Digital Commons Network^™

Post-Covid-19 Cognitive Symptoms In Patients Assisted By A Teleassistance Service: A Retrospective Cohort Study, Lívia Paula Freire Bonfim, Thais Rotsen Correa, Bruno Cabaleiro Cortizo Freire, Thais Marques Pedroso, Daniella Nunes Pereira, Thalita Baptisteli Fernandes, Luciane Kopittke, Clara Rodrigues Alves De Oliveira, Antonio Lucio Teixeira, Milena Soriano Marcolino

Faculty, Staff and Student Publications

INTRODUCTION: Four years after the onset of the COVID-19 pandemic, the frequency of long-term post-COVID-19 cognitive symptoms is a matter of concern given the impact it may have on the work and quality of life of affected people.

OBJECTIVE: To evaluate the incidence of post-acute COVID-19 cognitive symptoms, as well as the associated risk factors.

METHODS: Retrospective cohort, including outpatients with laboratory-confirmed COVID-19 and who were assisted by a public telehealth service provided by the Telehealth Network of Minas Gerais (TNMG), during the acute phase of the disease, between December/2020 and March/2022. Data were collected through a structured questionnaire, applied …

Healthcare Resource Utilization, Costs And Treatment Associated With Myasthenia Gravis Exacerbations Among Patients With Myasthenia Gravis In The Usa: A Retrospective Analysis Of Claims Data, Julia Pisc, Angela Ting, Michelle Skornicki, Omar Sinno, Edward Lee

Faculty, Staff and Student Publications

Aim: There are limited data on the clinical and economic burden of exacerbations in patients with myasthenia gravis (MG). We assessed patient clinical characteristics, treatments and healthcare resource utilization (HCRU) associated with MG exacerbation. Patients & methods: This was a retrospective analysis of adult patients with MG identified by commercial, Medicare or Medicaid insurance claims from the IBM® MarketScan® database. Eligible patients had two or more MG diagnosis codes, without evidence of exacerbation or crisis in the baseline period (12 months prior to index [first eligible MG diagnosis]). Clinical characteristics were evaluated at baseline and 12 weeks before each exacerbation. …

Image-Guided Deployment And Monitoring Of A Novel Tungsten Nanoparticle-Infused Radiopaque Absorbable Inferior Vena Cava Filter In A Swine Model, Erin Marie San Valentin, Jossana A Damasco, Marvin Bernardino, Karem A Court, Biana Godin, Gino Martin Canlas, Adam Melancon, Gouthami Chintalapani, Megan C Jacobsen, William Norton, Rick R Layman, Natalie Fowlkes, Stephen R Chen, Steven Y Huang, Marites P Melancon

Faculty, Staff and Student Publications

PURPOSE: To improve radiopacity of radiolucent absorbable poly-p-dioxanone (PPDO) inferior vena cava filters (IVCFs) and demostrate their effectiveness in clot-trapping ability.

MATERIALS AND METHODS: Tungsten nanoparticles (WNPs) were incorporated along with polyhydroxybutyrate (PHB), polycaprolactone (PCL), and polyvinylpyrrolidone (PVP) polymers to increase the surface adsorption of WNPs. The physicochemical and in vitro and in vivo imaging properties of PPDO IVCFs with WNPs with single-polymer PHB (W-P) were compared with those of WNPs with polymer blends consisting of PHB, PCL, and PVP (W-PB).

RESULTS: In vitro analyses using PPDO sutures showed enhanced radiopacity with either W-P or W-PB coating, without compromising the …

Fitness Consequences Of Depressive Symptoms Vary Between Generations: Evidence From A Large Cohort Of Women Across The 20th Century, Christopher I Gurguis, Renée A Duckworth, Nicole M Bucaro, Consuelo Walss-Bass

Faculty, Staff and Student Publications

Depression has strong negative impacts on how individuals function, leading to the assumption that there is strong negative selection on this trait that should deplete genetic variation and decrease its prevalence in human populations. Yet, depressive symptoms remain common. While there has been a large body of work trying to resolve this paradox by mapping genetic variation of this complex trait, there have been few direct empirical tests of the core assumption that there is consistent negative selection on depression in human populations. Here, we use a unique long-term dataset from the National Health and Nutrition Examination Survey that spans …

Multi-Task Learning With High-Dimensional Noisy Images, Xin Ma, Suprateek Kundu

Faculty, Staff and Student Publications

Recent medical imaging studies have given rise to distinct but inter-related datasets corresponding to multiple experimental tasks or longitudinal visits. Standard scalar-on-image regression models that fit each dataset separately are not equipped to leverage information across inter-related images, and existing multi-task learning approaches are compromised by the inability to account for the noise that is often observed in images. We propose a novel joint scalar-on-image regression framework involving wavelet-based image representations with grouped penalties that are designed to pool information across inter-related images for joint learning, and which explicitly accounts for noise in high-dimensional images via a projection-based approach. In …

Single-Cell Rna Sequencing Analysis Identifies Acute Changes In The Tumor Microenvironment Induced By Interferon Α Gene Therapy In A Murine Bladder Cancer Model, Alexis R Steinmetz, Morgan Pierce, Alberto Martini, Come Tholomier, Ganiraju Manyam, Yan Chen, Akshay Sood, Jonathan J Duplisea, Burles A Johnson, Bogdan A Czerniak, Byron H Lee, Chinnaswamy Jagannath, Seppo Yla-Herttuala, Nigel R Parker, David J Mcconkey, Colin P Dinney, Sharada Mokkapati

Faculty, Staff and Student Publications

Introduction: Nadofaragene firadenovec (Ad-IFNα/Syn3) is now approved for BCG-unresponsive bladder cancer (BLCA). IFNα is a pleiotropic cytokine that causes direct tumor cell killing via TRAIL-mediated apoptosis, angiogenesis inhibition, and activation of the innate and adaptive immune system. We established an immunocompetent murine BLCA model to study the effects of murine adenoviral IFNα (muAd-Ifnα) gene therapy on cancer cells and the tumor microenvironment using a novel murine equivalent of Nadofaragene firadenovec (muAd-Ifnα).

Methods: Tumors were induced by instilling MB49 cells into the bladders of mice; luciferase imaging confirmed tumor development. Mice were treated with adenovirus control (Ad-Ctrl; empty vector), or muAd-Ifnα …

Chronic Lymphocytic Leukemia: Novel Perspectives - How To Teach An Old Dog New Tricks, Tamar Tadmor, Jan Burger

Faculty, Staff and Student Publications

No abstract provided.

First-In-Human Phase 1 Study Of The Arginase Inhibitor Incb001158 Alone Or Combined With Pembrolizumab In Patients With Advanced Or Metastatic Solid Tumours, Aung Naing, Kyriakos P Papadopoulos, Michael J Pishvaian, Osama Rahma, Glenn J Hanna, Elena Garralda, Omar Saavedra, Sven Gogov, Howard Kallender, Lulu Cheng, Michael Smith, Xuejun Chen, Emil Kuriakose, Todd Bauer

Faculty, Staff and Student Publications

Objective: The arginase inhibitor INCB001158 was evaluated for safety (primary endpoint) in locally advanced or metastatic solid tumours; pharmacokinetics, pharmacodynamics and efficacy were also assessed.

Methods and analysis: In this non-randomised, open-label, three-part phase 1 study, INCB001158 was orally administered two times per day as monotherapy or in combination with intravenous pembrolizumab 200 mg every 3 weeks. Dose expansion was conducted in tumour-type cohorts (with or without prior anti-PD-1/PD-L1 (programmed death protein 1/programmed death ligand 1) therapy).

Results: A total of 107 patients received INCB001158 50-150 mg two times per day as monotherapy, and 153 patients, including 6 with moderate …

Systemic Treatment Of Patients With Metastatic Breast Cancer: Asco Resource-Stratified Guideline, Sana Al Sukhun, Sarah Temin, Carlos H Barrios, Nicoleta Zenovia Antone, Yanin Chavarri Guerra, Mariana Chavez-Macgregor, Rakesh Chopra, Michael A Danso, Henry Leonidas Gomez, N'Da Marcelin Homian, Alaa Kandil, Benda Kithaka, Bogda Koczwara, Beverly Moy, Gertrude Nakigudde, Fernando Enrique Petracci, Hope S Rugo, Nagi S El Saghir, Banu K Arun

Faculty, Staff and Student Publications

Purpose: To guide clinicians and policymakers in three global resource-constrained settings on treating patients with metastatic breast cancer (MBC) when Maximal setting-guideline recommended treatment is unavailable.

Methods: A multidisciplinary, multinational panel reviewed existing ASCO guidelines and conducted modified ADAPTE and formal consensus processes.

Results: Four published resource-agnostic guidelines were adapted for resource-constrained settings; informing two rounds of formal consensus; recommendations received ≥75% agreement.

Recommendations: Clinicians should recommend treatment according to menopausal status, pathological and biomarker features when quality results are available. In first-line, for hormone receptor (HR)-positive MBC, when a non-steroidal aromatase inhibitor and CDK 4/6 inhibitor combination is unavailable, …

Pathophysiology Of Pain And Mechanisms Of Neuromodulation: A Narrative Review (A Neuron Project)., Marcin Karcz, Alaa Abd-Elsayed, Krishnan Chakravarthy, Mansoor M Aman, Natalie Strand, Mark N Malinowski, Usman Latif, David Dickerson, Tolga Suvar, Timothy Lubenow, Evan Peskin, Ryan D'Souza, Eric Cornidez, Andrew Dudas, Christopher Lam, Michael Farrell Ii, Geum Yeon Sim, Mohamad Sebai, Rosa Garcia, Lucas Bracero, Yussr Ibrahim, Syed Jafar Mahmood, Marco Lawandy, Daniel Jimenez, Leili Shahgholi, Kamil Sochacki, Mohamed Ehab Ramadan, Vinicius Tieppo Francio, Dawood Sayed, Timothy Deer

Neuroscience Articles

Pain serves as a vital innate defense mechanism that can significantly impact an individual's quality of life. Understanding the physiological effects of pain well plays an important role in developing novel pain treatments. Nociceptor neurons play a key role in pain and inflammation. Interactions between nociceptors and the immune system occur both at the site of injury and within the central nervous system. Modulating chemical mediators and nociceptor activity offers promising new approaches to pain management. Essentially, the sensory nervous system is essential for modulating the body's protective response, making it critical to understand these interactions to discover new pain …

A Scoping Review Of Population Diversity In The Common Genomic Aberrations Of Clear Cell Renal Cell Carcinoma, Sean S. Kumar, Ninad Khandekar, Komal Dani, Saina R. Bhatt, Vinay Duddalwar, Anishka D'Souza

Department of Medicine Faculty Publications

Introduction: Previous literature has shown that clear cell renal cell carcinoma (ccRCC) is becoming a more prevalent diagnosis and that the incidence and mortality differ both regionally and racially. While the molecular profiles for ccRCC are studied regionally through biopsy and sequencing techniques, the genomic landscape and ccRCC diversity data are not well-studied. We conducted a review of the known genomic data on 6 of the most clinically relevant DNA biomarkers in ccRCC: Von Hippel-Landau (vHL), Polybromo-1 (PBRM1), Breast Cancer Gene 1-Associated Protein 1 (BAP1), Histone-Lysine N-Methyltransferase Domain-Containing 2 (SETD2), Mammalian Target of Rapamycin (mTOR), and Lysine-Specific Demethylase 5C (KDM5C). …

Anticancer Effects Of Wild Baicalin On Hepatocellular Carcinoma: Downregulation Of Akr1b10 And Pi3k/Akt Signaling Pathways, Longjun Sun, Wenjuan Chen, Peixi Zhao, Bin Zhao, Guangyan Lei, Le Han, Yili Zhang

Faculty, Staff and Student Publications

ntroduction

Hepatocellular carcinoma (HCC) is a common and deadly malignancy. Traditional Chinese medicine, such as the compound Astragalus (wild Baicalin), has shown promise in improving outcomes for HCC patients. This study aimed to investigate the effects of wild Baicalin on the human hepatoma cell line HepG2 and elucidate the underlying mechanisms, particularly the role of the AKR1B10 and PI3K/AKT signaling pathways.

Methods

HepG2 cells were treated with varying concentrations of wild Baicalin. Cell proliferation, apoptosis, migration, invasion, and cell cycle were evaluated using CCK-8, flow cytometry, scratch, Transwell, and clonogenic assays, respectively. Transcriptome sequencing was performed to analyze gene expression …

A Systems Biology Approach Unveils A Critical Role Of Dpp4 In Upper Gastrointestinal Cancer Patient Outcomes, Sudhir Kotnala, Anupam Dhasmana, Swati Dhasmana, Shafiul Haque, Murali Yallapu, Manish Tripathi, Meena Jaggi, Subhash Chauhan

School of Medicine Publications

Gastrointestinal (GI) cancers comprise of cancers that affect the digestive system and its accessory organs. The late detection and poor prognosis of GI cancer emphasizes the importance of identifying reliable and precise biomarkers for early diagnosis and prediction of prognosis. The membrane-bound glycoprotein dipeptidyl-peptidase 4 (DPP4), also known as CD26, is ubiquitously expressed and has a wide spectrum of biological roles. The role of DPP4/CD26 in tumor progression in different types of cancers remains elusive. However, the link between DPP4 and tumor-infiltrating cells, as well as its prognostic significance in malignancies, still require further investigation. This study was intended to …

Nonalcoholic Fatty Liver Disease, Liver Fibrosis, And Structural Brain Imaging: The Cross-Cohort Collaboration, Galit Weinstein, Adrienne O'Donnell, Stefan Frenzel, Tian Xiao, Amber Yaqub, Pinar Yilmaz, Robert J. De Knegt, Gladys E. Maestre, Debora Melo Van Lent, Michelle Long

School of Medicine Publications

Background and purpose

Prior studies reported conflicting findings regarding the association of nonalcoholic fatty liver disease (NAFLD) and liver fibrosis with measures of brain health. We examined whether NAFLD and liver fibrosis are associated with structural brain imaging measures in middle- and old-age adults.

Methods

In this cross-sectional study among dementia- and stroke-free individuals, data were pooled from the Offspring and Third Generation cohorts of the Framingham Heart Study (FHS), the Rotterdam Study (RS), and the Study of Health in Pomerania. NAFLD was assessed through abdominal imaging. Transient hepatic elastography (FibroScan) was used to assess liver fibrosis in FHS and …

Does Serum Uric Acid To Creatinine Ratio Predict Mortality Risk In Patients With Heart Failure, Xiaoqing Xi, Jinfeng Cai, Chen Zhang, Xuefei Wang

The Texas Heart Institute Journal

BACKGROUND: Previous studies have established a positive correlation between serum uric acid to creatinine (SUA/Cr) ratio and cardiovascular disease, but the relationship between SUA/Cr ratio and the prognosis of heart failure (HF) remains unknown. This study investigated the potential of SUA/Cr ratio as a prognostic predictor for patients with HF.

METHODS: This single-center prospective cohort study enrolled 2,122 patients with HF between March 2013 and June 2017. All patients were divided into 3 groups according to SUA/Cr ratio tertiles and were followed up with until December 31, 2022. The association between SUA/Cr ratio and the prognosis of HF was assessed …

Outcomes For Patients With Head And Neck Sarcoma Treated Curatively With Radiation Therapy And Surgery, Alison K Yoder, Ahsan Farooqi, Devarati Mitra, J Andrew Livingston, Dejka M Araujo, Erich M Sturgis, Ryan Goepfert, Andrew J Bishop, B Ashleigh Guadagnolo

Faculty, Staff and Student Publications

PURPOSE: Soft tissue sarcomas (STSs) of the head and neck (H&N) are rare malignancies that are challenging to manage. We sought to describe the outcomes of patients treated with curative intent using combined surgery and radiation therapy (RT) for H&N STS.

METHODS AND MATERIALS: We performed a single-institution retrospective review of patients with nonmetastatic STS of the H&N who were treated from 1968 to 2020. The Kaplan-Meier method was used to estimate disease-specific survival (DSS) and local control (LC). Multivariable analyses (MVAs) were conducted using Cox proportional hazards model.

RESULTS: One hundred ninety-two patients had a median follow-up of 82 …

Patient Perceptions On The Advancement Of Noninvasive Prenatal Testing For Sickle Cell Disease Among Black Women In The United States, Shameka P Thomas, Faith E Fletcher, Rachele Willard, Tiara Monet Ranson, Vence L Bonham

Center for Medical Ethics and Health Policy Staff Publications

Background: Noninvasive prenatal testing (NIPT) designed to screen for fetal genetic conditions, is increasingly being implemented as a part of routine prenatal care screening in the United States (US). However, these advances in reproductive genetic technology necessitate empirical research on the ethical and social implications of NIPT among populations underrepresented in genetic research, particularly Black women with sickle cell disease (SCD).

Methods: Forty (N = 40) semi-structured interviews were conducted virtually with Black women in the US (19 participants with SCD; 21 participants without SCD) from June 2021 to January 2022. We employed a qualitative approach to examine the …

Geospatial Hotspots And Coldspots In Us Cancer Disparities And Associated Risk Factors, 2004-2008 To 2014-2018, Lei Guo, M. Courtney Hughes, Margaret E. Wright, Alyssa H. Harris, Meredith C. Osias

Faculty Articles, Papers, and Other Scholarship

Introduction

Despite declining cancer death rates in the US, cancer remains the second deadliest disease and disparities persist. Although research has focused on identifying risk factors for cancer deaths and associated disparities, few studies have examined how these relationships vary over time and space. The primary objective of this study was to identify cancer mortality hot spots and cold spots — areas where cancer death rates decreased less than or more than neighboring areas over time. A secondary objective was to identify risk factors of cancer mortality hot spots and cold spots.

Methods

We analyzed county-level cancer death rates from …

Folate Regulation Of Planar Cell Polarity Pathway And F-Actin Through Folate Receptor Alpha, Xiao Han, Xuanye Cao, Robert M Cabrera, Paula Andrea Pimienta Ramirez, Ying Linda Lin, Bogdan J Wlodarczyk, Cuilian Zhang, Richard H Finnell, Yunping Lei

Faculty, Staff and Students Publications

Folate deficiency contribute to neural tube defects (NTDs) which could be rescued by folate supplementation. However, the underlying mechanisms are still not fully understood. Besides, there is considerable controversy concerning the forms of folate used for supplementation. To address this controversy, we prepared culture medium with different forms of folate, Folic acid (FA) and 5-methyltetrahydrofolate(5mTHF), at concentration of 5uM, 500nM, 50nM and folate free, respectively. Mouse embryonic fibroblasts (MEFs) were treated with different folates continuously for three passages and cell proliferation and F-actin was monitored. We determined that compared to 5mTHF, FA showed stronger effects on promoting cell proliferation and …

Spatial Transcriptomics Resolve An Emphysema-Specific Lymphoid Follicle B Cell Signature In Chronic Obstructive Pulmonary Disease, Joselyn Rojas-Quintero, Scott A Ochsner, Felicia New, Prajan Divakar, Chen Xi Yang, Tianshi David Wu, Jerid Robinson, Darshan Shimoga Chandrashekar, Nicholas E Banovich, Ivan O Rosas, Maor Sauler, Farrah Kheradmand, Amit Gaggar, Camilla Margaroli, Raul San Jose Estepar, Neil J Mckenna, Francesca Polverino

Faculty, Staff and Students Publications

Rationale

Within chronic obstructive pulmonary disease (COPD), emphysema is characterized by a significant yet partially understood B cell immune component.

Objectives

To characterize the transcriptomic signatures from lymphoid follicles (LFs) in ever-smokers without COPD and patients with COPD with varying degrees of emphysema.

Methods

Lung sections from 40 patients with COPD and ever-smokers were used for LF proteomic and transcriptomic spatial profiling. Formalin- and O.C.T.-fixed lung samples obtained from biopsies or lung explants were assessed for LF presence. Emphysema measurements were obtained from clinical chest computed tomographic scans. High-confidence transcriptional target intersection analyses were conducted to resolve emphysema-induced transcriptional networks. …

Effects And Plasma Proteomic Analysis Of Glp-1ra Versus Cpa/Ee, In Combination With Metformin, On Overweight Pcos Women: A Randomized Controlled Trial, Mingyu Liao, Xing Li, Hao Zhang, Ling Zhou, Liu Shi, Weixin Li, Rufei Shen, Guiliang Peng, Huan Zhao, Jiaqing Shao, Xiujie Wang, Zheng Sun, Hongting Zheng, Min Long

Faculty, Staff and Students Publications

PURPOSE: Polycystic ovary syndrome (PCOS) is characterized by reproductive dysfunctions and metabolic disorders. This study aims to compare the therapeutic effectiveness of glucagon-like peptide-1 receptor agonist (GLP-1RA) + Metformin (Met) versus cyproterone acetate/ethinylestradiol (CPA/EE) + Met in overweight PCOS women and identify potential proteomic biomarkers of disease risk in women with PCOS.

METHODS: In this prospective, open-label randomized controlled trial, we recruited 60 overweight PCOS women into two groups at a 1:1 ratio to receive CPA/EE (2 mg/day: 2 mg cyproterone acetate and 35-μg ethinylestradiol,) +Met (1500 mg/day) or GLP-1 RA (liraglutide, 1.2-1.8 mg/day) +Met (1500 mg/day) for 12 weeks. …

Cffdna Screening For Niemann-Pick Disease, Type C1: A Case Series, Sydney A Lau, Romy I Fawaz, Robert Rigobello, Shahad Bawazeer, Nouf M Alajaji, Eissa Faqeih, Yanchun Li, Yanming Feng, Fan Xia, Christine M Eng, Malak Abedalthagafi

Faculty, Staff and Students Publications

Cell-free fetal DNA (cffDNA) screening is a valuable tool in clinical practice for detecting chromosomal abnormalities and autosomal dominant (AD) conditions. This study introduces a novel proof-of-concept assay designed for autosomal recessive (AR) cffDNA screening, focusing on cases involving the NPC1 gene. We aim to illustrate the significant benefits of AR cffDNA screening in managing high-risk pregnancies, specifically where biallelic pathogenic variants in NPC1 cause Niemann-Pick disease, type C1 (NPC), a disorder marked by progressive neurodegeneration. Three participants for this study were recruited and gave consent to a hospital in Saudi Arabia. These participants were either carriers of NPC or …

Succinic Semialdehyde Dehydrogenase Deficiency: A Metabolic And Genomic Approach To Diagnosis, Kevin E Glinton, Charul Gijavanekar, Abbhirami Rajagopal, Laura P Mackay, Kirt A Martin, Phillip L Pearl, K Michael Gibson, Theresa A Wilson, V Reid Sutton, Sarah H Elsea

Faculty, Staff and Students Publications

Genomic sequencing offers an untargeted, data-driven approach to genetic diagnosis; however, variants of uncertain significance often hinder the diagnostic process. The discovery of rare genomic variants without previously known functional evidence of pathogenicity often results in variants being overlooked as potentially causative, particularly in individuals with undifferentiated phenotypes. Consequently, many neurometabolic conditions, including those in the GABA (gamma-aminobutyric acid) catabolism pathway, are underdiagnosed. Succinic semialdehyde dehydrogenase deficiency (SSADHD, OMIM #271980) is a neurometabolic disorder in the GABA catabolism pathway. The disorder is due to bi-allelic pathogenic variants in

Tracking Updates In Clinical Databases Increases Efficiency For Variant Reanalysis, Lele Li, Xia Tian, Vaughan Woodzell, Richard A Gibbs, Bo Yuan, Eric Venner

Faculty, Staff and Students Publications

PURPOSE: Variant interpretation, guided by American College of Medical Genetics and Genomics guidelines, can inform clinical decision-making. However, interpretations may change over time for a variety of reasons. Periodic reanalysis of previous variant interpretations is important to ensure that reported genetic findings remain accurate according to current knowledge.

METHODS: We performed automated filtering by comparing ClinVar variants available in August 2020 with those from August 2021 to screen for potential reanalysis candidates from 3 projects. These variants were subsequently interpreted based on the American College of Medical Genetics and Genomics/Association for Molecular Pathology variant interpretation guideline or ClinGen revised gene-specific …

Comparative Exploration Of Mammalian Deafness Gene Homologues In The Drosophila Auditory Organ Shows Genetic Correlation Between Insect And Vertebrate Hearing, Daniel C Sutton, Jonathan C Andrews, Dylan M Dolezal, Ye Jin Park, Hongjie Li, Daniel F Eberl, Shinya Yamamoto, Andrew K Groves

Faculty, Staff and Students Publications

Johnston's organ, the Drosophila auditory organ, is anatomically very different from the mammalian organ of Corti. However, recent evidence indicates significant cellular and molecular similarities exist between vertebrate and invertebrate hearing, suggesting that Drosophila may be a useful platform to determine the function of the many mammalian deafness genes whose underlying biological mechanisms are poorly characterized. Our goal was a comprehensive screen of all known orthologues of mammalian deafness genes in the fruit fly to better understand conservation of hearing mechanisms between the insect and the fly and ultimately gain insight into human hereditary deafness. We used bioinformatic comparisons to …

The Challenges And Opportunities Of Offering And Integrating Training In Clinical Molecular Genetics And Clinical Cytogenetics: A Survey Of Lgg Fellowship Program Directors, Joshua L Deignan, Vimla Aggarwal, Allen E Bale, Daniel B Bellissimo, Jessica K Booker, Yang Cao, Kristy R Crooks, Kristen L Deak, Daniela Del Gaudio, Birgit Funke, Nicole L Hoppman, Vanessa Horner, Robert B Hufnagel, Colleen Jackson-Cook, Prasad Koduru, Marco L Leung, Shibo Li, Pengfei Liu, Minjie Luo, Rong Mao, Heather Mason-Suares, Fady M Mikhail, Stephen R Moore, Rizwan C Naeem, Laura M Pollard, Elena A Repnikova, Lina Shao, Brandon M Shaw, Shashirekha Shetty, Teresa A Smolarek, Elizabeth Spiteri, Jessica Van Ziffle, Gail H Vance, Cindy L Vnencak-Jones, Eli S Williams

Faculty, Staff and Students Publications

PURPOSE: The specialty of Laboratory Genetics and Genomics (LGG) was created in 2017 in an effort to reflect the increasing convergence in technologies and approaches between clinical molecular genetics and clinical cytogenetics. However, there has not yet been any formal evaluation of the merging of these disciplines and the challenges faced by Program Directors (PDs) tasked with ensuring the successful training of laboratory geneticists under the new model.

METHODS: An electronic multi-question Qualtrics survey was created and was sent to the PD for each of the Accreditation Council for Graduate Medical Education-accredited LGG fellowship programs at the time. The data …

Human Plcg2 Haploinsufficiency Results In A Novel Natural Killer Cell Immunodeficiency, Joshua B Alinger, Emily M Mace, Justin R Porter, Annelise Y Mah-Som, Allyssa L Daugherty, Stephanie Li, Allison A Throm, Jeanette T Pingel, Nermina Saucier, Albert Yao, Ivan K Chinn, James R Lupski, Mohammad Ehlayel, Michael Keller, Greg R Bowman, Megan A Cooper, Jordan S Orange, Anthony R French

Faculty, Staff and Students Publications

Background:

Although most individuals effectively control herpesvirus infections, some suffer from severe and/or recurrent infections. A subset of these patients possess defects in NK cells, lymphocytes which recognize and lyse herpesvirus-infected cells; however, the genetic etiology is rarely diagnosed. PLCG2 encodes a signaling protein in NK cell and B cell signaling. Dominant-negative or gain-of-function variants in PLCG2 cause cold urticaria, antibody deficiency, and autoinflammation. However, loss-of-function variants and haploinsufficiency have not been reported to date.

Objective:

We aimed to identify the genetic cause of NK cell immunodeficiency in two families, and herein describe the functional consequences of two novel loss-of-function …

Case Report: P40phox Deficiency Underlying Pediatric-Onset Systemic Lupus Erythematosus, Alejandro Nieto-Patlán, Natalia S Fernández Dávila, Yuqing Wang, Michelle Zelnick, Eyal Muscal, Martha Curry, James R Lupski, Steven M Holland, Bo Yuan, Douglas B Kuhns, Tiphanie P Vogel, Ivan K Chinn

Faculty, Staff and Students Publications

Introduction

Systemic lupus erythematosus is a multi-faceted autoimmune disorder of complex etiology. Pre-pubertal onset of pediatric systemic lupus erythematosus (pSLE) is uncommon and should raise suspicion for a genetic driver of disease. Autosomal recessive p40^phox deficiency is a rare immunologic disorder characterized by defective but not abolished NADPH oxidase activity with residual production of reactive oxygen species (ROS) by phagocytic cells.

Case presentation

We report the case of a now 18-year-old female with pSLE onset at 7 years of age. She presented with recurrent fever and malar rash. Aspects of her immune dysregulation over time have included typical pSLE …

Thinking Twice About The Cervical Mass: A Case Report Of Primary Vaginal Leiomyosarcoma And Review Of The Literature, Caroline C Davitt, Yingao Zhang, Anthony B Costales

Faculty, Staff and Students Publications

Primary vaginal leiomyosarcoma (LMS) is an unusual cause of aggressive gynecologic cancer which requires prompt surgical treatment for favorable outcomes. Definitive diagnosis and treatment render unique challenges to clinicians based on vague presentation and limited evidence for management. Here, we describe a case of vaginal LMS in a middle-aged woman with a history of cervical dysplasia found to have a proximal vaginal mass after presenting with vaginal discharge and cramping pain. The patient was diagnosed on pathologic surgical specimen and subsequently underwent definitive surgical treatment. She remains with no evidence of disease 20 months later. In our report, we emphasize …

Comparison Of Four Protocols For In Vitro Differentiation Of Human Embryonic Stem Cells Into Trophoblast Lineages By Bmp4 And Dual Inhibition Of Activin/Nodal And Fgf2 Signaling, Zahra Anvar, Imen Chakchouk, Momal Sharif, Sangeetha Mahadevan, Li Su, Swathi Anikar, Fatemeh Alavi Naini, Alloysius Budi Utama, Ignatia B Van Den Veyver

Faculty, Staff and Students Publications

Human embryonic stem cells (hESCs) cultured in media containing bone morphogenic protein 4 (BMP4; B) differentiate into trophoblast-like cells. Supplementing media with inhibitors of activin/nodal signaling (A83-01) and of fibroblast growth factor 2 (PD173074) suppresses mesoderm and endoderm formation and improves specification of trophoblast-like lineages, but with variable effectiveness. We compared differentiation in four BMP4-containing media: mTeSR1-BMP4 only, mTeSR1-BAP, basal medium with BAP (basal-BAP), and a newly defined medium, E7-BAP. These media variably drive early differentiation towards trophoblast-like lineages with upregulation of early trophoblast markers CDX2 and KRT7 and downregulation of pluripotency markers (OCT4 and NANOG). As expected, based on …