Digital Commons Network^™

Bigh3 Mediates Apoptosis And Gap Junction Failure In Osteocytes During Renal Cell Carcinoma Bone Metastasis Progression, Tianhong Pan, Fengshuo Liu, Xiaoxin Hao, Shubo Wang, Murtaza Wasi, Jian H Song, Valerae O Lewis, Patrick P Lin, Bryan Moon, Justin E Bird, Theocharis Panaretakis, Sue-Hwa Lin, Danielle Wu, Mary C Farach-Carson, Liyun Wang, Ningyan Zhang, Zhiqiang An, Xiang H-F Zhang, Robert L Satcher

Faculty, Staff and Student Publications

Renal cell carcinoma (RCC) bone metastatis progression is driven by crosstalk between tumor cells and the bone microenvironment, which includes osteoblasts, osteoclasts, and osteocytes. RCC bone metastases (RCCBM) are predominantly osteolytic and resistant to antiresorptive therapy. The molecular mechanisms underlying pathologic osteolysis and disruption of bone homeostasis remain incompletely understood. We previously reported that BIGH3/TGFBI (transforming growth factor-beta-induced protein ig-h3, shortened to BIGH3 henceforth) secreted by colonizing RCC cells drives osteolysis by inhibiting osteoblast differentiation, impairing healing of osteolytic lesions, which is reversible with osteoanabolic agents. Here, we report that BIGH3 induces osteocyte apoptosis in both human RCCBM tissue specimens …

Preeclampsia In The Context Of Covid-19: Mechanisms, Pathophysiology, And Clinical Outcomes, Guilherme M Nobrega, Brittany R Jones, Indira U Mysorekar, Maria Laura Costa

Center on Aging Staff Publications

The emergence of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to the global COVID-19 pandemic, significantly impacting the health of pregnant women. Obstetric populations, already vulnerable, face increased morbidity and mortality related to COVID-19, aggravated by preexisting comorbidities. Recent studies have shed light on the potential correlation between COVID-19 and preeclampsia (PE), a leading cause of maternal and perinatal morbidity worldwide, emphasizing the significance of exploring the relationship between these two conditions. Here, we review the pathophysiological similarities that PE shares with COVID-19, with a particular focus on severe COVID-19 cases and in PE-like syndrome cases related with …

Activated Sputum Eosinophils Associated With Exacerbations In Children On Mepolizumab, Gabriella E Wilson, Michelle Gill, Et Al.

2020-Current year OA Pubs

BACKGROUND: MUPPITS-2 was a randomized, placebo-controlled clinical trial that demonstrated mepolizumab (anti-IL-5) reduced exacerbations and blood and airway eosinophils in urban children with severe eosinophilic asthma. Despite this reduction in eosinophilia, exacerbation risk persisted in certain patients treated with mepolizumab. This raises the possibility that subpopulations of airway eosinophils exist that contribute to breakthrough exacerbations.

OBJECTIVE: We aimed to determine the effect of mepolizumab on airway eosinophils in childhood asthma.

METHODS: Sputum samples were obtained from 53 MUPPITS-2 participants. Airway eosinophils were characterized using mass cytometry and grouped into subpopulations using unsupervised clustering analyses of 38 surface and intracellular markers. …

Opioid Use Disorder Risk Alleles In Self-Reported Assigned African American/Afro-Caribbean And European Biogeographical Genetic Ancestry Groups And In Males And Females, Jon E Sprague, Caroline E Freiermuth, Joshua Lambert, Robert Braun, Jennifer A Frey, Daniel J Bachmann, Jason J Bischof, Lauren Beaumont, Michael S Lyons, Michael V Pantalon, Brittany E Punches, Rachel Ancona, David F Kisor

2020-Current year OA Pubs

The influence of genetic variants related to opioid use disorder (OUD) was evaluated using multiple logistic regression analysis in self-reported assigned African American/Afro-Caribbean and European biogeographical ancestry groups (BGAGs) and by sex. From a sample size of 1301 adult patients (>18 years of age) seen in emergency departments of three medical centers in Ohio, six variants were found to be associated with OUD. Two of the variants, rs2740574 (CYP3A4) and rs324029 (DRD3), were included in the analysis having met criteria of at least five subjects for each BGAG, variant carrier status, and OUD status combinations. Variant carriers in the …

Community-Based Participatory Research And System Dynamics Modeling For Improving Retention In Hypertension Care, Jiancheng Ye, Ikechukwu A Orji, Michelle A Birkett, Lisa R Hirschhorn, Theresa L Walunas, Justin D Smith, Namratha R Kandula, Gabriel L Shedul, Mark D Huffman, Dike B Ojji

2020-Current year OA Pubs

IMPORTANCE: The high prevalence of hypertension calls for broad, multisector responses that foster prevention and care services, with the goal of leveraging high-quality treatment as a means of reducing hypertension incidence. Health care system improvements require stakeholder input from across the care continuum to identify gaps and inform interventions that improve hypertension care service, delivery, and retention; system dynamics modeling offers a participatory research approach through which stakeholders learn about system complexity and ways to model sustainable system-level improvements.

OBJECTIVE: To assess the association of simulated interventions with hypertension care retention rates in the Nigerian primary health care system using …

A Protocol For The Inclusion Of Minoritized Persons In Alzheimer Disease Research From The Adni3 Diversity Taskforce, Ozioma C Okonkwo, Beau M Ances, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Black or African American (hereinafter, Black) and Hispanic or Latino/a/x (hereinafter, Latinx) adults are disproportionally affected by Alzheimer disease, but most research studies do not enroll adequate numbers of both of these populations. The Alzheimer's Disease Neuroimaging Initiative-3 (ADNI3) launched a diversity taskforce to pilot a multipronged effort to increase the study inclusion of Black and Latinx older adults.

OBJECTIVE: To describe and evaluate the culturally informed and community-engaged inclusion efforts to increase the screening and enrollment of Black and Latinx older adults in ADNI3.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used baseline data from a longitudinal, multisite, …

Racial And Geographic Disparities In Neonatal Brain Care, Zachary A Vesoulis, Stephanie Diggs, Cherise Brackett, Brynne Sullivan

2020-Current year OA Pubs

In this review, we explore race-based disparities in neonatology and their impact on brain injury and neurodevelopmental outcomes. We discuss the historical context of healthcare discrimination, focusing on the post-Civil War era and the segregation of healthcare facilities. We highlight the increasing disparity in infant mortality rates between Black and White infants, with premature birth being a major contributing factor, and emphasize the role of prenatal factors such as metabolic syndrome and toxic stress in affecting neonatal health. Furthermore, we examine the geographic and historical aspects of racial disparities, including the consequences of redlining and limited access to healthcare facilities …

Sex-Dependent Differences In Vulnerability To Early Risk Factors For Posttraumatic Stress Disorder: Results From The Aurora Study, Stephanie Haering, Stacey L House, Et Al.

2020-Current year OA Pubs

BACKGROUND: Knowledge of sex differences in risk factors for posttraumatic stress disorder (PTSD) can contribute to the development of refined preventive interventions. Therefore, the aim of this study was to examine if women and men differ in their vulnerability to risk factors for PTSD.

METHODS: As part of the longitudinal AURORA study, 2924 patients seeking emergency department (ED) treatment in the acute aftermath of trauma provided self-report assessments of pre- peri- and post-traumatic risk factors, as well as 3-month PTSD severity. We systematically examined sex-dependent effects of 16 risk factors that have previously been hypothesized to show different associations with …

An Atypical Form Of 60s Ribosomal Subunit In Diamond-Blackfan Anemia Linked To Rpl17 Variants., Florence Fellmann, Carol J. Saunders, Marie-Françoise O'Donohue, David W. Reid, Kelsey A. Mcfadden, Nathalie Montel-Lehry, Cong Yu, Mingyan Fang, Jianguo Zhang, Beryl Royer-Bertrand, Pietro Farinelli, Narjesse Karboul, Jason R. Willer, Lorraine Fievet, Zahurul Alam Bhuiyan, Alissa Lw Kleinhenz, Julie Jadeau, Joy M. Fulbright, Carlo Rivolta, Raffaele Renella, Nicholas Katsanis, Jacques S. Beckmann, Christopher V. Nicchitta, Lydie Da Costa, Erica E. Davis, Pierre-Emmanuel Gleizes

Manuscripts, Articles, Book Chapters and Other Papers

Diamond-Blackfan anemia syndrome (DBA) is a ribosomopathy associated with loss-of-function variants in more than 20 ribosomal protein (RP) genes. Here, we report the genetic, functional, and biochemical dissection of 2 multigenerational pedigrees with variants in RPL17, a large ribosomal subunit protein-encoding gene. Affected individuals had clinical features and erythroid proliferation defects consistent with DBA. Further, RPL17/uL22 depletion resulted in anemia and micrognathia in zebrafish larvae, and in vivo complementation studies indicated that RPL17 variants were pathogenic. Lymphoblastoid cell lines (LCLs) derived from patients displayed a ribosomal RNA maturation defect reflecting haploinsufficiency of RPL17. The proteins encoded by RPL17 variants were …

Loneliness Among Black/African American Adults Living With Hiv: Sociodemographic And Psychosocial Correlates And Implications For Adherence., Nipher Malika, Laura M. Bogart, Matt G. Mutchler, Kathy Goggin, David J. Klein, Sean J. Lawrence, Glenn J. Wagner

Manuscripts, Articles, Book Chapters and Other Papers

Loneliness, an emerging public health problem, is higher among people living with HIV and is associated with negative health outcomes. Black/African Americans have a high burden of HIV, and little is known about the characteristics of loneliness among Black adults living with HIV; therefore, this study sought to understand the sociodemographic and psychosocial correlates of Black adults living with HIV who are lonely and the implications of loneliness for their health outcomes. A sample of 304 Black adults living with HIV (73.8% sexual minority men) in Los Angeles County, CA, USA, completed the survey items assessing sociodemographic and psychosocial characteristics, …

Management Of Diabetic Ketoacidosis In Children: Does Early Insulin Glargine Help Improve Outcomes?, Rebecca Ohman-Hanson, G Todd Alonso, Laura Pyle, Ryan Mcdonough, Mark A. Clements

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Rebound hyperglycemia following the resolution of diabetic ketoacidosis (DKA) is common in pediatric patients with type 1 diabetes, increasing the risk of recurrent DKA and complicating the transition to subcutaneous insulin. Multiple studies suggest that early administration of long-acting insulin analogs during DKA management safely improves this transition.

OBJECTIVE: This study aimed to determine whether early insulin glargine administration in children with DKA prevents rebound hyperglycemia and recurrent ketosis without increasing the rate of hypoglycemia or hypokalemia.

METHODS: Patients agedChildren's Mercy Kansas City between October 2012 and October 2016 were reviewed. They were categorized as Early (>4 h …

Genomic Insights Into Pediatric Intestinal Inflammatory And Eosinophilic Disorders Using Single-Cell Rna-Sequencing., Marissa R. Keever-Keigher, Lisa Harvey, Veronica Williams, Carrie A Vyhlidal, Atif A Ahmed, Jeffrey J. Johnston, Daniel A. Louiselle, Elin Grundberg, Tomi Pastinen, Craig A. Friesen, Rachel Chevalier, Craig Smail, Valentina Shakhnovich

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: Chronic inflammation of the gastrointestinal tissues underlies gastrointestinal inflammatory disorders, leading to tissue damage and a constellation of painful and debilitating symptoms. These disorders include inflammatory bowel diseases (Crohn's disease and ulcerative colitis), and eosinophilic disorders (eosinophilic esophagitis and eosinophilic duodenitis). Gastrointestinal inflammatory disorders can often present with overlapping symptoms necessitating the use of invasive procedures to give an accurate diagnosis.

METHODS: This study used peripheral blood mononuclear cells from individuals with Crohn's disease, ulcerative colitis, eosinophilic esophagitis, and eosinophilic duodenitis to better understand the alterations to the transcriptome of individuals with these diseases and identify potential markers of …

Meta-Analysis Identifies Common Gut Microbiota Associated With Multiple Sclerosis, Qingqi Lin, Yair Dorsett, Ali Mirza, Helen Tremlett, Laura Piccio, Erin E Longbrake, Siobhan Ni Choileain, David A Hafler, Laura M Cox, Howard L Weiner, Takashi Yamamura, Kun Chen, Yufeng Wu, Yanjiao Zhou

2020-Current year OA Pubs

BACKGROUND: Previous studies have identified a diverse group of microbial taxa that differ between patients with multiple sclerosis (MS) and the healthy population. However, interpreting findings on MS-associated microbiota is challenging, as there is no true consensus. It is unclear whether there is gut microbiota commonly altered in MS across studies.

METHODS: To answer this, we performed a meta-analysis based on the 16S rRNA gene sequencing data from seven geographically and technically diverse studies comprising a total of 524 adult subjects (257 MS and 267 healthy controls). Analysis was conducted for each individual study after reprocessing the data and also …

Treatment Of Large Intracranial Aneurysms Using The Woven Endobridge (Web): A Propensity Score-Matched Analysis, Basel Musmar, Hamza Salim, Nimer Adeeb, Assala Aslan, Bahaa Aljeradat, Jose Diestro, Rachel Mclellan, Oktay Algin, Sherief Ghozy, Mahmoud Dibas, Sovann Lay, Adrien Guenego, Leonardo Renieri, Nicole Cancelliere, Joseph Carnevale, Guillaume Saliou, Panagiotis Mastorakos, Kareem El Naamani, Eimad Shotar, Kevin Premat, Markus Möhlenbruch, Michael Kral, Justin Vranic, Charlotte Chung, Mohamed Salem, Ivan Lylyk, Paul Foreman, Jay Vachhani, Hamza Shaikh, Vedran Župančić, Muhammad Hafeez, Joshua Catapano, Muhammad Waqas, Vincent Tutino, Mohamed Ibrahim, Marwa Mohammed, M. Ozgur Ozates, Giyas Ayberk, James Rabinov, Yifan Ren, Clemens Schirmer, Mariangela Piano, Anna Kühn, Caterina Michelozzi, Stéphanie Elens, Robert Starke, Ameer Hassan, Mark Ogilvie, Anh Nguyen, Jesse Jones, Waleed Brinjikji, Marie Nawka, Marios Psychogios, Christian Ulfert, Julian Spears, Brian Jankowitz, Jan-Karl Burkhardt, Ricardo Domingo, Thien Huynh, Juan Carlos Martinez-Gutierrez, Muhammed Essibayi, Sunil Sheth, Gary Spiegel, Rabih Tawk, Boris Lubicz, Pietro Panni, Ajit Puri, Guglielmo Pero, Erez Nossek, Eytan Raz, Monika Killer-Oberfalzer, Christoph Griessenauer, Hamed Asadi, Adnan Siddiqui, Allan Brook, David Altschul, Andrew Ducruet, Felipe Albuquerque, Robert Regenhardt, Christopher Stapleton, Peter Kan, Vladimir Kalousek, Pedro Lylyk, Srikanth Boddu, Jared Knopman, Mohammad A Aziz-Sultan, Stavropoula Tjoumakaris, Frédéric Clarençon, Nicola Limbucci, Hugo Cuellar-Saenz, Pascal Jabbour, Vitor Pereira, Aman Patel, Adam Dmytriw

Department of Neurosurgery Faculty Papers

The Woven EndoBridge (WEB) device is primarily used for treating wide-neck intracranial bifurcation aneurysms under 10 mm. Limited data exists on its efficacy for large aneurysms. We aim to assess angiographic and clinical outcomes of the WEB device in treating large versus small aneurysms. We conducted a retrospective review of the WorldWide WEB Consortium database, from 2011 to 2022, across 30 academic institutions globally. Propensity score matching (PSM) was employed to compare small and large aneurysms on baseline characteristics. A total of 898 patients were included. There was no significant difference observed in clinical presentations, smoking status, pretreatment mRS, presence …

A Mixed Methods Exploration Of Young Women's Agency And Mental Health During Covid-19 In Low-Income Communities In Mumbai, India, Marie A Brault, Melissa F Peskin, Anastasia N Jones, Amrita Saikia, Rinchen O Bhutia, Sai Sammitha Cheruvu, Vaishali M Jagtap, Rajendra Singh, Poornima Nair, Rajesh Vedanthan, Sten H Vermund, Shubhada Maitra

Faculty, Staff and Student Publications

Introduction: Adolescent girls and young women (AGYW) in India face additional health inequities compared to their male peers, as gender norms constrain agency for prevention and self-care. The onset of the COVID-19 pandemic and associated lockdowns deepened health inequities and often worsened mental health, but the impacts on agency are unclear. This exploratory sequential mixed methods paper examined mental health and COVID-19 elements that exacerbated or mitigated adverse consequences for AGYW in low-income communities in Mumbai.

Methods: We conducted semi-structured interviews with AGYW (aged 15-25 years; N = 60) and adults (parents, healthcare providers, community-based organization representative; N = 30). …

Treatment Of Large Intracranial Aneurysms Using The Woven Endobridge (Web): A Propensity Score-Matched Analysis, Basel Musmar, Hamza Adel Salim, Nimer Adeeb, Assala Aslan, Bahaa Aljeradat, Jose Danilo Bengzon Diestro, Rachel M Mclellan, Oktay Algin, Sherief Ghozy, Mahmoud Dibas, Sovann V Lay, Adrien Guenego, Leonardo Renieri, Nicole M Cancelliere, Joseph Carnevale, Guillaume Saliou, Panagiotis Mastorakos, Kareem El Naamani, Eimad Shotar, Kevin Premat, Markus Möhlenbruch, Michael Kral, Justin E Vranic, Charlotte Chung, Mohamed M Salem, Ivan Lylyk, Paul M Foreman, Jay A Vachhani, Hamza Shaikh, Vedran Župančić, Muhammad U Hafeez, Joshua Catapano, Muhammad Waqas, Vincent M Tutino, Mohamed K Ibrahim, Marwa A Mohammed, M Ozgur Ozates, Giyas Ayberk, James D Rabinov, Yifan Ren, Clemens M Schirmer, Mariangela Piano, Anna L Kühn, Caterina Michelozzi, Stéphanie Elens, Robert M Starke, Ameer Hassan, Mark Ogilvie, Anh Nguyen, Jesse Jones, Waleed Brinjikji, Marie T Nawka, Marios Psychogios, Christian Ulfert, Julian Spears, Brian T Jankowitz, Jan-Karl Burkhardt, Ricardo A Domingo, Thien Huynh, Juan Carlos Martinez-Gutierrez, Muhammed Amir Essibayi, Sunil A Sheth, Gary Spiegel, Rabih Tawk, Boris Lubicz, Pietro Panni, Ajit S Puri, Guglielmo Pero, Erez Nossek, Eytan Raz, Monika Killer-Oberfalzer, Christoph J Griessenauer, Hamed Asadi, Adnan Siddiqui, Allan Brook, David Altschul, Andrew F Ducruet, Felipe C Albuquerque, Robert W Regenhardt, Christopher J Stapleton, Peter Kan, Vladimir Kalousek, Pedro Lylyk, Srikanth Boddu, Jared Knopman, Mohammad A Aziz-Sultan, Stavropoula I Tjoumakaris, Frédéric Clarençon, Nicola Limbucci, Hugo H Cuellar-Saenz, Pascal M Jabbour, Vitor Mendes Pereira, Aman B Patel, Adam A Dmytriw

Faculty, Staff and Student Publications

The Woven EndoBridge (WEB) device is primarily used for treating wide-neck intracranial bifurcation aneurysms under 10 mm. Limited data exists on its efficacy for large aneurysms. We aim to assess angiographic and clinical outcomes of the WEB device in treating large versus small aneurysms. We conducted a retrospective review of the WorldWide WEB Consortium database, from 2011 to 2022, across 30 academic institutions globally. Propensity score matching (PSM) was employed to compare small and large aneurysms on baseline characteristics. A total of 898 patients were included. There was no significant difference observed in clinical presentations, smoking status, pretreatment mRS, presence …

Iatrogenic Atrial Septal Defect After Mitraclip Transcatheter Edge-To-Edge Repair: To Close Or Not To Close??, Mariem Abdelsalam, Raghad Younus, Lamis F Abdalla, Abdelkader Almanfi

The Texas Heart Institute Journal

The evolution of percutaneous procedures that use transseptal puncture to treat left-sided structural heart disease has led to the emergence of iatrogenic atrial septal defects as a potential complication. These defects can result in hemodynamic decompensation and worsening clinical outcomes. Some iatrogenic atrial septal defects require immediate closure, others do not. This case report presents 2 patients who underwent transcatheter edge-to-edge mitral valve repair with transseptal puncture and required iatrogenic atrial septal defect closure (1 immediate and 1 delayed). The goal of this report is to highlight iatrogenic atrial septal defect assessment and the possible need for closure after transseptal …

Novel Pathogenic Variants In Polr3k Cause Polr3-Related Leukodystrophy, Stefanie Perrier, Julia Macintosh, Agata D. Misiaszek, Gabrielle Lambert, Kether Guerrero, Luan T. Tran, Christoph W. Müller, Tomi Pastinen, Gustavo H B Maegawa, Isabelle Thiffault, Geneviève Bernard

Manuscripts, Articles, Book Chapters and Other Papers

POLR3-related hypomyelinating leukodystrophy (POLR3-HLD) is a rare inherited neurological disorder caused by biallelic pathogenic variants in specific genes encoding subunits of RNA polymerase III (Pol III). Here, we report the third patient worldwide with pathogenic variants in POLR3K and clinical features consistent with POLR3-HLD. The female patient presented with mild intellectual and behavioural disturbances in childhood, as well as growth delay, with brain MRI revealing diffuse hypomyelination and a pattern consistent with POLR3-HLD. In adolescence, she manifested minor motor dysfunction. Next-generation sequencing revealed a paternally inherited missense variant in POLR3K (c.322G>T; p.D108Y) and a maternally inherited large deletion, spanning …

Potential S1 Nerve Root Blocks Associated With Sacroiliac Joint Injections, Andrew Ng, Jesse Lou, Dajie Wang

Department of Anesthesiology Faculty Papers

BACKGROUND: Sacroiliac (SI) joint dysfunction is a common cause of lower back pain. The diagnosis of SI joint pain remains challenging. Sacroiliac joint injection remains the gold standard of diagnosis of SI joint pain as well as providing therapeutic effect. One complication related to SI joint injection is temporary numbness and weakness of the leg.

OBJECTIVES: To evaluate the anatomy of the SI joint and the flow of the contrast in the sacroiliac joint and to understand how local anesthetic can affect the nerve roots and cause temporary weakness and numbness of the leg.

METHODS: Patients who underwent SI joint …

Statistical Methods For Predicting E-Cigarette Use Events Based On Beat-To-Beat Interval (Bbi) Data Collected From Wearable Devices, James J Yang, Megan E Piper, Premananda Indic, Anne Buu

Faculty, Staff and Student Publications

The prevalence of e-cigarette use among young adults in the USA is high (14%). Although the majority of users plan to quit vaping, the motivation to make a quit attempt is low and available support during a quit attempt is limited. Using wearable sensors to collect physiological data (eg, heart rate) holds promise for capturing the right timing to deliver intervention messages. This study aims to fill the current knowledge gap by proposing statistical methods to (1) de-noise beat-to-beat interval (BBI) data from smartwatches worn by 12 young adult regular e-cigarette users for 7 days; and (2) summarize the de-noised …

Adaptive Fine-Tuning Based Transfer Learning For The Identification Of Mgmt Promoter Methylation Status, Erich Schmitz, Yunhui Guo, Jing Wang

Faculty, Staff and Student Publications

Background. Glioblastoma Multiforme (GBM) is an aggressive form of malignant brain tumor with a generally poor prognosis. O 6-methylguanine-DNA methyltransferase (MGMT) promoter methylation has been shown to be a predictive bio-marker for resistance to treatment of GBM, but it is invasive and time-consuming to determine methylation status. There has been effort to predict the MGMT methylation status through analyzing MRI scans using machine learning, which only requires pre-operative scans that are already part of standard-of-care for GBM patients. Purpose. To improve the performance of conventional transfer learning in the identification of MGMT promoter methylation status, we developed a 3D SpotTune …

The Interaction Of Endorepellin And Neurexin Triggers Neuroepithelial Autophagy And Maintains Neural Tube Development, Lei Lu, Meizhu Bai, Yufang Zheng, Xiukun Wang, Zhongzhong Chen, Rui Peng, Richard H Finnell, Tongjin Zhao, Chengtao Li, Bo Wu, Yunping Lei, Jinsong Li, Hongyan Wang

Faculty, Staff and Students Publications

Heparan sulfate proteoglycan 2 (HSPG2) gene encodes the matrix protein Perlecan, and genetic inactivation of this gene creates mice that are embryonic lethal with severe neural tube defects (NTDs). We discovered rare genetic variants of HSPG2 in 10% cases compared to only 4% in controls among a cohort of 369 NTDs. Endorepellin, a peptide cleaved from the domain V of Perlecan, is known to promote angiogenesis and autophagy in endothelial cells. The roles of enderepellin in neurodevelopment remain unclear so far. Our study revealed that endorepellin can migrate to the neuroepithelial cells and then be recognized and bind with the …

Gemykibivirus Detection In Acute Encephalitis Patients From Nepal, Eans Tara Tuladhar, Smita Shrestha, Susan Vernon, Lindsay Droit, Kathie A Mihindukulasuriya, Mamta Tamang, Lata Karki, Annie Elong Ngono, Bimlesh Jha, Bal Krishna Awal, Bimal Sharma Chalise, Runa Jha, Sujan Shresta, David Wang, Krishna Das Manandhar

2020-Current year OA Pubs

UNLABELLED: Acute encephalitis syndrome (AES) causes significant morbidity and mortality worldwide. In Nepal, Japanese encephalitis virus (JEV) accounts for ~5-20% of AES cases, but ~75% of AES cases are of unknown etiology. We identified a gemykibivirus in CSF collected in 2020 from an 8-year-old male patient with AES using metagenomic next-generation sequencing. Gemykibiviruses are single stranded, circular DNA viruses in the family

IMPORTANCE: Viral encephalitis is a devastating disease, but unfortunately, worldwide, the causative virus in many cases is unknown. Therefore, it is important to identify viruses that could be responsible for cases of human encephalitis. Here, using metagenomic sequencing …

Developing A Fair And Interpretable Representation Of The Clock Drawing Test For Mitigating Low Education And Racial Bias., Jiaqing Zhang, Sabyasachi Bandyopadhyay, Faith Kimmet, Jack Wittmayer, Kia Khezeli, David J. Libon, Catherine C Price, Parisa Rashidi

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The clock drawing test (CDT) is a neuropsychological assessment tool to screen an individual's cognitive ability. In this study, we developed a Fair and Interpretable Representation of Clock drawing test (FaIRClocks) to evaluate and mitigate classification bias against people with less than 8 years of education, while screening their cognitive function using an array of neuropsychological measures. In this study, we represented clock drawings by a priorly published 10-dimensional deep learning feature set trained on publicly available data from the National Health and Aging Trends Study (NHATS). These embeddings were further fine-tuned with clocks from a preoperative cognitive screening program …

Veritac-2: A Phase Iii Study Of Vepdegestrant, A Protac Er Degrader, Versus Fulvestrant In Er+/Her2- Advanced Breast Cancer, Erika P Hamilton, Cynthia Ma, Michelino De Laurentiis, Hiroji Iwata, Sara A Hurvitz, Seth A Wander, Michael Danso, Dongrui R Lu, Julia Perkins Smith, Yuan Liu, Lana Tran, Sibyl Anderson, Mario Campone

2020-Current year OA Pubs

Vepdegestrant (ARV-471) is an oral PROTAC ER degrader that binds an E3 ubiquitin ligase and ER to directly trigger ubiquitination of ER and its subsequent proteasomal degradation. In a first-in-human Phase I/II study, vepdegestrant monotherapy was well tolerated with clinical activity in pretreated patients with ER+/HER2- advanced breast cancer. The global, randomized Phase III VERITAC-2 study compares efficacy and safety of vepdegestrant versus fulvestrant in adults with ER+/HER2- advanced breast cancer after treatment with a CDK4/6 inhibitor plus endocrine therapy. Progression-free survival by blinded independent central review (primary end point) will be assessed in the intention-to-treat population and

"It Shouldn't Be Just Hush-Hush": A Qualitative Community-Based Study Of Menstrual Health Communication Among Women In Philadelphia, Allison R. Casola, Lynette Medley, Brianna C. Kunes, Nya Mcglone, Alexis Silverio

Department of Family & Community Medicine Faculty Papers

INTRODUCTION: Although menstruation is a natural biological process, many people feel embarrassed of their menses and struggle to discuss it. To mitigate menstrual communication stigma, it is necessary to first elucidate communication experiences and perceptions. Thus, we qualitatively explore menstrual communication among cisgender women who menstruate and their family, friends, healthcare providers, and community.

METHODOLOGY: In partnership with No More Secrets (NMS), a Philadelphia menstrual health non-profit, we conducted a community-based participatory research (CBPR) project in Fall 2020. Cisgender, menstruating individuals ages 18-45 recruited from NMS' catchment in Philadelphia participated in semi-structured interviews about their menstrual experiences and communication (N …

Cerebellar Nuclei Cells Produce Distinct Pathogenic Spike Signatures In Mouse Models Of Ataxia, Dystonia, And Tremor, Meike E Van Der Heijden, Amanda M Brown, Dominic J Kizek, Roy V Sillitoe

Duncan NRI Faculty and Staff Publications

The cerebellum contributes to a diverse array of motor conditions, including ataxia, dystonia, and tremor. The neural substrates that encode this diversity are unclear. Here, we tested whether the neural spike activity of cerebellar output neurons is distinct between movement disorders with different impairments, generalizable across movement disorders with similar impairments, and capable of causing distinct movement impairments. Using in vivo awake recordings as input data, we trained a supervised classifier model to differentiate the spike parameters between mouse models for ataxia, dystonia, and tremor. The classifier model correctly assigned mouse phenotypes based on single-neuron signatures. Spike signatures were shared …

The Association Between Prolonged Sars-Cov-2 Symptoms And Work Outcomes, Arjun K Venkatesh, Huihui Yu, Caitlin Malicki, Michael Gottlieb, Joann G Elmore, Mandy J Hill, Ahamed H Idris, Juan Carlos C Montoy, Kelli N O'Laughlin, Kristin L. Rising, Kari A Stephens, Erica S Spatz, Robert A Weinstein

Department of Emergency Medicine Faculty Papers

While the early effects of the COVID-19 pandemic on the United States labor market are well-established, less is known about the long-term impact of SARS-CoV-2 infection and Long COVID on employment. To address this gap, we analyzed self-reported data from a prospective, national cohort study to estimate the effects of SARS-CoV-2 symptoms at three months post-infection on missed workdays and return to work. The analysis included 2,939 adults in the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE) study who tested positive for their initial SARS-CoV-2 infection at the time of enrollment, were employed before the pandemic, and completed …

Phase Ii Basket Trial Of Dual Anti-Ctla-4 And Anti-Pd-1 Blockade In Rare Tumors (Dart) Swog S1609: Adrenocortical Carcinoma Cohort, Sandip P Patel, Megan Othus, Young Kwang Chae, Tridu Huynh, Benjamin Tan, Timothy Kuzel, Christine Mcleod, Gabby Lopez, Helen X Chen, Elad Sharon, Howard Streicher, Christopher W Ryan, Charles Blanke, Razelle Kurzrock

2020-Current year OA Pubs

OBJECTIVES: Multiple common cancers benefit from immunotherapy; however, less is known about efficacy in rare tumors. We report the results of the adrenocortical carcinoma cohort of NCI/SWOG S1609 Dual Anti-CTLA-4 and Anti-PD-1 blockade in Rare Tumors.

DESIGN/SETTING: A prospective, phase 2 clinical trial of ipilimumab plus nivolumab was conducted by the SWOG Early Therapeutics and Rare Cancers Committee for multiple rare tumor cohorts across >1,000 National Clinical Trial Network sites.

PARTICIPANTS: 21 eligible patients were registered. Median age was 53 years (range 26-69); 16 (76%) were women.

INTERVENTIONS: Ipilimumab 1 mg/kg intravenously every 6 weeks with nivolumab 240 mg intravenously …

Dna Methylation Patterns In Umbilical Cord Blood From Infants Of Methadone Maintained Opioid Dependent Mothers, Oluwatobi Adegboyega, Suhita Gayen Nee' Betal, Pedro Urday, Rachel Huang, Katherine Bodycot, Huda Al-Kouatly, Kolawole Solarin, Joanna Chan, Sankar Addya, Rupsa Boelig, Zubair Aghai

Department of Pediatrics Faculty Papers

Methadone maintenance treatment for opioid dependent mothers is standard of care. Infants of methadone maintained opioid dependent (MMOD) mothers have better outcomes compared to infants of opioid dependent mothers without treatment. However, when compared to non-exposed infants, infants of MMOD mothers are associated with worse outcomes. We conducted a pilot study to examine genome wide differential DNA methylation using cord blood samples from sixteen term and near-term infants of MMOD and opioid naïve mothers, excluding Infants with chorioamnionitis. A total of 152 differentially methylated loci were identified at a difference >  + 2, < - 2 and p-value < 0.05. There were 90 hypermethylated loci (59 annotated genes) and 62 hypomethylated loci (38 annotated genes) observed. The hypermethylated and hypomethylated DNA changes involved multiple genes, pathways and networks that may explain some of the changes seen in infants of MMOD mothers. Top hypermethylated and hypomethylated genes involved areas of cell growth, neurodevelopment, vision and xenobiotic metabolism functions. Our data may explain the role of key pathways and genes relevant to neonatal outcomes seen from methadone exposure in pregnancy. Functional studies on the identified pathways and genes could lead to improved understanding of the mechanisms and identify areas for intervention.