Medicine and Health Sciences Commons^™

From Static Web To Metaverse: Reinventing Medical Education In The Post-Pandemic Era, Kadriye O. Lewis, Vitaliy Popov, Syeda Sadia Fatima

Department of Biological & Biomedical Sciences

The World Wide Web and the advancement of computer technology in the 1960s and 1990s respectively set the ground for a substantial and simultaneous change in many facets of our life, including medicine, health care, and medical education. The traditional didactic approach has shifted towards more dynamic and interactive methods, leveraging technologies such as simulation tools, virtual reality, and online platforms. At the forefront is the remarkable evolution that has revolutionized how medical knowledge is accessed, disseminated, and integrated into pedagogical practices. The COVID-19 pandemic also led to rapid and large-scale adoption of e-learning and digital resources in medical education …

Investigating Clot-Flow Interactions By Integrating Intravital Imaging With In Silico Modeling For Analysis Of Flow, Transport, And Hemodynamic Forces, Chayut Teeraratkul, Maurizio Tomaiuolo, Timothy Stalker, Debanjan Mukherjee

Cardeza Foundation for Hematologic Research

As a blood clot forms, grows, deforms, and embolizes following a vascular injury, local clot-flow interactions lead to a highly dynamic flow environment. The local flow influences transport of biochemical species relevant for clotting, and determines the forces on the clot that in turn lead to clot deformation and embolization. Despite this central role, quantitative characterization of this dynamic clot-flow interaction and flow environment in the clot neighborhood remains a major challenge. Here, we propose an approach that integrates dynamic intravital imaging with computer geometric modeling and computational flow and transport modeling to develop a unified in silico framework to …

Can Vpac-Targeted Cu-67-Tp3805 Play A Theranostic Role For Prostate Cancer?: A Quest, Mathew L. Thakur

Department of Radiology Faculty Papers

Early and accurate detection of prostate cancer (PCa) together with effective treatment can save lives. Despite the recent advances in its treatment, the mortality trends due to PCa, in the USA, continue to be alarming with annual increase of 3%. In this brief communication, we propose a novel approach to treat PCa, its metastasis and recurrence. This is guided by a large quantity of preliminary data driven by targeting an endogenous genetic product, VPAC, expressed in high density on the cell surface at the onset of genetic mutation that ignites the cancerous transformation. A large body of preclinical and clinical …

Course Portfolio For Biochemistry 1: Structure And Metabolism (Bioc431), Didier Mena

UNL Faculty Course Portfolios

This benchmark portfolio encapsulates a comprehensive exploration aimed at enhancing the educational landscape of the BIOC431 course, a part of the general biochemistry course series (431 and 432). These courses are designed to offer a general introduction to the structure and function of cells in the body, along with their chemical reactions. Specifically, BIOC431 focuses on the structure, function, and metabolism of proteins, lipids, carbohydrates, and other major metabolic pathways. The three primary objectives addressed in this portfolio were the reevaluation of learning objectives, reassessment of assessment methods, and documentation of effective classroom strategies. Through background design, the learning objectives …

Comparison Of Energy Budget Of Cockroach Nymph (Hemimetabolous) And Hornworm (Holometabolous) Under Food Restriction, Charles J Green, Chen Hou

Faculty, Staff and Student Publications

Animals with different life histories budget their intake energy differently when food availability is low. It has been shown previously that hornworm (larva of Manduca sexta), a holometabolous insect species with a short development stage, prioritizes growth at the price of metabolism under food restriction, but it is unclear how hemimetabolous insect species with a relatively long development period budget their intake energy under food scarcity. Here, we use orange head cockroaches (Eublaberus posticus) to investigate this question. We found that for both species under food restriction, rates of metabolism and growth were suppressed, but the degree …

Clinical Efficacy Of 5-Fluorouracil And Bleomycin In Dermatology, Suyeon Kim, Yu Ri Woo, Sang Hyun Cho, Jeong Deuk Lee, Hei Sung Kim

Faculty, Staff and Student Publications

Bleomycin and 5-fluorouracil (5-FU) are widely used in various dermatological disorders. Both drugs are well-recognized as antineoplastic drugs and exert their effect by blocking the cell cycle. Topical and intralesional formulations are available and have been studied in both non-neoplastic and cancerous lesions. However, data comparing the effect of bleomycin and 5-FU in the dermatological disorders are limited. This review outlines the action mechanisms of both drugs and compares their clinical efficacies in a wide range of dermatologic diseases including hypertrophic scar, wart, skin cancer, vascular malformation, hemangioma, and vitiligo, and discusses the overall safety of the drugs. Intralesional bleomycin …

“Everything Seems To Be The Right Eye In Our Family”: Intergenerational Family Living With Facial Eye Disfigurement: An Interpretative Phenomenological Analysis, Zali M. O'Dea Ms, Jane Southcott

The Qualitative Report

This paper presents the lived experience of an intergenerational family, spanning three generations living with Facial Eye Disfigurement (FED). Living with vision loss and FED is estimated to affect nearly 8 billion people worldwide. Inadequate attention is paid to the impact of Living with FED (LwFED) on the lives of individuals. This research offers a deep dive into the lived experiences of one family LwFED. This family comprises a grandfather (deceased), son, wife, and child, all of whom have lived or live with FED. In this Interpretive Phenomenological Analysis (IPA) study three interviewees are deemed the experts. Data were collected …

Mechanism Of Anion Exchange And Small-Molecule Inhibition Of Pendrin, Lie Wang, Anthony Hoang, Eva Gil-Iturbe, Arthur Laganowsky, Matthias Quick, Ming Zhou

Faculty, Staff and Students Publications

Pendrin (SLC26A4) is an anion exchanger that mediates bicarbonate (HCO3−) exchange for chloride (Cl−) and is crucial for maintaining pH and salt homeostasis in the kidney, lung, and cochlea. Pendrin also exports iodide (I−) in the thyroid gland. Pendrin mutations in humans lead to Pendred syndrome, causing hearing loss and goiter. Inhibition of pendrin is a validated approach for attenuating airway hyperresponsiveness in asthma and for treating hypertension. However, the mechanism of anion exchange and its inhibition by drugs remains poorly understood. We applied cryo-electron microscopy to determine structures of pendrin from Sus scrofa in the presence of either Cl−, …

County-Level Trends And Potential Disparities In The Suicide Rates In Virginia, 2020 – 2022, Sharon A. Olowoyo, Oluwatosin M. Oduneye, Glodi B. Bokanya, Ayooluwa G. Olowoyo, Coralie E. Mugenga, Yuhan Yan, Robyn L. Anderson

Montview Journal of Research & Scholarship

Abstract

Objectives

This study aims to investigate the influence of social determinants of health (SDH) on suicide patterns in the state of Virginia.

Methods

A secondary statistical analysis was conducted using publicly accessible data from the County Health Rankings & Roadmaps database for Virginia. Data from 2020 to 2022 were analyzed, focusing on age-adjusted suicide rates and SDH factors, including % rural, mental health provider rate, median household income, high school completion, and unemployment rates. Multiple regression analysis and visualizations were employed for data interpretation.

Results

The analysis revealed that SDH factors significantly predicted suicide rates across the study period. …

Characteristics Of Patients Undergoing Electrophysiologic Procedures In A Tertiary Hospital In Saudi Arabia, Abdullah A. Aljammaz, Meshaal K. Alghanim, Ibraheem Altamimi, Mohammed A. Alshwieer, Albaraa Sabbagh, Abdulrahman S. Alsayed, Faisal G. Al-Zahrani, Mohammad F. Almanjomi, Sameer Qutub, Wael A. Alqarawi

Journal of the Saudi Heart Association

Introduction: The electrophysiology field has progressed rapidly over the last 2 decades. No study has examined the characteristics of patients and types of electrophysiology procedures performed in the Kingdom of Saudi Arabia. This is important given our distinctly different demographic composition and health system. As such, we sought to describe the characteristics of consecutive patients presenting for electrophysiology procedures in our tertiary care hospital.

Methods: Data was collected from the electrophysiology database at King Khalid University Hospital for procedures performed between April 2016 and November 2022. Patients’ characteristics were retrieved from the electronic medical record. Procedures were categorized into supraventricular …

Epidemiological, Bacteriological, And Evolutive Features Of Children Hospitalized For Infective Endocarditis In A Tertiary Tunisian Pediatric Department, Houda Ajmi, Rahma Herch, Hela Elghali, Dalel Ben Sliman, Mohamed Ben Rejeb, Sameh Mabrouk, Fadoua Majdoub, Salsabil Nouir, Lamia Tilouche, Abdelhalim Trabelsi, Saoussan Abroug, Jalel Chemli

Journal of the Saudi Heart Association

Background: Infective endocarditis is a rare condition in childhood, and there is limited data on this disease in Tunisia.

Objective: This study aims to analyze the epidemiological profile, bacteriological data, and prognosis of infective endocarditis in children admitted to the pediatric department of a University Hospital in Tunisia.

Methods: We conducted a comparative cross-sectional study in the pediatric department of Sahloul Teaching Hospital in Sousse, a tertiary referral hospital in Tunisia. The study included all children aged ≤ 18 years with infective endocarditis admitted to the tertiary referral center for pediatrics in Sahloul University Hospital from January 1994 to December …

Expansion Of Osteopathic Medicine Practitioner Education On Substance Use Disorders, Joanna Petrides, Stuti Jha, Alexander Kowalski, Suzanna Hosein, Philip B Collins, Joshua Coren

Rowan-Virtua School of Osteopathic Medicine Departmental Research

CONTEXT: Medical school graduates are generally not well prepared to treat patients with substance use disorders (SUDs), even though opioid overdose deaths in the United States have increased in recent years. When it comes to training in SUDs, osteopathic medicine lags far behind allopathic medicine. It was only in 2019 that the American Osteopathic Association approved Board Certification in Addiction Medicine to help combat the opioid epidemic. Few articles have been published in the literature pertaining to substance use education for osteopathic students and trainees.

OBJECTIVES: The goal of this study was to expand the education of osteopathic medical students …

Tail-Tape-Fused Virion And Non-Virion Rna Polymerases Of A Thermophilic Virus With An Extremely Long Tail, Anastasiia Chaban, Leonid Minakhin, Ekaterina Goldobina, Brain Bae, Yue Hao, Sergei Borukhov, Leena Putzeys, Maarten Boon, Florian Kabinger, Rob Lavigne, Kira S Makarova, Eugene V Koonin, Satish K Nair, Shunsuke Tagami, Konstantin Severinov, Maria L Sokolova

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Thermus thermophilus bacteriophage P23-45 encodes a giant 5,002-residue tail tape measure protein (TMP) that defines the length of its extraordinarily long tail. Here, we show that the N-terminal portion of P23-45 TMP is an unusual RNA polymerase (RNAP) homologous to cellular RNAPs. The TMP-fused virion RNAP transcribes pre-early phage genes, including a gene that encodes another, non-virion RNAP, that transcribes early and some middle phage genes. We report the crystal structures of both P23-45 RNAPs. The non-virion RNAP has a crab-claw-like architecture. By contrast, the virion RNAP adopts a unique flat structure without a clamp. Structure and sequence comparisons of …

Reproducibility And Validity Of Muscle Strength In Hip Abduction With Flexion While Seated In Older Adults Who Need Nursing Care, Akio Goda, Hideki Nakano, Hisami Iwai, Kento Suruga, Mai Watanabe, Shin Murata

Asian Journal of Physical Therapy

Objective: This study aimed to determine the usefulness of the strength of the muscles in hip abduction with flexion while seated (SMHAF-S) in older adults who need nursing care. To achieve this, we examined the reproducibility and validity of a method to measure the SMHAF-S in older adults who need nursing care using a hand-held dynamometer. Methods: This cross-sectional study enrolled 40 older women who needed nursing care in September 2021 and completed the SMHAF-S and underwent quadriceps muscle strength, grip strength, 10-s chair stand test for frail older adults (FCS-10), one-legged stance test (OLST), and timed-up-and-go (TUG) test. The …

Emerging Perspectives Of Synaptic Biomarkers In Als And Ftd, Karthik Krishnamurthy, Raj Kumar Pradhan

Farber Institute for Neuroscience Staff Papers and Presentations

Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) are debilitating neurodegenerative diseases with shared pathological features like transactive response DNA-binding protein of 43 kDa (TDP-43) inclusions and genetic mutations. Both diseases involve synaptic dysfunction, contributing to their clinical features. Synaptic biomarkers, representing proteins associated with synaptic function or structure, offer insights into disease mechanisms, progression, and treatment responses. These biomarkers can detect disease early, track its progression, and evaluate therapeutic efficacy. ALS is characterized by elevated neurofilament light chain (NfL) levels in cerebrospinal fluid (CSF) and blood, correlating with disease progression. TDP-43 is another key ALS biomarker, its mislocalization linked …

Open-Label Extension Of A Randomized Trial Investigating Safety And Efficacy Of Rhpth(1-84) In Hypoparathyroidism, Aliya A. Khan, Lisa G. Abbott, Intekhab Ahmed, Olulade Ayodele, Claudia Gagnon, Richard D. Finkelman, Emese Mezosi, Lars Rejnmark, Istvan Takacs, Shaoming Yin, Steven W. Ing

Division of Endocrinology, Diabetes and Metabolic Diseases Faculty Papers

Hypoparathyroidism (HypoPT) is a rare disease, often inadequately controlled by conventional treatment. PARALLAX was a mandatory post-marketing trial assessing pharmacokinetics and pharmacodynamics of different dosing regimens of recombinant human parathyroid hormone 1-84 (rhPTH[1-84]) for treating HypoPT. The present study (NCT03364738) was a phase 4, 1-yr open-label extension of PARALLAX. Patients received only 2 doses of rhPTH(1-84) in PARALLAX and were considered treatment-naive at the start of the current study. rhPTH(1-84) was initiated at 50 μg once daily, with doses adjusted based on albumin-corrected serum calcium levels. Albumin-corrected serum calcium (primary outcome measure), health-related quality of life (HRQoL), adverse events, and …

Fusionneoantigen: : A Resource Of Fusion Gene-Specific Neoantigens, Himansu Kumar, Ruihan Luo, Jianguo Wen, Chengyuan Yang, Xiaobo Zhou, Pora Kim

Faculty, Staff and Student Publications

Among the diverse sources of neoantigens (i.e. single-nucleotide variants (SNVs), insertions or deletions (Indels) and fusion genes), fusion gene-derived neoantigens are generally more immunogenic, have multiple targets per mutation and are more widely distributed across various cancer types. Therefore, fusion gene-derived neoantigens are a potential source of highly immunogenic neoantigens and hold great promise for cancer immunotherapy. However, the lack of fusion protein sequence resources and knowledge prevents this application. We introduce 'FusionNeoAntigen', a dedicated resource for fusion-specific neoantigens, accessible at https://compbio.uth.edu/FusionNeoAntigen. In this resource, we provide fusion gene breakpoint crossing neoantigens focused on ∼43K fusion proteins of ∼16K in-frame …

Drmref: Comprehensive Reference Map Of Drug Resistance Mechanisms In Human Cancer, Xiaona Liu, Jiahao Yi, Tina Li, Jianguo Wen, Kexin Huang, Jiajia Liu, Grant Wang, Pora Kim, Qianqian Song, Xiaobo Zhou

Faculty, Staff and Student Publications

Drug resistance poses a significant challenge in cancer treatment. Despite the initial effectiveness of therapies such as chemotherapy, targeted therapy and immunotherapy, many patients eventually develop resistance. To gain deep insights into the underlying mechanisms, single-cell profiling has been performed to interrogate drug resistance at cell level. Herein, we have built the DRMref database (https://ccsm.uth.edu/DRMref/) to provide comprehensive characterization of drug resistance using single-cell data from drug treatment settings. The current version of DRMref includes 42 single-cell datasets from 30 studies, covering 382 samples, 13 major cancer types, 26 cancer subtypes, 35 treatment regimens and 42 drugs. All datasets in …

Minimally Invasive Periodontal Regeneration With The Buccal Approach: A Systematic Review And Meta-Analysis Of Clinical Studies, Elisa Pasqualini, Filipe Castro, Denise Curado, Ana Martelete, Artak Heboyan, Muhammad H. Saleh, Juliana Campos Hasse Fernandes, Gustavo Fernandes

MOSDOH Faculty Publications

OBJECTIVE: The aim of this study was to investigate clinical periodontal parameters after treatment using the Minimally Invasive Surgical Technique (MIST), Modified Minimally Invasive Surgical Technique (M-MIST), and/or any technique for papilla preservation, such as Entire Papilla Preservation (EPP), modified-papilla preservation technique (M-PPT), or simplified-papilla preservation technique (SPPT). METHODS: The focus question was “For patients with periodontal intrabony defects (P), what is the best minimally invasive regenerative approach (I), comparing MIST, M-MIST, and papilla preservation techniques’ outcomes (C) to improve PD, CAL, GR, and periodontal stability (O)?” An online search was conducted on PubMed, Cochrane Library, and Embase. Only randomized …

Comparison Of Pre And Post Foley Catheter Bishop’S Score: A Retrospective Record Review At Aga Khan University Hospital Karachi, Pakistan, Ayesha Malik, Sheikh Irfan Ahmed, Farheen Yousuf, Azra Amerjee, Sumaira Naz, Safna Naozer Virji Safna Naozer Virji

Department of Obstetrics & Gynaecology

Objective: To compare pre and post Foley's catheter Bishop Score during labour induction.
Methods: This study was a retrospective study conducted at the Aga Khan University Hospital Karachi, Pakistan after approval from ethical review board. All women who underwent induction of labour with Foley's Catheter at gestation of 37 weeks or more from September 2014-October 2015 were included. Data was entered and analyzed in Statistical Package for Social Sciences (SPSS) version 19.0. The comparison between pre and post Foley's catheter Bishop Score during labour induction will be calculated by Wilcoxon sign test.
Results: There were 981 cases of inductions of …

Evaluating The Effect Of Maternal Non-Communicable Disease On Adverse Pregnancy Outcomes And Birthweight In Pakistan, A Facility Based Retrospective Cohort Study, Esther Wainwright, Sheikh Irfan Ahmed, Rahat Qureshi, Sana Yousuf, Raheela Khan, Matthew Elmes

Department of Obstetrics & Gynaecology

Non-communicable diseases (NCDs) claim 74% of global lives, disproportionately affecting lower and middle-income countries like Pakistan. NCDs may increase the risk of preterm birth (PTB), caesarean section (CS), and low birthweight. This study aims to determine whether the high prevalence of NCDs in Pakistan play a role in the high rates of preterm births, and CS. This retrospective cohort study from Aga Khan University Hospital, Pakistan, investigated effects of pre-existing NCDs on pregnancy outcomes of 817 pregnant women. Medical records were used to generate odds ratios for the risk of PTB, labour outcome and birthweight in women with type 1 …

Exploring Functional Connectivity In Chronic Spinal Cord Injury Patients With Neuropathic Pain Versus Without Neuropathic Pain, Shreya Mandloi, Mashaal Syed, Isaiah Ailes, Omid Shoraka, Benjamin Leiby, J. Miao, Sara Thalheimer, Joshua Pelta-Heller, Feroze Mohamed, Ashwini Sharan, James Harrop, Laura Krisa, M. Alizadeh

Farber Institute for Neuroscience Faculty Papers

The great majority of spinal cord injury (SCI) patients have debilitating chronic pain. Despite decades of research, these pain pathways of neuropathic pain (NP) are unknown. SCI patients have been shown to have abnormal brain pain pathways. We hypothesize that SCI NP patients’ pain matrix is altered compared to SCI patients without NP. This study examines the functional connectivity (FC) in SCI patients with moderate-severe chronic NP compared to SCI patients with mild-no NP. These groups were compared to control subjects. The Neuropathic Pain Questionnaire and neurological evaluation based on the International Standard Neurological Classification of SCI were utilized to …

Cov2var, A Function Annotation Database Of Sars-Cov-2 Genetic Variation, Yuzhou Feng, Jiahao Yi, Lin Yang, Yanfei Wang, Jianguo Wen, Weiling Zhao, Pora Kim, Xiaobo Zhou

Faculty, Staff and Student Publications

The COVID-19 pandemic, caused by the coronavirus SARS-CoV-2, has resulted in the loss of millions of lives and severe global economic consequences. Every time SARS-CoV-2 replicates, the viruses acquire new mutations in their genomes. Mutations in SARS-CoV-2 genomes led to increased transmissibility, severe disease outcomes, evasion of the immune response, changes in clinical manifestations and reducing the efficacy of vaccines or treatments. To date, the multiple resources provide lists of detected mutations without key functional annotations. There is a lack of research examining the relationship between mutations and various factors such as disease severity, pathogenicity, patient age, patient gender, cross-species …

Impact Of Elexacaftor/Tezacaftor/Ivacaftor On Lipid And Fat‐Soluble Vitamin Levels And Association With Body Mass Index, Tanvi Patel, Kimberly Mcbennett, Senthilkumar Sankararaman, Teresa Schindler, Nori Mercuri Minich, Katherine Kutney

Faculty Scholarship

Introduction:Cystic fibrosis transmembrane conductance regulator (CFTR) modulators improve gastrointestinal absorption of nutrients and may result in changes in body mass index (BMI), serum lipids, and fat-soluble vitamin levels. We hypothesized that serum lipids and vitamin levels would increase with CFTR modulator therapy and that greater increase in lipids and vitamin levels would be related to greater increase in BMI. Methods:A retrospective study was performed to evaluate the impact of elexacaftor/tezacaftor/ivacaftor (ETI) on nutritional parameters, serum lipids, and fat-soluble vitamin levels. Pre-ETI values (<2 years prior) and post-ETI values (>1 month after) were compared. Linear regression was used to evaluate whether change in BMI is associated …

Current And Future Therapeutic Strategies For High-Grade Gliomas Leveraging The Interplay Between Epigenetic Regulators And Kinase Signaling Networks, Lea M Stitzlein, Jack T Adams, Erin N Stitzlein, Richard W Dudley, Joya Chandra

Faculty, Staff and Student Publications

Targeted therapies, including small molecule inhibitors directed against aberrant kinase signaling and chromatin regulators, are emerging treatment options for high-grade gliomas (HGG). However, when translating these inhibitors into the clinic, their efficacy is generally limited to partial and transient responses. Recent studies in models of high-grade gliomas reveal a convergence of epigenetic regulators and kinase signaling networks that often cooperate to promote malignant properties and drug resistance. This review examines the interplay between five well-characterized groups of chromatin regulators, including the histone deacetylase (HDAC) family, bromodomain and extraterminal (BET)-containing proteins, protein arginine methyltransferase (PRMT) family, Enhancer of zeste homolog 2 …

Ageannomo: A Knowledgebase Of Multi-Omics Annotation For Animal Aging, Kexin Huang, Xi Liu, Zhaocan Zhang, Tiangang Wang, Haixia Xu, Qingxuan Li, Yuhao Jia, Liyu Huang, Pora Kim, Xiaobo Zhou

Faculty, Staff and Student Publications

Aging entails gradual functional decline influenced by interconnected factors. Multiple hallmarks proposed as common and conserved underlying denominators of aging on the molecular, cellular and systemic levels across multiple species. Thus, understanding the function of aging hallmarks and their relationships across species can facilitate the translation of anti-aging drug development from model organisms to humans. Here, we built AgeAnnoMO (https://relab.xidian.edu.cn/AgeAnnoMO/#/), a knowledgebase of multi-omics annotation for animal aging. AgeAnnoMO encompasses an extensive collection of 136 datasets from eight modalities, encompassing 8596 samples from 50 representative species, making it a comprehensive resource for aging and longevity research. AgeAnnoMO characterizes …

Stemdriver: A Knowledgebase Of Gene Functions For Hematopoietic Stem Cell Fate Determination, Yangyang Luo, Jingjing Guo, Jianguo Wen, Weiling Zhao, Kexin Huang, Yang Liu, Grant Wang, Ruihan Luo, Ting Niu, Yuzhou Feng, Haixia Xu, Pora Kim, Xiaobo Zhou

Faculty, Staff and Student Publications

StemDriver is a comprehensive knowledgebase dedicated to the functional annotation of genes participating in the determination of hematopoietic stem cell fate, available at http://biomedbdc.wchscu.cn/StemDriver/. By utilizing single-cell RNA sequencing data, StemDriver has successfully assembled a comprehensive lineage map of hematopoiesis, capturing the entire continuum from the initial formation of hematopoietic stem cells to the fully developed mature cells. Extensive exploration and characterization were conducted on gene expression features corresponding to each lineage commitment. At the current version, StemDriver integrates data from 42 studies, encompassing a diverse range of 14 tissue types spanning from the embryonic phase to adulthood. In order …

Sirtuin 2 Inhibition Modulates Chromatin Landscapes Genome-Wide To Induce Senescence In Atrx-Deficient Malignant Glioma, Prit Benny Malgulwar, Carla Danussi, Sharvari Dharmaiah, William Johnson, Anand Singh, Kunal Rai, Arvind Rao, Jason T Huse

Faculty, Staff and Student Publications

BACKGROUND: Functional inactivation of ATRX characterizes large subgroups of malignant gliomas in adults and children. ATRX deficiency in glioma induces widespread chromatin remodeling, driving transcriptional shifts and oncogenic phenotypes. Effective strategies to therapeutically target these broad epigenomic sequelae remain undeveloped.

METHODS: We utilized integrated multiomics and the Broad Institute Connectivity Map (CMAP) to identify drug candidates that could potentially revert ATRX-deficient transcriptional changes. We then employed disease-relevant experimental models to evaluate functional phenotypes, coupling these studies with epigenomic profiling to elucidate molecular mechanism(s).

RESULTS: CMAP analysis and transcriptional/epigenomic profiling implicated the Class III HDAC Sirtuin2 (SIRT2) as a central mediator …

Macrocephaly And Digital Anomalies Expand The Phenotypic Spectrum Of Pgap2 Variants In Hyperphosphatasia With Impaired Intellectual Development Syndrome 3 (Hpmrs3), Seda Susgun, Afif Ben-Mahmoud, Franz Rüschendorf, Bonsu Ku, Syeda Iqra Hussain, Solveig Schulz, Oliver Puk, Saskia Biskup, Jonathan D.J. Labonne, Dilan Wellalage Don, Vijay Gupta, Tae Ik Choi, Saadullah Khan, Naveed Wasif, Yves Lacassie, Lawrence C. Layman, Sibel Aylin Ugur Iseri, Cheol Hee Kim, Hyung Goo Kim

School of Medicine Faculty Publications

Glycosylphosphatidylinositols (GPIs) anchor over 150 proteins as GPI-anchored proteins (GPI-APs) with crucial roles in diverse biological processes. The highly conserved biosynthesis of GPI-APs involves precise steps with at least 21 genes, categorized as PIG and PGAP genes. Pathogenic variants in these genes are linked to human diseases, highlighting the importance of each biosynthesis step. PGAP2 stands out among these genes due to its association with an expanded clinical spectrum of neurodevelopmental disorder (NDD) phenotypes with biallelic pathogenic variants. We present four patients from two families, one consanguineous and the other nonconsanguineous, each displaying distinct clinical presentations, including intellectual disability, hyperphosphatasia, …

Minrbase: A Comprehensive Database Of Nuclear- And Mitochondrial-Ribosomal-Rna-Derived Fragments (Rrfs), Venetia Pliatsika, Tess Cherlin, Phillipe Loher, Panagiotis Vlantis, Parth Nagarkar, Stepan Nersisyan, Isidore Rigoutsos

Computational Medicine Center Faculty Papers

We describe the Mitochondrial and Nuclear rRNA fragment database (MINRbase), a knowledge repository aimed at facilitating the study of ribosomal RNA-derived fragments (rRFs). MINRbase provides interactive access to the profiles of 130 238 expressed rRFs arising from the four human nuclear rRNAs (18S, 5.8S, 28S, 5S), two mitochondrial rRNAs (12S, 16S) or four spacers of 45S pre-rRNA. We compiled these profiles by analyzing 11 632 datasets, including the GEUVADIS and The Cancer Genome Atlas (TCGA) repositories. MINRbase offers a user-friendly interface that lets researchers issue complex queries based on one or more criteria, such as parental rRNA identity, nucleotide sequence, …