Digital Commons Network^™

Female Representation In The Film Industry: Bringing Women In Film To Universities Around The Nation, Allison Mays

Journalism

The following study explores the lack of gender parity in the film industry and dives into the nuts and bolts of what makes up female representation in the industry. It also explores the potential a national organization like Women In Film has on a university campus. Despite the majority of people believing women make up nearly half of the film industry, the reality is that only 23% of the key behind-the-scenes roles in the film industry are occupied by women. Since 1998 up to the year 2020, female representation has only grown by 6% (17% in 1998 to 23% in …

Clinical Characterization Of Pediatric Gastroparesis Using A Four-Hour Gastric Emptying Scintigraphy Standard, Sharon Wolfson, Zoe Wilhelm, Antone R Opekun, Robert Orth, Robert J Shulman, Bruno P Chumpitazi

Children’s Nutrition Research Center Staff Publications

Objectives: Four-hour gastric emptying scintigraphy (GES) is the recommended method to identify both adult and childhood gastroparesis (GP). Previous pediatric studies have, however, not used this standard. We sought to determine the characteristics and outcomes of children versus adolescents with GP using the 4-hour GES evaluation.

Methods: We performed a retrospective chart review of pediatric patients diagnosed with GP by 4-hour GES (>10% retention at 4 hours). Demographics, body mass index, GP-related symptoms, comorbidities, etiologies, therapies (eg, medications), healthcare utilization, and response to therapy were captured systematically. Symptoms were compared from the initial versus last gastroenterology visit. Outcomes were …

Defining Vdr Expression In The Brain Using A Novel Vdrcre Mouse, Hailan Liu, Yang He, Jessie Beck, Silvania Da Silva Teixeira, Keisha Harrison, Yong Xu, Stephanie Sisley

Children’s Nutrition Research Center Staff Publications

Vitamin D action has been linked to several diseases regulated by the brain including obesity, diabetes, autism, and Parkinson’s. However, the location of the vitamin D receptor (VDR) in the brain is not clear due to conflicting reports. We found that two antibodies previously published as specific in peripheral tissues are not specific in the brain. We thus created a new knockin mouse with cre recombinase expression under the control of the endogenous VDR promoter (VDRCre). We demonstrated that the cre activity in the VDRCre mouse brain (as reported by a cre-dependent tdTomato expression) is highly overlapping with endogenous VDR …

Immunological And Hematological Outcomes Following Protracted Low Dose/Low Dose Rate Ionizing Radiation And Simulated Microgravity, Amber M. Paul, Eliah G. Overbey, Willian A. Da Silveira, Nathaniel Szewczyk, Nina C. Nishiyama, Michael J. Pecaut, Sulekha Anand, Jonathan M. Galazka, Xiao Wen Mao

Publications

Using a ground-based model to simulate spaceflight [21-days of single-housed, hindlimb unloading (HLU) combined with continuous low-dose gamma irradiation (LDR, total dose of 0.04 Gy)], an in-depth survey of the immune and hematological systems of mice at 7-days post-exposure was performed. Collected blood was profiled with a hematology analyzer and spleens were analyzed by whole transcriptome shotgun sequencing (RNA-sequencing). The results revealed negligible differences in immune differentials. However, hematological system analyses of whole blood indicated large disparities in red blood cell differentials and morphology, suggestive of anemia. Murine Reactome networks indicated majority of spleen cells displayed differentially expressed genes (DEG) …

Advantage Of 16s Rrna Amplicon Sequencing In Helicobacter Pylori Diagnosis, Boldbaatar Gantuya, Hashem B El Serag, Batsaikhan Saruuljavkhlan, Dashdorj Azzaya, Takashi Matsumoto, Tomohisa Uchida, Khasag Oyuntsetseg, Nyamdorj Oyunbileg, Duger Davaadorj, Yoshio Yamaoka

Faculty, Staff and Students Publications

BACKGROUND: 16S rRNA amplicon sequencing is an accurate method of detecting microbial infection without culture. It is unclear if sequencing has additional benefits over routine diagnostic methods for Helicobacter pylori testing.

METHODS: We enrolled Mongolian volunteers with dyspepsia. Using routine diagnostic methods, positive H. pylori was defined as positive results on histology/immunohistochemistry, culture, rapid urease test, or serology; negative H. pylori was defined by negative results from all these tests. We performed 16S rRNA sequencing on gastric biopsy specimens and calculated cutoffs for operational taxonomic units (OTUs) and relative abundance (RA) to define positive results using ROC curves.

RESULTS: We …

Psychological Impact Of Genetic And Clinical Screening For Pulmonary Fibrosis On Asymptomatic First-Degree Relatives Of Affected Individuals, Nikkola Carmichael, Jose M Martinez Manzano, Luisa D Quesada-Arias, Sergio De Frías Poli, Maura Alvarez Baumgartner, Maria A Planchart Ferretto, Lisa Digianni, Shannon Gampala-Sagar, Dominick A Leone, Swati Gulati, Souheil Y El-Chemaly, Hilary J Goldberg, Rachel Putman, Hiroto Hatabu, Ivan O Rosas, Gary M Hunninghake, Benjamin A Raby

Faculty, Staff and Students Publications

Screening for pulmonary fibrosis may help to identify early stages of the disease. We assessed the psychological impact of screening undiagnosed first-degree relatives of patients with pulmonary fibrosis by administering two validated measures after participants received their results: the Decisional Regret Scale and the Feelings About genomiC Testing Results Questionnaire. More than 90% of relatives reported either no or mild decisional regret. Increased measures of decisional regret and negative feelings were present in those found to have a low diffusion capacity of carbon monoxide or interstitial lung abnormalities. Results of telomere length and genetic testing did not significantly impact regret.

Outcomes And Risk Factors Associated With Sars-Cov-2 Infection In A North American Registry Of Patients With Multiple Sclerosis, Amber Salter, Robert J Fox, Scott D Newsome, June Halper, David K B Li, Pamela Kanellis, Kathleen Costello, Bruce Bebo, Kottil Rammohan, Gary R Cutter, Anne H Cross

2020-Current year OA Pubs

Importance: Emergence of SARS-CoV-2 causing COVID-19 prompted the need to gather information on clinical outcomes and risk factors associated with morbidity and mortality in patients with multiple sclerosis (MS) and concomitant SARS-CoV-2 infections.

Objective: To examine outcomes and risk factors associated with COVID-19 clinical severity in a large, diverse cohort of North American patients with MS.

Design, Setting, and Participants: This analysis used deidentified, cross-sectional data on patients with MS and SARS-CoV-2 infection reported by health care professionals in North American academic and community practices between April 1, 2020, and December 12, 2020, in the COVID-19 Infections in MS Registry. …

Ube2i Deletion In Adipocytes Causes Lipoatrophy In Mice, Aaron R Cox, Natasha Chernis, Kang Ho Kim, Peter M Masschelin, Pradip K Saha, Shawn M Briley, Robert Sharp, Xin Li, Jessica B Felix, Zheng Sun, David D Moore, Stephanie A Pangas, Sean M Hartig

Faculty, Staff and Students Publications

OBJECTIVE: White adipose tissue (WAT) expansion regulates energy balance and overall metabolic homeostasis. The absence or loss of WAT occurring through lipodystrophy and lipoatrophy contributes to the development of hepatic steatosis and insulin resistance. We previously demonstrated that sole small ubiquitin-like modifier (SUMO) E2-conjugating enzyme Ube2i represses human adipocyte differentiation. The role of Ube2i during WAT development remains unknown.

METHODS: To determine how Ube2i impacts body composition and energy balance, we generated adipocyte-specific Ube2i knockout mice (Ube2i

RESULTS: Surprisingly, Ube2i

CONCLUSIONS: Our results demonstrate that Ube2i expression in mature adipocytes allows WAT expansion during postnatal growth. Deletion of Ube2i in …

Safety And Efficacy Of Umbilical Cord-Derived Wharton's Jelly Compared To Hyaluronic Acid And Saline For Knee Osteoarthritis: Study Protocol For A Randomized, Controlled, Single-Blind, Multi-Center Trial, Ashim Gupta, Nicola Maffulli, Hugo C Rodriguez, Eric W Carson, Randa A Bascharon, Kristin Delfino, Howard J Levy, Saadiq F El-Amin

2020-Current year OA Pubs

BACKGROUND: Osteoarthritis (OA) is the most common joint disorder in the United States of America (USA) with a fast-rising prevalence. Current treatment modalities are limited, and total knee replacement surgeries have shown disadvantages, especially for grade II/III OA. The interest in the use of biologics, including umbilical cord (UC)-derived Wharton's jelly (WJ), has grown in recent years. The results from a preliminary study demonstrated the presence of essential components of regenerative medicine, namely growth factors, cytokines, hyaluronic acid (HA), and extracellular vesicles, including exosomes, in WJ. The proposed study aims to evaluate the safety and efficacy of intra-articular injection of …

Secondary Cytogenetic Abnormalities In Core-Binding Factor Aml Harboring Inv(16) Vs T(8;21), Se Young Han, Krzysztof Mrózek, Jenna Voutsinas, Qian Wu, Elizabeth A. Morgan, Hanne Vestergaard, Robert Ohgami, Philip M. Kluin, Thomas Kielsgaard Kristensen, Sheeja Pullarkat, Michael Boe Møller, Ana-Iris Schiefer, Linda B. Baughn, Young Kim, David Czuchlewski, Jacobien R. Hilberink, Hans-Peter Horny, Tracy I. George, Michelle Dolan, Nam K. Ku, Cecilia Arana Yi, Vinod Pullarkat, Jessica Kohlschmidt, Amandeep Salhotra, Lori Soma, Clara D. Bloomfield, Dong Chen, Wolfgang R. Sperr, Guido Marcucci, Christina Cho, Cem Akin, Jason Gotlib, Sigurd Broesby-Olsen, Melissa Larson, Michael A. Linden, H Joachim Deeg, Gregor Hoermann, Miguel-Angel Perales, Jason L. Hornick, Mark R. Litzow, Ryotaro Nakamura, Daniel Weisdorf, Gautam Borthakur, Gerwin Huls, Peter Valent, Celalettin Ustun, Cecilia C S Yeung

Pathology Research and Scholarship

Patients with core-binding factor (CBF) acute myeloid leukemia (AML), caused by either t(8;21)(q22;q22) or inv(16)(p13q22)/t(16;16)(p13;q22), have higher complete remission rates and longer survival than patients with other subtypes of AML. However, ∼40% of patients relapse, and the literature suggests that patients with inv(16) fare differently from those with t(8;21). We retrospectively analyzed 537 patients with CBF-AML, focusing on additional cytogenetic aberrations to examine their impact on clinical outcomes. Trisomies of chromosomes 8, 21, or 22 were significantly more common in patients with inv(16)/t(16;16): 16% vs 7%, 6% vs 0%, and 17% vs 0%, respectively. In contrast, del(9q) and loss of …

Cell Lineage Tracing Links Erα Loss In Erbb2-Positive Breast Cancers To The Arising Of A Highly Aggressive Breast Cancer Subtype, Yunfeng Ding, Yonghong Liu, Dong-Kee Lee, Zhangwei Tong, Xiaobin Yu, Yi Li, Yong Xu, Rainer B Lanz, Bert W O'Malley, Jianming Xu

Children’s Nutrition Research Center Staff Publications

HER2-positive (HER2+) breast cancers (BrCs) contain approximately equal numbers of ERα+HER2+ and ERα−HER2+ cases. An enduring obstacle is the unclear cell lineage-related characteristics of these BrCs. Although ERα+HER2+ BrCs could lose ERα to become ERα−HER2+ BrCs, direct evidence is missing. To investigate ERα dependencies and their implications during BrC growth and metastasis, we generated ERαCreRFP-T mice that produce an RFP-marked ERα+ mammary gland epithelial cell (MGEC) lineage. RCAS virus-mediated expression of Erbb2, a rodent Her2 homolog, first produced comparable numbers of ERα+RFP+Erbb2+ and ERα−RFP−Erbb2+ MGECs. Early hyperplasia developed mostly from ERα+RFP+Erbb2+ cells and ERα−RFP−Erbb2+ cells in these lesions were rare. …

Common Dna Methylation Dynamics In Endometriod Adenocarcinoma And Glioblastoma Suggest Universal Epigenomic Alterations In Tumorigenesis, Jennifer A Karlow, Benpeng Miao, Xiaoyun Xing, Ting Wang, Bo Zhang

Open Access Publications

Trends in altered DNA methylation have been defined across human cancers, revealing global loss of methylation (hypomethylation) and focal gain of methylation (hypermethylation) as frequent cancer hallmarks. Although many cancers share these trends, little is known about the specific differences in DNA methylation changes across cancer types, particularly outside of promoters. Here, we present a comprehensive comparison of DNA methylation changes between two distinct cancers, endometrioid adenocarcinoma (EAC) and glioblastoma multiforme (GBM), to elucidate common rules of methylation dysregulation and changes unique to cancers derived from specific cells. Both cancers exhibit significant changes in methylation over regulatory elements. Notably, hypermethylated …

Efficacy Of As04-Adjuvanted Vaccine Against Human Papillomavirus (Hpv) Types 16 And 18 In Clearing Incident Hpv Infections: Pooled Analysis Of Data From The Costa Rica Vaccine Trial And The Patricia Study, Joseph E. Tota, Frank Struyf, Allan Hildesheim, Paula Gonzalez, Martin Ryser, Rolando Herrero, John Schussler, Naveen Karkada, Ana Cecilia Rodriguez, Nicolas Folschweiller, Carolina Porras, Mark Schiffman, John T. Schiller, Wim Quint, Aimée R. Kreimer, Matti Lehtinen, Cosette M. Wheeler, Joshua N Sampson

Pathology Research and Scholarship

Clinical trial data and real-world evidence suggest that the AS04-adjuvanted vaccine targeting human papillomavirus types 16 and 18 (AS04-HPV-16/18) vaccine provides nearly 90% protection against cervical intraepithelial neoplasia grade 3 or higher irrespective of type, among women vaccinated before sexual debut. This high efficacy is not fully explained by cross-protection. Although AS04-HPV-16/18 vaccination does not affect clearance of prevalent infections, it may accelerate clearance of newly acquired infections. We pooled data from 2 large-scale randomized controlled trials to evaluate efficacy of the AS04-HPV-16/18 vaccine against clearance of nontargeted incident infections. Results of our analysis do not suggest an effect in …

Experience With Liposomal Amphotericin B In Outpatient Parenteral Antimicrobial Therapy, Yvonne J Burnett, Andrej Spec, Mohamed M Ahmed, William G Powderly, Yasir Hamad

Open Access Publications

Outpatient parenteral antimicrobial therapy (OPAT) is a safe, effective, and convenient treatment strategy for patients receiving intravenous antimicrobials in the outpatient setting; however, data are limited describing the use and safety of liposomal amphotericin B (L-AMB). Records of patients receiving L-AMB OPAT between 1/1/2015 and 7/31/2018 were retrospectively reviewed. The primary objective was to describe the OPAT patient population discharged on L-AMB and evaluate factors associated with readmission and adverse events (AEs). Analysis was performed to evaluate for predictors of worse outcomes. Forty-two patients (67% male, median age 50 years) were identified, most of whom were treated for histoplasmosis. The …

Cancer-Associated Mutations Reveal A Novel Role For Epcam As An Inhibitor Of Cathepsin-L And Tumor Cell Invasion, Narendra V Sankpal, Taylor C Brown, Timothy P Fleming, John M Herndon, Anusha A Amaravati, Allison N Loynd, William E Gillanders

2020-Current year OA Pubs

BACKGROUND: EpCAM (Epithelial cell adhesion molecule) is often dysregulated in epithelial cancers. Prior studies implicate EpCAM in the regulation of oncogenic signaling pathways and epithelial-to-mesenchymal transition. It was recently demonstrated that EpCAM contains a thyroglobulin type-1 (TY-1) domain. Multiple proteins with TY-1 domains are known to inhibit cathepsin-L (CTSL), a cysteine protease that promotes tumor cell invasion and metastasis. Analysis of human cancer sequencing studies reveals that somatic EpCAM mutations are present in up to 5.1% of tested tumors.

METHODS: The Catalogue of Somatic Mutations in Cancer (COSMIC) database was queried to tabulate the position and amino acid changes of …

Neurocognitive Empowerment For Addiction Treatment (Neat): Study Protocol For A Randomized Controlled Trial., Hamed Ekhtiari, Tara Rezapour, Brionne Sawyer, Hung-Wen Yeh, Rayus Kuplicki, Mimi Tarrasch, Martin P. Paulus, Robin Aupperle

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Neurocognitive deficits (NCDs) and associated meta-cognition difficulties associated with chronic substance use often delay the learning and change process necessary for addiction recovery and relapse prevention. However, very few cognitive remediation programs have been developed to target NCDs and meta-cognition for substance users. The study described herein aims to investigate the efficacy of a multi-component neurocognitive rehabilitation and awareness program termed "Neurocognitive Empowerment for Addiction Treatment" (NEAT). NEAT is a fully manualized, cartoon-based intervention involving psychoeducation, cognitive practice, and compensatory strategies relevant across 10 major cognitive domains, including aspects of attention, memory, executive functions, and decision-making.

METHOD/DESIGN: In a …

Immunodeficiency And Bone Marrow Failure With Mosaic And Germline Tlr8 Gain Of Function, Jahnavi Aluri, Alicia Bach, Saara Kaviany, Luana Chiquetto Paracatu, Maleewan Kitcharoensakkul, Magdalena A. Walkiewicz, Christopher D. Putnam, Marwan Shinawi, Nermina Saucier, Elise M. Rizzi, Michael T. Harmon, Molly P. Keppel, Michelle Ritter, Morgan Similuk, Elaine Kulm, Michael Joyce, Adriana A. De Jesus, Raphaela Goldbach-Mansky, Yi-Shan Lee, Marina Cella, Peggy L. Kendall, Mary C. Dinauer, Jeffrey J. Bednarski, Christina Bemrich-Stolz, Scott W. Canna, Shirley M. Abraham, Matthew M. Demczko, Jonathan Powell, Stacie M. Jones, Amy M. Scurlock, Suk See De Ravin, Jack J. Bleesing, James A. Connelly, V Koneti Rao, Laura G. Schuettpelz, Megan A. Cooper

Pediatrics Research and Scholarship

Inborn errors of immunity (IEI) are a genetically heterogeneous group of disorders with a broad clinical spectrum. Identification of molecular and functional bases of these disorders is important for diagnosis, treatment, and an understanding of the human immune response. We identified 6 unrelated males with neutropenia, infections, lymphoproliferation, humoral immune defects, and in some cases bone marrow failure associated with 3 different variants in the X-linked gene TLR8, encoding the endosomal Toll-like receptor 8 (TLR8). Interestingly, 5 patients had somatic variants in TLR8 with

Neurological Diseases And Covid-19: Prospective Analyses Using The Uk Biobank, Nicola Veronese, Lee Smith, Mario Barbagallo, Gianluigi Giannelli, Maria Gabriella Caruso, Anna Maria Cisternino, Maria Notarnicola, Chao Cao, Thomas Waldhoer, Lin Yang

2020-Current year OA Pubs

COVID-19 (Coronavirus disease-19) may present with neurological signs, but whether people already affected by neurological conditions are at a higher risk of contracting COVID-19 is still not known. We, therefore, aimed to investigate the association of previously diagnosed neurological conditions with COVID-19. 502,536 community-dwelling UK Biobank participants (54.4% male, mean age 56.6 ± 10.3 years) were included. Among these, 57,463 participants had a diagnosis of neurological conditions (11.43%) and a total of 1326 COVID-19-positive cases were identified (0.26%). Neurological conditions were identified through medical history and linkage to data on hospital admissions (ICD-10 code G00-G99). COVID-19 presence was diagnosed using …

Effectiveness Of Diet/Exercise In Prevention Of Gestational Diabetes Mellitus And Associated Cesarean Section Delivery, Jonathyn Andrew Marx

Physician Assistant Scholarly Project Papers

Gestational diabetes mellitus (GDM) is becoming a more common diagnosis during pregnancy. GDM is defined as glucose intolerance diagnosed during pregnancy. Women diagnosed with GDM during pregnancy are at an increased risk for emergent or planned cesarean section delivery and the development of overt diabetes mellitus post pregnancy. Complications related to GDM include eclampsia, macrosomia, shoulder dystocia, stillbirth, and cesarean section delivery. Initial treatment consists of diet and exercise and if glucose can not be controlled then pharmacotherapy is introduced. A literature review was performed utilizing scientific databases, mesh terms, and keywords to gather statistically relevant research to analyze the …

Exercise-Induced Alterations In Phospholipid Hydrolysis, Airway Surfactant, And Eicosanoids And Their Role In Airway Hyperresponsiveness In Asthma, Ryan C Murphy, Ying Lai, James D Nolin, Robier A Aguillon Prada, Arindam Chakrabarti, Michael V Novotny, Michael C Seeds, William A Altemeier, Michael H Gelb, Robert Duncan Hite, Teal S Hallstrand

Faculty, Staff and Student Publications

The mechanisms responsible for driving endogenous airway hyperresponsiveness (AHR) in the form of exercise-induced bronchoconstriction (EIB) are not fully understood. We examined alterations in airway phospholipid hydrolysis, surfactant degradation, and lipid mediator release in relation to AHR severity and changes induced by exercise challenge. Paired induced sputum (

Placental Sampling For Understanding Viral Infections - A Simplified Protocol For The Covid-19 Pandemic, Guilherme De Moraes Nobrega, José Paulo Siqueira Guida, Rodolfo Rosa Japecanga, Arthur Antolini-Tavares, Indira Mysorekar, Maria Laura Costa

Open Access Publications

OBJECTIVE:  The coronavirus disease 2019 (COVID-19) is a pandemic viral disease, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The impact of the disease among the obstetric population remains unclear, and the study of the placenta can provide valuable information. Adequate sampling of the placental tissue can help characterize the pathways of viral infections.

METHODS:  A protocol of placental sampling is proposed, aiming at guaranteeing representativity of the placenta and describing the adequate conservation of samples and their integrity for future analysis. The protocol is presented in its complete and simplified versions, allowing its implementation in different complexity settings. …

Soluble Angiotensin-Converting Enzyme 2, Cardiac Biomarkers, Structure, And Function, And Cardiovascular Events (From The Atherosclerosis Risk In Communities Study), Aliza Hussain, Olive Tang, Caroline Sun, Xiaoming Jia, Elizabeth Selvin, Vijay Nambi, Aaron Folsom, Gerardo Heiss, Faiez Zannad, Thomas Mosley, Salim S Virani, Josef Coresh, Eric Boerwinkle, Bing Yu, Jonathan W Cunningham, Amil M Shah, Scott D Solomon, James A De Lemos, Ron C Hoogeveen, Christie M Ballantyne

Faculty, Staff and Students Publications

Membrane-bound angiotensin-converting enzyme 2 is important in regulation of the renin-angiotensin-aldosterone system, but the association of cleaved soluble ACE2 (sACE2) with cardiovascular disease (CVD) is unclear. We evaluated the association of sACE2 with cardiac biomarkers, structure, and function and cardiovascular events in the Atherosclerosis Risk in Communities Study. sACE2 was measured in a subset of 497 participants (mean age 78±5.4 years, 53% men, 27% black); Cox regression analyses assessed prospective associations of sACE2 with time to first CVD event at median 6.1-year follow-up. sACE2 was higher in men, blacks, and participants with prevalent CVD, diabetes, or hypertension. Higher sACE2 levels …

A Blood-Based Diagnostic Test Incorporating Plasma Aβ42/40 Ratio, Apoe Proteotype, And Age Accurately Identifies Brain Amyloid Status: Findings From A Multi Cohort Validity Analysis, Tim West, Kristopher M Kirmess, Matthew R Meyer, Mary S Holubasch, Stephanie S Knapik, Yan Hu, John H Contois, Erin N Jackson, Scott E Harpstrite, Randall J Bateman, David M Holtzman, Philip B Verghese, Ilana Fogelman, Joel B Braunstein, Kevin E Yarasheski

2020-Current year OA Pubs

BACKGROUND: The development of blood-based biomarker tests that are accurate and robust for Alzheimer's disease (AD) pathology have the potential to aid clinical diagnosis and facilitate enrollment in AD drug trials. We developed a high-resolution mass spectrometry (MS)-based test that quantifies plasma Aβ42 and Aβ40 concentrations and identifies the ApoE proteotype. We evaluated robustness, clinical performance, and commercial viability of this MS biomarker assay for distinguishing brain amyloid status.

METHODS: We used the novel MS assay to analyze 414 plasma samples that were collected, processed, and stored using site-specific protocols, from six independent US cohorts. We used receiver operating characteristic …

Oncolytic Hsv-1 G207 Immunovirotherapy For Pediatric High-Grade Gliomas, Gregory K Friedman, Mohamed S Abdelbaki, Et Al

Open Access Publications

BACKGROUND: Outcomes in children and adolescents with recurrent or progressive high-grade glioma are poor, with a historical median overall survival of 5.6 months. Pediatric high-grade gliomas are largely immunologically silent or "cold," with few tumor-infiltrating lymphocytes. Preclinically, pediatric brain tumors are highly sensitive to oncolytic virotherapy with genetically engineered herpes simplex virus type 1 (HSV-1) G207, which lacks genes essential for replication in normal brain tissue.

METHODS: We conducted a phase 1 trial of G207, which used a 3+3 design with four dose cohorts of children and adolescents with biopsy-confirmed recurrent or progressive supratentorial brain tumors. Patients underwent stereotactic placement …

A Microbiota-Directed Food Intervention For Undernourished Children, Robert Y Chen, Matthew C Hibberd, Arjun S Raman, Daniel Webber, Cyrus Zhou, Vinaik Sundaresan, Kazi Ahsan, Martin F Meier, Michael J Barratt, Jeffrey I Gordon, Et Al

Open Access Publications

BACKGROUND: More than 30 million children worldwide have moderate acute malnutrition. Current treatments have limited effectiveness, and much remains unknown about the pathogenesis of this condition. Children with moderate acute malnutrition have perturbed development of their gut microbiota.

METHODS: In this study, we provided a microbiota-directed complementary food prototype (MDCF-2) or a ready-to-use supplementary food (RUSF) to 123 slum-dwelling Bangladeshi children with moderate acute malnutrition between the ages of 12 months and 18 months. The supplementation was given twice daily for 3 months, followed by 1 month of monitoring. We obtained weight-for-length, weight-for-age, and length-for-age z scores and mid-upper-arm circumference …

Tocilizumab In Hospitalized Patients With Severe Covid-19 Pneumonia, Ivan O Rosas, Norbert Bräu, Michael Waters, Ronaldo C Go, Bradley D Hunter, Sanjay Bhagani, Daniel Skiest, Mariam S Aziz, Nichola Cooper, Ivor S Douglas, Sinisa Savic, Taryn Youngstein, Lorenzo Del Sorbo, Antonio Cubillo Gracian, David J De La Zerda, Andrew Ustianowski, Min Bao, Sophie Dimonaco, Emily Graham, Balpreet Matharu, Helen Spotswood, Larry Tsai, Atul Malhotra

Faculty, Staff and Students Publications

BACKGROUND: Coronavirus disease 2019 (Covid-19) is associated with immune dysregulation and hyperinflammation, including elevated interleukin-6 levels. The use of tocilizumab, a monoclonal antibody against the interleukin-6 receptor, has resulted in better outcomes in patients with severe Covid-19 pneumonia in case reports and retrospective observational cohort studies. Data are needed from randomized, placebo-controlled trials.

METHODS: In this phase 3 trial, we randomly assigned patients who were hospitalized with severe Covid-19 pneumonia in a 2:1 ratio receive a single intravenous infusion of tocilizumab (at a dose of 8 mg per kilogram of body weight) or placebo. Approximately one quarter of the participants …

Optimized Polyepitope Neoantigen Dna Vaccines Elicit Neoantigen-Specific Immune Responses In Preclinical Models And In Clinical Translation, Lijin Li, Xiuli Zhang, Xiaoli Wang, Samuel W Kim, John M Herndon, Michelle K Becker-Hapak, Beatriz M Carreno, Nancy B Myers, Mark A Sturmoski, Michael D Mclellan, Christopher A Miller, Tanner M Johanns, Benjamin R Tan, Gavin P Dunn, Timothy P Fleming, Ted H Hansen, S Peter Goedegebuure, William E Gillanders

2020-Current year OA Pubs

BACKGROUND: Preclinical studies and early clinical trials have shown that targeting cancer neoantigens is a promising approach towards the development of personalized cancer immunotherapies. DNA vaccines can be rapidly and efficiently manufactured and can integrate multiple neoantigens simultaneously. We therefore sought to optimize the design of polyepitope DNA vaccines and test optimized polyepitope neoantigen DNA vaccines in preclinical models and in clinical translation.

METHODS: We developed and optimized a DNA vaccine platform to target multiple neoantigens. The polyepitope DNA vaccine platform was first optimized using model antigens in vitro and in vivo. We then identified neoantigens in preclinical breast cancer …

Dorsal Anterior Cingulate Cortex Encodes The Integrated Incentive Motivational Value Of Cognitive Task Performance, Debbie M Yee, Jennifer L Crawford, Bidhan Lamichhane, Todd S Braver

2020-Current year OA Pubs

Humans can seamlessly combine value signals from diverse motivational incentives, yet it is not well understood how these signals are "bundled" in the brain to modulate cognitive control. The dorsal ACC (dACC) is theorized to integrate motivational value dimensions in the service of goal-directed action, although this hypothesis has yet to receive rigorous confirmation. In the present study, we examined the role of human dACC in motivational incentive integration. Healthy young adult men and women were scanned with fMRI while engaged in an experimental paradigm that quantifies the combined effects of liquid (e.g., juice, neutral, saltwater) and monetary incentives on …

Functional Interpretation Of Atad3a Variants In Neuro-Mitochondrial Phenotypes, Zheng Yie Yap, Yo Han Park, Saskia B Wortmann, Adam C Gunning, Shlomit Ezer, Sukyeong Lee, Lita Duraine, Ekkehard Wilichowski, Kate Wilson, Johannes A Mayr, Matias Wagner, Hong Li, Usha Kini, Emily Davis Black, Kristin G Monaghan, James R Lupski, Sian Ellard, Dominik S Westphal, Tamar Harel, Wan Hee Yoon

Faculty, Staff and Students Publications

BACKGROUND: ATPase family AAA-domain containing protein 3A (ATAD3A) is a nuclear-encoded mitochondrial membrane-anchored protein involved in diverse processes including mitochondrial dynamics, mitochondrial DNA organization, and cholesterol metabolism. Biallelic deletions (null), recessive missense variants (hypomorph), and heterozygous missense variants or duplications (antimorph) in ATAD3A lead to neurological syndromes in humans.

METHODS: To expand the mutational spectrum of ATAD3A variants and to provide functional interpretation of missense alleles in trans to deletion alleles, we performed exome sequencing for identification of single nucleotide variants (SNVs) and copy number variants (CNVs) in ATAD3A in individuals with neurological and mitochondrial phenotypes. A Drosophila Atad3a Gal4 …

Dietary Intake Is Associated With Neuropsychological Impairment In Women With Hiv, Leah H. Rubin, Deborah R. Gustafson, Lakshmi Warrior, Lila Sheira, Kathryn C. Fitzgerald, Raha Dastgheyb, Kathleen M. Weber, Phyllis C. Tien, Audrey French, Amanda B. Spence, Anjali Sharma, Dionna W. Williams, Cory J. White, Eric C. Seaberg, Edward A. Frongillo Jr., Sheri D. Weiser

Faculty Publications

Background

Diet is a modifiable risk factor that may influence cognition in people with HIV.

Objectives

We examined the association between dietary intake and cognition in women with HIV (WWH) and HIV-seronegative women.

Methods

An 18-item dietary National Cancer Institute screener was completed by 729 WWH and 346 HIV-seronegative Women's Interagency HIV Study participants. Daily intake frequencies of processed meats, sweet beverages, fish, whole milk, and vegetables were calculated. Participants completed biennial neuropsychological (NP) testing. NP domains included attention/working memory, executive function, processing speed, memory, learning, fluency, and motor function. NP impairment was defined as demographically adjusted T-scores (mean = …