Digital Commons Network^™

System-Dependent Image Distortion Related To Gantry Positions Of A 0.35 T Mrgrt: Characterization And The Corresponding Correction, Shanti Marasini, Benjamin Quinn, Mike Cole, Rocco Flores, Taeho Kim

2020-Current year OA Pubs

PURPOSE: MR-guided radiotherapy with high accuracy treatment planning requires addressing MR imaging artifacts that originate from system imperfections. This work presents the characterization and corresponding correction of gantry-related imaging distortions including geometric distortion and isocenter shift in a 0.35 T magnetic resonance imaging (MRI)-guided radiotherapy (MRgRT) system using distortion vector fields (DVFs).

METHODS: Two phantoms, the magnetic resonance imaging distortion in 3D (MRID

RESULTS: Geometric distortion with "mean (± SD) distortion" of 3.2 ± 0.02, 2.9 ± 0.02, and 1.8 ± 0.01 mm and isocenter shift (±SD) of 0.49 ± 0.3, 0.05 ± 0.2, and 0.01 ± 0.03 mm were …

Associations Of Snfl With Clinico-Radiological Measures In A Large Ms Population, Elias S Sotirchos, Robert T Naismith, Min Qiao, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Evaluation of serum neurofilament light chain (sNfL), measured using high-throughput assays on widely accessible platforms in large, real-world MS populations, is a critical step for sNfL to be utilized in clinical practice.

METHODS: Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) is a network of healthcare institutions in the United States and Europe collecting standardized clinical/imaging data and biospecimens during routine clinic visits. sNfL was measured in 6974 MS and 201 healthy control (HC) participants, using a high-throughput, scalable immunoassay.

RESULTS: Elevated sNfL levels for age (sNfL-E) were found in 1238 MS participants (17.8%). Factors associated with …

Sting Suppresses Mitochondrial Vdac2 To Govern Rcc Growth Independent Of Innate Immunity, Zhichuan Zhu, Xin Zhou, Hongwei Du, Erica W Cloer, Jiaming Zhang, Liu Mei, Ying Wang, Xianming Tan, Austin J Hepperla, Jeremy M Simon, Jeanette Gowen Cook, Michael B Major, Gianpietro Dotti, Pengda Liu

2020-Current year OA Pubs

STING is an innate immune sensor for immune surveillance of viral/bacterial infection and maintenance of an immune-friendly microenvironment to prevent tumorigenesis. However, if and how STING exerts innate immunity-independent function remains elusive. Here, the authors report that STING expression is increased in renal cell carcinoma (RCC) patients and governs tumor growth through non-canonical innate immune signaling involving mitochondrial ROS maintenance and calcium homeostasis. Mitochondrial voltage-dependent anion channel VDAC2 is identified as a new STING binding partner. STING depletion potentiates VDAC2/GRP75-mediated MERC (mitochondria-ER contact) formation to increase mitochondrial ROS/calcium levels, impairs mitochondria function, and suppresses mTORC1/S6K signaling leading to RCC growth …

Computerized Electrocardiogram Data Transformation Enables Effective Algorithmic Differentiation Of Wide Qrs Complex Tachycardias, Anthony H Kashou, Sarah Lococo, Preet A Shaikh, Bhavesh B Katbamna, Ojasav Sehrawat, Daniel H Cooper, Sandeep S Sodhi, Phillip S Cuculich, Marye J Gleva, Elena Deych, Ruiwen Zhou, Lei Liu, Abhishek J Deshmukh, Samuel J Asirvatham, Peter A Noseworthy, Christopher V Desimone, Adam M May

2020-Current year OA Pubs

BACKGROUND: Accurate automated wide QRS complex tachycardia (WCT) differentiation into ventricular tachycardia (VT) and supraventricular wide complex tachycardia (SWCT) can be accomplished using calculations derived from computerized electrocardiogram (ECG) data of paired WCT and baseline ECGs.

OBJECTIVE: Develop and trial novel WCT differentiation approaches for patients with and without a corresponding baseline ECG.

METHODS: We developed and trialed WCT differentiation models comprised of novel and previously described parameters derived from WCT and baseline ECG data. In Part 1, a derivation cohort was used to evaluate five different classification models: logistic regression (LR), artificial neural network (ANN), Random Forests [RF], support …

Quality Improvements In Radiation Oncology Clinical Trials, Koren Smith, Jeff Michalski, Et Al.

2020-Current year OA Pubs

Clinical trials have become the primary mechanism to validate process improvements in oncology clinical practice. Over the past two decades there have been considerable process improvements in the practice of radiation oncology within the structure of a modern department using advanced technology for patient care. Treatment planning is accomplished with volume definition including fusion of multiple series of diagnostic images into volumetric planning studies to optimize the definition of tumor and define the relationship of tumor to normal tissue. Daily treatment is validated by multiple tools of image guidance. Computer planning has been optimized and supported by the increasing use …

From Perception To Behavior: The Neural Circuits Underlying Prey Hunting In Larval Zebrafish, Shuyu I Zhu, Geoffrey J Goodhill

2020-Current year OA Pubs

A key challenge for neural systems is to extract relevant information from the environment and make appropriate behavioral responses. The larval zebrafish offers an exciting opportunity for studying these sensing processes and sensory-motor transformations. Prey hunting is an instinctual behavior of zebrafish that requires the brain to extract and combine different attributes of the sensory input and form appropriate motor outputs. Due to its small size and transparency the larval zebrafish brain allows optical recording of whole-brain activity to reveal the neural mechanisms involved in prey hunting and capture. In this review we discuss how the larval zebrafish brain processes …

Histopathological Evaluation Of Onchocerca Volvulus Nodules By Microscopy And By Digital Image Analysis For The Study Of Macrofilaricidal Drug Efficacy, Kerstin Fischer, Bettina Dubben, Linda B Debrah, Janina M Kuehlwein, Arcangelo Ricchiuto, Alexander Y Debrah, Achim Hoerauf, Gary J Weil, Peter U Fischer, Ute Klarmann-Schulz

2020-Current year OA Pubs

BACKGROUND: Novel drugs or drug combinations that kill or permanently sterilize adult

MATERIAL AND METHODS: Two expert microscopists independently assessed 605 nodules by direct microscopy. At least two sections with two different stains hematoxylin & eosin (H&E, APR immunostain) of paraffin-embedded, ethanol-fixed whole-nodule cross-sections were analyzed. After variables were identified prone to observer discrepancies, we performed a second study to compare consolidated results for 100 nodules obtained by the two readers by microscopy and by analysis of scanned, high resolution digital images (20x magnification). The last data set analyzed was a quality panel of 100 nodules that has been previously …

Health Disparities In Aging: Improving Dementia Care For Black Women, Caleigh A Findley, Makayla F Cox, Adam B Lipson, Ratasha Bradley, Kevin N Hascup, Carla Yuede, Erin R Hascup

2020-Current year OA Pubs

In the United States, 80% of surveyed Black patients report experiencing barriers to healthcare for Alzheimer's disease and related dementias (ADRD), delaying the time-sensitive treatment of a progressive neurodegenerative disease. According to the National Institute on Aging, Black study participants are 35% less likely to be given a diagnosis of ADRD than white participants, despite being twice as likely to suffer from ADRD than their white counterparts. Prior analysis of prevalence for sex, race, and ethnicity by the Centers for Disease Control indicated the highest incidence of ADRD in Black women. Older (≥65 years) Black women are at a disproportionately …

The Plasma Virome In Longitudinal Samples From Pregnant Patients, Molly J Stout, Anoop K Brar, Brandi N Herter, Ananda Rankin, Kristine M Wylie

2020-Current year OA Pubs

INTRODUCTION: Nucleic acid from viruses is common in peripheral blood, even in asymptomatic individuals. How physiologic changes of pregnancy impact host-virus dynamics for acute, chronic, and latent viral infections is not well described. Previously we found higher viral diversity in the vagina during pregnancy associated with preterm birth (PTB) and Black race. We hypothesized that higher diversity and viral copy numbers in the plasma would show similar trends.

METHODS: To test this hypothesis, we evaluated longitudinally collected plasma samples from 23 pregnant patients (11 term and 12 preterm) using metagenomic sequencing with ViroCap enrichment to enhance virus detection. Sequence data …

Conserved Gene Signatures Shared Among Mapt Mutations Reveal Defects In Calcium Signaling, Miguel A Minaya, Sidhartha Mahali, Abhirami K Iyer, Abdallah M Eteleeb, Rita Martinez, Guangming Huang, John Budde, Sally Temple, Alissa L Nana, William W Seeley, Salvatore Spina, Lea T Grinberg, Oscar Harari, Celeste M Karch

2020-Current year OA Pubs

No abstract provided.

Interactions Of Pathogenic Escherichia Coli With Ceacams, Alaullah Sheikh, James M Fleckenstein

2020-Current year OA Pubs

The pathogenic

3′-Sulfated Lewisa/C: An Oncofetal Epitope Associated With Metaplastic And Oncogenic Plasticity Of The Gastrointestinal Foregut, Koushik K Das, Jeffrey W Brown

2020-Current year OA Pubs

Metaplasia, dysplasia, and cancer arise from normal epithelia

Exploring The Villalta Scale To Capture Postthrombotic Syndrome Using Alternative Approaches: A Subanalysis Of The Attract Trial, Cristina T Pop, Chu-Shu Gu, Suresh Vedantham, Jean-Philippe Galanaud, Susan R Kahn

2020-Current year OA Pubs

BACKGROUND: Clinical trials that evaluated interventions to prevent postthrombotic syndrome (PTS) used the Villalta scale (VS) to define PTS, but there is a lack of consistency in its use.

OBJECTIVES: This study aimed to improve the ability to identify patients with clinically meaningful PTS after DVT in participants of the ATTRACT trial.

METHODS: We conducted a post hoc exploratory analysis of 691 patients from the ATTRACT study, a randomized trial evaluating the effectiveness of pharmacomechanical thrombolysis to prevent PTS in proximal deep vein thrombosis. We compared 8 VS approaches to classify patients with or without PTS in terms of their …

A Practitioner's Guide To Geospatial Analysis In A Neuroimaging Context, Julie K Wisch, Ganesh M Babulal, Kalen Petersen, Peter R Millar, Enbal Shacham, Stephen Scroggins, Anna H Boerwinkle, Shaney Flores, Sarah Keefe, Brian A Gordon, John C Morris, Beau M Ances

2020-Current year OA Pubs

INTRODUCTION: Health disparities arise from biological-environmental interactions. Neuroimaging cohorts are reaching sufficiently large sample sizes such that analyses could evaluate how the environment affects the brain. We present a practical guide for applying geospatial methods to a neuroimaging cohort.

METHODS: We estimated brain age gap (BAG) from structural magnetic resonance imaging (MRI) from 239 city-dwelling participants in St. Louis, Missouri. We compared these participants to population-level estimates from the American Community Survey (ACS). We used geospatial analysis to identify neighborhoods associated with patterns of altered brain structure. We also evaluated the relationship between Area Deprivation Index (ADI) and BAG.

RESULTS: …

Predicting Continuous Amyloid Pet Values With Csf And Plasma Aβ42/Aβ40, Julie K Wisch, Brian A Gordon, Anna H Boerwinkle, Patrick H Luckett, James G Bollinger, Vitaliy Ovod, Yan Li, Rachel L Henson, Tim West, Mathew R Meyer, Kristopher M Kirmess, Tammie L S Benzinger, Anne M Fagan, John C Morris, Randall J Bateman, Beau M Ances, Suzanne E Schindler

2020-Current year OA Pubs

INTRODUCTION: Continuous measures of amyloid burden as measured by positron emission tomography (PET) are being used increasingly to stage Alzheimer's disease (AD). This study examined whether cerebrospinal fluid (CSF) and plasma amyloid beta (Aβ)42/Aβ40 could predict continuous values for amyloid PET.

METHODS: CSF Aβ42 and Aβ40 were measured with automated immunoassays. Plasma Aβ42 and Aβ40 were measured with an immunoprecipitation-mass spectrometry assay. Amyloid PET was performed with Pittsburgh compound B (PiB). The continuous relationships of CSF and plasma Aβ42/Aβ40 with amyloid PET burden were modeled.

RESULTS: Most participants were cognitively normal (427 of 491 [87%]) and the mean age was …

The Pace Of Biological Aging Helps Explain The Association Between Insomnia And Chronic Low Back Pain, Edwin N Aroke, Asia M Wiggins, Joanna M Hobson, Vinodh Srinivasasainagendra, Tammie L Quinn, Pooja Kottae, Hemant K Tiwari, Robert E Sorge, Burel R Goodin

2020-Current year OA Pubs

Chronic low back pain (cLBP) is associated with insomnia and advanced age. Emerging evidence suggests that the severity of both sleep disorders (like insomnia) and chronic pain are associated with a faster pace of biological aging. We aimed to determine whether the pace of biological age mediates the relationship between insomnia and the impact of cLBP in a sample of community-dwelling adults ages 19 to 85 years. Participants (49 with no pain, 32 with low-impact pain, and 37 with high-impact pain) completed sociodemographic, pain, insomnia, and short physical performance battery assessments. We calculated the pace of biological aging using DunedinPACE …

Predicting Incident Cardiovascular Disease Among African-American Adults: A Deep Learning Approach To Evaluate Social Determinants Of Health In The Jackson Heart Study, Matthew C. Morris, Hamidreza Moradi, Maryam Aslani, Mario Sims, David Schlundt, Chrystyna D. Kouros, Burel Goodin, Crystal Lim, Kerry Kinney

2020-Current year OA Pubs

The present study sought to leverage machine learning approaches to determine whether social determinants of health improve prediction of incident cardiovascular disease (CVD). Participants in the Jackson Heart study with no history of CVD at baseline were followed over a 10-year period to determine first CVD events (i.e., coronary heart disease, stroke, heart failure). Three modeling algorithms (i.e., Deep Neural Network, Random Survival Forest, Penalized Cox Proportional Hazards) were used to evaluate three feature sets (i.e., demographics and standard/biobehavioral CVD risk factors [FS1], FS1 combined with psychosocial and socioeconomic CVD risk factors [FS2], and FS2 combined with environmental features [FS3]) …

Expression Of Non-Phosphorylatable S5a-L-Plastin Exerts Phenotypes Distinct From L-Plastin Deficiency During Podosome Formation And Phagocytosis, Xue Lin, Praveen Krishnamoorthy, Emma C Walker, Hemant Joshi, Sharon Celeste Morley

2020-Current year OA Pubs

No abstract provided.

Symmetric Data-Driven Fusion Of Diffusion Tensor Mri: Age Differences In White Matter, Andrea Mendez Colmenares, Michelle B Hefner, Vince D Calhoun, Elizabeth A Salerno, Jason Fanning, Neha P Gothe, Edward Mcauley, Arthur F Kramer, Agnieszka Z Burzynska

2020-Current year OA Pubs

In the past 20 years, white matter (WM) microstructure has been studied predominantly using diffusion tensor imaging (DTI). Decreases in fractional anisotropy (FA) and increases in mean (MD) and radial diffusivity (RD) have been consistently reported in healthy aging and neurodegenerative diseases. To date, DTI parameters have been studied individually (e.g., only FA) and separately (i.e., without using the joint information across them). This approach gives limited insights into WM pathology, increases the number of multiple comparisons, and yields inconsistent correlations with cognition. To take full advantage of the information in a DTI dataset, we present the first application of …

The Relationship Of Trait-Like Compassion With Epigenetic Aging: The Population-Based Prospective Young Finns Study, Henrik Dobewall, Liisa Keltikangas-Järvinen, Saara Marttila, Pashupati P Mishra, Aino Saarinen, C Robert Cloninger, Igor Zwir, Mika Kähönen, Mikko Hurme, Olli Raitakari, Terho Lehtimäki, Mirka Hintsanen

2020-Current year OA Pubs

INTRODUCTION: Helping others within and beyond the family has been related to living a healthy and long life. Compassion is a prosocial personality trait characterized by concern for another person who is suffering and the motivation to help. The current study examines whether epigenetic aging is a potential biological mechanism that explains the link between prosociality and longevity.

METHODS: We used data from the Young Finns Study that follows six birth-cohorts from age 3-18 to 19-49. Trait-like compassion for others was measured with the Temperament and Character Inventory in the years 1997 and 2001. Epigenetic age acceleration and telomere length …

Treg-Specific Deletion Of The Phosphatase Shp-1 Impairs Control Of Inflammation In Vivo, Qinlei Gu, Kenneth S Tung, Ulrike M Lorenz

2020-Current year OA Pubs

INTRODUCTION: To achieve a healthy and functional immune system, a delicate balance exists between the activation of conventional T cells (Tcon cells) and the suppression by regulatory T cells (Treg). The tyrosine phosphatase SHP-1, a negative regulator of TCR signaling, shapes this 'activation-suppression' balance by modulating Tcon cell resistance to Treg-mediated suppression. Treg cells also express SHP-1, but its role in influencing Treg function is still not fully understood.

METHODS: We generated a Treg-specific SHP-1 deletion model,

RESULTS: We show that SHP-1 modulates Treg suppressive function at different levels. First, at the intracellular signaling level in Treg cells, SHP-1 attenuates …

The In Vivo Study Of Cardiac Mechano-Electric And Mechano-Mechanical Coupling During Heart Development In Zebrafish, Jonathan S Baillie, Alex Gendernalik, Deborah M Garrity, David Bark Jr, T Alexander Quinn

2020-Current year OA Pubs

In the adult heart, acute adaptation of electrical and mechanical activity to changes in mechanical load occurs

Phagocytosis Is A Primary Determinant Of Pulmonary Clearance Of Clinical Klebsiella Pneumoniae Isolates, Rick Van Der Geest, Hongye Fan, Hernán F Peñaloza, William G Bain, Zeyu Xiong, Naina Kohli, Emily Larson, Mara L G Sullivan, Jonathan M Franks, Donna B Stolz, Ryota Ito, Kong Chen, Yohei Doi, Melanie J Harriff, Janet S Lee

2020-Current year OA Pubs

INTRODUCTION:

METHODS: We screened 19 clinical respiratory

RESULTS: The respiratory

CONCLUSION: Altogether, these findings show that phagocytosis is a primary determinant of pulmonary clearance of clinical

The Cerebrospinal Fluid Immune Cell Landscape In Animal Models Of Multiple Sclerosis, Gregory F Wu

2020-Current year OA Pubs

The fluid compartment surrounding the central nervous system (CNS) is a unique source of immune cells capable of reflecting the pathophysiology of neurologic diseases. While human clinical and experimental studies often employ cerebrospinal fluid (CSF) analysis, assessment of CSF in animal models of disease are wholly uncommon, particularly in examining the cellular component. Barriers to routine assessment of CSF in animal models of multiple sclerosis (MS) include limited sample volume, blood contamination, and lack of feasible longitudinal approaches. The few studies characterizing CSF immune cells in animal models of MS are largely outdated, but recent work employing transcriptomics have been …

Mora And Ensembletfpredictor: An Ensemble Approach To Reveal Functional Transcription Factor Regulatory Networks, Kevin Boyer, Louis Li, Tiandao Li, Bo Zhang, Guoyan Zhao

2020-Current year OA Pubs

MOTIVATION: Our study aimed to identify biologically relevant transcription factors (TFs) that control the expression of a set of co-expressed or co-regulated genes.

RESULTS: We developed a fully automated pipeline, Motif Over Representation Analysis (MORA), to detect enrichment of known TF binding motifs in any query sequences. MORA performed better than or comparable to five other TF-prediction tools as evaluated using hundreds of differentially expressed gene sets and ChIP-seq datasets derived from known TFs. Additionally, we developed EnsembleTFpredictor to harness the power of multiple TF-prediction tools to provide a list of functional TFs ranked by prediction confidence. When applied to …

Rev-Erb Activation As A Novel Pharmacological Approach For Treating Inflammatory Pain, Sangeet Makhija, Joshua D Griffett, Giri Babu Veerakanellore, Thomas P Burris, Bahaa Elgendy, Kristine Griffett

2020-Current year OA Pubs

Pain is a complex problem affecting millions of people worldwide. The current therapies to reduce pain are limited as many treatment options inadequately address the causes of pain, lead to tolerance of the drug, or have adverse effects including abuse potential. While there are many causes of pain, one underlying mechanism to the pathogenesis and maintenance of pain conditions is chronic inflammation driven by the NLRP3 inflammasome. Several inflammasome inhibitors are currently under investigation however have the potential to suppress the functioning of the innate immune system, which may cause unwanted affects in patients. Here, we show that the nuclear …

Barriers To And Solutions For Representative Inclusion Across The Lifespan And In Life Course Research: The Need For Structural Competency Highlighted By The Covid-19 Pandemic, Madison N Lecroy, Ebony B Carter, Sarah S Farabi, Dominic N Reeds, Et Al.

2020-Current year OA Pubs

Exclusion of special populations (older adults; pregnant women, children, and adolescents; individuals of lower socioeconomic status and/or who live in rural communities; people from racial and ethnic minority groups; individuals from sexual or gender minority groups; and individuals with disabilities) in research is a pervasive problem, despite efforts and policy changes by the National Institutes of Health and other organizations. These populations are adversely impacted by social determinants of health (SDOH) that reduce access and ability to participate in biomedical research. In March 2020, the Northwestern University Clinical and Translational Sciences Institute hosted the "Lifespan and Life Course Research: integrating …

How Penalizing Substance Use In Pregnancy Affects Treatment And Research: A Qualitative Examination Of Researchers' Perspectives, Seema K Shah, Leishla Perez-Cardona, Khrystyna Helner, Suena H Massey, Ashish Premkumar, Renee Edwards, Elizabeth S Norton, Cynthia E Rogers, Emily S Miller, Christopher D Smyser, Matthew M Davis, Lauren S Wakschlag

2020-Current year OA Pubs

INTRODUCTION: Laws regulating substance use in pregnancy are changing and may have unintended consequences on scientific efforts to address the opioid epidemic. Yet, how these laws affect care and research is poorly understood.

METHODS: We conducted semi-structured qualitative interviews using purposive and snowball sampling of researchers who have engaged pregnant people experiencing substance use. We explored views on laws governing substance use in pregnancy and legal reform possibilities. Interviews were double coded. Data were examined using thematic analysis.

RESULTS: We interviewed 22 researchers (response rate: 71 per cent) and identified four themes: (i) harms of punitive laws, (ii) negative legal …

Study Protocol: A Cross-Sectional Survey Of Clinicians To Identify Barriers To Clinical Practice Guideline Implementation In The Assessment And Treatment Of Persistent Tic Disorders, Jaclyn M. Martindale, Harini Sarva, Davide Martino, Donald L. Gilbert, Christos Ganos, Tamara Pringsheim, Kevin J. Black, Irene A. Malaty

2020-Current year OA Pubs

INTRODUCTION: Eight members of the International Parkinson's Disease and Movement Disorders Society Tic and Tourette Syndrome Study Group formed a subcommittee to discuss further barriers to practice guideline implementation. Based on expert opinion and literature review, the consensus was that practice variations continue to be quite broad and that many barriers in different clinical settings might negatively influence the adoption of the American Academy of Neurology and the European Society for the Study of Tourette Syndrome published guidelines.

OBJECTIVES: 1) To identify how clinical practices diverge from the existing American Academy of Neurology and European Society for the Study of …

Promis Physical Function And Pain Interference Scores Correlate With The Lower Extremity Toronto Extremity Salvage Score, Julie Jin, Zachery Hong, Lee Rhea, Douglas J. Mcdonald, Regis J. O'Keefe, Cara A. Cipriano

2020-Current year OA Pubs

UNLABELLED: The Toronto Extremity Salvage Score (TESS) and the National Institutes of Health Patient-Reported Outcomes Measurement Information System (PROMIS) are both utilized to measure patient-reported outcomes in adults with musculoskeletal oncologic conditions. However, the relationship between them has not been studied. We sought to describe a link between Lower Extremity (LE) TESS and PROMIS Physical Function (PF) scores, as well as between LE TESS and Pain Interference (PI) scores, to develop a method for converting scores between TESS and PROMIS and to examine whether TESS and PROMIS captured differences in pain and function between clinically relevant subgroups in our population. …