Digital Commons Network^™

Mild Chronic Perturbation Of Inhibition Severely Alters Hippocampal Function, Min-Yu Sun, Luke Ziolkowski, Peter Lambert, Hong-Jin Shu, Micah Keiser, Nicholas Rensing, Natasha Warikoo, Monika Martinek, Carson Platnick, Ann Benz, John Bracamontes, Gustav Akk, Joe Henry Steinbach, Charles F. Zorumski, Michael Wong, Steven Mennerick

Open Access Publications

No abstract provided.

An Overview Of Mechanical Circulatory Support In Single-Ventricle Patients, Jacob R Miller, Timothy S Lancaster, Connor Callahan, Aaron M Abarbanell, Pirooz Eghtesady

Open Access Publications

The population of people with a single-ventricle is continually increasing due to improvements across the spectrum of medical care. Unfortunately, a proportion of these patients will develop heart failure. Often, for these patients, mechanical circulatory support (MCS) represents the only available treatment option. While single-ventricle patients currently represent a small proportion of the total number of patients who receive MCS, as the single-ventricle patient population increases, this number will increase as well. Outcomes for these complex single-ventricle patients who require MCS has begun to be evaluated. When considering the entire population, survival to hospital discharge is 30-50%, though this must …

Insulin-Independent Reversal Of Type-1 Diabetes Following Transplantation Of Adult Brown Adipose Tissue Supplemented With Igf-1, Subhadra C. Gunawardana, David W. Piston

Open Access Publications

No abstract provided.

Graft Immaturity And Safety Concerns In Transplanted Human Kidney Organoids, Sun Ah Nam, Kohei Uchimura, Benjamin D. Humphreys, Et Al.

Open Access Publications

No abstract provided.

Multi-Ancestry Sleep-By-Snp Interaction Analysis In 126,926 Individuals Reveals Lipid Loci Stratified By Sleep Duration, Raymond Noordam, Yun Ju Sung, Karen Schwander, Lisa De Las Fuentes, Treva K. Rice, Dabeeru C. Rao, Mary Feitosa, Aldi Kraja, Mike Province, Et Al.

Open Access Publications

No abstract provided.

A Neural Network For Information Seeking, J. Kael White, Ethan S. Bromberg-Martin, Sarah R. Heilbronner, Kaining Zhang, Julia Pai, Suzanne N. Haber, Ilya E. Monosov

Open Access Publications

No abstract provided.

A Regulatory Variant Of Chrm3 Is Associated With Cannabis-Induced Hallucinations In European Americans, Zhongshan Cheng, Chureerat Phokaew, Yi-Ling Chou, Dongbing Lai, Jacquelyn L. Meyers, Arpana Agrawal, Lindsay A. Farrer, Henry R. Kranzler, Joel Gelernter

Open Access Publications

No abstract provided.

Allogeneic Transplantation In Elderly Patients ≥65 Years With Non-Hodgkin Lymphoma: A Time-Trend Analysis, Nirav N. Shah, Ravi Vij, Et Al.

Open Access Publications

No abstract provided.

A Review Of The Immunomodulating Components Of Maternal Breast Milk And Protection Against Necrotizing Enterocolitis, Lila S Nolan, Olivia B Parks, Misty Good

Open Access Publications

Breast milk contains immunomodulating components that are beneficial to newborns during maturation of their immune system. Human breast milk composition is influenced by an infant's gestational and chronological age, lactation stage, and the mother and infant's health status. Major immunologic components in human milk, such as secretory immunoglobulin A (IgA) and growth factors, have a known role in regulating gut barrier integrity and microbial colonization, which therefore protect against the development of a life-threatening gastrointestinal illness affecting newborn infants called necrotizing enterocolitis (NEC). Breast milk is a known protective factor in the prevention of NEC when compared with feeding with …

Trpv1 Activity And Substance P Release Are Required For Corneal Cold Nociception, Fengxian Li, Weishan Yang, Haowu Jiang, Changxiong Guo, Andrew J.W. Huang, Hongzhen Hu, Qin Liu

Open Access Publications

No abstract provided.

Report From A Multidisciplinary Meeting On Anxiety As A Non-Motor Manifestation Of Parkinson’S Disease, Gregory M. Pontone, Eric J. Lenze, Et Al.

Open Access Publications

No abstract provided.

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

Open Access Publications

No abstract provided.

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 …

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 …

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 …

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)." …

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 …

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 …

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.

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 …

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 …

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 …

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

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) …

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 …

Genome-Wide Association Study Of Brain Amyloid Deposition As Measured By Pittsburgh Compound-B (Pib)-Pet Imaging, Qi Yan, Jorge L Del-Aguila, Carlos Cruchaga, Et Al

Open Access Publications

Deposition of amyloid plaques in the brain is one of the two main pathological hallmarks of Alzheimer's disease (AD). Amyloid positron emission tomography (PET) is a neuroimaging tool that selectively detects in vivo amyloid deposition in the brain and is a reliable endophenotype for AD that complements cerebrospinal fluid biomarkers with regional information. We measured in vivo amyloid deposition in the brains of ~1000 subjects from three collaborative AD centers and ADNI using

A Novel Mode Of Capping Protein-Regulation By Twinfilin, Adam B. Johnston, Denise M. Hilton, Patrick Mcconnell, Britney Johnson, Meghan T. Harris, Avital Simone, Gaya K. Amarasinghe, John A. Cooper, Bruce L. Goode

Open Access Publications

Cellular actin assembly is controlled at the barbed ends of actin filaments, where capping protein (CP) limits polymerization. Twinfilin is a conserved in vivo binding partner of CP, yet the significance of this interaction has remained a mystery. Here, we discover that the C-terminal tail of Twinfilin harbors a CP-interacting (CPI) motif, identifying it as a novel CPI-motif protein. Twinfilin and the CPI-motif protein CARMIL have overlapping binding sites on CP. Further, Twinfilin binds competitively with CARMIL to CP, protecting CP from barbed-end displacement by CARMIL. Twinfilin also accelerates dissociation of the CP inhibitor V-1, restoring CP to an active …

Simulation Of Spontaneous G Protein Activation Reveals A New Intermediate Driving Gdp Unbinding, Xianqiang Sun, Sukrit Singh, Kendall J. Blumer, Gregory R. Bowman

Open Access Publications

Activation of heterotrimeric G proteins is a key step in many signaling cascades. However, a complete mechanism for this process, which requires allosteric communication between binding sites that are ~30 Å apart, remains elusive. We construct an atomically detailed model of G protein activation by combining three powerful computational methods: metadynamics, Markov state models (MSMs), and CARDS analysis of correlated motions. We uncover a mechanism that is consistent with a wide variety of structural and biochemical data. Surprisingly, the rate-limiting step for GDP release correlates with tilting rather than translation of the GPCR-binding helix 5. β-Strands 1 - 3 and …