Digital Commons Network^™

Expanding Acta2 Genotypes With Corresponding Phenotypes Overlapping With Smooth Muscle Dysfunction Syndrome, Anita Kaw, Kaveeta Kaw, Ellen M Hostetler, Ana Beleza-Meireles, Adam Smith-Collins, Catherine Armstrong, Ingrid Scurr, Timothy Cotts, Rajani Aatre, Michael J Bamshad, Dawn Earl, Abraham Groner, Katherine Agre, Yehuda Raveh, Callie S Kwartler, Dianna M Milewicz

Faculty, Staff and Student Publications

Pathogenic variants in ACTA2, encoding smooth muscle α-actin, predispose to thoracic aortic aneurysms and dissections. ACTA2 variants altering arginine 179 predispose to a more severe, multisystemic disease termed smooth muscle dysfunction syndrome (SMDS; OMIM 613834). Vascular complications of SMDS include patent ductus arteriosus (PDA) or aortopulmonary window, early-onset thoracic aortic disease (TAD), moyamoya-like cerebrovascular disease, and primary pulmonary hypertension. Patients also have dysfunction of other smooth muscle-dependent systems, including congenital mydriasis, hypotonic bladder, and gut hypoperistalsis. Here, we describe five patients with novel heterozygous ACTA2 missense variants, p.Arg179Gly, p.Met46Arg, p.Thr204Ile, p.Arg39Cys, and p.Ile66Asn, who have clinical complications that align or …

Influenza-Induced Thrombotic Microangiopathy In A Patient With Cancer On Proteasome Inhibitor: A Diagnostic Dilemma, Christopher D Hamad, Zachary C Hoelscher, Amanda Tchakarov, Jaya Kala

Faculty, Staff and Student Publications

Thrombotic microangiopathy (TMA) in a cancer patient is a common complication of either cancer itself or anticancer therapy. Incidence of TMA from anticancer therapy was found to be > 15%, since the introduction of anti-angiogenic drugs like anti-vascular endothelial growth factor agents. It is, however, important to not ignore other causes of TMA such as bacteria, viruses, antiplatelet drugs, hereditary complement mutations, and autoimmune disorders. We present such a diagnostic dilemma in our patient who was admitted with influenza and was found to have TMA on renal biopsy, while on proteasome inhibitor (PI) therapy. With this case, we would like to …

Rationale And Design Of Savi-Aos: A Physiologic Study Of Patients With Symptomatic Moderate Aortic Valve Stenosis And Preserved Left Ventricular Ejection Fraction, Rob Eerdekens, Pim Tonino, Jo Zelis, Rik Adrichem, Jung-Min Ahn, Jesse Demandt, Ashkan Eftekhari, Mohamed El Farissi, Phillip Freeman, Abdul Rahman Ihdayhid, Nikolaos Kakouros, Dae-Hee Kim, Seung-Ah Lee, Nicolas M Van Mieghem, Waqas Qureshi, Nils P Johnson

Faculty, Staff and Student Publications

Background: Moderate aortic valve stenosis occurs twice as often as severe aortic stenosis (AS) and carries a similarly poor prognosis. Current European and American guidelines offer limited insight into moderate AS (MAS) patients with unexplained symptoms. Measuring valve physiology at rest while most patients experience symptoms during exertion might represent a conceptual limitation in the current grading of AS severity. The stress aortic valve index (SAVI) may delineate hemodynamically significant AS among patients with MAS.

Objectives: To investigate the diagnostic value of SAVI in symptomatic MAS patients with normal left ventricular ejection fraction (LVEF ≥ 50%): aortic valve area (AVA) …

Placental Pathology In Spontaneous And Iatrogenic Preterm Birth: Different Entities With Unique Pathologic Features, Lucy T Brink, Drucilla J Roberts, Colleen A Wright, Daan G Nel, Pawel T Schubert, Theonia K Boyd, David R Hall, Hein Odendaal

Faculty, Staff and Student Publications

INTRODUCTION: Placental pathology is an important contributor to the understanding of preterm birth and reveals major differences between spontaneous preterm birth (SPTB) and iatrogenic preterm birth (IPTB). The aim of this study was to investigate these relationships.

METHODS: Research midwives collected placentas from 1101 women with singleton pregnancies who were enrolled in the Safe Passage Study. Trained pathology technologists prepared and processed placenta specimens for macroscopic and microscopic examination by designated pathologists. Statistical analyses were done with STATISTICA version 13.

RESULTS: In SPTB we found more cases of accelerated villous maturation; however, the other features of maternal vascular malperfusion (MVM) …

Management Of Adrenocorticotropic Hormone-Secreting Neuroendocrine Tumors And The Role Of Bilateral Adrenalectomy In Ectopic Cushing Syndrome, Jace P Landry, Uriel Clemente-Gutierrez, Carolina R C Pieterman, Yi-Ju Chiang, Steven G Waguespack, Camilo Jimenez, Mouhammed A Habra, Daniel M Halperin, Sarah B Fisher, Paul H Graham, Nancy D Perrier

Faculty, Staff and Student Publications

BACKGROUND: Neuroendocrine tumors can cause ectopic Cushing syndrome, and most patients have metastatic disease at diagnosis. We identified risk factors for outcome, evaluated ectopic Cushing syndrome management, and explored the role of bilateral adrenalectomy in this population.

METHODS: This was a retrospective study including patients with diagnosis of ectopic Cushing Syndrome secondary to neuroendocrine tumors with adrenocorticotropic hormone secretion treated at our quaternary referral center over a 40-year period (1980-2020).

RESULTS: Seventy-six patients were included. Mean age at diagnosis was 46.3 ± 15.8 years. Most patients (N = 61, 80%) had metastases at ectopic Cushing syndrome diagnosis. Average follow-up was …

Final Evaluation Of La Door: Proposition 47 Grant Program, Melissa M Labriola, Danielle Sobol, Stephanie Brooks Holliday, Heather Sims

Faculty, Staff and Student Publications

The Los Angeles Diversion, Outreach, and Opportunities for Recovery program (LA DOOR) was designed by the Los Angeles City Attorney's Office (LACA) to provide a comprehensive, health-focused, preventative approach that proactively engages individuals at elevated risk of returning to LACA on a new misdemeanor offense related to substance use, mental illness, or homelessness. LA DOOR was funded through the grant program of Proposition 47. Programs funded through Proposition 47 are intended to serve individuals with a history of criminal justice involvement and mental health issues or substance use disorders and to offer mental health services, substance use disorder treatment, and …

Dynamic Expression Of Schlafen 11 (Slfn11) In Circulating Tumour Cells As A Liquid Biomarker In Small Cell Lung Cancer, Bingnan Zhang, C Allison Stewart, Qi Wang, Robert J Cardnell, Pedro Rocha, Junya Fujimoto, Luisa M Solis Soto, Runsheng Wang, Veronica Novegil, Peter Ansell, Lei He, Luisa Fernandez, Adam Jendrisak, Cole Gilbertson, Joseph D Schonhoft, Jiyun Byun, Joshua Jones, Amanda K L Anderson, Ana Aparicio, Hai Tran, Marcelo V Negrao, Jianjun Zhang, Wei-Lien Wang, Ignacio I Wistuba, Jing Wang, Rick Wenstrup, Lauren A Byers, Carl M Gay

Faculty, Staff and Student Publications

Introduction: Small cell lung cancer (SCLC) is an aggressive malignancy with no established biomarkers. Schlafen 11(SLFN11), a DNA/RNA helicase that sensitises cancer cells to DNA-damaging agents, has emerged as a promising predictive biomarker for several drug classes including platinum and PARP inhibitors. Detection of SLFN11 in circulating tumour cells (CTCs) may provide a valuable alternative to tissue sampling.

Methods: SLFN11 expression was evaluated in tumour samples and characterised in circulating tumour cells (CTC) longitudinally to determine its potential role as a biomarker of response.

Results: Among 196 SCLC tumours, 51% expressed SLFN11 by IHC. In addition, 20/29 extra-thoracic high-grade neuroendocrine …

Ablation Of Long Noncoding Rna Malat1 Activates Antioxidant Pathway And Alleviates Sepsis In Mice, Jingshu Chen, Shu Tang, Sui Ke, James J Cai, Daniel Osorio, Andrei Golovko, Benjamin Morpurgo, Shaodong Guo, Yuxiang Sun, Melanie Winkle, George A Calin, Yanan Tian

Faculty, Staff and Student Publications

The metastasis-associated lung adenocarcinoma transcript1 (MALAT1) is a long noncoding RNA (lncRNA) and is known for its role in cancer development and prognosis. In this study, we report that MALAT1 plays an important role in regulating acute inflammatory responses in sepsis. In patient samples, MALAT1 expression was positively correlated with severity of sepsis. In cultured macrophages, LPS treatment significantly induced MALAT1 expression, while genetic ablation of MALAT1 greatly reduced proinflammatory cytokine levels. Furthermore, MALAT1-ablated mice had significantly increased survival rates in cecal ligation and puncture (CLP)-induced sepsis and LPS-induced endotoxemia. One novel and salient feature of MALAT1-ablated mice is greatly …

Sexual Orientation And Gender Identity Data Collection In Oncology Practice: Findings Of An Asco Survey, Charles S Kamen, Mandi L Pratt-Chapman, Stephen C Meersman, Gwendolyn P Quinn, Matthew B Schabath, Shail Maingi, Janette K Merrill, Elizabeth Garrett-Mayer, Melinda Kaltenbaugh, Caroline Schenkel, Shine Chang

Faculty, Staff and Student Publications

Purpose: Lack of collection of sexual orientation and gender identity (SOGI) data in oncology practices limits assessment of sexual and gender minority (SGM) cancer patients' experiences and restricts opportunities to improve health outcomes of SGM patients. Despite national calls for routine SOGI data collection, individual-level and institutional barriers hinder progress. This study aimed to identify these barriers in oncology.

Methods: An online survey of ASCO members and others assessed SOGI data collection in oncology practices, institutional characteristics related to SOGI data collection, respondents' attitudes about SOGI data and SGM patients, and respondent demographics. Logistic regression calculated adjusted odds ratios (ORs) …

The Intricate Interplay Between Cancer Stem Cells And Cell-Of-Origin Of Cancer: Implications For Therapeutic Strategies, Luis Alberto Vega, Misu A Sanson, María Belén Cubria, Shrijana Regmi, Brittany J Shah, Samuel A Shelburne, Anthony R Flores

Faculty, Staff and Student Publications

Antimicrobial resistance-encoding mobile genetic elements (MGEs) may contribute to the disease potential of bacterial pathogens. We previously described the association of Group A Streptococcus (GAS) derived from invasive disease with increasingly frequent antimicrobial resistance (AMR). We hypothesized that a 65-kb AMR-encoding MGE (ICESpyM92), highly conserved among closely related emergent invasive emm92 GAS, contributes to GAS disease potential. Here, we provide evidence that a combination of ICESpyM92- and core genome-dependent differential gene expression (DGE) contributes to invasive disease phenotypes of emergent emm92 GAS. Using isogenic ICESpyM92 mutants generated in distinct emm92 genomic backgrounds, we determined the presence of ICESpyM92 enhances GAS …

International Prevalence And Mechanisms Of Sars-Cov-2 In Childhood Arterial Ischemic Stroke During The Covid-19 Pandemic, Lauren A Beslow, Shannon C Agner, Jonathan D Santoro, Dipak Ram, Jenny L Wilson, Dana Harrar, Brian Appavu, Stuart M Fraser, Thomas Rossor, Marcela D Torres, Manoëlle Kossorotoff, Yenny C Zuñiga Zambrano, Marta Hernández-Chávez, Sahar M A Hassanein, Dimitrios Zafeiriou, Michael M Dowling, Ilona Kopyta, Nicholas V Stence, Timothy J Bernard, Nomazulu Dlamini

Faculty, Staff and Student Publications

BACKGROUND: Data from the early pandemic revealed that 0.62% of children hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had an acute arterial ischemic stroke (AIS). In a larger cohort from June 2020 to December 2020, we sought to determine whether our initial point estimate was stable as the pandemic continued and to understand radiographic and laboratory data that may clarify mechanisms of pediatric AIS in the setting of SARS-CoV-2.

METHODS: We surveyed international sites with pediatric stroke expertise to determine numbers of hospitalized SARS-CoV-2 patients <18 >years, numbers of incident AIS cases among children (29 days to <18 >years), frequency …

Generation Of A Homozygous Knock-In Human Embryonic Stem Cell Line Expressing Meos4b-Tagged Ctr1, Yi-Hung Chen, Pei-San Huang, Meng-Hsuan Wen, Manhua Pan, Dung-Fang Lee, Tai-Yen Chen

Faculty, Staff and Student Publications

Copper transporter 1 (CTR1) is the major membrane protein responsible for cellular copper (Cu) uptake and mediates cellular copper homeostasis. To elucidate CTR1's behavior using imaging approaches, we generated a homozygous knock-in human embryonic stem cell (hESC) clone expressing photoconvertible fluorescence protein mEos4b-tagged endogenous CTR1 using CRISPR-Cas9 mediated homologous recombination. The engineered cells express functional CTR1-mEos4b fusion and have normal stem cell morphology. They remain pluripotent and can be differentiated into all three germ layers in vitro. This resource allows the study of CTR1 at an endogenous level in different cellular contexts using microscopy.

Mettl14-Mediated Epitranscriptome Modification Of Mn1 Mrna Promote Tumorigenicity And All-Trans-Retinoic Acid Resistance In Osteosarcoma, Hong-Bo Li, Gang Huang, Jian Tu, Dong-Ming Lv, Qing-Lin Jin, Jun-Kai Chen, Yu-Tong Zou, Dung-Fang Lee, Jing-Nan Shen, Xian-Biao Xie

Faculty, Staff and Student Publications

BACKGROUND: Osteosarcoma (OS) is the most common primary malignant bone tumor in adolescents. The molecular mechanism behind OS progression and metastasis remains poorly understood, which limits the effectiveness of current therapies. RNA N

METHODS: Liquid chromatography-tandem mass spectrometry (LC-MS/MS), dot blotting, and colorimetric ELISA were used to detect m

FINDINGS: We observed the abundance of m

INTERPRETATION: Our study revealed that METTL14 contributes to OS progression and ATRA resistance as an m

FUNDING: This work was supported by the National Natural Science Foundation of China (Grants 81972510 and 81772864).

Patient Preference For Virtual Versus In-Person Visits In Neuromuscular Clinical Practice, Komal Hafeez, Hani Kushlaf, Husam Al-Sultani, Anny-Claude Joseph, Zoya Zaeem, Zaeem Siddiqi, Shannon Laboy, Michael Pulley, Ali A Habib, Nathaniel M Robbins, Sean Zadeh, Muhammad Ubaid Hafeez, Yessar Hussain, Alexandria Melendez-Zaidi, Charles Kassardjian, Kristin Johnson, Holly Leonhard, Suur Biliciler, Jorge E Patino Murillas, Aziz I Shaibani

Faculty, Staff and Student Publications

INTRODUCTION/AIMS: It is unknown if patients with neuromuscular diseases prefer in-person or virtual telemedicine visits. We studied patient opinions and preference on virtual versus in-person visits, and the factors influencing such preferences.

METHODS: Telephone surveys, consisting of 11 questions, of patients from 10 neuromuscular centers were completed.

RESULTS: Five hundred and twenty surveys were completed. Twenty-six percent of respondents preferred virtual visits, while 50% preferred in-person visits. Sixty-four percent reported physical interaction as "very important." For receiving a new diagnosis, 55% preferred in-person vs 35% reporting no preference. Forty percent were concerned about a lack of physical examination vs 20% …

The Effects Of Supplemental Dietary Chitosan On Broiler Performance And Myopathic Features Of White Striping, Mary F Love, Andrea Nicole Brooks, Sonya D Cox, Munachi Okpala, Gail Cooksey, Audrey Sarah Cohen, Anjail Z Sharrief

Faculty, Staff and Student Publications

Introduction

Stroke, a life-threatening stressor, often negatively impacts stroke-survivor (SS) quality of life (QoL). Annual age-adjusted incidence and death rates for stroke are significantly higher among Black Americans than among White Americans. Racism, a significant stressor, occurs at structural, cultural, and interpersonal levels and contributes to health disparities for Black SS. Resilience, a dynamic process of positive adaptation to significant stress, is impacted by factors or resources both internal and external to the individual. This study aims to examine the effects of experiences of racism and resilience on Black SS QoL during early stroke recovery. This article presents the study …

Adipose Tissue-Specific Ablation Of Ces1d Causes Metabolic Dysregulation In Mice, Gang Li, Xin Li, Li Yang, Shuyue Wang, Yulin Dai, Baharan Fekry, Lucas Veillon, Lin Tan, Rebecca Berdeaux, Kristin Eckel-Mahan, Philip L Lorenzi, Zhongming Zhao, Richard Lehner, Kai Sun

Faculty, Staff and Student Publications

Carboxylesterase 1d (Ces1d) is a crucial enzyme with a wide range of activities in multiple tissues. It has been reported to localize predominantly in ER. Here, we found that Ces1d levels are significantly increased in obese patients with type 2 diabetes. Intriguingly, a high level of Ces1d translocates onto lipid droplets where it digests the lipids to produce a unique set of fatty acids. We further revealed that adipose tissue-specific Ces1d knock-out (FKO) mice gained more body weight with increased fat mass during a high fat-diet challenge. The FKO mice exhibited impaired glucose and lipid metabolism and developed exacerbated liver …

Preventing Cholesterol-Induced Perk (Protein Kinase Rna-Like Endoplasmic Reticulum Kinase) Signaling In Smooth Muscle Cells Blocks Atherosclerotic Plaque Formation, Abhijnan Chattopadhyay, Pujun Guan, Suravi Majumder, Kaveeta Kaw, Zhen Zhou, Chen Zhang, Siddharth K Prakash, Anita Kaw, L Maximillian Buja, Callie S Kwartler, Dianna M Milewicz

Faculty, Staff and Student Publications

BACKGROUND: Vascular smooth muscle cells (SMCs) undergo complex phenotypic modulation with atherosclerotic plaque formation in hyperlipidemic mice, which is characterized by de-differentiation and heterogeneous increases in the expression of macrophage, fibroblast, osteogenic, and stem cell markers. An increase of cellular cholesterol in SMCs triggers similar phenotypic changes in vitro with exposure to free cholesterol due to cholesterol entering the endoplasmic reticulum, triggering endoplasmic reticulum stress and activating Perk (protein kinase RNA-like endoplasmic reticulum kinase) signaling.

METHODS: We generated an SMC-specific

RESULTS: SMC-specific deletion of Perk reduces atherosclerotic plaque formation in male hyperlipidemic mice by 80%. Single-cell transcriptomic data identify 2 …

Sars-Cov-2 Infection: Host Response, Immunity, And Therapeutic Targets, Pooja Shivshankar, Harry Karmouty-Quintana, Tingting Mills, Marie-Francoise Doursout, Yanyu Wang, Agnieszka K Czopik, Scott E Evans, Holger K Eltzschig, Xiaoyi Yuan

Faculty, Staff and Student Publications

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in a global pandemic with severe socioeconomic effects. Immunopathogenesis of COVID-19 leads to acute respiratory distress syndrome (ARDS) and organ failure. Binding of SARS-CoV-2 spike protein to human angiotensin-converting enzyme 2 (hACE2) on bronchiolar and alveolar epithelial cells triggers host inflammatory pathways that lead to pathophysiological changes. Proinflammatory cytokines and type I interferon (IFN) signaling in alveolar epithelial cells counter barrier disruption, modulate host innate immune response to induce chemotaxis, and initiate the resolution of inflammation. Here, we discuss experimental models to study SARS-CoV-2 …

Acylcarnitines And Genetic Variation In Fat Oxidation Genes In Hiv-Infected, Antiretroviral-Treated Children With And Without Myopathy, Brian Kirmse, Charlotte Hobbs, Lisa Aaron, Grace Montepiedra, Marshall Summar, Paige L Williams, Caitlin J Smith, Russell Van Dyke, Chunli Yu, Kelli K Ryckman, William Borkowsky

Faculty, Staff and Student Publications

BACKGROUND: Mitochondrial toxicity resulting in myopathy and lactic acidosis has been described in antiretroviral (ARV)-exposed patients. We hypothesized that myopathy in HIV-infected, ARV-treated children would be associated with metabolic (acylcarnitines) and genetic (variants in metabolic genes) markers of dysfunctional fatty acid oxidation (FAO).

METHODS: Acylcarnitine profiles (ACP) were analyzed for 74 HIV-infected children on nucleoside reverse transcriptase inhibitor (NRTI)-containing ARV. Thirty-seven participants with ≥2 creatine kinase measurements >500 IU (n = 18) or evidence of echocardiographic cardiomyopathy (n = 19) were matched with 37 participants without myopathy. Single nucleotide polymorphisms (SNPs) in FAO genes were also evaluated.

RESULTS: Abnormal ACP …

Clinical Research In Ovarian Cancer: Consensus Recommendations From The Gynecologic Cancer Intergroup, Ignace Vergote, Antonio Gonzalez-Martin, Domenica Lorusso, Charlie Gourley, Mansoor Raza Mirza, Jean-Emmanuel Kurtz, Aikou Okamoto, Kathleen Moore, Frédéric Kridelka, Iain Mcneish, Alexander Reuss, Bénédicte Votan, Andreas Du Bois, Sven Mahner, Isabelle Ray-Coquard, Elise C Kohn, Jonathan S Berek, David S P Tan, Nicoletta Colombo, Rongyu Zang, Nicole Concin, Dearbhaile O'Donnell, Alejandro Rauh-Hain, C Simon Herrington, Christian Marth, Andres Poveda, Keiichi Fujiwara, Gavin C E Stuart, Amit M Oza, Michael A Bookman, Participants Of The 6th Gynecologic Cancer Intergroup (Gcig) Ovarian Cancer Consensus Conference On Clinical Research

Faculty, Staff and Student Publications

The Gynecologic Cancer InterGroup (GCIG) sixth Ovarian Cancer Conference on Clinical Research was held virtually in October, 2021, following published consensus guidelines. The goal of the consensus meeting was to achieve harmonisation on the design elements of upcoming trials in ovarian cancer, to select important questions for future study, and to identify unmet needs. All 33 GCIG member groups participated in the development, refinement, and adoption of 20 statements within four topic groups on clinical research in ovarian cancer including first line treatment, recurrent disease, disease subgroups, and future trials. Unanimous consensus was obtained for 14 of 20 statements, with …

Novel Mitochondria-Targeting Compounds Selectively Kill Human Leukemia Cells, Svetlana B Panina, Jingqi Pei, Natalia Baran, Elissa Tjahjono, Shraddha Patel, Gheath Alatrash, Sergej Konoplev, Leonid A Stolbov, Vladimir V Poroikov, Marina Konopleva, Natalia V Kirienko

Faculty, Staff and Student Publications

Acute myeloid leukemia (AML) is a heterogeneous group of aggressive hematological malignancies commonly associated with treatment resistance, high risk of relapse, and mitochondrial dysregulation. We identified six mitochondria-affecting compounds (PS compounds) that exhibit selective cytotoxicity against AML cells in vitro. Structure-activity relationship studies identified six analogs from two original scaffolds that had over an order of magnitude difference between LD50 in AML and healthy peripheral blood mononuclear cells. Mechanistically, all hit compounds reduced ATP and selectively impaired both basal and ATP-linked oxygen consumption in leukemic cells. Compounds derived from PS127 significantly upregulated production of reactive oxygen species (ROS) in AML …

Advances In Head And Neck Cancer Pain, Y Ye, D D Jensen, C T Viet, H L Pan, W M Campana, M Amit, M D Boada

Faculty, Staff and Student Publications

Head and neck cancer (HNC) affects over 890,000 people annually worldwide and has a mortality rate of 50%. Aside from poor survival, HNC pain impairs eating, drinking, and talking in patients, severely reducing quality of life. Different pain phenotype in patients (allodynia, hyperalgesia, and spontaneous pain) results from a combination of anatomical, histopathological, and molecular differences between cancers. Poor pathologic features (e.g., perineural invasion, lymph node metastasis) are associated with increased pain. The use of syngeneic/immunocompetent animal models, as well as a new mouse model of perineural invasion, provides novel insights into the pathobiology of HNC pain. Glial and immune …

Venetoclax Combined With Flag-Ida Induction And Consolidation In Newly Diagnosed Acute Myeloid Leukemia, Courtney D Dinardo, Curtis A Lachowiez, Koichi Takahashi, Sanam Loghavi, Tapan Kadia, Naval Daver, Lianchun Xiao, Maria Adeoti, Nicholas J Short, Koji Sasaki, Sa A Wang, Gautam Borthakur, Ghayas Issa, Abhishek Maiti, Yesid Alvarado, Naveen Pemmaraju, Guillermo Montalban Bravo, Lucia Masarova, Musa Yilmaz, Nitin Jain, Michael Andreeff, Guillermo Garcia-Manero, Steven Kornblau, Farhad Ravandi, Elias Jabbour, Marina Y Konopleva, Hagop M Kantarjian

Faculty, Staff and Student Publications

Multi-agent induction chemotherapy (IC) improves response rates in younger patients with acute myeloid leukemia (AML); however, relapse remains the principal cause of treatment failure. Improved induction regimens are needed. A prospective single-center phase Ib/II study evaluating fludarabine, cytarabine, G-CSF, and idarubicin combined with venetoclax (FLAG-IDA + VEN) in patients with newly diagnosed (ND) or relapsed/refractory AML. The primary efficacy endpoint was assessment of overall activity (overall response rate [ORR]: complete remission [CR] + CR with partial hematologic recovery [CRh] + CR with incomplete hematologic recovery [CRi] + morphologic leukemia free state + partial response). Secondary objectives included additional assessments of …

Preventing Cholesterol-Induced Perk (Protein Kinase Rna-Like Endoplasmic Reticulum Kinase) Signaling In Smooth Muscle Cells Blocks Atherosclerotic Plaque Formation, Abhijnan Chattopadhyay, Pujun Guan, Suravi Majumder, Kaveeta Kaw, Zhen Zhou, Chen Zhang, Siddharth K Prakash, Anita Kaw, L Maximillian Buja, Callie S Kwartler, Dianna M Milewicz

Faculty, Staff and Student Publications

BACKGROUND: Vascular smooth muscle cells (SMCs) undergo complex phenotypic modulation with atherosclerotic plaque formation in hyperlipidemic mice, which is characterized by de-differentiation and heterogeneous increases in the expression of macrophage, fibroblast, osteogenic, and stem cell markers. An increase of cellular cholesterol in SMCs triggers similar phenotypic changes in vitro with exposure to free cholesterol due to cholesterol entering the endoplasmic reticulum, triggering endoplasmic reticulum stress and activating Perk (protein kinase RNA-like endoplasmic reticulum kinase) signaling.

METHODS: We generated an SMC-specific

RESULTS: SMC-specific deletion of Perk reduces atherosclerotic plaque formation in male hyperlipidemic mice by 80%. Single-cell transcriptomic data identify 2 …

Unilateral Radiation Therapy For Tonsillar Cancer: Treatment Outcomes In The Era Of Human Papillomavirus, Positron-Emission Tomography, And Intensity Modulated Radiation Therapy, Nicolette Taku, Gregory Chronowski, G Brandon Gunn, William H Morrison, Neil D Gross, Amy C Moreno, Renata Ferrarotto, Steven J Frank, C David Fuller, Ryan P Goepfert, Jack Phan, Stephen Y Lai, Jay P Reddy, David I Rosenthal, Adam S Garden

Faculty, Staff and Student Publications

Purpose: The goal of this study was to evaluate disease, survival, and toxic effects after unilateral radiation therapy treatment for tonsillar cancer.

Methods and materials: A retrospective study was performed of patients treated at our institution within the period from 2000 to 2018. Summary statistics were used to assess the cohort by patient characteristics and treatments delivered. The Kaplan-Meier method was used to determine survival outcomes.

Results: The cohort comprised 403 patients, including 343 (85%) with clinical and/or radiographic evidence of ipsilateral cervical nodal disease and 181 (45%) with multiple involved nodes. Human papillomavirus was detected in 294 (73%) tumors. …

Anesthesia For Echocardiography And Magnetic Resonance Imaging In The African Clawed Frog (Xenopus Laevis), Antonio F Corno, Noelia E Flores, Wen Li, Thomas H Gomez, Jorge D Salazar

Faculty, Staff and Student Publications

This report describes an anesthesia technique that we used to study cardiovascular anatomy and physiology with echocardiography and cardiac magnetic resonance (CMR) in 46 African clawed frogs (Xenopus laevis) (n = 24 for electrocardiography and n = 22 for CMR). For administration of anesthesia, 3 holding tanks, one each for transportation, sedation, and recovery, were filled with filtered water, with 0.05% buffered tricaine methasulfonate solution (MS-222) added into the sedation tank. Fifteen minutes after the frog was placed in the sedation tank, a paper towel was soaked in MS-222 solution, and the frog was placed in a …

Supporting Self-Management For Patients With Interstitial Lung Diseases: Utility And Acceptability Of Digital Devices, Shima Aran, Orest O Kayder, Teena Chopra, Hani Abujudeh

Faculty, Staff and Student Publications

On December 2020, the US Food and Drug Administration issued the first emergency use authorization for a vaccine for the prevention of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report development of superficial thrombophlebitis in the ipsilateral breast of a 43-year-old female 7 days after receiving the first dose of the Pfizer-BioNTech COVID-19 vaccine. Given that this is the first case of superficial thrombophlebitis in the breast shortly after mRNA vaccination for COVID-19 reported to our knowledge, we suggest that this may be a rare vaccine-related event.

Aapm Task Group Report 303 Endorsed By The Abs: Mri Implementation In Hdr Brachytherapy-Considerations From Simulation To Treatment, Joann Prisciandaro, Jacqueline Esthappan Zoberi, Gil'ad Cohen, Yusung Kim, Perry Johnson, Eric Paulson, William Song, Ken-Pin Hwang, Beth Erickson, Sushil Beriwal, Christian Kirisits, Firas Mourtada

Faculty, Staff and Student Publications

The task group (TG) on magnetic resonance imaging (MRI) implementation in high-dose-rate (HDR) brachytherapy (BT)-Considerations from simulation to treatment, TG 303, was constituted by the American Association of Physicists in Medicine's (AAPM's) Science Council under the direction of the Therapy Physics Committee, the Brachytherapy Subcommittee, and the Working Group on Brachytherapy Clinical Applications. The TG was charged with developing recommendations for commissioning, clinical implementation, and on-going quality assurance (QA). Additionally, the TG was charged with describing HDR BT workflows and evaluating practical consideration that arise when implementing MR imaging. For brevity, the report is focused on the treatment of gynecologic …

Hepatic Recruitment Of Eosinophils And Their Protective Function During Acute Liver Injury, Long Xu, Yang Yang, Yankai Wen, Jong-Min Jeong, Christoph Emontzpohl, Constance L Atkins, Zhaoli Sun, Kyle L Poulsen, David R Hall, J Steve Bynon, Bin Gao, William M Lee, Jody Rule, Elizabeth A Jacobsen, Hua Wang, Cynthia Ju

Faculty, Staff and Student Publications

BACKGROUND & AIMS: Beyond the classical description of eosinophil functions in parasite infections and allergic diseases, emerging evidence supports a critical role of eosinophils in resolving inflammation and promoting tissue remodeling. However, the role of eosinophils in liver injury and the underlying mechanism of their recruitment into the liver remain unclear.

METHODS: Hepatic eosinophils were detected and quantified using flow cytometry and immunohistochemical staining. Eosinophil-deficient (ΔdblGata1) mice were used to investigate the role of eosinophils in 3 models of acute liver injury. In vivo experiments using Il33

RESULTS: Hepatic accumulation of eosinophils was observed in patients with acetaminophen (APAP)-induced liver …

Pulmonary Fibrosis Model Using Micro-Ct Analyzable Human Psc-Derived Alveolar Organoids Containing Alveolar Macrophage-Like Cells, Seri Choi, Jiwoong Choi, Seongmin Cheon, Jihong Song, Seung-Yeon Kim, Ji-Eun Kim, Dae-Hwan Nam, Gohar Manzar, Su-Man Kim, Hyung-Sik Kang, Kee K Kim, Sang Hoon Jeong, Ju-Han Lee, Eun-Kee Park, Minseob Lee, Hyang-Ae Lee, Ki-Suk Kim, Han-Jin Park, Won Keun Oh, Chungoo Park, Chang Hyun Lee, Eun-Mi Kim

Faculty, Staff and Student Publications

Human lung organoids (hLOs) are useful for disease modelling and drug screening. However, a lack of immune cells in hLOs limits the recapitulation of in vivo cellular physiology. Here, we generated hLOs containing alveolar macrophage (AMφ)-like cells derived from pluripotent stem cells (PSC). To bridge hLOs with advanced human lung high-resolution X-ray computed tomography (CT), we acquired quantitative micro-CT images. Three hLO types were observed during differentiation. Among them, alveolar hLOs highly expressed not only lung epithelial cell markers but also AMφ-specific markers. Furthermore, CD68