Digital Commons Network^™

Persistent Microbial Infections And Idiopathic Pulmonary Fibrosis – An Insight Into Non-Typeable Haemophilus Influenza Pathogenesis, Dong Hun Lee, Minseong Kim, Sarah S Chang, Raham Lee, Andrew J Jang, Juyoung Kim, Jing Ma, Michael J Passineau, Raymond L Benza, Harry Karmouty-Quintana, Wilbur A Lam, Benjamin T Kopp, Roy L Sutliff, C Michael Hart, Changwon Park, Bum-Yong Kang

Faculty, Staff and Student Publications

Endothelial-to-mesenchymal transition (EndoMT) plays an important role in pulmonary hypertension (PH) but the molecular mechanisms regulating EndoMT remain to be defined. We demonstrate that the axis of the transcription factors PPARγ (Peroxisome Proliferator-Activated Receptor gamma) and ETV2 (ETS variant 2) play important roles in the pathogenesis of PH. Decreased levels of the expression of PPARγ and ETV2 along with reduced endothelial and increased EndoMT markers are consistently observed in lungs and pulmonary artery endothelial cells (PAECs) of idiopathic pulmonary arterial hypertension patients, in hypoxia-exposed mouse lungs, human PAECs, and in induced-EndoMT cells. Etv2 +/- mice spontaneously developed PH and right …

Impact Of Race And Ethnicity On Outcomes After Umbilical Cord Blood Transplantation, Karen Ballen, Tao Wang, Naya He, Jennifer M Knight, Sanghee Hong, Haydar Frangoul, Leo F Verdonck, Amir Steinberg, Miguel A Diaz, C Fred Lemaistre, Sherif M Badawy, Jeffrey J Pu, Hasan Hashem, Bipin Savani, Akshay Sharma, Hillard M Lazarus, Muhammad Bilal Abid, Jason Tay, Hemalatha G Rangarajan, Tamila Kindwall-Keller, Cesar O Freytes, Amer Beitinjaneh, Lena E Winestone, Usama Gergis, Nosha Farhadfar, Neel S Bhatt, Raquel M Schears, David Gómez-Almaguer, Mahmoud Aljurf, Vaibhav Agrawal, Yachiyo Kuwatsuka, Sachiko Seo, David I Marks, Leslie Lehmann, William A Wood, Shahrukh Hashmi, Wael Saber

Faculty, Staff and Student Publications

Background: Umbilical cord blood transplant (UCBT) improves access to transplant for patients lacking a fully matched donor. Previous Center for International Blood and Marrow Transplant Research (CIBMTR) showed that Black patients had a lower overall survival (OS) than White patients following single UCBT. The current study draws on a larger modern cohort and compares outcomes among White, Latinx, Black, and Asian patients.

Objective: To compare outcomes by social determinants of health.

Study design: We designed a retrospective study using CIBMTR data. US patients were between ages 1 and 80; 983 received single and 1529 double UCBT as reported to CIBMTR, …

Cardiac Manifestations And Outcomes Of Covid-19 Vaccine-Associated Myocarditis In The Young In The Usa: Longitudinal Results From The Myocarditis After Covid Vaccination (Maciv) Multicenter Study, Supriya S Jain, Steven A Anderson, Jeremy M Steele, Hunter C Wilson, Juan Carlos Muniz, Jonathan H Soslow, Rebecca S Beroukhim, Victoria Maksymiuk, Xander Jacquemyn, Olivia H Frosch, Brian Fonseca, Ashraf S Harahsheh, Sujatha Buddhe, Ravi C Ashwath, Deepika Thacker, Shiraz A Maskatia, Nilanjana Misra, Jennifer A Su, Saira Siddiqui, Danish Vaiyani, Aswathy K Vaikom-House, M Jay Campbell, Jared Klein, Sihong Huang, Christopher Mathis, Matthew D Cornicelli, Madhu Sharma, Lakshmi Nagaraju, Jocelyn Y Ang, Santosh C Uppu, Preeti Ramachandran, Jyoti K Patel, Frank Han, Jason G Mandell, Jyothsna Akam-Venkata, Michael P Dilorenzo, Michael Brumund, Puneet Bhatla, Parham Eshtehardi, Karina Mehta, Katherine Glover, Matthew L Dove, Khalifah A Aldawsari, Anupam Kumar, Spencer B Barfuss, Adam L Dorfman, Prashant K Minocha, Alexandra B Yonts, Jenna Schauer, Andrew L Cheng, Joshua D Robinson, Zachary Powell, Shubhika Srivastava, Anjali Chelliah, Yamuna Sanil, Lazaro E Hernandez, Lasya Gaur, Michael Antonchak, Marla Johnston, Jonathan D Reich, Narayan Nair, Elizabeth D Drugge, Lars Grosse-Wortmann

Faculty, Staff and Student Publications

Background: We aimed to study the clinical characteristics, myocardial injury, and longitudinal outcomes of COVID-19 vaccine-associated myocarditis (C-VAM).

Methods: In this longitudinal retrospective observational cohort multicenter study across 38 hospitals in the United States, 333 patients with C-VAM were compared with 100 patients with multisystem inflammatory syndrome in children (MIS-C). We included patients ≤30 years of age with a clinical diagnosis of acute myocarditis after COVID-19 vaccination based on clinical presentation, abnormal biomarkers and/or cardiovascular imaging findings. Demographics, past medical history, hospital course, biochemistry results, cardiovascular imaging, and follow-up information from April 2021 to November 2022 were collected. The primary …

Training Nurses In Trauma-Informed Care To Address Workplace Violence In Inpatient Settings, Kelly Kearney, Elaheh Ashtari, Stephanie Emhoff, Calvary Fielden, Sarah Hernandez, Ana Ruiz

Faculty, Staff and Student Publications

Background: Frontline workers in psychiatric facilities are exposed to considerable risks of verbal and physical assaults, with 40% to 65% of mental health nurses experiencing violence in the workplace. The goal of this pilot study was to assess the readiness and motivation for adopting trauma-informed care (TIC) to address workplace violence in an acute care psychiatric hospital.

Method: A pre-post quality improvement study was conducted in two pilot units of a 274-bed acute care psychiatric hospital, involving a discussion-based seminar and a practical exercise. Surveys assessed participants' readiness and motivation posttraining.

Results: Sixty-eight staff members completed part 1 training, with …

Intimate Partner Violence And Parenting, Jeff R Temple, Elizabeth Baumler, Leila Wood

Faculty, Staff and Student Publications

This cohort study evaluates parental stress and protective factors mitigating risks for child maltreatment in the context of intimate partner violence.

Abstinence Beliefs In Early Adolescence And Sexual Risk Behavior Two Years Later, Shristi Bhochhibhoya, Briana Edison, Elizabeth R Baumler, Christine M Markham, Susan T Emery, Melissa F Peskin, Ross Shegog, Robert C Addy, Jeff R Temple, Dennis E Reidy

Faculty, Staff and Student Publications

Introduction: The United States has the highest teen pregnancy rate and sexually transmitted infection rates among developed countries. One common approach that has been implemented to reduce these rates is abstinence-only-until-marriage programs that advocate for delaying sexual intercourse until marriage. These programs focus on changing adolescents' beliefs toward abstinence until marriage; however, it is unclear whether adolescents' beliefs about abstinence predict their sexual behavior, including sexual risk behavior (SRB). An alternative approach may be encouraging youth to delay their sexual debut until they reach the age of maturity, but not necessarily until marriage.

Methods: To address this question, we compare …

Lhcgr Inactivating Variants: Single Center Experience And Systematic Review Of Phenotype-Genotype Of 46, Xy And 46, Xx Patients, Rohit Barnabas, Swati Jadhav, Anurag Ranjan Lila, Sirisha Kusuma Boddu, Saba Samad Memon, Sneha Arya, Samiksha Chandrashekhar Hegishte, Manjiri Karlekar, Virendra A Patil, Vijaya Sarathi, Nalini S Shah, Tushar Bandgar

Faculty, Staff and Student Publications

Background: The data on Leydig cell hypoplasia (LCH) resulting from biallelic Luteinizing hormone/chorionic gonadotropin receptor (LHCGR) inactivating variants is limited to case series.

Methods: We aim to describe our patients and perform systematic review of the patients with LHCGR inactivating variants in the literature. Detailed phenotype and genotype data of three patients from our centre and 85 (46,XY: 67; 46,XX: 18) patients from 59 families with LHCGR-inactivating variants from literature were described.

Results: Three 46,XY patients (age 6-18 years) from our center, with two reared as females, had two novel variants in LHCGR. Systematic review (including our patients) revealed 72 …

The Toxicology Investigators Consortium 2023 Annual Report, Adrienne Hughes, Alexandra Amaducci, Sharan L Campleman, Shao Li, Mari Costantini, Meghan B Spyres, Hannah Spungen, Jessica Kent, Alyssa Falise, Rachel Culbreth, Paul M Wax, Jeffery Brent, Kim Aldy, Toxicology Investigators Consortium Study Group

Faculty, Staff and Student Publications

Since 2010, the American College of Medical Toxicology (ACMT) Toxicology Investigators Consortium (ToxIC) has maintained the ToxIC Core Registry, a national case registry of in-hospital and clinic patient consultations submitted by medical toxicology physicians. Deidentified patient data entered into the registry includes patient demographics, reason for medical toxicology evaluation, exposure agents, clinical signs and symptoms, treatments and antidotes administered, and mortality. This fourteenth annual report provides data from 7392 patients entered into the Core Registry in 2023 by 36 participating sites comprising 61 distinct healthcare facilities, bringing the total case count to 102331 between 2010 and 2023. Ethanol was the …

Hyperfibrinolysis: A Crucial Phenotypic Abnormality Of Posttraumatic Fibrinolytic Dysfunction, Kyosuke Takahashi, Kazuma Yamakawa, Anaar E Siletz, Morihiro Katsura, John B Holcomb, Charles E Wade, Jessica C Cardenas, Erin E Fox, Morgan Schellenberg, Matthew Martin, Kenji Inaba, Kazuhide Matsushima

Faculty, Staff and Student Publications

Background: Traumatic fibrinolytic dysfunction is often categorized into 3 phenotypes based on the result of thromboelastography (TEG) lysis at 30 minutes (LY30): fibrinolysis shutdown, physiologic fibrinolysis, and hyperfibrinolysis. However, the molecular pathophysiology of fibrinolytic dysfunction and the association with clinical outcomes have not been fully evaluated.

Objectives: To assess whether posttraumatic fibrinolysis phenotypes identified by TEG correlate with levels of key fibrinolysis-related serum markers and with risk of mortality and hospital complications.

Methods: This is a secondary analysis of the Pragmatic, Randomized Optimal Platelet and Plasma Ratios trial. Patients were stratified according to the degree of fibrinolysis upon arrival using …

Vessel-Targeted Compensation Of Deformable Motion In Interventional Cone-Beam Ct, Alexander Lu, Heyuan Huang, Yicheng Hu, Wojciech Zbijewski, Mathias Unberath, Jeffrey H Siewerdsen, Clifford R Weiss, Alejandro Sisniega

Faculty, Staff and Student Publications

The present standard of care for unresectable liver cancer is transarterial chemoembolization (TACE), which involves using chemotherapeutic particles to selectively embolize the arteries supplying hepatic tumors. Accurate volumetric identification of intricate fine vascularity is crucial for selective embolization. Three-dimensional imaging, particularly cone-beam CT (CBCT), aids in visualization and targeting of small vessels in such highly variable anatomy, but long image acquisition time results in intra-scan patient motion, which distorts vascular structures and tissue boundaries. To improve clarity of vascular anatomy and intra-procedural utility, this work proposes a targeted motion estimation and compensation framework that removes the need for any prior …

Late Subsequent Leukemia After Childhood Cancer: A Report From The Childhood Cancer Survivor Study (Ccss), Taumoha Ghosh, Geehong Hyun, Rikeenkumar Dhaduk, Miriam Conces, Michael A Arnold, Rebecca M Howell, Tara O Henderson, Aaron Mcdonald, Leslie L Robison, Yutaka Yasui, Kirsten K Ness, Gregory T Armstrong, Joseph P Neglia, Lucie M Turcotte

Faculty, Staff and Student Publications

Background: Subsequent short-latency leukemias are well-described among survivors of childhood cancer. However, late (5-14.9 years from diagnosis, LL) and very late (≥15 years from diagnosis, VLL) subsequent leukemias have not been well studied. We assessed risk factors, prevalence, and outcomes for LL and VLL in the Childhood Cancer Survivor Study cohort.

Methods: Subsequent leukemias, among 25,656 five-year survivors, were self-reported and confirmed by pathology review. Standardized incidence ratios (SIR) and cumulative incidences were calculated, and relative risks (RR) were estimated using Cox regression for exposures.

Results: Seventy-seven survivors developed subsequent leukemia, 49 survivors with LL (median time from diagnosis 7.8 …

A Brave New Framework For Glioma Drug Development, Kelly M Hotchkiss, Philipp Karschnia, Karisa C Schreck, Marjolein Geurts, Timothy F Cloughesy, Jason Huse, Elizabeth S Duke, Justin Lathia, David M Ashley, Edjah K Nduom, Georgina Long, Kirit Singh, Anthony Chalmers, Manmeet S Ahluwalia, Amy Heimberger, Stephen Bagley, Tomoki Todo, Roel Verhaak, Patrick D Kelly, Shawn Hervey-Jumper, John De Groot, Anoop Patel, Peter Fecci, Ian Parney, Victoria Wykes, Colin Watts, Terry C Burns, Nader Sanai, Matthias Preusser, Joerg Christian Tonn, Katharine J Drummond, Michael Platten, Sunit Das, Kirk Tanner, Michael A Vogelbaum, Michael Weller, James R Whittle, Mitchel S Berger, Mustafa Khasraw

Faculty, Staff and Student Publications

Patients with brain tumours are motivated to participate in clinical trials involving repeat tissue sampling. Normalising the use of neoadjuvant and staged surgical trials necessitates collaboration among patients, regulatory agencies, and researchers. Initial and repetitive tissue sampling plays a crucial role in enhancing our understanding of resistance mechanisms and vulnerabilities in brain tumour therapy. Standardising biopsy techniques and ensuring technical uniformity across institutions are vital for effective interinstitutional collaboration. Although liquid biopsy technologies hold promise, they are not yet ready to replace tissue analysis. Clear communication about the risks and benefits of biopsies is essential, particularly regarding potential postoperative deficits. …

A Molecular Switch From Tumor Suppressor To Oncogene In Er+Ve Breast Cancer: Role Of Androgen Receptor, Jak-Stat, And Lineage Plasticity, Sarah Asemota, Wendy Effah, Jeremiah Holt, Daniel Johnson, Linnea Cripe, Suriyan Ponnusamy, Thirumagal Thiyagarajan, Yekta Khosrosereshki, Dong-Jin Hwang, Yali He, Brandy Grimes, Martin D Fleming, Frances E Pritchard, Ashley Hendrix, Meiyun Fan, Abhinav Jain, Hyo Young Choi, Liza Makowski, D Neil Hayes, Duane D Miller, Lawrence M Pfeffer, Balaji Santhanam, Ramesh Narayanan

Faculty, Staff and Student Publications

Cancers develop resistance to inhibitors of oncogenes mainly due to target-centric mechanisms such as mutations and splicing. While inhibitors or antagonists force targets to unnatural conformation contributing to protein instability and resistance, activating tumor suppressors may maintain the protein in an agonistic conformation to elicit sustainable growth inhibition. Due to the lack of tumor suppressor agonists, this hypothesis and the mechanisms underlying resistance are not understood. In estrogen receptor (ER)-positive breast cancer (BC), androgen receptor (AR) is a druggable tumor suppressor offering a promising avenue for this investigation. Spatial genomics suggests that the molecular portrait of AR-expressing BC cells in …

A Commissioning Protocol For Portal Imaging-Based Radiotherapy In Vivo Dosimetry Systems, Marco Esposito, Riccardo Baldoni, Evy Bossuyt, Sara Bresciani, Catharine H Clark, Matthew Jones, Stephen Kry, Joseph Perry, Jeroen Van De Kamer, Dirk Verellen, Nuria Jornet

Faculty, Staff and Student Publications

Background and purpose: With the availability of commercial electronic portal imaging detector-based in vivo dosimetry (EPID-based IVD) solutions, many radiotherapy departments are adopting this technology. However, comprehensive commissioning guidance is lacking. This study aims to provide a protocol for testing the accuracy and sensitivity of EPID-based IVD systems.

Material and methods: The protocol was tested across four institutions using two different systems. Accuracy was evaluated with homogeneous slab phantoms using different square regular fields, and clinical plans in a CIRS lung phantom. Multiple forward and back-projected algorithm implementations were assessed for different energies. Sensitivity analysis in the lung phantom examined …

Prognostic Scores For Ursodeoxycholic Acid-Treated Patients Predict Graft Loss And Mortality In Recurrent Primary Biliary Cholangitis After Liver Transplantation, Aldo J Montano-Loza, Ellina Lytvyak, Gideon Hirschfield, Bettina E Hansen, Maryam Ebadi, Thierry Berney, Christian Toso, Giulia Magini, Alejandra Villamil, Frederik Nevens, Natalie Van Den Ende, Albert Pares, Pablo Ruiz, Débora Terrabuio, Palak J Trivedi, Nadir Abbas, Maria Francesca Donato, Lei Yu, Charles Landis, Jérôme Dumortier, Jessica Katharine Dyson, Adriaan J Van Der Meer, Rozanne De Veer, Mark Pedersen, Marlyn Mayo, Michael P Manns, Richard Taubert, Theresa Kirchner, Luca S Belli, Chiara Mazzarelli, Guido Stirnimann, Annarosa Floreani, Nora Cazzagon, Francesco Paolo Russo, Patrizia Burra, Udi Zigmound, Inbal Houri, Marco Carbone, Giacomo Mulinacci, Stefano Fagiuoli, Daniel Stephan Pratt, Alan Bonder, Thomas D Schiano, Brandy Haydel, Ansgar Lohse, Christoph Schramm, Darius Rüther, Stefania Casu, Xavier Verhelst, Benedetta Terziroli Beretta-Piccoli, Mercedes Robles, Andrew L Mason, Christophe Corpechot, Global Pbc Study Group

Faculty, Staff and Student Publications

Background & aims: Recurrent primary biliary cholangitis (rPBC) develops in approximately 30% of patients and negatively impacts graft and overall patient survival after liver transplantation (LT). There is a lack of data regarding the response rate to ursodeoxycholic acid (UDCA) in rPBC. We evaluated a large, international, multi-center cohort to assess the performance of PBC scores in predicting the risk of graft and overall survival after LT in patients with rPBC.

Methods: A total of 332 patients with rPBC after LT were evaluated from 28 centers across Europe, North and South America. The median age at the time of rPBC …

Inulin-Gel-Based Oral Immunotherapy Remodels The Small Intestinal Microbiome And Suppresses Food Allergy, Kai Han, Fang Xie, Olamide Animasahun, Minal Nenwani, Sho Kitamoto, Yeji Kim, May Thazin Phoo, Jin Xu, Fulei Wuchu, Kehinde Omoloja, Abhinav Achreja, Srinadh Choppara, Zhaoheng Li, Wang Gong, Young Seok Cho, Hannah Dobson, Jinsung Ahn, Xingwu Zhou, Xuehui Huang, Xinran An, Alexander Kim, Yao Xu, Qi Wu, Soo-Hong Lee, Jessica J O'Konek, Yuying Xie, Yu Leo Lei, Nobuhiko Kamada, Deepak Nagrath, James J Moon

Faculty, Staff and Student Publications

Despite the potential of oral immunotherapy against food allergy, adverse reactions and loss of desensitization hinder its clinical uptake. Dysbiosis of the gut microbiota is implicated in the increasing prevalence of food allergy, which will need to be regulated to enable for an effective oral immunotherapy against food allergy. Here we report an inulin gel formulated with an allergen that normalizes the dysregulated ileal microbiota and metabolites in allergic mice, establishes allergen-specific oral tolerance and achieves robust oral immunotherapy efficacy with sustained unresponsiveness in food allergy models. These positive outcomes are associated with enhanced allergen uptake by antigen-sampling dendritic cells …

Simultaneous Ipsilateral Hip And Knee Dislocation: Management And Outcome – A Case Report, Christian G Falgons, Stephen J Warner

Faculty, Staff and Student Publications

Case: This clinical case report presents a 40-year-old male who sustained an ipsilateral hip and knee dislocation with ipsilateral femoral head fracture and incomplete femoral neck fracture following a motorcycle collision.

Conclusion: This report describes acute and later definitive orthopedic care and management, with focus on urgent interventions and timing of immediate treatments. Given the presented patient's favorable clinical outcomes, return to baseline activities, and absence of significant sequelae following injury, the considerations from the acute management and surgical planning of this patient's injuries can be used as a reference for treating the rare injury of ipsilateral knee and hip …

Diffusion Tensor Imaging For Characterizing Changes In Triple-Negative Breast Cancer During Neoadjuvant Systemic Therapy, Benjamin C Musall, David E Rauch, Rania M M Mohamed, Bikash Panthi, Medine Boge, Rosalind P Candelaria, Huiqin Chen, Mary S Guirguis, Kelly K Hunt, Lei Huo, Ken-Pin Hwang, Anil Korkut, Jennifer K Litton, Tanya W Moseley, Sanaz Pashapoor, Miral M Patel, Brandy J Reed, Marion E Scoggins, Jong Bum Son, Debu Tripathy, Vicente Valero, Peng Wei, Jason B White, Gary J Whitman, Zhan Xu, Wei T Yang, Clinton Yam, Beatriz E Adrada, Jingfei Ma

Faculty, Staff and Student Publications

Background: Assessment of treatment response in triple-negative breast cancer (TNBC) may guide individualized care for improved patient outcomes. Diffusion tensor imaging (DTI) measures tissue anisotropy and could be useful for characterizing changes in the tumors and adjacent fibroglandular tissue (FGT) of TNBC patients undergoing neoadjuvant systemic treatment (NAST).

Purpose: To evaluate the potential of DTI parameters for prediction of treatment response in TNBC patients undergoing NAST.

Study type: Prospective.

Population: Eighty-six women (average age: 51 ± 11 years) with biopsy-proven clinical stage I-III TNBC who underwent NAST followed by definitive surgery. 47% of patients (40/86) had pathologic complete response (pCR). …

Tailoring Neoadjuvant Systemic Therapy In Breast Cancer: “The Advent Of A Personalized Approach”-The Breast-Gynecological And Immuno-Oncology International Cancer Conference (Bgicc) Consensus And Recommendations, Hesham Elghazaly, Hamdy A Azim, Hope S Rugo, David Cameron, Sandra M Swain, Giuseppe Curigliano, Nadia Harbeck, Debu Tripathy, Banu Arun, Matti Aapro, Martine Piccart, Fatima Cardoso, Joseph Gligorov, Hagar Elghazawy, Nagi S El Saghir, Frederique Penault-Llorca, Edith A Perez, Philip Poortmans, Hany Abdelaziz, Heba M El-Zawahry, Loay Kassem, Mohamed Sabry, Giuseppe Viale, Sana Al-Sukhun, Neven Gado, Jessica W T Leung, Lobna Ezz Elarab, Maria João Cardoso, Khaled Abdel Karim, Meteb Foheidi, Merit M Elmaadawy, Pierfranco Conte, Ashraf S M Selim, Alaa Kandil, Rasha M Kamal, Ruslan M Paltuev, Valentina Guarneri, Omalkhair Abulkhair, Omar Zakaria, Mehra Golshan, Roberto Orecchia, Manal Elmahdy, Ahmed M Abdel-Aziz, Nermean Bahie Eldin

Faculty, Staff and Student Publications

Background: The management of early breast cancer (BC) has witnessed an uprise in the use of neoadjuvant therapy and a remarkable reshaping of the systemic therapy postneoadjuvant treatment in the last few years, with the evolution of many controversial clinical situations that require consensus.

Methods: During the 14th Breast-Gynecological and Immuno-Oncology International Cancer Conference held in Egypt in 2022, a panel of 44 BC experts from 13 countries voted on statements concerning debatable challenges in the neo/adjuvant treatment setting. The recommendations were subsequently updated based on the most recent data emerging. A modified Delphi approach was used to develop this …

Batchflex: Feature-Level Equalization Of X-Batch., Joshua T. Davis, Alyssa N. Obermayer, Alex C. Soupir, Rebecca S. Hesterberg, Thac Duong, Ching-Yao Yang, Ken Phong Dao, Brandon J. Manley, G Daniel Grass, Dorina Avram, Paulo C. Rodriguez, Brooke L. Fridley, Xiaoqing Yu, Mingxiang Teng, Xuefeng Wang, Timothy I. Shaw

Manuscripts, Articles, Book Chapters and Other Papers

MOTIVATION: Integrative analysis of heterogeneous expression data remains challenging due to variations in platform, RNA quality, sample processing, and other unknown technical effects. Selecting the approach for removing unwanted batch effects can be a time-consuming and tedious process, especially for more biologically focused investigators.

RESULTS: Here, we present BatchFLEX, a Shiny app that can facilitate visualization and correction of batch effects using several established methods. BatchFLEX can visualize the variance contribution of a factor before and after correction. As an example, we have analyzed ImmGen microarray data and enhanced its expression signals that distinguishes each immune cell type. Moreover, our …

A Love That Harms: Violent Love Imagery In Hadewijch Of Brabant And The Influence Of Richard Of Saint Victor, Kenneth Hoyt

Dissertations (1934 -)

That medieval women mystics utilized violent imagery in regards to Love, and, subsequently, their union with it, is well established in the scholarly literature. The approaches to this imagery differ in their conceptions and approaches to the women: some approach via the influence of courtly literature and thus see it as an expression of a literary genre; others apply more modern critiques, seen in feminist and gender theory approaches, where, usually following Foucault, the emphasis is on how the language effects or disrupts medieval power structures; others approach the women from a historical lens, placing the women’s language as an …

Exploring The Influence Of Molecular Chaperones On The Aggregation Of Transthyretin, Adam S. Knier

Dissertations (1934 -)

Molecular chaperones assist in maintaining protein homeostasis by limiting protein aggregation, including populations of protein aggregates that may be associated with the onset of debilitating and/or often fatal diseases. Chaperones are known to limit protein aggregate populations through disaggregase activity, in which chaperone complexes work together to disassemble multi-subunit aggregate species into smaller populations, or holdase activity, in which chaperones bind to proteins or smaller aggregates to prevent further aggregation. In this dissertation we assess if molecular chaperones can limit the aggregation of human transthyretin (TTR) expressed within a yeast system and explore the relationship between chaperone concentration and activity. …

The Tragedy Of Our Trajectory, Marisola Xhelili Ciaccio

Dissertations (1934 -)

In this project, I argue that the trajectory of Western European civilization has resulted in increasingly tragic predicaments that are not to be taken as given features of being human. Though both Ancient Western and Eastern wisdom traditions concur that suffering is a part of life, the point of living is not to suffer but to learn to overcome it and flourish. But because the purported successes of Western “progress” necessarily depend on structural oppression, and oppression produces superfluous sufferings that interfere with our capacities to actualize our freedom and flourish, they ultimately make us all worse-off. Reflecting on such …

The Role Of Aldh1a1 In Glioblastoma Proliferation And Invasion, Yu-Kai Huang, Tzu-Ming Wang, Chi-Yu Chen, Chia-Yang Li, Shu-Chi Wang, Khushboo Irshad, Yuan Pan, Kun-Che Chang

Faculty, Staff and Student Publications

High-grade gliomas, including glioblastoma multiforme (GBM), continue to be a leading aggressive brain tumor in adults, marked by its rapid growth and invasive nature. Aldehyde dehydrogenase 1 family, member A1 (ALDH1A1), an enzyme, plays a significant role in tumor progression, yet its function in high-grade gliomas is still poorly investigated. In this study, we evaluated ALDH1A1 levels in clinical samples of GBM. We also assessed the prognostic significance of ALDH1A1 expression in GBM and LGG (low grade glioma) patients using TCGA (The Cancer Genome Atlas) database analysis. The MTT and transwell assays were utilized to examine cell growth and the …

Emergency Physicians Spend More Time Caring For Patients Who Prefer A Language Other Than English Which May Not Be Accounted For In Reimbursement Structures, Martin A Reznek, Jennifer Edwards, Sean S Michael, Jacqueline Furbacher, Alexandra Sanseverino, Payal K Modi, Kevin A Kotkowski, Celine Larkin

Faculty, Staff and Student Publications

Background: Emergency departments increasingly serve patients who prefer a language other than English. Honoring patients' language preferences is crucial for quality and cultural appropriateness of care. We sought to assess whether time spent in caring for patients who preferred a language other than English differed from patients whose language preference was English. Secondarily, we sought to assess professional reimbursement across the two groups.

Methods: We retrospectively analyzed an existing dataset from a time-in-motion study that included direct observation measurements of emergency physicians' time spent during patient encounters. Our primary outcome was physician time spent conducting patient care, comparing patients who …

Does Time To Initiation Of Adjuvant Radiotherapy Affect Reconstruction Outcomes After Endoscopic Resection Of Skull Base Malignancies?, Franco Rubino, Bledi Brahimaj, Ehab Y Hanna, Shirley Y Su, Jack Phan, David R Grosshans, Franco Demonte, Shaan M Raza

Faculty, Staff and Student Publications

No abstract provided.

Menin Inhibitors In Pediatric Acute Leukemia: A Comprehensive Review And Recommendations To Accelerate Progress In Collaboration With Adult Leukemia And The International Community, Branko Cuglievan, Hagop Kantarjian, Jeffrey E Rubnitz, Todd M Cooper, C Michel Zwaan, Jessica A Pollard, Courtney D Dinardo, Tapan M Kadia, Erin Guest, Nicholas J Short, David Mccall, Naval Daver, Cesar Nunez, Fadi G Haddad, Miriam Garcia, Kapil N Bhalla, Abhishek Maiti, Samanta Catueno, Warren Fiskus, Bing Z Carter, Amber Gibson, Michael Roth, Sajad Khazal, Priti Tewari, Hussein A Abbas, Wallace Bourgeois, Michael Andreeff, Neerav N Shukla, Danh D Truong, Jeremy Connors, Joseph A Ludwig, Janine Stutterheim, Elisabeth Salzer, Kristian L Juul-Dam, Koji Sasaki, Kris M Mahadeo, Sarah K Tasian, Gautam Borthakur, Samantha Dickson, Nitin Jain, Elias Jabbour, Soheil Meshinchi, Guillermo Garcia-Manero, Farhad Ravandi, Eytan M Stein, E Anders Kolb, Ghayas C Issa

Faculty, Staff and Student Publications

Aberrant expression of HOX and MEIS1 family genes, as seen in KMT2A-rearranged, NUP98-rearranged, or NPM1-mutated leukemias leads to arrested differentiation and leukemia development. HOX family genes are essential gatekeepers of physiologic hematopoiesis, and their expression is regulated by the interaction between KMT2A and menin. Menin inhibitors block this interaction, downregulate the abnormal expression of MEIS1 and other transcription factors and thereby release the differentiation block. Menin inhibitors show significant clinical efficacy against KMT2A-rearranged and NPM1-mutated acute leukemias, with promising potential to address unmet needs in various pediatric leukemia subtypes. In this collaborative initiative, pediatric and adult hematologists/oncologists, and stem cell …

Il-22 Resolves Masld Via Enterocyte Stat3 Restoration Of Diet-Perturbed Intestinal Homeostasis, Peng Zhang, Junlai Liu, Allen Lee, Irene Tsaur, Masafumi Ohira, Vivian Duong, Nicholas Vo, Kosuke Watari, Hua Su, Ju Youn Kim, Li Gu, Mandy Zhu, Shabnam Shalapour, Mojgan Hosseini, Gautam Bandyopadhyay, Suling Zeng, Cristina Llorente, Haoqi Nina Zhao, Santosh Lamichhane, Siddharth Mohan, Pieter C Dorrestein, Jerrold M Olefsky, Bernd Schnabl, Pejman Soroosh, Michael Karin

Faculty, Staff and Student Publications

The exponential rise in metabolic dysfunction-associated steatotic liver disease (MASLD) parallels the ever-increasing consumption of energy-dense diets, underscoring the need for effective MASLD-resolving drugs. MASLD pathogenesis is linked to obesity, diabetes, "gut-liver axis" alterations, and defective interleukin-22 (IL-22) signaling. Although barrier-protective IL-22 blunts diet-induced metabolic alterations, inhibits lipid intake, and reverses microbial dysbiosis, obesogenic diets rapidly suppress its production by small intestine-localized innate lymphocytes. This results in STAT3 inhibition in intestinal epithelial cells (IECs) and expansion of the absorptive enterocyte compartment. These MASLD-sustaining aberrations were reversed by administration of recombinant IL-22, which resolved hepatosteatosis, inflammation, fibrosis, and insulin resistance. Exogenous …

Methods For Pragmatic Randomized Clinical Trials Of Pain Therapies: Immpact Statement, David Hohenschurz-Schmidt, Dan Cherkin, Andrew S C Rice, Robert H Dworkin, Dennis C Turk, Michael P Mcdermott, Matthew J Bair, Lynn L Debar, Robert R Edwards, Scott R Evans, John T Farrar, Robert D Kerns, Michael C Rowbotham, Ajay D Wasan, Penney Cowan, Mckenzie Ferguson, Roy Freeman, Jennifer S Gewandter, Ian Gilron, Hanna Grol-Prokopczyk, Smriti Iyengar, Cornelia Kamp, Barbara I Karp, Bethea A Kleykamp, John D Loeser, Sean Mackey, Richard Malamut, Ewan Mcnicol, Kushang V Patel, Kenneth Schmader, Lee Simon, Deborah J Steiner, Christin Veasley, Jan Vollert

Faculty, Staff and Student Publications

Pragmatic, randomized, controlled trials hold the potential to directly inform clinical decision making and health policy regarding the treatment of people experiencing pain. Pragmatic trials are designed to replicate or are embedded within routine clinical care and are increasingly valued to bridge the gap between trial research and clinical practice, especially in multidimensional conditions, such as pain and in nonpharmacological intervention research. To maximize the potential of pragmatic trials in pain research, the careful consideration of each methodological decision is required. Trials aligned with routine practice pose several challenges, such as determining and enrolling appropriate study participants, deciding on the …

Astrocyte-Induced Cdk5 Expedites Breast Cancer Brain Metastasis By Suppressing Mhc-I Expression To Evade Immune Recognition, Arseniy E Yuzhalin, Frank J Lowery, Yohei Saito, Xiangliang Yuan, Jun Yao, Yimin Duan, Jingzhen Ding, Sunil Acharya, Chenyu Zhang, Abigail Fajardo, Hao-Nien Chen, Yongkun Wei, Yutong Sun, Lin Zhang, Yi Xiao, Ping Li, Philip L Lorenzi, Jason T Huse, Huihui Fan, Zhongming Zhao, Mien-Chie Hung, Dihua Yu

Faculty, Staff and Student Publications

Brain metastases (BrMs) evade the immune response to develop in the brain, yet the mechanisms of BrM immune evasion remains unclear. This study shows that brain astrocytes induce the overexpression of neuronal-specific cyclin-dependent kinase 5 (Cdk5) in breast cancer-derived BrMs, which facilitates BrM outgrowth in mice. Cdk5-overexpressing BrMs exhibit reduced expression and function of the class I major histocompatibility complex (MHC-I) and antigen-presentation pathway, which are restored by inhibiting Cdk5 genetically or pharmacologically, as evidenced by single-cell RNA sequencing and functional studies. Mechanistically, Cdk5 suppresses MHC-I expression on the cancer cell membrane through the Irf2bp1-Stat1-importin α-Nlrc5 pathway, enabling BrMs to …