Medicine and Health Sciences Commons^™

Prm-Reactive Antibodies Reveal A Role For Partially Mature Virions In Dengue Virus Pathogenesis, Kimberly A Dowd, Laura A Vanblargan, Rita E Chen, Bradley M Whitener, Jennifer Govero, Soila Sukupolvi-Petty, Michael S Diamond, Et Al.

2020-Current year OA Pubs

Cleavage of the flavivirus premembrane (prM) structural protein during maturation can be inefficient. The contribution of partially mature flavivirus virions that retain uncleaved prM to pathogenesis during primary infection is unknown. To investigate this question, we characterized the functional properties of newly-generated dengue virus (DENV) prM-reactive monoclonal antibodies (mAbs) in vitro and using a mouse model of DENV disease. Anti-prM mAbs neutralized DENV infection in a virion maturation state-dependent manner. Alanine scanning mutagenesis and cryoelectron microscopy of anti-prM mAbs in complex with immature DENV defined two modes of attachment to a single antigenic site. In vivo, passive transfer of intact …

Fifty Years Of A National Program For The Treatment Of Kidney Failure, Kevin F Erickson, Melandrea Worsley, Wolfgang C Winkelmayer

Faculty, Staff and Students Publications

No abstract provided.

Biorisk Management, Laboratory Acquired Infections And Clinical Containment, Kashif Ali, Furqan Kabir, Esmeralda Meyer

Department of Paediatrics and Child Health

No abstract provided.

Mechanisms Of Mcl-1 Protein Stability Induced By Mcl-1 Antagonists In B-Cell Malignancies, Shady I Tantawy, Aloke Sarkar, Stefan Hubner, Zhi Tan, William G Wierda, Abdelraouf Eldeib, Shuxing Zhang, Steven Kornblau, Varsha Gandhi

Faculty, Staff and Student Publications

PURPOSE: Several MCL-1 inhibitors (MCL-1i), including AMG-176 and AZD5991, have shown promise in preclinical studies and are being tested for the treatment of hematologic malignancies. A unique feature of these agents is induction and stability of Mcl-1 protein; however, the precise mechanism is unknown. We aim to study the mechanism of MCL-1i-induced Mcl-1 protein stability.

EXPERIMENTAL DESIGN: Using several B-cell leukemia and lymphoma cell lines and primary chronic lymphocytic leukemia (CLL) lymphocytes, we evaluated molecular events associated with Mcl-1 protein stability including protein half-life, reverse-phase protein array, protein-protein interaction, phosphorylation, ubiquitination, and de-ubiquitination, followed by molecular simulation and modeling.

RESULTS: …

Mechanism Of Ca2+ Transport By Ferroportin, Jiemin Shen, Azaan Saalim Wilbon, Ming Zhou, Yaping Pan

Faculty, Staff and Students Publications

Ferroportin (Fpn) is a transporter that releases ferrous ion (Fe2+) from cells and is important for homeostasis of iron in circulation. Export of one Fe2+ by Fpn is coupled to import of two H+ to maintain charge balance. Here, we show that human Fpn (HsFpn) binds to and mediates Ca2+ transport. We determine the structure of Ca2+-bound HsFpn and identify a single Ca2+ binding site distinct from the Fe2+ binding sites. Further studies validate the Ca2+ binding site and show that Ca2+ transport is not coupled to transport of another ion. In addition, Ca2+ transport is significantly inhibited in the …

Diagnosis Of Amyotrophic Lateral Sclerosis By Respiratory Function Test, Francesca Polverino, Simone Sampaolo, Antonio Capuozzo, Marco Fasolino, Michele Aliberti, Ersilia Satta, Carlo Santoriello, Mario Polverino

Faculty, Staff and Students Publications

The diagnostic criterion for amyotrophic lateral sclerosis (ALS) based on the findings of concomitant clinical and electrophysiological evidence of upper and lower motor neuron involvement may remain unsatisfied for months and in some patients, even for years in the early stage of the disease. Since respiratory involvement is an onset symptom of ALS in only 1-3% of patients, pulmonary assessment has never been considered useful in the early diagnosis of ALS. However, studies on pulmonary function are lacking, especially in those early stages where neurologic tests are also inconclusive. In contrast to the scarcity of data in the early stages, …

Take Your Mother’S Ferry: Preimplantation Embryo Development Requires Maternal Karyopherins For Nuclear Transport, Momal Sharif, Laura Detti, Ignatia B Van Den Veyver

Faculty, Staff and Students Publications

The genetic basis of preimplantation embryo arrest is slowly being unraveled. Recent discoveries point to maternally expressed proteins required for cellular functions before the embryonic genome is activated. In this issue of the JCI, Wang, Miyamoto, et al. suggest a critical role for karyopherin-mediated protein cargo transport between oocyte cytoplasm and nucleus. Defective maternal oocyte-expressed human karyopherin subunit α7 (KPNA7) and mouse KPNA2 fail to bind a critical substrate, ribosomal L1 domain-containing protein 1 (RSL1D1), affecting its transport to the nucleus. As shown in embryos of Kpna2-null females, the consequences are disrupted zygotic genome activation and arrest of development. These …

Posoleucel, An Allogeneic, Off-The-Shelf Multivirus-Specific T-Cell Therapy, For The Treatment Of Refractory Viral Infections In The Post-Hct Setting, Thomas Pfeiffer, Ifigeneia Tzannou, Mengfen Wu, Carlos Ramos, Ghadir Sasa, Caridad Martinez, Premal Lulla, Robert A Krance, Lauren Scherer, Daniel Ruderfer, Swati Naik, Claire Bocchini, Iain P Fraser, Badrish Patel, Dany Ward, Tao Wang, Helen E Heslop, Ann M Leen, Bilal Omer

Faculty, Staff and Students Publications

PURPOSE: Viral infections are a major cause of morbidity and mortality following allogeneic hematopoietic cell transplantation (allo-HCT). In the absence of safe and effective antiviral treatments, virus-specific T cells have emerged as a promising therapeutic option. Posoleucel is a multivirus-specific T-cell therapy for off-the-shelf use against six viral infections that commonly occur in allo-HCT recipients: adenovirus, BK virus (BKV), cytomegalovirus, Epstein-Barr virus, human herpes virus-6, and JC virus.

PATIENTS AND METHODS: We conducted an open-label, phase II trial to determine the feasibility and safety of posoleucel in allo-HCT recipients infected with one or more of these viruses. Infections were either …

Automating The High-Throughput Screening Of Protein-Based Optical Indicators And Actuators, Jihwan Lee, Beatriz Campillo, Shaminta Hamidian, Zhuohe Liu, Matthew Shorey, François St-Pierre

Faculty, Staff and Students Publications

Over the last 25 years, protein engineers have developed an impressive collection of optical tools to interface with biological systems: indicators to eavesdrop on cellular activity and actuators to poke and prod native processes. To reach the performance level required for their downstream applications, protein-based tools are usually sculpted by iterative rounds of mutagenesis. In each round, libraries of variants are made and evaluated, and the most promising hits are then retrieved, sequenced, and further characterized. Early efforts to engineer protein-based optical tools were largely manual, suffering from low throughput, human error, and tedium. Here, we describe approaches to automating …

Physical Activity, Seasonal Sensitivity And Psychological Well-Being Of People Of Different Age Groups Living In Extreme Environments, Caren Alvarado, Matías Castillo-Aguilar, Valeska Villegas, Claudia Estrada Goic, Katherine Harris, Patricio Barria, Michele M Moraes, Thiago T Mendes, Rosa M E Arantes, Pablo Valdés-Badilla, Cristian Núñez-Espinosa

Faculty, Staff and Student Publications

Physical activity can prevent many organic and mental pathologies. For people living in extreme southern high-latitude environments, weather conditions can affect these activities, altering their psychological well-being and favoring the prevalence of seasonal sensitivity (SS). This study aims to determine the relationships between the practice of physical activity, seasonal sensitivity and well-being in people living in high southern latitudes. A cross-sectional study was conducted, using the Seasonal Pattern Assessment Questionnaire (SPAQ), applying a psychological well-being scale, and determining sports practice according to the recommendations of the World Health Organization (WHO) for the 370 male (n = 209; 55%) and female …

Differential Effects Of Anti-Cd20 Therapy On Cd4 And Cd8 T Cells And Implication Of Cd20-Expressing Cd8 T Cells In Ms Disease Activity, Koji Shinoda, Anne H Cross, Et Al.

2020-Current year OA Pubs

A small proportion of multiple sclerosis (MS) patients develop new disease activity soon after starting anti-CD20 therapy. This activity does not recur with further dosing, possibly reflecting deeper depletion of CD20-expressing cells with repeat infusions. We assessed cellular immune profiles and their association with transient disease activity following anti-CD20 initiation as a window into relapsing disease biology. Peripheral blood mononuclear cells from independent discovery and validation cohorts of MS patients initiating ocrelizumab were assessed for phenotypic and functional profiles using multiparametric flow cytometry. Pretreatment CD20-expressing T cells, especially CD20

Entry Receptors - The Gateway To Alphavirus Infection, Ofer Zimmerman, Autumn C. Holmes, Natasha M. Kafai, Lucas J. Adams, Michael S. Diamond

2020-Current year OA Pubs

Alphaviruses are enveloped, insect-transmitted, positive-sense RNA viruses that infect humans and other animals and cause a range of clinical manifestations, including arthritis, musculoskeletal disease, meningitis, encephalitis, and death. Over the past four years, aided by CRISPR/Cas9-based genetic screening approaches, intensive research efforts have focused on identifying entry receptors for alphaviruses to better understand the basis for cellular and species tropism. Herein, we review approaches to alphavirus receptor identification and how these were used for discovery. The identification of new receptors advances our understanding of viral pathogenesis, tropism, and evolution and is expected to contribute to the development of novel strategies …

Posoleucel, An Allogeneic, Off-The-Shelf Multivirus-Specific T-Cell Therapy, For The Treatment Of Refractory Viral Infections In The Post-Hct Setting, Thomas Pfeiffer, Et Al.

2020-Current year OA Pubs

PURPOSE: Viral infections are a major cause of morbidity and mortality following allogeneic hematopoietic cell transplantation (allo-HCT). In the absence of safe and effective antiviral treatments, virus-specific T cells have emerged as a promising therapeutic option. Posoleucel is a multivirus-specific T-cell therapy for off-the-shelf use against six viral infections that commonly occur in allo-HCT recipients: adenovirus, BK virus (BKV), cytomegalovirus, Epstein-Barr virus, human herpes virus-6, and JC virus.

PATIENTS AND METHODS: We conducted an open-label, phase II trial to determine the feasibility and safety of posoleucel in allo-HCT recipients infected with one or more of these viruses. Infections were either …

Conserved Angio-Immune Subtypes Of The Tumor Microenvironment Predict Response To Immune Checkpoint Blockade Therapy, Madhav Subramanian, Ashraf Ul Kabir, Derek Barisas, Karen Krchma, Kyunghee Choi

2020-Current year OA Pubs

Immune checkpoint blockade (ICB) therapy has revolutionized cancer treatment. However, only a fraction of patients respond to ICB therapy. Accurate prediction of patients to likely respond to ICB would maximize the efficacy of ICB therapy. The tumor microenvironment (TME) dictates tumor progression and therapy outcome. Here, we classify the TME by analyzing the transcriptome from 11,069 cancer patients based on angiogenesis and T cell activity. We find three distinct angio-immune TME subtypes conserved across 30 non-hematological cancers. There is a clear inverse relationship between angiogenesis and anti-tumor immunity in TME. Remarkably, patients displaying TME with low angiogenesis with strong anti-tumor …

I Don't Believe A Person Has To Die When Trying To Get High: Overdose Prevention And Response Strategies In Rural Illinois, Suzan M. Walters, Marisa Felsher, David Frank, Jessica Jaiswal, Tarlise Townsend, Brandon Muncan, Alex S. Bennett, Samuel R. Friedman, Wiley Jenkins, Mai T. Pho, Scott Fletcher, Danielle C. Ompad

College of Population Health Faculty Papers

BACKGROUND: Overdose is a leading cause of morbidity and mortality among people who inject drugs. Illicitly manufactured fentanyl is now a major driver of opioid overdose deaths.

METHODS: Semi-structured interviews were conducted with 23 participants (19 persons who inject drugs and 4 service providers) from rural southern Illinois. Data were analyzed using constant comparison and theoretical sampling methods.

RESULTS: Participants were concerned about the growing presence of fentanyl in both opioids and stimulants, and many disclosed overdose experiences. Strategies participants reported using to lower overdose risk included purchasing drugs from trusted sellers and modifying drug use practices by partially injecting …

Retrospective Study Of Healthcare Resources Developed For Patients By Interprofessional Teams, Rebecca White, Ashley Walczybock, Jennifer Mendez, Ashley Reed, Shannon Maloney, Michelle Malik, Christine Kivlen

Internal Medicine Faculty Publications

Wayne State University (WSU) emphasizes the importance of interdisciplinary education by having students participate in an Interprofessional Team Visit (IPTV) program. A 60-minute virtual visit is conducted to assess adults aged over 50 years within the Detroit Metropolitan Area (Metro Detroit) community. This project was designed to prepare healthcare students in evaluating the mental, physical, and social health aspects of assigned patients based on specific disciplinary assessments. Upon completion of assessments, the interdisciplinary team provided the patient with resources based on the team and the patient's agreed-upon area of concern. Twenty-eight IPTV teams, consisting of a medical and occupational therapy …

Relation Of Maternal Pre-Pregnancy Factors And Childhood Asthma: A Cross-Sectional Survey In Pre-School Children Aged 2–5 Years Old, Dimitrios Papandreou, Eleni Pavlidou, Stefanos Tyrovolas, Maria Mantzorou, Eleni Andreou, Evmorfia Psara, Georgios Antasouras, Georgios K. Vasios, Efthymios Poulios, Constantinos Giaginis

All Works

Background and Objectives: Asthma constitutes a constant, prolonged, inflammation-related pulmonary disorder in childhood with serious public health concerns. Several maternal risk factors can enhance the prevalence of its development in this stage of life; however, the currently available data remain contradictory and/or inconsistent. We aim to evaluate the potential impacts of mothers' sociodemographic, anthropometric and prenatal and perinatal factors on the prevalence of developing asthma in pre-school children. Materials and Methods: This is a retrospective cross-sectional survey, which includes 5133 women and their matched pre-school children. Childhood asthma was diagnosed using validated questionnaires. Statistical analysis was accomplished to evaluate whether …

Total Hip Arthroplasty In The Setting Of Post-Traumatic Arthritis Following Acetabular Fracture: A Systematic Review, Conor S O'Driscoll, Martin S Davey, Andrew J Hughes, John M O'Byrne, Michael Leonard, Brendan J O'Daly

Rothman Institute Papers

Background: Acetabular fractures are frequently associated with post-traumatic arthritis (PTA), for which total hip arthroplasty (THA) has emerged as the established procedure. The purpose of this systematic review is to report the patient outcomes, complications, and implant survival of delayed THA for patients with PTA following acetabular fracture.

Methods: A systematic review was performed in December 2021 as per Preferred Reporting Items for Systematic Review and Meta-Analysis Guidelines to identify all studies reporting outcomes of delayed THA performed for PTA with a history of acetabular fracture. From an initial screen of 893 studies, 29 studies which met defined inclusion criteria …

A Deep Learning Based Dual Encoder–Decoder Framework For Anatomical Structure Segmentation In Chest X-Ray Images, Ihsan Ullah, Farman Ali, Babar Shah, Shaker El-Sappagh, Tamer Abuhmed, Sang Hyun Park

All Works

Automated multi-organ segmentation plays an essential part in the computer-aided diagnostic (CAD) of chest X-ray fluoroscopy. However, developing a CAD system for the anatomical structure segmentation remains challenging due to several indistinct structures, variations in the anatomical structure shape among different individuals, the presence of medical tools, such as pacemakers and catheters, and various artifacts in the chest radiographic images. In this paper, we propose a robust deep learning segmentation framework for the anatomical structure in chest radiographs that utilizes a dual encoder–decoder convolutional neural network (CNN). The first network in the dual encoder–decoder structure effectively utilizes a pre-trained VGG19 …

Planarians To Schistosomes: An Overview Of Flatworm Cell-Types And Regulators, J Lee

Faculty, Staff and Student Publications

Schistosomiasis remains a major neglected tropical disease that afflicts over 200 million people globally. Schistosomes, the aetiological agent of schistosomiasis, are parasitic flatworms that propagate between molluscan and mammalian hosts. Inside the mammalian host, schistosomes rapidly grow over 100-fold in size and develop into a sexually mature male or female that thrives in the bloodstream for several decades. Recent work has identified schistosome stem cells as the source that drives parasite transmission, reproduction and longevity. Moreover, studies have begun to uncover molecular programmes deployed by stem cells that are essential for tissue development and maintenance, parasite survival and immune evasion. …

Exploring Therapeutic Strategies For Infantile Neuronal Axonal Dystrophy (Inad/Park14), Guang Lin, Burak Tepe, Geoff Mcgrane, Regine C Tipon, Gist Croft, Leena Panwala, Amanda Hope, Agnes J H Liang, Zhongyuan Zuo, Seul Kee Byeon, Lily Wang, Akhilesh Pandey, Hugo J Bellen

Faculty, Staff and Students Publications

Infantile neuroaxonal dystrophy (INAD) is caused by recessive variants in PLA2G6 and is a lethal pediatric neurodegenerative disorder. Loss of the Drosophila homolog of PLA2G6, leads to ceramide accumulation, lysosome expansion, and mitochondrial defects. Here, we report that retromer function, ceramide metabolism, the endolysosomal pathway, and mitochondrial morphology are affected in INAD patient-derived neurons. We show that in INAD mouse models, the same features are affected in Purkinje cells, arguing that the neuropathological mechanisms are evolutionary conserved and that these features can be used as biomarkers. We tested 20 drugs that target these pathways and found that Ambroxol, Desipramine, …

Approaches To Clinical Guideline Development In Healthcare: A Scoping Review And Document Analysis, Annemarie De Leo, Dianne Bloxsome, Sara Bayes

Research outputs 2022 to 2026

Background: Over the past decade, an industry has emerged around Clinical Practice Guideline (CPG) development in healthcare, which has increased pressure on guideline-producing organisations to develop CPGs at an accelerated rate. These are intended to improve the quality of care provided to patients while containing healthcare costs and reducing variability in clinical practice. However, this has inadvertently led to discrepancies in CPG recommendations between health organisations, also challenging healthcare providers who rely on these for decision-making and to inform clinical care. From a global perspective, although some countries have initiated national protocols regarding developing, appraising and implementing high-quality CPGs, there …

Validation Of Various Prediction Scores For Cardiac Surgery-Associated Acute Kidney Injury, Anwar Abdullatif Alhulaibi, Abdulrahman Mashatel Alruwaili, Abdullah Saad Alotaibi, ​Fatima Nabih Alshakhs​, Habib Samir Alramadhan, ​Mohammed Salman Koudieh

Journal of the Saudi Heart Association

Background and Objectives: Following cardiac surgery, acute kidney injury (AKI) is a well-known complication that increases morbidity and mortality. This study was carried out to determine the factors associated with acute kidney injury and to assess the predictive value of three predictive scores for the development of AKI post-cardiac surgery in the Saudi community. Methods: In this retrospective study, the medical records of patients aged 18 years and above who underwent cardiac surgery on cardiopulmonary bypass (CPB) at Saud Albabtin Cardiac Center between January 2018 and March 2021 were reviewed. The first stage of both Kidney Disease Improving Global Outcomes …

Review Of Storytelling In Queer Appalachia: Imagining The Unspeakable Other, Sandra L. Cotton Dnp, Rn, Anp-Bc, Fnap, Laurie A. Theeke Phd, James Messer

Journal of Appalachian Health

The Journal of Appalachian Health is committed to reviewing published media that relates to contemporary concepts affecting the health of residents of Appalachia. Improving the health in the region of Appalachia means knowing our people as they live and thrive in communities. The book reviewed here, Storytelling in Queer Appalachia: Imagining the Unspeakable Other (Edited by Glasby, Gradin, and Ryerson), is a must read for people who wish to gain insight on the real experience of being queer in Appalachia.

Providers’ Stigmas And The Effects On Patients With Opioid Use Disorder: A Scoping Review, Peyton Mashni, Sarah Beth Bell, F. Douglas Scutchfield Md, Lauren E. Robinson

Journal of Appalachian Health

Introduction: One of the most prevalent, dangerous stigmas in health care is the complex bias toward patients with opioid use disorder (OUD). This stigma damages the vital patient–provider relationship, further perpetuating the opioid epidemic.

Purpose: Unfortunately, research on the relationship between OUD and provider stigma is greatly lacking. To fill this gap, the present in-depth study undertakes a scoping review of research on providers’ stigma toward OUD in order to determine how enacted stigma affects treatment plans.

Methods: Four databases were used to identify articles published from 1999 to 2021. A comprehensive search strategy was developed through a collaborative process …

Evaluating The Association Between Depressive Symptoms And Glycemic Control Among Residents Of Rural Appalachia, Brittany L. Smalls, Adebola Adegboyega, Ellen Combs, Eli W. Travis, Felipe De La Barra, Lovoria B. Williams, Nancy Schoenberg

Journal of Appalachian Health

Introduction: Type 2 diabetes mellitus (T2DM) is associated with a range of co-morbid physical and psychological conditions, including depression. Yet there is a dearth of evidence regarding the prevalence of depression among those in Appalachia living with T2DM; this gap persists despite the higher regional prevalence of T2DM and challenging social determinants of health.

Purpose: This study aimed to provide greater detail about the relationships between T2DM and depressive symptoms in adults living in Appalachia Kentucky.

Methods: The present study was a cross-sectional analysis of baseline data derived from an ongoing study of Appalachia Kentucky adults living with T2DM. Outcome …

Association Between Low Health Literacy And Adverse Health Behaviors In North Carolina, 2016, Manan Roy, Adam Hege, Erin D. Bouldin

Journal of Appalachian Health

Introduction: Health literacy (HL) is an urgent public health challenge facing the U.S. HL is a critical factor in health inequities and exacerbates underlying social determinants of health.

Purpose: This study assesses the association between low HL (LHL) and adverse health behaviors, which contribute to poor health.

Methods: Researchers used North Carolina’s 2016 Behavioral Risk Factor Surveillance System data, namely, the Health Literacy optional module which asks respondents to rate how difficult it is for them to get health-related advice or to understand medical information (verbal or written). Health behaviors analyzed were excessive alcohol consumption, lack of adequate exercise and …

The Relationship Between Psychosocial Factors, Self-Care, And Blood Sugar In An Appalachian Population, Brittany L. Smalls, Md. Tofial Azam, Madeline Dunfee, Philip M. Westgate, Susan C. Westneat, Nancy Schoenberg

Journal of Appalachian Health

Introduction: Appalachian residents are more likely than other populations to have Type 2 Diabetes Mellitus (T2DM) and to experience more severe complications from the disease, including excess and premature mortality.

Methods: This study examines health alongside sociodemographic factors, psychosocial factors (including knowledge, empowerment, social support/function, religiosity, distress), and perceived problems in diabetes management that may influence self-care and HbA1c among vulnerable rural residents. A survey of a community–based sample of 356 adults with diagnosed diabetes or HbA1c > 6.5 was conducted in six counties in Appalachian Kentucky.

Results: Findings suggest that neither religiosity nor social support/function mediate/moderate the relationship between psychosocial …

‘Can You See What I See?’: An Art Project Promoting Living Well With Dementia, Jennifer K. Fortuna

The Open Journal of Occupational Therapy

Caroline Hyland, an illustrator and former occupational therapist based in Dublin, Ireland, provided the cover art for the Winter 2023 edition of The Open Journal of Occupational Therapy (OJOT). “Can You See What I See?” is an acrylic painting on black textured paper. The piece was inspired by Caroline’s grandmother Kathleen Duhig, her love of flowers, and the song “The Dutchman.” Kathleen and three of her sisters lived with dementia. This painting, and several others, are featured in a book Caroline wrote to support living well with dementia. By combining her artistic talents and training as an occupational therapist, Caroline …

If Reasoning, Reflection, And Evidence-Based Practice Are Essential To Practice, We Must Define Them, Hannah K. Burke, Anita C. Bundy, Shelly J. Lane

The Open Journal of Occupational Therapy

Reasoning, reflection, and evidence-based practice are considered essential to the delivery of high-quality occupational therapy services. These skills are highlighted in occupational therapy practice acts and educational standards. Unfortunately, although clearly integral to practice, reasoning, reflection, and evidence-based practice are rarely and inconsistently defined in the profession of occupational therapy. Because the terms reasoning, reflection, and evidence-based practice are used so frequently, and so often their definitions are assumed, occupational therapy students may be unclear on how they will be evaluated and, ultimately, what they will be expected to do in practice in relation to these skills. Through a review …