Digital Commons Network^™

Anti-Grp-R Monoclonal Antibody Antitumor Therapy Against Neuroblastoma, Jingbo Qiao, Junquan Liu, Jillian C Jacobson, Rachael A Clark, Sora Lee, Li Liu, Zhiqiang An, Ningyan Zhang, Dai H Chung

Faculty, Staff and Student Publications

Standard treatment for patients with high-risk neuroblastoma remains multimodal therapy including chemoradiation, surgical resection, and autologous stem cell rescue. Immunotherapy has demonstrated success in treating many types of cancers; however, its use in pediatric solid tumors has been limited by low tumor mutation burdens. Gastrin-releasing peptide receptor (GRP-R) is overexpressed in numerous malignancies, including poorly-differentiated neuroblastoma. Monoclonal antibodies (mAbs) to GRP-R have yet to be developed but could serve as a potential novel immunotherapy. This preclinical study aims to evaluate the efficacy of a novel GRP-R mAb immunotherapy against neuroblastoma. We established four candidate anti-GRP-R mAbs by screening a single-chain …

A Nomogram For Predicting Upper Urinary Tract Damage Risk In Children With Neurogenic Bladder, Qi Li, Miao Cai, Qingsong Pu, Shengde Wu, Xing Liu, Tao Lin, Dawei He, Jianguo Wen, Guanghui Wei

Faculty, Staff and Student Publications

PURPOSE: To establish a predictive model for upper urinary tract damage (UUTD) in children with neurogenic bladder (NB) and verify its efficacy.

METHODS: A retrospective study was conducted that consisted of a training cohort with 167 NB patients and a validation cohort with 100 NB children. The clinical data of the two groups were compared first, and then univariate and multivariate logistic regression analyses were performed on the training cohort to identify predictors and develop the nomogram. The accuracy and clinical usefulness of the nomogram were verified by receiver operating characteristic (ROC) curve, calibration curve and decision curve analyses.

RESULTS: …

Racial Disparities In Treatments And Mortality Among A Large Population-Based Cohort Of Older Men And Women With Colorectal Cancer, Xianglin L Du, Lulu Song

Faculty, Staff and Student Publications

BACKGROUND: There were racial disparities in treatment and mortality among patients with colorectal cancer, but few studies incorporated information on hypertension and diabetes and their treatment status.

PATIENTS AND METHODS: The study identified 101,250 patients from Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database in the United States who were diagnosed with colorectal cancer at age ≥65 years between 2007 and 2015 with follow-up to December 2016.

RESULTS: There were substantial racial and ethnic disparities in the prevalence of hypertension and diabetes in patients with colorectal cancer, in receiving chemotherapy and radiation therapy, and in receiving antihypertensive and antidiabetic treatment. …

Comorbidities, Health-Related Quality Of Life, Health-Care Utilization In Older Persons With Hemophilia-Hematology Utilization Group Study Part Vii (Hugs Vii), Randall Curtis, Marilyn Manco-Johnson, Barbara A Konkle, Roshni Kulkarni, Joanne Wu, Judith R Baker, Megan Ullman, Duc Quang Tran, Michael B Nichol

Faculty, Staff and Student Publications

PURPOSE: We compare the impact of hemophilia on comorbidities, joint problems, health-related quality of life (HRQoL) and health-care utilization between two age groups: 40-49 years and ≥50 years.

PATIENTS AND METHODS: The HUGS VII study recruited persons with hemophilia A or B age ≥40 years. Participants completed surveys to collect data on sociodemographic and clinical characteristics, hemophilia treatment regimen, pain, joint problems, comorbidities, HRQoL, depression and anxiety, at baseline and 6-months later. Clinical chart reviews documented hemophilic severity and treatment.

RESULTS: The sample includes 69 males, 65.2% aged ≥50 years, 75.4% with hemophilia A. Individuals ≥50 years were more likely …

Blood Metabolites Predicting Mild Cognitive Impairment In The Study Of Latinos-Investigation Of Neurocognitive Aging (Hchs/So), Shan He, Einat Granot-Hershkovitz, Ying Zhang, Jan Bressler, Wassim Tarraf, Bing Yu, Tianyi Huang, Donglin Zeng, Sylvia Wassertheil-Smoller, Melissa Lamar, Martha Daviglus, Maria J Marquine, Jianwen Cai, Thomas Mosley, Robert Kaplan, Eric Boerwinkle, Myriam Fornage, Charles Decarli, Bruce Kristal, Hector M Gonzalez, Tamar Sofer

Faculty, Staff and Student Publications

INTRODUCTION: Blood metabolomics-based biomarkers may be useful to predict measures of neurocognitive aging.

METHODS: We tested the association between 707 blood metabolites measured in 1451 participants from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), with mild cognitive impairment (MCI) and global cognitive change assessed 7 years later. We further used Lasso penalized regression to construct a metabolomics risk score (MRS) that predicts MCI, potentially identifying a different set of metabolites than those discovered in individual-metabolite analysis.

RESULTS: We identified 20 metabolites predicting prevalent MCI and/or global cognitive change. Six of them were novel and 14 were previously reported as …

Incidence Rate Of Psychiatric Disorders In 2020: The Pivotal Role Played By Sars-Cov-2 Infection, Antonio L Teixeira, Regina M Hansen, Joseph S Wozny, Caroline M Schaefer, Rodrigo Machado-Vieira, Lokesh Shahani, Scott D Lane, Jair C Soares, Trudy M Krause

Faculty, Staff and Student Publications

IMPORTANCE: The Coronavirus Disease (COVID-19) pandemic has significantly impacted mental health outcomes. While the frequency of anxiety and depressive symptoms has increased in the whole population, the relationship between COVID-19 and new psychiatric diagnoses remains unclear.

OBJECTIVE: to compare the population incidence rate of emergence of de novo psychiatric disorders in 2020 compared to the previous years, and to compare the incidence rate of new psychiatric disorder diagnoses between people with vs without COVID-19.

DESIGN, SETTING, AND PARTICIPANTS: This study utilized administrative claims data from the Clinformatics® Data Mart database, licensed from Optum®. The study is a cross-sectional analysis that …

Catalytic Asymmetric Synthesis Of Carbocyclic C-Nucleosides, Sourabh Mishra, Florian C T Modicom, Conor L Dean, Stephen P Fletcher

Faculty, Staff and Student Publications

Access to carbocyclic C-nucleosides (CC-Ns) is currently restricted. The few methods available to make CC-Ns suffer from long syntheses and poor modularity, hindering the examination of potentially important chemical space. Here we report an approach to CC-Ns which uses an asymmetric Suzuki-Miyaura type reaction as the key C-C bond forming step. After coupling the densely functionalized racemic bicyclic allyl chloride and heterocyclic boronic acids, the trisubstituted cyclopentenyl core is elaborated to RNA analogues via a hydroborylation-homologation-oxidation sequence. We demonstrate that the approach can be used to produce a variety of enantiomerically enriched CC-Ns, including a carbocyclic derivative of Showdomycin.

Immunotherapy Approaches For The Treatment Of Diffuse Midline Gliomas, Joshua D Bernstock, Samantha E Hoffman, Ari D Kappel, Pablo A Valdes, Walid Ibn Essayed, Neil V Klinger, Kyung-Don Kang, Stacie K Totsch, Hannah E Olsen, Charles W Schlappi, Katharina Filipski, Florian A Gessler, Lissa Baird, Mariella G Filbin, Rintaro Hashizume, Oren J Becher, Gregory K Friedman

Faculty, Staff and Student Publications

Diffuse midline gliomas (DMG) are a highly aggressive and universally fatal subgroup of pediatric tumors responsible for the majority of childhood brain tumor deaths. Median overall survival is less than 12 months with a 90% mortality rate at 2 years from diagnosis. Research into the underlying tumor biology and numerous clinical trials have done little to change the invariably poor prognosis. Continued development of novel, efficacious therapeutic options for DMGs remains a critically important area of active investigation. Given that DMGs are not amenable to surgical resection, have only limited response to radiation, and are refractory to traditional chemotherapy, immunotherapy …

Oscillations Of The Circadian Clock Protein, Bmal-1, Align To Daily Cycles Of Mechanical Stimuli: A Novel Means To Integrate Biological Time Within Predictive In Vitro Model Systems, Hannah K Heywood, Laurence Gardner, Martin M Knight, David A Lee

Faculty, Staff and Student Publications

PURPOSE: In vivo, the circadian clock drives 24-h rhythms in human physiology. Isolated cells in vitro retain a functional clockwork but lack necessary timing cues resulting in the rapid loss of tissue-level circadian rhythms. This study tests the hypothesis that repeated daily mechanical stimulation acts as a timing cue for the circadian clockwork. The delineation and integration of circadian timing cues into predictive in vitro model systems, including organ-on-a-chip (OOAC) devices, represent a novel concept that introduces a key component of in vivo physiology into predictive in vitro model systems.

METHODS: Quiescent bovine chondrocytes were entrained for 3 days by …

Stat6 Suppression Prevents Bleomycin-Induced Dermal Fibrosis, Hua Sun, Ashish Damania, Megan L Mair, Eniola Otukoya, Yi-Dong Li, Katherine Polsky, Yuying Zeng, Jeremiah A Alt, Martin J Citardi, David B Corry, Amber U Luong, John Morgan Knight

Faculty, Staff and Student Publications

Unified airway disease, including concurrent asthma and chronic rhinosinusitis (CRS), is a common, but poorly understood disorder with no curative treatment options. To establish a murine model of chronic unified eosinophilic airway inflammation, mice were challenged with Aspergillus niger, and sinonasal mucosa and lung tissue were evaluated by immunohistochemistry, flow cytometry, and gene expression. Inhalation of A niger conidia resulted in a Th2-biased lung and sinus inflammation that typifies allergic asthma and CRS. Gene network and pathway analysis correlated with human disease with upregulation of not only the JAK-STAT and helper T-cell pathways, but also less expected pathways governing …

Clinicopathological Correlations In Heart Transplantation Recipients Complicated By Death Or Re-Transplantation, Michelle M Mcdonald, Maks Mihalj, Bihong Zhao, Sriram Nathan, Stanislava Matejin, Giulia Ottaviani, Mateja K Jezovnik, Rajko Radovancevic, Biswajit Kar, Igor D Gregoric, L Maximilian Buja

Faculty, Staff and Student Publications

PURPOSE: This study aimed to identify and correlate pathological findings with clinical outcomes in patients after orthotopic heart transplantation (OHT) who either died or underwent a re-transplantation.

METHODOLOGY AND STUDY DESIGN: Single-center retrospective analysis of primary OHT patients who died or were re-transplanted between October 2012 and July 2021. Clinical data were matched with corresponding pathological findings from endomyocardial biopsies on antibody-mediated rejection, cellular rejection, and cardiac allograft vasculopathy. Re-assessment of available tissue samples was performed to investigate acute myocardial injury (AMI) as a distinct phenomenon. These were correlated with clinical outcomes, which included severe primary graft dysfunction. Patients were …

Enhancing Mesenchymal Stromal Cell Potency: Inflammatory Licensing Via Mechanotransduction, Max A Skibber, Scott D Olson, Karthik S Prabhakara, Brijesh S Gill, Charles S Cox

Faculty, Staff and Student Publications

Mesenchymal stromal cells (MSC) undergo functional maturation upon their migration from bone marrow and introduction to a site of injury. This inflammatory licensing leads to heightened immune regulation via cell-to-cell interaction and the secretion of immunomodulatory molecules, such as anti-inflammatory mediators and antioxidants. Pro-inflammatory cytokines are a recognized catalyst of inflammatory licensing; however, biomechanical forces, such as fluid shear stress, are a second, distinct class of stimuli that incite functional maturation. Here we show mechanotransduction, achieved by exposing MSC to various grades of wall shear stress (WSS) within a scalable conditioning platform, enhances the immunomodulatory potential of MSC independent of …

Putting The “Comprehensive” In Comprehensive Sexuality Education: A Review Exploring Young Adult Literature As A School-Based Intervention, Margaret M Palmer, Jennifer S Hirsch

Faculty, Staff and Student Publications

INTRODUCTION: In this article, we review research on the impact of young adult literature (YAL) on young people's sexuality-related beliefs. This research points to the potential of YAL as a tool through which schools can offer sex education that is truly "comprehensive" by providing young people an opportunity to grapple with questions about gender, sexuality, and healthy relationships in literature classes, and to complement CSE in health education classes. This broader approach addresses a potential limitation of school-based comprehensive sex education (CSE). CSE certainly promotes young people's health and well-being, but an emphasis on biological dimensions of sexual and reproductive …

Targeting Etosis By Mir-155 Inhibition Mitigates Mixed Granulocytic Asthmatic Lung Inflammation, Ji Young Kim, Patrick Stevens, Manjula Karpurapu, Hyunwook Lee, Joshua A Englert, Pearlly Yan, Tae Jin Lee, Navjot Pabla, Maciej Pietrzak, Gye Young Park, John W Christman, Sangwoon Chung

Faculty, Staff and Student Publications

Asthma is phenotypically heterogeneous with several distinctive pathological mechanistic pathways. Previous studies indicate that neutrophilic asthma has a poor response to standard asthma treatments comprising inhaled corticosteroids. Therefore, it is important to identify critical factors that contribute to increased numbers of neutrophils in asthma patients whose symptoms are poorly controlled by conventional therapy. Leukocytes release chromatin fibers, referred to as extracellular traps (ETs) consisting of double-stranded (ds) DNA, histones, and granule contents. Excessive components of ETs contribute to the pathophysiology of asthma; however, it is unclear how ETs drive asthma phenotypes and whether they could be a potential therapeutic target. …

Emerging Evidence For Intrathecal Management Of Neuropathic Pain Following Spinal Cord Injury, Jay Karri, James Doan, Christian Vangeison, Marissa Catalanotto, Ameet S Nagpal, Sheng Li

Faculty, Staff and Student Publications

A high prevalence of patients with spinal cord injury (SCI) suffer from chronic neuropathic pain. Unfortunately, the precise pathophysiological mechanisms underlying this phenomenon have yet to be clearly elucidated and targeted treatments are largely lacking. As an unfortunate consequence, neuropathic pain in the population with SCI is refractory to standard of care treatments and represents a significant contributor to morbidity and suffering. In recent years, advances from SCI-specific animal studies and translational models have furthered our understanding of the neuronal excitability, glial dysregulation, and chronic inflammation processes that facilitate neuropathic pain. These developments have served advantageously to facilitate exploration into …

Mri Free Water As A Biomarker For Cognitive Performance: Validation In The Markvcid Consortium, Pauline Maillard, Laura J Hillmer, Hanzhang Lu, Konstantinos Arfanakis, Brian T Gold, Christopher E Bauer, Joel H Kramer, Adam M Staffaroni, Lara Stables, Danny J J Wang, Sudha Seshadri, Claudia L Satizabal, Alexa Beiser, Mohamad Habes, Myriam Fornage, Thomas H Mosley, Gary A Rosenberg, Baljeet Singh, Herpreet Singh, Kristin Schwab, Karl G Helmer, Steven M Greenberg, Charles Decarli, Arvind Caprihan

Faculty, Staff and Student Publications

Introduction: To evaluate the clinical validity of free water (FW), a diffusion tensor imaging-based biomarker kit proposed by the MarkVCID consortium, by investigating the association between mean FW (mFW) and executive function.

Methods: Baseline mFW was related to a baseline composite measure of executive function (EFC), adjusting for relevant covariates, in three MarkVCID sub-cohorts, and replicated in five, large, independent legacy cohorts. In addition, we tested whether baseline mFW predicted accelerated EFC score decline (mean follow-up time: 1.29 years).

Results: Higher mFW was found to be associated with lower EFC scores in MarkVCID legacy and sub-cohorts (p-values < 0.05). In addition, higher baseline mFW was associated significantly with accelerated decline in EFC scores (p …