Digital Commons Network^™

Development And Pilot Testing Of An Addiction Clinic-Based Pre-Exposure Prophylaxis Uptake And Adherence Intervention For Women With Substance Use Disorders: Protocol For A Pilot Randomized Trial, Angela M Heads, Diane Santa Maria, Mandy J Hill, Robert Suchting, Kimberly N Evans, Zaneta Gaul, Luba Yammine, Constanza De Dios, Joy M Schmitz

Faculty, Staff and Student Publications

Background: Black and Hispanic women in the United States continue to bear disproportionate incidence of HIV related to sexual transmission and injection drug use. Specifically, women with substance use disorders (SUDs) are more likely to engage in vaginal or anal condomless sex associated with HIV transmission. Pre-exposure prophylaxis (PrEP) is a highly effective HIV prevention tool but is not widely used by racial or ethnic minority women. Effective interventions for engaging women with SUDs in HIV prevention interventions that are culturally appropriate and, therefore, more appealing to racial or ethnic minority women with SUDs are critically needed.

Objective: This 3-phased …

Personalizing Neoadjuvant Chemotherapy Regimens For Triple-Negative Breast Cancer Using A Biology-Based Digital Twin, Chase Christenson, Chengyue Wu, David A Hormuth, Jingfei Ma, Clinton Yam, Gaiane M Rauch, Thomas E Yankeelov

Faculty, Staff and Student Publications

Despite advances triple negative breast cancer treatment, ~50% of patients will not achieve a pathological complete response prior to surgery with standard of care neoadjuvant therapy (NAT). We hypothesize that personalized regimens for NAT could significantly improve patient outcomes, which we address with a patient-specific digital twin framework. This framework is established by calibrating a biology-based model to longitudinal magnetic resonance images with approximate Bayesian computation. We then apply optimal control theory to either (1) reduce the final tumor cell number with equivalent dose, or (2) reduce the total dose of NAT with equivalent response. For (1), the personalized regimens …

A Hierarchy Of Pdz Domain Scaffolding Proteins Clusters The Kv1 K+ Channel Protein Complex At The Axon Initial Segment, Wei Zhang, Victoria L Palfini, Yu Wu, Xiaoyun Ding, Allison J Melton, Yudong Gao, Yuki Ogawa, Matthew N Rasband

Faculty, Staff and Students Publications

Action potentials are initiated and modulated at the axon initial segment (AIS) by highly clustered ion channels. Voltage-gated Kv1 potassium channels underlie most outward AIS K+ current. AIS Kv1 channels exist in a large protein complex including ADAM22, Caspr2, and LGI1. However, their clustering mechanisms remain unknown. Because Kv1 channels have a highly conserved PDZ-binding motif, we used CRISPR-based genome editing to screen 18 PDZ domain-containing proteins identified in our previous AIS proximity proteome for their AIS localization. Among these, we found that the scaffolding proteins SCRIB and PSD93 are highly enriched at the AIS. Using CRISPR-mediated knockout, cell surface …

Cost-Effective Solutions For High-Throughput Enzymatic Dna Methylation Sequencing, Amy Longtin, Marina M. Watowich, Baptiste Sadoughi, Rachel M. Petersen, Sarah F. Brosnan, Kenneth Buetow, Qiuyin Cai, Cayo Biobank Research Unit, Vanderbilt University, Michael D. Gurven, James P. Higham, Heather M. Highland, Yi-Ting Huang, Hillard Kaplan, Thomas S. Kraft, Yvonne A. L. Lim, Jirong Long, Amanda D. Melin, Michael J. Montagne, Jamie Roberson, Kee Seong Ng, Michael L. Platt, India A. Schneider-Crease, Jonathan Stieglitz, Benjamin C. Trumble, Vivek Venkataraman, Ian J. Wallace, Jie Wu, Noah Snyder-Mackler, Angela Jones, Alexander G. Bick, Amanda J. Lea

ESI Publications

Characterizing DNA methylation patterns is important for addressing key questions in evolutionary biology, development, geroscience, and medical genomics. While costs are decreasing, whole-genome DNA methylation profiling remains prohibitively expensive for most population-scale studies, creating a need for cost-effective, reduced representation approaches (i.e., assays that rely on microarrays, enzyme digests, or sequence capture to target a subset of the genome). Most common whole genome and reduced representation techniques rely on bisulfite conversion, which can damage DNA resulting in DNA loss and sequencing biases. Enzymatic methyl sequencing (EM-seq) was recently proposed to overcome these issues, but thorough benchmarking of EM-seq combined with …

Renal Denervation Improves Cardiac Function And Exercise Duration In A Miniswine Model Of Heart Failure With Preserved Ejection Fraction, David J. Lefer, Thomas E. Sharp, Amy L. Scarborough, Amelia G. Haydel, Sanjiv J. Shah, Zhen Li, Traci T. Goodchild

School of Medicine Faculty Publications

Aims: Overactivity of the sympathetic nervous system is a common underlying mechanism in development and progression of several heart failure with preserved ejection fraction (HFpEF) comorbidities. Decreasing renal sympathetic nerve activity using catheter-based renal denervation (RDN) systems have shown efficacy in treating resistant hypertension and cardiac dysfunction in heart failure with reduced ejection fraction. The purpose of this study was to determine if modulation of renal sympathetic nerve activity by RDN improves cardiac function and exercise tolerance in a clinically-relevant minipig model of cardiometabolic HFpEF. Methods and results: Multiple HFpEF comorbidities were induced in adult female Göttingen minipigs by mineralocorticoid …

Post-Recovery Viral Shedding Shapes Wastewater-Based Epidemiological Inferences, Tin Phan, Samantha Brozak, Bruce Pell, Stanca M Ciupe, Ruian Ke, Ruy M Ribeiro, Anna Gitter, Kristina D Mena, Alan S Perelson, Yang Kuang, Fuqing Wu

Faculty, Staff and Student Publications

Background: The prolonged viral shedding from the gastrointestinal tract is well documented for numerous pathogens, including SARS-CoV-2. However, the impact of prolonged viral shedding on epidemiological inferences using wastewater data is not yet fully understood.

Methods: To gain a better understanding of this phenomenon at the population level, we extended a wastewater-based modeling framework that integrates viral shedding dynamics, viral load data in wastewater, case report data, and an epidemic model.

Results: Our results indicate that as an outbreak progresses, the viral load from recovered individuals gradually becomes predominant, surpassing that from the infectious population. This phenomenon leads to a …

Predicting Pathologic ≥N2 Disease In Women With Breast Cancer, Kerollos Nashat Wanis, Wenli Dong, Yu Shen, Funda Meric-Bernstam, Taiwo Adesoye, Henry M Kuerer, Abigail S Caudle, Nina Tamirisa, Sarah M Desnyder, Susie X Sun, Isabelle Bedrosian, Puneet Singh, Solange E Cox, Kelly K Hunt, Rosa F Hwang

Faculty, Staff and Student Publications

The distinction between pN1 and ≥pN2 breast cancer impacts treatment decisions. Using data from a single institution on women with cN0 invasive breast cancer who were treated with upfront surgery, had 1-3 positive SLNs, and underwent completion ALND, we used gradient boosted trees (XGBoost) to develop a model for predicting ≥pN2 disease using clinicopathologic variables. Model performance was tested in a held-out subsample (20%) and validated using data from the National Cancer Database (NCDB). Of 3574 patients with cN0 breast cancer, 587 underwent upfront surgery and had 1-3 positive SLNs. Of these, 415 (70.7%) underwent completion ALND, with 64 (15.4%) …

Whole Genome Sequencing Identifies Monogenic Disease In 56.1% Of Families With Early-Onset Steroid-Resistant Nephrotic Syndrome, Eman Ramadan

Pharmacy

Genetic causes of steroid-resistant-nephrotic-syndrome (SRNS) represent a rapidly growing number of monogenic diseases. The reported diagnostic yield of various studies applying genetic panels and exome-sequencing to diagnose SRNS is usually < 30%. We performed genome-sequencing in a cohort of Egyptian SRNS patients. We recruited 47 SRNS patients belonging to 41 unrelated families [28 males/19 females; median (range): 6 (0.5-22 years)]. We established a pipeline for genome sequencing, bioinformatics analysis, variant curation and protein modeling at the Egypt Center for Research and Regenerative Medicine (ECRRM). Disease-causing variants were detected in 27/47 patients (57.4%) belonging to 23/41 families (56.1%), including nine novel variants in NPHS1, NPHS2, COL4A3, MYO1E, NUP93, PLCE1, PODXL, SMARCAL1 and WT1. Novel variants were confirmed by Sanger sequencing and were segregated in families of affected patients. NPHS2 was the most common causative gene in 8/23 (34.8%) of confirmed families, followed by NPHS1, WT1, and SMARCAL1 in 2/23 families (8.7%) each. All detected missense variants were evaluated through protein modeling and were predicted deleterious. Our study expanded the spectrum of SRNS disease-causing variants and revealed a monogenic cause in 56.1% of investigated families. In our cohort, no deep intronic or regulatory variants were detected by genome-sequencing. Pursuing genetic diagnosis in SRNS patients is crucial to inform clinical decision making, genetic counseling, transplantation strategy and prenatal diagnosis thus improving clinical outcome of affected patients.

A Review Of Medical Ethics In Orthopaedic Surgery: Current Foci And Future Considerations, Ryan X Lam, Zhi Mei Sonia He, Ruhi Thapar, Maggie Wang, Dion G Birhiray, Matthew Milad, Lara Ouellette, Umar Ghilzai, Tucker J Cushing, M Brent Price, Brenden B Ronna, Omar H Atassi, Christopher H Perkins, John R Dawson, William M Granberry, Melvyn A Harrington, Douglas R Dirschl, Lorenzo R Deveza

Library Staff Publications

Medical ethics education is a required component of orthopaedic surgery resident training per the Accreditation Council for Graduate Medical Education (ACGME) guidelines, although no standardized curriculum currently exists.

Beyond the 4 principles of bioethics (autonomy, beneficence, nonmaleficence, justice), additional ethical concepts relevant to orthopaedic care include utilitarianism, deontology, virtue ethics, moral intuitionism, microethics, and narrative ethics.

Ethical themes identified in the literature relevant to orthopaedic surgery include the ethics involved in medical decision-making, use of new technologies, caring for vulnerable patients, performing high-stakes procedures, the impacts of trainee status on patient care, and patient attitude regarding conflict of interest.

Ethical …

The Joint Association Of Diet Quality And Sleep Regularity With Incident Cardiovascular Disease In The Multi-Ethnic Study Of Atherosclerosis, Kaitlin S Potts, Claire Veldkamp, Alexis C Wood, Erin D Michos, Raymond Noordam, Tianyi Huang, Susan Redline, Heming Wang

Children’s Nutrition Research Center Staff Publications

Background/objectives: Diet quality and sleep regularity both influence cardiovascular disease (CVD) risk and may influence each other, but there is scarce evidence for their joint or interacting associations in relation to CVD. We assessed these associations in the Multi-Ethnic Study of Atherosclerosis (MESA).

Methods: Participants free of CVD with valid diet and sleep measures in 2010-2013 were included and followed through 2020 for detection of incident CVD (188 events detected over 8.8 years among 1782 participants; 55% women). Sleep timing and duration regularity were assessed via the intra-individual SD of sleep onset time and duration across 5- to 7-day actigraphy. …

A Near Telomere-To-Telomere Phased Reference Assembly For The Male Mountain Gorilla, David R Nelson, Richard Muvunyi, Khaled M Hazzouri, Jean-Claude Tumushime, Gaspard Nzayisenga, Nziza Julius, Wim Meert, Latifa Karim, Wouter Coppieters, Katherine M Munson, Dongahn Yoo, Evan E Eichler, Kourosh Salehi-Ashtiani, Jean-Claude Twizere

Faculty, Staff and Students Publications

The endangered mountain gorilla, Gorilla beringei beringei, faces numerous threats to its survival, highlighting the urgent need for genomic resources to aid conservation efforts. Here, we present a near telomere-to-telomere, haplotype-phased reference genome assembly for a male mountain gorilla generated using PacBio HiFi (26.77× ave. coverage) and Oxford Nanopore Technologies (52.87× ave. coverage) data. The resulting non-scaffolded assembly exhibits exceptional contiguity, with contig N50 of ~95 Mbp for the combined pseudohaplotype (3,540,458,497 bp), 56.5 Mbp (3.1 Gbp) and 51.0 Mbp (3.2 Gbp) for each haplotype, an average QV of 65.15 (error rate = 3.1 × 10−7), and a BUSCO …

The Perk/Atf4 Pathway Is Required For Metabolic Reprogramming And Progressive Lung Fibrosis, Jyotsana Pandey, Jennifer L Larson-Casey, Mallikarjun H Patil, Chao He, Nisarat Pinthong, A Brent Carter

Faculty, Staff and Students Publications

Asbestosis is a prototypical type of fibrosis that is progressive and does not resolve. ER stress is increased in multiple cell types that contribute to fibrosis; however, the mechanism(s) by which ER stress in lung macrophages contributes to fibrosis is poorly understood. Here, we show that ER stress resulted in protein kinase RNA-like ER kinase (PERK; Eif2ak3) activation in humans with asbestosis. Similar results were seen in asbestos-injured mice. Mice harboring a conditional deletion of Eif2ak3 were protected from fibrosis. Lung macrophages from asbestosis individuals had evidence of metabolic reprogramming to fatty acid oxidation (FAO). Eif2ak3fl/fl mice had increased oxygen …

Comprehensive Evaluation Of Phosphoproteomic-Based Kinase Activity Inference, Sophia Müller-Dott, Eric J Jaehnig, Khoi Pham Munchic, Wen Jiang, Tomer M Yaron-Barir, Sara R Savage, Martin Garrido-Rodriguez, Jared L Johnson, Alessandro Lussana, Evangelia Petsalaki, Jonathan T Lei, Aurelien Dugourd, Karsten Krug, Lewis C Cantley, D R Mani, Bing Zhang, Julio Saez-Rodriguez

Faculty, Staff and Students Publications

Kinases regulate cellular processes and are essential for understanding cellular function and disease. To investigate the regulatory state of a kinase, numerous methods have been developed to infer kinase activities from phosphoproteomics data using kinase-substrate libraries. However, few phosphorylation sites can be attributed to an upstream kinase in these libraries, limiting the scope of kinase activity inference. Moreover, inferred activities vary across methods, necessitating evaluation for accurate interpretation. Here, we present benchmarKIN, an R package enabling comprehensive evaluation of kinase activity inference methods. Alongside classical perturbation experiments, benchmarKIN introduces a tumor-based benchmarking approach utilizing multi-omics data to identify highly active …

Untargeted Proteomics Enables Ultra-Rapid Variant Prioritisation In Mitochondrial And Other Rare Diseases, Daniella H Hock, Nikeisha J Caruana, Liana N Semcesen, Nicole J Lake, Luke E Formosa, Sumudu S C Amarasekera, Tegan Stait, Simone Tregoning, Leah E Frajman, Adam M Bournazos, David R L Robinson, Megan Ball, Boris Reljic, Bryony Ryder, Mathew J Wallis, Anand Vasudevan, Cara Beck, Heidi Peters, Joy Lee, Natalie B Tan, Mary-Louise Freckmann, Mitomdt Diagnostic Network For Genomics And Omics, Vasiliki Karlaftis, Chantal Attard, Paul Monagle, Amanda Samarasinghe, Rosie Brown, Weimin Bi, Monkol Lek, Robert Mcfarland, Robert W Taylor, Michael T Ryan, Sandra T Cooper, Zornitza Stark, John Christodoulou, Alison G Compton, David R Thorburn, David A Stroud

Faculty, Staff and Students Publications

Background: Only half of individuals with suspected rare diseases receive a genetic diagnosis following genomic testing. A genetic diagnosis allows access to appropriate care, restores reproductive confidence and reduces the number of potentially unnecessary interventions. A major barrier is the lack of disease agnostic functional tests suitable for implementation in routine diagnostics that can provide evidence supporting pathogenicity of novel variants, especially those refractory to RNA sequencing.

Methods: Focusing on mitochondrial disease, we describe an untargeted mass-spectrometry based proteomics pipeline that can quantify proteins encoded by > 50% of Mendelian disease genes and > 80% of known mitochondrial disease genes in clinically …

Current Paradigm And Futuristic Vision On New-Onset Diabetes And Pancreatic Cancer Research, Russell Moreland Iii, Abigail Arredondo, Anupam Dhasmana, Swati Dhasmana, Shabia Shabir, Asfia Siddiqua, Bonny Bannerjee, Murali Yallapu, Stephen Behrman, Subhash Chauhan, Sheema Khan

School of Medicine Publications

New-onset diabetes (NOD) has emerged as a potential early indicator of pancreatic cancer (PC), necessitating a refined clinical approach for risk assessment and early detection. This study discusses critical gaps in understanding the NOD-PC relationship and proposes a multifaceted approach to enhance early detection and risk assessment. We present a comprehensive clinical workflow for evaluating NOD patients, incorporating biomarker discovery, genetic screening, and AI-driven imaging to improve PC risk stratification. While existing models consider metabolic factors, they often overlook germline genetic predispositions that may influence disease development. We propose integrating germline genetic testing to identify individuals carrying pathogenic variants in …

Multicomponent Parenteral Lipid Emulsions Do Not Prevent Liver Injury In Neonatal Pigs With Obstructive Cholestasis, Greg Guthrie, Caitlin Vonderohe, Valeria Meléndez Hebib, Barbara Stoll, Douglas Burrin

Children’s Nutrition Research Center Staff Publications

Biliary atresia (BA) is a pediatric liver disease that often necessitates parenteral nutrition (PN) to support growth due to impaired liver function. While soy-based lipid emulsions (SLE) are commonly used in PN, they may contribute to cholestatic liver injury. In contrast, mixed lipid emulsions (MLE) show promise in preventing cholestasis in infants without BA, potentially by restoring bile flow. However, their effectiveness in patients of complete bile duct obstruction, as seen in BA, remains uncertain. To explore the potential benefits of MLE in BA, we utilized a neonatal pig model of bile duct ligation (BDL). Pigs underwent either BDL or …

Characterization Of Immunogenicity Of Hiv Mrna Vaccine In Humanized Mice, Omoyeni Precious Adejare

Biotechnology Theses

Human Immunodeficiency Virus (HIV) remains a leading global cause of mortality. Despite decades of research, a definitive cure or an effective vaccine for HIV infection has yet to be discovered. The major target for HIV vaccine development is the envelope (Env) trimeric protein that is responsible for host cell attachment and fusion. This comprises gp120 and the transmembrane gp41. Gp140, a truncated form of gp160(full envelope trimer) lacks the transmembrane and cytoplasmic domains of gp41, closely mimics the native HIV envelope has been shown to enhance the induction of broadly neutralizing antibodies (BnAbs) when used as protein vaccine in previous …

Reducing Surgery For Pediatric Posttonsillectomy Hemorrhage Using Tranexamic Acid: A Quality Improvement Initiative, Laura A. Petrauskas, Janavi Sethurathnam, Ansley J. Kunnath, Rahul K. Sharma, John Ceremsak, Ryan H. Belcher, James D. Phillips, Jay A. Werkhaven, Amy S. Whigham, Lyndy J. Wilcox, Christopher T. Wootten, Frank W. Virgin, Jason S. Park

School of Medicine Faculty Publications

Objective: Evaluate the use of tranexamic acid (TXA) and observation as a management option for pediatric patients presenting with posttonsillectomy hemorrhage (PTH). Study Design: Retrospective analysis of a prospectively implemented quality improvement initiative with a historical control comparison group. Setting: Tertiary children's hospital. Methods: Patients < 18 years of age who underwent adenotonsillectomy (AT) and returned to the Emergency Department for PTH were included. Patients who were stable without large volume or active bleeding were given intravenous TXA and admitted for overnight observation. Data were compared in a before-and-after analysis: preprotocol (April 2022 to March 2023) versus postprotocol (April 2023 to March 2024). For cost-effectiveness analysis, we analyzed aggregated claims data from a commercial claims database. Results: Preprotocol 1800 adenotonsillectomies were performed, and 40 procedures were performed for control of hemorrhage (2.2 per 100 AT). Postprotocol 2356 adenotonsillectomies were performed, and 30 procedures were performed to control hemorrhage (1.3 per 100 AT) showing a significant reduction in return to the operating room (relative risk [RR] = 0.59, 95% confidence interval [CI] [0.358, 0.916], P-value.020). There were no reported adverse events attributable to TXA. An estimated 21 surgeries were avoided, and 26 additional patients were observed in the hospital during the postprotocol period, for an estimated net cost savings of $174,970. Conclusion: The implementation of a standardized TXA protocol significantly reduced the need for return to the operating room for PTH in pediatric patients, without complications and with net cost savings to the health care system.

From M. Chelonae To M. Immunogenum: A Rare Case Of Dual Nontuberculous Mycobacterial Infection, Ifeanyi Kingsley Uche, Nathalia Simonetti, Andrea Murina

School of Medicine Faculty Publications

No abstract provided.

Global Dna Methylation Differences Involving Germline Structural Variation Impact Gene Expression In Pediatric Brain Tumors, Fengju Chen, Yiqun Zhang, Wei Li, Fritz J Sedlazeck, Lanlan Shen, Chad J Creighton

Children’s Nutrition Research Center Staff Publications

The extent of genetic variation and its influence on gene expression across multiple tissue and cellular contexts is still being characterized, with germline Structural Variants (SVs) being historically understudied. DNA methylation also represents a component of normal germline variation across individuals. Here, we combine germline SVs (by short-read sequencing) with tumor DNA methylation across 1292 pediatric brain tumor patients. For thousands of methylation probes for CpG Islands (CGIs) or enhancers, rare and common SV breakpoints upstream or downstream associate with differential methylation in tumors spanning various histologic types, a significant subset involving genes with SV-associated differential expression. Cancer predisposition genes …

Imaging Hallmarks Of Idiopathic Intracranial Hypertension And Insights Into Pathogenesis, Albalooshy Basimah, Scott Faro, Hsiangkuo Yuan, Kiran Talekar, Prabath Mondel, Enchao Qiu, Joga Chaganti

Department of Radiology Faculty Papers

Idiopathic Intracranial hypertension (IIH), also referred to as pseudotumor cerebri, is a term used to describe increased intracranial pressure in the absence of a known identifiable secondary cause. Despite advancements of neuroimaging techniques, imaging of the pathological underpinnings in the diagnosis of IIH has been limited. Although the causation of IIH has been ascribed to increased Cerebrospinal Fluid production and disordered drainage through the dural sinuses, new evidence shows that the glymphatic system which is an alternate pathway of drainage is likely to play a pivotal role. In this review, we address the pathophysiological underpinnings in the causation of IIH …

Antifreezing Hydrogels From Mechanisms, Strategies, To Applications, Jie Zheng, Dong Zhang, Hong Cheng, Yanxian Zhang

University Research

Antifreezing hydrogels have emerged as an innovative solution for maintaining functional performance and mechanical integrity in subzero environments, offering a robust alternative to traditional water-free antifreezing materials that often fail under wet and cold conditions. These water-rich hydrogels leverage their porous, crosslinked, polymeric networks, which serve as the structural basis for implementing two parallel strategies: the incorporation of antifreezing additives (peptides/proteins, salts, ionic liquids, and organics) and the meticulous engineering of polymer systems and network structures for manipulating the water–ice phase equilibrium to significantly enhance antifreezing properties. This review synthesizes recent findings to provide a fundamental overview of the important …

A Multi-Level Gene-Diet Interaction Analysis Of Fish Oil And 14 Polyunsaturated Fatty Acid Traits Identifies The Fads And Gpr12 Loci, Susan Adanna Ihejirika, Alexandra Huong Chiang, Aryaman Singh, Eunice Stephen, Han Chen, Kaixiong Ye

Faculty, Staff and Student Publications

Fish oil supplements (FOS) are known to alter circulating levels of polyunsaturated fatty acids (PUFAs) but in a heterogeneous manner across individuals. These varied responses may result from unidentified gene-FOS interactions. To identify genetic factors that interact with FOS to alter the circulating levels of PUFAs, we performed a multi-level genome-wide interaction study (GWIS) of FOS on 14 plasma measurements in 200,060 unrelated European-ancestry individuals from the UK Biobank. From our single-variant tests, we identified genome-wide significant interacting SNPs (p < 5 × 10-8) in the FADS1-FADS2 gene cluster for total omega-3, omega-3%, docosapentaenoic acid (DHA), DHA%, and the omega-6 to omega-3 ratio. Among the interaction signals for omega-3%, the lead SNP, rs35473591 (C>CT, CT allele frequency = 0.34), had a lower association effect size in the FOS-taking group (β = 0.35 for …

A Review Of Mirvetuximab Soravtansine-Gynx In Folate Receptor Alpha-Expressing Platinum-Resistant Ovarian Cancer, Judith A Smith, Patrick Medina, Mary Miao, Kathleen N Moore

Faculty, Staff and Student Publications

Purpose: To evaluate the pharmacology, efficacy, safety, and dosing and administration considerations (including adjusted ideal body weight [AIBW] dosing) for mirvetuximab soravtansine-gynx, a first-in-class folate receptor alpha (FRα)-directed antibody-drug conjugate for platinum-resistant ovarian cancer (PROC).

Summary: A literature search was conducted in PubMed using the terms "ovarian cancer" and "mirvetuximab soravtansine" of articles published from inception to April 16, 2024. Relevant publications, abstracts, and clinical trials were reviewed. Mirvetuximab soravtansine-gynx is dosed at 6 mg/kg AIBW every 3 weeks and comprises an FRα-binding antibody, a hydrophilic disulfide linker, and a maytansinoid DM4 payload. Mirvetuximab soravtansine-gynx binds to FRα, which induces …

A Multicenter, Propensity Score-Matched Analysis Of Functional Outcomes And Recanalization Success With Or Without Trevo For Medium And Distal Vessel Occlusion, James E Siegler, Manisha Koneru, Hamza Shaikh, Hamza Adel Salim, Basel Musmar, Nimer Adeeb, Vivek Yedavalli, Motaz Daraghma, Kareem El Naamani, Nils Henninger, Sri Hari Sundararajan, Anna Luisa Kühn, Sherief Ghozy, Luca Scarcia, Benjamin Yq Tan, Jeremy J Heit, Robert W Regenhardt, Rami Z Morsi, Tareq Kass-Hout, Nicholas Vigilante, Nicole M Cancelliere, Joshua D Bernstock, Aymeric Rouchaud, Jens Fiehler, Sunil A Sheth, Muhammed Amir Essibayi, Ajit S Puri, Christian Dyzmann, Marco Colasurdo, Xavier Barreau, Leonardo Renieri, João Pedro Filipe, Pablo Harker, Răzvan Alexandru Radu, Thomas R Marotta, Julian Spears, Takahiro Ota, Ashkan Mowla, Pascal Jabbour, Arundhati Biswas, Frédéric Clarençon, Piers Klein, Mohamad Abdalkader, Thanh N Nguyen, Ricardo Varela, Amanda Baker, David Altschul, Nestor R Gonzalez, Markus A Möhlenbruch, Vincent Costalat, Benjamin Gory, Christian Paul Stracke, Constantin Hecker, Christoph J Griessenauer, David S Liebeskind, Alessandro Pedicelli, Andrea M Alexandre, Illario Tancredi, Tobias D Faizy, Erwah Kalsoum, Boris Lubicz, Aman B Patel, Vitor Mendes Pereira, Jane Khalife, Ankit Rana, Adrien Guenego, Adam A Dmytriw, Mad Mt Investigators

Faculty, Staff and Student Publications

BackgroundEndovascular therapy (EVT) for stroke due to distal or medium vessel occlusion (DMVO) is safe. Due to the distinct anatomical characteristics of DMVOs, further evaluation of EVT is crucial to determine which devices may yield better outcomes.MethodsA retrospective analysis of adults with DMVO treated in 37 centers (11 countries) was queried. The primary outcome of favorable shift in 90-day modified Rankin Scale (mRS) was compared between patients treated with Trevo versus other devices on first pass using 1:1 propensity score matching (PSM) with multivariable adjustment. Secondary outcomes included the number of pass attempts, final thrombolysis in cerebral infarction (TICI) score …

In Vivo Crispr Activation Screen Identifies Acyl-Coa-Binding Protein As A Driver Of Bone Metastasis, Hongqi Teng, Qinglei Hang, Caishang Zheng, Yuelong Yan, Shaomin Liu, Yang Zhao, Yalan Deng, Litong Nie, Weiche Wu, Marisela Sheldon, Zachary Yu, Wei Shi, Jianxuan Gao, Chenling Meng, Consuelo Martinez, Jie Zhang, Fan Yao, Yutong Sun, Di Zhao, Boyi Gan, Tong Meng, Li Ma

Faculty, Staff and Student Publications

One of the most common sites of cancer metastasis is to the bone. Bone metastasis is associated with substantial morbidity and mortality, and current therapeutic interventions remain largely palliative. Metastasizing tumor cells need to reprogram their metabolic states to adapt to the nutrient environment of distant organs; however, the role and translational relevance of lipid metabolism in bone metastasis remain unclear. Here, we used an in vivo CRISPR activation screening system coupled with positive selection to identify acyl-coenzyme A (CoA) binding protein (ACBP) as a bone metastasis driver. In nonmetastatic and weakly metastatic cancer cells, overexpression of wild-type ACBP, but …

Simultaneous Targeting Of Tumor Cells And Tumor-Associated Macrophages To Reprogram Glioblastoma Using Trypsinized Extracellular Vesicles Carrying Tumor Suppressive Microrna, Grace H Nguyen, Minhye Noh, Jin Muk Kang, Alexandra A Miller, Minxin Huang, Jiyeon Kim, Jeong-Yeon Lee, Sangwoon Chung, Hongyu Wang, George A Calin, Cynthia Ju, Holger K Eltzschig, Yeshavanth Banasavadi-Siddegowda, Zhongming Zhao, Ji Young Yoo, Tae Jin Lee

Faculty, Staff and Student Publications

Glioblastoma (GBM) remains difficult to treat due to poor drug delivery across the blood-brain barrier and an immunosuppressive tumor microenvironment (TME). Tumor-suppressive microRNAs (miRNAs) offer a promising strategy to reprogram both tumor cells and the TME, but inefficient delivery systems limit their clinical application. We previously reported that tumor-suppressive miR-138 regresses tumor growth in preclinical GBM models. Here, we demonstrate that trypsin digestion of extracellular vesicles (EVs) enhances labeling efficiency with folate (FA), enhancing selective targeting of folate receptor (FR)-positive GBM cells and enabling simultaneous targeting of tumor-associated macrophages (TAMs). FA-labeled trypsinized EVs (tEVs) loaded with miR-138 inhibit tumor growth, …

Correction: Targeting Of Epigenetic Co-Dependencies Enhances Anti-Aml Efficacy Of Menin Inhibitor In Aml With Mll1-R Or Mutant Npm1, Warren Fiskus, Christopher P Mill, Christine Birdwell, John A Davis, Kaberi Das, Steffen Boettcher, Tapan M Kadia, Courtney D Dinardo, Koichi Takahashi, Sanam Loghavi, Michael J Soth, Tim Heffernan, Gerard M Mcgeehan, Xinjia Ruan, Xiaoping Su, Christopher R Vakoc, Naval Daver, Kapil N Bhalla

Faculty, Staff and Student Publications

No abstract provided.

Emotional Contagion Of Fear And Joy From Humans To Horses Using A Combination Of Facial And Vocal Cues, Plotine Jardat, Shinya Yamamoto, Monamie Ringhofer, Noa Tanguy-Guillo, Céline Parias, Fabrice Reigner, Ludovic Calandreau, Léa Lansade

Faculty, Staff and Students Publications

Emotional contagion, the emotional state-matching of two individuals, has been documented in various species. Recent findings suggest emotional contagion could also take place between humans and domestic mammals. However, the range of targeted animal species and human emotions that have been studied is still limited, and the methodology to investigate emotional contagion in this context is not fully established. This study examined emotional contagion of fear and joy from humans to horses by measuring physiological (heart rate, infrared thermography) and behavioral responses (posture, laterality bias, facial expressions) to videos of human fear, joy, or neutral emotions. Horses (n = 45) …

Turning Analysis Into Action: Opportunities And Challenges In Implementing Wastewater Science For Public Health Decision-Making, Anna Gitter, Valeria Ruvalcaba, Katelyn Clark, Theresa Tran Carapucci, Fuqing Wu, Blake M Hanson, Jennifer Deegan, John Balliew, Eric Boerwinkle, Anthony W Maresso, Kristina D Mena

Faculty, Staff and Students Publications

In the 5 years since the emergence of the COVID-19 pandemic, the field of wastewater-based epidemiology (WBE) has dramatically expanded with programs implemented across the globe to monitor for SARS-CoV-2 and other viruses of public health concern. However, the best way to use wastewater surveillance data and inform local communities of the utility of wastewater science remains limited and sporadically discussed. Specifically, there is vague guidance regarding interpreting varying levels of viral loads in wastewater for public health significance. While collaborative efforts are key to implementing these community-specific wastewater surveillance programs, effectively using the data for public health decision-making still …