Digital Commons Network^™

Joint Degeneration In A Mouse Model Of Pseudoachondroplasia: Er Stress, Inflammation, And Block Of Autophagy, Jacqueline T Hecht, Alka C Veerisetty, Mohammad G Hossain, Debabrata Patra, Frankie Chiu, Francoise Coustry, Karen L Posey

Open Access Publications

Pseudoachondroplasia (PSACH), a short limb skeletal dysplasia associated with premature joint degeneration, is caused by misfolding mutations in cartilage oligomeric matrix protein (COMP). Here, we define mutant-COMP-induced stress mechanisms that occur in articular chondrocytes of MT-COMP mice, a murine model of PSACH. The accumulation of mutant-COMP in the ER occurred early in MT-COMP articular chondrocytes and stimulated inflammation (TNFα) at 4 weeks, and articular chondrocyte death increased at 8 weeks while ER stress through CHOP was elevated by 12 weeks. Importantly, blockage of autophagy (pS6), the major mechanism that clears the ER, sustained cellular stress in MT-COMP articular chondrocytes. Degeneration …

Genetic And Biochemical Characterization Of The Na+/H+ Antiporters Of Pseudomonas Aeruginosa, Sara Foreman, Kristina Ferrara, Teri N Hreha, Ana E Duran-Pinedo, Jorge Frias-Lopez, Blanca Barquera

Open Access Publications

Pseudomonas aeruginosa has four Na

Outcomes Associated With Social Distancing Policies In St Louis, Missouri, During The Early Phase Of The Covid-19 Pandemic, Elvin H. Geng, Joshua Schwab, Randi Foraker, Branson Fox, Christine M. Hoehner, Mario Schootman, Aaloke Mody, William Powderly, Byron Yount, Keith Woeltje, Maya Petersen

Open Access Publications

Importance: In the absence of a national strategy in response to the COVID-19 pandemic, many public health decisions fell to local elected officials and agencies. Outcomes of such policies depend on a complex combination of local epidemic conditions and demographic features as well as the intensity and timing of such policies and are therefore unclear.

Objective: To use a decision analytical model of the COVID-19 epidemic to investigate potential outcomes if actual policies enacted in March 2020 (during the first wave of the epidemic) in the St Louis region of Missouri had been delayed.

Design, Setting, and Participants: A previously …

Glial-Specific Deletion Of Med12 Results In Rapid Hearing Loss Via Degradation Of The Stria Vascularis, Teng-Wei Huang, Amrita A. Iyer, Jeanne M. Manalo, Junsung Woo, Navish A. Bosquez Huerta, Melissa M. Mcgovern, Heinrich Schrewe, Fredrick A. Pereira, Andrew K. Groves, Kevin K. Ohlemiller, Benjamin Deneen

Open Access Publications

Mediator protein complex subunit 12 (Med12) is a core component of the basal transcriptional apparatus and plays a critical role in the development of many tissues. Mutations in Med12 are associated with X-linked intellectual disability syndromes and hearing loss; however, its role in nervous system function remains undefined. Here, we show that temporal conditional deletion of Med12 in astrocytes in the adult CNS results in region-specific alterations in astrocyte morphology. Surprisingly, behavioral studies revealed rapid hearing loss after adult deletion of Med12 that was confirmed by a complete abrogation of auditory brainstem responses. Cellular analysis of the cochlea revealed degeneration …

Cholestatic Hepatitis In Graves' Disease: A Diagnostic Challenge, Metri Haddaden, Angy Hanna, Fadi Odish, Samir Husami, Zaid Imam, Mamon Tahhan

Open Access Publications

Cholestatic hepatitis is a rare presentation of thyrotoxicosis potentially confused as an adverse effect of antithyroid therapy. We report a 37-year-old man with cholestatic hepatitis as an initial presentation of Graves' disease. Diagnostic evaluation demonstrated (i) elevated transaminases and alkaline phosphatase (R-factor value: 2.6), and marked cholestasis (total bilirubin: 17.3 mg/dL, direct bilirubin: 9.4 mg/dL); (ii) negative hepatitis, viral, and autoimmune serologies; (iii) normal magnetic resonance cholangiopancreatography; (iv) liver biopsy with marked cholestasis and no fibrosis; (v) thyroid-stimulating hormone <0.01, fT4 (free thyroxine): 1.5, fT4 (free triiodothyronine): 4.3 and positive thyroid-stimulating immunoglobulins. Radioiodine uptake scan confirmed Graves' disease. Clinical resolution was achieved with propranolol, prednisone, methimazole, and thyroidectomy.

Diagnosis Of Mast Cell Activation Syndrome: A Global “Consensus-2”, Lawrence B. Afrin, Leonard B. Weinstock, Et Al

Open Access Publications

No abstract provided.

Dynamically Linking Influenza Virus Infection Kinetics, Lung Injury, Inflammation, And Disease Severity, Margaret A. Myers, Amanda P. Smith, Lindey C. Lane, David J. Moquin, Rosemary Aogo, Stacie Woolard, Paul Thomas, Peter Vogel, Amber M. Smith

Open Access Publications

Influenza viruses cause a significant amount of morbidity and mortality. Understanding host immune control efficacy and how different factors influence lung injury and disease severity are critical. We established and validated dynamical connections between viral loads, infected cells, CD8

Molecular Characterization Of Microbiota In Cerebrospinal Fluid From Patients With Csf Shunt Infections Using Whole Genome Amplification Followed By Shotgun Sequencing, Paul Hodor, Christopher E Pope, Kathryn B Whitlock, Lucas R Hoffman, David L Limbrick, Patrick J Mcdonald, Jason S Hauptman, Jeffrey G Ojemann, Tamara D Simon

Open Access Publications

Understanding the etiology of cerebrospinal fluid (CSF) shunt infections and reinfections requires detailed characterization of associated microorganisms. Traditionally, identification of bacteria present in the CSF has relied on culture methods, but recent studies have used high throughput sequencing of 16S rRNA genes. Here we evaluated the method of shotgun DNA sequencing for its potential to provide additional genomic information. CSF samples were collected from 3 patients near the beginning and end of each of 2 infection episodes. Extracted total DNA was sequenced by: (1) whole genome amplification followed by shotgun sequencing (WGA) and (2) high-throughput sequencing of the 16S rRNA …

Using Optical Coherence Tomography And Intravascular Ultrasound Imaging To Quantify Coronary Plaque Cap Stress/Strain And Progression: A Follow-Up Study Using 3d Thin-Layer Models, Rui Lv, Akiko Maehara, Mitsuaki Matsumura, Liang Wang, Caining Zhang, Mengde Huang, Xiaoya Guo, Habib Samady, Don P Giddens, Jie Zheng, Gary S Mintz, Dalin Tang

Open Access Publications

Accurate plaque cap thickness quantification and cap stress/strain calculations are of fundamental importance for vulnerable plaque research. To overcome uncertainties due to intravascular ultrasound (IVUS) resolution limitation, IVUS and optical coherence tomography (OCT) coronary plaque image data were combined together to obtain accurate and reliable cap thickness data, stress/strain calculations, and reliable plaque progression predictions. IVUS, OCT, and angiography baseline and follow-up data were collected from nine patients (mean age: 69; m: 5) at Cardiovascular Research Foundation with informed consent obtained. IVUS and OCT slices were coregistered and merged to form IVUS + OCT (IO) slices. A total of 114 …

Identification Of Genes Encoding Antimicrobial Proteins In Langerhans Cells, Aislyn Oulee, Feiyang Ma, Rosane M B Teles, Bruno J De Andrade Silva, Matteo Pellegrini, Eynav Klechevsky, Andrew N Harman, Jake W Rhodes, Robert L Modlin

Open Access Publications

Langerhans cells (LCs) reside in the epidermis where they are poised to mount an antimicrobial response against microbial pathogens invading from the outside environment. To elucidate potential pathways by which LCs contribute to host defense, we mined published LC transcriptomes deposited in GEO and the scientific literature for genes that participate in antimicrobial responses. Overall, we identified 31 genes in LCs that encode proteins that contribute to antimicrobial activity, ten of which were cross-validated in at least two separate experiments. Seven of these ten antimicrobial genes encode chemokines,

Genomic Determinants Of Homologous Recombination Deficiency Across Human Cancers, Tao Qing, Xinfeng Wang, Tomi Jun, Li Ding, Lajos Pusztai, Kuanlin Huang

Open Access Publications

Germline

Pitch And Rhythm Perception And Verbal Short-Term Memory In Acute Traumatic Brain Injury, Kirsten S Anderson, Nathalie Gosselin, Abbas F Sadikot, Maude Laguë-Beauvais, Esther S H Kang, Alexandra E Fogarty, Judith Marcoux, Jehane Dagher, Elaine De Guise

Open Access Publications

Music perception deficits are common following acquired brain injury due to stroke, epilepsy surgeries, and aneurysmal clipping. Few studies have examined these deficits following traumatic brain injury (TBI), resulting in an under-diagnosis in this population. We aimed to (1) compare TBI patients to controls on pitch and rhythm perception during the acute phase; (2) determine whether pitch and rhythm perception disorders co-occur; (3) examine lateralization of injury in the context of pitch and rhythm perception; and (4) determine the relationship between verbal short-term memory (STM) and pitch and rhythm perception. Music perception was examined using the Scale and Rhythm tests …

A Bone-Specific Adipogenesis Pathway In Fat-Free Mice Defines Key Origins And Adaptations Of Bone Marrow Adipocytes With Age And Disease, Xiao Zhang, Hero Robles, Kristann L. Magee, Madelyn R. Lorenz, Zhaohua Wang, Charles A. Harris, Clarissa S. Craft, Erica L. Scheller

Open Access Publications

Bone marrow adipocytes accumulate with age and in diverse disease states. However, their origins and adaptations in these conditions remain unclear, impairing our understanding of their context-specific endocrine functions and relationship with surrounding tissues. In this study, by analyzing bone and adipose tissues in the lipodystrophic 'fat-free' mouse, we define a novel, secondary adipogenesis pathway that relies on the recruitment of adiponectin-negative stromal progenitors. This pathway is unique to the bone marrow and is activated with age and in states of metabolic stress in the fat-free mouse model, resulting in the expansion of bone marrow adipocytes specialized for lipid storage …

Planning And Delivery Of Intensity Modulated Bolus Electron Conformal Therapy, Elizabeth N Hilliard, Robert L Carver, Erin L Chambers, James A Kavanaugh, Kevin J Erhart, Andrew S Mcguffey, Kenneth R Hogstrom

Open Access Publications

PURPOSE: Bolus electron conformal therapy (BECT) is a clinically useful, well-documented, and available technology. The addition of intensity modulation (IM) to BECT reduces volumes of high dose and dose spread in the planning target volume (PTV). This paper demonstrates new techniques for a process that should be suitable for planning and delivering IM-BECT using passive radiotherapy intensity modulation for electrons (PRIME) devices.

METHODS: The IM-BECT planning and delivery process is an addition to the BECT process that includes intensity modulator design, fabrication, and quality assurance. The intensity modulator (PRIME device) is a hexagonal matrix of small island blocks (tungsten pins …

Parrot Is A Flexible Recurrent Neural Network Framework For Analysis Of Large Protein Datasets, Daniel Griffith, Alex S. Holehouse

Open Access Publications

The rise of high-throughput experiments has transformed how scientists approach biological questions. The ubiquity of large-scale assays that can test thousands of samples in a day has necessitated the development of new computational approaches to interpret this data. Among these tools, machine learning approaches are increasingly being utilized due to their ability to infer complex nonlinear patterns from high-dimensional data. Despite their effectiveness, machine learning (and in particular deep learning) approaches are not always accessible or easy to implement for those with limited computational expertise. Here we present PARROT, a general framework for training and applying deep learning-based predictors on …

Maternal Fructose Diet-Induced Developmental Programming, Michael D Thompson, Brian J Debosch

Open Access Publications

Developmental programming of chronic diseases by perinatal exposures/events is the basic tenet of the developmental origins hypothesis of adult disease (DOHaD). With consumption of fructose becoming more common in the diet, the effect of fructose exposure during pregnancy and lactation is of increasing relevance. Human studies have identified a clear effect of fructose consumption on maternal health, but little is known of the direct or indirect effects on offspring. Animal models have been utilized to evaluate this concept and an association between maternal fructose and offspring chronic disease, including hypertension and metabolic syndrome. This review will address the mechanisms of …

Intent To Vaccinate Sars-Cov-2 Infected Children In Us Households: A Survey, Mehgan Teherani, Samridhi Banskota, Andres Camacho-Gonzalez, Alison G C Smith, Evan J Anderson, Carol M Kao, Charles Crepy D'Orleans, Andi L Shane, Austin Lu, Preeti Jaggi

Open Access Publications

A paucity of data exists evaluating a guardian's intent to vaccinate their child against COVID-19 in the United States. We administered 102 first (April-November 2020) and 45 second (December-January 2020-2021) surveys to guardians of children (<18 years) who had a laboratory-confirmed diagnosis of COVID-19 and assessed their intent to give a COVID-19 vaccine to their child, when one becomes available. The first and second surveys of the same cohort of guardians were conducted before and following the press releases detailing the adult Pfizer-BioNTech and Moderna Phase 3 results. Both surveys included an intent-to-vaccinate question using the subjective language of "if a safe and effective vaccine" became available, and a second question was added to second surveys using the objective language of "would prevent 19 of 20 people from getting disease". When using subjective language, 24 of 45 (53%) guardians endorsed vaccine administration for their children in the first survey, which decreased to 21 (46%) in the second survey. When adding objective language, acceptance of vaccination increased to 31 (69%,

Classification Of Cardiomyopathies From Mr Cine Images Using Convolutional Neural Network With Transfer Learning, Philippe Germain, Armine Vardazaryan, Nicolas Padoy, Aissam Labani, Catherine Roy, Thomas Hellmut Schindler, Soraya El Ghannudi

Open Access Publications

The automatic classification of various types of cardiomyopathies is desirable but has never been performed using a convolutional neural network (CNN). The purpose of this study was to evaluate currently available CNN models to classify cine magnetic resonance (cine-MR) images of cardiomyopathies.

METHOD: Diastolic and systolic frames of 1200 cine-MR sequences of three categories of subjects (395 normal, 411 hypertrophic cardiomyopathy, and 394 dilated cardiomyopathy) were selected, preprocessed, and labeled. Pretrained, fine-tuned deep learning models (VGG) were used for image classification (sixfold cross-validation and double split testing with hold-out data). The heat activation map algorithm (Grad-CAM) was applied to reveal …

An Essential, Kinetoplastid-Specific Gdp-Fuc: Β-D-Gal Α-1,2-Fucosyltransferase Is Located In The Mitochondrion Of Trypanosoma Brucei, Giulia Bandini, Sebastian Damerow, Maria Lucia Sempaio Guther, Hongjie Guo, Angela Mehlert, Jose Carlos Paredes Franco, Stephen Beverley, Michael A.J. Ferguson

Open Access Publications

Fucose is a common component of eukaryotic cell-surface glycoconjugates, generally added by Golgi-resident fucosyltransferases. Whereas fucosylated glycoconjugates are rare in kinetoplastids, the biosynthesis of the nucleotide sugar GDP-Fuc has been shown to be essential in

Critical Period After Stroke Study (Cpass): A Phase Ii Clinical Trial Testing An Optimal Time For Motor Recovery After Stroke In Humans, Alexander W. Dromerick, Shashwati Geed, Jessica Barth, Kathaleen Brady, Margot L. Gianetti, Abigail Mitchell, Matthew A. Edwardson, Ming T. Tan, Yizhao Zhou, Elissa L. Newport, Dorothy F. Edwards

Open Access Publications

No abstract provided.

Cholecystitis Masquerading As Cardiac Chest Pain: A Case Report, Vasudev Malik Daliparty, Behzad Amoozgar, Alejandra Razzeto, Syed Usman Mohsin Ehsanullah, Faseeha Rehman

Open Access Publications

No abstract provided.

Racial Comparison Of Patients Undergoing Minimally Invasive Partial Nephrectomy For Renal Masses At A Large Volume Tertiary Center, Kenneth G. Sands, Rohit Bhatt, Joel Vetter, Alethea Paradis, Alexander K. Chow, Sam Bhayani, Robert S. Figenshau, Ramakrishna Venkatesh

Open Access Publications

No abstract provided.

Metabolite-Specific Echo-Planar Imaging Of Hyperpolarized [1-- 13 C]Pyruvate At 4.7 T, Tyler Blazey, Galen D. Reed, Joel R. Garbow, Cornelius Von Morze

Open Access Publications

Although hyperpolarization (HP) greatly increases the sensitivity of

American Society Of Hematology 2021 Guidelines For Sickle Cell Disease: Stem Cell Transplantation, Julie Kanter, Robert I. Liem, Françoise Bernaudin, Javier Bolaños-Meade, Courtney D. Fitzhugh, Jane S. Hankins, M. Hassan Murad, Julie A. Panepinto, Damiano Rondelli, Shalini Shenoy, John Wagner, Mark C. Walters, Teonna Woolford, Joerg J. Meerpohl, John Tisdale

Open Access Publications

No abstract provided.

Predictors Of Annual Prostate-Specific Antigen (Psa) Screening Among Black Men: Results From An Urban Community-Based Prostate Cancer Screening Program, Marquita W. Lewis-Thames, Saira Khan, Veronica Hicks, Bettina F. Drake

Open Access Publications

No abstract provided.

Contemporary Pure Laparoscopic Vs Robot-Assisted Laparoscopic Radical Nephrectomy: Is The Transition Worth It?, Kenneth G. Sands, Robert S. Figenshau, Joel Vetter, Alethea Paradis, Andrew Pierce, Eric H. Kim, Kefu Du, Alexander Chow, Ramakrishna Venkatesh

Open Access Publications

No abstract provided.

Comparison Of Newly Optimized Moses Technology Vs Standard Holmium: Yag For Endoscopic Laser Enucleation Of The Prostate, Charles U. Nottingham, Tim Large, Deepak K. Agarwal, Marcelino E. Rivera, Amy E. Krambeck

Open Access Publications

No abstract provided.

Outcomes Of Artificial Intelligence Volumetric Assessment Of Kidneys And Renal Tumors For Preoperative Assessment Of Nephron-Sparing Interventions, Roozbeh Houshyar, Justin Glavis-Bloom, Thanh-Lan Bui, Chantal Chahine, Michelle D. Bardis, Alexander Ushinsky, Hanna Liu, Param Bhatter, Elliott Lebby, Dylann Fujimoto, William Grant, Karen Tran-Harding, Jaime Landman, Daniel S. Chow, Peter D. Chang

Open Access Publications

No abstract provided.

Spontaneous Multimodal Neural Transmission Suggests That Adult Spinal Networks Maintain An Intrinsic State Of Readiness To Execute Sensorimotor Behaviors, Maria F. Bandres, Jefferson Gomes, Jacob G. Mcpherson

Open Access Publications

Spontaneous action potential discharge (spAP) is both ubiquitous and functionally relevant during neural development. spAP remains a prominent feature of supraspinal networks in maturity, even during unconsciousness. Evidence suggests that spAP persists in mature spinal networks during wakefulness, and one function of spAP in this context could be maintenance of a "ready state" to execute behaviors. The extent to which spAP persists in mature spinal networks during unconsciousness remains unclear, and its function(s), if any, are likewise unresolved. Here, we attempt to reconcile some of the questions and contradictions that emerge from the disintegrated picture of adult spinal spAP currently …

Breast Cancer Derived Gm-Csf Regulates Arginase 1 In Myeloid Cells To Promote An Immunosuppressive Microenvironment, Xinming Su, Yalin Xu, Gregory C Fox, Jingyu Xiang, Kristin A Kwakwa, Jennifer L Davis, Jad I Belle, Wen-Chih Lee, Wing H Wong, Francesca Fontana, Leonel Hernandez-Aya, Takayuki Kobayashi, Helen M Tomasson, Junyi Su, Suzanne J Bakewell, Sheila A Stewart, Christopher Egbulefu, Partha Karmakar, Melissa A Meyer, Deborah J Veis, David G Denardo, Gregory M Lanza, Samuel Achilefu, Katherine N Weilbaecher

Open Access Publications

Tumor-infiltrating myeloid cells contribute to the development of the immunosuppressive tumor microenvironment. Myeloid cell expression of arginase 1 (Arg-1) promotes a protumor phenotype by inhibiting T cell function and depleting extracellular L-arginine, but the mechanism underlying this expression, especially in breast cancer, is poorly understood. In breast cancer clinical samples and in our mouse models, we identified tumor derived GM-CSF as the primary regulator of myeloid cell Arg-1 expression and local immune suppression through a gene knockout screen of breast tumor cell-produced factors. The induction of myeloid cell Arg-1 required GM-CSF and a low pH environment. GM-CSF signaling through STAT3, …