Digital Commons Network^™

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 …

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

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

A Representational Similarity Analysis Of Cognitive Control During Color-Word Stroop, Michael C. Freund, Julie M. Bugg, Todd S. Braver

Open Access Publications

Progress in understanding the neural bases of cognitive control has been supported by the paradigmatic color-word Stroop task, in which a target response (color name) must be selected over a more automatic, yet potentially incongruent, distractor response (word). For this paradigm, models have postulated complementary coding schemes: dorsomedial frontal cortex (DMFC) is proposed to evaluate the demand for control via incongruency-related coding, whereas dorsolateral PFC (DLPFC) is proposed to implement control via goal and target-related coding. Yet, mapping these theorized schemes to measured neural activity within this task has been challenging. Here, we tested for these coding schemes relatively directly, …

Basal Epithelial Stem Cells Cross An Alarmin Checkpoint For Postviral Lung Disease, Kangyun Wu, Kenji Kamimoto, Yong Zhang, Kuangying Yang, Shamus P Keeler, Benjamin J Gerovac, Eugene V Agapov, Stephen P Austin, Jennifer Yantis, Kelly A Gissy, Derek E Byers, Jennifer Alexander-Brett, Christy M Hoffmann, Matthew Wallace, Michael E Hughes, Erika C Crouch, Samantha A Morris, Michael J Holtzman

Open Access Publications

Epithelial cells are charged with protection at barrier sites, but whether this normally beneficial response might sometimes become dysfunctional still needs definition. Here, we recognized a pattern of imbalance marked by basal epithelial cell growth and differentiation that replaced normal airspaces in a mouse model of progressive postviral lung disease due to the Sendai virus. Single-cell and lineage-tracing technologies identified a distinct subset of basal epithelial stem cells (basal ESCs) that extended into gas-exchange tissue to form long-term bronchiolar-alveolar remodeling regions. Moreover, this cell subset was selectively expanded by crossing a cell-growth and survival checkpoint linked to the nuclear-localized alarmin …

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 …

Determining Subpopulation Methylation Profiles From Bisulfite Sequencing Data Of Heterogeneous Samples Using Dxm, Jerry Fong, Jacob R. Gardner, Jared M. Andrews, Amanda F. Cashen, Jacqueline E. Payton, Kilian Q. Weinberger, John R. Edwards

Open Access Publications

Epigenetic changes, such as aberrant DNA methylation, contribute to cancer clonal expansion and disease progression. However, identifying subpopulation-level changes in a heterogeneous sample remains challenging. Thus, we have developed a computational approach, DXM, to deconvolve the methylation profiles of major allelic subpopulations from the bisulfite sequencing data of a heterogeneous sample. DXM does not require prior knowledge of the number of subpopulations or types of cells to expect. We benchmark DXM's performance and demonstrate improvement over existing methods. We further experimentally validate DXM predicted allelic subpopulation-methylation profiles in four Diffuse Large B-Cell Lymphomas (DLBCLs). Lastly, as proof-of-concept, we apply DXM …

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, …

Insights Into The Expanding Phenotypic Spectrum Of Inherited Disorders Of Biogenic Amines, Oya Kuseyri Hübschmann, Toni S. Pearson, Et Al

Open Access Publications

No abstract provided.

Application Of A Time-Series Deep Learning Model To Predict Cardiac Dysrhythmias In Electronic Health Records, Aixia Guo, Sakima Smith, Yosef M. Khan, James R. Langabeer Ii, Randi E. Foraker

Open Access Publications

BACKGROUND: Cardiac dysrhythmias (CD) affect millions of Americans in the United States (US), and are associated with considerable morbidity and mortality. New strategies to combat this growing problem are urgently needed.

OBJECTIVES: Predicting CD using electronic health record (EHR) data would allow for earlier diagnosis and treatment of the condition, thus improving overall cardiovascular outcomes. The Guideline Advantage (TGA) is an American Heart Association ambulatory quality clinical data registry of EHR data representing 70 clinics distributed throughout the US, and has been used to monitor outpatient prevention and disease management outcome measures across populations and for longitudinal research on the …

Community Hospice Nurses' Perspectives On Needs, Preferences, And Challenges Related To Caring For Children With Serious Illness, Amy S. Porter, Kristina Zalud, Jacob Applegarth, Cameka Woods, Melanie Gattas, Emily Rutt, Karen Williams, Justin N. Baker, Erica C. Kaye

Open Access Publications

Importance: Many of the 50 000 children who die annually are eligible for provision of community-based hospice care, yet few hospice organizations offer formal pediatric services. Population-level data demonstrate that hospice nurses lack training, experience, and comfort in caring for children, but their specific educational needs and preferences are poorly understood.

Objective: To assess the pediatric-specific training and support needs of hospice nurses caring for children in the community.

Design, Setting, and Participants: For this qualitative study, 41 nurses were purposively seletected from a population-level cohort of 551 hospice nurses who completed a previous mixed-methods survey; these 41 nurses participated …

Tracheal Aspirate Rna Sequencing Identifies Distinct Immunological Features Of Covid-19 Ards, Aartik Sarma, Pratik Sinha, Et Al

Open Access Publications

No abstract provided.

Isolation Of Reconstructed Functional Ribonucleoprotein Complexes Of Machupo Virus, Jesse D. Pyle, Sean P.J. Whelan

Open Access Publications

Arenaviruses initiate infection by delivering a transcriptionally competent ribonucleoprotein (RNP) complex into the cytosol of host cells. The arenavirus RNP consists of the large (L) RNA-dependent RNA polymerase (RdRP) bound to a nucleoprotein (NP)-encapsidated genomic RNA (viral RNA [vRNA]) template. During transcription and replication, L must transiently displace RNA-bound NP to allow for template access into the RdRP active site. Concomitant with RNA replication, new subunits of NP must be added to the nascent complementary RNAs (cRNA) as they emerge from the product exit channel of L. Interactions between L and NP thus play a central role in arenavirus gene …

Charge Syndrome Protein Chd7 Regulates Epigenomic Activation Of Enhancers In Granule Cell Precursors And Gyrification Of The Cerebellum, Naveen C. Reddy, Shahriyar P. Majidi, Lingchun Kong, Mati Nemera, Cole J. Ferguson, Michael Moore, Tassia M. Goncalves, Hai-Kun Liu, James A. J. Fitzpatrick, Guoyan Zhao, Tomoko Yamada, Azad Bonni, Harrison W. Gabel

Open Access Publications

No abstract provided.

Circulating Cd5l Is Associated With Cardiovascular Events And All-Cause Mortality In Individuals With Chronic Kidney Disease, Esmeralda Castelblanco, Maria R. Sarrias, Àngels Betriu, Berta Soldevila, Maria Barranco-Altirriba, Josep Franch-Nadal, Jose M. Valdivielso, Marcelino Bermudez-Lopez, Per-Henrik Groop, Elvira Fernández, Núria Alonso, Didac Mauricio

Open Access Publications

This study assessed the association of CD5L and soluble CD36 (sCD36) with the risk of a cardiovascular event (CVE), including CV death and all-cause mortality in CKD. We evaluated the association of CD5L and sCD36 with a predefined composite CV endpoint (unstable angina, myocardial infarction, transient ischemic attack, cerebrovascular accident, congestive heart failure, arrhythmia, peripheral arterial disease [PAD] or amputation by PAD, aortic aneurysm, or death from CV causes) and all-cause mortality using Cox proportional hazards regression, adjusted for CV risk factors. The analysis included 1,516 participants free from pre-existing CV disease followed up for 4 years. The median age …

Comprehensive Assessment Of A Nationwide Simulation-Based Course For Artificial Life Support, Mateusz Puslecki, Ahmed S Said, Et Al

Open Access Publications

BACKGROUND: Successful implementation of medical technologies applied in life-threatening conditions, including extracorporeal membrane oxygenation (ECMO) requires appropriate preparation and training of medical personnel. The pandemic has accelerated the creation of new ECMO centers and has highlighted continuous training in adapting to new pandemic standards. To reach high standards of patients' care, we created the first of its kind, National Education Centre for Artificial Life Support (NEC-ALS) in 40 million inhabitants' country in the Central and Eastern Europe (CEE). The role of the Center is to test and promote the novel or commonly used procedures as well as to develop staff …

Modeling Spinal Locomotor Circuits For Movements In Developing Zebrafish, Yann Roussel, Stephanie F. Gaudreau, Emily R. Kacer, Mohini Sengupta, Tuan V. Bui

Open Access Publications

Many spinal circuits dedicated to locomotor control have been identified in the developing zebrafish. How these circuits operate together to generate the various swimming movements during development remains to be clarified. In this study, we iteratively built models of developing zebrafish spinal circuits coupled to simplified musculoskeletal models that reproduce coiling and swimming movements. The neurons of the models were based upon morphologically or genetically identified populations in the developing zebrafish spinal cord. We simulated intact spinal circuits as well as circuits with silenced neurons or altered synaptic transmission to better understand the role of specific spinal neurons. Analysis of …

Analysis Of Amyloid-Like Secondary Structure In The Cryab-R120g Knock-In Mouse Model Of Hereditary Cataracts By Two-Dimensional Infrared Spectroscopy, Ariel M. Alperstein, Kathleen S. Molnar, Sidney S. Dicke, Kieran M. Farrell, Leah N. Makley, Martin T. Zanni, Usha P Andley

Open Access Publications

αB-crystallin is a small heat shock protein that forms a heterooligomeric complex with αA-crystallin in the ocular lens. It is also widely distributed in tissues throughout the body and has been linked with neurodegenerative diseases such as Alzheimer's, where it is associated with amyloid fibrils. Crystallins can form amorphous aggregates in cataracts as well as more structured amyloid-like fibrils. The arginine 120 to glycine (R120G) mutation in αB-crystallin (Cryab-R120G) results in high molecular weight crystallin protein aggregates and loss of the chaperone activity of the protein in vitro, and it is associated with human hereditary cataracts and myopathy. Characterizing the …

Is Left-Behind A Real Reason For Children's Social Cognition Deficit? An Fnirs Study On The Effect Of Social Interaction On Left-Behind Preschooler's Prefrontal Activation, Keya Ding, Chuanjiang Li, Huibin Jia, Mingming Zhang, Dongchuan Yu

Open Access Publications

The left-behind phenomenon, caused by parent out-migration, has become a common social issue and might lead to long-term and potential risks for children in rural areas of China. It is important to investigate the effect of social interaction on prefrontal activation of left-behind children in China because of possible effects of parent out-migration on children's social cognition. We recruited 81 rural Chinese preschoolers aged 52-76 months (mean = 64.98 ± 6.321 months) preschoolers with three different statuses of parental out-migration (including non-, partially, and completely left-behind children). Using functional Near-Infrared Spectroscopy (fNIRS), we compared behavior and brain activation and in …

Neuronal Activity In Dorsal Anterior Cingulate Cortex During Economic Choices Under Variable Action Costs, Xinying Cai, Camillo Padoa-Schioppa

Open Access Publications

The role of the dorsal anterior cingulate cortex (ACCd) in decision making has often been discussed but remains somewhat unclear. On the one hand, numerous studies implicated this area in decisions driven by effort or action cost. On the other hand, work on economic choices between goods (under fixed action costs) found that neurons in ACCd encoded only post-decision variables. To advance our understanding of the role played by this area in decision making, we trained monkeys to choose between different goods (juice types) offered in variable amounts and with different action costs. Importantly, the task design dissociated computation of …

Development And Assessment Of A Clinical Calculator For Estimating The Likelihood Of Recurrence And Survival Among Patients With Locally Advanced Rectal Cancer Treated With Chemotherapy, Radiotherapy, And Surgery, Martin R Weiser, William C. Chapman, Philip S. Bauer, Matthew G. Mutch, Parag J. Parikh, Et Al

Open Access Publications

Importance: Predicting outcomes in patients receiving neoadjuvant therapy for rectal cancer is challenging because of tumor downstaging. Validated clinical calculators that can estimate recurrence-free survival (RFS) and overall survival (OS) among patients with rectal cancer who have received multimodal therapy are needed.

Objective: To develop and validate clinical calculators providing estimates of rectal cancer recurrence and survival that are better for individualized decision-making than the American Joint Committee on Cancer (AJCC) staging system or the neoadjuvant rectal (NAR) score.

Design, Setting, and Participants: This prognostic study developed risk models, graphically represented as nomograms, for patients with incomplete pathological response using …

Inflammatory Myoglandular Polyps Presenting With Diarrhea, Cassandra D. L. Fritz, Pooja Navale, Matthew Mutch, Vladimir Kushnir

Open Access Publications

No abstract provided.

Live Imaging Reveals The Cellular Events Downstream Of Sarm1 Activation, Kwang Woo Ko, Laura Devault, Yo Sasaki, Jeffrey Milbrandt, Aaron Diantonio

Open Access Publications

SARM1 is an inducible NAD

Intestinal Goblet Cells Sample And Deliver Lumenal Antigens By Regulated Endocytic Uptake And Transcytosis, Jenny K. Gustafsson, Jazmyne E. Davis, Tracy Rappai, Keely G. Mcdonald, Devesha H. Kulkarni, Kathryn A. Knoop, Simon P. Hogan, James A.J. Fitzpatrick, Wayne I. Lencer, Rodney D. Newberry

Open Access Publications

Intestinal goblet cells maintain the protective epithelial barrier through mucus secretion and yet sample lumenal substances for immune processing through formation of goblet cell associated antigen passages (GAPs). The cellular biology of GAPs and how these divergent processes are balanced and regulated by goblet cells remains unknown. Using high-resolution light and electron microscopy, we found that in mice, GAPs were formed by an acetylcholine (ACh)-dependent endocytic event remarkable for delivery of fluid-phase cargo retrograde into the trans-golgi network and across the cell by transcytosis - in addition to the expected transport of fluid-phase cargo by endosomes to multi-vesicular bodies and …

Practical Considerations For Quantitative Clinical Spect/Ct Imaging Of Alpha Particle Emitting Radioisotopes, Nadia Benabdallah, William Scheve, Nicholas Dunn, Delynn Silvestros, Paul Schelker, Diane Abou, Uday Jammalamadaka, Richard Laforest, Zekun Li, Jonathan Liu, David Ballard, Nichole Maughan, Hiram Gay, Brian Baumann, Robert Hobbs, Buck Rogers, Amir Iravani, Abhinav Jha, Farrokh Dehdashti, Daniel Thorek

Open Access Publications

No abstract provided.

Phase Ii Study Of Dacarbazine Given With Modern Prophylactic Anti-Emetics And Growth Factor Support To Patients With Metastatic, Resistant Soft Tissue, And Bone Sarcoma, Brian Van Tine, Mia Weiss, Angela Hirbe, Peter Oppelt, Sarah Abaricia, Kathryn Trinkaus, Jingqin Luo, Shellie Berry, Tyler Ruff, Cheryl Callahan, Jacqui Toensikoetter, Jessica Ley, Marilyn Siegel, Farrokh Dehdashti, Barry Siegel, Douglas Adkins

Open Access Publications

No abstract provided.

Processing Pipeline For Image Reconstructed Fnirs Analysis Using Both Mri Templates And Individual Anatomy, Samuel Forbes, Sobanawartiny Wijeakumar, Adam Eggebrecht, Vincent Magnotta, John Spencer

Open Access Publications

No abstract provided.

Bacterial Meta-Analysis Of Chicken Cecal Microbiota, Luis Alberto Chica Cardenas, Viviana Clavijo, Martha Vives, Alejandro Reyes

Open Access Publications

Poultry production is an industry that generates 90,000 metric tons of chicken meat worldwide. Thus, optimizing chicken growth and sustainable production is of great importance. A central factor determining not only production parameters, but also stability of the immune system and chicken health, is the diversity and variability of the microbiota present throughout the gastrointestinal tract. To date, several studies have investigated the relationship between bacterial communities and the gut microbiome, with limited data to compare. This study aims to create a bacterial meta-analysis based on studies using amplicon sequencing with Illumina sequencing technologies in order to build a baseline …

Pet Study Of Sphingosine-1-Phosphate Receptor 1 Expression In Response To S. Aureus Infection, Hao Jiang, Jiwei Gu, Haiyang Zhao, Sumit Joshi, Joel Perlmutter, Robert Gropler, Robyn Klein, Tammie Benzinger, Zhude Tu

Open Access Publications

Sphingosine-1-phosphate receptor 1 (S1PR1) plays a crucial role in infectious diseases. Targeting S1PR1 provides protection against pathogens, such as influenza viruses. This study is aimed at investigating S1PR1 in response to bacterial infection by assessing S1PR1 expression in