Digital Commons Network^™

Differential In Vitro Infection Of Neural Cells By Astroviruses, Andrew B. Janowski, Robyn S. Klein, David Wang

Open Access Publications

No abstract provided.

A Herpesvirus Encoded Qa-1 Mimic Inhibits Natural Killer Cell Cytotoxicity Through Cd94/Nkg2a Receptor Engagement, Xiaoli Wang, Sytse J. Piersma, Christopher A. Nelson, Ya-Nan Dai, Ted Christensen, Eric Lazear, Liping Yang, Marjolein Sluijter, Thorbald Van Hall, Ted H. Hansen, Wayne M. Yokoyama, Daved H. Fremont

Open Access Publications

A recurrent theme in viral immune evasion is the sabotage of MHC-I antigen presentation, which brings virus the concomitant issue of 'missing-self' recognition by NK cells that use inhibitory receptors to detect surface MHC-I proteins. Here, we report that rodent herpesvirus Peru (RHVP) encodes a Qa-1 like protein (pQa-1) via RNA splicing to counteract NK activation. While pQa-1 surface expression is stabilized by the same canonical peptides presented by murine Qa-1, pQa-1 is GPI-anchored and resistant to the activity of RHVP pK3, a ubiquitin ligase that targets MHC-I for degradation. pQa-1 tetramer staining indicates that it recognizes CD94/NKG2A receptors. Consistently, …

Aberrant Structural And Functional Connectivity And Neurodevelopmental Impairment In Preterm Children, Cynthia E Rogers, Rachel E Lean, Muriah D Wheelock, Christopher D Smyser

Open Access Publications

BACKGROUND: Despite advances in antenatal and neonatal care, preterm birth remains a leading cause of neurological disabilities in children. Infants born prematurely, particularly those delivered at the earliest gestational ages, commonly demonstrate increased rates of impairment across multiple neurodevelopmental domains. Indeed, the current literature establishes that preterm birth is a leading risk factor for cerebral palsy, is associated with executive function deficits, increases risk for impaired receptive and expressive language skills, and is linked with higher rates of co-occurring attention deficit hyperactivity disorder, anxiety, and autism spectrum disorders. These same infants also demonstrate elevated rates of aberrant cerebral structural and …

Association Of Alcohol Consumption After Development Of Heart Failure With Survival Among Older Adults In The Cardiovascular Health Study, Justin S. Sadhu, Eric Novak, Kenneth J. Mukamal, Jorge R. Kizer, Bruce M. Psaty, Phyllis K. Stein, David L. Brown

Open Access Publications

Importance: More than 1 million older adults develop heart failure annually. The association of alcohol consumption with survival among these individuals after diagnosis is unknown.

Objective: To determine whether alcohol use is associated with increased survival among older adults with incident heart failure.

Design, Setting, and Participants: This prospective cohort study included 5888 community-dwelling adults aged 65 years or older who were recruited to participate in the Cardiovascular Health Study between June 12, 1989, and June 1993, from 4 US sites. Of the total participants, 393 individuals had a new diagnosis of heart failure within the first 9 years of …

Cd4+ T Cells Induce Rejection Of Urothelial Tumors After Immune Checkpoint Blockade, Yuji Sato, Jennifer K Bolzenius, Abdallah M Eteleeb, Xinming Su, Christopher A Maher, Jennifer K Sehn, Vivek K Arora

Open Access Publications

Immune checkpoint blockade (ICB) provides clinical benefit to a minority of patients with urothelial carcinoma (UC). The role of CD4+ T cells in ICB-induced antitumor activity is not well defined; however, CD4+ T cells are speculated to play a supportive role in the development of CD8+ T cells that kill tumor cells after recognition of tumor antigens presented by MHC class I. To investigate the mechanisms of ICB-induced activity against UC, we developed mouse organoid-based transplantable models that have histologic and genetic similarity to human bladder cancer. We found that ICB can induce tumor rejection and protective immunity with these …

Electroencephalographic Abnormalities In Sepsis Patients In Correlation To The Calculated Prognostic Scores: A Case Series, Dimitrios Velissaris, Nikolaos-Dimitrios Pantzaris, Anastasia Skroumpelou, Panagiotis Polychronopoulos, Vasilios Karamouzos, Charalampos Pierrakos, Charalampos Gogos, Menelaos Karanikolas

Open Access Publications

OBJECTIVE: To evaluate the electroencephalographic (EEG) findings and correlate EEG findings with inflammatory biomarkers and the sepsis prognostic scores SOFA, SAPS II and APACHE II in patients who present in the Emergency Department with sepsis without clinical central nervous system involvement.

METHODS: The study included seventeen patients (< 70 years old) with sepsis without central nervous system involvement presenting in the Emergency Department of the University Hospital of Patras, Greece. All patients underwent neurologic examination and EEG analysis on admission to the hospital and were treated according to the international guideline protocols for sepsis.

RESULTS: Six of seventeen sepsis patients had mild or moderate EEG abnormalities. We did not find any significant correlation between EEG abnormalities and inflammatory biomarkers (CRP, WBC) or commonly used prognostic sepsis scores.

CONCLUSIONS: EEG could serve as a useful tool to identify brain alterations at an early stage in sepsis, before …

In Vivo Characterization Of Connective Tissue Remodeling Using Infrared Photoacoustic Spectra, Yuan Qu, Peng Hu, Junhui Shi, Konstantin Maslov, Peinan Zhao, Chiye Li, Jun Ma, Alejandro Garcia-Uribe, Karen Meyers, Emily Diveley, Stephanie Pizzella, Lisa Muench, Nina Punyamurthy, Naomi Goldstein, Oji Onwumere, Mariana Alisio, Kaytelyn Meyenburg, Jennifer Maynard, Kristi Helm, Emma Altieri, Janessia Slaughter, Sabrina Barber, Tracy Burger, Christine Kramer, Jessica Chubiz, Monica Anderson, Ronald Mccarthy, Sarah K England, George A Macones, Molly J Stout, Methodius Tuuli, Lihong V Wang

Open Access Publications

Premature cervical remodeling is a critical precursor of spontaneous preterm birth, and the remodeling process is characterized by an increase in tissue hydration. Nevertheless, current clinical measurements of cervical remodeling are subjective and detect only late events, such as cervical effacement and dilation. Here, we present a photoacoustic endoscope that can quantify tissue hydration by measuring near-infrared cervical spectra. We quantify the water contents of tissue-mimicking hydrogel phantoms as an analog of cervical connective tissue. Applying this method to pregnant women in vivo, we observed an increase in the water content of the cervix throughout pregnancy. The application of this …

What About The Partner? -Factors Associated With Patient-Perceived Partner Dyspareunia In Men With Peyronie's Disease, Yifan Meng, David Y Yang, Kevin M Hebert, Josh B Savage, Manaf Alom, Tobias S Kohler, Landon Trost

Open Access Publications

Background: Limited data are available on how partners of men with Peyronie's disease (PD) are affected by the disease. We sought to characterize PD patients whose curvatures result in pain for their partners during penetrative intercourse.

Methods: We queried a database of all men undergoing initial evaluation for PD at a single clinic between March 2014 and June 2016. Patients were administered a questionnaire regarding sexual health concerns with domains including erectile dysfunction, ejaculatory dysfunction, libido, and penile curvature. In the penile curvature section, patients were specifically asked: "Does the curvature cause your partner any pain during penetrative intercourse? (Y/N)." …

Lrrk1 Regulation Of Actin Assembly In Osteoclasts Involves Serine 5 Phosphorylation Of L-Plastin, Mingjue Si, Helen Goodluck, Canjun Zeng, Songqin Pan, Elizabeth M Todd, Sharon Celeste Morley, Xuezhong Qin, Subburaman Mohan, Weirong Xing

Open Access Publications

Mice with disruption of Lrrk1 and patients with nonfunctional mutant Lrrk1 exhibit severe osteopetrosis phenotypes because of osteoclast cytoskeletal dysfunction. To understand how Lrrk1 regulates osteoclast function by modulating cytoskeleton rearrangement, we examined the proteins that are differentially phosphorylated in wild-type mice and Lrrk1-deficient osteoclasts by metal affinity purification coupled liquid chromatography/mass spectrometry (LC/MS) analyses. One of the candidates that we identified by LC/MS is L-plastin, an actin bundling protein. We found that phosphorylation of L-plastin at serine (Ser) residues 5 was present in wild-type osteoclasts but not in Lrrk1-deficient cells. Western blot analyses with antibodies specific for Ser5 phosphorylated …

A Prospective Adaptive Utility Trial To Validate Performance Of A Novel Urine Exosome Gene Expression Assay To Predict High-Grade Prostate Cancer In Patients With Prostate-Specific Antigen 2-10ng/Ml At Initial Biopsy, James Mckiernan, Michael J Donovan, Eric Margolis, Alan Partin, Ballentine Carter, Gordon Brown, Phillipp Torkler, Mikkel Noerholm, Johan Skog, Neal Shore, Gerry Andriole, Ian Thompson, Peter Carroll

Open Access Publications

BACKGROUND: Discriminating indolent from clinically significant prostate cancer (PCa) in the initial biopsy setting remains an important issue. Prospectively evaluated diagnostic assays are necessary to ensure efficacy and clinical adoption.

OBJECTIVE: Performance and utility assessment of ExoDx Prostate (IntelliScore) (EPI) urine exosome gene expression assay versus standard clinical parameters for discriminating Grade Group (GG) ≥2 PCa from GG1 PCa and benign disease on initial biopsy.

DESIGN, SETTING, AND PARTICIPANTS: A two-phase adaptive clinical utility study (NCT03031418) comparing EPI results with biopsy outcomes in men, with age ≥50 yr and prostate-specific antigen (PSA) 2-10ng/ml, scheduled for initial prostate biopsy. After EPI …

New Advances In Amblyopia Therapy Ii: Refractive Therapies, Courtney L Kraus, Susan M Culican

Open Access Publications

The treatment of anisometropic or ametropic amblyopia has traditionally enjoyed a high treatment success rate. Early initiation and consistent use of spectacle correction can completely resolve amblyopia in a majority of patients. For those with anisometropic amblyopia that fail to improve with glasses wear alone, patching or atropine penalisation can lead to equalisation of visual acuity. However, successful treatment requires full-time compliance with refractive correction and this can be a challenge for a patient population that often has one eye with good acuity without correction. Other barriers for a select population with high anisometropic or ametropic amblyopia include rejection of …

Reengineering Workflow For Curation Of Dicom Datasets, William Bennett, Kirk Smith, Quasar Jarosz, Tracy Nolan, Walter Bosch

Open Access Publications

Reusable, publicly available data is a pillar of open science and rapid advancement of cancer imaging research. Sharing data from completed research studies not only saves research dollars required to collect data, but also helps insure that studies are both replicable and reproducible. The Cancer Imaging Archive (TCIA) is a global shared repository for imaging data related to cancer. Insuring the consistency, scientific utility, and anonymity of data stored in TCIA is of utmost importance. As the rate of submission to TCIA has been increasing, both in volume and complexity of DICOM objects stored, the process of curation of collections …

Rare Presentation Of An Atrial Myxoma In An Adolescent Patient: A Case Report And Literature Review, Eduardo Macias, Elizabeth Nieman, Kentaro Yomogida, Orlando Petrucci, Cylen Javidan, Kevin Baszis, Shafkat Anwar

Open Access Publications

BACKGROUND: Cardiac tumors are uncommon in the pediatric population. When present, cardiac manifestations stem from the tumor causing inflow or outflow obstruction. While common in adults, cardiac myxomas presenting with generalized systemic illness or peripheral emboli especially with no cardiac or neurological symptoms are rare in children.

CASE PRESENTATION: We report a case of a previously healthy adolescent girl who presented with a 6-month history of constitutional symptoms and a purpuric rash with no cardiac or neurologic symptoms, found to have a cardiac myxoma.

CONCLUSIONS: A vasculopathic rash in the setting of atrial myxomas has been shown be a precursor …

Unilateral, 3d Arm Movement Kinematics Are Encoded In Ipsilateral Human Cortex, David T. Bundy, Nicholas Szrama, Mrinal Pahwa, Eric C. Leuthardt

Open Access Publications

There is increasing evidence that the hemisphere ipsilateral to a moving limb plays a role in planning and executing movements. However, the exact relationship between cortical activity and ipsilateral limb movements is uncertain. We sought to determine whether 3D arm movement kinematics (speed, velocity, and position) could be decoded from cortical signals recorded from the hemisphere ipsilateral to the moving limb. By having invasively monitored patients perform unilateral reaches with each arm, we also compared the encoding of contralateral and ipsilateral limb kinematics from a single cortical hemisphere. In four motor-intact human patients (three male, one female) implanted with electrocorticography …

A Rare Regulatory Variant In The Mef2d Gene Affects Gene Regulation And Splicing And Is Associated With A Sle Sub-Phenotype In Swedish Cohorts, Fabiana H G Farias, Et Al

Open Access Publications

Systemic lupus erythematosus (SLE) is an autoimmune disorder with heterogeneous clinical presentation and complex etiology involving the interplay between genetic, epigenetic, environmental and hormonal factors. Many common SNPs identified by genome wide-association studies (GWAS) explain only a small part of the disease heritability suggesting the contribution from rare genetic variants, undetectable in GWAS, and complex epistatic interactions. Using targeted re-sequencing of coding and conserved regulatory regions within and around 215 candidate genes selected on the basis of their known role in autoimmunity and genes associated with canine immune-mediated diseases, we identified a rare regulatory variant rs200395694:G > T located in intron …

Dysregulated Nk Cell Plcγ2 Signaling And Activity In Juvenile Dermatomyositis, Allison A Throm, Joshua B Alinger, Jeanette T Pingel, Allyssa L Daugherty, Lauren M Pachman, Anthony R French

Open Access Publications

Juvenile dermatomyositis (JDM) is a debilitating pediatric autoimmune disease manifesting with characteristic rash and muscle weakness. To delineate signaling abnormalities in JDM, mass cytometry was performed with PBMCs from treatment-naive JDM patients and controls. NK cell percentages were lower while frequencies of naive B cells and naive CD4+ T cells were higher in JDM patients than in controls. These cell frequency differences were attenuated with cessation of active disease. A large number of signaling differences were identified in treatment-naive JDM patients compared with controls. Classification models incorporating feature selection demonstrated that differences in phospholipase Cγ2 (PLCγ2) phosphorylation comprised 10 of …

A Web-Based Calculator For The Prediction Of Severe Neurodevelopmental Impairment In Preterm Infants Using Clinical And Imaging Characteristics, Zachary A Vesoulis, Nathalie M El Ters, Maja Herco, Halana V Whitehead, Amit M Mathur

Open Access Publications

Although the most common forms of brain injury in preterm infants have been associated with adverse neurodevelopmental outcomes, existing MRI scoring systems lack specificity, do not incorporate clinical factors, and are technically challenging to perform. The objective of this study was to develop a web-based, clinically-focused prediction system which differentiates severe neurodevelopmental outcomes from normal-moderate outcomes at two years. Infants were retrospectively identified as those who were born ≤30 weeks gestation and who had MRI imaging at term-equivalent age and neurodevelopmental testing at 18⁻24 months. Each MRI was scored on injury in three domains (intraventricular hemorrhage, white matter injury, and …

Novel Pleiotropic Risk Loci For Melanoma And Nevus Density Implicate Multiple Biological Pathways, David L Duffy, Gu Zhu, Xin Li, Marianna Sanna, Mark M Iles, Leonie C Jacobs, David M Evans, Seyhan Yazar, Jonathan Beesley, Matthew H Law, Peter Kraft, Alessia Visconti, John C Taylor, Fan Liu, Margaret J Wright, Anjali K Henders, Lisa Bowdler, Dan Glass, M Arfan Ikram, André G Uitterlinden, Pamela A Madden, Andrew C Heath, Elliot C Nelson, Adele C Green, Stephen Chanock, Jennifer H Barrett, Matthew A Brown, Nicholas K Hayward, Stuart Macgregor, Richard A Sturm, Alex W Hewitt, Manfred Kayser, David J Hunter, Julia A Newton Bishop, Timothy D Spector, Grant W Montgomery, David A Mackey, George Davey Smith, Tamar E Nijsten, D Timothy Bishop, Veronique Bataille, Mario Falchi, Jiali Han, Nicholas G Martin

Open Access Publications

No abstract provided.

Recurrent Acute Pancreatitis From A Displaced Ivc Filter, Natalie D. Cosgrove, Pavan K. Kavali, Daniel K. Mullady

Open Access Publications

No abstract provided.

Lymph Nodes Go With The Flow, Rafael S. Czepielewski, Gwendalyn J. Randolph

Open Access Publications

In this issue, Bovay et al. (https://doi.org/10.1084/jem.20180217) invoke a compelling model of interplay between the venous and lymphatic vasculature in regulating the developmental genesis and early expansion of LNs. This work supports an emerging model that lymph-venous crosstalk supports LN functionality at all stages.

Association Between Health Insurance Literacy And Avoidance Of Health Care Services Owing To Cost, Renuka Tipirneni, Mary C. Politi, Jeffrey T. Kullgren, Edith C. Kieffer, Susan D. Goold, Aaron M. Scherer

Open Access Publications

Importance: Navigating health insurance and health care choices requires considerable health insurance literacy. Although recommended preventive services are exempt from out-of-pocket costs under the Affordable Care Act, many people may remain unaware of this provision and its effect on their required payment. Little is known about the association between individuals' health insurance literacy and their use of preventive or nonpreventive health care services.

Objective: To assess the association between health insurance literacy and self-reported avoidance of health care services owing to cost.

Design, Setting, and Participants: In this survey study, a US national, geographically diverse, nonprobability sample of 506 US …

Dietary Protein Restriction Reduces Circulating Vldl Triglyceride Levels Via Crebh-Apoa5-Dependent And -Independent Mechanisms, J Humberto Treviño-Villarreal, Valeria Tosti, Nicola Veronese, Beatrice Bertozzi, Arnold D Bullock, Robert S Figenshau, Gerald L Andriole, Luigi Fontana, Et Al

Open Access Publications

Hypertriglyceridemia is an independent risk factor for cardiovascular disease. Dietary interventions based on protein restriction (PR) reduce circulating triglycerides (TGs), but underlying mechanisms and clinical relevance remain unclear. Here, we show that 1 week of a protein-free diet without enforced calorie restriction significantly lowered circulating TGs in both lean and diet-induced obese mice. Mechanistically, the TG-lowering effect of PR was due, in part, to changes in very low-density lipoprotein (VLDL) metabolism both in liver and peripheral tissues. In the periphery, PR stimulated VLDL-TG consumption by increasing VLDL-bound APOA5 expression and promoting VLDL-TG hydrolysis and clearance from circulation. The PR-mediated increase …

Changes In The Us Burden Of Chronic Kidney Disease From 2002 To 2016: An Analysis Of The Global Burden Of Disease Study, Benjamin Bowe, Yan Xie, Tingting Li, Ali H. Mokdad, Hong Xian, Yan Yan, Geetha Maddukuri, Ziyad Al-Aly

Open Access Publications

Introduction: Over the past 15 years, changes in demographic, social, and epidemiologic trends occurred in the United States. These changes likely contributed to changes in chronic kidney disease (CKD) epidemiology.

Objective: To describe the change in burden of CKD at the US state level from 2002 to 2016.

Design, Setting, and Participants: This systematic analysis used data and methodologies from the 2016 Global Burden of Disease study in the United States. Data on CKD from 2002 to 2016 were examined at the state level.

Main Outcomes and Measures: Disability-adjusted life years (DALYs) and death due to CKD.

Results: In this …

Trex1 Is Expressed By Microglia In Normal Human Brain And Increases In Regions Affected By Ischemia, Parul H Kothari, Grant R Kolar, Joanna C Jen, Rula Hajj-Ali, Paula Bertram, Robert E Schmidt, John P Atkinson

Open Access Publications

BACKGROUND: Mutations in the three-prime repair exonuclease 1 (TREX1) gene have been associated with neurological diseases, including Retinal Vasculopathy with Cerebral Leukoencephalopathy (RVCL). However, the endogenous expression of TREX1 in human brain has not been studied.

METHODS: We produced a rabbit polyclonal antibody (pAb) to TREX1 to characterize TREX1 by Western blotting (WB) of cell lysates from normal controls and subjects carrying an RVCL frame-shift mutation. Dual staining was performed to determine cell types expressing TREX1 in human brain tissue. TREX1 distribution in human brain was further evaluated by immunohistochemical analyses of formalin-fixed, paraffin-embedded samples from normal controls and patients …

Mouse Models Of Preterm Birth: Suggested Assessment And Reporting Guidelines, Ronald Mccarthy, Carmel Martin-Fairey, Dorothy K. Sojka, Erik D. Herzog, Emily S. Jungheim, Molly J. Stout, Justin C. Fay, Mala Mahendroo, Jeff Reese, Jennifer L. Herington, Erin J. Plosa, Elaine L. Shelton, Sarah K. England

Open Access Publications

Preterm birth affects approximately 1 out of every 10 births in the United States, leading to high rates of mortality and long-term negative health consequences. To investigate the mechanisms leading to preterm birth so as to develop prevention strategies, researchers have developed numerous mouse models of preterm birth. However, the lack of standard definitions for preterm birth in mice limits our field's ability to compare models and make inferences about preterm birth in humans. In this review, we discuss numerous mouse preterm birth models, propose guidelines for experiments and reporting, and suggest markers that can be used to assess whether …

Teenage Exercise Is Associated With Earlier Symptom Onset In Dysferlinopathy: A Retrospective Cohort Study, Ursula R Moore, Matthew Harms, Alan Pestronk, Et Al

Open Access Publications

No abstract provided.

Testing A Brief Web-Based Intervention To Increase Recognition Of Tobacco Constituents, Elizabeth G Klein, Amanda J Quisenberry, Abigail B Shoben, Tiffany Thomson, Susandi Htut, Randi E Foraker, Albert M Lai, Michael D Slater

Open Access Publications

Objective: We examined website formats to increase smokers' recognition of harmful and potentially harmful constituents (HPHCs) in cigarettes.

Methods: Adult, daily smokers (N = 279) were randomized to view a brief, single-page study website showing HPHC names and uses. The intervention site was tailored + interactive, labeled by cigarette brand/subbrand showing color imagery and pop-up boxes; the generic + static website (control) was unbranded in greyscale. Eye tracking equipment measured attention (dwell time) to precise website features. Linear regression analyses compared attention to HPHC descriptions and the correct recognition of 15 HPHC chemicals. A randomly selected sub-sample (N = 30) …

Glasdegib In Combination With Cytarabine And Daunorubicin In Patients With Aml Or High-Risk Mds: Phase 2 Study Results, Jorge E Cortes, Mark A Schroeder, Et Al

Open Access Publications

Glasdegib is a Hedgehog pathway inhibitor. This ongoing, open-label, phase 2 study (NCT01546038) evaluated glasdegib plus cytarabine/daunorubicin in patients with untreated acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (MDS). Patients received glasdegib 100 mg orally, once daily in continuous 28-day cycles from day -3, with intravenous cytarabine 100 mg/m

Adapting Crowdsourced Clinical Cancer Curation In Civic To The Clingen Minimum Variant Level Data Community-Driven Standards, Arpad M Danos, Alex H Wagner, Kilannin Krysiak, Erica K Barnell, Joshua F Mcmichael, Susanna Kiwala, Adam C Coffman, Lynzey Kujan, Malachi Griffith, Obi L Griffith, Et Al

Open Access Publications

Harmonization of cancer variant representation, efficient communication, and free distribution of clinical variant-associated knowledge are central problems that arise with increased usage of clinical next-generation sequencing. The Clinical Genome Resource (ClinGen) Somatic Working Group (WG) developed a minimal variant level data (MVLD) representation of cancer variants, and has an ongoing collaboration with Clinical Interpretations of Variants in Cancer (CIViC), an open-source platform supporting crowdsourced and expert-moderated cancer variant curation. Harmonization between MVLD and CIViC variant formats was assessed by formal field-by-field analysis. Adjustments to the CIViC format were made to harmonize with MVLD and support ClinGen Somatic WG curation activities, …

Eruption Of Solitary Reticulohistiocytoma After Intense Pulsed Light Burn, Elaine Otchere, Cynthia X Wang, Leigh A Compton, Zachary Nahmias

Open Access Publications

No abstract provided.