Digital Commons Network^™

Author Correction: A Ck2 And Sumo-Dependent, Pml Nb-Involved Regulatory Mechanism Controlling Blm Ubiquitination And G-Quadruplex Resolution, Shichang Liu, Erin Atkinson, Adriana Paulucci-Holthauzen, Bin Wang

Faculty, Staff and Student Publications

No abstract provided.

Identification Of New Egfr Inhibitors By Structure-Based Virtual Screening And Biological Evaluation, Shuyi Wang, Xiaotian Xu, Chuxin Pan, Qian Guo, Qinlan Li, Shanhe Wan, Zhonghuang Li, Jiajie Zhang, Xiaoyun Wu

Faculty, Staff and Student Publications

Epidermal growth factor receptor (EGFR) inhibitors have been used in clinical for the treatment of non-small-cell lung cancer for years. However, the emergence of drug resistance continues to be a major problem. To identify potential inhibitors, molecular docking-based virtual screening was conducted on ChemDiv and Enamine commercial databases using the Glide program. After multi-step VS and visual inspection, a total of 23 compounds with novel and varied structures were selected, and the predicted ADMET properties were within the satisfactory range. Further molecular dynamics simulations revealed that the reprehensive compound ZINC49691377 formed a stable complex with the allosteric pocket of EGFR …

Gestational Diabetes Augments Group B Streptococcus Infection By Disrupting Maternal Immunity And The Vaginal Microbiota, Vicki Mercado-Evans, Marlyd E Mejia, Jacob J Zulk, Samantha Ottinger, Zainab A Hameed, Camille Serchejian, Madelynn G Marunde, Clare M Robertson, Mallory B Ballard, Simone H Ruano, Natalia Korotkova, Anthony R Flores, Kathleen A Pennington, Kathryn A Patras

Faculty, Staff and Student Publications

Group B Streptococcus (GBS) is a pervasive perinatal pathogen, yet factors driving GBS dissemination in utero are poorly defined. Gestational diabetes mellitus (GDM), a complication marked by dysregulated immunity and maternal microbial dysbiosis, increases risk for GBS perinatal disease. Using a murine GDM model of GBS colonization and perinatal transmission, we find that GDM mice display greater GBS in utero dissemination and subsequently worse neonatal outcomes. Dual-RNA sequencing reveals differential GBS adaptation to the GDM reproductive tract, including a putative glycosyltransferase (yfhO), and altered host responses. GDM immune disruptions include reduced uterine natural killer cell activation, impaired recruitment to placentae, …

Impact Of Kras Mutations And Co-Mutations On Clinical Outcomes In Pancreatic Ductal Adenocarcinoma, Abdelrahman Yousef, Mahmoud Yousef, Saikat Chowdhury, Kawther Abdilleh, Mark Knafl, Paul Edelkamp, Kristin Alfaro-Munoz, Ray Chacko, Jennifer Peterson, Brandon G Smaglo, Robert A Wolff, Shubham Pant, Michael S Lee, Jason Willis, Michael Overman, Sudheer Doss, Lynn Matrisian, Mark W Hurd, Rebecca Snyder, Matthew H G Katz, Huamin Wang, Anirban Maitra, John Paul Shen, Dan Zhao

Faculty, Staff and Student Publications

The relevance of KRAS mutation alleles to clinical outcome remains inconclusive in pancreatic adenocarcinoma (PDAC). We conducted a retrospective study of 803 patients with PDAC (42% with metastatic disease) at MD Anderson Cancer Center. Overall survival (OS) analysis demonstrated that KRAS mutation status and subtypes were prognostic (p < 0.001). Relative to patients with KRAS wildtype tumors (median OS 38 months), patients with KRASG12R had a similar OS (median 34 months), while patients with KRASQ61 and KRASG12D mutated tumors had shorter OS (median 20 months [HR: 1.9, 95% CI 1.2-3.0, p = 0.006] and 22 months [HR: 1.7, 95% CI 1.3-2.3, p < 0.001], respectively). There was enrichment of KRASG12D mutation in metastatic tumors (34% vs 24%, OR: 1.7, 95% CI 1.2-2.4, p = 0.001) and enrichment of KRASG12R in well and moderately differentiated tumors (14% vs 9%, OR: 1.7, 95% CI 1.05-2.99, p = 0.04). Similar findings were observed in the external validation cohort (PanCAN's Know Your Tumor® dataset, n = 408).

Targeting Prostate Tumor Low-Molecular Weight Tyrosine Phosphatase For Oxidation-Sensitizing Therapy, Stephanie M Stanford, Tiffany P Nguyen, Joseph Chang, Zixuan Zhao, G Lavender Hackman, Eugenio Santelli, Colton M Sanders, Madhusudhanarao Katiki, Eleonora Dondossola, Brooke L Brauer, Michael A Diaz, Yuan Zhan, Sterling H Ramsey, Philip A Watson, Banumathi Sankaran, Claudia Paindelli, Vanessa Parietti, Antonios G Mikos, Alessia Lodi, Aditya Bagrodia, Andrew Elliott, Rana R Mckay, Ramachandran Murali, Stefano Tiziani, Arminja N Kettenbach, Nunzio Bottini

Faculty, Staff and Student Publications

Protein tyrosine phosphatases (PTPs) play major roles in cancer and are emerging as therapeutic targets. Recent reports suggest low-molecular weight PTP (LMPTP)-encoded by the ACP1 gene-is overexpressed in prostate tumors. We found ACP1 up-regulated in human prostate tumors and ACP1 expression inversely correlated with overall survival. Using CRISPR-Cas9-generated LMPTP knockout C4-2B and MyC-CaP cells, we identified LMPTP as a critical promoter of prostate cancer (PCa) growth and bone metastasis. Through metabolomics, we found that LMPTP promotes PCa cell glutathione synthesis by dephosphorylating glutathione synthetase on inhibitory Tyr270. PCa cells lacking LMPTP showed reduced glutathione, enhanced activation of eukaryotic initiation factor …

Efficacy And Safety Of Autologous Tumor-Infiltrating Lymphocytes In Recurrent Or Refractory Ovarian Cancer, Colorectal Cancer, And Pancreatic Ductal Adenocarcinoma, Rodabe Amaria, Anne Knisely, David Vining, Scott Kopetz, Michael J Overman, Milind Javle, Mara B Antonoff, Ching-Wei D Tzeng, Robert A Wolff, Shubham Pant, Kathryn Lito, Kelly Rangel, Bryan Fellman, Ying Yuan, Karen H Lu, Donastas Sakellariou-Thompson, Cara L Haymaker, Marie-Andrée Forget, Patrick Hwu, Chantale Bernatchez, Amir A Jazaeri

Faculty, Staff and Student Publications

BACKGROUND: Tumor-infiltrating lymphocyte (TIL) therapy has shown efficacy in metastatic melanoma, non-small cell lung cancer, and other solid tumors. Our preclinical work demonstrated more robust CD8 predominant TIL production when agonistic anti-4-1BB and CD3 antibodies were used in early ex vivo TIL culture.

METHODS: Patients with treatment-refractory metastatic colorectal (CRC), pancreatic (PDAC) and ovarian (OVCA) cancers were eligible. Lymphodepleting chemotherapy was followed by infusion of ex vivo expanded TIL, manufactured at MD Anderson Cancer Center with IL-2 and agonistic stimulation of CD3 and 4-1BB (urelumab). Patients received up to six doses of high-dose IL-2 after TIL infusion. Primary endpoint was …

Low Molecular Weight Heparin Decreases Pro-Coagulant Activity In Clinical Msc Products, Jacob B Schriner, Fabio Triolo, Brijesh S Gill, Jessica C Cardenas, Scott D Olson, Charles S Cox

Faculty, Staff and Student Publications

Background aims: Mesenchymal stromal cells (MSCs) are multipotent adult cells that can be isolated from tissues including bone marrow [MSC(BM)], adipose [MSC(AT)] and umbilical cord [MSC(CT)]. Previous studies have linked expression of tissue factor (TF) on MSC surfaces to a procoagulant effect. Venous thromboembolism (VTE), immediate blood-mediated inflammatory reaction (IBMIR) and microvascular thrombosis remain a risk with intravascular MSC therapy. We examined the effect of low molecular weight heparin (LMWH) on clinical-grade MSCs using calibrated automated thrombography (CAT).

Methods: Clinical grade MSC(BM)s, MSC(AT)s and MSC(CT)s harvested at passage 4 were added to normal pooled plasma (NPP) to a final concentration …

Improved Mortality Prediction For Pediatric Acute Liver Failure Using Dynamic Prediction Strategy, Ruosha Li, Jingyan Wang, Cuihong Zhang, James E Squires, Steven H Belle, Jing Ning, Jianwen Cai, Robert H Squires

Faculty, Staff and Student Publications

OBJECTIVES: To develop and validate a prediction tool for pediatric acute liver failure (PALF) mortality risks that captures the rapid and heterogeneous clinical course for accurate and updated prediction.

METHODS: Data included 1144 participants with PALF enrolled during three phases of the PALF registry study over 15 years. Using joint modeling, we built a dynamic prediction tool for mortality by combining longitudinal trajectories of multiple laboratory and clinical variables. The predictive performance for 7-day and 21-day mortality was assessed using the area under curve (AUC) through cross-validation and split-by-time validation.

RESULTS: We constructed a prognostic joint model that combines the …

Regression Analysis Of Multivariate Recurrent Event Data Allowing Time-Varying Dependence With Application To Stroke Registry Data, Wen Li, Mohammad H Rahbar, Sean I Savitz, Jing Zhang, Sori Kim Lundin, Amirali Tahanan, Jing Ning

Faculty, Staff and Student Publications

In multivariate recurrent event data, each patient may repeatedly experience more than one type of event. Analysis of such data gets further complicated by the time-varying dependence structure among different types of recurrent events. The available literature regarding the joint modeling of multivariate recurrent events assumes a constant dependency over time, which is strict and often violated in practice. To close the knowledge gap, we propose a class of flexible shared random effects models for multivariate recurrent event data that allow for time-varying dependence to adequately capture complex correlation structures among different types of recurrent events. We developed an expectation-maximization …

Absence Of Btk, Bcl2, And Plcg2 Mutations In Chronic Lymphocytic Leukemia Relapsing After First-Line Treatment With Fixed-Duration Ibrutinib Plus Venetoclax, Nitin Jain, Lisa J Croner, John N Allan, Tanya Siddiqi, Alessandra Tedeschi, Xavier C Badoux, Karl Eckert, Leo W K Cheung, Anwesha Mukherjee, James P Dean, Edith Szafer-Glusman, John F Seymour

Faculty, Staff and Student Publications

Purpose: Mutations in BTK, PLCG2, and BCL2 have been reported in patients with progressive disease (PD) on continuous single-agent BTK or BCL2 inhibitor treatment. We tested for these mutations in samples from patients with PD after completion of first-line treatment with fixed-duration ibrutinib plus venetoclax for chronic lymphocytic leukemia (CLL) in the phase II CAPTIVATE study.

Patients and methods: A total of 191 patients completed fixed-duration ibrutinib plus venetoclax (three cycles of ibrutinib then 12-13 cycles of ibrutinib plus venetoclax). Genomic risk features [del(11q), del(13q), del(17p), trisomy 12, complex karyotype, unmutated IGHV, TP53 mutated] and mutations in genes recurrently mutated …

Aneuploidy And Complex Genomic Rearrangements In Cancer Evolution, Toby M Baker, Sara Waise, Maxime Tarabichi, Peter Van Loo

Faculty, Staff and Student Publications

Mutational processes that alter large genomic regions occur frequently in developing tumors. They range from simple copy number gains and losses to the shattering and reassembly of entire chromosomes. These catastrophic events, such as chromothripsis, chromoplexy and the formation of extrachromosomal DNA, affect the expression of many genes and therefore have a substantial effect on the fitness of the cells in which they arise. In this review, we cover large genomic alterations, the mechanisms that cause them and their effect on tumor development and evolution.

Enhancing Anti-Aml Activity Of Venetoclax By Isoflavone Me-344 Through Suppression Of Oxphos And/Or Purine Biosynthesis In Vitro, Katie H Hurrish, Yongwei Su, Shraddha Patel, Cassandra L Ramage, Jianlei Zhao, Brianna R Temby, Jenna L Carter, Holly Edwards, Steven A Buck, Sandra E Wiley, Maik Hüttemann, Lisa Polin, Juiwanna Kushner, Sijana H Dzinic, Kathryn White, Xun Bao, Jing Li, Jay Yang, Julie Boerner, Zhanjun Hou, Gheath Al-Atrash, Sergej N Konoplev, Jonathan Busquets, Stefano Tiziani, Larry H Matherly, Jeffrey W Taub, Marina Konopleva, Yubin Ge, Natalia Baran

Faculty, Staff and Student Publications

Venetoclax (VEN), in combination with low dose cytarabine (AraC) or a hypomethylating agent, is FDA approved to treat acute myeloid leukemia (AML) in patients who are over the age of 75 or cannot tolerate standard chemotherapy. Despite high response rates to these therapies, most patients succumb to the disease due to relapse and/or drug resistance, providing an unmet clinical need for novel therapies to improve AML patient survival. ME-344 is a potent isoflavone with demonstrated inhibitory activity toward oxidative phosphorylation (OXPHOS) and clinical activity in solid tumors. Given that OXPHOS inhibition enhances VEN antileukemic activity against AML, we hypothesized that …

The Influence Of Incubation Temperature On Offspring Traits Varies Across Northern And Southern Populations Of The American Alligator (Alligator Mississippiensis), Christopher R Smaga, Samantha L Bock, Josiah M Johnson, Thomas Rainwater, Randeep Singh, Vincent Deem, Andrew Letter, Arnold Brunell, Benjamin B Parrott

Faculty, Staff and Student Publications

Maternal provisioning and the developmental environment are fundamental determinants of offspring traits, particularly in oviparous species. However, the extent to which embryonic responses to these factors differ across populations to drive phenotypic variation is not well understood. Here, we examine the contributions of maternal provisioning and incubation temperature to hatchling morphological and metabolic traits across four populations of the American alligator (Alligator mississippiensis), encompassing a large portion of the species' latitudinal range. Our results show that whereas the influence of egg mass is generally consistent across populations, responses to incubation temperature show population-level variation in several traits, including …

Glucose Metabolism In Posterior Cingulate Cortex Has Supplementary Value To Predict The Progression Of Cognitively Unimpaired To Dementia Due To Alzheimer’S Disease: An Exploratory Study Of 18f-Fdg-Pet, Qi Zhang, Chunqiu Fan, Luyao Wang, Taoran Li, Min Wang, Ying Han, Jiehui Jiang, Alzheimer’S Disease Neuroimaging Initiative

Faculty, Staff and Student Publications

Amyloid-β (Aβ) and tau are important biomarkers to predict the progression of cognitively unimpaired (CU) to dementia due to Alzheimer's disease (AD), according to the diagnosis framework from the US National Institute on Aging and the Alzheimer's Association (NIA-AA). However, it is clinically difficult to predict those subjects who were already with Aβ positive (A +) or tau positive (T +). As a typical characteristic of neurodegeneration in the diagnosis framework, the hypometabolism of the posterior cingulate cortex (PCC) has significant clinical value in the early prediction and prevention of AD. In this paper, we proposed the glucose metabolism in …

Development Of Resistance To Type Ii Jak2 Inhibitors In Mpn Depends On Axl Kinase And Is Targetable, Tamara Codilupi, Jakub Szybinski, Stefanie Arunasalam, Sarah Jungius, Andrew C Dunbar, Simona Stivala, Sime Brkic, Camille Albrecht, Lenka Vokalova, Julie L Yang, Katarzyna Buczak, Nilabh Ghosh, Jakob R Passweg, Alicia Rovo, Anne Angelillo-Scherrer, Dmitry Pankov, Stefan Dirnhofer, Ross L Levine, Richard Koche, Sara C Meyer

Faculty, Staff and Student Publications

PURPOSE: Myeloproliferative neoplasms (MPN) dysregulate JAK2 signaling. Because clinical JAK2 inhibitors have limited disease-modifying effects, type II JAK2 inhibitors such as CHZ868 stabilizing inactive JAK2 and reducing MPN clones, gain interest. We studied whether MPN cells escape from type ll inhibition.

EXPERIMENTAL DESIGN: MPN cells were continuously exposed to CHZ868. We used phosphoproteomic analyses and ATAC/RNA sequencing to characterize acquired resistance to type II JAK2 inhibition, and targeted candidate mediators in MPN cells and mice.

RESULTS: MPN cells showed increased IC50 and reduced apoptosis upon CHZ868 reflecting acquired resistance to JAK2 inhibition. Among >2,500 differential phospho-sites, MAPK pathway activation was …

Large-Scale Investigation Of White Matter Structural Differences In Bilingual And Monolingual Children: An Adolescent Brain Cognitive Development Data Study, Juliana Ronderos, Jennifer Zuk, Arturo E Hernandez, Kelly A Vaughn

Faculty, Staff and Student Publications

Emerging research has provided valuable insights into the structural characteristics of the bilingual brain from studies of bilingual adults; however, there is a dearth of evidence examining brain structural alterations in childhood associated with the bilingual experience. This study examined the associations between bilingualism and white matter organization in bilingual children compared to monolingual peers leveraging the large-scale data from the Adolescent Brain Cognitive Development (ABCD) Study. Then, 446 bilingual children (ages 9-10) were identified from the participants in the ABCD data and rigorously matched to a group of 446 monolingual peers. Multiple regression models for selected language and cognitive …

Girth-Based Administered Activity For Pediatric 99mtc-Dmsa Spect, Ye Li, Justin L Brown, Jingyan Xu, Junyu Chen, Michael Ghaly, Monet Dugan, Xinhua Cao, Yong Du, Frederic H Fahey, Wesley Bolch, George Sgouros, Eric C Frey

Faculty, Staff and Student Publications

Background: Pediatric molecular imaging requires a balance between administering an activity that will yield sufficient diagnostic image quality while maintaining patient radiation exposure at acceptable levels. In current clinical practice, this balance is arrived at by the current North American Consensus Guidelines in which patient weight is used to recommend the administered activity (AA).

Purpose: We have previously demonstrated that girth (waist circumference at the level of the kidneys) is better at equalizing image quality than patient weight for pediatric Tc-99m DMSA renal function imaging. However, the correlation between image quality (IQ), AA, and patient girth has not been rigorously …

Impact Of Intra-Operative Shock And Resuscitation On Surgical Site Infections After Trauma Laparotomy, Shah-Jahan M Dodwad, Krislynn M Mueck, Heather R Kregel, Chelsea J Guy-Frank, Kayla D Isbell, James M Klugh, Charles E Wade, John A Harvin, Lillian S Kao, Michael W Wandling

Faculty, Staff and Student Publications

Background: Patients undergoing trauma laparotomy experience high rates of surgical site infection (SSI). Although intra-operative shock is a likely contributor to SSI risk, little is known about the relation between shock, intra-operative restoration of physiologic normalcy, and SSI development.

Patients and Methods: A retrospective review of trauma patients who underwent emergent definitive laparotomy was performed. Using shock index and base excess at the beginning and end of laparotomy, patients were classified as normal, persistent shock, resuscitated, or new shock. Univariable and multivariable analyses were performed to identify predictors of organ/space SSI, superficial/deep SSI, and any SSI.

Results: Of 1,191 …

Impact And Efficiency Of Treatment Across Two Ptsd Clinical Trials Comparing In-Person And Telehealth Service Delivery Formats, Cindy A Mcgeary, Leslie A Morland, Patricia A Resick, Casey L Straud, John C Moring, Min Ji Sohn, Margaret-Anne Mackintosh, Stacey Young-Mccaughan, Ron Acierno, Sheila A M Rauch, Jim Mintz, Donald D Mcgeary, Stephanie Y Wells, Kathleen Grubbs, Paul S Nabity, Chelsea J Mcmahon, Brett T Litz, Dawn I Velligan, Alexandra Macdonald, Emma Mata-Galan, Stephen L Holliday, Kirsten H Dillon, John D Roache, Alan L Peterson

Faculty, Staff and Student Publications

The intent of this study is to examine treatment impact and efficiency observed when cognitive behavioral treatments for posttraumatic stress disorder (PTSD) are delivered in-person or using telehealth. This study pooled data from 268 veterans enrolled in two PTSD clinical trials. In both trials, treatment was delivered using in-home telehealth (telehealth arm), in-home in-person (in-home arm), and in-office care, where patients traveled to the Department of Veterans Affairs for either office-based telehealth or office-based in-person care (office arm). Average age was 44 (SD = 12.57); 80.9% were males. The PTSD Checklist for DSM-5 (PCL-5) was used …

A Surgical Desirability Of Outcome Ranking (Door) Reveals Complex Relationships Between Race/Ethnicity, Insurance Type, And Neighborhood Deprivation, Michael A Jacobs, Susanne Schmidt, Daniel E Hall, Karyn B Stitzenberg, Lillian S Kao, Bradley B Brimhall, Chen-Pin Wang, Laura S Manuel, Hoah-Der Su, Jonathan C Silverstein, Paula K Shireman

Faculty, Staff and Student Publications

Objective: Develop an ordinal Desirability of Outcome Ranking (DOOR) for surgical outcomes to examine complex associations of Social Determinants of Health.

Background: Studies focused on single or binary composite outcomes may not detect health disparities.

Methods: Three health care system cohort study using NSQIP (2013-2019) linked with EHR and risk-adjusted for frailty, preoperative acute serious conditions (PASC), case status and operative stress assessing associations of multilevel Social Determinants of Health of race/ethnicity, insurance type (Private 13,957; Medicare 15,198; Medicaid 2835; Uninsured 2963) and Area Deprivation Index (ADI) on DOOR and the binary Textbook Outcomes (TO).

Results: Patients living in highly …

Inspiring New Science To Guide Healthcare In Turner Syndrome: Rationale, Design, And Methods For The Insights Registry, Roopa Kanakatti Shankar, Alexandra Carl, Jennifer R Law, Vaneeta Bamba, Wendy J Brickman, Siddharth K Prakash, Tazim Dowlut Mcelroy, Susan Howell, Iris Gutmark Little, Karen O Klein, Catherina T Pinnaro, Kelly Ranallo, Marybel Good, Shanlee M Davis

Faculty, Staff and Student Publications

Inspiring New Science to Guide Healthcare in Turner Syndrome (InsighTS) Registry is a national, multicenter registry for individuals with Turner syndrome (TS) designed to collect and store validated longitudinal clinical data from a diverse cohort of patients with TS. Herein, we describe the rationale, design, and approach used to develop the InsighTS registry, as well as the demographics of the initial participants to illustrate the registry's diversity and future utility. Multiple stakeholder groups have been involved from project conceptualization through dissemination, ensuring the registry serves the priorities of the TS community. Key features of InsighTS include recruitment strategies to facilitate …

Limited Independent Follow-Up With Germline Testing Of Variants Detected In Brca1 And Brca2 By Tumor-Only Sequencing, Carol J Nowlen, Molly Daniels, Burak Uzunparmak, Ecaterina E Ileana Dumbrava, Ying Yuan, Keyur P Patel, Nadine Rayes, Jacqueline Harkenrider, Chetna Wathoo, Jennifer Veazie, Krystle A Luna, Wanlin Wang, Chacha Horombe, Milind Javle, Jordi Rodon Ahnert, Timothy A Yap, Banu Arun, Karen H Lu, Funda Meric-Bernstam

Faculty, Staff and Student Publications

Introduction

Genomic profiling is performed in patients with advanced or metastatic cancer, in order to direct cancer treatment, often sequencing tumor-only, without a matched germline comparator. However, because many of the genes analyzed on tumor profiling overlap with those known to be associated with hereditary cancer predisposition syndromes (HCPS), tumor-only profiling can unknowingly uncover germline pathogenic (P) and likely pathogenic variants (LPV). In this study, we evaluated the number of patients with P/LPVs identified in BRCA1 and BRCA2 (BRCA1/2) via tumor-only profiling, then determined the germline testing outcomes for those patients.

Methods

A retrospective chart review was performed …

Rationale And Design Of The Nephrotic Syndrome Study Network (Neptune) Match In Glomerular Diseases: Designing The Right Trial For The Right Patient, Today, Howard Trachtman, Hailey Desmond, Amanda L Williams, Laura H Mariani, Sean Eddy, Wenjun Ju, Laura Barisoni, Heather K Ascani, Wendy R Uhlmann, Cathie Spino, Lawrence B Holzman, John R Sedor, Crystal Gadegbeku, Lalita Subramanian, Chrysta C Lienczewski, Tina Manieri, Scott J Roberts, Debbie S Gipson, Matthias Kretzler, Neptune Investigators

Faculty, Staff and Student Publications

Glomerular diseases are classified using a descriptive taxonomy that is not reflective of the heterogeneous underlying molecular drivers. This limits not only diagnostic and therapeutic patient management, but also impacts clinical trials evaluating targeted interventions. The Nephrotic Syndrome Study Network (NEPTUNE) is poised to address these challenges. The study has enrolled >850 pediatric and adult patients with proteinuric glomerular diseases who have contributed to deep clinical, histologic, genetic, and molecular profiles linked to long-term outcomes. The NEPTUNE Knowledge Network, comprising combined, multiscalar data sets, captures each participant's molecular disease processes at the time of kidney biopsy. In this editorial, we …

A Kinesin-13 Family Kinesin In Trypanosoma Brucei Regulates Cytokinesis And Cytoskeleton Morphogenesis By Promoting Microtubule Bundling, Huiqing Hu, Yasuhiro Kurasawa, Qing Zhou, Ziyin Li

Faculty, Staff and Student Publications

The early branching eukaryote Trypanosoma brucei divides uni-directionally along the longitudinal cell axis from the cell anterior toward the cell posterior, and the cleavage furrow ingresses along the cell division plane between the new and the old flagella of a dividing bi-flagellated cell. Regulation of cytokinesis in T. brucei involves actomyosin-independent machineries and trypanosome-specific signaling pathways, but the molecular mechanisms underlying cell division plane positioning remain poorly understood. Here we report a kinesin-13 family protein, KIN13-5, that functions downstream of FPRC in the cytokinesis regulatory pathway and determines cell division plane placement. KIN13-5 localizes to multiple cytoskeletal structures, interacts …

Gut Microbiome Of Patients With Breast Cancer In Vietnam, Sang M Nguyen, Huong T T Tran, Jirong Long, Martha J Shrubsole, Hui Cai, Yaohua Yang, Lan M Nguyen, Giang H Nguyen, Chu V Nguyen, To V Ta, Jie Wu, Qiuyin Cai, Wei Zheng, Thuan V Tran, Xiao-Ou Shu

Faculty, Staff and Student Publications

PURPOSE: Gut microbiota play an important role in human health, including cancer. Cancer and its treatment, in turn, may alter the gut microbiome. To understand this complex relationship, we profiled the gut microbiome of 356 Vietnamese patients with breast cancer.

MATERIALS AND METHODS: Stool samples were collected before chemotherapy, with 162 pre- and 194 postsurgery. The gut microbiome was measured by shotgun metagenomic sequencing. Associations of gut microbial diversity, taxa abundance, and gut microbiome health index (GMHI) with sociodemographic, clinical factors, and tumor characteristics were evaluated.

RESULTS: Postsurgery samples were associated with significantly lower α- and β-diversities (

CONCLUSION: Our …

Shape Anisotropy-Governed High-Performance Nanomagnetosol For In Vivo Magnetic Particle Imaging Of Lungs, Saumya Nigam, Jeotikanta Mohapatra, Ashley V Makela, Hanaan Hayat, Jessi Mercedes Rodriguez, Aixia Sun, Elizabeth Kenyon, Nathan A Redman, Dana Spence, George Jabin, Bin Gu, Mohamed Ashry, Lorenzo F Sempere, Arijit Mitra, Jinxing Li, Jiahui Chen, Guo-Wei Wei, Steven Bolin, Brett Etchebarne, J Ping Liu, Christopher H Contag, Ping Wang

Faculty, Staff and Student Publications

Caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), coronavirus disease 2019 (COVID-19) has shown extensive lung manifestations in vulnerable individuals, putting lung imaging and monitoring at the forefront of early detection and treatment. Magnetic particle imaging (MPI) is an imaging modality, which can bring excellent contrast, sensitivity, and signal-to-noise ratios to lung imaging for the development of new theranostic approaches for respiratory diseases. Advances in MPI tracers would offer additional improvements and increase the potential for clinical translation of MPI. Here, a high-performance nanotracer based on shape anisotropy of magnetic nanoparticles is developed and its use in MPI imaging …

Correction: Il-1Α Mediates Innate And Acquired Resistance To Immunotherapy In Melanoma, Shubhra Singh, Zhilan Xiao, Karishma Bavisi, Jason Roszik, Brenda D Melendez, Zhiqiang Wang, Mark J Cantwell, Richard E Davis, Greg Lizee, Patrick Hwu, Sattva S Neelapu, Willem W Overwijk, Manisha Singh

Faculty, Staff and Student Publications

No abstract provided.

The Artificial Intelligence-Based Model Anorak Improves Histopathological Grading Of Lung Adenocarcinoma, Xiaoxi Pan, Khalid Abduljabbar, Jose Coelho-Lima, Anca-Ioana Grapa, Hanyun Zhang, Alvin Ho Kwan Cheung, Juvenal Baena, Takahiro Karasaki, Claire Rachel Wilson, Marco Sereno, Selvaraju Veeriah, Sarah J Aitken, Allan Hackshaw, Andrew G Nicholson, Mariam Jamal-Hanjani, Charles Swanton, Yinyin Yuan, John Le Quesne, David A Moore

Faculty, Staff and Student Publications

The introduction of the International Association for the Study of Lung Cancer grading system has furthered interest in histopathological grading for risk stratification in lung adenocarcinoma. Complex morphology and high intratumoral heterogeneity present challenges to pathologists, prompting the development of artificial intelligence (AI) methods. Here we developed ANORAK (pyrAmid pooliNg crOss stReam Attention networK), encoding multiresolution inputs with an attention mechanism, to delineate growth patterns from hematoxylin and eosin-stained slides. In 1,372 lung adenocarcinomas across four independent cohorts, AI-based grading was prognostic of disease-free survival, and further assisted pathologists by consistently improving prognostication in stage I tumors. Tumors with discrepant …

Increased Prevalence Of Clostridioides Difficile Infection Among Pediatric Oncology Patients: Risk Factors For Infection And Complications, Brianna R Murphy, Natalie J Dailey Garnes, Hyunsoo Hwang, Christine B Peterson, Kevin W Garey, Pablo Okhuysen

Faculty, Staff and Student Publications

Background: Pediatric oncology patients, who are typically immunosuppressed, exposed to medications associated with increased Clostridioides difficile infection (CDI) risk and hospitalized, are expected to be at substantial risk for infection and complications. Although certain C. difficile ribotypes have been associated with more severe infection in adults, such an association has not been described in children.

Methods: To characterize CDI epidemiology, including risk factors and complications among pediatric oncology patients, we retrospectively reviewed charts of patients 1-18 years old treated at a designated cancer center during 2000-2017. We used fluorescence-based polymerase chain reaction to identify ribotypes causing disease at our institution. …

Deep Learning-Based Automatic Segmentation Of Cardiac Substructures For Lung Cancers, Xinru Chen, Raymond P Mumme, Kelsey L Corrigan, Yuki Mukai-Sasaki, Efstratios Koutroumpakis, Nicolas L Palaskas, Callistus M Nguyen, Yao Zhao, Kai Huang, Cenji Yu, Ting Xu, Aji Daniel, Peter A Balter, Xiaodong Zhang, Joshua S Niedzielski, Sanjay S Shete, Anita Deswal, Laurence E Court, Zhongxing Liao, Jinzhong Yang

Faculty, Staff and Student Publications

Purpose: Accurate and comprehensive segmentation of cardiac substructures is crucial for minimizing the risk of radiation-induced heart disease in lung cancer radiotherapy. We sought to develop and validate deep learning-based auto-segmentation models for cardiac substructures.

Materials and methods: Nineteen cardiac substructures (whole heart, 4 heart chambers, 6 great vessels, 4 valves, and 4 coronary arteries) in 100 patients treated for non-small cell lung cancer were manually delineated by two radiation oncologists. The valves and coronary arteries were delineated as planning risk volumes. An nnU-Net auto-segmentation model was trained, validated, and tested on this dataset with a split ratio of 75:5:20. …