Digital Commons Network^™

Progesterone Signaling In Oviductal Epithelial Cells Modulates The Immune Response To Support Preimplantation Embryonic Development, Emily A Mcglade, Jiude Mao, Kalli K Stephens, Ryan M Marquardt, Feyza Nur Arguc, Peter F Lais, San-Pin Wu, Sarayut Winuthayanon, Haval Shirwan, Esma S Yolcu, Mark I Hunter, James K Pru, John P Lydon, Francesco J Demayo, Wipawee Winuthayanon

Faculty, Staff and Students Publications

More than 60% of pregnancy losses occur during the first trimester, highlighting the need to understand the role of the oviduct in early pregnancy. In this study, we conditionally ablated the classical progesterone receptor (Pgr) in oviductal epithelial cells, called the Pgrd/d mouse model. We found that 40% of embryos collected from Pgrd/d females were nonviable or developmentally delayed, indicating that epithelial PGR expression is crucial for embryonic development. Single-cell RNA sequencing revealed up-regulation of proinflammatory genes, including interleukin-22 (IL-22), in the epithelial cells of Pgrd/d females. Pharmacological inhibition of inflammation using nonsteroidal anti-inflammatory drugs …

The Impact Of An Iron-Rich Diet On Fatigue In Menstruating Women With Non-Anemic Iron Deficiency, Meagan Seraydar, Lauren Latimer, Sam Miragliatto

Department of Nutrition Student Projects

Fatigue without diagnosed anemia is prevalent in menstruating women, with iron deficiency being a potential contributor. While iron supplementation is a standard intervention, dietary sources of iron may offer a sustainable alternative. This study aims to assess the impact of an iron-rich diet on fatigue levels in menstruating women. A 12-week randomized controlled trial (RCT) will be conducted, assigning participants to either an iron-rich diet group or a control group following their usual diet without specific iron recommendations. Fatigue will be measured using the Fatigue Severity Scale (FSS) at baseline, six weeks, and twelve weeks, alongside iron status biomarkers, including …

Humanized Saccharomyces Cerevisiae Provides A Facile And Effective Tool To Identify Damaging Human Variants That Cause Exosomopathies, Khondakar Sayef Ahammed, Milo B Fasken, Anita H Corbett, Ambro Van Hoof

Faculty, Staff and Student Publications

The RNA exosome is an evolutionarily conserved, multiprotein complex that is the major RNase in 3' processing and degradation of a wide range of RNAs in eukaryotes. Single amino acid changes in RNA exosome subunits cause rare genetic diseases collectively called exosomopathies. However, distinguishing disease-causing variants from nonpathogenic ones remains challenging, and the mechanism by which these variants cause disease is largely unknown. Previous studies have employed a budding yeast model of RNA exosome-linked diseases that relies on mutating the orthologous yeast genes. Here, we develop a humanized yeast model of exosomopathies that allows us to unambiguously assess damaging effects …

Developing An Online Community Advisory Board (Cab) Of Parents From Social Media To Co-Design An Human Papillomavirus Vaccine Intervention: Participatory Research Study, Regan M. Murray, Shawn C. Chiang, Ann C. Klassen, Jennifer A. Manganello, Amy E. Leader, Wen-Juo Lo, Philip M. Massey

Department of Medical Oncology Faculty Papers

BACKGROUND: Social media health interventions have grown significantly in recent years. However, researchers are still developing innovative methods to meaningfully engage online communities to inform research activities. Little has been documented describing this approach of using online community advisory boards (CABs) to co-create health communication interventions on social media.

OBJECTIVE: This study describes the formation, engagement, and maintenance of an online CAB focused on co-creating a health education intervention for parents regarding the human papillomavirus (HPV) vaccine. The study provides guiding principles for public health researchers implementing such CABs in future digital health interventions.

METHODS: In May 2020, Twitter was …

Exploring The Acute Effects Of Sedentary Behaviors On Cardiometabolic Risk In Hispanic Adolescents With Obesity: A Randomized Crossover Study, Erica G Soltero, Osamah Salim, Yiming Mirabile, Salma M Musaad

Children’s Nutrition Research Center Staff Publications

Background/Objectives: Time spent in sedentary pursuits is associated with adverse metabolic profiles. Adolescents spend 65-75% of their day in sedentary pursuits; however, evidence among youth is less conclusive. This study examined the effects of an acute 4 h bout of sedentary behaviors on cardiometabolic outcomes and energy expenditure in Hispanic adolescents (12-16 years old) with obesity (BMI% ≥ 95th).

Methods: This study used a randomized cross-over design to engage participants (N = 12) in two sedentary conditions, an active condition where youth were engaged in two hours of 'active' sitting activities (e.g., reading and puzzles) and two hours …

Acute Pain Treatment In Patients With Sickle Cell Disease Transitioned To Buprenorphine: Evidence Of Equivalent Pain Relief, Christopher P. Carroll, Elizabeth J. Prince, Ashley P. Lauriello, Lydia H. Pecker, Sophie M. Lanzkron

Cardeza Foundation for Hematologic Research

Objectives Buprenorphine is a novel opioid analgesic with complex receptor pharmacology. It is safer than high dose chronic treatment with full agonist opioids. However, buprenorphine can inhibit conventional opioids, complicating acute pain treatment. Methods We compare acute pain treatment outcomes in 55 sickle cell disease patients in the year before and after transition to buprenorphine. Infusion center visits, ED visits, and hospital admissions were compared before and after transition, and pain outcomes were compared using linear mixed effects models with patients entered as random effects to account for differential contribution to the outcomes by visit rates. Results Acute care visits …

Single-Cell Analyses Reveal A Functionally Heterogeneous Exhausted Cd8+ T-Cell Subpopulation That Is Correlated With Response To Checkpoint Therapy In Melanoma, Kelly M Mahuron, Osmaan Shahid, Prachi Sao, Clinton Wu, Alexandra M Haugh, Laura A Huppert, Lauren S Levine, Margaret M Lowe, Michael Alvarado, Markee Micu, Katy K Tsai, Melissa Chow, Meromit Singer, Jason M Schenkel, Arlene H Sharpe, Michael D Rosenblum, Kristen E Pauken, Adil I Daud

Faculty, Staff and Student Publications

PD-1 pathway inhibitors have revolutionized cancer therapy. However, most patients do not durably benefit, highlighting the need for biomarkers to stratify patients as responders or nonresponders. Although CD8+ tumor-infiltrating lymphocytes (TIL) have been associated with immune checkpoint therapy response, there is no consensus on which CD8+ TIL subpopulations have the most prognostic value. Preclinical studies have focused on progenitor-like exhausted CD8+ T cells (TPEX) because TPEX proliferate more in response to PD-1 inhibitors than other exhausted T-cell (TEX) subpopulations. However, immune checkpoint inhibitor treatment drives TPEX differentiation into other TEX populations that can mediate antitumor immunity. These data complicate the …

Lineage Tracing And Single-Cell Rna Sequencing Reveal A Common Transcriptional State In Breast Cancer Tumor-Initiating Cells Characterized By Ifn/Stat1 Activity, Eric P Souto, Ping Gong, John D Landua, Ramakrishnan Rajaram Srinivasan, Abhinaya Ganesan, Lacey E Dobrolecki, Stephen C Purdy, Xingxin Pan, Michael Zeosky, Anna Chung, S Stephen Yi, Heide L Ford, Michael T Lewis

Faculty, Staff and Students Publications

A tumor cell subpopulation of tumor-initiating cells (TIC) or "cancer stem cells" is associated with therapeutic resistance, as well as both local and distant recurrences. Signal transducer and activator of transcription (STAT) activity is elevated in TICs in claudin-low models of human triple-negative breast cancer, which enables enrichment of TICs using a STAT-responsive reporter. Lineage tracing of TICs as they undergo cell state changes could enable a better understanding of the molecular phenotypes of TIC and uncover strategies to selectively target TICs. In this study, we developed a STAT-responsive lineage-tracing system and used it in conjunction with the original reporter …

A Space-Occupying Lesion Manifesting As Unilateral Optic Disc Edema, Len V. Koh Od, Phd, Anna Wells Od, Lindsay Jansen Od

Optometric Clinical Practice

Background: Primary and secondary orbital diseases can arise from different tissues in the periorbital regions as space-occupying lesion leading to ophthalmic symptoms. Therefore, eye care providers are often the first encounter for these patients.

Case report: A 54-year-old Caucasian male presented as a new patient at the eye clinic with an incidental finding of edema of the left optic disc. After a thorough optometric evaluation, a referral was made to a local ear-nose-throat (ENT) specialist who confirmed a diagnosis of cavernous hemangioma by further neuroimaging. Surgical removal eventuated in resolution of disc edema with restoration of vision.

Conclusion: An insidious …

Global And Regional Disparities In Access To Specialist Sarcoma Services, Tomas Zamora, Eduardo Botello, Thomas Jenkins, Charlotte Jeys, Minna Laitinen, Ajay Puri, Lee Jeys, Boom Consensus Meeting Participants, Santiago Abad Repiso, Hesham Abdelbary, Alejandro Abiad Mejia, Ahmed Abood, Juan C Abril Martin, Adesegun Abudu, Ayman Abu Elhamd, Marthelena Acosta, Keisuke Ae, Manish Agarwal, Vivek Ajit Singh, Toru Akiyama, Ibrahim Alshaygy, Jose I Albergo, John Alexander, Patricio A Alfaro, Bugra Alpan, Jose Amaya-Valero, Megan Anderson, Dimosthenis Andreou, Lucas Annabell, Christopher Anthony, Ahmed Aoude, William Aston, Libe Asua Mentxaka, Christine Azzopardi, Thomas Baad-Hansen, Ismail T Badr, Francisco Baixauli-Garcia, Gavin Baker, Tessa Balach, Giacomo G Baldi, Janie Barry, Georges Basile, Stefano Bastoni, Mohammad H Basuki, Henrik Bauer, Lee Bayliss, Ricardo G Becker, Angad Bedi, Joseph Benevenia, Francisco Bengoa, Peter Bergh, Marko Bergovec, Nicholas Bernthal, Odion Binitie, David Boddie, Michele Boffano, Patricia Bonilla Huertas, Anna B Borgognoni, Rajesh Botchu, Richard A Boyle, Jos Bramer, Rahat Brar, Harriet Branford-White, Demien Broekhuis, Samuel E Broida, Tymoteusz Budny, Zachary D Burke, Jorge Cabrolier, Jose A Calvo-Haro, Jorge R Calvo-Tapies, Domenico A Campanacci, Rodrigo Cardoso, Richard Carey Smith, Pedro I Carvallo, Nicolas Casales Fresenga, Jose M Casanova, Oscar Ceballos, Juan L Cebrian Parra, Laura K Certain, Sara Chancon Cartaya, Chung M Chan, Yoon Joo Cho, Peter Choong, Yang-Guk Chung, David Ciechanowicz, David Clever, Sebastian Colina, Luis Consuegra, Cory Couch, Gillian Cribb, Carlos Cuervo, Laurence A Cusick, Solomon Dadia, Tanios Dagher, Dietmar Dammerer, Mark Davies, Nerys Davies, Luis P De La Rosa Martino, Francisco J De Santos De La Fuente, Marieke De Vaal, Claudia Deckers, Javier Delgado Obando, Shaneel Deo, Niklas Deventer, Claudia Di Bella, Gregory Domson, Davide M Donati, Desiree M Dorleijn, Jacques Du Toit, Debra Dunne, Rodolfo Duran Ciarrochi, Walid Ebeid, Elina Ekman, Ahmed M El Ghoneimy, Makoto Endo, Levent Eralp, Mahmoud Etaiwi, Scott Evans, Robin Evrard, Will Eward, Alberto Farese, Peter C Ferguson, Pedro F Ferreira Cardoso, Fabrice Fiorenza, Michael Flint, Hector Flores, Joao Freitas, Bruno Fuchs, Tomohiro Fujiwara, Philipp T Funovics, Marcos Galli Serra, Zakareya Gamie, Carlos Garces-Zarzalejo, Aaron Gazendam, Carsten Gebert, Jasper G Gerbers, Craig Gerrand, Ghaith Abou-Nouar, Michelle Ghert, Kanishka M Ghosh, Max Gibbons, Luis C Gomez-Mier, Jesus Gomez-Vallejo, Anne Gomez-Mascard, Marcos R Gonzalez, Fausto Gonzalez-Lizan, Georg Gosheger, Stuart Goudie, Krista Goulding, Stavros D Goumenos, Anthony Griffin, Ashish Gulia, Sanjay Gupta, Amit Gupta, Maurice Guzman, Mohammed Haitham, Jendrik Hardes, Francisco Hardoy, Yusuf Hasan, Georg Hauer, Helard Havard, Rex Haydon, John Healey, Nerea Hernandez Gonzalez, Adriana Hernandez-Lopez, Asle Hesla, Matthew Hess, Chindanai Hongsaprabhas, Francis Hornicek, Keith Hosking, Matthew T Houdek, Eleanor Houghton, Oluwaseyi K Idowu, Joseph Ippolito, Marc Isler, Shintaro Iwata, Jake Jagiello, Neil Jenkins, Tom Jeys, Luke Johnson, Andy Johnston, Min Wook Joo, Paul C Jutte, Kadri Kaldas, Amar Kamat, Sudhir Kannan, Bilal Kapanci, Zeeshan Khan, Hiroshi Kobayashi, Yehuda Kollender, Sebastian Koob, Daniel Kotrych, Vineet Kurisunkal, Richard Kyte, Jose M Lamo De Espinosa, Alexander L Lazarides, Louis-Romee Le Nail, Pawel Legosz, Burkhard Lehner, Andreas Leithner, Maryse Lejoly, Valerae O Lewis, Peng Lin, Francisco Linares, Santiago A Lozano-Calderon, Ashish Mahendra, Ferdiansyah Mahyudin, Fermin J Mandia Mancebo, Sara Martos Torrejon, Christian Marx, Eric Mascard, Jean-Camille Mattei, Louise Mccullough, Sam Mcmahon, Manuel R Medellin Rincon, Benjamin Miller, Shinji Miwa, Gustavo Molina Uribe, Bryan Moon, Thomas Hilton, Diego J Moriel Garcesco, Carol Morris, Guy Morris, Steward Morrison, Sophie Mottard, Marcio Moura, Linde Muster, Robert Nakayama, Prashant Narhari, Ana Navas, Prakash Nayak, Johannes Neugebauer, Erik T Newman, Jyrki Nieminen, Emmy Nyqvist, Lukas Nystrom, Sarah O'Reilly-Harbidge, Gary O'Toole, Vania Oliveira, André Olivier, Mohamed Omar, Eduardo J Ortiz-Cruz, Harzem Ozger, Korhan Ozkan, Elisa Pala, Emanuela Palmerini, Grant Pang, Panayiotis Papagelopoulos, Giovanni Paraliticci, Michael C Parry, Sam Patton, David Peake, Ana Peiro Ibanez, Israel Perez Munoz, Ganapathy R Perianayagam, Michael M Petersen, Joris Ploegmakers, Robin Pollock, Gerard Powell, Juan Pretell, Jan Puetzler, Faisal Qamar, Anand Raja, Raja B Rajasekaran, Dipak Ramkumar, R L Randall, Kenneth Rankin, Kevin A Raskin, Kumaran Rassppan, Lauris Repsa, Mickael Ropars, Peter Rose, Pietro Ruggieri, Wael Sadek, German Salcedo, Aasim Saleemi, Andrea Sambri, Hartej Sar, Roberto Scanferla, Thomas Schubert, Jan Schwarze, Guido Scoccianti, Ashley Scrimshire, Tetsuya Sekita, Ahmad Shehadeh, Ahmed Shoaib, Bhim Shreemal, Felix Shumelinsky, Geoffrey Siegel, Claudio Silveri, Robert Silverwood, Friedl Sinnaeve, Jerome Sison, Andrea Slade, Maria A Smolle, Franz Snyman, Scott Sommerville, Sahil Sood, Andre Spiguel, Hugo St-Yves, Eric L Staals, Silvia Stacchiotti, Nikolas Stavropoulos, Peter Steadman, Jonathan D Stevenson, Mikaela Sullivan, Gwen Sys, Bartlomiej Szostakowski, Angela Tamburini, Yuta Taniguchi, Thomas Temple, Christoph Theil, Joachim Thorkildsen, Meagan Tibbo, Roger Tillman, Yu Toda, Kaspar Tootsi, Ferran Torner-Rubies, Frank Traub, Ioannis Trikoupis, Panagiotis Tsagkozis, Kim Tsoi, Hiroyuki Tsuchiya, Veli-Matti Vainio, Antonio Valcarcel, Juan Valencia, Annelies Van Beeck, Michiel Van De Sande, Thomas Van Den Berghe, Ingrid Van Der Geest, Lizz Van Der Heijden, Robert Van Der Wal, Kirsten Van Langevelde, Gualter Vaz, Roberto Velez Villa, Floortje Verspoor, Koenraad Verstraete, Julia Visgauss, Oleg Vyrva, Hazem Wafa, Sebastian Walter, Wan F Wan Ismail, Edward Wang, Patrick Q Wang, David Warnock, Joel Werier, Wolfram Weschenfelder, Kwok-Chuen Wong, Marjan Wouthuyzen-Bakker, Jay Wunder, Indica Wysinghe, Norio Yamamoto, Zhaoming Ye, Seung-Jae Yoon, Suraya Zainul Abidin, Pierluca Zecchetto, Liuzhe Zhang, Juan P Zumarraga, Miguel A Clara-Altamirano

Faculty, Staff and Student Publications

Aims: Cancer care guidelines have been developed in many subspecialities, usually in advanced health systems. However, there are notable global disparities in healthcare access, which can impact sarcoma care. Unfortunately, there is a lack of global data on this subject. Our aim was to describe access to sarcoma care based on a comprehensive global survey among orthopaedic oncologists, and assess for global as well as regional differences.

Methods: A 25-question survey was emailed to the attendees of the 2024 Birmingham Orthopaedic Oncology Meeting and included questions about the respondents' training and practice, access to sarcoma centres, and specific items for …

Natural Killer Cells’ Functional Impairment Drives The Immune Escape Of Pre-Malignant Clones In Early-Stage Myelodysplastic Syndromes, Juan Jose Rodriguez-Sevilla, Irene Ganan-Gomez, Bijender Kumar, Natthakan Thongon, Feiyang Ma, Kelly S Chien, Yi J Kim, Hui Yang, Sanam Loghavi, Roselyn Tan, Vera Adema, Zongrui Li, Tomoyuki Tanaka, Hidetaka Uryu, Rashmi Kanagal-Shamanna, Gheath Al-Atrash, Rafael Bejar, Pinaki Prosad Banerjee, Sophia Lynn Cha, Guillermo Montalban-Bravo, Max Dougherty, Maria Claudina Fernandez Laurita, Noelle Wheeler, Baosen Jia, Eirini P Papapetrou, Franco Izzo, Daniela E Dueñas, Salome Mcallen, Yiqian Gu, Gabriele Todisco, Francesca Ficara, Matteo Giovanni Della Porta, Abhinav Jain, Koichi Takahashi, Karen Clise-Dwyer, Stephanie Halene, Maria Teresa Sabrina Bertilaccio, Guillermo Garcia-Manero, May Daher, Simona Colla

Faculty, Staff and Student Publications

Dissecting the preneoplastic disease states' biological mechanisms that precede tumorigenesis can lead to interventions that can slow down disease progression and/or mitigate disease-related comorbidities. Myelodysplastic syndromes (MDS) cannot be cured by currently available pharmacological therapies, which fail to eradicate aberrant hematopoietic stem cells (HSCs), most of which are mutated by the time of diagnosis. Here, we sought to elucidate how MDS HSCs evade immune surveillance and expand in patients with clonal cytopenias of undetermined significance (CCUS), the pre-malignant stage of MDS. We used multi-omic single-cell approaches and functional in vitro studies to show that immune escape at disease initiation is …

Histone H3 Cysteine 110 Enhances Iron Metabolism And Modulates Replicative Life Span In Saccharomyces Cerevisiae, Chen Cheng, Brenna S Mccauley, Nedas Matulionis, Maria Vogelauer, Dimitrios Camacho, Heather R Christofk, Weiwei Dang, Nicholas A T Irwin, Siavash K Kurdistani

Center on Aging Staff Publications

The discovery of histone H3 copper reductase activity provides a novel metabolic framework for understanding the functions of core histone residues, which, unlike N-terminal residues, have remained largely unexplored. We previously demonstrated that histone H3 cysteine 110 (H3C110) contributes to cupric (Cu2+) ion binding and its reduction to the cuprous (Cu1+) form. However, this residue is absent in Saccharomyces cerevisiae, raising questions about its evolutionary and functional significance. Here, we report that H3C110 has been lost in many fungal lineages despite near-universal conservation across eukaryotes. Introduction of H3C110 into S. cerevisiae increased intracellular Cu1+ levels and ameliorated the iron …

Self-Management Program For Dyslipidemia: Impact On Health Behaviors To Modifiable Risk Factors And Compliance, Michael S. Lespron

Student Scholarly Projects

Practice Problem: Dyslipidemia management requires participation by both the healthcare provider and the patient alike. The inability to control lipid levels, including modifiable risk factors, can lead to cardiovascular disease which is the leading cause of death globally.

PICOT: In patients at a federally qualified health center that are 18-99 years of age and have a diagnosis of any type of dyslipidemia (P), does the implementation of a self-management program (SMP) via continued access to video recordings, take-home booklets, and biweekly follow-up calls (I) compared to current practices (C), increase compliance to medication adherence and lifestyle modification recommendations (O) within …

Hierarchical Lineage Tracing To Unravel Mechanisms Of Cancer Treatment Resistance, Rachel Danielle Saxe

Dartmouth College Ph.D Dissertations

Cancer cells adapt to treatment, leading to the emergence of clones that are more aggressive and resistant to anti-cancer therapies. We have a limited understanding of the development of treatment resistance as we lack technologies to map the evolution of cancer under the selective pressure of treatment. To address this, we developed a hierarchical, dynamic lineage tracing method called FLARE (Following Lineage Adaptation and Resistance Evolution). We use this technique to track the progression of acute myeloid leukemia (AML) cell lines through exposure to Cytarabine (AraC), a front-line treatment in AML, in vitro and in vivo. We map distinct cellular …

Geographic Divergence Of Methicillin-Resistant Staphylococcus Aureus St5-Scc Mec I In The Aftermath Of A Major Earthquake And Tsunami: Impact Of A Plasmid Harboring Heavy Metal Resistance Genes, Jose R W Martínez, Manuel Alcalde-Rico, Estefanía Jara-Videla, Jinnethe Reyes, Lina P Carvajal, Sandra Rincon, Rafael Ríos, Lorena Diaz, Ana Quesille-Villalobos, Roberto Riquelme-Neira, Lina Rivas, Ahmed M Moustafa, Blake Hanson, Eduardo A Undurraga, Jorge Olivares-Pacheco, Patricia García, Rafael Araos, Paul J Planet, César A Arias, Jose M Munita

Faculty, Staff and Student Publications

Methicillin-resistant Staphylococcus aureus (MRSA) is a major public health menace. The global spread of MRSA is characterized by successive waves of epidemic clones dominating specific geographical regions. The acquisition of genes encoding resistance to heavy metals (HMRGs) is thought to be a key feature in the geographic divergence of MRSA. However, the cause-effect relationship between the presence of HMRGs and the divergence of MRSA clones remains to be clarified. In this study, we assessed the role that HMRGs may have played in the evolutionary divergence of the MRSA ST5-SCCmecI lineage in Latin America. We conducted a genomic characterization …

Mitochondrial Responses To Conventional And Ultra-High Dose Rate (Flash) Radiation, Emily G Caggiano, Alan Lopez Hernandez, Trey Waldrop, Kevin Liu, Henry Gatica-Gutierrez, Sofía Vargas-Hernández, Nefetiti Mims, Ariana Acevedo-Diaz, Brett Velasquez, Denae Neil, Edgardo Aguilar, Matthew D Meyer, Gloria V Echeverria, Albert C Koong, Michael T Spiotto, Anna-Karin Gustavsson, Emil Schüler

Faculty, Staff and Students Publications

Purpose: Ultra-high dose rate (>40 Gy/s, FLASH) radiation therapy (RT) provides equivalent tumor control while reducing normal tissue toxicity relative to conventional dose rate (CONV) RT. However, the mechanisms underlying the observed FLASH effect are unknown. We hypothesized that the preservation of mitochondrial integrity in nontumorigenic cells by FLASH RT could be a key factor in reducing normal tissue toxicity and improving overall treatment outcomes.

Methods: We examined mitochondrial health and function after CONV and FLASH in vitro, ex vivo, and in vivo through assays of metabolic flux, mitochondrial membrane potential, mitochondrial reactive oxygen species (ROS), mitochondrial DNA damage …

The Medial Olivocochlear Efferent Pathway Potentiates Cochlear Amplification In Response To Hearing Loss, Patricia M Quiñones, Michelle Pei, Hemant Srivastava, Ariadna Cobo-Cuan, Marcela A Morán, Bong Jik Kim, Clayton B Walker, Michael J Serafino, Frank Macias-Escriva, Juemei Wang, James B Dewey, Brian E Applegate, Matthew J Mcginley, John S Oghalai

Faculty, Staff and Students Publications

The mammalian cochlea receives efferent feedback from the brain. Many functions for this feedback have been hypothesized, including on short timescales, such as mediating attentional states, and long timescales, such as buffering acoustic trauma. Testing these hypotheses has been impeded by an inability to make direct measurements of efferent effects in awake animals. Here, we assessed the role of the medial olivocochlear (MOC) efferent nerve fibers on cochlear amplification by measuring organ of Corti vibratory responses to sound in both sexes of awake and anesthetized mice. We studied long-term effects by genetically ablating the efferents and/or afferents. Cochlear amplification increased …

Molecular Subtyping Of Hypertensive Disorders Of Pregnancy, Michal Elovitz, Elaine Gee, Nathaniel Delaney-Busch, Alison Moe, Mitsu Reddy, Arkady Khodursky, Johnny La, Ilma Abbas, Kay Mekaru, Hunter Collins, Farooq Siddiqui, Rory Nolan, Rupsa Boelig, Daniel Kiefer, Pamela Simmons, George Saade, Antonio Saad, Ebony Carter, Thomas Mcelrath, Stephen Quake, Mark Depristo, Carrie Haverty, Manfred Lee, Eugeni Namsaraev, Vincenzo Berghella, Ai-Ris Collier, Antonia Frolova, Esther Park-Hwang, Luis Pacheco, Elizabeth Sutton, Maneesh Jain, Kara Rood, William A Grobman, Joseph Biggio, Cynthia Gyamfi-Bannerman, Arun Jeyabalan, Morten Rasmussen

Department of Obstetrics and Gynecology Faculty Papers

Hypertensive disorders of pregnancy (HDP), including preeclampsia, affect 1 in 6 pregnancies, are major contributors to maternal morbidity and mortality, yet lack precision medicine strategies. Analyzing transcriptomic data from a prospectively-collected diverse cohort (n = 9102), this study reveals distinct RNA subtypes in maternal blood, reclassifying clinical HDP phenotypes like early/late-onset preeclampsia. The placental gene PAPPA2 strongly predicts the most severe forms of preeclampsia in individuals without pre-existing high risk factors, months before symptoms, and its overexpression correlates with earlier delivery in a dose-dependent manner. Further, molecular subtypes characterized by immune genes are upregulated in less severe forms of HDP. …

Working Conditions Of Perfusionists In North America: A Scoping Review, James Strong

Student Works

Perfusionists face significant challenges, including long hours, high workloads, burnout, and workplace risks like sleep deprivation and discrimination, which impact both their well-being and patient outcomes. Despite these concerns, no comprehensive review has mapped workforce trends, and the lack of widespread American Society of Extracorporeal Technology (AmSECT) guideline implementation worsens the situation. This scoping review highlights these issues, emphasizing the need for standardized assessments, better enforcement of guidelines, and proactive strategies to improve perfusionist well-being and patient safety. This scoping review aims to describe the working conditions of North American Certified Clinical Perfusionists (CCPs).

Structural Updates To The Implant And Refill Needle Of The Port Delivery Platform, Dante J. Pieramici, Peter A. Campochiaro, Margaret Chang, Ian Pearce, Carl D. Regillo, Shamika Gune, Nancy Holekamp, Carlos Quezada-Ruiz, Shrirang V. Ranade, Natasha Singh, Geoffrey Wise, Joshua Horvath

Wills Eye Hospital Papers

PURPOSE: The purpose of this study was to report the impact of component-level changes and manufacturing process improvements on septum durability in the ocular implant of the Port Delivery Platform (PD-P), more commonly known as the Port Delivery System with ranibizumab (PDS) with its current formulation.

METHODS: Laboratory tests were conducted to determine (1) the bond strength of the septum to the overmold, (2) the amount of force utilized for the refill needle to puncture the septum, and (3) septum durability over 50 years. To simulate multiple refill-exchanges over long-term clinical use, implants were aged at elevated temperature in saline …

Targeted Ehr-Based Communication Of Diagnostic Uncertainty (Tecu) In The Emergency Department: Protocol For An Effectiveness Implementation Trial, Danielle M Mccarthy, Sara Malone, Dimitrios Papanagnou, Benjamin E Leiby, Amandy M B Doty, Phillip Watts, Rahul Yadav, Julia K Pugliese, Jonathan Woodworth, Tracy Esteves Camacho, Efrat Kean, Kristin L Rising

Department of Emergency Medicine Faculty Papers

BACKGROUND: At least 37 % emergency department (ED) patients are discharged without a definitive diagnosis, resulting in diagnostic uncertainty. Transitions of care are high-risk periods for patient safety, especially for patients discharged with diagnostic uncertainty. Effective communication between clinicians and patients improves these care transitions. Previous research developed tools to support high quality discharge in the setting of diagnostic uncertainty, including: a communication checklist, a physician training program, and a patient-facing information sheet.

METHODS: This study aims to enhance transitions for patients leaving the ED with diagnostic uncertainty through an electronic health record (EHR)-based strategy. The intervention, the Targeted EHR-based …

Protocol For A Multisite, Observational Clinical Study Of The Association Between Skin Colour And Pulse Oximeter Accuracy In Children Undergoing Cardiac Catheterisation (Pach Study), Halley Ruppel, Liming Huang, Christopher J Petit, Athar M Qureshi, Christopher P Bonafide, Elizabeth E Foglia, Jeffery Feldman, Meghan B Lane-Fall, Jennifer M Lynch, Anna Chien, Michelle Dunn, Michael L O'Byrne

Faculty, Staff and Students Publications

Introduction: Prospective, real-world clinical studies of the association between skin color and pulse oximeter (SpO2) accuracy in children are needed to address the limitations of previous research. Such studies are essential for generating evidence for clinicians, regulators and industry. This is the protocol for a multisite study funded by the National Heart, Lung, and Blood Institute (R01HL171313; 1 January 2024-31 December 2028).

Methods and analysis: In this pragmatic, observational study conducted in three large paediatric cardiac catheterisation centres in the USA, children undergoing cardiac catheterisation with directly measured arterial oxygen saturation will be prospectively enrolled. The outcome variable (SpO2 bias) …

Tobacco Smoke Exposure Is A Driver Of Altered Oxidative Stress Response And Immunity In Head And Neck Cancer, Yang Li, Pedram Yadollahi, Fonma N Essien, Vasanta Putluri, Chandra Shekar R Ambati, Karthik Reddy Kami Reddy, Abu Hena Mostafa Kamal, Nagireddy Putluri, Lama M Abdurrahman, Maria E Ruiz Echartea, Keenan J Ernste, Akshar J Trivedi, Jonathan Vazquez-Perez, William H Hudson, William K Decker, Rutulkumar Patel, Abdullah A Osman, Farrah Kheradmand, Stephen Y Lai, Jeffrey N Myers, Heath D Skinner, Cristian Coarfa, Kwangwon Lee, Antrix Jain, Anna Malovannaya, Mitchell J Frederick, Vlad C Sandulache

Faculty, Staff and Student Publications

Background: Exposomes are critical drivers of carcinogenesis. However, how they modulate tumor behavior remains unclear. Extensive clinical data show cigarette smoke to be a key exposome that promotes aggressive tumors, higher rates of metastasis, reduced response to chemoradiotherapy, and suppressed anti-tumor immunity. We sought to determine whether smoke itself can modulate aggressive tumor behavior in head and neck squamous cell carcinoma (HNSCC) through reprogramming of the cellular reductive state.

Methods: Using established human and murine HNSCC cell lines and syngeneic mouse models, we utilized conventional western blotting, steady state and flux metabolomics, RNA sequencing, quantitative proteomics and flow cytometry to …

Findings From A Qualitative Analysis: Social Media Influencers Of Color As Trusted Messengers Of Hpv Vaccination Messages, Amelia Burke-Garcia, Erin Cutroneo, Dasha Afanaseva, Kayla Madden, Angela Sustaita-Ruiz, Preethi Selvan, Estefany Rivera Sanchez, Amy Leader

Department of Medical Oncology Faculty Papers

BACKGROUND: Despite HPV vaccination reducing the prevalence of cervical cancer by 90%, vaccination rates remain lower among communities of color due to vaccine hesitancy and mistrust in traditional public health messengers. The emergence of social media influencers, a newer kind of messenger, presents a unique opportunity to share immunization messages in new ways with a variety of communities. This paper reviews the qualitative findings from a study aimed at assessing influencers' perceptions of and approaches to sharing messaging about the HPV vaccine.

METHODS: Guided by several theories (Theory of Planned Behavior, Narrative Theory, and Opinion Leader Theory), the study team …

"I Know Who I Am": Draw-And-Tell Conversations With Gender-Creative Children, Eline Leemans Lenne

Dissertations and Theses

A growing number of children identify in various gender-creative ways, likely due to broader social awareness and affirmation of transgenderism. Gender-creative children face higher risks for adverse social, academic, mental health, and healthcare outcomes compared to non-transgender peers. Support from loved ones along with guidance from pediatric providers can mitigate poor outcomes and ensure that gender-creative children live healthy and happy lives. Young gender-creative children's perspectives about the aforementioned topics are markedly absent from the literature, which instead highlights adolescent and adult proxy perspectives.

In this participatory arts-based study anchored by a constructivist epistemology and informed by post-structuralist, queer, and …

Chronic Viral Mimicry Induction Following P53 Loss Promotes Immune Evasion, Charles A Ishak, Sajid A Marhon, Naïri Tchrakian, Anjelica Hodgson, Helen Loo Yau, Isabela M Gonzaga, Melanie Peralta, Ilinca M Lungu, Stephanie Gomez, Sheng-Ben Liang, Shu Yi Shen, Raymond Chen, Jocelyn Chen, Biji Chatterjee, Kevin N Wanniarachchi, Junwoo Lee, Nicholas Zehrbach, Amir Hosseini, Parinaz Mehdipour, Siyu Sun, Alexander Solovyov, Ilias Ettayebi, Kyle E Francis, Aobo He, Taiyi Wu, Shengrui Feng, Tiago Da Silva Medina, Felipe Campos De Almeida, Jane Bayani, Jason Li, Spencer Macdonald, Yadong Wang, Sarah S Garcia, Elisa Arthofer, Noor Diab, Aneil Srivastava, Paul Tran Austin, Peter J B Sabatini, Benjamin D Greenbaum, Catherine A O'Brien, Trevor G Shepherd, Ming Sound Tsao, Katherine B Chiappinelli, Amit M Oza, Blaise A Clarke, Robert Rottapel, Stephanie Lheureux, Daniel D De Carvalho

Faculty, Staff and Student Publications

Epigenetic therapies facilitate transcription of immunogenic repetitive elements that cull cancer cells through ‘viral mimicry’ responses. Paradoxically, cancer-initiating events also facilitate transcription of repetitive elements. Contributions of repetitive element transcription towards cancer initiation, and the mechanisms by which cancer cells evade lethal viral mimicry responses during tumor initiation remain poorly understood. In this report, we characterize premalignant lesions of the fallopian tube along with syngeneic epithelial ovarian cancer models to explore the earliest events of tumorigenesis following loss of the p53 tumor suppressor protein. We report that p53 loss permits transcription of immunogenic repetitive elements and chronic viral mimicry activation …

Computational Sensitivity Evaluation Of Ultrasound Neuromodulation Resolution To Brain Tissue Sound Speed With Robust Beamforming, Boqiang Fan, Wayne Goodman, Sameer A Sheth, Richard R Bouchard, Behnaam Aazhang

Faculty, Staff and Student Publications

Low-intensity focused ultrasound (LIFU) neuromodulation requires precise targeting and high resolution enabled by phased array transducers and beamforming. However, focusing optimization usually relies on phantom measurements or simulations with inaccurate acoustic properties to degrade neuromodulation resolution. Therefore, this work analyzes the sensitivity of neuromodulation resolution, measured by off-target activation area (OTAA), to brain tissue sound speed. A Robust Optimal Resolution (ROR) beamforming method is proposed to minimize the worst-case OTAA with restricted sound speed inaccuracy and propagation information estimated with deviated sound speed. The propagation estimation model utilizes equivalent source method (ESM) to map sound field between different acoustic parameter …

Prdm1 Is A Key Regulator Of The Nkt-Cell Central Memory Program And Effector Function, Gengwen Tian, Gabriel A Barragan, Hangjin Yu, Claudia Martinez-Amador, Akshaya Adaikkalavan, Xavier Rios, Linjie Guo, Janice M Drabek, Osmay Pardias, Xin Xu, Antonino Montalbano, Chunchao Zhang, Yanchuan Li, Amy N Courtney, Erica J Di Pierro, Leonid S Metelitsa

Faculty, Staff and Students Publications

Natural killer T cells (NKTs) are a promising platform for cancer immunotherapy, but few genes involved in the regulation of NKT therapeutic activity have been identified. To find regulators of NKT functional fitness, we developed a CRISPR/Cas9-based mutagenesis screen that uses a guide RNA (gRNA) library targeting 1,118 immune-related genes. Unmodified NKTs and NKTs expressing a GD2-specific chimeric antigen receptor (GD2.CAR) were transduced with the gRNA library and exposed to CD1d+ leukemia or CD1d-GD2+ neuroblastoma cells, respectively, over six challenge cycles in vitro. Quantification of gRNA abundance revealed enrichment of PRDM1-specific gRNAs in both NKTs and GD2.CAR NKTs, a result …

Bone-Induced Her2 Promotes Secondary Metastasis In Hr+/Her2- Breast Cancer, Rahat Alam, Anna Reva, David G Edwards, Bree M Lege, Laura S Munoz-Arcos, Carolina Reduzzi, Swarnima Singh, Xiaoxin Hao, Yi-Hsuan Wu, Zeru Tian, Laura M Natalee, Gargi Damle, Deniz Demircioglu, Yixian Wang, Ling Wu, Elisabetta Molteni, Dan Hasson, Bora Lim, Zbigniew Gugala, Jerry E Chipuk, Julie E Lang, Joseph A Sparano, Chonghui Cheng, Massimo Cristofanilli, Han Xiao, Xiang H-F Zhang, Igor L Bado

Faculty, Staff and Students Publications

Bone metastases can disseminate to secondary sites and promote breast cancer progression creating additional clinical challenges. The mechanisms contributing to secondary metastasis are barely understood. Here, we evaluate the prediction power of Her2-expressing (Her2E) circulating tumor cells (CTCs) after analyzing over 13,000 CTCs from a cohort of 137 metastatic breast cancer (MBC) patients with initial HR+/Her2− status and employ preclinical models of bone metastasis (BM) to validate the role of Her2E CTCs in multi-organ metastases. While Her2 expression was higher in patients with bone metastasis, experimental analyses revealed that Her2E CTCs derived from bone lesions were more dependent on Her2 …

The Effects Of E-Liquid Aerosol ± Flavors On The Planktonic Growth Of Porphyromonas Gingivalis, Taylor Ahles, Skyler Gronkiewicz, Saskia Mourra, Dominic Palazzolo

Research Projects

A balance of commensal and pathogenic bacteria in the oral cavity is essential for optimal oral and systemic health. Our previous studies demonstrate that E- liquid aerosol ± flavors (particularly cinnamon) are detrimental to several strains of oral commensal streptococcal bacteria. However, very little information is available concerning the effects of E-liquid aerosols on oral pathogens. For this reason, Porphyromonas gingivalis, a pathogenic anaerobe and critical contributor to periodontal disease, was chosen for this study. Objective: This study aims to determine the effect of E-liquid aerosol ± flavors on the planktonic growth of P. gingivalis. Methods: P. gingivalis, initially grown …