Medical Specialties Commons^™

A Polygenic Risk Score For Alzheimer’S Disease Constructed Using Apoe-Region Variants Has Stronger Association Than Apoe Alleles With Mild Cognitive Impairment In Hispanic/Latino Adults In The Us, Tamar Sofer, Nuzulul Kurniansyah, Einat Granot-Hershkovitz, Matthew O Goodman, Wassim Tarraf, Iris Broce, Richard B Lipton, Martha Daviglus, Melissa Lamar, Sylvia Wassertheil-Smoller, Jianwen Cai, Charles S Decarli, Hector M Gonzalez, Myriam Fornage

Faculty, Staff and Student Publications

INTRODUCTION: Polygenic Risk Scores (PRSs) are summaries of genetic risk alleles for an outcome.

METHODS: We used summary statistics from five GWASs of AD to construct PRSs in 4,189 diverse Hispanics/Latinos (mean age 63 years) from the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA). We assessed the PRS associations with MCI in the combined set of people and in diverse subgroups, and when including and excluding the APOE gene region. We also assessed PRS associations with MCI in an independent dataset from the Mass General Brigham Biobank.

RESULTS: A simple sum of 5 PRSs ("PRSsum"), each constructed based on a …

Pulmonary Outcomes Of Congenital Diaphragmatic Hernia Patients Based On Defect Size (Cdh Study Group Stage), Hina Emanuel, Hannah V Breitschopf, Matthew T Harting, Diana J Martinez Castillo, Aravind Yadav, Katrina Mcbeth, S Syed Hashmi, Ashley H Ebanks, Tomika S Harris, Kevin P Lally, Cindy K Jon, James M Stark, Ricardo A Mosquera

Faculty, Staff and Student Publications

BACKGROUND: Congenital diaphragmatic hernia (CDH) is associated with significant pulmonary morbidity. Previous investigation has shown that postnatal inpatient morbidity is linked to diaphragmatic defect size. The objective of this study was to evaluate long-term pulmonary outcomes by CDH study group defect size.

METHODS: A retrospective analysis was conducted for CDH patients (n=133) managed in a neonatal intensive care unit (NICU) at a single children's hospital within an adult hospital system and subsequently followed up at a comprehensive multidisciplinary CDH clinic (n=102) from January 2012 to April 2022. CDH patients were stratified according to Congenital Diaphragmatic Hernia Study Group (CDHSG) Stage, …

Pimavanserin Treatment Increases Plasma Brain-Derived Neurotrophic Factor Levels In Rats, Ashutosh Tripathi, Henry A Nasrallah, Anilkumar Pillai

Faculty, Staff and Student Publications

BACKGROUND: Pimavanserin, a serotonin 5HT-2A receptor inverse agonist is the first-line, FDA-approved treatment of hallucinations and delusions associated with Parkinson's Disease psychosis (PDP), which occurs in up to 50% of PD patients. The neurobiological mechanism underlying the therapeutic effectiveness of Pimavanserin in PDP remains unknown. Several earlier studies have shown that treatment with 5HT-2A antagonists and other drugs acting on the serotonergic system such as SSRIs increase Brain derived neurotrophic factor (BDNF) levels in rodents. BDNF is synthesized as the precursor proBDNF, that undergoes cleavage intra or extracellularly to produce a mature BDNF (mBDNF) protein. mBDNF is believed to play …

A Narrative Review On Treatment Strategies For Neonatal Hypoxic Ischemic Encephalopathy, Janelle M Korf, Louise D Mccullough, Viola Caretti

Faculty, Staff and Student Publications

Background and Objective

Hypoxic-ischemic encephalopathy (HIE) is a leading cause of death and disability worldwide. Therapeutic hypothermia (TH) represents a significant achievement in the translation of scientific research to clinical application, but it is currently the only neuroprotective treatment for HIE. This review aims to revisit the use of TH for HIE and its longitudinal impact on patient outcomes to readers new to the field of HIE. We discuss how emerging therapies address the broader pathophysiology of injury progression in the neonatal brain days to years after HIE.

Methods

We included full articles and book chapters published in English on …

Game-Based Intradialytic Non-Weight-Bearing Exercise Training On Gait Speed And Balance In Older Adults With Diabetes: A Single-Blind Randomized Controlled Trial, M G Finco, Bijan Najafi, He Zhou, Abdullah Hamad, Rania Ibrahim, Fadwa Al-Ali

Center on Aging Staff Publications

Older adults with diabetes receiving hemodialysis have impaired gait speed and balance compared to the general population, which have been associated with increased risks of falls and mortality. This study evaluated the effectiveness of a game-based intradialytic exercise training program (iExergame) on improving gait speed and balance. This was a single-blind randomized controlled trial. The intervention group (IG) received iExergame training using real-time audiovisual feedback with wearable inertial sensors. The control group (CG) received conventional training without any technology. Both trainings were intradialytic, non-weight-bearing, and used ankle range of motion. Gait and balance parameters were collected at baseline and 4-week …

Car-T Cells Targeting Cd38 And Lmp1 Exhibit Robust Antitumour Activity Against Nk/T Cell Lymphoma, Hongwen Li, Wenting Song, Jiazhuo Wu, Zhuangzhuang Shi, Yuyang Gao, Jiwei Li, Lijuan Han, Jianxiang Zhang, Zhaoming Li, Yong Li, Mingzhi Zhang

Faculty, Staff and Students Publications

BACKGROUND: Natural killer/T cell lymphoma (NKTCL) is an aggressive lymphoma with a poor prognosis. Chimeric antigen receptor-transduced T (CAR-T) cell therapy has become a promising immunotherapeutic strategy against haematologic malignancies.

METHODS: In this study, four CAR-T cell lines (CD38-CAR, LMP1-CAR, CD38-LMP1 tandem CAR 1 and CD38-LMP1 tandem CAR 2) were generated. The effect of CAR-T cells against NKTCL cells was evaluated both in vitro and in vivo. Expression of T cell activation markers and cytokines produced by CAR-T cells were detected by flow cytometry.

RESULTS: The four CAR-T cell lines could effectively eliminate malignant NKTCL cells. They could be activated …

Educational Case: Endometrial Ectopia In Endometriosis And Adenomyosis, Carolyn G. Chen, Joanna S.Y. Chan

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

No abstract provided.

Atmospheric Pressure Plasma Treatment Of Skin: Penetration Into Hair Follicles, Kseniia Konina, Theresa A. Freeman, Mark J. Kushner

Department of Orthopaedic Surgery Faculty Papers

Sterilization of skin prior to surgery is challenged by the reservoir of bacteria that resides in hair follicles. Atmospheric pressure plasma jets (APPJs) have been proposed as a method to treat and deactivate these bacteria as atmospheric plasmas are able to penetrate into structures and crevices with dimensions similar to those found in hair follicles. In this paper, we discuss results from a computational investigation of an APPJ sustained in helium flowing into ambient air, and incident onto a layered dielectric similar to human skin in which there are idealized hair follicles. We found that, depending on the location of …

Small-Vessel Disease In The Brain, Cynthia V Pagba, Amit K Gupta, Alemayehu A Gorfe

Faculty, Staff and Student Publications

Mutations in KRAS account for about 20% of human cancers. Despite the major progress in recent years toward the development of KRAS inhibitors, including the discovery of covalent inhibitors of the G12C KRAS variant for the treatment of non-small-cell lung cancer, much work remains to be done to discover broad-acting inhibitors to treat many other KRAS-driven cancers. In a previous report, we showed that a 308.4 Da small-molecule ligand [(2R)-2-(N'-(1H-indole-3-carbonyl)hydrazino)-2-phenyl-acetamide] binds to KRAS with low micro-molar affinity [Chem. Biol. Drug Des.2019; 94(2):1441-1456]. Binding of this ligand, which we call ACA22, to …

Ecmo Clinical Practice Committee: Empowering The Frontline Staff, Michelle Mckain, Shayna Evans, Johanna I. Orrick, Kari L. Davidson

Posters

Background: Extracorporeal Membrane Oxygenation (ECMO) is a complex artificial life support for patients with severe respiratory and cardiac failure. Children’s Mercy was an early ECMO pioneer, establishing a program in 1987. Despite CM’s successful history, wide variations existed between regional management of ECMO (Schwartz et al., 2022). Studies show that patient outcomes, resources, staff satisfaction, and financial metrics improve with implementation of an interprofessional shared governance team (Olender et al., 2019; Schwartz et al., 2022). In 2016, the ECMO Clinical Practice Committee (ECP) was created, tasked with addressing projects aimed at ECMO process improvements. Methods: ECP members include Registered Nurses …

One Cluster Per Condition Is Not A Valid Design In Cluster-Randomized Trials Comment On Wang Et Al The Effect Of Different Physical Exercise Programs On Physical Fitness Among Preschool Children: A Cluster-Randomized Controlled Trial Int J Environ Res Public Health 2023, 20, 4254, Yasaman Jamshidi-Naeini, Armando Pena, Abu Bakkar Siddique, Andrew W Brown, David B Allison

Children’s Nutrition Research Center Staff Publications

Wang et al. [...].

Impact Of Feeding Volumes In The First 24 H Of Life On Neonatal Feeding Intolerance., Navin Kumar, Igbagbosanmi Oredein, Mohammed Al-Nahar, Nathalee Harris, Venkatesh Sampath

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: This study investigates whether volumes of intake in the first 24 h of life (24 HOL), in relation to birth weight (BW) and gestational age (GA), impact neonatal feeding intolerance (FI).

METHODS: This study employed a retrospective chart review of 6,650 infants born at ≥35 weeks. The volumes of each formula feed per kg BW in the first 24 HOL were assessed. FI was defined as evidenced by chart documentation of emesis, abdominal distension, abdominal x-ray, and/or switching to a sensitive formula.

RESULTS: Overall, the maximum volume of formula intake per feed was inversely correlated with GA and was …

An Evolutionarily Nascent Architecture Underlying The Formation And Emergence Of Biomolecular Condensates, Nima Jaberi-Lashkari, Byron Lee, Fardin Aryan, Eliezer Calo

Faculty, Staff and Student Publications

Biomolecular condensates are implicated in core cellular processes such as gene regulation and ribosome biogenesis. Although the architecture of biomolecular condensates is thought to rely on collective interactions between many components, it is unclear how the collective interactions required for their formation emerge during evolution. Here, we show that the structure and evolution of a recently emerged biomolecular condensate, the nucleolar fibrillar center (FC), is explained by a single self-assembling scaffold, TCOF1. TCOF1 is necessary to form the FC, and it structurally defines the FC through self-assembly mediated by homotypic interactions of serine/glutamate-rich low-complexity regions (LCRs). Finally, introduction of TCOF1 …

Mapping The Evolution Of T Cell States During Response And Resistance To Adoptive Cellular Therapy, Pavan Bachireddy, Elham Azizi, Cassandra Burdziak, Vinhkhang N Nguyen, Christina S Ennis, Katie Maurer, Cameron Y Park, Zi-Ning Choo, Shuqiang Li, Satyen H Gohil, Neil G Ruthen, Zhongqi Ge, Derin B Keskin, Nicoletta Cieri, Kenneth J Livak, Haesook T Kim, Donna S Neuberg, Robert J Soiffer, Jerome Ritz, Edwin P Alyea, Dana Pe'er, Catherine J Wu

Faculty, Staff and Student Publications

No abstract provided.

Bcl-2 Inhibition Combined With Pparα Activation Synergistically Targets Leukemic Stem Cell-Like Cells In Acute Myeloid Leukemia, Chendi Xie, Hui Zhou, Dongmei Qin, Huijian Zheng, Yuanfang Tang, Wenjuan Li, Jie Zhou, Long Liu, Xinxin Yu, Hongpeng Duan, Yong Zhou, Zhifeng Li, Zhihong Fang, Yiming Luo, Bing Z Carter, Bing Xu, Jie Zha

Faculty, Staff and Student Publications

Persistence of leukemic stem cells (LSCs) is one of the determining factors to acute myeloid leukemia (AML) treatment failure and responsible for the poor prognosis of the disease. Hence, novel therapeutic strategies that target LSCs are crucial for treatment success. We investigated if targeting Bcl-2 and peroxisome proliferator activated receptor α (PPARα), two distinct cell survival regulating mechanisms could eliminate LSCs. This study demonstrate that the Bcl-2 inhibitor venetoclax combined with the PPARα agonist chiglitazar resulted in synergistic killing of LSC-like cell lines and CD34+ primary AML cells while sparing their normal counterparts. Furthermore, the combination regimen significantly suppressed AML …

Lanthanide-Mofs As Multi-Responsive Photoluminescence Sensor For Sensitively Detecting Fe3+, Cr2o72− And Nitrofuran Antibiotics, Jingjuan Feng, Cunding Kong, Yunhui Chen, Peipei Cen, Yi Ding, Yan Guo, Fengyuan Zhang, Xiangyu Liu

Faculty, Staff and Student Publications

Fast and selective detection of contaminants plays a key role in meeting human health and environmental concerns. Herein, two groups of isostructural lanthanide MOFs, [Ln(Hpta)(oxalic acid)]·H

Hypothyroidism Following Radiotherapy For Head And Neck Cancer: A Systematic Review Of The Literature And Opportunities To Improve The Therapeutic Ratio, Michael K Rooney, Lauren M Andring, Kelsey L Corrigan, Vincent Bernard, Tyler D Williamson, Clifton D Fuller, Adam S Garden, Brandon Gunn, Anna Lee, Amy C Moreno, William H Morrison, Jack Phan, David I Rosenthal, Michael Spiotto, Steven J Frank

Faculty, Staff and Student Publications

(1) Background: Radiotherapy (RT) is a central component for the treatment of many head and neck cancers. In this systematic review of the literature, we aimed to characterize and quantify the published evidence on RT-related hypothyroidism, including estimated incidence, clinical risk factors, and dosimetric parameters that may be used to guide clinical decision making. Furthermore, we aimed to identify potential areas of improvement in the prevention and clinical management of RT-induced hypothyroidism, including the role of modern advanced therapeutic techniques. (2) Methods: We conducted a systemic review of the literature in accordance with Preferred Reporting Items for Systematic Reviews and …

Hypothyroidism Following Radiotherapy For Head And Neck Cancer: A Systematic Review Of The Literature And Opportunities To Improve The Therapeutic Ratio, Michael K Rooney, Lauren M Andring, Kelsey L Corrigan, Vincent Bernard, Tyler D Williamson, Clifton D Fuller, Adam S Garden, Brandon Gunn, Anna Lee, Amy C Moreno, William H Morrison, Jack Phan, David I Rosenthal, Michael Spiotto, Steven J Frank

Faculty, Staff and Student Publications

(1) Background: Radiotherapy (RT) is a central component for the treatment of many head and neck cancers. In this systematic review of the literature, we aimed to characterize and quantify the published evidence on RT-related hypothyroidism, including estimated incidence, clinical risk factors, and dosimetric parameters that may be used to guide clinical decision making. Furthermore, we aimed to identify potential areas of improvement in the prevention and clinical management of RT-induced hypothyroidism, including the role of modern advanced therapeutic techniques. (2) Methods: We conducted a systemic review of the literature in accordance with Preferred Reporting Items for Systematic Reviews and …

A Comprehensive Drosophila Resource To Identify Key Functional Interactions Between Sars-Cov-2 Factors And Host Proteins, Annabel Guichard, Shenzhao Lu, Oguz Kanca, Daniel Bressan, Yan Huang, Mengqi Ma, Sara Sanz Juste, Jonathan C Andrews, Kristy L Jay, Marketta Sneider, Ruth Schwartz, Mei-Chu Huang, Danqing Bei, Hongling Pan, Liwen Ma, Wen-Wen Lin, Ankush Auradkar, Pranjali Bhagwat, Soo Park, Kenneth H Wan, Takashi Ohsako, Toshiyuki Takano-Shimizu, Susan E Celniker, Michael F Wangler, Shinya Yamamoto, Hugo J Bellen, Ethan Bier

Faculty, Staff and Students Publications

Development of effective therapies against SARS-CoV-2 infections relies on mechanistic knowledge of virus-host interface. Abundant physical interactions between viral and host proteins have been identified, but few have been functionally characterized. Harnessing the power of fly genetics, we develop a comprehensive Drosophila COVID-19 resource (DCR) consisting of publicly available strains for conditional tissue-specific expression of all SARS-CoV-2 encoded proteins, UAS-human cDNA transgenic lines encoding established host-viral interacting factors, and GAL4 insertion lines disrupting fly homologs of SARS-CoV-2 human interacting proteins. We demonstrate the utility of the DCR to functionally assess SARS-CoV-2 genes and candidate human binding partners. We show that …

Daam2 Phosphorylation By Ck2Α Negatively Regulates Wnt Activity During White Matter Development And Injury, Chih-Yen Wang, Zhongyuan Zuo, Juyeon Jo, Kyoung In Kim, Christine Madamba, Qi Ye, Sung Yun Jung, Hugo J Bellen, Hyun Kyoung Lee

Faculty, Staff and Students Publications

Wnt signaling plays a vital role in oligodendrocyte (OL) development and has been implicated as an adverse event for myelin repair after white matter injury. Emerging studies have shed light on multimodal roles of Wnt effectors in the OL lineage, but the underlying molecular mechanisms and modifiable targets in OL remyelination remain unclear. Using genetic mouse development and injury model systems, we delineate a unique stage-specific function of Daam2 in Wnt signaling and OL development via a S704/T705 phosphorylation mechanism and determine a different role of the kinase CK2α in the regulation of OL development and myelin regeneration.

Aggregated Molecular Phenotype Scores: Enhancing Assessment And Visualization Of Mass Spectrometry Imaging Data For Tissue-Based Diagnostics, Jessie R Chappel, Mary E King, Jonathon Fleming, Livia S Eberlin, David M Reif, Erin S Baker

Faculty, Staff and Students Publications

Mass spectrometry imaging (MSI) has gained increasing popularity for tissue-based diagnostics due to its ability to identify and visualize molecular characteristics unique to different phenotypes within heterogeneous samples. Data from MSI experiments are often assessed and visualized using various supervised and unsupervised statistical approaches. However, these approaches tend to fall short in identifying and concisely visualizing subtle, phenotype-relevant molecular changes. To address these shortcomings, we developed aggregated molecular phenotype (AMP) scores. AMP scores are generated using an ensemble machine learning approach to first select features differentiating phenotypes, weight the features using logistic regression, and combine the weights and feature abundances. …

Inducing Accelerated Lung Toxicity In Mice Using A Partial Arc Sbrt Technique, Andrew Gerry, Charita Kunta, Noelle Francois, Tiziana Deangelis, Anuradha Shastri, Nicole Simone, Reza Taleei

Department of Radiation Oncology Posters

Background

• Radiation-induced pulmonary fibrosis (RIPF) is a frequent outcome of thoracic radiation therapy, constraining safe tumor radiation dosage. Various animal models, such as mice, rats, and pigs, have been devised to study RIPF
• Current methods for inducing lung fibrosis in mice involve whole lung irradiation with doses between 2-20 Gy. These methods used fixed anterior and posterior (AP/PA) x-ray beams at 0º and 180º with analysis typically commencing 24 to 52 weeks post-radiation
• Current methods are unrepresentative of modern radiation therapy techniques and are limited by the associated long latency of RIPF

Examining The Latent Structure And Correlates Of Sensory Reactivity In Autism: A Multi-Site Integrative Data Analysis By The Autism Sensory Research Consortium, Zachary J. Williams, Roseann Schaaf, Karla K. Ausderau, Grace T. Baranek, D. Jonah Barrett, Carissa J. Cascio, Rachel L. Dumont, Ekomobong E. Eyoh, Michelle D. Failla, Jacob I. Feldman, Jennifer H. Foss-Feig, Heather L. Green, Shulamite A. Green, Jason L. He, Elizabeth A. Kaplan-Kahn, Bahar Keçeli-Kaysılı, Keren Maclennan, Zoe Mailloux, Elysa J. Marco, Lisa E. Mash, Elizabeth P. Mckernan, Sophie Molholm, Stewart H. Mostofsky, Nicolaas A.J. Puts, Caroline E. Robertson, Natalie Russo, Nicole Shea, John Sideris, James S. Sutcliffe, Teresa Tavassoli, Mark T. Wallace, Ericka L. Wodka, Tiffany G. Woynaroski

Department of Occupational Therapy Faculty Papers

BACKGROUND: Differences in responding to sensory stimuli, including sensory hyperreactivity (HYPER), hyporeactivity (HYPO), and sensory seeking (SEEK) have been observed in autistic individuals across sensory modalities, but few studies have examined the structure of these "supra-modal" traits in the autistic population.

METHODS: Leveraging a combined sample of 3868 autistic youth drawn from 12 distinct data sources (ages 3-18 years and representing the full range of cognitive ability), the current study used modern psychometric and meta-analytic techniques to interrogate the latent structure and correlates of caregiver-reported HYPER, HYPO, and SEEK within and across sensory modalities. Bifactor statistical indices were used to …

Burnout As Chronic Disease, Benjamin Doolittle

Journal of Wellness

Burnout is endemic. The prevalence of burnout (~50%) among healthcare providers has been stable over the past 20 years. Acknowledging variability from year to year, burnout is pervasive, with no signs of abating. Despite increased awareness of mental health issues, the rise of Chief Wellness Officers, and the expansion of Employee Assistance Programs, there has not been much improvement. We are even burned out from burnout. Survey responses are low and often do not result in action. Longitudinal intervention trials are often small and of short duration. We need a new paradigm to manage physician burnout. A chronic care management …

Impact Of Detectable Monoclonal Protein At Diagnosis On Outcomes In Marginal Zone Lymphoma: A Multicenter Cohort Study, Narendranath Epperla, Qiuhong Zhao, Reem Karmali, Pallawi Torka, Lauren Shea, Timothy S. Oh, Andrea Anampa-Guzmán, Heather Reves, Montreh Tavakkoli, Irl Brian Greenwell, Emily Hansinger, Elvira Umyarova, Kaitlin Annunzio, Yazeed Sawalha, Beth Christian, Colin Thomas, Stefan K. Barta, Praveen Ramakrishnan Geethakumari, Nancy L. Bartlett, Natalie S. Grover, Adam J Olszewski

Department of Medicine Faculty Papers

Given the paucity of data surrounding the prognostic relevance of monoclonal paraprotein (M-protein) in marginal zone lymphoma (MZL), we sought to evaluate the impact of detecting M-protein at diagnosis on outcomes in patients with MZL in a large retrospective cohort. The study included 547 patients receiving first-line therapy for MZL. M-protein was detectable at diagnosis in 173 (32%) patients. There was no significant difference in the time from diagnosis to initiation of any therapy (systemic and local) between the M-protein and no M-protein groups. Patients with M-protein at diagnosis had significantly inferior progression-free survival (PFS) compared with those without M-protein …

Early Treatment With Vigabatrin Does Not Decrease Focal Seizures Or Improve Cognition In Tuberous Sclerosis Complex: The Prevent Trial, Elizabeth Martina Bebin, Jurriaan M Peters, Brenda E Porter, Tarrant O Mcpherson, Sarah O'Kelley, Mustafa Sahin, Katherine S Taub, Rajsekar Rajaraman, Stephanie C Randle, William M Mcclintock, Mary Kay Koenig, Mike D Frost, Hope A Northrup, Klaus Werner, Danielle A Nolan, Michael Wong, Jessica L Krefting, Fred Biasini, Kalyani Peri, Gary Cutter, Darcy A Krueger

Faculty, Staff and Student Publications

Objective: This study was undertaken to test the hypothesis that early vigabatrin treatment in tuberous sclerosis complex (TSC) infants improves neurocognitive outcome at 24 months of age.

Methods: A phase IIb multicenter randomized double-blind placebo-controlled trial was conducted of vigabatrin at first epileptiform electroencephalogram (EEG) versus vigabatrin at seizure onset in infants with TSC. Primary outcome was Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) cognitive assessment score at 24 months. Secondary outcomes were prevalence of drug-resistant epilepsy, additional developmental outcomes, and safety of vigabatrin.

Results: Of 84 infants enrolled, 12 were screen failures, 4 went straight to …

Mavs Is A Double-Edged Sword, Christina Huang, Jack L. Arbiser

Student Papers, Posters & Projects

No abstract provided.

Early Treatment With Vigabatrin Does Not Decrease Focal Seizures Or Improve Cognition In Tuberous Sclerosis Complex: The Prevent Trial, Elizabeth Martina Bebin, Jurriaan M Peters, Brenda E Porter, Tarrant O Mcpherson, Sarah O'Kelley, Mustafa Sahin, Katherine S Taub, Rajsekar Rajaraman, Stephanie C Randle, William M Mcclintock, Mary Kay Koenig, Mike D Frost, Hope A Northrup, Klaus Werner, Danielle A Nolan, Michael Wong, Jessica L Krefting, Fred Biasini, Kalyani Peri, Gary Cutter, Darcy A Krueger

Faculty, Staff and Student Publications

Objective: This study was undertaken to test the hypothesis that early vigabatrin treatment in tuberous sclerosis complex (TSC) infants improves neurocognitive outcome at 24 months of age.

Methods: A phase IIb multicenter randomized double-blind placebo-controlled trial was conducted of vigabatrin at first epileptiform electroencephalogram (EEG) versus vigabatrin at seizure onset in infants with TSC. Primary outcome was Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) cognitive assessment score at 24 months. Secondary outcomes were prevalence of drug-resistant epilepsy, additional developmental outcomes, and safety of vigabatrin.

Results: Of 84 infants enrolled, 12 were screen failures, 4 went straight to …

Non-Coding Rnas: Foes Or Friends For Targeting Tumor Microenvironment, Anna Szymanowska, Cristian Rodriguez-Aguayo, Gabriel Lopez-Berestein, Paola Amero

Faculty, Staff and Student Publications

Non-coding RNAs (ncRNAs) are a group of molecules critical for cell development and growth regulation. They are key regulators of important cellular pathways in the tumor microenvironment. To analyze ncRNAs in the tumor microenvironment, the use of RNA sequencing technology has revolutionized the field. The advancement of this technique has broadened our understanding of the molecular biology of cancer, presenting abundant possibilities for the exploration of novel biomarkers for cancer treatment. In this review, we will summarize recent achievements in understanding the complex role of ncRNA in the tumor microenvironment, we will report the latest studies on the tumor microenvironment …

Flavonoids Quercetin And Kaempferol Are Nr4a1 Antagonists And Suppress Endometriosis In Female Mice, Lei Zhang, Kumaravel Mohankumar, Gregory Martin, Fuada Mariyam, Yuri Park, Sang Jun Han, Stephen Safe

Faculty, Staff and Students Publications

Nuclear receptor 4A1 (NR4A1) plays an important role in endometriosis progression; levels of NR4A1 in endometriotic lesions are higher than in normal endometrium, and substituted bis-indole analogs (NR4A1) antagonists suppress endometriosis progression in mice with endometriosis. In addition, the flavonoids kaempferol and quercetin are natural products that directly bind NR4A1 and significantly repress the intrinsic NR4A1-dependent transcriptional activity in human endometriotic epithelial and stromal cells and Ishikawa endometrial cancer cells. NR4A1 knockdown and inhibition of NR4A1 by kaempferol and quercetin suppressed proliferation of human endometriotic epithelial cells and Ishikawa cells by inhibiting epidermal growth factor receptor/c-Myc/survivin-mediated growth-promoting and survival pathways, …