Digital Commons Network^™

Multi-Omic Association Study Identifies Dna Methylation-Mediated Genotype And Smoking Exposure Effects On Lung Function In Children Living In Urban Settings, Matthew Dapas, Michelle A. Gill, Et Al

2020-Current year OA Pubs

Impaired lung function in early life is associated with the subsequent development of chronic respiratory disease. Most genetic associations with lung function have been identified in adults of European descent and therefore may not represent those most relevant to pediatric populations and populations of different ancestries. In this study, we performed genome-wide association analyses of lung function in a multiethnic cohort of children (n = 1,035) living in low-income urban neighborhoods. We identified one novel locus at the TDRD9 gene in chromosome 14q32.33 associated with percent predicted forced expiratory volume in one second (FEV1) (p = 2.4x10-9; βz = -0.31, …

Sik3 And Wnk Converge On Fray To Regulate Glial K+ Buffering And Seizure Susceptibility, Lorenzo Lones, Aaron Diantonio

2020-Current year OA Pubs

Glial cells play a critical role in maintaining homeostatic ion concentration gradients. Salt-inducible kinase 3 (SIK3) regulates a gene expression program that controls K+ buffering in glia, and upregulation of this pathway suppresses seizure behavior in the eag, Shaker hyperexcitability mutant. Here we show that boosting the glial SIK3 K+ buffering pathway suppresses seizures in three additional molecularly diverse hyperexcitable mutants, highlighting the therapeutic potential of upregulating glial K+ buffering. We then explore additional mechanisms regulating glial K+ buffering. Fray, a transcriptional target of the SIK3 K+ buffering program, is a kinase that promotes K+ uptake by activating the Na+/K+/Cl- …

A Novel Biosignature Identifies Patients With Dcis With High Risk Of Local Recurrence After Breast Conserving Surgery And Radiation Therapy, Frank A Vicini, G Bruce Mann, Chirag Shah, Sheila Weinmann, Michael C Leo, Pat Whitworth, Rachel Rabinovitch, Mylin A Torres, Julie A Margenthaler, David Dabbs, Jess Savala, Steven C Shivers, Karuna Mittal, Fredrik Wärnberg, Troy Bremer

2020-Current year OA Pubs

PURPOSE: There is an unmet need to identify women diagnosed with ductal carcinoma in situ (DCIS) with a low risk of in-breast recurrence (IBR) after breast conserving surgery (BCS), which could omit radiation therapy (RT), and also to identify those with elevated IBR risk remaining after BCS plus RT. We evaluated a novel biosignature for a residual risk subtype (RRt) to help identify patients with elevated IBR risk after BCS plus RT.

METHODS AND MATERIALS: Women with DCIS treated with BCS with or without RT at centers in the US, Australia, and Sweden (n = 926) were evaluated. Patients were …

The Mutational Landscape In Chronic Myelomonocytic Leukemia And Its Impact On Allogeneic Hematopoietic Cell Transplantation Outcomes: A Center For Blood And Marrow Transplantation Research (Cibmtr) Analysis, Matthew Mei, Ravi Vij, Et Al.

2020-Current year OA Pubs

Somatic mutations are recognized as an important prognostic factor in chronic myelomonocytic leukemia (CMML). However, limited data are available regarding their impact on outcomes after allogeneic hematopoietic cell transplantation (HCT). In this registry analysis conducted in collaboration with the Center for International Blood and Marrow Transplantation Registry database/sample repository, we identified 313 adult patients with CMML (median age: 64 years, range, 28- 77) who underwent allogeneic HCT during 2001-2017 and had an available biospecimen in the form of a peripheral blood sample obtained prior to the start of conditioning. In multivariate analysis, a CMML-specific prognostic scoring system (CPSS) score of …

Characterization Of High-Gamma Activity In Electrocorticographic Signals, Johannes Gruenwald, Sebastian Sieghartsleitner, Christoph Kapeller, Josef Scharinger, Kyousuke Kamada, Peter Brunner, Christoph Guger

2020-Current year OA Pubs

INTRODUCTION: Electrocorticographic (ECoG) high-gamma activity (HGA) is a widely recognized and robust neural correlate of cognition and behavior. However, fundamental signal properties of HGA, such as the high-gamma frequency band or temporal dynamics of HGA, have never been systematically characterized. As a result, HGA estimators are often poorly adjusted, such that they miss valuable physiological information.

METHODS: To address these issues, we conducted a thorough qualitative and quantitative characterization of HGA in ECoG signals. Our study is based on ECoG signals recorded from 18 epilepsy patients while performing motor control, listening, and visual perception tasks. In this study, we first …

Functional Divergence Of The Sarcomeric Myosin, Myh7b, Supports Species-Specific Biological Roles, Lindsey A. Lee, Samantha K. Barrick, Artur Meller, Jonathan Walklate, Jeffrey M. Lotthammer, Jian Wei Tay, W. Tom Stump, Gregory Bowman, Michael A. Geeves, Michael J. Greenberg, Leslie A Leinwand

2020-Current year OA Pubs

Myosin heavy chain 7b (MYH7b) is an evolutionarily ancient member of the sarcomeric myosin family, which typically supports striated muscle function. However, in mammals, alternative splicing prevents MYH7b protein production in cardiac and most skeletal muscles and limits expression to a subset of specialized muscles and certain nonmuscle environments. In contrast, MYH7b protein is abundant in python cardiac and skeletal muscles. Although the MYH7b expression pattern diverges in mammals versus reptiles, MYH7b shares high sequence identity across species. So, it remains unclear how mammalian MYH7b function may differ from that of other sarcomeric myosins and whether human and python MYH7b …

Mri-Based Classification Of Idh Mutation And 1p/19q Codeletion Status Of Gliomas Using A 2.5d Hybrid Multi-Task Convolutional Neural Network, Satrajit Chakrabarty, Pamela Lamontagne, Joshua Shimony, Daniel S Marcus, Aristeidis Sotiras

2020-Current year OA Pubs

BACKGROUND: IDH mutation and 1p/19q codeletion status are important prognostic markers for glioma that are currently determined using invasive procedures. Our goal was to develop artificial intelligence-based methods to noninvasively determine molecular alterations from MRI.

METHODS: Pre-operative MRI scans of 2648 glioma patients were collected from Washington University School of Medicine (WUSM;

RESULTS: For IDH, the best-performing model achieved areas under the receiver operating characteristic (AUROC) of 0.925, 0.874, 0.933 and areas under the precision-recall curves (AUPRC) of 0.899, 0.702, 0.853 on the internal, WUSM, and EGD test sets, respectively. For 1p/19q, the best model achieved AUROCs of 0.782, 0.754, …

Structural Gray Matter Alterations In Glioblastoma And High-Grade Glioma- A Potential Biomarker Of Survival, Bidhan Lamichhane, Patrick H Luckett, Donna Dierker, Ki Yun Park, Harold Burton, Michael Olufawo, Gabriel Trevino, John J Lee, Andy G S Daniel, Carl D Hacker, Daniel S Marcus, Joshua S Shimony, Eric C Leuthardt

2020-Current year OA Pubs

BACKGROUND: Patients with glioblastoma (GBM) and high-grade glioma (HGG, World Health Organization [WHO] grade IV glioma) have a poor prognosis. Consequently, there is an unmet clinical need for accessible and noninvasively acquired predictive biomarkers of overall survival in patients. This study evaluated morphological changes in the brain separated from the tumor invasion site (ie, contralateral hemisphere). Specifically, we examined the prognostic value of widespread alterations of cortical thickness (CT) in GBM/HGG patients.

METHODS: We used FreeSurfer, applied with high-resolution T1-weighted MRI, to examine CT, evaluated prior to standard treatment with surgery and chemoradiation in patients (GBM/HGG,

RESULTS: Compared to HC …

Plug Inguinal Hernia Repair Mimicking Nodal Spread Of Prostate Cancer On Psma-Pet/Ct, Genevieve C. Muñoz, Tyler J. Fraum

2020-Current year OA Pubs

A variety of non-prostatic or non-malignant findings exhibiting prostate specific membrane antigen (PSMA) tracer uptake and resemble metastatic disease on positron emission tomography (PET) imaging. In this case, a 72-year-old man presenting for initial staging of prostate cancer was found to have PSMA tracer uptake along the left external iliac vessels corresponding to a structure resembling a lymph node on computed tomography (CT). This finding was initially concerning for nodal spread of the patient's primary neoplasm. However, chart review revealed a remote history of left inguinal hernia plug repair with location corresponding to the area of PSMA activity. This case …

Aberrant T-Cell Exhaustion In Severe Combined Immunodeficiency Survivors With Poor T-Cell Reconstitution After Transplantation, Roxane Labrosse, Shalini Shenoy, Et Al.

2020-Current year OA Pubs

BACKGROUND: Severe combined immunodeficiency (SCID) comprises rare inherited disorders of immunity that require definitive treatment through hematopoietic cell transplantation (HCT) or gene therapy for survival. Despite successes of allogeneic HCT, many SCID patients experience incomplete immune reconstitution, persistent T-cell lymphopenia, and poor long-term outcomes.

OBJECTIVE: We hypothesized that CD4

METHODS: We analyzed markers of exhaustion in blood samples from 61 SCID patients at a median of 10.4 years after HCT.

RESULTS: Compared to post-HCT SCID patients with normal CD4

CONCLUSIONS: Recipients of unconditioned HCT for SCID may develop late post-HCT T-cell exhaustion as a result of diminished production of T-lineage …

Necrotic Cardiac Myocytes Skew Macrophage Polarization Towards A Classically Activated Phenotype, Wenlong Jiang, Luigi Adamo, Kenji Lim, Scot J Matkovich, Sarah Evans, Cibele Rocha-Resende, Douglas L. Mann

2020-Current year OA Pubs

Necrotic and dying cells release damage-associated molecular patterns (DAMPs) that can initiate sterile inflammatory responses in the heart. Although macrophages are essential for myocardial repair and regeneration, the effect of DAMPs on macrophage activation remains unclear. To address this gap in knowledge we studied the effect of necrotic cardiac myocyte extracts on primary peritoneal macrophage (PPM) cultures in vitro. We first performed unbiased transcriptomic profiling with RNA-sequencing of PPMs cultured for up to 72 hours in the presence and absence of: 1) necrotic cell extracts (NCEs) from necrotic cardiac myocytes in order to mimic the release of DAMPs; 2) lipopolysaccharide …

Health Utilities And Quality-Adjusted Life Years For Patients With Amyotrophic Lateral Sclerosis Receiving Reldesemtiv Or Placebo In Fortitude-Als, Paulos Gebrehiwet, Lisa Meng, Stacy A Rudnicki, Phil Sarocco, Jenny Wei, Andrew A Wolff, Michael Butzner, Adriano Chiò, Jinsy A Andrews, Angela Genge, Dyfrig A Hughes, Carlayne E Jackson, Noah Lechtzin, Timothy M Miller, Jeremy M Shefner

2020-Current year OA Pubs

AIMS: To estimate the health utilities and quality-adjusted life years (QALYs) in patients with amyotrophic lateral sclerosis (ALS) receiving

MATERIALS AND METHODS: We performed a post hoc analysis of clinical trial data from FORTITUDE-ALS (NCT03160898). This Phase IIb, double-blind, randomized, dose-ranging, placebo-controlled, parallel-group, 12-week trial evaluated

RESULTS: The full analysis set consisted of 456 patients (

CONCLUSIONS: This post hoc analysis of FORTITUDE-ALS suggests that

CLINICALTRIALS.GOV IDENTIFIER: NCT03160898.

Risk And Protection Of Different Rare Protein-Coding Variants Of Complement Component C4a In Age-Related Macular Degeneration, Johanna M Seddon, Dikha De, William Casazza, Shun-Yun Cheng, Claudio Punzo, Mark Daly, Danlei Zhou, Samantha L Coss, John P Atkinson, Chack-Yung Yu

2020-Current year OA Pubs

No abstract provided.

Impact Of Successful Recanalization And Clinical Outcomes Of Patients With Acute Ichemic Stroke With 5 Or More Thrombectomy Passes, Kazutaka Uchida, Joshua Osbun, Et Al.

2020-Current year OA Pubs

No abstract provided.

Safety And Efficacy Of Mca‐M2 Thrombectomy In Delayed Time Window: A Propensity Score Analysis From The Star Registry, Kaustubh Limaye, Joshua Osbun, Et Al.

2020-Current year OA Pubs

No abstract provided.

Transferrin Receptor In Primary And Metastatic Breast Cancer: Evaluation Of Expression And Experimental Modulation To Improve Molecular Targeting, Francesca Fontana, Alison K. Esser, Christopher Egbulefu, Partha Karmakar, Xinming Su, John S. Allen, Yalin Xu, Jennifer L. Davis, Ariel Gabay, Jingyu Xiang, Kristin A. Kwakwa, Brad Manion, Suzanne Bakewell, Shunqiang Li, Haeseong Park, Gregory M. Lanza, Samuel Achilefu, Katherine N. Weilbaecher

2020-Current year OA Pubs

BACKGROUND: Conjugation of transferrin (Tf) to imaging or nanotherapeutic agents is a promising strategy to target breast cancer. Since the efficacy of these biomaterials often depends on the overexpression of the targeted receptor, we set out to survey expression of transferrin receptor (TfR) in primary and metastatic breast cancer samples, including metastases and relapse, and investigate its modulation in experimental models.

METHODS: Gene expression was investigated by datamining in twelve publicly-available datasets. Dedicated Tissue microarrays (TMAs) were generated to evaluate matched primary and bone metastases as well as and pre and post chemotherapy tumors from the same patient. TMA were …

Social Media For Research Discourse, Dissemination, And Collaboration In Rheumatology, Ariella Coler-Reilly, Elizabeth R. Graef, Alfred H J Kim, Jean W. Liew, Michael S. Putman, Sebastian E. Sattui, Kristen J. Young, Jeffrey A. Sparks

2020-Current year OA Pubs

Social media has become an important venue for rheumatologists, patients, organizations, and other stakeholders to discuss recent research advances in diagnosis and management of rheumatic disorders. In this article, we describe the current state of how social media may enhance dissemination, discourse, and collaboration in rheumatology research. Social media may refer to social platforms like Twitter and Instagram or digital media like podcasts and other websites that are operated for providing as free, open-access medical education (FOAM). Twitter has been one of the most active social media venues and continues to host a vibrant rheumatology community. Examples of research discussions …

Studies Of Parenchymal Texture Added To Mammographic Breast Density And Risk Of Breast Cancer: A Systematic Review Of The Methods Used In The Literature, Akila Anandarajah, Yongzhen Chen, Graham A Colditz, Angela Hardi, Carolyn Stoll, Shu Jiang

2020-Current year OA Pubs

This systematic review aimed to assess the methods used to classify mammographic breast parenchymal features in relation to the prediction of future breast cancer. The databases including Medline (Ovid) 1946-, Embase.com 1947-, CINAHL Plus 1937-, Scopus 1823-, Cochrane Library (including CENTRAL), and Clinicaltrials.gov were searched through October 2021 to extract published articles in English describing the relationship of parenchymal texture features with the risk of breast cancer. Twenty-eight articles published since 2016 were included in the final review. The identification of parenchymal texture features varied from using a predefined list to machine-driven identification. A reduction in the number of features …

Bioimpedance-Derived Membrane Capacitance: Clinically Relevant Sources Of Variability, Precision, And Reliability, Valene Garr Barry, Jasmine L Chiang, Kaylan G Bowman, Kristina D Johnson, Barbara A Gower

2020-Current year OA Pubs

Membrane capacitance (C

A Randomized Phase 2 Study Of Neoadjuvant Carboplatin And Paclitaxel With Or Without Atezolizumab In Triple Negative Breast Cancer (Tnbc) - Nci 10013, Foluso O Ademuyiwa, Feng Gao, Cherease R Street, Ina Chen, John M Herndon, Madelyn Carmody, Sherri R Davies, Sarah Larson, Zheng Liu, Ian S Hagemann, William E Gillanders, Et Al.

2020-Current year OA Pubs

Atezolizumab with chemotherapy has shown improved progression-free and overall survival in patients with metastatic PD-L1 positive triple negative breast cancer (TNBC). Atezolizumab with anthracycline- and taxane-based neoadjuvant chemotherapy has also shown increased pathological complete response (pCR) rates in early TNBC. This trial evaluated neoadjuvant carboplatin and paclitaxel with or without atezolizumab in patients with clinical stages II-III TNBC. The co-primary objectives were to evaluate if chemotherapy and atezolizumab increase pCR rate and tumor infiltrating lymphocyte (TIL) percentage compared to chemotherapy alone in the mITT population. Sixty-seven patients (ages 25-78 years; median, 52 years) were randomly assigned - 22 patients to …

Clonally Related, Notch-Differentiated Spinal Neurons Integrate Into Distinct Circuits, Saul Bello-Rojas, Martha W Bagnall

2020-Current year OA Pubs

Shared lineage has diverse effects on patterns of neuronal connectivity. In mammalian cortex, excitatory sister neurons assemble into shared microcircuits. In

Interventions To Treat And Prevent Postpartum Depression: A Protocol For Systematic Review Of The Literature And Parallel Network Meta-Analyses, David Thomas Monks, Basavaraj Ankalagi, Preet Mohinder Singh, Ebony Carter, Michelle Doering, Meg Guard, Shannon Lenze

2020-Current year OA Pubs

INTRODUCTION: Postpartum depression has costly consequences for the mother, baby, and society. Numerous pharmacological and non-pharmacological interventions are available for the prevention and treatment of postpartum depression. To date, no attempt has been made to synthesize the evidence from comparisons of interventions both within and across these categories.

METHODS: We will perform a systematic review of the literature and perform network meta-analysis of interventions to (a) prevent and (b) treat postpartum depression. This review will include studies of primiparous or multiparous women during pregnancy or within 12 months of delivery of their baby that assess either interventions initiated during pregnancy …

Socioecological Predictors Of Breastfeeding Practices In Rural Eastern Ethiopia, Marina Magalhães, Amanda Ojeda, Karah Mechlowitz, Kaitlin Brittain, Jenna Daniel, Kedir Teji Roba, Jemal Yousuf Hassen, Mark J Manary, Wondwossen A Gebreyes, Arie H Havelaar, Sarah L Mckune

2020-Current year OA Pubs

BACKGROUND: Estimates by the World Health Organization indicate that over 800,000 global neonatal deaths each year are attributed to deviations from recommended best practices in infant feeding. Identifying factors promoting ideal breastfeeding practices may facilitate efforts to decrease neonatal and infant death rates and progress towards achieving the Sustainable Development Goals set for 2030. Though numerous studies have identified the benefits of breastfeeding in reducing the risk of childhood undernutrition, infection and illness, and mortality in low- and middle-income countries, no studies have explored predictors of breastfeeding practices in rural eastern Ethiopia, where undernutrition is widespread. The aim of this …

An Rna Interference (Rnai) Toolkit And Its Utility For Functional Genetic Analysis Of Leishmania (Viannia), Lon-Fye Lye, Katherine L Owens, Soojin Jang, Joseph E Marcus, Erin A Brettmann, Stephen M Beverley

2020-Current year OA Pubs

RNA interference (RNAi) is a powerful tool whose efficacy against a broad range of targets enables functional genetic tests individually or systematically. However, the RNAi pathway has been lost in evolution by a variety of eukaryotes including most Leishmania sp. RNAi was retained in species of the

The Performance Of Plasma Amyloid Beta Measurements In Identifying Amyloid Plaques In Alzheimer's Disease: A Literature Review, Abby L Brand, Paige E Lawler, James G Bollinger, Yan Li, Suzanne E Schindler, Melody Li, Samir Lopez, Vitaliy Ovod, Akinori Nakamura, Leslie M Shaw, Henrik Zetterberg, Oskar Hansson, Randall J Bateman

2020-Current year OA Pubs

The extracellular buildup of amyloid beta (Aβ) plaques in the brain is a hallmark of Alzheimer's disease (AD). Detection of Aβ pathology is essential for AD diagnosis and for identifying and recruiting research participants for clinical trials evaluating disease-modifying therapies. Currently, AD diagnoses are usually made by clinical assessments, although detection of AD pathology with positron emission tomography (PET) scans or cerebrospinal fluid (CSF) analysis can be used by specialty clinics. These measures of Aβ aggregation, e.g. plaques, protofibrils, and oligomers, are medically invasive and often only available at specialized medical centers or not covered by medical insurance, and PET …

Diverse Monogenic Subforms Of Human Spermatogenic Failure, Liina Nagirnaja, Wu-Lin Charng, Christina A Gurnett, Kenan R Omurtag, Et Al.

2020-Current year OA Pubs

Non-obstructive azoospermia (NOA) is the most severe form of male infertility and typically incurable. Defining the genetic basis of NOA has proven challenging, and the most advanced classification of NOA subforms is not based on genetics, but simple description of testis histology. In this study, we exome-sequenced over 1000 clinically diagnosed NOA cases and identified a plausible recessive Mendelian cause in 20%. We find further support for 21 genes in a 2-stage burden test with 2072 cases and 11,587 fertile controls. The disrupted genes are primarily on the autosomes, enriched for undescribed human "knockouts", and, for the most part, have …

Promoting Rigor And Sustainment In Implementation Science Capacity Building Programs: A Multi-Method Study., Amy G Huebschmann, Shelly Johnston, Rachel Davis, Bethany M Kwan, Elvin Geng, Debra Haire-Joshu, Brittney Sandler, Demetria M Mcneal, Ross C Brownson, Borsika A Rabin

2020-Current year OA Pubs

BACKGROUND: The field of Implementation science (IS) continues to evolve, and the number and type of IS capacity building Programs (ISCBPs) are in flux. These changes push the field to revisit the accepted IS competencies and to guide sustainment of ISCBPs. Our objectives were: (1) compare characteristics of current ISCBPs; (2) identify recommendations to support ISCBP sustainment; (3) measure how often ISCBPs address IS competencies; (4) identify novel and important IS competencies for the field.

METHOD: This multi-method study included ISCBPs delivering structured, longitudinal IS training, excluding single courses and brief workshops. We used three complementary methods to meet our …

Epigenetic Clock Explains White Matter Hyperintensity Burden Irrespective Of Chronological Age, Joan Jiménez-Balado, Carolina Soriano-Tárraga, Et Al.

2020-Current year OA Pubs

In this manuscript we studied the relationship between WMH and biological age (B-age) in patients with acute stroke. We included in this study 247 patients with acute stroke recruited at Hospital del Mar having both epigenetic (DNA methylation) and magnetic resonance imaging data. WMH were measured using a semi-automated method. B-age was calculated using two widely used methods: the Hannum and Horvath formulas. We used multiple linear regression models to interrogate the role of B-age on WMH volume after adjusting for chronological age (C-age) and other covariables. Average C-age of the sample was 68.4 (±11.8) and we observed a relatively …

The Role Of Er Stress In Diabetes: Exploring Pathological Mechanisms Using Wolfram Syndrome, Shuntaro Morikawa, Fumihiko Urano

2020-Current year OA Pubs

The endoplasmic reticulum (ER) is a cytosolic organelle that plays an essential role in the folding and processing of new secretory proteins, including insulin. The pathogenesis of diabetes, a group of metabolic disorders caused by dysfunctional insulin secretion (Type 1 diabetes, T1DM) or insulin sensitivity (Type 2 diabetes, T2DM), is known to involve the excess accumulation of "poorly folded proteins", namely, the induction of pathogenic ER stress in pancreatic β-cells. ER stress is known to contribute to the dysfunction of the insulin-producing pancreatic β-cells. T1DM and T2DM are multifactorial diseases, especially T2DM; both environmental and genetic factors are involved in …

In Silico Activity And Admet Profiling Of Phytochemicals From Ethiopian Indigenous Aloes Using Pharmacophore Models, Lemessa Etana Bultum, Gemechu Bekele Tolossa, Gwangmin Kim, Ohhyeon Kwon, Doheon Lee

2020-Current year OA Pubs

In silico profiling is used in identification of active compounds and guide rational use of traditional medicines. Previous studies on Ethiopian indigenous aloes focused on documentation of phytochemical compositions and traditional uses. In this study, ADMET and drug-likeness properties of phytochemicals from Ethiopian indigenous aloes were evaluated, and pharmacophore-based profiling was done using Discovery Studio to predict therapeutic targets. The targets were examined using KEGG pathway, gene ontology and network analysis. Using random-walk with restart algorithm, network propagation was performed in CODA network to find diseases associated with the targets. As a result, 82 human targets were predicted and found …