scored positively with a multicancer early detection (MCED) test. All eight participants were diagnosed with cancer within 4 months after blood collection. In six of these 8 participants, we were able to assess an earlier plasma sample collected 3.1 to 3.5 years prior to clinical diagnosis. In four of these six …

Implementing A Training Resource For Large-Scale Genomic Data Analysis In The All Of Us Researcher Workbench, Jasmine Baker, Erik Stricker, Julie Coleman, Shamika Ketkar, Taotao Tan, Ashley M Butler, Laterrica Williams, Latanya Hammonds-Odie, Debra Murray, Brendan Lee, Kim C Worley, Elizabeth G Atkinson

Duncan NRI Faculty and Staff Publications

A lack of representation in genomic research and limited access to computational training create barriers for many researchers seeking to analyze large-scale genetic datasets. The All of Us Research Program provides an unprecedented opportunity to address these gaps by offering genomic data from a broad range of participants, but its impact depends on equipping researchers with the necessary skills to use it effectively. The All of Us Biomedical Researcher (BR) Scholars Program at Baylor College of Medicine aims to break down these barriers by providing early-career researchers with hands-on training in computational genomics through the All of Us Evenings with …

The Causal Pivot: A Structural Approach To Genetic Heterogeneity And Variant Discovery In Complex Diseases, Chad A Shaw, C J Williams, Taotao Tan, Daniel Illera, Nicholas Di, Joshua M Shulman, John W Belmont

Center on Aging Staff Publications

We present the Causal Pivot (CP) as a structural causal model (SCM) for analyzing genetic heterogeneity in complex diseases. The CP leverages an established causal factor or factors to detect the contribution of additional suspected causes. Specifically, polygenic risk scores (PRSs) serve as known causes, while rare variants (RVs) or RV ensembles are evaluated as candidate causes. The CP incorporates outcome-induced association by conditioning on disease status. We derive a conditional maximum-likelihood procedure for binary and quantitative traits and develop the Causal Pivot likelihood ratio test (CP-LRT) to detect causal signals. Through simulations, we demonstrate the CP-LRT’s robust power and …