Digital Commons Network^™

Flortaucipir (Tau) Pet In Lgi1 Antibody Encephalitis, Gregory S Day, Brian A Gordon, Austin Mccullough, Robert C Bucelli, Richard J Perrin, Tammie L S Benzinger, Beau M Ances

Open Access Publications

The contributors to persistent cognitive impairment and hippocampal atrophy in leucine-rich glioma-inactivated 1 antibody encephalitis (LGI1) patients are unknown. We evaluated whether tau neuropathology measured with [

Evaluating Cognitive Relationships With Resting-State And Task-Driven Blood Oxygen Level-Dependent Variability, Peter R Millar, Beau M Ances, Brian A Gordon, Tammie L S Benzinger, John C Morris, David A Balota

Open Access Publications

Recent functional magnetic resonance imaging studies have reported that moment-to-moment variability in the blood oxygen level-dependent (BOLD) signal is positively associated with task performance and, thus, may reflect a behaviorally sensitive signal. However, it is not clear whether estimates of resting-state and task-driven BOLD variability are differentially related to cognition, as they may be driven by distinct sources of variance in the BOLD signal. Moreover, other studies have suggested that age differences in resting-state BOLD variability may be particularly sensitive to individual differences in cardiovascular, rather than neural, factors. In this study, we tested relationships between measures of behavioral task …

Global, Cell Non-Autonomous Gene Regulation Drives Individual Lifespan Among Isogenic C. Elegans, Holly E. Kinser, Matthew C. Mosley, Isaac B. Plutzer, Zachary Pincus

Open Access Publications

Across species, lifespan is highly variable among individuals within a population. Even genetically identical

Progress Towards Onchocerciasis Elimination In Côte D'Ivoire: A Geospatial Modelling Study, Obiora A. Eneanya, Benjamin G. Koudou, Meite Aboulaye, Aba Ange Elvis, Yeo Souleymane, Marie-Madeleine Kouakou, Gary J. Weil, Peter U. Fischer

Open Access Publications

BACKGROUND: Côte d'Ivoire has had 45 years of intervention for onchocerciasis by vector control (from 1975 to 1991), ivermectin mass drug administration (MDA) (from 1992 to 1994) and community directed treatment with ivermectin (CDTi) from 1995 to the present. We modeled onchocerciasis endemicity during two time periods that correspond to the scale up of vector control and ivermectin distribution, respectively. This analysis illustrates progress towards elimination during these periods, and it has identified potential hotspots areas that are at risk for ongoing transmission.

METHODS AND FINDINGS: The analysis used Ministry of Health skin snip microfilaria (MF) prevalence and intensity data …

Genomic Characterization Of Emerging Bacterial Uropathogen Neisseria Meningitidis, Which Was Misidentified As Neisseria Gonorrhoeae By Nucleic Acid Amplification Testing, Kimberley V Sukhum, Sophonie Jean, Meghan Wallace, Neil Anderson, C A Burnham, Gautam Dantas

Open Access Publications

No abstract provided.

Short-Term Effects Of Appropriate Empirical Antimicrobial Treatment With Ceftolozane/Tazobactam In A Swine Model Of Nosocomial Pneumonia, Ana Motos, Marin Kollef, Et Al

Open Access Publications

The rising frequency of multidrug-resistant and extensively drug-resistant (MDR/XDR) pathogens is making more frequent the inappropriate empirical antimicrobial therapy (IEAT) in nosocomial pneumonia, which is associated with increased mortality. We aim to determine the short-term benefits of appropriate empirical antimicrobial treatment (AEAT) with ceftolozane/tazobactam (C/T) compared with IEAT with piperacillin/tazobactam (TZP) in MDR

Naturalistic Language Input Is Associated With Resting-State Functional Connectivity In Infancy, Lucy S. King, M. Catalina Camacho, David F. Montez, Kathryn L. Humphreys, Ian H. Gotlib

Open Access Publications

The quantity and quality of the language input that infants receive from their caregivers affects their future language abilities; however, it is unclear how variation in this input relates to preverbal brain circuitry. The current study investigated the relation between naturalistic language input and the functional connectivity (FC) of language networks in human infancy using resting-state functional magnetic resonance imaging (rsfMRI). We recorded the naturalistic language environments of five- to eight-month-old male and female infants using the Linguistic ENvironment Analysis (LENA) system and measured the quantity and consistency of their exposure to adult words (AWs) and adult-infant conversational turns (CTs). …

Hypoxia Enhances Ilc3 Responses Through Hif-1Α-Dependent Mechanism, J L Fachi, L P Pral, J A C Dos Santos, A C Codo, S De Oliveira, J S Felipe, F F F Zambom, N O S Câmara, P M M M Vieira, M Colonna, M A R Vinolo

Open Access Publications

Group 3 innate lymphoid cells (ILC3) have a prominent role in the maintenance of intestine mucosa homeostasis. The hypoxia-inducible factor (HIF) is an important modulator of immune cell activation and a key mechanism for cellular adaptation to oxygen deprivation. However, its role on ILC3 is not well known. In this study, we investigated how a hypoxic environment modulates ILC3 response and the subsequent participation of HIF-1 signaling in this process. We found increased proliferation and activation of intestinal ILC3 at low oxygen levels, a response that was phenocopied when HIF-1α was chemically stabilized and was reversed when HIF-1 was blocked. …

Oct4 Cooperates With Distinct Atp-Dependent Chromatin Remodelers In Naïve And Primed Pluripotent States In Human, Xin Huang, Kyoung-Mi Park, Paul Gontarz, Bo Zhang, Laura A. Fischer, Chen Dong, Sabine Dietmann, Xiaoyun Xing, Shafqat A. Khan, Nick Jensen, Ting Wang, Thorold W. Theunissen, Et Al

Open Access Publications

No abstract provided.

Effect And Correction Of Optode Coupling Errors In Breast Imaging Using Diffuse Optical Tomography, Shuying Li, Kexin Huang, Menghao Zhang, K. M. Shihab Uddin, Quing Zhu

Open Access Publications

No abstract provided.

Optimal Method For Fetal Brain Age Prediction Using Multiplanar Slices From Structural Magnetic Resonance Imaging, Jinwoo Hong, Hyuk Jin Yun, Gilsoon Park, Seonggyu Kim, Yangming Ou, Lana Vasung, Caitlin K Rollins, Cynthia M Ortinau, Emiko Takeoka, Shizuko Akiyama, Tomo Tarui, Judy A Estroff, Patricia Ellen Grant, Jong-Min Lee, Kiho Im

Open Access Publications

The accurate prediction of fetal brain age using magnetic resonance imaging (MRI) may contribute to the identification of brain abnormalities and the risk of adverse developmental outcomes. This study aimed to propose a method for predicting fetal brain age using MRIs from 220 healthy fetuses between 15.9 and 38.7 weeks of gestational age (GA). We built a 2D single-channel convolutional neural network (CNN) with multiplanar MRI slices in different orthogonal planes without correction for interslice motion. In each fetus, multiple age predictions from different slices were generated, and the brain age was obtained using the mode that determined the most …

Association Of Pet-Based Estradiol-Challenge Test For Breast Cancer Progesterone Receptors With Response To Endocrine Therapy, Farrokh Dehdashti, Ningying Wu, Cynthia X. Ma, Michael J. Naughton, John A. Katzenellenbogen, Barry A. Siegel

Open Access Publications

No abstract provided.

Parental Factors Associated With The Decision To Participate In A Neonatal Clinical Trial, Elliott Mark Weiss, Rakesh Rao, Et Al

Open Access Publications

Importance: It remains poorly understood how parents decide whether to enroll a child in a neonatal clinical trial. This is particularly true for parents from racial or ethnic minority populations. Understanding factors associated with enrollment decisions may improve recruitment processes for families, increase enrollment rates, and decrease disparities in research participation.

Objective: To assess differences in parental factors between parents who enrolled their infant and those who declined enrollment for a neonatal randomized clinical trial.

Design, Setting, and Participants: This survey study conducted from July 2017 to October 2019 in 12 US level 3 and 4 neonatal intensive care units …

Mechanical Overstimulation Causes Acute Injury And Synapse Loss Followed By Fast Recovery In Lateral-Line Neuromasts Of Larval Zebrafish, Melanie Holmgren, Michael E. Ravicz, Kenneth E. Hancock, Olga Strelkova, Dorina Kallogjeri, Artur A. Indzhykulian, Mark E. Warchol, Lavinia Sheets

Open Access Publications

Excess noise damages sensory hair cells, resulting in loss of synaptic connections with auditory nerves and, in some cases, hair-cell death. The cellular mechanisms underlying mechanically induced hair-cell damage and subsequent repair are not completely understood. Hair cells in neuromasts of larval zebrafish are structurally and functionally comparable to mammalian hair cells but undergo robust regeneration following ototoxic damage. We therefore developed a model for mechanically induced hair-cell damage in this highly tractable system. Free swimming larvae exposed to strong water wave stimulus for 2 hr displayed mechanical injury to neuromasts, including afferent neurite retraction, damaged hair bundles, and reduced …

Tissue Biodistribution And Tumor Targeting Of Near-Infrared Labelled Anti-Cd38 Antibody-Drug Conjugate In Preclinical Multiple Myeloma, Nicholas Cho, Sooah Ko, Monica Shokeen

Open Access Publications

Daratumumab (DARA) is an FDA-approved high-affinity monoclonal antibody targeting CD38 that has shown promising therapeutic efficacy in double refractory multiple myeloma (MM) patients. Despite the well-established clinical efficacy of DARA, not all heavily pretreated patients respond to single-agent DARA, and the majority of patients who initially respond eventually progress. Antibody-drug conjugates (ADCs) combine the highly targeted tumor antigen recognition of antibodies with the cell killing properties of chemotherapy for effective internalization and processing of the drug. In this study, we evaluated the anti-tumor efficacy of DARA conjugated to the maytansine derivative, mertansine (DM1), linked via a non-cleavable bifunctional linker. The …

Deep Learning Segmentation Of Triple-Negative Breast Cancer (Tnbc) Patient Derived Tumor Xenograft (Pdx) And Sensitivity Of Radiomic Pipeline To Tumor Probability Boundary, Kaushik Dutta, Sudipta Roy, Timothy Daniel Whitehead, Jingqin Luo, Abhinav Kumar Jha, Shunqiang Li, James Dennis Quirk, Kooresh Isaac Shoghi

Open Access Publications

Preclinical magnetic resonance imaging (MRI) is a critical component in a co-clinical research pipeline. Importantly, segmentation of tumors in MRI is a necessary step in tumor phenotyping and assessment of response to therapy. However, manual segmentation is time-intensive and suffers from inter- and intra- observer variability and lack of reproducibility. This study aimed to develop an automated pipeline for accurate localization and delineation of TNBC PDX tumors from preclinical T1w and T2w MR images using a deep learning (DL) algorithm and to assess the sensitivity of radiomic features to tumor boundaries. We tested five network architectures including U-Net, dense U-Net, …

Phentolamine Mesylate Ophthalmic Solution Provides Lasting Pupil Modulation And Improves Near Visual Acuity In Presbyopic Glaucoma Patients In A Randomized Phase 2b Clinical Trial, Jay S Pepose, Et Al

Open Access Publications

Purpose: Phentolamine mesylate ophthalmic solution (PMOS), applied to the eye topically, was shown previously to have beneficial effects in patients with dim light vision disturbances (DLD), including decreased pupil diameter (PD), improved best-corrected distance visual acuity (BCDVA), as well as lower intraocular pressure (IOP). The ORION-1 trial evaluated the long-term safety and efficacy of PMOS in a glaucomatous, presbyopic population.

Patients and Methods: In this randomized, double-masked, multi-center, placebo-controlled, multiple-dose Phase 2b trial, 39 patients with elevated IOP were randomized to receive one evening dose of study medication or placebo for 14 days. The primary outcome measure was mean change …

Dynamics Of Oddball Sound Processing: Trial-By-Trial Modeling Of Ecog Signals, Françoise Lecaignard, Raphaëlle Bertrand, Peter Brunner, Anne Caclin, Gerwin Schalk, Jérémie Mattout

Open Access Publications

Recent computational models of perception conceptualize auditory oddball responses as signatures of a (Bayesian) learning process, in line with the influential view of the mismatch negativity (MMN) as a prediction error signal. Novel MMN experimental paradigms have put an emphasis on neurophysiological effects of manipulating regularity and predictability in sound sequences. This raises the question of the contextual adaptation of the learning process itself, which on the computational side speaks to the mechanisms of gain-modulated (or precision-weighted) prediction error. In this study using electrocorticographic (ECoG) signals, we manipulated the predictability of oddball sound sequences with two objectives: (i) Uncovering the …

An International Virtual Hackathon To Build Tools For The Analysis Of Structural Variants Within Species Ranging From Coronaviruses To Vertebrates [Version 2; Peer Review: 1 Approved, 3 Approved With Reservations], Ann M. Mccartney, Daniel Paiva Agustinho, Et Al

Open Access Publications

No abstract provided.

Air Pollution Particulate Matter Amplifies White Matter Vascular Pathology And Demyelination Caused By Hypoperfusion, Mikko T Huuskonen, Qinghai Liu, Krista Lamorie-Foote, Kristina Shkirkova, Michelle Connor, Arati Patel, Axel Montagne, Hans Baertsch, Constantinos Sioutas, Todd E Morgan, Caleb E Finch, Berislav V Zlokovic, William J Mack

Open Access Publications

Cerebrovascular pathologies are commonly associated with dementia. Because air pollution increases arterial disease in humans and rodent models, we hypothesized that air pollution would also contribute to brain vascular dysfunction. We examined the effects of exposing mice to nanoparticulate matter (nPM; aerodynamic diameter ≤200 nm) from urban traffic and interactions with cerebral hypoperfusion. C57BL/6 mice were exposed to filtered air or nPM with and without bilateral carotid artery stenosis (BCAS) and analyzed by multiparametric MRI and histochemistry. Exposure to nPM alone did not alter regional cerebral blood flow (CBF) or blood brain barrier (BBB) integrity. However, nPM worsened the white …

Metavariables Resuming Host Immune Features And Nodal Involvement Are Associated With Oncological Outcomes In Oral Cavity Squamous Cell Carcinoma, Francesco Missale, Mattia Bugatti, Davide Mattavelli, Silvia Lonardi, Davide Lombardi, Piero Nicolai, Cesare Piazza, Simonetta Battocchio, Anna Maria Bozzola, Stefano Calza, William Vermi

Open Access Publications

Oral cavity squamous cell carcinoma (OSCC) is a common head and neck cancer characterized by a poor prognosis associated with locoregional or distant failure. Among the predictors of prognosis, a dense infiltration of adaptive immune cells is protective and associated with improved clinical outcomes. However, few tools are available to integrate immune contexture variables into clinical settings. By using digital microscopy analysis of a large retrospective OSCC cohort (n = 182), we explored the clinical significance of tumor-infiltrating CD8

Pharmacokinetics Of Single Domain Antibodies And Conjugated Nanoparticles Using A Hybrid Near Infrared Method, Shiran Su, Thomas J Esparza, Duong Nguyen, Simone Mastrogiacomo, Joong H Kim, David L Brody

Open Access Publications

Iron oxide nanoparticles and single domain antibodies from camelids (VHHs) have been increasingly recognized for their potential uses for medical diagnosis and treatment. However, there have been relatively few detailed characterizations of their pharmacokinetics (PK). The aim of this study was to develop imaging methods and pharmacokinetic models to aid the future development of a novel family of brain MRI molecular contrast agents. An efficient near-infrared (NIR) imaging method was established to monitor VHH and VHH conjugated nanoparticle kinetics in mice using a hybrid approach: kinetics in blood were assessed by direct sampling, and kinetics in kidney, liver, and brain …

Glucose-Mediated De Novo Lipogenesis In Photoreceptors Drives Early Diabetic Retinopathy, Rithwick Rajagopal, Beau Sylvester, Sheng Zhang, Sangeeta Adak, Xiaochao Wei, Megan Bowers, Sebastian Jessberger, Fong-Fu Hsu, Clay F. Semenkovich

Open Access Publications

No abstract provided.

The Risks Of Stone Diagnosis And Stone Removal Procedure After Different Bariatric Surgeries, Steven M. Monda, Joel M. Vetter, Margaret A. Olsen, Matthew R. Keller, J. Christopher Eagon, Michael S. Chevinsky, Vasian Markollari, Ramakrishna Venkatesh, Alana C. Desai

Open Access Publications

No abstract provided.

Local Field Potentials In The Parietal Reach Region Reveal Mechanisms Of Bimanual Coordination, Eric Mooshagian, Charles D. Holmes, Lawrence H. Snyder

Open Access Publications

No abstract provided.

Unexpected Role Of Sterol Synthesis In Rna Stability And Translation In Leishmania, Zemfira N Karamysheva, Samrat Moitra, Andrea Perez, Sumit Mukherjee, Elena B Tikhonova, Andrey L Karamyshev, Kai Zhang

Open Access Publications

No abstract provided.

Development And External Validation Of Deep-Learning-Based Tumor Grading Models In Soft-Tissue Sarcoma Patients Using Mr Imaging, Fernando Navarro, Matthew B Spraker, Et Al

Open Access Publications

BACKGROUND: In patients with soft-tissue sarcomas, tumor grading constitutes a decisive factor to determine the best treatment decision. Tumor grading is obtained by pathological work-up after focal biopsies. Deep learning (DL)-based imaging analysis may pose an alternative way to characterize STS tissue. In this work, we sought to non-invasively differentiate tumor grading into low-grade (G1) and high-grade (G2/G3) STS using DL techniques based on MR-imaging.

METHODS: Contrast-enhanced T1-weighted fat-saturated (T1FSGd) MRI sequences and fat-saturated T2-weighted (T2FS) sequences were collected from two independent retrospective cohorts (training: 148 patients, testing: 158 patients). Tumor grading was determined following the French Federation of Cancer …

Engaging Caregivers And Providers Of Children With Sickle Cell Anemia In Shared Decision Making For Hydroxyurea: Protocol For A Multicenter Randomized Controlled Trial, Anna M Hood, Allison A King, Cecelia Calhoun, Et Al

Open Access Publications

BACKGROUND: Sickle cell anemia (SCA) is a genetic blood disorder that puts children at a risk of serious medical complications, early morbidity and mortality, and high health care utilization. Until recently, hydroxyurea was the only disease-modifying treatment for this life-threatening disease and has remained the only option for children younger than 5 years. Evidence-based guidelines recommend using a shared decision-making (SDM) approach for offering hydroxyurea to children with SCA (HbSS or HbS/β0 thalassemia) aged as early as 9 months. However, the uptake remains suboptimal, likely because caregivers lack information about hydroxyurea and have concerns about its safety and potential long-term …

Development And Validation Of A Multivariable Prediction Model For Missed Hiv Health Care Provider Visits In A Large Us Clinical Cohort, April C. Pettit, Aihua Bian, Cassandra O. Schember, Peter F. Rebeiro, Jeanne C. Keruly, Kenneth H. Mayer, W. Christopher Mathews, Richard D. Moore, Heidi M. Crane, Elvin Geng, Sonia Napravnik, Bryan E. Shepherd, Michael J. Mugavero

Open Access Publications

Background: Identifying individuals at high risk of missing HIV care provider visits could support proactive intervention. Previous prediction models for missed visits have not incorporated data beyond the individual level.

Methods: We developed prediction models for missed visits among people with HIV (PWH) with ≥1 follow-up visit in the Center for AIDS Research Network of Integrated Clinical Systems from 2010 to 2016. Individual-level (medical record data and patient-reported outcomes), community-level (American Community Survey), HIV care site-level (standardized clinic leadership survey), and structural-level (HIV criminalization laws, Medicaid expansion, and state AIDS Drug Assistance Program budget) predictors were included. Models were developed …

Cd16+Cd163+ Monocytes Traffic To Sites Of Inflammation During Necrotizing Enterocolitis In Premature Infants, Oluwabunmi O. Olaloye, Misty Good, Et Al

Open Access Publications

Necrotizing enterocolitis (NEC) is a severe gastrointestinal complication of prematurity. Using suspension and imaging mass cytometry coupled with single-cell RNA sequencing, we demonstrate severe inflammation in patients with NEC. NEC mucosa could be subtyped by an influx of three distinct neutrophil phenotypes (immature, newly emigrated, and aged). Furthermore, CD16+CD163+ monocytes/Mϕ, correlated with newly emigrated neutrophils, were specifically enriched in NEC mucosa, found adjacent to the blood vessels, and increased in circulation of infants with surgical NEC, suggesting trafficking from the periphery to areas of inflammation. NEC-specific monocytes/Mϕ transcribed inflammatory genes, including TREM1, IL1A, IL1B, and calprotectin, and neutrophil recruitment genes …