Digital Commons Network^™

Continuous Renal Replacement Therapy For Two Neonates With Hyperammonemia, Christopher Markham, Caroline Williams, Cory Miller, Dorothy K Grange, T Keefe Davis, Kenneth E Remy

Open Access Publications

No abstract provided.

Noninvasive Immuno-Pet Imaging Of Cd8 + T Cell Behavior In Influenza A Virus-Infected Mice, Paul W Rothlauf, Zeyang Li, Novalia Pishesha, Yushu Joy Xie, Andrew W Woodham, Djenet Bousbaine, Stephen C Kolifrath, Vincent L Verschoor, Hidde L Ploegh

Open Access Publications

Immuno-positron emission tomography (immuno-PET) is a noninvasive imaging method that enables tracking of immune cells in living animals. We used a nanobody that recognizes mouse CD8α and labeled it with

Association Of Immunosuppression And Viral Load With Subcortical Brain Volume In An International Sample Of People Living With Hiv, Talia M. Nir, Beau M. Ances, Et Al

Open Access Publications

Importance: Despite more widely accessible combination antiretroviral therapy (cART), HIV-1 infection remains a global public health challenge. Even in treated patients with chronic HIV infection, neurocognitive impairment often persists, affecting quality of life. Identifying the neuroanatomical pathways associated with infection in vivo may delineate the neuropathologic processes underlying these deficits. However, published neuroimaging findings from relatively small, heterogeneous cohorts are inconsistent, limiting the generalizability of the conclusions drawn to date.

Objective: To examine structural brain associations with the most commonly collected clinical assessments of HIV burden (CD4+ T-cell count and viral load), which are generalizable across demographically and clinically diverse …

Increased Utilization Of Total Joint Arthroplasty After Medicaid Expansion, Christopher J Dy, Amber Salter, Abigail Barker, Derek Brown, Matthew Keller, Margaret A Olsen

Open Access Publications

BACKGROUND: The expansion of state Medicaid programs under the U.S. Affordable Care Act has led to a dramatic increase in the number of Americans with health insurance coverage. Prior analyses of a limited number of states have suggested that greater utilization of total hip arthroplasty (THA) and total knee arthroplasty (TKA) should be expected after Medicaid expansion. The purpose of our study was to examine whether increased utilization of THA and TKA occurred across a broader range of states after Medicaid expansion.

METHODS: We analyzed administrative data from the Healthcare Cost and Utilization Project from 9 states (Arkansas, Arizona, Colorado, …

Chemoprevention Agents To Reduce Mammographic Breast Density In Premenopausal Women: A Systematic Review Of Clinical Trials, Ana S. Salazar, Malika Rakhmankulova, Laura E. Simon, Adetunji T. Toriola

Open Access Publications

Background: Higher mammographic breast density (MBD) is associated with an increased risk of breast cancer when compared with lower MBD, especially in premenopausal women. However, little is known about the effectiveness of chemoprevention agents in reducing MBD in premenopausal women without a history of breast cancer. Findings from this review should provide insight on how to target MBD in breast cancer prevention in premenopausal women with dense breasts.

Methods: We searched 9 electronic databases for clinical trials in English, Spanish, French, or German published until January 2020. Articles evaluating the association of pharmacological agents and MBD were included. Data were …

Cerebrospinal Fluid Ncam-1 Concentration Is Associated With Neurodevelopmental Outcome In Post-Hemorrhagic Hydrocephalus Of Prematurity, David D. Limbrick, Diego M. Morales, Et Al.

Open Access Publications

OBJECTIVE: Efforts directed at mitigating neurological disability in preterm infants with intraventricular hemorrhage (IVH) and post hemorrhagic hydrocephalus (PHH) are limited by a dearth of quantifiable metrics capable of predicting long-term outcome. The objective of this study was to examine the relationships between candidate cerebrospinal fluid (CSF) biomarkers of PHH and neurodevelopmental outcomes in infants undergoing neurosurgical treatment for PHH.

STUDY DESIGN: Preterm infants with PHH were enrolled across the Hydrocephalus Clinical Research Network. CSF samples were collected at the time of temporizing neurosurgical procedure (n = 98). Amyloid precursor protein (APP), L1CAM, NCAM-1, and total protein (TP) were compared …

Are Fc Gamma Receptor Polymorphisms Important In Hiv-1 Infection Outcomes And Latent Reservoir Size?, Helena Lamptey, Evelyn Y Bonney, Bright Adu, George B Kyei

Open Access Publications

Fc gamma receptors (FcγR) are cell surface glycoproteins which trigger specific effector-cell responses when cross-linked with the Fc portions of immunoglobulin (IgG) antibodies. During HIV-1 infection, the course of disease progression, ART response, and viral reservoir size vary in different individuals. Several factors may account for these differences; however, Fc gamma receptor gene polymorphisms, which influence receptor binding to IgG antibodies, are likely to play a key role. FcγRIIa (CD32) was recently reported as a potential marker for latent HIV reservoir, however, this assertion is still inconclusive. Whether FcγR polymorphisms influence the size of the viral reservoir, remains an important …

Mri Radiomic Signature Of White Matter Hyperintensities Is Associated With Clinical Phenotypes, Martin Bretzner, Laura Heitsch, Chia-Ling Phuah, Et Al

Open Access Publications

Objective: Neuroimaging measurements of brain structural integrity are thought to be surrogates for brain health, but precise assessments require dedicated advanced image acquisitions. By means of quantitatively describing conventional images, radiomic analyses hold potential for evaluating brain health. We sought to: (1) evaluate radiomics to assess brain structural integrity by predicting white matter hyperintensities burdens (WMH) and (2) uncover associations between predictive radiomic features and clinical phenotypes.

Methods: We analyzed a multi-site cohort of 4,163 acute ischemic strokes (AIS) patients with T2-FLAIR MR images with total brain and WMH segmentations. Radiomic features were extracted from normal-appearing brain tissue (brain mask-WMH …

Maturation Of Heterogeneity In Afferent Synapse Ultrastructure In The Mouse Cochlea, Shelby A Payne, Matthew S Joens, Heather Chung, Natalie Skigen, Adam Frank, Sonali Gattani, Kya Vaughn, Allison Schwed, Matt Nester, Atri Bhattacharyya, Guhan Iyer, Bethany Davis, Jason Carlquist, Honey Patel, James A J Fitzpatrick, Mark A Rutherford

Open Access Publications

Auditory nerve fibers (ANFs) innervating the same inner hair cell (IHC) may have identical frequency tuning but different sound response properties. In cat and guinea pig, ANF response properties correlate with afferent synapse morphology and position on the IHC, suggesting a causal structure-function relationship. In mice, this relationship has not been fully characterized. Here we measured the emergence of synaptic morphological heterogeneities during maturation of the C57BL/6J mouse cochlea by comparing postnatal day 17 (p17, ∼3 days after hearing onset) with p34, when the mouse cochlea is mature. Using serial block face scanning electron microscopy and three-dimensional reconstruction we measured …

Cancer-Associated Mesothelial Cells Promote Ovarian Cancer Chemoresistance Through Paracrine Osteopontin Signaling, Jin Qian, Bauer L Lesavage, Kelsea M Hubka, Chenkai Ma, Suchitra Natarajan, Joshua T Eggold, Yiren Xiao, Katherine C Fuh, Venkatesh Krishnan, Annika Enejder, Sarah C Heilshorn, Oliver Dorigo, Erinn B Rankin

Open Access Publications

Ovarian cancer is the leading cause of gynecological malignancy-related deaths, due to its widespread intraperitoneal metastases and acquired chemoresistance. Mesothelial cells are an important cellular component of the ovarian cancer microenvironment that promote metastasis. However, their role in chemoresistance is unclear. Here, we investigated whether cancer-associated mesothelial cells promote ovarian cancer chemoresistance and stemness in vitro and in vivo. We found that osteopontin is a key secreted factor that drives mesothelial-mediated ovarian cancer chemoresistance and stemness. Osteopontin is a secreted glycoprotein that is clinically associated with poor prognosis and chemoresistance in ovarian cancer. Mechanistically, ovarian cancer cells induced osteopontin expression …

Innovations In Md-Only Physician-Scientist Training: Experiences From The Burroughs Wellcome Fund Physician-Scientist Institutional Award Initiative, Allison T Mcelvaine, Jacqueline A Hawkins-Salsbury, Wayne M Yokoyama, Et Al

Open Access Publications

No abstract provided.

Activated Microglia Mitigate Aβ-Associated Tau Seeding And Spreading, Maud Gratuze, Yun Chen, Samira Parhizkar, Nimansha Jain, Michael R. Strickland, Javier Remolina Serrano, Marco Colonna, Jason D. Ulrich, David M. Holtzman

Open Access Publications

In Alzheimer's disease (AD) models, AD risk variants in the microglial-expressed TREM2 gene decrease Aβ plaque-associated microgliosis and increase neuritic dystrophy as well as plaque-associated seeding and spreading of tau aggregates. Whether this Aβ-enhanced tau seeding/spreading is due to loss of microglial function or a toxic gain of function in TREM2-deficient microglia is unclear. Depletion of microglia in mice with established brain amyloid has no effect on amyloid but results in less spine and neuronal loss. Microglial repopulation in aged mice improved cognitive and neuronal deficits. In the context of AD pathology, we asked whether microglial removal and repopulation decreased …

Dengue And The Lectin Pathway Of The Complement System, Romchat Kraivong, Nuntaya Punyadee, M Kathryn Liszewski, John P Atkinson, Panisadee Avirutnan

Open Access Publications

Dengue is a mosquito-borne viral disease causing significant health and economic burdens globally. The dengue virus (DENV) comprises four serotypes (DENV1-4). Usually, the primary infection is asymptomatic or causes mild dengue fever (DF), while secondary infections with a different serotype increase the risk of severe dengue disease (dengue hemorrhagic fever, DHF). Complement system activation induces inflammation and tissue injury, contributing to disease pathogenesis. However, in asymptomatic or primary infections, protective immunity largely results from the complement system's lectin pathway (LP), which is activated through foreign glycan recognition. Differences in N-glycans displayed on the DENV envelope membrane influence the lectin pattern …

A Microfluidic-Based Filtration System To Enrich For Bone Marrow Disseminated Tumor Cells From Breast Cancer Patients, Sreeraj G. Pillai, Chidananda M. Siddappa, Cynthia Ma, Jackie Snider, Madhurima Kaushal, Mark A. Watson, Rebecca Aft

Open Access Publications

Disseminated tumors cells (DTCs) present in the bone marrow (BM) are believed to be the progenitors of distant metastatic spread, a major cause of mortality in breast cancer patients. To better understand the behavior and therapeutic vulnerabilities of these rare cell populations, unbiased methods for selective cell enrichment are required. In this study, we have evaluated a microfluidic-based filtration system (ParsortixR, Angle PLC), previously demonstrated for use in circulating tumor cell (CTC) capture, to capture BM DTCs. Performance using BM samples was also compared directly to enrichment of CTCs in the peripheral blood (PB) from both metastatic and non-metastatic breast …

Humanized Neurofibroma Model From Induced Pluripotent Stem Cells Delineates Tumor Pathogenesis And Developmental Origins, Juan Mo, Corina Anastasaki, Zhiguo Chen, Tracey Shipman, Jason Papke, Kevin Yin, David H Gutmann, Lu Q Le

Open Access Publications

Neurofibromatosis type 1 (NF1) is a common tumor predisposition syndrome caused by NF1 gene mutation, in which affected patients develop Schwann cell lineage peripheral nerve sheath tumors (neurofibromas). To investigate human neurofibroma pathogenesis, we differentiated a series of isogenic, patient-specific NF1-mutant human induced pluripotent stem cells (hiPSCs) into Schwannian lineage cells (SLCs). We found that, although WT and heterozygous NF1-mutant hiPSCs-SLCs did not form tumors following mouse sciatic nerve implantation, NF1-null SLCs formed bona fide neurofibromas with high levels of SOX10 expression. To confirm that SOX10+ SLCs contained the cells of origin for neurofibromas, both Nf1 alleles were inactivated in …

Plasma Amyloid-Beta Levels In A Pre-Symptomatic Dutch-Type Hereditary Cerebral Amyloid Angiopathy Pedigree: A Cross-Sectional And Longitudinal Investigation, Pratishtha Chatterjee, Anne M Fagan, Chengjie Xiong, Tammie L S Benzinger, John C Morris, Randall J Bateman, Et Al

Open Access Publications

Plasma amyloid-beta (Aβ) has long been investigated as a blood biomarker candidate for Cerebral Amyloid Angiopathy (CAA), however previous findings have been inconsistent which could be attributed to the use of less sensitive assays. This study investigates plasma Aβ alterations between pre-symptomatic Dutch-type hereditary CAA (D-CAA) mutation-carriers (MC) and non-carriers (NC) using two Aβ measurement platforms. Seventeen pre-symptomatic members of a D-CAA pedigree were assembled and followed up 3-4 years later (NC = 8; MC = 9). Plasma Aβ1-40 and Aβ1-42 were cross-sectionally and longitudinally analysed at baseline (T1) and follow-up (T2) and were found to be lower in MCs …

Exploring Social Media Recruitment Strategies And Preliminary Acceptability Of An Mhealth Tool For Teens With Eating Disorders, Erin Kasson, Melissa M Vázquez, Christine Doroshenko, Ellen E Fitzsimmons-Craft, Denise E Wilfley, C Barr Taylor, Patricia A Cavazos-Rehg

Open Access Publications

(1) Background: The current study leveraged social media to connect with teens with EDs to identify population specific characteristics and to gather feedback on an mHealth intervention. (2) Methods: We recruited teens with EDs from social media in two phases: (1) Discovery Group, (2) Testing Group. The Discovery Group (

Defining Surgical Terminology And Risk For Brain Computer Interface Technologies, Eric C Leuthardt, Daniel W Moran, Tim R Mullen

Open Access Publications

With the emergence of numerous brain computer interfaces (BCI), their form factors, and clinical applications the terminology to describe their clinical deployment and the associated risk has been vague. The terms "minimally invasive" or "non-invasive" have been commonly used, but the risk can vary widely based on the form factor and anatomic location. Thus, taken together, there needs to be a terminology that best accommodates the surgical footprint of a BCI and their attendant risks. This work presents a semantic framework that describes the BCI from a procedural standpoint and its attendant clinical risk profile. We propose extending the common …

Get Privacy Trending: Best Practices For The Social Media Educator, Sara W. Dong, Nathanial S. Nolan, Miguel A. Chavez, Yijia Li, Gerome V. Escota, Wendy Stead

Open Access Publications

Social media is an increasingly popular forum for medical education. Many educators, including those in infectious diseases, are now creating and sharing unique and educational patient cases online. Unfortunately, some educators unknowingly threaten patient privacy and open themselves to legal liability. Further, the use of published figures or tables creates risk of copyright infringement. As more and more infectious diseases physicians engage in social media, it is imperative to create best practices to protect both patients and physicians. This summary will define the legal requirements of patient de-identification as well as other practical recommendations as they relate to use of …

Predicting Outcomes In Patients Undergoing Pancreatectomy Using Wearable Technology And Machine Learning: Prospective Cohort Study, Heidy Cos, Dingwen Li, Gregory Williams, Jeffrey Chininis, Ruixuan Dai, Jingwen Zhang, Rohit Srivastava, Lacey Raper, Dominic Sanford, William Hawkins, Chenyang Lu, Chet W Hammill

Open Access Publications

BACKGROUND: Pancreatic cancer is the third leading cause of cancer-related deaths, and although pancreatectomy is currently the only curative treatment, it is associated with significant morbidity.

OBJECTIVE: The objective of this study was to evaluate the utility of wearable telemonitoring technologies to predict treatment outcomes using patient activity metrics and machine learning.

METHODS: In this prospective, single-center, single-cohort study, patients scheduled for pancreatectomy were provided with a wearable telemonitoring device to be worn prior to surgery. Patient clinical data were collected and all patients were evaluated using the American College of Surgeons National Surgical Quality Improvement Program surgical risk calculator …

Thermoneutrality Alters Gastrointestinal Antigen Passage Patterning And Predisposes To Oral Antigen Sensitization In Mice, Taeko K Noah, Jee-Boong Lee, Christopher A Brown, Amnah Yamani, Sunil Tomar, Varsha Ganesan, Rodney D Newberry, Gary B Huffnagle, Senad Divanovic, Simon P Hogan

Open Access Publications

Food allergy is an emerging epidemic, and the underlying mechanisms are not well defined partly due to the lack of robust adjuvant free experimental models of dietary antigen sensitization. As housing mice at thermoneutrality (Tn) - the temperature of metabolic homeostasis (26-30°C) - has been shown to improve modeling various human diseases involved in inflammation, we tested the impact of Tn housing on an experimental model of food sensitization. Here we demonstrate that WT BALB/c mice housed under standard temperature (18-20°C, Ts) conditions translocated the luminal antigens in the small intestine (SI) across the epithelium

Ontogenetic Oxycodone Exposure Affects Early Life Communicative Behaviors, Sensorimotor Reflexes, And Weight Trajectory In Mice, Elena Minakova, Simona Sarafinovska, Marwa O Mikati, Kia M Barclay, Katherine B Mccullough, Joseph D Dougherty, Ream Al-Hasani, Susan E Maloney

Open Access Publications

Nationwide, opioid misuse among pregnant women has risen four-fold from 1999 to 2014, with commensurate increase in neonates hospitalized for neonatal abstinence syndrome (NAS). NAS occurs when a fetus exposed to opioids

Apathy, Cognitive Impairment, And Social Support Contribute To Participation In Cognitively Demanding Activities Poststroke, Amy Ho, Marjorie L. Nicholas, Chaitali Dagli, Lisa Tabor Connor

Open Access Publications

No abstract provided.

Mr-Guided Adaptive Radiotherapy For Bladder Cancer, Adham Hijab, Boris Tocco, Ian Hanson, Hanneke Meijer, Christina Junker Nyborg, Anders Smedegaard Bertelsen, Robert Jan Smeenk, Gillian Smith, Jeff Michalski, Brian C Baumann, Shaista Hafeez

Open Access Publications

Radiotherapy has an important role in the curative and palliative treatment settings for bladder cancer. As a target for radiotherapy the bladder presents a number of technical challenges. These include poor tumor visualization and the variability in bladder size and position both between and during treatment delivery. Evidence favors the use of magnetic resonance imaging (MRI) as an important means of tumor visualization and local staging. The availability of hybrid systems incorporating both MRI scanning capabilities with the linear accelerator (MR-Linac) offers opportunity for in-room and real-time MRI scanning with ability of plan adaption at each fraction while the patient …

The Dystonia Coalition: A Multicenter Network For Clinical And Translational Studies, Gamze Kilic-Berkmen, Laura J Wright, Joel S Perlmutter, Cynthia Comella, Mark Hallett, Jan Teller, Sarah Pirio Richardson, David A Peterson, Carlos Cruchaga, Codrin Lungu, H A Jinnah

Open Access Publications

Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal postures, repetitive movements, or both. Research in dystonia has been challenged by several factors. First, dystonia is uncommon. Dystonia is not a single disorder but a family of heterogenous disorders with varied clinical manifestations and different causes. The different subtypes may be seen by providers in different clinical specialties including neurology, ophthalmology, otolaryngology, and others. These issues have made it difficult for any single center to recruit large numbers of subjects with specific types of dystonia for research studies in a timely manner. The Dystonia Coalition …

Genomic And Neoantigen Evolution From Primary Tumor To First Metastases In Head And Neck Squamous Cell Carcinoma, Charles R. Schutt, Hua Sun, Jaya Sarin Pradhan, Yvonne Saenger, Jessica Ley, Douglas Adkins, Matthew Ingham, Li Ding, Brian A. Van Tine

Open Access Publications

Head and neck cell squamous-cell carcinomas (HNSCC) are a group of common cancers typically associated with tobacco use and human papilloma virus infection. Up to half of all cases will suffer a recurrence after primary treatment. As such, new therapies are needed, including therapies which promote the anti-tumor immune response. Prior work has characterized changes in the mutation burden between primary and recurrent tumors; however, little work has characterized the changes in neoantigen evolution. We characterized genomic and neoantigen changes between 23 paired primary and recurrent HNSCC tumors. Twenty-three biopsies from patients originally diagnosed with locally advanced disease were identified …

Blood Leukocytes Recapitulate Diabetogenic Peptide-Mhc-Ii Complexes Displayed In The Pancreatic Islets, Anthony N. Vomund, Cheryl F. Lichti, Orion J. Peterson, Ana Maria Arbelaez, Xiaoxiao Wan, Emil R. Unanue

Open Access Publications

Assessing the self-peptides presented by susceptible major histocompatibility complex (MHC) molecules is crucial for evaluating the pathogenesis and therapeutics of tissue-specific autoimmune diseases. However, direct examination of such MHC-bound peptides displayed in the target organ remains largely impractical. Here, we demonstrate that the blood leukocytes from the nonobese diabetic (NOD) mice presented peptide epitopes to autoreactive CD4 T cells. These peptides were bound to the autoimmune class II MHC molecule (MHC-II) I-Ag7 and originated from insulin B-chain and C-peptide. The presentation required a glucose challenge, which stimulated the release of the insulin peptides from the pancreatic islets. The circulating leukocytes, …

Whipworm-Associated Intestinal Microbiome Members Consistent Across Both Human And Mouse Hosts, Bruce A Rosa, Caroline Snowden, John Martin, Kerstin Fischer, Jonah Kupritz, Ethiopia Beshah, Taniawati Supali, Lincoln Gankpala, Peter U Fischer, Joseph F Urban, Makedonka Mitreva

Open Access Publications

The human whipworm

The Impact Of Covid-19 On Dual-Physician Couples: A Disproportionate Burden On Women Physicians, Andrea Soares, Prashanth Thakker, Elena Deych, Shikha Jain, Rakhee K. Bhayani

Open Access Publications

No abstract provided.

4Β-Hydroxycholesterol Is A Prolipogenic Factor That Promotes Srebp1c Expression And Activity Through The Liver X Receptor, Ofer Moldavski, Peter-James H. Zushin, Charles A. Berdan, Robert J. Van Eijkeren, Xuntian Jiang, Mingxing Qian, Daniel S. Ory, Douglas F. Covey, Daniel K. Nomura, Andreas Stahl, Ethan J. Weiss, Roberto Zoncu

Open Access Publications

No abstract provided.