Digital Commons Network^™

Mycoplasmoides Genitalium Nucleic Acid Semi-Quantitation And Molecular Macrolide Resistance Detection Via Automated Assays: Gender And Specimen Source Considerations, Erik Munson, Josephine Moore, Trinity Krueger, Amanda Zapp, Stephen C Lavey, Kimber L Munson, Irene A Stafford, Brian Mustanski

Faculty, Staff and Student Publications

A laboratory-developed test (LDT) using analyte-specific reagents has been optimized on a commercial platform to detect macrolide resistance-associated mutations (MRM) in 23S rRNA from Mycoplasmoides genitalium from primary clinical specimens. In this study, MRM-LDT was applied to a multi-specimen source study set. One thousand four hundred ninety-five primary specimens testing positive for M. genitalium by commercial transcription-mediated amplification (TMA) were initially titered by the TMA assay using serial 10-fold dilutions to semi-quantitate target nucleic acid burden. Primary specimens were then processed for MRM detection using the MRM-LDT. Findings were stratified by gender and specimen source. The mean log10 target nucleic …

Small Rna Signatures Of Acute Ischemic Stroke In L1cam Positive Extracellular Vesicles, Bharti Manwani, Nivetha Brathaban, Abiya Baqai, Yashee Munshi, Hilda W Ahnstedt, Mengqi Zhang, Kajsa Arkelius, Ted Llera, Edilberto Amorim, Fanny M Elahi, Neel S Singhal

Faculty, Staff and Student Publications

L1CAM-positive extracellular vesicles (L1EV) are an emerging biomarker that may better reflect ongoing neuronal damage than other blood-based biomarkers. The physiological roles and regulation of L1EVs and their small RNA cargoes following stroke is unknown. We sought to characterize L1EV small RNAs following stroke and assess L1EV RNA signatures for diagnosing stroke using weighted gene co-expression network analysis and random forest (RF) machine learning algorithms. Interestingly, small RNA sequencing of plasma L1EVs from patients with stroke and control patients (n = 28) identified micro(mi)RNAs known to be enriched in the brain. Weighted gene co-expression network analysis (WGCNA) revealed small RNA …

Rest-Dependent Downregulation Of Von Hippel-Lindau Tumor Suppressor Promotes Autophagy In Shh-Medulloblastoma, Ashutosh Singh, Donghang Cheng, Jyothishmathi Swaminathan, Yanwen Yang, Yan Zheng, Nancy Gordon, Vidya Gopalakrishnan

Faculty, Staff and Student Publications

The RE1 silencing transcription factor (REST) is a driver of sonic hedgehog (SHH) medulloblastoma genesis. Our previous studies showed that REST enhances cell proliferation, metastasis and vascular growth and blocks neuronal differentiation to drive progression of SHH medulloblastoma tumors. Here, we demonstrate that REST promotes autophagy, a pathway that is found to be significantly enriched in human medulloblastoma tumors relative to normal cerebella. In SHH medulloblastoma tumor xenografts, REST elevation is strongly correlated with increased expression of the hypoxia-inducible factor 1-alpha (HIF1α)-a positive regulator of autophagy, and with reduced expression of the von Hippel-Lindau (VHL) tumor suppressor protein - a …

Role Of Ethanolamine Utilization And Bacterial Microcompartment Formation In Listeria Monocytogenes Intracellular Infection, Ayan Chatterjee, Karan Gautam Kaval, Danielle A Garsin

Faculty, Staff and Student Publications

Ethanolamine (EA) affects the colonization and pathogenicity of certain human bacterial pathogens in the gastrointestinal tract. However, EA can also affect the intracellular survival and replication of host cell invasive bacteria such as Listeria monocytogenes (LMO) and Salmonella enterica serovar Typhimurium (S. Typhimurium). The EA utilization (eut) genes can be categorized as regulatory, enzymatic, or structural, and previous work in LMO showed that loss of genes encoding functions for the enzymatic breakdown of EA inhibited LMO intracellular replication. In this work, we sought to further characterize the role of EA utilization during LMO infection of host …

Author Correction: Long Noncoding Rna Malat1 Protects Against Osteoporosis And Bone Metastasis, Yang Zhao, Jingyuan Ning, Hongqi Teng, Yalan Deng, Marisela Sheldon, Lei Shi, Consuelo Martinez, Jie Zhang, Annie Tian, Yutong Sun, Shinichi Nakagawa, Fan Yao, Hai Wang, Li Ma

Faculty, Staff and Student Publications

This corrects the article "Long noncoding RNA Malat1 protects against osteoporosis and bone metastasis", 2384.

Application Of Simultaneous Uncertainty Quantification And Segmentation For Oropharyngeal Cancer Use-Case With Bayesian Deep Learning, Jaakko Sahlsten, Joel Jaskari, Kareem A Wahid, Sara Ahmed, Enrico Glerean, Renjie He, Benjamin H Kann, Antti Mäkitie, Clifton D Fuller, Mohamed A Naser, Kimmo Kaski

Faculty, Staff and Student Publications

BACKGROUND: Radiotherapy is a core treatment modality for oropharyngeal cancer (OPC), where the primary gross tumor volume (GTVp) is manually segmented with high interobserver variability. This calls for reliable and trustworthy automated tools in clinician workflow. Therefore, accurate uncertainty quantification and its downstream utilization is critical.

METHODS: Here we propose uncertainty-aware deep learning for OPC GTVp segmentation, and illustrate the utility of uncertainty in multiple applications. We examine two Bayesian deep learning (BDL) models and eight uncertainty measures, and utilize a large multi-institute dataset of 292 PET/CT scans to systematically analyze our approach.

RESULTS: We show that our uncertainty-based approach …

Improved Liver Disease Prediction From Clinical Data Through An Evaluation Of Ensemble Learning Approaches, Shahid Mohammad Ganie, Pijush Kanti Dutta Pramanik, Zhongming Zhao

Faculty, Staff and Student Publications

PURPOSE: Liver disease causes two million deaths annually, accounting for 4% of all deaths globally. Prediction or early detection of the disease via machine learning algorithms on large clinical data have become promising and potentially powerful, but such methods often have some limitations due to the complexity of the data. In this regard, ensemble learning has shown promising results. There is an urgent need to evaluate different algorithms and then suggest a robust ensemble algorithm in liver disease prediction.

METHOD: Three ensemble approaches with nine algorithms are evaluated on a large dataset of liver patients comprising 30,691 samples with 11 …

Defining The Kras- And Erk-Dependent Transcriptome In Kras-Mutant Cancers, Jeffrey A Klomp, Jennifer E Klomp, Clint A Stalnecker, Kirsten L Bryant, A Cole Edwards, Kristina Drizyte-Miller, Priya S Hibshman, J Nathaniel Diehl, Ye S Lee, Alexis J Morales, Khalilah E Taylor, Sen Peng, Nhan L Tran, Laura E Herring, Alex W Prevatte, Natalie K Barker, Laura D Hover, Jill Hallin, Alexey Sorokin, Preeti Marie Kanikarla, Saikat Chowdhury, Oluwadara Coker, Hey Min Lee, Craig M Goodwin, Prson Gautam, Peter Olson, James G Christensen, John P Shen, Scott Kopetz, Lee M Graves, Kian-Huat Lim, Andrea Wang-Gillam, Krister Wennerberg, Adrienne D Cox, Channing J Der

Faculty, Staff and Student Publications

How the KRAS oncogene drives cancer growth remains poorly understood. Therefore, we established a systemwide portrait of KRAS- and ERK-dependent gene transcription in KRAS-mutant cancer to delineate the molecular mechanisms of growth and of inhibitor resistance. Unexpectedly, our KRAS-dependent gene signature diverges significantly from the frequently cited Hallmark KRAS signaling gene signature, is driven predominantly through the ERK mitogen-activated protein kinase (MAPK) cascade, and accurately reflects KRAS- and ERK-regulated gene transcription in KRAS-mutant cancer patients. Integration with our ERK-regulated phospho- and total proteome highlights ERK deregulation of the anaphase promoting complex/cyclosome and other components of the cell cycle machinery as …

A Multilevel Intervention To Promote Hpv Vaccination Among Young Adults In Texas: Protocol For A Randomized Controlled Trial, Qian Lu, Lenna Dawkins-Moultin, Dalnim Cho, Naomi Q P Tan, Suellen Hopfer, Yisheng Li, Lois Ramondetta, Yusi Xu, Di Lun, Minxing Chen

Faculty, Staff and Student Publications

BACKGROUND: Human papillomavirus (HPV) infections can cause cancers of the cervix, vagina, vulva, penis, anus, and oropharynx. The most recently approved HPV vaccine, Gardasil-9, protects against HPV infection and can prevent HPV-associated invasive cancers. However, Gardasil-9 is one of the most underused vaccines in the US today. Young adults are at risk for HPV infection, but many are not vaccinated. This study uses a randomized controlled trial (RCT) to test an innovative multilevel intervention to increase HPV vaccination rates among young adults. In this paper, we describe the research protocol.

METHODS: The study uses a two by three factorial design. …

Quantitative Proteomic Analysis Reveals Unique Hsp90 Cycle-Dependent Client Interactions, Erick I Rios, Davi Gonçalves, Kevin A Morano, Jill L Johnson

Faculty, Staff and Student Publications

Hsp90 is an abundant and essential molecular chaperone that mediates the folding and activation of client proteins in a nucleotide-dependent cycle. Hsp90 inhibition directly or indirectly impacts the function of 10-15% of all proteins due to degradation of client proteins or indirect downstream effects. Due to its role in chaperoning oncogenic proteins, Hsp90 is an important drug target. However, compounds that occupy the ATP-binding pocket and broadly inhibit function have not achieved widespread use due to negative effects. More selective inhibitors are needed; however, it is unclear how to achieve selective inhibition. We conducted a quantitative proteomic analysis of soluble …

Orthogonal Proteogenomic Analysis Identifies The Druggable Pa2g4-Myc Axis In 3q26 Aml, Matteo Marchesini, Andrea Gherli, Elisa Simoncini, Lucas Moron Dalla Tor, Anna Montanaro, Natthakan Thongon, Federica Vento, Chiara Liverani, Elisa Cerretani, Anna D'Antuono, Luca Pagliaro, Raffaella Zamponi, Chiara Spadazzi, Elena Follini, Benedetta Cambò, Mariateresa Giaimo, Angela Falco, Gabriella Sammarelli, Giannalisa Todaro, Sabrina Bonomini, Valentina Adami, Silvano Piazza, Claudia Corbo, Bruno Lorusso, Federica Mezzasoma, Costanza Anna Maria Lagrasta, Maria Paola Martelli, Roberta La Starza, Antonio Cuneo, Franco Aversa, Cristina Mecucci, Federico Quaini, Simona Colla, Giovanni Roti

Faculty, Staff and Student Publications

The overexpression of the ecotropic viral integration site-1 gene (EVI1/MECOM) marks the most lethal acute myeloid leukemia (AML) subgroup carrying chromosome 3q26 abnormalities. By taking advantage of the intersectionality of high-throughput cell-based and gene expression screens selective and pan-histone deacetylase inhibitors (HDACis) emerge as potent repressors of EVI1. To understand the mechanism driving on-target anti-leukemia activity of this compound class, here we dissect the expression dynamics of the bone marrow leukemia cells of patients treated with HDACi and reconstitute the EVI1 chromatin-associated co-transcriptional complex merging on the role of proliferation-associated 2G4 (PA2G4) protein. PA2G4 overexpression rescues AML cells from the …

Piga Mutations And Glycosylphosphatidylinositol Anchor Dysregulation In Polyposis-Associated Duodenal Tumorigenesis, Elena Meuser, Kyle Chang, Angharad Walters, Joanna J Hurley, Hannah D West, Iain Perry, Matthew Mort, Laura Reyes-Uribe, Rebekah Truscott, Nicholas Jones, Rachel Lawrence, Gareth Jenkins, Peter Giles, Sunil Dolwani, Bilal Al-Sarireh, Neil Hawkes, Emma Short, Geraint T Williams, Melissa W Taggart, Kim Luetchford, Patrick M Lynch, Diantha Terlouw, Maartje Nielsen, Sarah-Jane Walton, Andrew Latchford, Susan K Clark, Julian R Sampson, Eduardo Vilar, Laura E Thomas

Faculty, Staff and Student Publications

The pathogenesis of duodenal tumors in the inherited tumor syndromes familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP) is poorly understood. This study aimed to identify genes that are significantly mutated in these tumors and to explore the effects of these mutations. Whole exome and whole transcriptome sequencing identified recurrent somatic coding variants of phosphatidylinositol N-acetylglucosaminyltransferase subunit A (PIGA) in 19/70 (27%) FAP and MAP duodenal adenomas, and further confirmed the established driver roles for APC and KRAS. PIGA catalyzes the first step in glycosylphosphatidylinositol (GPI) anchor biosynthesis. Flow cytometry of PIGA-mutant adenoma-derived and CRISPR-edited duodenal organoids confirmed loss of …

Epicardial Inflow Versus Myocardial Distribution: Average Regional Transmural Coronary Flow Is Not Enough, Nils P Johnson, K Lance Gould

Faculty, Staff and Student Publications

No abstract provided.

Methylthioadenosine Phosphorylase Genomic Loss In Advanced Gastrointestinal Cancers, Natalie Y L Ngoi, Tin-Yun Tang, Catia F Gaspar, Dean C Pavlick, Gregory M Buchold, Emma L Scholefield, Vamsi Parimi, Richard S P Huang, Tyler Janovitz, Natalie Danziger, Mia A Levy, Shubham Pant, Anaemy Danner De Armas, David Kumpula, Jeffrey S Ross, Milind Javle, Jordi Rodon Ahnert

Faculty, Staff and Student Publications

BACKGROUND: One of the most common sporadic homozygous deletions in cancers is 9p21 loss, which includes the genes methylthioadenosine phosphorylase (MTAP), CDKN2A, and CDKN2B, and has been correlated with worsened outcomes and immunotherapy resistance. MTAP-loss is a developing drug target through synthetic lethality with MAT2A and PMRT5 inhibitors. The purpose of this study is to investigate the prevalence and genomic landscape of MTAP-loss in advanced gastrointestinal (GI) tumors and investigate its role as a prognostic biomarker.

MATERIALS AND METHODS: We performed next-generation sequencing and comparative genomic and clinical analysis on an extensive cohort of 64 860 tumors comprising 5 GI …

Cell-Free Dna Concentration As A Biomarker Of Response And Recurrence In Her2-Negative Breast Cancer Receiving Neoadjuvant Chemotherapy, Mark Jesus M Magbanua, Ziad Ahmed, Rosalyn W Sayaman, Lamorna Brown Swigart, Gillian L Hirst, Christina Yau, Denise M Wolf, Wen Li, Amy L Delson, Jane Perlmutter, Paula Pohlmann, W Fraser Symmans, Douglas Yee, Nola M Hylton, Laura J Esserman, Angela M Demichele, Hope S Rugo, Laura J Van 'T Veer

Faculty, Staff and Student Publications

Purpose: We previously demonstrated the clinical significance of circulating tumor DNA (ctDNA) in patients with HER2-negative breast cancer receiving neoadjuvant chemotherapy (NAC). Here, we compared its predictive and prognostic value with cell-free DNA (cfDNA) concentration measured in the same samples from the same patients.

Experimental design: 145 patients with hormone receptor (HR)-positive/HER2-negative and 138 triple-negative breast cancer (TNBC) with ctDNA data from a previous study were included in the analysis. Associations of serial cfDNA concentration with residual cancer burden (RCB) and distant recurrence-free survival (DRFS) were examined.

Results: In TNBC, we observed a modest negative correlation between cfDNA concentration 3 …

Klrg1 Cell Depletion As A Novel Therapeutic Strategy In Patients With Mature T-Cell Lymphoma Subtypes, Bimarzhan Assatova, Robert Willim, Christopher Trevisani, Garrett Haskett, Khyati Maulik Kariya, Kusha Chopra, Sung Rye Park, Michael Yevgeniy Tolstorukov, Sean M Mccabe, Jessica Duffy, Abner Louissaint, Jani Huuhtanen, Dipabarna Bhattacharya, Satu Mustjoki, Min Jung Koh, Foster Powers, Elizabeth A Morgan, Lei Yang, Brandy Pinckney, Matthew J Cotton, Andrew Crabbe, Jessica Beth Ziemba, Ian Brain, Tayla B Heavican-Foral, Javeed Iqbal, Ronald Nemec, Anna Baird Rider, Josie Germain Ford, Min Ji Koh, Nora Scanlan, David J Feith, Thomas P Loughran, Won Seog Kim, Jaehyuk Choi, Juliette Roels, Lena Boehme, Tom Putteman, Tom Taghon, Jeffrey A Barnes, P Connor Johnson, Eric D Jacobsen, Steven A Greenberg, David M Weinstock, Salvia Jain

Faculty, Staff and Student Publications

Purpose: Develop a novel therapeutic strategy for patients with subtypes of mature T-cell and NK-cell neoplasms.

Experimental design: Primary specimens, cell lines, patient-derived xenograft models, commercially available, and proprietary anti-KLRG1 antibodies were used for screening, target, and functional validation.

Results: Here we demonstrate that surface KLRG1 is highly expressed on tumor cells in subsets of patients with extranodal NK/T-cell lymphoma (ENKTCL), T-prolymphocytic leukemia (T-PLL), and gamma/delta T-cell lymphoma (G/D TCL). The majority of the CD8+/CD57+ or CD3-/CD56+ leukemic cells derived from patients with T- and NK-large granular lymphocytic leukemia (T-LGLL and NK-LGLL), respectively, expressed surface KLRG1. The humanized afucosylated anti-KLRG1 …

Semirecumbent Positioning During Anesthesia Recovery And Postoperative Hypoxemia: A Randomized Clinical Trial, Xinghe Wang, Kedi Guo, Jia Sun, Yuping Yang, Yan Wu, Xihui Tang, Yuqing Xu, Qingsong Chen, Si Zeng, Liwei Wang, Su Liu

Faculty, Staff and Student Publications

IMPORTANCE: The efficacy of a semirecumbent position (SRP) in reducing postoperative hypoxemia during anesthesia emergence is unclear despite its widespread use.

OBJECTIVE: To determine the differences in postoperative hypoxemia between patients in an SRP and a supine position.

DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial was performed at a tertiary hospital in China between March 20, 2021, and May 10, 2022. Patients scheduled to undergo laparoscopic upper abdominal surgery under general anesthesia were enrolled. Study recruitment and follow-up are complete.

INTERVENTIONS: Patients were randomized to 1 of the following positions at the end of the operation until leaving the …

Irx4204 Induces Senescence And Cell Death In Her2-Positive Breast Cancer And Synergizes With Anti-Her2 Therapy, Cassandra L Moyer, Amanda Lanier, Jing Qian, Darian Coleman, Jamal Hill, Vidyasagar Vuligonda, Martin E Sanders, Abhijit Mazumdar, Powel H Brown

Faculty, Staff and Student Publications

PURPOSE: Rexinoids, agonists of nuclear retinoid X receptor (RXR), have been used for the treatment of cancers and are well tolerated in both animals and humans. However, the usefulness of rexinoids in treatment of breast cancer remains unknown. This study examines the efficacy of IRX4204, a highly specific rexinoid, in breast cancer cell lines and preclinical models to identify a biomarker for response and potential mechanism of action.

EXPERIMENTAL DESIGN: IRX4204 effects on breast cancer cell growth and viability were determined using cell lines, syngeneic mouse models, and primary patient-derived xenograft (PDX) tumors. In vitro assays of cell cycle, apoptosis, …

Telomere Dysfunction Alters Intestinal Stem Cell Dynamics To Promote Cancer, Kyle A Labella, Wen-Hao Hsu, Jiexi Li, Yutao Qi, Yonghong Liu, Jingjing Liu, Chia-Chin Wu, Yang Liu, Zingzhi Song, Yiyun Lin, Jonathan M Blecher, Shan Jiang, Xiaoying Shang, Jincheng Han, Denise J Spring, Jianhua Zhang, Yan Xia, Ronald A Depinho

Faculty, Staff and Student Publications

Telomere dynamics are linked to aging hallmarks, and age-associated telomere loss fuels the development of epithelial cancers. In Apc-mutant mice, the onset of DNA damage associated with telomere dysfunction has been shown to accelerate adenoma initiation via unknown mechanisms. Here, we observed that Apc-mutant mice engineered to experience telomere dysfunction show accelerated adenoma formation resulting from augmented cell competition and clonal expansion. Mechanistically, telomere dysfunction induces the repression of EZH2, resulting in the derepression of Wnt antagonists, which causes the differentiation of adjacent stem cells and a relative growth advantage to Apc-deficient telomere dysfunctional cells. Correspondingly, in this mouse model, …

Differentiation Between Descending Thoracic Aortic Diseases Using Machine Learning And Plasma Proteomic Signatures, Amanda Momenzadeh, Simion Kreimer, Dongchuan Guo, Matthew Ayres, Daniel Berman, Kuang-Yuh Chyu, Prediman K Shah, Dianna Milewicz, Ali Azizzadeh, Jesse G Meyer, Sarah Parker

Faculty, Staff and Student Publications

BACKGROUND: Descending thoracic aortic aneurysms and dissections can go undetected until severe and catastrophic, and few clinical indices exist to screen for aneurysms or predict risk of dissection.

METHODS: This study generated a plasma proteomic dataset from 75 patients with descending type B dissection (Type B) and 62 patients with descending thoracic aortic aneurysm (DTAA). Standard statistical approaches were compared to supervised machine learning (ML) algorithms to distinguish Type B from DTAA cases. Quantitatively similar proteins were clustered based on linkage distance from hierarchical clustering and ML models were trained with uncorrelated protein lists across various linkage distances with hyperparameter …

On Blockwise And Reference Panel-Based Estimators For Genetic Data Prediction In High Dimensions, Bingxin Zhao, Shurong Zheng, Hongtu Zhu

Faculty, Staff and Student Publications

Genetic prediction holds immense promise for translating genetic discoveries into medical advances. As the high-dimensional covariance matrix (or the linkage disequilibrium (LD) pattern) of genetic variants often presents a block-diagonal structure, numerous methods account for the dependence among variants in predetermined local LD blocks. Moreover, due to privacy considerations and data protection concerns, genetic variant dependence in each LD block is typically estimated from external reference panels rather than the original training data set. This paper presents a unified analysis of blockwise and reference panel-based estimators in a high-dimensional prediction framework without sparsity restrictions. We find that, surprisingly, even when …

Radiogenomics-Based Risk Prediction Of Glioblastoma Multiforme With Clinical Relevance, Xiaohua Qian, Hua Tan, Xiaona Liu, Weiling Zhao, Michael D Chan, Pora Kim, Xiaobo Zhou

Faculty, Staff and Student Publications

Glioblastoma multiforme (GBM)is the most common and aggressive primary brain tumor. Although temozolomide (TMZ)-based radiochemotherapy improves overall GBM patients' survival, it also increases the frequency of false positive post-treatment magnetic resonance imaging (MRI) assessments for tumor progression. Pseudo-progression (PsP) is a treatment-related reaction with an increased contrast-enhancing lesion size at the tumor site or resection margins miming tumor recurrence on MRI. The accurate and reliable prognostication of GBM progression is urgently needed in the clinical management of GBM patients. Clinical data analysis indicates that the patients with PsP had superior overall and progression-free survival rates. In this study, we aimed …

Persistent ∆Fosb Expression Limits Recurrent Seizure Activity And Provides Neuroprotection In The Dentate Gyrus Of App Mice, Gabriel S Stephens, Jin Park, Andrew Eagle, Jason You, Manuel Silva-Pérez, Chia-Hsuan Fu, Sumin Choi, Corey P St Romain, Chiho Sugimoto, Shelly A Buffington, Yi Zheng, Mauro Costa-Mattioli, Yin Liu, A J Robison, Jeannie Chin

Faculty, Staff and Student Publications

Recurrent seizures lead to accumulation of the activity-dependent transcription factor ∆FosB in hippocampal dentate granule cells in both mouse models of epilepsy and mouse models of Alzheimer's disease (AD), which is also associated with increased incidence of seizures. In patients with AD and related mouse models, the degree of ∆FosB accumulation corresponds with increasing severity of cognitive deficits. We previously found that ∆FosB impairs spatial memory in mice by epigenetically regulating expression of target genes such as calbindin that are involved in synaptic plasticity. However, the suppression of calbindin in conditions of neuronal hyperexcitability has been demonstrated to provide neuroprotection …

Immune Infiltration At The Primary Tumor Is Associated With Clinical Outcome Of Patients With Extranodal Extension Of Lymph Node Metastasis In Oral Cancer, Chieko Michikawa, Frederico O Gleber-Netto, Curtis R Pickering, Xiayu Rao, Jing Wang, Andrew G Sikora, Jeffrey N Myers, Mitchell J Frederick

Faculty, Staff and Student Publications

Background: Extranodal extension (ENE) of lymph node metastasis is one of the most reliable prognostic indicators for patients with locally advanced oral cancer. Although multiple reports have found a close relationship between immune infiltration of tumors and patient clinical outcomes, its association with ENE is unknown.

Methods: We identified 234 human papillomavirus-negative (HPV-) oral cavity squamous cell carcinoma (OSCC) patients in The Cancer Genome Atlas and investigated the immune infiltration profiles of primary tumors and their association with survival.

Results: Hierarchical clustering analysis clearly classified the overall immune infiltration status in OSCC into high immune or low immune groups. The …

Effect Of Home-Based Transcranial Direct Current Stimulation On Cognitive Function In Patients With Mild Cognitive Impairment: A Two-Week Intervention, Jaesub Park, Kyungmi Chung, Yoonkyung Oh, Kwang Joon Kim, Chang Oh Kim, Jin Young Park

Faculty, Staff and Student Publications

PURPOSE: Repeated transcranial direct current stimulation (tDCS) is expected to have the potential to improve cognitive function in patients with mild cognitive impairment (MCI). We aimed to evaluate the efficacy and safety of at-home tDCS for elderly patients with MCI.

MATERIALS AND METHODS: Patients aged 60-80 years, who maintained normal daily living but reported objective memory impairments, were enrolled. Active or sham stimulations were applied to the dorsal frontal cortex (left: anode; right: cathode) at home for 2 weeks. Changes in cognitive function were assessed using visual recognition tasks and the Mini-Mental State Exam (MMSE), and safety and efficacy were …

Contemporary Analysis Of Reexcision And Conversion To Mastectomy Rates And Associated Healthcare Costs For Women Undergoing Breast-Conserving Surgery, Youngran Kim, Cecilia Ganduglia-Cazaban, Nina Tamirisa, Anthony Lucci, Trudy Millard Krause

Faculty, Staff and Student Publications

PURPOSE: This study was designed to provide a comprehensive and up-to-date understanding of population-level reoperation rates and incremental healthcare costs associated with reoperation for patients who underwent breast-conserving surgery (BCS).

METHODS: This is a retrospective cohort study using Merative™ MarketScan® commercial insurance data and Medicare 5% fee-for-service claims data. The study included females aged 18-64 years in the commercial cohort and females aged 18 years and older in the Medicare cohort, who underwent initial BCS for breast cancer in 2017-2019. Reoperation rates within a year of the initial BCS and overall 1-year healthcare costs stratified by reoperation status were measured. …

Fibroblast Subpopulations In Systemic Sclerosis: Functional Implications Of Individual Subpopulations And Correlations With Clinical Features, Honglin Zhu, Hui Luo, Brian Skaug, Tracy Tabib, Yi-Nan Li, Yongguang Tao, Alexandru-Emil Matei, Marka A Lyons, Georg Schett, Robert Lafyatis, Shervin Assassi, Jörg H W Distler

Faculty, Staff and Student Publications

Fibroblasts constitute a heterogeneous population of cells. In this study, we integrated single-cell RNA-sequencing and bulk RNA-sequencing data as well as clinical information to study the role of individual fibroblast populations in systemic sclerosis (SSc). SSc skin demonstrated an increased abundance of COMP+, COL11A1+, MYOC+, CCL19+, SFRP4/SFRP2+, and PRSS23/SFRP2+ fibroblasts signatures and decreased proportions of CXCL12+ and PI16+ fibroblast signatures in the Prospective Registry of Early Systemic Sclerosis and Genetics versus Environment in Scleroderma Outcome Study cohorts. Numerical differences were confirmed by multicolor immunofluorescence for selected fibroblast populations. COMP+, COL11A1+, SFRP4/SFRP2+, PRSS23/SFRP2+, and PI16+ fibroblasts were similarly altered between normal …

Correction: Contemporary Analysis Of Reexcision And Conversion To Mastectomy Rates And Associated Healthcare Costs For Women Undergoing Breast-Conserving Surgery, Youngran Kim, Cecilia Ganduglia-Cazaban, Nina Tamirisa, Anthony Lucci, Trudy Millard Krause

Faculty, Staff and Student Publications

Correction: Annals of Surgical Oncology 10.1245/s10434-024-14902-z

The article “Contemporary Analysis of Reexcision and Conversion to Mastectomy Rates and Associated Healthcare Costs for Women Undergoing Breast‑Conserving Surgery”, written by Kim et al. was originally published electronically on the publisher’s internet portal on February 6, 2024, without open access. With the authors‘ decision to opt for Open Choice the copyright of the article changed on March 14, 2024, to © The Author(s) 2024, and the article is forthwith distributed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long …

Time-To-Event Genome-Wide Association Study For Incident Cardiovascular Disease In People With Type 2 Diabetes, Soo Heon Kwak, Ryan B Hernandez-Cancela, Daniel A Dicorpo, David E Condon, Jordi Merino, Peitao Wu, Jennifer A Brody, Jie Yao, Xiuqing Guo, Fariba Ahmadizar, Mariah Meyer, Murat Sincan, Josep M Mercader, Sujin Lee, Jeffrey Haessler, Ha My T Vy, Zhaotong Lin, Nicole D Armstrong, Shaopeng Gu, Noah L Tsao, Leslie A Lange, Ningyuan Wang, Kerri L Wiggins, Stella Trompet, Simin Liu, Ruth J F Loos, Renae Judy, Philip H Schroeder, Natalie R Hasbani, Maxime M Bos, Alanna C Morrison, Rebecca D Jackson, Alexander P Reiner, Joann E Manson, Ninad S Chaudhary, Lynn K Carmichael, Yii-Der Ida Chen, Kent D Taylor, Mohsen Ghanbari, Joyce Van Meurs, Achilleas N Pitsillides, Bruce M Psaty, Raymond Noordam, Ron Do, Kyong Soo Park, J Wouter Jukema, Maryam Kavousi, Adolfo Correa, Stephen S Rich, Scott M Damrauer, Catherine Hajek, Nam H Cho, Marguerite R Irvin, James S Pankow, Girish N Nadkarni, Robert Sladek, Mark O Goodarzi, Jose C Florez, Daniel I Chasman, Susan R Heckbert, Charles Kooperberg, Josée Dupuis, Rajeev Malhotra, Paul S De Vries, Ching-Ti Liu, Jerome I Rotter, James B Meigs

Faculty, Staff and Student Publications

Objective: To identify genetic risk factors for incident cardiovascular disease (CVD) among people with type 2 diabetes (T2D).

Research design and methods: We conducted a multiancestry time-to-event genome-wide association study for incident CVD among people with T2D. We also tested 204 known coronary artery disease (CAD) variants for association with incident CVD.

Results: Among 49,230 participants with T2D, 8,956 had incident CVD events (event rate 18.2%). We identified three novel genetic loci for incident CVD: rs147138607 (near CACNA1E/ZNF648, hazard ratio [HR] 1.23, P = 3.6 × 10-9), rs77142250 (near HS3ST1, HR 1.89, P = 9.9 × 10-9), and rs335407 (near …

Prioritization Of Kidney Cell Types Highlights Myofibroblast Cells In Regulating Human Blood Pressure, Mahboube Ganji-Arjenaki, Zoha Kamali, International Consortium Of Blood Pressure; Soroush Sardari, Soroush Sardari, Martin De Borst, Harold Snieder, Ahmad Vaez

Faculty, Staff and Student Publications

INTRODUCTION: Blood pressure (BP) is a highly heritable trait with over 2000 underlying genomic loci identified to date. Although the kidney plays a key role, little is known about specific cell types involved in the genetic regulation of BP.

METHODS: Here, we applied stratified linkage disequilibrium score (LDSC) regression to connect BP genome-wide association studies (GWAS) results to specific cell types of the mature human kidney. We used the largest single-stage BP genome-wide analysis to date, including up to 1,028,980 adults of European ancestry, and single-cell transcriptomic data from 14 mature human kidneys, with mean age of 41 years.

RESULTS: …