Digital Commons Network^™

Activity-Dependent Transit Dose Assessment In 192ir High-Dose-Rate Brachytherapy Surface Applicator Using Gafchromictm Ebt4 Film, Daniel Liu, Emily Draeger, Christopher J Tien, Fada Guan

Faculty, Staff and Student Publications

Purpose: To characterize the newly released GafChromicTM EBT4 film for transit dose measurement in high-dose rate brachytherapy (HDR-BT) surface applicators and to systematically investigate the relationship between transit dose and 192Ir source activity.

Methods: EBT4 film was used to measure dose at 3 mm depth from a horizontally oriented Leipzig-style surface applicator connected to a 192Ir HDR-BT remote afterloading unit. Transit dose was systematically characterized across eight different source activities ranging from 3.372 to 9.716 Ci (13,724 U to 39,544 U) using measurements with seven nominal dwell times (5-100 seconds, scaled to 10 Ci (40,700 U)). Transit dose was derived …

Utility Of Serum Matrix Metalloproteinase-7 As A Biomarker In Cholestatic Infants With Congenital Heart Disease, Sindhu Pandurangi, Michael E Kim, Nicolas Noriega, Bradley Conant, Jangdong Seo, Reena Mourya, Pranavkumar Shivakumar, Anna L Peters, Andrew Misfeldt, Meghan Chlebowski

Faculty, Staff and Student Publications

Background: Matrix metalloproteinase 7 (MMP-7) is a novel biomarker for diagnosis of biliary atresia (BA), the most common cholestatic liver disease in infancy. There is a pressing need to determine the utility of MMP-7 levels in infants with congenital heart disease (CHD) to avoid unnecessary invasive diagnostic procedures in this high-risk population. We investigated the utility of MMP-7 in discriminating BA from non-BA cholestasis in infants with CHD and whether MMP-7 elevation was present in infants requiring treatment for clinically significant PH.

Methods: This is a single-center cross-sectional study including infants < 180 days of age with cholestasis and serum MMP-7 levels collected from 2019 to 2023. Demographic data and descriptive statistics were summarized with medians with interquartile ranges and frequencies with percentages. Median MMP-7 levels were assessed via Wilcoxon rank-sum test.

Results: A total of 149 patients were included. Patients …

Pancreatic Cancer-Related Diabetes And Type 2 Diabetes Differ In Multiple Aspects Of Glucose Homeostasis, Frederico G S Toledo, Yisheng Li, Fuchenchu Wang, Melena D Bellin, Randall Brand, Kenneth Cusi, William Fisher, Yogish C Kudva, Walter G Park, Zeb I Saeed, Dhiraj Yadav, Robert V Considine, Sarah C Graham, Dana K Andersen, Jose Serrano, Mark O Goodarzi, Phil A Hart

Faculty, Staff and Student Publications

Aims/hypothesis: Pancreatic ductal adenocarcinoma-related diabetes mellitus (PDAC-DM) is a paraneoplastic syndrome with a poorly understood pathophysiology. PDAC-DM is often clinically confused with type 2 diabetes, resulting in delayed cancer detection and poorly individualised hyperglycaemia treatment. We investigated whether these forms of diabetes can be distinguished at the metabolic level.

Methods: Adults with either cancer treatment-naive PDAC-DM (n=28) or type 2 diabetes (n=97), and with diabetes onset within 3 years, underwent mixed-meal tolerance tests to investigate glucose metabolism. Outcomes included insulin sensitivity (Matsuda index), insulin secretion (insulinogenic index), beta cell function (oral disposition index), insulin clearance, and postprandial glucagon, glucagon-like peptide-1 …

The Role Of Neutrophils In Vasospasm And Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage: Is It Time For A Sah Clinical Trial Targeting Neutrophils?, William W Wroe, Hussein A Zeineddine, Spiros L Blackburn, Jaroslaw Aronowski, Devin W Mcbride

Faculty, Staff and Student Publications

Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating neurological disease, and one of the primary drivers of morbidity after aneurysm rupture is the phenomenon of delayed cerebral ischemia (DCI). Significant knowledge has been gained over the past two decades of the impact of neuroinflammation in DCI; and neutrophils are now believed to play a major role. There is significant human subject data showing the rise of neutrophil related inflammatory markers and neutrophil's association with poor outcome after aSAH, but as of yet no trials involving human subjects have been done specifically targeting neutrophils. There is however a growing body of evidence …

Sars-Cov-2 Rna-Binding Protein Suppresses Extracellular Mirna Release, Hyejin Mun, Chang Hoon Shin, Qingxuan Fei, Andrea Estefania Lopez Giraldo, Kyoung-Min Choi, Ji Won Lee, Kyungmin Kim, Kyung-Won Min, Leilei Shi, Mark T Bedford, Dong-Chan Kim, Yoo Lim Chun, Seonghyun Ryu, Dongin Kim, Jeong Ho Chang, Ryan T Westrope, Michelle Shay, Edward Nguyen, Junho K Hur, Abigail Agyenda, Nam Chul Kim, Sung-Ung Kang, Woonghee Lee, Je-Hyun Yoon

Faculty, Staff and Student Publications

SARS-CoV-2 is the betacoronavirus causing the COVID-19 pandemic. Although the SARS-CoV-2 genome and transcriptome were reported previously, the function of individual viral proteins is largely unknown. Utilizing biochemical and molecular biology methods, we identified that four SARS-CoV-2 RNA-binding proteins (RBPs) regulate the host RNA metabolism by direct interaction with mature miRNA let-7b revealed by Nuclear Magnetic Resonance spectroscopy (NMR). SARS-CoV-2 RBP Nsp9 primarily binds mature miRNA let-7b, a direct ligand of the Toll-like Receptor 7 (TLR7), one of the potential SARS-CoV-2 therapeutics. Nsp9 suppresses host gene expression possibly by promoting let-7b-mediated silencing of a cellular RNA polymerase, POLR2D. In addition, …

Normalization Of Temperature Effects For Quality Assurance Of Quantitative Prostate Apparent Diffusion Coefficient Imaging Across Multiple Sites, Ken-Pin Hwang, Joshua Yung, R Jason Stafford, Caroline Chung, Aradhana M Venkatesan

Faculty, Staff and Student Publications

Background: Apparent Diffusion Coefficient (ADC) as measured by diffusion weighted imaging is known to negatively correlate with prostate tumor aggressiveness. Heterogeneity in system and protocol performance causes potential variability in ADC acquired across a large scanner network, prompting a need to evaluate quantitative ADC from a prostate-specific MR diffusion protocol as part of quality assurance (QA). Due to the temperature dependence of ADC, repeatability and reproducibility assessments typically require phantoms to maintain a temperature of 0°C, imposing a considerable burden when assessing large numbers of scanners.

Purpose: To develop a QA procedure at room temperature for assessing the reproducibility of …

Addressing Controversy In Fusobacterium Nomenclature: What Exactly Does “F Nucleatum” Refer To?, Martha A Zepeda-Rivera, Floyd E Dewhirst, Susan Bullman, Christopher D Johnston

Faculty, Staff and Student Publications

The F. nucleatum group (sensu lato) is historically composed of four subspecies (F. nucleatum subsp. animalis, F. nucleatum subsp. nucleatum, F. nucleatum subsp. polymorphum, F. nucleatum subsp. vincentii). Although F. nucleatum sensu lato members are typically associated with oral disease, they have recently been shown to disseminate to the gastrointestinal tract and are associated with adverse health conditions such as inflammatory bowel disease and colorectal cancer (CRC). A growing debate over the nomenclature applied to Fusobacterium taxonomy has resulted in different names for these lineages, shifting them from their historic subspecies designations to …

Fusobacterium Sphaericum Sp Nov, Isolated From A Human Colon Tumor Adheres To Colonic Epithelial Cells And Induces Il-8 Secretion, Martha A Zepeda-Rivera, Yannick Eisele, Alexander Baryiames, Hanrui Wu, Claudia Mengoni, Gianmarco Piccinno, Elsa F Mcmahon, Kaitlyn D Lacourse, Dakota S Jones, Hans Hauner, Samuel S Minot, Nicola Segata, Floyd E Dewhirst, Christopher D Johnston, Susan Bullman

Faculty, Staff and Student Publications

Cancerous tissue is a largely unexplored microbial niche that provides a unique environment for the colonization and growth of specific bacterial communities, and with it, the opportunity to identify novel bacterial species. Here, we report distinct features of a novel Fusobacterium species, F. sphaericum sp. nov. (Fs), isolated from primary colon adenocarcinoma tissue. We acquire the complete closed genome and associated methylome of this organism and phylogenetically confirm its classification into the Fusobacterium genus, with F. perfoetens as its closest neighbor. Fs is phenotypically and genetically distinct, with morphological analysis revealing its coccoid shape, that while similar to …

A Review Of Engraftment Assessments Following Fecal Microbiota Transplant, Chloe Herman, Bridget M Barker, Thais F Bartelli, Vidhi Chandra, Rosa Krajmalnik-Brown, Mary Jewell, Le Li, Chen Liao, Florencia Mcallister, Khemlal Nirmalkar, Joao B Xavier, J Gregory Caporaso

Faculty, Staff and Student Publications

Fecal Microbiota Transplant (FMT) is a treatment for recurrent Clostridium difficile infections and is being explored for other clinical applications, from alleviating digestive and neurological disorders, to restoring microbiomes impacted by cancer treatment. Quantifying the extent of engraftment following an FMT is important in understanding a recipient's response to treatment. Engraftment and clinical response need to be investigated independently to evaluate an FMT's role (or lack thereof) in achieving a clinical response. Standardized bioinformatics methodologies for quantifying engraftment extent would not only improve assessment and understanding of FMT outcomes, but also facilitate comparison of FMT results and protocols across studies. …

Secretory Iga Dysfunction Underlies Poor Prognosis In Fusobacterium-Infected Colorectal Cancer, Ilseok Choi, Kyung-A Kim, Sang Cheol Kim, Donghwan Park, Ki Taek Nam, Jun Hyung Cha, Seungbyn Baek, Junha Cha, Hye-Yeong Jo, Minsun Jung, Melody Y Zeng, Irina Matei, Susan Bullman, Joong Bae Ahn, Yoon Dae Han, Han Sang Kim, Insuk Lee

Faculty, Staff and Student Publications

Fusobacterium nucleatum (Fn) is commonly enriched in colorectal cancer (CRC) and associated with poor outcomes, though its mechanisms remain unclear. Our study investigated how Fn affects the tumor microenvironment through single-cell transcriptomic analyses of 42 CRC patient tissues, comparing Fn-positive and Fn-negative tumors. We discovered that Fn impairs IgA plasma cell development and secretory IgA (sIgA) production by disrupting communication with tumor-associated macrophages. Additional experiments in germ-free mice, together with our re-analysis of a publicly available single-cell RNA-seq data set from a CRC mouse model with an intact gut microbiome–both models having been orally gavaged with Fn–jointly validated the causal …

Smags-Lasso: A Novel Feature Selection Method For Sensitivity Maximization In Early Cancer Detection, Hamid Khoshfekr Rudsari, Sara Khorami-Sarvestani, Johannes F Fahrmann, James P Long, Samir Hanash, Kim-Anh Do, Ehsan Irajizad

Faculty, Staff and Student Publications

Background: Sensitivity and specificity are foundational metrics for cancer detection tools. However, most machine learning algorithms prioritize overall accuracy during optimization, which fails to align with clinical priorities of early detection. We aim to develop a feature selection machine learning algorithm while maximizing sensitivity at a given specificity.

Methods: We developed SMAGS-LASSO, a machine learning algorithm that combines our developed Sensitivity Maximization at a Given Specificity (SMAGS) framework with L1 regularization for feature selection. This approach simultaneously optimizes sensitivity at user-defined specificity thresholds while performing feature selection. SMAGS-LASSO utilizes a custom loss function with L1 regularization and multiple parallel optimization …

Peripheral Blood Gene Expression Profiling And Prognostic Significance For The Course Of Interstitial Lung Disease In Patients With Systemic Sclerosis, Shervin Assassi, Christopher P Denton, Matthias Zwick, Ramona Schmid, Carina Ittrich, Tobias Litzenburger, Sudha Visvanathan

Faculty, Staff and Student Publications

Objective: We used data from the placebo arm of the Safety and Efficacy of Nintedanib in Systemic Sclerosis (SENSCIS) trial to determine the prognostic/predictive significance of peripheral blood cell (PBC) transcript modules for the course of forced vital capacity (FVC) in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) with and without mycophenolate mofetil (MMF) treatment.

Methods: Patients had SSc-ILD with first non-Raynaud symptom within 7 years. MMF treatment was permitted if taken at a stable dose for ≥6 months. PBC RNA samples were taken at baseline. Global RNA sequencing was performed, followed by a modular analysis using 62 curated …

Benzodioxane-Benzamides Targeting Bacterial Cell Division Protein Ftsz Potentially Disrupt Slma-Mediated Nucleoid Occlusion And Reversible Biomolecular Condensation, Marta Sobrinos-Sanguino, Inés Barros-Medina, Lorenzo Suigo, Alessia Lanzini, Ermanno Valoti, William Margolin, Valentina Straniero, Begoña Monterroso, Silvia Zorrilla

Faculty, Staff and Student Publications

New strategies are urgently needed against antimicrobial resistance, a major health threat, and the different mechanisms regulating the bacterial cell division machinery offer multiple opportunities for developing novel therapeutics. FtsZ, an essential protein of this process, is targeted by multiple small molecules, and benzodioxane-benzamides (BDOBs) are among the most potent inhibitors in several bacterial species. BDOBs mechanisms are however poorly understood, particularly their impact on FtsZ's interplay with partners and ability to assemble phase-separated biomolecular condensates potentially involved in stress sensing. We show that certain BDOBs shielded FtsZ against depolymerization induced by the nucleoprotein complexes of SlmA, which inhibit Z-ring …

Molecular And Immunological Features Associated With Long-Term Benefits In Metastatic Nsclc Patients Undergoing Immune Checkpoint Blockade, Pedro Rocha, Rafael Bach, Laura Masfarré, Sharia Hernandez, Nil Navarro-Gorro, Adrià Rossell, Xavier Villanueva, Mario Giner, Ignacio Sanchéz, Miguel Galindo, Raúl Del Rey-Vergara, Albert Iñañez, Beatriz Sanchéz-Espiridion, Wei Lu, Ariadna Acedo-Terrades, Pau Berenguer-Molins, Albert Sánchez-Font, Roberto Chalela, Victor Curull, Álvaro Taus, Max Hardy-Werbin, Mark Sausen, Andrew Georgiadis, James White, Jennifer B Jackson, Laura Moliner, Sergi Clavé, Beatriz Bellosillo, Ana Rovira, Ignacio Wistuba, Luisa M Solis Soto, Júlia Perera-Bel, Edurne Arriola

Faculty, Staff and Student Publications

Introduction: Immunotherapy is firmly established as a treatment regimen in various solid tumors, driven by its exceptional benefits in a selected group of patients. Despite widespread adoption of immune checkpoint blockade (ICB) across diverse solid tumors, the quest for a clinically informative biomarker for long-term benefit remains unmet.

Methods: A total of 49 patients with metastatic NSCLC treated with ICB were included. Long-term (LTR) and short-term responders (STR) were defined as those with a response to ICB lasting more than 24 months or less than 6 months, respectively. Longitudinal blood specimens were collected before ICB treatment initiation and early-on treatment. …

Caspase 3-Specific Cleavage Of Ubiquitin-Specific Peptidase 48 Enhances Drug-Induced Apoptosis In Aml, Zhanglin Zhang, Xiang Lin, Yaling Yang, Xuemei Wang, Yi Wang, Xianbao Huang, Miao Hong, Wei Gao, Hua He, M James You, Yi Yang, Guangyao Kong

Faculty, Staff and Student Publications

Dysfunction or dysregulation of deubiquitination is closely related to the initiation and development of multiple cancers. Targeted regulation of deubiquitination has been recognized as an important strategy in tumor therapy. However, the mechanism by which drugs regulate deubiquitinase is not clear. Here, we identified ubiquitin-specific peptidase 48 (USP48), a member of the ubiquitin-specific protease family highly expressed in various tumors, as a specific substrate for the activated caspase-3. During drug induced apoptosis of AML cells, activated caspase-3 cleaves USP48 through recognizing the conservative motif DEQD located at 611-614 sites of human USP48. Subsequent analysis showed that the cleavage USP48 N-terminal …

Impact Of Peripheral Circadian Misalignment And Alcohol On The Resiliency Of Intestinal Barrier And Microbiota, Laura Tran, Maliha Shaikh, Phillip A Engen, Ankur Naqib, Dulce M Frausto, Vivian Ramirez, Malia Gasteier, Zlata Bogin, Kristi Lawrence, Lijuan Zhang, Shiwen Song, Stefan J Green, Faraz Bishehsari, Christopher B Forsyth, Ali Keshavarzian, Garth R Swanson

Faculty, Staff and Student Publications

Circadian organization is involved in many gastrointestinal tract (GIT) functions such as the maintenance of intestinal barrier integrity. There is compelling evidence that perturbation of the circadian clock decreases intestinal epithelial cells' resiliency to alcohol-induced injury. One of the most common causes of circadian misalignment is wrong-time eating (largest meal at dinner) in modern societies. Yet, few studies have examined the importance of peripheral circadian rhythms of the GIT to alcohol consumption. Eating patterns during physiologic rest time, defined as wrong-time eating (WTE), misalign the peripheral circadian clock of the GIT and the body's central clock. This study aims to …

Meniscal Repair In The Setting Of Revision Anterior Cruciate Ligament Reconstruction: 6-Year Follow-Up Results From The Mars Cohort, Jake A Fox, Laura J Huston, Amanda K Haas, Jacquelyn S Pennings, Christina R Allen, Daniel E Cooper, Thomas M Deberardino, Warren R Dunn, Brett Brick A Lantz, Kurt P Spindler, Michael J Stuart, Annunziato Ned Amendola, Christopher C Annunziata, Robert A Arciero, Bernard R Bach, Champ L Baker, Arthur R Bartolozzi, Keith M Baumgarten, Jeffrey H Berg, Geoffrey A Bernas, Stephen F Brockmeier, Robert H Brophy, Charles A Bush-Joseph, J Brad Butler V, James L Carey, James E Carpenter, Brian J Cole, Jonathan M Cooper, Charles L Cox, R Alexander Creighton, Tal S David, David C Flanigan, Robert W Frederick, Theodore J Ganley, Charles J Gatt, Steven R Gecha, James Robert Giffin, Sharon L Hame, Jo A Hannafin, Christopher D Harner, Norman Lindsay Harris, Keith S Hechtman, Elliott B Hershman, Rudolf G Hoellrich, David C Johnson, Timothy S Johnson, Morgan H Jones, Christopher C Kaeding, Ganesh V Kamath, Thomas E Klootwyk, Bruce A Levy, C Benjamin Ma, G Peter Maiers, Robert G Marx, Matthew J Matava, Gregory M Mathien, David R Mcallister, Eric C Mccarty, Robert G Mccormack, Bruce S Miller, Carl W Nissen, Daniel F O'Neill, Brett D Owens, Richard D Parker, Mark L Purnell, Arun J Ramappa, Michael A Rauh, Arthur C Rettig, Jon K Sekiya, Kevin G Shea, Orrin H Sherman, James R Slauterbeck, Matthew V Smith, Jeffrey T Spang, Col Ret Steven J Svoboda, Timothy N Taft, Joachim J Tenuta, Edwin M Tingstad, Armando F Vidal, Darius G Viskontas, Richard A White, James S Williams, Michelle L Wolcott, Brian R Wolf, James J York, Rick W Wright

Faculty, Staff and Student Publications

Background: Meniscal preservation has been demonstrated to contribute to long-term knee health and has been a successful intervention in isolation and in patients with anterior cruciate ligament reconstruction (ACLR). The long-term results of meniscal repair in the setting of revision ACLR have yet to be documented.

Purpose: To report the incidence of meniscal repair failures at the 6-year follow-up in a cohort of patients who underwent concurrent revision ACLR and primary meniscal repair.

Study design: Prospective cohort study; Level of evidence, 2.

Methods: All revision ACLRs with concomitant primary meniscal repair cases from a multicenter group between 2006 and 2011 …

Tubulin Regulates Stability And Localization Of Stmn2 By Binding Preferentially To Its Soluble Form, Xiang Deng, Gary A Bradshaw, Marian Kalocsay, Timothy Mitchison

Faculty, Staff and Student Publications

The small, tubulin-binding protein STMN2 is highly expressed in neurons and is implicated in amyotrophic lateral sclerosis. STMN2 degrades rapidly and accumulates at axotomy sites, suggesting fast turnover is crucial for its neuroprotective function. We show that STMN2 was primarily degraded by the ubiquitin-proteasome system. Its membrane-targeting N-terminal domain promoted fast turnover, whereas its tubulin-binding domain promoted stabilization. Proximity labeling and imaging showed that tubulin binding reduced STMN2 targeting to trans-Golgi network membranes. Pull-down assays showed that tubulin binds preferentially to soluble over membrane-bound STMN2. Our observations suggest that STMN2 interconverts between a soluble, tubulin-bound form and a membrane-bound, tubulin-free …

Stage- And Smoking-Associated Microrna Expression In Lung Adenocarcinoma, Min Huang, Yimin Ge, Huiqin Chen, Caimiao Wei, David Cogdell, Cristina Ivan, Meng Chen, Wei Zhang, George A Calin, Ming Guo

Faculty, Staff and Student Publications

Background: Altered expression of microRNAs (miRNAs) is implicated in lung carcinogenesis, but little research has investigated the association of miRNA alterations with lung cancer stage or smoking status. To identify such alterations in lung adenocarcinoma, we conducted miRNA profiling.

Methods: Lung adenocarcinoma specimens and paired nonneoplastic lung tissues from 58 patients who had received no preoperative therapy and underwent tumor resection from 1991 to 2006 were collected from tumor tissue banks. Thirty (52%) of the tumors were stage I and 28 (48%) stage II or higher. Twenty-five (43%) patients were nonsmokers and 33 (57%) were smokers. To identify miRNAs of …

Real-World First-Line Outcomes Of Alectinib And Brigatinib In Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer: A Nationwide South Korean Cohort Study Using The Health Insurance Review And Assessment Data, Hee Jun Kim, Eunyoung Angela Lee, Jin-Hee Park, Hyun Woo Lee

Faculty, Staff and Student Publications

Background: Lung cancer remains the leading cause of cancer-related mortality worldwide. Anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) presents unique clinical challenges, including frequent central nervous system (CNS) metastases. At present, comparative real-world data on ALK inhibitors remain limited. This study aimed to compare real-world progression-free survival (PFS) and overall survival (OS) among patients with ALK-positive NSCLC treated with first-line alectinib or brigatinib using nationwide South Korean data.

Methods: This retrospective cohort study analyzed anonymized data from South Korea's Health Insurance Review and Assessment Service, covering January 2007 to December 2023. Patients diagnosed with ALK-positive NSCLC (ICD-10: C34x) …

Early Determination Of The Dorsal-Ventral Axis In Endochondral Ossification In Mice, Sixun Wu, Hirotaka Matsumoto, Jumpei Morita, Mina Yamabe, Azumi Noguchi, Shinsuke Ohba, Noriaki Ono, Yuki Matsushita

Faculty, Staff and Student Publications

Endochondral ossification is a highly coordinated process involving distinct progenitor cell populations within the mesenchymal condensation and subsequent cartilage anlage and perichondrium, all of which drive skeletal formation. Cell-type specific lineage tracing conducted to understand fetal bone development has revealed various fates of early skeletal cells. However, the underlying continuous and precise cellular dynamics of fetal skeletal cells, particularly along the dorsoventral axis, remain unclear. Here, we show that spatiotemporally specific skeletal progenitor cells in the early developmental stage contribute to the dorsal-ventral axis in a manner that is strictly determined during initial developmental stages. Lineage-tracing experiments using Fgfr3-creER and …

Recombination Suppression Drives Expansion Of The Drosophila Dot Chromosome, Timothy J Stanek, Wilson Leung, Christopher D Shaffer, Ishtar Olaveja, Annabelle Laughlin, Jaquelyn Hester, Darwin Garrido, Emily K Oh, Maria Volski, Nistha Panda, Mia Mo, Ethan Cordes, Martin Dalling, Kacie Kershaw, Malcolm Arnott, Stephen Daly, Silvia Garcia Valenzuela, Paige Thompson, Kayla L Hastert, Destiny Sabb, Kathryn Karpinski, Meher Naaz Arora, Nicholas Rius, Larissa Lobello, Sebastian Jaramillo, Omkar Sonavane, Alice Herrmann, Laura K Reed, Sarah C R Elgin, Cindy Arrigo, Christopher E Ellison

Faculty, Staff and Student Publications

Genome size varies widely, even among closely related species, yet much less is known about chromosome size variation. Here we use the fourth chromosome of Drosophila, also known as the "Muller F element" or "dot chromosome", as a model to investigate chromosome-specific size expansion. The F element of most Drosophila species is small (∼1.3 Mb) and almost entirely heterochromatic, yet harbors approximately 80 protein-coding genes. Here, we study D. kikkawai, D. takahashii, D. ananassae, and D. bipectinata, whose F elements are 2- to 15-fold larger in size compared to D. melanogaster. Through manual gene curation and comparative genomic analysis, we …

Met Overexpression Is Associated With Superior Immunotherapy Benefit In Advanced Non-Small Cell Lung Cancer, Hui Li, Lingzhi Hong, Pedro Rocha, Rafael Bach, Luisa M Solis Soto, Waree Rinsurongkawong, Bingnan Zhang, Haniel A Araujo, Yasir Y Elamin, Mehmet Altan, Claudio A Arrechedera, Jianling Zhou, Khaja B Khan, Wei Lu, Elliana Young, Carl M Gay, Tina Cascone, Lauren A Byers, Ferdinandos Skoulidis, George Blumenschein, Frank V Fossella, Anne Tsao, Marcelo V Negrao, Natalie Vokes, Jia Wu, Hai T Tran, Ignacio I Wistuba, J Jack Lee, Don L Gibbons, Ara A Vaporciyan, John V Heymach, Xiuning Le, Jianjun Zhang

Faculty, Staff and Student Publications

Background/objectives: MET overexpression is common in non-small cell lung cancer (NSCLC). The correlation between MET overexpression and immune checkpoint inhibitor (ICI) efficacy in NSCLC is underexplored.

Methods: In this retrospective observational cohort study, we curated a dataset of 279 stage IV NSCLC patients who received ICI treatment and had MET expression assessed by CLIA-certified immunohistochemistry (IHC) assay. MET expression was graded on a scale from 0 to 3+, with overexpression defined as 2+ or 3+. Clinicopathological features associated with MET expression were assessed using logistic regression. Overall survival (OS) and progression-free survival (PFS) were evaluated via Kaplan-Meier analysis and the …

Prior Incarceration And Dental Insurance Trajectories Throughout Older Adulthood, A Testa, L Mijares, D B Jackson, V Maroufy, R Samper-Ternent, A C Neumann, R Mungia, K T Ganson, J M Nagata, T Oates

Faculty, Staff and Student Publications

Objectives: This study examines the relationship between prior incarceration and dental insurance trajectories throughout older adulthood.

Methods: A nationally representative sample of adults aged 55 y and older who participated in the 2012-2020 Health and Retirement Survey was analyzed (n = 6,383). Group-based trajectory modeling was used to identify distinct patterns of dental insurance coverage across the 8 survey waves. Multinomial logistic regression was used to assess the association between prior incarceration and dental insurance trajectory group membership.

Results: Four dental insurance trajectories were identified: persistent dental insurance (30.0%), intermittent high insurance (16.4%), intermittent low insurance (20.4%), and no …

Predicting The Response Of Triple Negative Breast Cancer To Neoadjuvant Systemic Therapy Via Biology-Based Modeling And Habitat Analysis, Casey E Stowers, Chengyue Wu, Clinton Yam, Jingfei Ma, Gaiane M Rauch, Thomas E Yankeelov

Faculty, Staff and Student Publications

Despite being the standard-of-care treatment, neoadjuvant therapy (NAT) attains a complete response only in approximately half of the patients with triple negative breast cancer. Thus, methods to predict and optimize patient response to NAT are needed. Previously, we employed patient-specific MRI data to calibrate a biology-based mathematical model that describes cell movement, proliferation, and death due to drug at the tumor level and cell proliferation at an image voxel level. We now extend our approach by using MRI data to group voxels into "habitats" whereby tumor cells of a habitat share the same proliferation. With this approach, we now calibrate …

Loss Of Idh1 And Idh2 Mutations During The Evolution Of Metastatic Chondrosarcoma, William Cross, Iben Lyskjær, Christopher Davies, Abigail Bunkum, Ana Maia Rocha, Tom Lesluyes, Fernanda Amary, Roberto Tirabosco, Cristina Naceur-Lombardelli, Mariam Jamal-Hanjani, Charles Swanton, Nischalan Pillay, Simone Zaccaria, Adrienne M Flanagan, Peter Van Loo

Faculty, Staff and Student Publications

Driver mutations in IDH1 and IDH2 are initiating events in the evolution of chondrosarcoma and several other cancer types. Here, we present evidence that mutant IDH1 is recurrently lost in metastatic central chondrosarcoma. This may reflect either relaxed positive selection for the mutant IDH1 locus, or negative selection for the hypermethylation phenotype later in tumor evolution. This finding highlights the challenge for therapeutic intervention by mutant IDH1 inhibitors in chondrosarcoma.

Botulinum Toxin Combined With Robot-Assisted Therapy For Post-Stroke Spasticity: A Systematic Review, Salvatore Facciorusso, Stefania Spina, Mirko Filippetti, Rajiv Reebye, Gerard E Francisco, Andrea Santamato

Faculty, Staff and Student Publications

Background: Post-stroke spasticity limits motor recovery and independence. Combining botulinum toxin type-A (BoNT-A) injection with intensive, task-specific robot-assisted therapy (RAT) might enhance neuroplasticity and functional gains, but its additive effect and optimal timing are uncertain. (

Methods: We systematically searched major medical databases and trial registries up to April 2025 for randomized controlled trials in adults with post-stroke spasticity comparing botulinum toxin type-A injection plus RAT with toxin injection plus conventional therapy, or RAT alone with RAT combined with toxin injection. Risk of bias was assessed using the RoB 2 tool, and findings were synthesized narratively.

Results: Seven trials ( …

Stiefel Md Anderson Oropharynx Cancer (Mda-Opc) Cohort: A Single-Institution, Prospective Longitudinal Outcomes Study, Amy Moreno, Ariana J Sahli, Faye Johnson, Xiaowen Sun, Carly Barbon, Waree Rinsurongkawong, Wenye Song, Flavie M Luciani, Han Liang, Jun Li, Wei Liu, J Jack Lee, S J Frank, Stephen Lai, Clifton Fuller, Katherine Hutcheson

Faculty, Staff and Student Publications

Purpose: The MD Anderson Oropharynx Cancer (MDA-OPC) cohort is a unique single-institution, prospective longitudinal cancer cohort. The cohort aims to enhance the therapeutic index of OPC management by supporting data needs for independent investigators to conduct rigorous observational studies examining exposures and factors associated with acute and late toxicities, cancer progression, recurrence, new malignancies and quality of life in OPC survivors.

Participants: A total of 1811 patients with OPC with a minimum follow-up of 6 months have been consented to our prospective registry between 18 March 2015 and 29 December 2023. Clinical and treatment (Tx) data are available on all …

Mycobacterium Chelonae Outbreak Investigation At A Quaternary Pediatric Hospital Following The Opening Of A Leed-Certified Critical Care Tower: Where Does Water Sustainability Intersect With Infection Control?, Andrea L Ankrum, Silvia M Caceres, Michael Torsell, Elaine Epperson, Vinicius Calado Nogueira De Moura, Jennifer J Gilick, Michael Strong, Qingyun Liu, Matthew J Strand, Rachel N Wilsey, Jennifer R Honda, Jane E Gross, Felicia A Scaggs-Huang

Faculty, Staff and Student Publications

Objective: Investigate the increased incidence of Mycobacterium chelonae positive respiratory cultures in hospitalized patients.

Design: Apply the Healthcare-Associated Links in Transmission of Nontuberculous Mycobacteria (HALT NTM) toolkit to an outbreak investigation of M. chelonae.

Setting: Quaternary-care pediatric hospital and medical center in the United States with a recently opened LEED-certified critical care tower.

Patients: Adult and pediatric patients with M. chelonae positive respiratory cultures between June 2022 and January 2024.

Methods: An epidemiological investigation involving clinical and laboratory practices, water management, building construction and renovation projects. Environmental sampling of air vents, water sources and endoscope reprocessing equipment was performed. M. …

Analysis Of A Deeply-Phenotyped Familial Hypercholesterolemia Cohort From Mexico Shows A Role For Both Rare And Common Alleles Across Known Dyslipidemia Genes And Reveals Structural Variation In A Novel Locus, Nicholas Katsanis, Niki Mourtzi, Consuelo D Quinto-Cortés, Alexandro J Martagon, Alexander G Ioannidis, Francisco M De La Vega, Jeff Gulcher, Ming Ta Michael Lee, Mohammad A Faghihi, Arturo Lopez-Pineda, Sonia Moreno-Grau, Daniel Mas Montserrat, Míriam Barrabés, David Bonet, Pavel Salazar Fernandez, Jeff Wall, Babak Moatamed, Roopa Mehta, Gabriela A Galan-Ramirez, Rafael Zubirán, Daniel Elias-Lopez, Teresa Tusié-Luna, Carlos A Aguilar-Salinas, Carlos D Bustamante

Faculty, Staff and Student Publications

Familial hypercholesterolemia (FH) is a genetic disorder driven in part by mutations in three genes that encode components of the cholesterol pathway: LDLR, APOB, and PCSK9. However, the majority of FH genetics has been performed in individuals of European descent. Here, we leveraged a cohort of 300 patients from the Mexican FH registry to understand how rare, high liability alleles and common variants might contribute to shaping individual risk. Using a combination of whole exome and of short- and long-read whole genome sequencing, we report three key findings. First, we observed that rare pathogenic point mutations and structural variants in …