Digital Commons Network^™

Cognitive Dysfunction After Analgesia And Sedation: Out Of The Operating Room And Into The Pediatric Intensive Care Unit, Ashley D Turner, Travis Sullivan, Kurt Drury, Trevor A Hall, Cydni N Williams, Kristin P Guilliams, Sarah Murphy, A M Iqbal O'Meara

Open Access Publications

In the midst of concerns for potential neurodevelopmental effects after surgical anesthesia, there is a growing awareness that children who require sedation during critical illness are susceptible to neurologic dysfunctions collectively termed pediatric post-intensive care syndrome, or PICS-p. In contrast to healthy children undergoing elective surgery, critically ill children are subject to inordinate neurologic stress or injury and need to be considered separately. Despite recognition of PICS-p, inconsistency in techniques and timing of post-discharge assessments continues to be a significant barrier to understanding the specific role of sedation in later cognitive dysfunction. Nonetheless, available pediatric studies that account for analgesia …

Decoding Neural Activity In Sulcal And White Matter Areas Of The Brain To Accurately Predict Individual Finger Movement And Tactile Stimuli Of The Human Hand, Chad Bouton, Nikunj Bhagat, Santosh Chandrasekaran, Jose Herrero, Noah Markowitz, Elizabeth Espinal, Joo-Won Kim, Richard Ramdeo, Junqian Xu, Matthew F Glasser, Stephan Bickel, Ashesh Mehta

Open Access Publications

Millions of people worldwide suffer motor or sensory impairment due to stroke, spinal cord injury, multiple sclerosis, traumatic brain injury, diabetes, and motor neuron diseases such as ALS (amyotrophic lateral sclerosis). A brain-computer interface (BCI), which links the brain directly to a computer, offers a new way to study the brain and potentially restore impairments in patients living with these debilitating conditions. One of the challenges currently facing BCI technology, however, is to minimize surgical risk while maintaining efficacy. Minimally invasive techniques, such as stereoelectroencephalography (SEEG) have become more widely used in clinical applications in epilepsy patients since they can …

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 …

Centering Inclusivity In The Design Of Online Conferences-An Ohbm-Open Science Perspective, Elizabeth Levitis, Janine D. Bijsterbosch, Et Al

Open Access Publications

As the global health crisis unfolded, many academic conferences moved online in 2020. This move has been hailed as a positive step towards inclusivity in its attenuation of economic, physical, and legal barriers and effectively enabled many individuals from groups that have traditionally been underrepresented to join and participate. A number of studies have outlined how moving online made it possible to gather a more global community and has increased opportunities for individuals with various constraints, e.g., caregiving responsibilities. Yet, the mere existence of online conferences is no guarantee that everyone can attend and participate meaningfully. In fact, many elements …

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 Characterization And Therapeutic Targeting Of Hpv Undetected Cervical Carcinomas, Fiona J Ruiz, Aishwarya Sundaresan, Jin Zhang, Chandra S Pedamallu, Mari K Halle, Vinodh Srinivasasainagendra, Jianqing Zhang, Naoshad Muhammad, Jennifer Stanley, Stephanie Markovina, Hemant K Tiwari, Perry W Grigsby, Camilla Krakstad, Julie K Schwarz, Akinyemi I Ojesina

Open Access Publications

Cervical cancer tumors with undetectable HPV (HPV

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 …

Biological Resurfacing In A Canine Model Of Hip Osteoarthritis, Bradley T Estes, Masataka Enomoto, Franklin T Moutos, Megan A Carson, Jeffrey M Toth, Peter Eggert, Jonathan Stallrich, Vincent P Willard, Deborah J Veis, Dianne Little, Farshid Guilak, B Duncan X Lascelles

Open Access Publications

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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 …

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

Ip3r-Driven Increases In Mitochondrial Ca2+ Promote Neuronal Death In Npc Disease, Scott A. Tiscione, Maria Casas, Jonathan D. Horvath, Vincent Lam, Keiko Hino, Daniel S. Ory, L. Fernando Santana, Sergi Simó, Rose E. Dixon, Eamonn J. Dickson

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.

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.

Postdischarge Prophylactic Antibiotics Following Mastectomy With And Without Breast Reconstruction, David K Warren, Kate M Peacock, Katelin B Nickel, Victoria J Fraser, Margaret A Olsen, Cdc Prevention Epicenter Program

Open Access Publications

BACKGROUND: Prophylactic antibiotics are commonly prescribed at discharge for mastectomy, despite guidelines recommending against this practice. We investigated factors associated with postdischarge prophylactic antibiotic use after mastectomy with and without immediate reconstruction and the impact on surgical-site infection (SSI).

STUDY DESIGN: We studied a cohort of women aged 18-64 years undergoing mastectomy between January 1, 2010, and June 30, 2015, using the MarketScan commercial database. Patients with nonsurgical perioperative infections were excluded. Postdischarge oral antibiotics were identified from outpatient drug claims. SSI was defined using International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9-CM) diagnosis codes. Generalized linear models were …

Elac2/Rnasez-Linked Cardiac Hypertrophy In Drosophila Melanogaster, Ekaterina Migunova, Joanna Theophilopoulos, Marisa Mercadante, Jing Men, Chao Zhou, Edward B Dubrovsky

Open Access Publications

A severe form of infantile cardiomyopathy (CM) has been linked to mutations in ELAC2, a highly conserved human gene. It encodes Zinc phosphodiesterase ELAC protein 2 (ELAC2), which plays an essential role in the production of mature tRNAs. To establish a causal connection between ELAC2 variants and CM, here we used the Drosophila melanogaster model organism, which carries the ELAC2 homolog RNaseZ. Even though RNaseZ and ELAC2 have diverged in some of their biological functions, our study demonstrates the use of the fly model to study the mechanism of ELAC2-related pathology. We established transgenic lines harboring RNaseZ with CM-linked mutations …

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 …

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.

A Pilot Study Of 3d Tissue‑Engineered Bone Marrow Culture As A Tool To Predict Patient Response To Therapy In Multiple Myeloma, Kinan Alhallak, Amanda Jeske, Pilar De La Puente, Jennifer Sun, Mark Fiala, Feda Azab, Barbara Muz, Ilyas Sahin, Ravi Vij, John F. Dipersio, Abdel Kareem Azab

Open Access Publications

No abstract provided.

Prevalence Of Elevated Serum Fatty Acid Synthase In Chronic Limb‑Threatening Ischemia, Shirli Tay, Gayan S. De Silva, Connor M. Engel, Nikolai Harroun, Amanda S. Penrose, Kshitij A. Desai, Yan Yan, Clay F. Semenkovich, Mohamed A. Zayed

Open Access Publications

No abstract provided.

Electroporation Safety Factor Of 300 Nanosecond And 10 Millisecond Defibrillation In Langendorff-Perfused Rabbit Hearts, Johanna U. Neuber, Andrei G. Pakhomov, Christian W. Zemlin

Open Access Publications

AIMS: Recently, a new defibrillation modality using nanosecond pulses was shown to be effective at much lower energies than conventional 10 millisecond monophasic shocks in ex vivo experiments. Here we compare the safety factors of 300 nanosecond and 10 millisecond shocks to assess the safety of nanosecond defibrillation.

METHODS AND RESULTS: The safety factor, i.e. the ratio of median effective doses (ED50) for electroporative damage and defibrillation, was assessed for nanosecond and conventional (millisecond) defibrillation shocks in Langendorff-perfused New Zealand white rabbit hearts. In order to allow for multiple shock applications in a single heart, a pair of needle electrodes …

Accelerated Functional Brain Aging In Pre-Clinical Familial Alzheimer’S Disease, Julie Gonneaud, Brian A. Gordon, Carlos Cruchaga, Tammie L. S. Benzinger, John C. Morris, Randall J. Bateman, Susan Brandon, Virginia Buckles, Tamara Donahue, Anne Fagan, Gigi Flynn, Erin Franklin, Cortaiga Gant, Julia Gray, Alexander Groves, Jason Hassenstab, Laura Hoechst-Swisher, David Holtzman, Russ Hornbeck, Gina Jerome, Celeste Karch, Denise Maue-Dreyfus, Eric Mcdade, Joanne Norton, Richard Perrin, Marc Raichle, Wendy Sigurdson, Peter Wang, Chengjie Xiong, Xiong Xu, Nigel J. Cairns, Erin Householder, Lisa Taylor Reinwald, Beau Ances, Maria Carroll, Sue Leon, Mark A. Mintun, Stacy Schneider, 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 …

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 …

Comprehensive Characterization Of 536 Patient-Derived Xenograft Models Prioritizes Candidates For Targeted Treatment, Hua Sun, Song Cao, R. Jay Mashl, Chia-Kuei Mo, Sherri R. Davies, Tina M. Primeau, Jeremy Hoog, Jacqueline L. Mudd, Matthew A. Wyczalkowski, Reyka G. Jayasinghe, Fernanda Martins Rodrigues, Nadezhda V. Terekhanova, Yize Li, Kian-Huat Lim, Andrea Wang-Gillam, Brian A. Van Tine, Cynthia X. Ma, Katherine C. Fuh, John F. Dipersio, Julie Belmar, Jason Held, Rose Tipton, Yige Wu, Lijun Yao, Daniel Cui Zhou, Feng Chen, Shunqiang Li, Ramaswamy Govindan, Li Ding, Michael C. Wendl, Rebecca Aft, Julie K. Schwarz, Jose P. Zevallos, Sidharth V. Puram, Jingqin Luo, Ryan C. Fields, Et Al

Open Access Publications

No abstract provided.

Zika Virus Infection Of Pregnant Ifnar1-/- Mice Triggers Strain-Specific Differences In Fetal Outcomes, Ellie K. Bohm, Jennifer T. Vangorder-Braid, Anna S. Jaeger, Ryan V. Moriarty, John J. Baczenas, Natalie C. Bennett, Shelby L. O'Connor, Michael K. Fritsch, Nicole A. Fuhler, Kevin K. Noguchi, Matthew T. Aliota

Open Access Publications

Zika virus (ZIKV) is a flavivirus that causes a constellation of adverse fetal outcomes collectively termed congenital Zika syndrome (CZS). However, not all pregnancies exposed to ZIKV result in an infant with apparent defects. During the 2015 to 2016 American outbreak of ZIKV, CZS rates varied by geographic location. The underlying mechanisms responsible for this heterogeneity in outcomes have not been well defined. Therefore, we sought to characterize and compare the pathogenic potential of multiple Asian-/American-lineage ZIKV strains in an established

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 …