Digital Commons Network^™

Deep Learning-Based Multimodality Classification Of Chronic Mild Traumatic Brain Injury Using Resting-State Functional Mri And Pet Imaging, Faezeh Vedaei, Najmeh Mashhadi, Mahdi Alizadeh, George Zabrecky, Daniel A. Monti, Md, Nancy Wintering, Emily Navarreto, Chloe Hriso, Andrew B. Newberg, Feroze B. Mohamed

Department of Radiology Faculty Papers

Mild traumatic brain injury (mTBI) is a public health concern. The present study aimed to develop an automatic classifier to distinguish between patients with chronic mTBI (n = 83) and healthy controls (HCs) (n = 40). Resting-state functional MRI (rs-fMRI) and positron emission tomography (PET) imaging were acquired from the subjects. We proposed a novel deep-learning-based framework, including an autoencoder (AE), to extract high-level latent and rectified linear unit (ReLU) and sigmoid activation functions. Single and multimodality algorithms integrating multiple rs-fMRI metrics and PET data were developed. We hypothesized that combining different imaging modalities provides complementary information and …

Making The Connection: How Membrane Contact Sites Have Changed Our View Of Organelle Biology, G. Voeltz, E. Sawyer, G. Hajnóczky, W. Prinz

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The view of organelles and how they operate together has changed dramatically over the last two decades. The textbook view of organelles was that they operated largely independently and were connected by vesicular trafficking and the diffusion of signals through the cytoplasm. We now know that all organelles make functional close contacts with one another, often called membrane contact sites. The study of these sites has moved to center stage in cell biology as it has become clear that they play critical roles in healthy and developing cells and during cell stress and disease states. Contact sites have important roles …

Long-Term Open-Label Vebicorvir For Chronic Hbv Infection: Safety And Off-Treatment Responses, Man-Fung Yuen, Scott Fung, Xiaoli Ma, Tuan Nguyen, Tarek Hassanein, Hie-Won Hann, Magdy Elkhashab, Ronald Nahass, James Park, Ira Jacobson, Walid Ayoub, Steven-Huy Han, Edward Gane, Katie Zomorodi, Ran Yan, Julie Ma, Steven Knox, Luisa Stamm, Maurizio Bonacini, Frank Weilert, Alnoor Ramji, Michael Bennett, Natarajan Ravendhran, Sing Chan, Douglas Dieterich, Paul Yien Kwo, Eugene Schiff, Ho Bae, Jacob Lalezari, Kosh Agarwal, Mark Sulkowski

Department of Medicine Faculty Papers

BACKGROUND & AIMS: The investigational first-generation core inhibitor vebicorvir (VBR) demonstrated safety and antiviral activity over 24 weeks in two phase IIa studies in patients with chronic HBV infection. In this long-term extension study, patients received open-label VBR with nucleos(t)ide reverse transcriptase inhibitors (NrtIs).

METHODS: Patients in this study (NCT03780543) previously received VBR + NrtI or placebo + NrtI in parent studies 201 (NCT03576066) or 202 (NCT03577171). After receiving VBR + NrtI for ≥52 weeks, stopping criteria (based on the treatment history and hepatitis B e antigen status in the parent studies) were applied, and patients either discontinued both VBR …

Standardized Pre-Clinical Surgical Animal Model Protocol To Investigate The Cellular And Molecular Mechanisms Of Ischemic Flap Healing, Edita Aksamitiene, Ryan Heffelfinger, Jan Hoek, Edmund Pribitkin

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

BACKGROUND: Some of the most complex surgical interventions to treat trauma and cancer include the use of locoregional pedicled and free autologous tissue transfer flaps. While the techniques used for these reconstructive surgery procedures have improved over time, flap complications and even failure remain a significant clinical challenge. Animal models are useful in studying the pathophysiology of ischemic flaps, but when repeatability is a primary focus of a study, conventional in-vivo designs, where one randomized subset of animals serves as a treatment group while a second subset serves as a control, are at a disadvantage instigated by greater subject-to-subject variability. …

Molecular Mechanisms In Pathophysiology Of Mucopolysaccharidosis And Prospects For Innovative Therapy, Yasuhiko Ago, Estera Rintz, Krishna Sai Musini, Zhengyu Ma, Shunji Tomatsu

Department of Pediatrics Faculty Papers

Mucopolysaccharidoses (MPSs) are a group of inborn errors of the metabolism caused by a deficiency in the lysosomal enzymes required to break down molecules called glycosaminoglycans (GAGs). These GAGs accumulate over time in various tissues and disrupt multiple biological systems, including catabolism of other substances, autophagy, and mitochondrial function. These pathological changes ultimately increase oxidative stress and activate innate immunity and inflammation. We have described the pathophysiology of MPS and activated inflammation in this paper, starting with accumulating the primary storage materials, GAGs. At the initial stage of GAG accumulation, affected tissues/cells are reversibly affected but progress irreversibly to: (1) …

Treatment Effects Of N-Acetyl Cysteine On Resting-State Functional Mri And Cognitive Performance In Patients With Chronic Mild Traumatic Brain Injury: A Longitudinal Study, Faezeh Vedaei, Andrew B. Newberg, M. Alizadeh, George Zabrecky, Emily Navarreto, Chloe Hriso, Nancy Wintering, Feroze Mohamed, Daniel A. Monti

Marcus Institute of Integrative Health Faculty Papers

Mild traumatic brain injury (mTBI) is a significant public health concern, specially characterized by a complex pattern of abnormal neural activity and functional connectivity. It is often associated with a broad spectrum of short-term and long-term cognitive and behavioral symptoms including memory dysfunction, headache, and balance difficulties. Furthermore, there is evidence that oxidative stress significantly contributes to these symptoms and neurophysiological changes. The purpose of this study was to assess the effect of N-acetylcysteine (NAC) on brain function and chronic symptoms in mTBI patients. Fifty patients diagnosed with chronic mTBI participated in this study. They were categorized into two groups …

Ephrinb2 Knockdown In Cervical Spinal Cord Preserves Diaphragm Innervation In A Mutant Sod1 Mouse Model Of Als, Mark W. Urban, Brittany A. Charsar, Nicolette M. Heinsinger, Shashirekha S. Markandaiah, Lindsay Sprimont, Wei Zhou, Eric V. Brown, Nathan T. Henderson, Samantha J. Thomas, Biswarup Ghosh, Rachel E. Cain, Davide Trotti, Piera Pasinelli, Megan C. Wright, Matthew B. Dalva, Angelo C. Lepore

Farber Institute for Neuroscience Staff Papers and Presentations

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by motor neuron loss. Importantly, non-neuronal cell types such as astrocytes also play significant roles in disease pathogenesis. However, mechanisms of astrocyte contribution to ALS remain incompletely understood. Astrocyte involvement suggests that transcellular signaling may play a role in disease. We examined contribution of transmembrane signaling molecule ephrinB2 to ALS pathogenesis, in particular its role in driving motor neuron damage by spinal cord astrocytes. In symptomatic SOD1G93A mice (a well-established ALS model), ephrinB2 expression was dramatically increased in ventral horn astrocytes. Reducing ephrinB2 in the cervical spinal cord ventral horn via …

Associations Of Galectin-3 Levels With Measures Of Vascular Disease In Patients With Rheumatoid Arthritis, Amanda Nussdorf, Elizabeth Park, Isabelle Amigues, Laura Geraldino-Pardilla, Sabahat Bokhari, Jon T. Giles, Joan M. Bathon

Division of Rheumatology Faculty Papers

OBJECTIVES: Galectin-3 is a beta-galactoside-binding lectin and is a marker of cardiovascular disease (CVD) in the general population. It may also play a role in joint inflammation. We asked whether serum galectin-3 is a useful marker of subclinical vascular disease in patients with rheumatoid arthritis (RA).

METHODS: RA patients without clinical CVD underwent assessment of coronary artery calcium (CAC) score, aortic inflammation (using 18Fluorodeoxyglucose positron emission-computed tomography [FDG PET/CT]), and myocardial flow reserve (MFR). Aorta FDG uptake was measured as standardized uptake values (SUV). Generalized linear models were constructed to explore the associations of galectin-3 levels with CAC score, aortic …

Structural Basis For Nuclear Import Of Hepatitis B Virus (Hbv) Nucleocapsid Core, Ruoyu Yang, Ying-Hui Ko, Fenglin Li, Ravi K. Lokareddy, Chun-Feng David Hou, Christine Kim, Shelby Klein, Santiago Antolínez, Juan F. Marín, Carolina Pérez-Segura, Martin F. Jarrold, Adam Zlotnick, Jodi A. Hadden-Perilla, Gino Cingolani

Student Papers, Posters & Projects

Nuclear import of the hepatitis B virus (HBV) nucleocapsid is essential for replication that occurs in the nucleus. The ~360-angstrom HBV capsid translocates to the nuclear pore complex (NPC) as an intact particle, hijacking human importins in a reaction stimulated by host kinases. This paper describes the mechanisms of HBV capsid recognition by importins. We found that importin α1 binds a nuclear localization signal (NLS) at the far end of the HBV coat protein Cp183 carboxyl-terminal domain (CTD). This NLS is exposed to the capsid surface through a pore at the icosahedral quasi-sixfold vertex. Phosphorylation at serine-155, serine-162, and serine-170 …

Sepsis Epidemiology In Australian And New Zealand Children (Sentinel): Protocol For A Multicountry Prospective Observational Study, Elliot Long, Meredith L. Borland, Shane George, Shefali Jani, Eunicia Tan, Jocelyn Neutze, Natalie Phillips, Amit Kochar, Simon Craig, Anna Lithgow, Arjun Rao, Stuart Dalziel, Ed Oakley, Stephen Hearps, Sonia Singh, Ben Gelbart, Sarah Mcnab, Fran Balamuth, Scott Weiss, Nathan Kuppermann, Amanda Williams, Franz E. Babl

Department of Pediatrics Faculty Papers

INTRODUCTION: Sepsis affects 25.2 million children per year globally and causes 3.4 million deaths, with an annual cost of hospitalisation in the USA of US$7.3 billion. Despite being common, severe and expensive, therapies and outcomes from sepsis have not substantially changed in decades. Variable case definitions, lack of a reference standard for diagnosis and broad spectrum of disease hamper efforts to evaluate therapies that may improve sepsis outcomes. This landscape analysis of community-acquired childhood sepsis in Australia and New Zealand will characterise the burden of disease, including incidence, severity, outcomes and cost. Sepsis diagnostic criteria and risk stratification tools will …

The Development Of A Rabies Virus-Vectored Vaccine Against Borrelia Burgdorferi, Targeting Bbi39, Shantel Rios, Bibek Bhattachan, Kruthi Vavilikolanu, Chrysoula Kitsou, Utpal Pal, Matthias J. Schnell

Department of Microbiology and Immunology Faculty Papers

Lyme disease (LD) is the most common tick-borne illness in the United States (U.S.), Europe, and Asia. Borrelia burgdorferi, a spirochete bacterium transmitted by the tick vector Ixodes scapularis, causes LD in the U.S. If untreated, Lyme arthritis, heart block, and meningitis can occur. Given the absence of a human Lyme disease vaccine, we developed a vaccine using the rabies virus (RABV) vaccine vector BNSP333 and an outer surface borrelial protein, BBI39. BBI39 was previously utilized as a recombinant protein vaccine and was protective in challenge experiments; therefore, we decided to utilize this protective antigen in a rabies virus-vectored vaccine …

Therapeutic Antibodies For The Prevention And Treatment Of Cancer, Mukesh Kumar, Akansha Jalota, Sushil Kumar Sahu, Shabirul Haque

Department of Medical Oncology Faculty Papers

The developments of antibodies for cancer therapeutics have made remarkable success in recent years. There are multiple factors contributing to the success of the biological molecule including origin of the antibody, isotype, affinity, avidity and mechanism of action. With better understanding of mechanism of cancer progression and immune manipulation, recombinant formats of antibodies are used to develop therapeutic modalities for manipulating the immune cells of patients by targeting specific molecules to control the disease. These molecules have been successful in minimizing the side effects instead caused by small molecules or systemic chemotherapy but because of the developing therapeutic resistance against …

Chlormethine Gel In Combination With Other Therapies For Treatment Of Mycosis Fungoides: A Review With Patient Cases, Marco Ardigò, Neda Nikbakht, Miriam Teoli, Laura Gleason, Liliana Crisan, Christiane Querfeld

Department of Dermatology and Cutaneous Biology Faculty Papers

Topical chlormethine gel has been approved as monotherapy for treatment of adult patients with mycosis fungoides (MF), the most common form of cutaneous T-cell lymphoma. In clinical practice, chlormethine gel is often combined with other skin-directed or systemic therapies to optimize response and target recalcitrant lesions. Positive outcomes with combination regimens using chlormethine gel and topical corticosteroids, phototherapy, retinoids, methotrexate, or interferon-α have been reported in literature. However, there are no treatment guidelines on the use of combination regimens with chlormethine gel. To provide real-world evidence and guidance on the use of chlormethine gel combination regimens, several cases of patients …

A Structurally Precise Mechanism Links An Epilepsy-Associated Kcnc2 Potassium Channel Mutation To Interneuron Dysfunction, Jerome Clatot, Christopher B. Currin, Qiansheng Liang, Tanadet Pipatpolkai, Shavonne L. Massey, Ingo Helbig, Lucie Delemotte, Tim P. Vogels, Manuel Covarrubias, Ethan M. Goldberg

Farber Institute for Neuroscience Staff Papers and Presentations

De novo heterozygous variants in KCNC2 encoding the voltage-gated potassium (K+) channel subunit Kv3.2 are a recently described cause of developmental and epileptic encephalopathy (DEE). A de novo variant in KCNC2 c.374G > A (p.Cys125Tyr) was identified via exome sequencing in a patient with DEE. Relative to wild-type Kv3.2, Kv3.2-p.Cys125Tyr induces K+ currents exhibiting a large hyperpolarizing shift in the voltage dependence of activation, accelerated activation, and delayed deactivation consistent with a relative stabilization of the open conformation, along with increased current density. Leveraging the cryogenic electron microscopy (cryo-EM) structure of Kv3.1, molecular dynamic simulations suggest that a strong π-π stacking …

Correlation Between Melphalan Chemotherapy With Longitudinal Global Strain Indices Of The Left Ventricle In Multiple Myeloma Patients: A Velocity Vector Imaging (Vvi) Echocardiography Study, Liaosadat Mirsafaee, Mohammad Dehghani Firouzabadi, Sayeh Parkhideh, Hassan Vahidnezhad, Fatemeh Dehghani Firouzabadi, Maryam Arab, David M. Yousem, Mersedeh Karvandi

Jefferson Institute of Molecular Medicine Papers and Presentations

Multiple myeloma (MM) is characterized by the neoplastic proliferation of plasma cells, leading to the production of monoclonal immunoglobulins. High-dose chemotherapy with autologous stem cell transplant has been used in the treatment of patients with MM (1). Melphalan (L-phenylalanine nitrogen mustard) is one of the most effective chemotherapeutic drugs in the treatment of MM (2). The side effects of melphalan include anemia, nausea, vomiting, allergic reactions, oral ulcers, nephrotoxicity, and arrhythmia at high doses (3). The effect of this drug on cardiac mechanics and heart damage is not well established, as previous studies have only focused on the electrocardiographic and …

Gastric Lipomas: A Case Series And Review Of The Literature, Simone A. Jarrett, Sahana Tito, Matthew Chan, Dominic E. Jarrett, Kevin B. Lo, Richard Depalma

Einstein Health Papers

INTRODUCTION: The purpose of this case series was to review a rare subset of tumors known as gastric lipomas, which are typically found incidentally. The motivation for this study arose from the identification of 2 cases within our institution in a short period.

CASE PRESENTATION: The study involved a review of the diagnosis and management of 2 patients presenting with gastric lipomas at our institution after symptoms of gastrointestinal bleeding. With the advent of new radiologic investigations such as computed tomography and magnetic resonance imaging and advances in endoscopy, there are new approaches to identifying and managing these tumors. On …

Refugee Health In Philadelphia, Marc Altshuler, Md

Academic Commons Workshops and Presentations

No abstract provided.

A Cyclin D1 Intrinsically Disordered Domain Accesses Modified Histone Motifs To Govern Gene Transcription, Xuanmao Jiao, Gabriele Di Sante, Mathew Casimiro, Agnes Tantos, Anthony Ashton, Zhiping Li, Yen Quach, Dharmendra Bhargava, Agnese Di Rocco, Claudia Pupo, Marco Crosariol, Tamas Lazar, Peter Tompa, Chenguang Wang, Zuoren Yu, Zhao Zhang, Kawthar Aldaaysi, Ratna Vadlamudi, Monica Mann, Emmanuel Skordalakes, Andrew Kossenkov, Yanming Du, Richard Pestell

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

The essential G₁-cyclin, CCND1, is frequently overexpressed in cancer, contributing to tumorigenesis by driving cell-cycle progression. D-type cyclins are rate-limiting regulators of G₁-S progression in mammalian cells via their ability to bind and activate CDK4 and CDK6. In addition, cyclin D1 conveys kinase-independent transcriptional functions of cyclin D1. Here we report that cyclin D1 associates with H2B^S14 via an intrinsically disordered domain (IDD). The same region of cyclin D1 was necessary for the induction of aneuploidy, induction of the DNA damage response, cyclin D1-mediated recruitment into chromatin, and CIN gene transcription. In response to …

Cyp26a1 Links Wnt And Retinoic Acid Signaling: A Target To Differentiate Aldh+ Stem Cells In Apc-Mutant Crc, Caroline O.B. Facey, Victoria O. Hunsu, Chi Zhang, Brian Osmond, Lynn M. Opdenaker, Bruce M. Boman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

APC mutation is the main driving mechanism of CRC development and leads to constitutively activated WNT signaling, overpopulation of ALDH+ stem cells (SCs), and incomplete differentiation. We previously reported that retinoic acid (RA) receptors are selectively expressed in ALDH+ SCs, which provides a way to target cancer SCs with retinoids to induce differentiation. Hypotheses: A functional link exists between the WNT and RA pathways, and APC mutation generates a WNT:RA imbalance that decreases retinoid-induced differentiation and increases ALDH+ SCs. Accordingly, to restore parity in WNT:RA signaling, we induce wt-APC expression in APC-mutant CRC cells, and we assess the ability of …

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 …

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 …

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 Makarova, Eugene V Koonin, Satish Nair, Shunsuke Tagami, Konstantin Severinov, Maria Sokolova

Department of Biochemistry and Molecular Biology Faculty Papers

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 …

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, …

Secreted Igm Modulates Il-10 Expression In B Cells, Shannon Mcgettigan, Lazaro Aira, Gaurav Kumar, Romain Ballet, Eugene Butcher, Nicole Baumgarth, Gudrun Debes

Department of Microbiology and Immunology Faculty Papers

IL-10⁺ B cells are critical for immune homeostasis and restraining immune responses in infection, cancer, and inflammation; however, the signals that govern IL-10⁺ B cell differentiation are ill-defined. Here we find that IL-10⁺ B cells expand in mice lacking secreted IgM ((s)IgM^–/–) up to 10-fold relative to wildtype (WT) among all major B cell and regulatory B cell subsets. The IL-10⁺ B cell increase is polyclonal and presents within 24 hours of birth. In WT mice, sIgM is produced prenatally and limits the expansion of IL-10⁺ B cells. Lack of the high affinity …

Alzheimer’S Disease And Microorganisms: The Non-Coding Rnas Crosstalk, Hanieh Mohammadi-Pilehdarboni, Mohammad Shenagari, Farahnaz Joukar, Hamed Naziri, Fariborz Mansour-Ghanaei

Department of Neurology Faculty Papers

Alzheimer’s disease (AD) is a complex, multifactorial disorder, influenced by a multitude of variables ranging from genetic factors, age, and head injuries to vascular diseases, infections, and various other environmental and demographic determinants. Among the environmental factors, the role of the microbiome in the genesis of neurodegenerative disorders (NDs) is gaining increased recognition. This paradigm shift is substantiated by an extensive body of scientific literature, which underscores the significant contributions of microorganisms, encompassing viruses and gut-derived bacteria, to the pathogenesis of AD. The mechanism by which microbial infection exerts its influence on AD hinges primarily on inflammation. Neuroinflammation, activated in …

Pharmacotherapy For Primary Biliary Cholangitis: An Assessment Of Medication Candidacy And Rates Of Treatment, Nicholas Macdonald, Rebecca Loh, Jonathan Fenkel, David Sass, Dina Halegoua-De Marzio

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND: Ursodeoxycholic acid is the preferred first-line therapy for primary biliary cholangitis. Alternative therapies, such as obeticholic acid, are recommended for patients who cannot tolerate ursodeoxycholic acid or who have an inadequate response to ursodeoxycholic acid monotherapy. Prior investigations have suggested that as many as 30% of patients with primary biliary cholangitis may have never received treatment with ursodeoxycholic acid. No prior investigations have examined usage rates of obeticholic acid in the treatment of primary biliary cholangitis.

METHODS: All patients with an ICD-10 diagnosis of primary biliary cholangitis who had any records within the health system were included. A review …

Identifying Opportunities For Prevention Of Adverse Outcomes Following Female Genital Fistula Repair: Protocol For A Mixed-Methods Study In Uganda, Alison El Ayadi, Susan Obore, Fred Kirya, Suellen Miller, Abner Korn, Hadija Nalubwama, John Neuhaus, Monica Getahun, Patrick Eyul, Robert Twine, Erin Andrew, Justus Barageine

Department of Obstetrics and Gynecology Faculty Papers

BACKGROUND: Female genital fistula is a traumatic debilitating injury, frequently caused by prolonged obstructed labor, affecting between 500,000-2 million women in lower-resource settings. Vesicovaginal fistula causes urinary incontinence, and other morbidity may occur during fistula development. Women with fistula are stigmatized, limit social and economic engagement, and experience psychiatric morbidity. Improved surgical access has reduced fistula consequences yet post-repair risks impacting quality of life and well-being include fistula repair breakdown or recurrence and ongoing or changing urine leakage or incontinence. Limited evidence on risk factors contributing to adverse outcomes hinders interventions to mitigate adverse events. This study aims to quantify …

Computational Analysis Of Cas Proteins Unlocks New Potential In Hiv-1 Targeted Gene Therapy, Will Dampier, Rachel Berman, Michael Nonnemacher, Brian Wigdahl

Kimmel Cancer Center Faculty Papers

Introduction: The human immunodeficiency virus type 1 (HIV-1) pandemic has been slowed with the advent of anti-retroviral therapy (ART). However, ART is not a cure and as such has pushed the disease into a chronic infection. One potential cure strategy that has shown promise is the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas gene editing system. It has recently been shown to successfully edit and/or excise the integrated provirus from infected cells and inhibit HIV-1 in vitro, ex vivo, and in vivo. These studies have primarily been conducted with SpCas9 or SaCas9. However, additional Cas proteins are …