Digital Commons Network^™

Encoding And Storage Of Information In Mechanical Metamaterials, Zhiqiang Meng, Hujie Yan, Mingchao Liu, Wenkai Qin, Guy M Genin, Chang Qing Chen

2020-Current year OA Pubs

Information processing using material's own properties has gained increasing interest. Mechanical metamaterials, due to their diversity of deformation modes and wide design space, can be used to realize information processing, such as computing and storage. Here a mechanical metamaterial system is demonstrated for material-based encoding and storage of data through programmed reconfigurations of the metamaterial's structured building blocks. Sequential encoding and decoding are achieved in the three-dimensional (3D) printed pixelated mechanical metamaterial via kirigami-based "pixels" with programmable, temperature-dependent bistability. The mechanical metamaterial is demonstrated via a multistep deformation of encoding messages of texts and surfaces with arrays of binary data, …

Identifying The Neural Correlates Of Anticipatory Postural Control: A Novel Fmri Paradigm, Jo Armour Smith, Rongwen Tain, Kelli G Sharp, Laura M Glynn, Linda R Van Dillen, Korinne Henslee, Jesse V Jacobs, Steven C Cramer

2020-Current year OA Pubs

Altered postural control in the trunk/hip musculature is a characteristic of multiple neurological and musculoskeletal conditions. Previously it was not possible to determine if altered cortical and subcortical sensorimotor brain activation underlies impairments in postural control. This study used a novel fMRI-compatible paradigm to identify the brain activation associated with postural control in the trunk and hip musculature. BOLD fMRI imaging was conducted as participants performed two versions of a lower limb task involving lifting the left leg to touch the foot to a target. For the supported leg raise (SLR) the leg is raised from the knee while the …

Economic Impact Of Recurrent Clostridioides Difficile Infection In The Usa: A Systematic Literature Review And Cost Synthesis, Kelly R Reveles, Min Yang, Viviana Garcia-Horton, Marie Louise Edwards, Amy Guo, Thomas Lodise, Markian Bochan, Glenn Tillotson, Erik R Dubberke

2020-Current year OA Pubs

INTRODUCTION: Up to 35% of patients with a first episode of Clostridioides difficile infection (CDI) develop recurrent CDI (rCDI), and of those, up to 65% experience multiple recurrences. A systematic literature review (SLR) was conducted to review and summarize the economic impact of rCDI in the United States of America.

METHODS: English-language publications reporting real-world healthcare resource utilization (HRU) and/or direct medical costs associated with rCDI in the USA were searched in MEDLINE, MEDLINE In-Process, Embase, and the Cochrane Library databases over the past 10 years (2012-2022), as well as in selected scientific conferences that publish research on rCDI and …

Staphylococcus Aureus Bacteremia In Pediatric Patients: Uncovering A Rural Health Challenge, Kyle J Whittington, Sara M Malone, Patrick G Hogan, Faria Ahmed, Jessieann Flowers, Grace Milburn, John J Morelli, Jason G Newland, Stephanie A Fritz

2020-Current year OA Pubs

BACKGROUND:

METHODS: To investigate factors influencing

RESULTS: Of 251 patients, 69 (27%) were from rural areas; 28 (11%) were initially admitted to an OSH. Treatment failure occurred in 39 (16%) patients. Patients from rural areas were more likely to be infected with methicillin-resistant

CONCLUSIONS: Children from rural areas face barriers to specialized health care. These challenges may contribute to severe illness and worse outcomes among children with

Autologous Humanized Pdx Modeling For Immuno-Oncology Recapitulates Features Of The Human Tumor Microenvironment, Michael Chiorazzi, Bradley Krasnick, Keenan J Robbins, Zachary Skidmore, Jacqueline Mudd, Ye Bi, S Peter Goedegebuure, Malachi Griffith, Obi Griffith, Abimbola Oyedeji, Ryan C Fields, Et Al.

2020-Current year OA Pubs

BACKGROUND: Interactions between immune and tumor cells are critical to determining cancer progression and response. In addition, preclinical prediction of immune-related drug efficacy is limited by interspecies differences between human and mouse, as well as inter-person germline and somatic variation. To address these gaps, we developed an autologous system that models the tumor microenvironment (TME) from individual patients with solid tumors.

METHOD: With patient-derived bone marrow hematopoietic stem and progenitor cells (HSPCs), we engrafted a patient's hematopoietic system in MISTRG6 mice, followed by transfer of patient-derived xenograft (PDX) tissue, providing a fully genetically matched model to recapitulate the individual's TME. …

Enhanced 3d Visualization Of Human Fallopian Tube Morphology Using A Miniature Optical Coherence Tomography Catheter, Hongbo Luo, Shuying Li, Sitai Kou, Yixiao Lin, Ian S Hagemann, Quing Zhu

2020-Current year OA Pubs

We demonstrate the use of our miniature optical coherence tomography catheter to acquire three-dimensional human fallopian tube images. Images of the fallopian tube's tissue morphology, vasculature, and tissue heterogeneity distribution are enhanced by adaptive thresholding, masking, and intensity inverting, making it easier to differentiate malignant tissue from normal tissue. The results show that normal fallopian tubes tend to have rich vasculature accompanied by a patterned tissue scattering background, features that do not appear in malignant cases. This finding suggests that miniature OCT catheters may have great potential for fast optical biopsy of the fallopian tube.

Dietary Patterns Are Not Associated With Disease Activity Among Patients With Inflammatory Conditions Of The Pouch In A Prospective Cohort, Edward L Barnes, Poonam Beniwal-Patel, Parakkal Deepak, Laura Raffals, Maia Kayal, Marla Dubinsky, Shannon Chang, Peter D R Higgins, Jennifer I Barr, Chelsea Anderson, Raymond K Cross, Millie D Long, Hans H Herfarth

2020-Current year OA Pubs

BACKGROUND: Evidence-based recommendations regarding the influence of diet on inflammatory conditions of the pouch after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) are limited.

METHODS: We analyzed dietary patterns at enrollment in a prospective registry of patients with 1 of 4 inflammatory conditions of the pouch (acute pouchitis, chronic antibiotic-dependent pouchitis, chronic antibiotic refractory pouchitis, and Crohn's disease of the pouch). We analyzed dietary intake by disease activity at enrollment and then compared dietary patterns among patients who remained in remission throughout the 12-month follow-up to those patients who experienced a disease relapse. We also compared dietary patterns among patients …

Healthcare Costs Of Clostridioides Difficile Infection In Commercially Insured Younger Adults, John M Sahrmann, Margaret A Olsen, Matthew R Keller, Holly Yu, Erik R Dubberke

2020-Current year OA Pubs

In a US adult population aged <65 years, attributable costs due to

Ethanolaminephosphate Cytidylyltransferase Is Essential For Survival, Lipid Homeostasis And Stress Tolerance In Leishmania Major, Somrita Basu, Mattie C. Pawlowic, Fong-Fu Hsu, Geoff Thomas, Kai Zhang

2020-Current year OA Pubs

Glycerophospholipids including phosphatidylethanolamine (PE) and phosphatidylcholine (PC) are vital components of biological membranes. Trypanosomatid parasites of the genus Leishmania can acquire PE and PC via de novo synthesis and the uptake/remodeling of host lipids. In this study, we investigated the ethanolaminephosphate cytidylyltransferase (EPCT) in Leishmania major, which is the causative agent for cutaneous leishmaniasis. EPCT is a key enzyme in the ethanolamine branch of the Kennedy pathway which is responsible for the de novo synthesis of PE. Our results demonstrate that L. major EPCT is a cytosolic protein capable of catalyzing the formation of CDP-ethanolamine from ethanolamine-phosphate and cytidine triphosphate. …

Real-World Outcomes Associated With Poly(Adp-Ribose) Polymerase Inhibitor Monotherapy Maintenance In Patients With Primary Advanced Ovarian Cancer, John K Chan, Jinan Liu, Jinlin Song, Cheryl Xiang, Eric Wu, Linda Kalilani, Jean A. Hurteau, Premal H. Thaker

2020-Current year OA Pubs

OBJECTIVE: This study used real-world population data to assess the trends of first-line (1L) poly(ADP-ribose) polymerase inhibitor (PARPi) maintenance treatment uptake and outcomes in patients with primary advanced ovarian cancer (AOC).

METHODS: Patients diagnosed with AOC between January 1, 2017, and June 30, 2021, who completed 1L chemotherapy were selected from a real-world database. Descriptive analyses were performed to evaluate patient demographics, clinicopathological characteristics, and 1L treatment patterns. Time to next treatment or death was used as a proxy for real-world progression-free survival (rwPFS). Kaplan-Meier methods and Cox models were used for statistical analyses.

RESULTS: Of 705 patients who completed …

Safety And Efficacy Of Ceftolozane/Tazobactam Plus Metronidazole Versus Meropenem From A Phase 2, Randomized Clinical Trial In Pediatric Participants With Complicated Intra-Abdominal Infection, Carl-Christian A. Jackson, Jason Newland, Nataliia Dementieva, Julia Lonchar, Feng-Hsiu Su, Jennifer A. Huntington, Mekki Bensaci, Myra W. Popejoy, Matthew G. Johnson, Carisa De Anda, Elizabeth G. Rhee, Christopher J. Bruno

2020-Current year OA Pubs

BACKGROUND: Ceftolozane/tazobactam, a cephalosporin-β-lactamase inhibitor combination, is approved for the treatment of complicated urinary tract infections and complicated intra-abdominal infections (cIAI). The safety and efficacy of ceftolozane/tazobactam in pediatric participants with cIAI were assessed.

METHODS: This phase 2 study (NCT03217136) randomized participants to either ceftolozane/tazobactam+metronidazole or meropenem for treatment of cIAI in pediatric participants (<18 years). The primary objective was to assess the safety and tolerability of intravenous ceftolozane/tazobactam+metronidazole. Clinical cure at end of treatment (EOT) and test of cure (TOC) visits were secondary end points.

RESULTS: The modified intent-to-treat (MITT) population included 91 participants (ceftolozane/tazobactam+metronidazole, n = 70; meropenem, n = 21). Complicated appendicitis was the most common diagnosis (93.4%); Escherichia coli was the most common pathogen (65.9%). Adverse events (AEs) occurred in 80.0% and 61.9% of participants receiving ceftolozane/tazobactam+metronidazole …

Apolipoprotein E O-Glycosylation Is Associated With Amyloid Plaques And Apoe Genotype, Paige E Lawler, James G Bollinger, Suzanne E Schindler, Cynthia R Hodge, Nicolas J Iglesias, Vishal Krishnan, John B Coulton, Yan Li, David M Holtzman, Randall J Bateman

2020-Current year OA Pubs

Although the APOE ε4 allele is the strongest genetic risk factor for sporadic Alzheimer's disease (AD), the relationship between apolipoprotein (apoE) and AD pathophysiology is not yet fully understood. Relatively little is known about the apoE protein species, including post-translational modifications, that exist in the human periphery and CNS. To better understand these apoE species, we developed a LC-MS/MS assay that simultaneously quantifies both unmodified and O-glycosylated apoE peptides. The study cohort included 47 older individuals (age 75.6 ± 5.7 years [mean ± standard deviation]), including 23 individuals (49%) with cognitive impairment. Paired plasma and cerebrospinal fluid samples underwent analysis. …

Complete Hydatidiform Mole With A Coexisting Viable Male Fetus Detected By Cell-Free Dna, Mackenzie Lemieux, Lauren Kus, Kali Stewart, Mai He, Jackson Rowe, Matthew Brady, Katherine Bligard, Megan Lawlor, Jeannie Kelly

2020-Current year OA Pubs

Complete hydatidiform mole with coexisting fetus (CHMCF) is rare, and diagnosis is challenging due to limited data. Here, we present the case of a patient with noninvasive prenatal test (NIPT) resulting in "likely molar pregnancy" in the second trimester. Subsequent ultrasound confirmed a cystic appearing portion of the placenta. At 22 weeks, the patient delivered a demised fetus and two placentas. Pathology was consistent with CHMCF. This case is the first to show primary detection of a CHMCF with single-nucleotide polymorphism (SNP)-based NIPT prior to ultrasound identification. Our case suggests the use of SNP-based NIPT as an alternative noninvasive method …

Aga Clinical Practice Update On Interventional Eus For Vascular Investigation And Therapy: Commentary, Marvin Ryou, John M Dewitt, Koushik K Das, Vanessa M Shami

2020-Current year OA Pubs

DESCRIPTION: The purpose of this AGA Institute Clinical Practice Update is to review the available evidence supporting and examine opportunities for future research in endoscopic ultrasound-guided vascular investigation and therapies.

METHODS: This Clinical Practice Update was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the Clinical Practice Updates Committee and external peer review through standard procedures of Clinical Gastroenterology and Hepatology. This expert commentary incorporates important as well as recently published …

Blood Neurofilament Light Levels Predict Non-Relapsing Progression Following Anti-Cd20 Therapy In Relapsing And Primary Progressive Multiple Sclerosis: Findings From The Ocrelizumab Randomised, Double-Blind Phase 3 Clinical Trials, Amit Bar-Or, Anne H Cross, Et Al.

2020-Current year OA Pubs

BACKGROUND: Neurofilament light chain (NfL), a neuronal cytoskeletal protein that is released upon neuroaxonal injury, is associated with multiple sclerosis (MS) relapsing activity and has demonstrated some prognostic ability for future relapse-related disease progression, yet its value in assessing non-relapsing disease progression remains unclear.

METHODS: We examined baseline and longitudinal blood NfL levels in 1421 persons with relapsing MS (RMS) and 596 persons with primary progressive MS (PPMS) from the pivotal ocrelizumab MS trials. NfL treatment-response and risk for disease worsening (including disability progression into the open-label extension period and slowly expanding lesions [SELs] on brain MRI) at baseline and …

Neuroinflammation And White Matter Alterations In Occupational Manganese Exposure Assessed By Diffusion Basis Spectrum Imaging, Susan R Criswell, Susan Searles Nielsen, Irene M Faust, Joshua S Shimony, Robert L White 3rd, Jason Lenox-Krug, Brad A Racette

2020-Current year OA Pubs

OBJECTIVE: To evaluate in-vivo neuroinflammation and white matter (WM) microstructural integrity in occupational manganese (Mn) exposure.

METHODS: We assessed brain inflammation using Diffusion Basis Spectrum Imaging (DBSI) in 26 Mn-exposed welders, 17 Mn-exposed workers, and 26 non-exposed participants. Cumulative Mn exposure was estimated from work histories and the Unified Parkinson's Disease Rating Scale motor subsection 3 (UPDRS3) scores were completed by a movement specialist. Tract-based Spatial Statistics allowed for whole-brain voxel-wise WM analyses to compare WM DBSI-derived measures between the Mn-exposed and non-exposed groups. Exploratory grey matter region of interest (ROI) analyses examined the presence of similar alterations in the …

Associated Radiation Exposure From Medical Imaging And Excess Lifetime Risk Of Developing Cancer In Pediatric Patients With Pulmonary Hypertension, Malini Mahendra, Philip Chu, Elena K Amin, Hythem Nawaytou, James R Duncan, Jeffrey R Fineman, Rebecca Smith-Bindman

2020-Current year OA Pubs

Pediatric patients with pulmonary hypertension (PH) receive imaging studies that use ionizing radiation (radiation) such as computed tomography (CT) and cardiac catheterization to guide clinical care. Radiation exposure is associated with increased cancer risk. It is unknown how much radiation pediatric PH patients receive. The objective of this study is to quantify radiation received from imaging and compute associated lifetime cancer risks for pediatric patients with PH. Electronic health records between 2012 and 2022 were reviewed and radiation dose data were extracted. Organ doses were estimated using Monte Carlo modeling. Cancer risks for each patient were calculated from accumulated exposures …

Postmortem Diagnosis Of Very Long Chain Acyl-Coa Dehydrogenase (Vlcad) Deficiency In A Neonate With Sudden Cardiac Death, Prapti Singh, Deirdre Amaro, Olugbemisola Obi, Fnu Kiran, Erin Hediger, Tomi L Toler, Patricia I Dickson, Dorothy K Grange

2020-Current year OA Pubs

Very long chain acyl-CoA dehydrogenase (VLCAD) deficiency is an autosomal recessive long chain fatty acid β-oxidation disorder with a variable clinical spectrum, ranging from an acute neonatal presentation with cardiac and hepatic failure to childhood or adult onset of symptoms with hepatomegaly or rhabdomyolysis provoked by illness or exertion. Neonatal cardiac arrest or sudden unexpected death can be the presenting phenotype in some patients, emphasizing the importance of early clinical suspicion and intervention. We report a patient who had a cardiac arrest and died at one day of age. Following her death, the newborn screen reported biochemical evidence of VLCAD …

Characteristics Of Patients With Pulmonary Arterial Hypertension From An Innovative, Comprehensive Real-World Patient Data Repository, Harrison W Farber, Murali M Chakinala, Michelle Cho, Robert P Frantz, Andrew Frick, Lisa Lancaster, Scott Milligan, Ronald Oudiz, Sumeet Panjabi, Yuen Tsang, Steven D Nathan

2020-Current year OA Pubs

Pulmonary arterial hypertension (PAH) is a rare, life-limiting disease. PAH registries provide real-world data that complement clinical trial data and inform treatment decisions. The TRIO comprehensive, integrated patient data repository (TRIO CIPDR), is an innovative US repository capturing data on contemporary patients diagnosed with pulmonary hypertension and receiving US Food and Drug Administration-approved PAH therapies. This repository uniquely combines clinical data from electronic medical records with the ability to track drug-prescription and drug-dispensing characteristics, and includes 946 adult patients with PAH (data collected January 2019 to December 2020) enrolled from nine representative US specialist tertiary care centers. Potentially eligible patients …

Validation Of A Farsi Version Of The Eating Disorder Examination Questionnaire (F-Ede-Q) In Adolescents And University Students From Iran, Reza N Sahlan, Jessica F Saunders, Patrycja Klimek-Johnson, Alexandra D Convertino, Jason M Lavender, Ellen E Fitzsimmons-Craft, Jason M Nagata

2020-Current year OA Pubs

BACKGROUND: Although the Farsi version of the Eating Disorder Examination-Questionnaire (F-EDE-Q) is frequently utilized to assess disordered eating in Iran, its factor structure, reliability, and validity have not been investigated in Iranian samples, which is the aim of the current investigation.

METHOD: Using convenience sampling, this study recruited 1112 adolescents and 637 university students to complete disordered eating and mental health-focused questionnaires, including the F-EDE-Q.

RESULTS: Confirmatory factor analyses of the 22 attitudinal items in the F-EDE-Q indicated that a brief seven-item, three-factor model (i.e., Dietary Restraint, Shape/Weight Overvaluation, Body Dissatisfaction with Shape and Weight) was the only factor structure …

Microrna-145 And Microrna-486 Are Potential Serum Biomarkers For Vascular Calcification, Sara Fernández-Villabrille, Beatriz Martín-Carro, Julia Martín-Vírgala, Cristina Alonso-Montes, Carmen Palomo-Antequera, Raúl García-Castro, Susana López-Ongil, Adriana S Dusso, José Luis Fernández-Martín, Manuel Naves-Díaz, Jorge B Cannata-Andía, Natalia Carrillo-López, Sara Panizo

2020-Current year OA Pubs

INTRODUCTION: MicroRNAs (miRs) regulate vascular calcification (VC), and their quantification may contribute to suspicion of the presence of VC.

METHODS: The study was performed in four phases. Phase 1: miRs sequencing of rat calcified and non-calcified aortas. Phase 2: miRs with the highest rate of change, plus miR-145 [the most abundant miR in vascular smooth muscle cells (VSMCs)], were validated in aortas and serum from rats with and without VC. Phase 3: the selected miRs were analyzed in epigastric arteries from kidney donors and recipients, and serum samples from general population. Phase 4: VSMCs were exposed to different phosphorus concentrations, …

Exploratory Genome-Wide Analyses Of Cortical Inhibition, Facilitation, And Plasticity In Late-Life Depression, Rafae A Wathra, Xiaoyu Men, Samar S M Elsheikh, Victoria S Marshe, Tarek K Rajji, Jennifer I Lissemore, Benoit H Mulsant, Jordan F Karp, Charles F Reynolds 3rd, Eric J Lenze, Zafiris J Daskalakis, Daniel J Müller, Daniel M Blumberger

2020-Current year OA Pubs

Late-life depression (LLD) is a heterogenous mood disorder influenced by genetic factors. Cortical physiological processes such as cortical inhibition, facilitation, and plasticity may be markers of illness that are more strongly associated with genetic factors than the clinical phenotype. Thus, exploring the relationship between genetic factors and these physiological processes may help to characterize the biological mechanisms underlying LLD and improve diagnosis and treatment selection. Transcranial magnetic stimulation (TMS) combined with electromyography was used to measure short interval intracortical inhibition (SICI), cortical silent period (CSP), intracortical facilitation (ICF), and paired associative stimulation (PAS) in 79 participants with LLD. We used …

The Highly Conserved Stem-Loop Ii Motif Is Dispensable For Sars-Cov-2, Hongbing Jiang, Astha Joshi, Tianyu Gan, Andrew B Janowski, Chika Fujii, Traci L Bricker, Tamarand L Darling, Houda H Harastani, Kuljeet Seehra, Stephen Tahan, Ana Jung, Binita Febles, Joshua A Blatter, Scott A Handley, Bijal A Parikh, David Wang, Adrianus C M Boon, Et Al.

2020-Current year OA Pubs

The stem-loop II motif (s2m) is an RNA structural element that is found in the 3' untranslated region (UTR) of many RNA viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Though the motif was discovered over 25 years ago, its functional significance is unknown. In order to understand the importance of s2m, we created viruses with deletions or mutations of the s2m by reverse genetics and also evaluated a clinical isolate harboring a unique s2m deletion. Deletion or mutation of the s2m had no effect on growth

Benefits Of A 12-Week Non-Drug "Brain Fitness Program" For Patients With Attention-Deficit/Hyperactive Disorder, Post-Concussion Syndrome, Or Memory Loss, Majid Fotuhi, Noah D Khorrami, Cyrus A Raji

2020-Current year OA Pubs

BACKGROUND: Non-pharmacologic interventions can potentially improve cognitive function, sleep, and/or mood in patients with attention-deficit/hyperactive disorder (ADHD), post-concussion syndrome (PCS), or memory loss.

OBJECTIVE: We evaluated the benefits of a brain rehabilitation program in an outpatient neurology practice that consists of targeted cognitive training, lifestyle coaching, and electroencephalography (EEG)-based neurofeedback, twice weekly (90 minutes each), for 12 weeks.

METHODS: 223 child and adult patients were included: 71 patients with ADHD, 88 with PCS, and 64 with memory loss (mild cognitive impairment or subjective cognitive decline). Patients underwent a complete neurocognitive evaluation, including tests for Verbal Memory, Complex Attention, Processing Speed, …

Esophageal Secondary Peristalsis Following Acid Infusion And Chemical Clearance Correlate With Mucosal Integrity And Acid Sensitivity In Gerd Patients, Ming-Wun Wong, Jui-Sheng Hung, Wei-Yi Lei, Tso-Tsai Liu, Chih-Hsun Yi, Shu-Wei Liang, Chandra Prakash Gyawali, Jen-Hung Wang, Chien-Lin Chen

2020-Current year OA Pubs

BACKGROUND: Acid sensitivity can be altered in patients with gastroesophageal reflux disease (GERD). Secondary peristalsis helps clear gastro-esophageal refluxate and residual ingested food bolus.

OBJECTIVES: The aim of this study was to investigate the associations among acid sensitivity, esophageal mucosal integrity, chemical clearance, and secondary peristalsis before and after esophageal acid infusion.

DESIGN: This was an investigator-initiated, prospective, cross-sectional study.

METHODS: Adult reflux patients underwent high resolution manometry and 24 h impedance-pH monitoring off acid suppression to identify GERD phenotypes, including non-erosive reflux disease (NERD), reflux hypersensitivity (RH), and functional heartburn (FH). Secondary peristalsis was assessed using five rapid 20 …

A Moment Kernel Machine For Clinical Data Mining To Inform Medical Decision Making, Yao-Chi Yu, Wei Zhang, David O'Gara, Jr-Shin Li, Su-Hsin Chang

2020-Current year OA Pubs

Machine learning-aided medical decision making presents three major challenges: achieving model parsimony, ensuring credible predictions, and providing real-time recommendations with high computational efficiency. In this paper, we formulate medical decision making as a classification problem and develop a moment kernel machine (MKM) to tackle these challenges. The main idea of our approach is to treat the clinical data of each patient as a probability distribution and leverage moment representations of these distributions to build the MKM, which transforms the high-dimensional clinical data to low-dimensional representations while retaining essential information. We then apply this machine to various pre-surgical clinical datasets to …

Etv2 Primes Hematoendothelial Gene Enhancers Prior To Hematoendothelial Fate Commitment, Jeffrey D Steimle, Chul Kim, Megan Rowton, Rangarajan D Nadadur, Zhezhen Wang, Matthew Stocker, Andrew D Hoffmann, Erika Hanson, Junghun Kweon, Tanvi Sinha, Kyunghee Choi, Brian L Black, John M Cunningham, Ivan P Moskowitz, Kohta Ikegami

2020-Current year OA Pubs

Mechanisms underlying distinct specification, commitment, and differentiation phases of cell fate determination remain undefined due to difficulties capturing these processes. Here, we interrogate the activity of ETV2, a transcription factor necessary and sufficient for hematoendothelial differentiation, within isolated fate intermediates. We observe transcriptional upregulation of Etv2 and opening of ETV2-binding sites, indicating new ETV2 binding, in a common cardiac-hematoendothelial progenitor population. Accessible ETV2-binding sites are active at the Etv2 locus but not at other hematoendothelial regulator genes. Hematoendothelial commitment coincides with the activation of a small repertoire of previously accessible ETV2-binding sites at hematoendothelial regulators. Hematoendothelial differentiation accompanies activation of …

Epigenome-Wide Association Study Identifies Novel Genes Associated With Ischemic Stroke, Hao Peng, Helena Palma-Gudiel, Carolina Soriano-Tarraga, Jordi Jimenez-Conde, Mingzhi Zhang, Yonghong Zhang, Jinying Zhao

2020-Current year OA Pubs

BACKGROUND: DNA methylation has previously been associated with ischemic stroke, but the specific genes and their functional roles in ischemic stroke remain to be determined. Here we aimed to identify differentially methylated genes that play a functional role in ischemic stroke in a Chinese population.

RESULTS: Genome-wide DNA methylation assessed with the Illumina Methylation EPIC Array in a discovery sample including 80 Chinese adults (40 cases vs. 40 controls) found that patients with ischemic stroke were characterized by increased DNA methylation at six CpG loci (individually located at TRIM6, FLRT2, SOX1, SOX17, AGBL4, and FAM84A, respectively) and decreased DNA methylation …

Inclusive Recruitment Strategies To Maximize Sociodemographic Diversity Among Participants: A St. Louis Case Study, Chelsey R. Carter, Julia Maki, Nicole Ackermann, Erika A. Waters

2020-Current year OA Pubs

UNLABELLED:

HIGHLIGHTS: We provide concrete strategies for recruiting, enrolling, and retaining a sociodemographically diverse study sample.We offer cost estimates for all stages of study recruitment and found that in-person recruitment was the most effective, but also the most expensive, way to identify Black participants and participants with no college experience.It is critical for investigators to have access to institutional infrastructure and resources to support conducting research that is inclusive of diverse sociodemographic groups.An intentionally diverse recruitment staff supports a diverse study sample.

Neuraminidase Activity Modulates Cellular Coinfection During Influenza A Virus Multicycle Growth, Zijian Guo, Yuanyuan He, Jian Xu, Ananya N. Benegal, Steven L. Brody, Michael D. Vahey

2020-Current year OA Pubs

Infection of individual cells by multiple virions plays critical roles in the replication and spread of many viruses, but mechanisms that control cellular coinfection during multicycle viral growth remain unclear. Here, we investigate virus-intrinsic factors that control cellular coinfection by influenza A virus (IAV). Using quantitative fluorescence to track the spread of virions from single infected cells, we identify the IAV surface protein neuraminidase (NA) as a key determinant of cellular coinfection. We map this effect to NA's ability to deplete viral receptors from both infected and neighboring uninfected cells. In cases in which viral infectious potential is low, genetic …