Digital Commons Network^™

Lesion Quantification Toolkit: A Matlab Software Tool For Estimating Grey Matter Damage And White Matter Disconnections In Patients With Focal Brain Lesions, Joseph C Griffis, Nicholas V Metcalf, Maurizio Corbetta, Gordon L Shulman

Open Access Publications

Lesion studies are an important tool for cognitive neuroscientists and neurologists. However, while brain lesion studies have traditionally aimed to localize neurological symptoms to specific anatomical loci, a growing body of evidence indicates that neurological diseases such as stroke are best conceptualized as brain network disorders. While researchers in the fields of neuroscience and neurology are therefore increasingly interested in quantifying the effects of focal brain lesions on the white matter connections that form the brain's structural connectome, few dedicated tools exist to facilitate this endeavor. Here, we present the Lesion Quantification Toolkit, a publicly available MATLAB software package for …

Brain/Minds Beyond Human Brain Mri Project: A Protocol For Multi-Level Harmonization Across Brain Disorders Throughout The Lifespan, Shinsuke Koike, Matthew F Glasser, David C Van Essen, Et Al

Open Access Publications

Psychiatric and neurological disorders are afflictions of the brain that can affect individuals throughout their lifespan. Many brain magnetic resonance imaging (MRI) studies have been conducted; however, imaging-based biomarkers are not yet well established for diagnostic and therapeutic use. This article describes an outline of the planned study, the Brain/MINDS Beyond human brain MRI project (BMB-HBM, FY2018 ~ FY2023), which aims to establish clinically-relevant imaging biomarkers with multi-site harmonization by collecting data from healthy traveling subjects (TS) at 13 research sites. Collection of data in psychiatric and neurological disorders across the lifespan is also scheduled at 13 sites, whereas designing …

Self-Reported Positive Impact Of Mentored Clinical Research Training Is Associated With Academic Success In Hematology, Allison A. King, Sara K. Vesely, Grace Dadzie, Cecelia Calhoun, Adam Cuker, Wendy Stock, Alison Walker, Josel Fritz, Lilian Sung

Open Access Publications

No abstract provided.

Genetic Association Study Of Childhood Aggression Across Raters, Instruments, And Age, Hill F. Ip, Andrew C. Heath, Pamela Madden, Et Al.

Open Access Publications

No abstract provided.

Strategies And Tools For Studying Microglial-Mediated Synapse Elimination And Refinement, Raffaella Morini, Matteo Bizzotto, Fabio Perrucci, Fabia Filipello, Michela Matteoli

Open Access Publications

The role of microglia in controlling synapse homeostasis is becoming increasingly recognized by the scientific community. In particular, the microglia-mediated elimination of supernumerary synapses during development lays the basis for the correct formation of neuronal circuits in adulthood, while the possible reactivation of this process in pathological conditions, such as schizophrenia or Alzheimer's Disease, provides a promising target for future therapeutic strategies. The methodological approaches to investigate microglial synaptic engulfment include different

Whole-Exome Sequencing And Hipsc Cardiomyocyte Models Identify Myrip, Trappc11, And Slc27a6 Of Potential Importance To Left Ventricular Hypertrophy In An African Ancestry Population, Marguerite R Irvin, Lisa De Las Fuentes, C Charles Gu, Karen Schwander, Dabeeru C Rao, Et Al

Open Access Publications

No abstract provided.

Sleep-Disordered Breathing In Pregnancy: A Developmental Origin Of Offspring Obesity?, Sarah S Farabi, Linda A Barbour, Teri L Hernandez

Open Access Publications

Sleep-disordered breathing (SDB) worsens over pregnancy, and obstructive sleep apnea is associated with serious maternal complications. Intrauterine exposures that provoke insulin resistance (IR), inflammation, or oxidative stress may have long-term offspring health consequences. In obesity, worsening maternal SDB appears to be an exposure that increases the risk for both small- or large-for-gestational-age (SGA, LGA, respectively), suggesting distinct outcomes linked to a common maternal phenotype. The aim of this paper is to systematically review and link data from both mechanistic rodent models and descriptive human studies to characterize the impact of maternal SDB on fetal development. A systematic review of the …

Peripheral Sensory Stimulation Elicits Global Slow Waves By Recruiting Somatosensory Cortex Bilaterally, Zachary P. Rosenthal, Ryan V. Raut, Ryan M. Bowen, Abraham Z. Snyder, Joseph P. Culver, Marcus E. Raichle, Jin-Moo Lee

Open Access Publications

No abstract provided.

Noise Exposure Potentiates Exocytosis From Cochlear Inner Hair Cells, Luis E Boero, Shelby Payne, Maria Eugenia Gómez-Casati, Mark A Rutherford, Juan D Goutman

Open Access Publications

Noise-induced hearing loss has gained relevance as one of the most common forms of hearing impairment. The anatomical correlates of hearing loss, principally cell damage and/or death, are relatively well-understood histologically. However, much less is known about the physiological aspects of damaged, surviving cells. Here we addressed the functional consequences of noise exposure on the capacity of inner hair cells (IHCs) to release synaptic vesicles at synapses with spiral ganglion neurons (SGNs). Mice of either sex at postnatal day (P) 15-16 were exposed to 1-12 kHz noise at 120 dB sound pressure level (SPL), for 1 h. Exocytosis was measured …

Development And Validation Of A Deep Learning Model To Quantify Glomerulosclerosis In Kidney Biopsy Specimens, Jon N. Marsh, Ta-Chiang Liu, Parker C. Wilson, S. Joshua Swamidass, Joseph P. Gaut

Open Access Publications

Importance: A chronic shortage of donor kidneys is compounded by a high discard rate, and this rate is directly associated with biopsy specimen evaluation, which shows poor reproducibility among pathologists. A deep learning algorithm for measuring percent global glomerulosclerosis (an important predictor of outcome) on images of kidney biopsy specimens could enable pathologists to more reproducibly and accurately quantify percent global glomerulosclerosis, potentially saving organs that would have been discarded.

Objective: To compare the performances of pathologists with a deep learning model on quantification of percent global glomerulosclerosis in whole-slide images of donor kidney biopsy specimens, and to determine the …

Sex-Dimorphic Genetic Effects And Novel Loci For Fasting Glucose And Insulin Variability, Vasiliki Lagou, Ping An, Michael A. Province, Et Al.

Open Access Publications

No abstract provided.

Dengue And The Lectin Pathway Of The Complement System, Romchat Kraivong, Nuntaya Punyadee, M Kathryn Liszewski, John P Atkinson, Panisadee Avirutnan

Open Access Publications

Dengue is a mosquito-borne viral disease causing significant health and economic burdens globally. The dengue virus (DENV) comprises four serotypes (DENV1-4). Usually, the primary infection is asymptomatic or causes mild dengue fever (DF), while secondary infections with a different serotype increase the risk of severe dengue disease (dengue hemorrhagic fever, DHF). Complement system activation induces inflammation and tissue injury, contributing to disease pathogenesis. However, in asymptomatic or primary infections, protective immunity largely results from the complement system's lectin pathway (LP), which is activated through foreign glycan recognition. Differences in N-glycans displayed on the DENV envelope membrane influence the lectin pattern …

Overlapping But Disparate Inflammatory And Immunosuppressive Responses To Sars-Cov-2 And Bacterial Sepsis: An Immunological Time Course Analysis, Tyler J Loftus, Ricardo Ungaro, Marvin Dirain, Philip A Efron, Monty B Mazer, Kenneth E Remy, Richard S Hotchkiss, Luer Zhong, Rhonda Bacher, Petr Starostik, Lyle L Moldawer, Scott C Brakenridge

Open Access Publications

Both severe SARS-CoV-2 infections and bacterial sepsis exhibit an immunological dyscrasia and propensity for secondary infections. The nature of the immunological dyscrasias for these differing etiologies and their time course remain unclear. In this study, thirty hospitalized patients with SARS-CoV-2 infection were compared with ten critically ill patients with bacterial sepsis over 21 days, as well as ten healthy control subjects. Blood was sampled between days 1 and 21 after admission for targeted plasma biomarker analysis, cellular phenotyping, and leukocyte functional analysis

Evaluation Of Diffusion-Weighted Mri And Geometric Distortion On A 0.35t Mr-Linac At Multiple Gantry Angles, Benjamin Lewis, Anamaria Guta, Stacie Mackey, H Michael Gach, Sasa Mutic, Olga Green, Taeho Kim

Open Access Publications

Diffusion-weighted imaging (DWI) provides a valuable diagnostic tool for tumor evaluation. Yet, it is difficult to acquire daily MRI data sets in the traditional radiotherapy clinical setting due to patient burden and limited resources. However, integrated MRI radiotherapy treatment systems facilitate daily functional MRI acquisitions like DWI during treatment exams. Before ADC values from MR-RT systems can be used clinically their reproducibility and accuracy must be quantified. This study used a NIST traceable DWI phantom to verify ADC values acquired on a 0.35 T MR-LINAC system at multiple gantry angles. A diffusion-weighted echo planar imaging sequence was used for all …

Cd11c+ Cd88+ Cd317+ Myeloid Cells Are Critical Mediators Of Persistent Cns Autoimmunity, Navid Manouchehri, Rehana Z. Hussain, Petra D. Cravens, Ekaterina Esaulova, Maxim N. Artyomov, Brian T. Edelson, Gregory F. Wu, Anne H. Cross, Richard Doelger, Nicolas Loof, Todd N. Eagar, Thomas G. Forsthuber, Laurent Calvier, Joachim Herz, Olaf Stüve

Open Access Publications

No abstract provided.

Monitoring The Variation In The Gut Microbiota Of Captive Woolly Monkeys Related To Changes In Diet During A Reintroduction Process, Camilo Quiroga-González, Luis Alberto Chica Cardenas, Mónica Ramírez, Alejandro Reyes, Camila González, Pablo R. Stevenson

Open Access Publications

No abstract provided.

A Systematic Review And Meta‑Analysis Of Obesity And Covid‑19 Outcomes, Xinya Zhang, Alexander M. Lewis, John R. Moley, Jonathan R. Brestoff

Open Access Publications

No abstract provided.

Use Of Machine Learning To Develop And Evaluate Models Using Preoperative And Intraoperative Data To Identify Risks Of Postoperative Complications, Bing Xue, Dingwen Li, Chenyang Lu, Christopher R. King, Troy Wildes, Michael S. Avidan, Thomas Kannampallil, Joanna Abraham

Open Access Publications

Importance: Postoperative complications can significantly impact perioperative care management and planning.

Objectives: To assess machine learning (ML) models for predicting postoperative complications using independent and combined preoperative and intraoperative data and their clinically meaningful model-agnostic interpretations.

Design, Setting, and Participants: This retrospective cohort study assessed 111 888 operations performed on adults at a single academic medical center from June 1, 2012, to August 31, 2016, with a mean duration of follow-up based on the length of postoperative hospital stay less than 7 days. Data analysis was performed from February 1 to September 31, 2020.

Main Outcomes and Measures: Outcomes included …

Older Adults With Newly Diagnosed High-Risk/Secondary Aml Who Achieved Remission With Cpx-351: Phase 3 Post Hoc Analyses, Tara L. Lin, Geoffrey L. Uy, Et Al.

Open Access Publications

No abstract provided.

Predicting Mortality Risk For Preterm Infants Using Random Forest, Jennifer Lee, Jinjin Cai, Fuhai Li, Zachary A. Vesoulis

Open Access Publications

No abstract provided.

Gene Expression Signature Predicts Relapse In Adult Patients With Cytogenetically Normal Acute Myeloid Leukemia, Christopher J. Walker, Geoffrey L. Uy, Et Al.

Open Access Publications

No abstract provided.

Predicting Alcohol Use Disorder Remission: A Longitudinal Multimodal Multi-Featured Machine Learning Approach, Sivan Kinreich, Vivia V. Mccutcheon, Jessica L. Bourdon, Andrey P. Anokhin, Kathleen K. Bucholz, Meredith W. Francis, Et Al.

Open Access Publications

No abstract provided.

Broadly Neutralizing Monoclonal Antibodies Protect Against Multiple Tick-Borne Flaviviruses, Laura A. Vanblargan, John M. Errico, Natasha M. Kafai, Prashant N. Jethva, Christopher A. Nelson, David Wang, Scott A. Handley, Michael L. Gross, Daved H. Fremont, Michael S. Diamond, Et Al

Open Access Publications

Although Powassan virus (POWV) is an emerging tick-transmitted flavivirus that causes severe or fatal neuroinvasive disease in humans, medical countermeasures have not yet been developed. Here, we developed a panel of neutralizing anti-POWV mAbs recognizing six distinct antigenic sites. The most potent of these mAbs bind sites within domain II or III of the envelope (E) protein and inhibit postattachment viral entry steps. A subset of these mAbs cross-react with other flaviviruses. Both POWV type-specific and cross-reactive neutralizing mAbs confer protection in mice against POWV infection when given as prophylaxis or postexposure therapy. Several cross-reactive mAbs mapping to either domain …

Mechanical Dysfunction Of The Sarcomere Induced By A Pathogenic Mutation In Troponin T Drives Cellular Adaptation, Sarah R. Clippinger, Paige E. Cloonan, Wei Wang, Lina Greenberg, W. Tom Stump, Paweorn Angsutararux, Jeanne M. Nerbonne, Michael J. Greenberg

Open Access Publications

Familial hypertrophic cardiomyopathy (HCM), a leading cause of sudden cardiac death, is primarily caused by mutations in sarcomeric proteins. The pathogenesis of HCM is complex, with functional changes that span scales, from molecules to tissues. This makes it challenging to deconvolve the biophysical molecular defect that drives the disease pathogenesis from downstream changes in cellular function. In this study, we examine an HCM mutation in troponin T, R92Q, for which several models explaining its effects in disease have been put forward. We demonstrate that the primary molecular insult driving disease pathogenesis is mutation-induced alterations in tropomyosin positioning, which causes increased …

Cannabis-Induced Hypodopaminergic Anhedonia And Cognitive Decline In Humans: Embracing Putative Induction Of Dopamine Homeostasis, Kenneth Blum, Jag Khalsa, Jean Lud Cadet, David Baron, Abdalla Bowirrat, Brent Boyett, Lisa Lott, Raymond Brewer, Marjorie Gondré-Lewis, Gregory Bunt, Shan Kazmi, Mark S Gold

Open Access Publications

Over years, the regular use of cannabis has substantially increased among young adults, as indicated by the rise in cannabis use disorder (CUD), with an estimated prevalence of 8. 3% in the United States. Research shows that exposure to cannabis is associated with hypodopaminergic anhedonia (depression), cognitive decline, poor memory, inattention, impaired learning performance, reduced dopamine brain response-associated emotionality, and increased addiction severity in young adults. The addiction medicine community is increasing concern because of the high content of delta-9-tetrahydrocannabinol (THC) currently found in oral and vaping cannabis products, the cognitive effects of cannabis may become more pronounced in young …

Cortical Regions Activated By Spectrally Degraded Speech In Adults With Single Sided Deafness Or Bilateral Normal Hearing, Harold Burton, Ruth M Reeder, Tim Holden, Alvin Agato, Jill B Firszt

Open Access Publications

Those with profound sensorineural hearing loss from single sided deafness (SSD) generally experience greater cognitive effort and fatigue in adverse sound environments. We studied cases with right ear, SSD compared to normal hearing (NH) individuals. SSD cases were significantly less correct in naming last words in spectrally degraded 8- and 16-band vocoded sentences, despite high semantic predictability. Group differences were not significant for less intelligible 4-band sentences, irrespective of predictability. SSD also had diminished BOLD percent signal changes to these same sentences in left hemisphere (LH) cortical regions of early auditory, association auditory, inferior frontal, premotor, inferior parietal, dorsolateral prefrontal, …

Myosin V Regulates Spatial Localization Of Different Forms Of Neurotransmitter Release In Central Synapses, Dario Maschi, Michael W Gramlich, Vitaly A Klyachko

Open Access Publications

Synaptic active zone (AZ) contains multiple specialized release sites for vesicle fusion. The utilization of release sites is regulated to determine spatiotemporal organization of the two main forms of synchronous release, uni-vesicular (UVR) and multi-vesicular (MVR). We previously found that the vesicle-associated molecular motor myosin V regulates temporal utilization of release sites by controlling vesicle anchoring at release sites in an activity-dependent manner. Here we show that acute inhibition of myosin V shifts preferential location of vesicle docking away from AZ center toward periphery, and results in a corresponding spatial shift in utilization of release sites during UVR. Similarly, inhibition …

Guidelines For Conducting Virtual Cognitive Interviews During A Pandemic, James A Shepperd, Gabrielle Pogge, Jean M Hunleth, Sienna Ruiz, Erika A Waters

Open Access Publications

The COVID-19 pandemic has challenged researchers working in physical contact with research participants. Cognitive interviews examine whether study components (most often questionnaire items) are worded or structured in a manner that allows study participants to interpret the items in a way intended by the researcher. We developed guidelines to conduct cognitive interviews virtually to accommodate interviewees who have limited access to the internet. The guidelines describe the essential communication and safety equipment requirements and outline a procedure for collecting responses while maintaining the safety of the participants and researchers. Furthermore, the guidelines provide suggestions regarding training of participants to use …

Predicting Outcomes In Patients Undergoing Pancreatectomy Using Wearable Technology And Machine Learning: Prospective Cohort Study, Heidy Cos, Dingwen Li, Gregory Williams, Jeffrey Chininis, Ruixuan Dai, Jingwen Zhang, Rohit Srivastava, Lacey Raper, Dominic Sanford, William Hawkins, Chenyang Lu, Chet W Hammill

Open Access Publications

BACKGROUND: Pancreatic cancer is the third leading cause of cancer-related deaths, and although pancreatectomy is currently the only curative treatment, it is associated with significant morbidity.

OBJECTIVE: The objective of this study was to evaluate the utility of wearable telemonitoring technologies to predict treatment outcomes using patient activity metrics and machine learning.

METHODS: In this prospective, single-center, single-cohort study, patients scheduled for pancreatectomy were provided with a wearable telemonitoring device to be worn prior to surgery. Patient clinical data were collected and all patients were evaluated using the American College of Surgeons National Surgical Quality Improvement Program surgical risk calculator …

Comprehensive Mirnome-Wide Profiling In A Neuronal Cell Model Of Synucleinopathy Implies Involvement Of Cell Cycle Genes, Elisabeth Findeiss, Sigrid C Schwarz, Valentin Evsyukov, Thomas W Rösler, Matthias Höllerhage, Tasnim Chakroun, Niko-Petteri Nykänen, Yimin Shen, Wolfgang Wurst, Michael Kohl, Jörg Tost, Günter U Höglinger

Open Access Publications

Growing evidence suggests that epigenetic mechanisms like microRNA-mediated transcriptional regulation contribute to the pathogenesis of parkinsonism. In order to study the influence of microRNAs (miRNAs), we analyzed the miRNome 2 days prior to major cell death in α-synuclein-overexpressing Lund human mesencephalic neurons, a well-established cell model of Parkinson's disease (PD), by next-generation sequencing. The expression levels of 23 miRNAs were significantly altered in α-synuclein-overexpressing cells, 11 were down- and 12 upregulated (