Digital Commons Network^™

Rodent Arena Tracker (Rat): A Machine Vision Rodent Tracking Camera And Closed Loop Control System, Jonathan Krynitsky, Alex A Legaria, Julia J Pai, Marcial Garmendia-Cedillos, Ghadi Salem, Tom Pohida, Alexxai V Kravitz

Open Access Publications

Video tracking is an essential tool in rodent research. Here, we demonstrate a machine vision rodent tracking camera based on a low-cost, open-source, machine vision camera, the OpenMV Cam M7. We call our device the rodent arena tracker (RAT), and it is a pocket-sized machine vision-based position tracker. The RAT does not require a tethered computer to operate and costs about $120 per device to build. These features make the RAT scalable to large installations and accessible to research institutions and educational settings where budgets may be limited. The RAT processes incoming video in real-time at 15 Hz and saves

Deep Learning With Diffusion Basis Spectrum Imaging For Classification Of Multiple Sclerosis Lesions, Zezhong Ye, Ajit George, Anthony T Wu, Xuan Niu, Joshua Lin, Gautam Adusumilli, Robert T Naismith, Anne H Cross, Peng Sun, Sheng-Kwei Song

Open Access Publications

OBJECTIVE: Multiple sclerosis (MS) lesions are heterogeneous with regard to inflammation, demyelination, axonal injury, and neuronal loss. We previously developed a diffusion basis spectrum imaging (DBSI) technique to better address MS lesion heterogeneity. We hypothesized that the profiles of multiple DBSI metrics can identify lesion-defining patterns. Here we test this hypothesis by combining a deep learning algorithm using deep neural network (DNN) with DBSI and other imaging methods.

METHODS: Thirty-eight MS patients were scanned with diffusion-weighted imaging, magnetization transfer imaging, and standard conventional MRI sequences (cMRI). A total of 499 regions of interest were identified on standard MRI and labeled …

Human Monoclonal Antibodies Against Ross River Virus Target Epitopes Within The E2 Protein And Protect Against Disease, Laura A Powell, Julie M. Fox, Nurgun Kose, Arthur S. Kim, Mahsa Majedi, Robin Bombardi, Robert H. Carnahan, James C. Slaughter, Thomas E. Morrison, Michael S. Diamond, James E. Crowe

Open Access Publications

Ross River fever is a mosquito-transmitted viral disease that is endemic to Australia and the surrounding Pacific Islands. Ross River virus (RRV) belongs to the arthritogenic group of alphaviruses, which largely cause disease characterized by debilitating polyarthritis, rash, and fever. There is no specific treatment or licensed vaccine available, and the mechanisms of protective humoral immunity in humans are poorly understood. Here, we describe naturally occurring human mAbs specific to RRV, isolated from subjects with a prior natural infection. These mAbs potently neutralize RRV infectivity in cell culture and block infection through multiple mechanisms, including prevention of viral attachment, entry, …

A Management Algorithm For Adult Patients With Both Brain Oxygen And Intracranial Pressure Monitoring: The Seattle International Severe Traumatic Brain Injury Consensus Conference (Sibicc), Randall Chesnut, Michael Diringer, Et Al

Open Access Publications

BACKGROUND: Current guidelines for the treatment of adult severe traumatic brain injury (sTBI) consist of high-quality evidence reports, but they are no longer accompanied by management protocols, as these require expert opinion to bridge the gap between published evidence and patient care. We aimed to establish a modern sTBI protocol for adult patients with both intracranial pressure (ICP) and brain oxygen monitors in place.

METHODS: Our consensus working group consisted of 42 experienced and actively practicing sTBI opinion leaders from six continents. Having previously established a protocol for the treatment of patients with ICP monitoring alone, we addressed patients who …

The Trajectory Of Gait Development In Mice, Shyam K Akula, Katherine B Mccullough, Claire Weichselbaum, Joseph D Dougherty, Susan E Maloney

Open Access Publications

OBJECTIVE: Gait irregularities are prevalent in neurodevelopmental disorders (NDDs). However, there is a paucity of information on gait phenotypes in NDD experimental models. This is in part due to the lack of understanding of the normal developmental trajectory of gait maturation in the mouse.

MATERIALS AND METHODS: Using the DigiGait system, we have developed a quantitative, standardized, and reproducible assay of developmental gait metrics in commonly used mouse strains that can be added to the battery of mouse model phenotyping. With this assay, we characterized the trajectory of gait in the developing C57BL/6J and FVB/AntJ mouse lines.

RESULTS: In both …

Reinforcement Biases Subsequent Perceptual Decisions When Confidence Is Low, A Widespread Behavioral Phenomenon, Armin Lak, Emily Hueske, Junya Hirokawa, Paul Masset, Torben Ott, Anne E. Urai, Tobias H. Donner, Matteo Carandini, Susumu Tonegawa, Naoshige Uchida, Adam Kepecs

Open Access Publications

Learning from successes and failures often improves the quality of subsequent decisions. Past outcomes, however, should not influence purely perceptual decisions after task acquisition is complete since these are designed so that only sensory evidence determines the correct choice. Yet, numerous studies report that outcomes can bias perceptual decisions, causing spurious changes in choice behavior without improving accuracy. Here we show that the effects of reward on perceptual decisions are principled: past rewards bias future choices specifically when previous choice was difficult and hence decision confidence was low. We identified this phenomenon in six datasets from four laboratories, across mice, …

Association Between Immune-Related Adverse Events And Recurrence-Free Survival Among Patients With Stage Iii Melanoma Randomized To Receive Pembrolizumab Or Placebo: A Secondary Analysis Of A Randomized Clinical Trial, Alexander M M Eggermont, Leonel Hernandez-Aya, Et Al

Open Access Publications

Importance: Whether immune-related adverse events (irAEs) indicate drug activity in patients treated with immune checkpoint inhibitors remains unknown.

Objective: To investigate the association between irAEs and recurrence-free survival (RFS) in the double-blind EORTC 1325/KEYNOTE-054 clinical trial comparing pembrolizumab therapy and placebo for the treatment of patients with high-risk stage III melanoma.

Design, Setting, and Participants: A total of 1019 adults with stage III melanoma were randomly assigned on a 1:1 ratio to receive treatment with pembrolizumab therapy or placebo. Eligible patients were adults 18 years and older with complete resection of cutaneous melanoma metastatic to lymph nodes, classified with stage …

Mining Reported Adverse Events Induced By Potential Opioid-Drug Interactions, Jinzhao Chen, Gaoyu Wu, Andrew Michelson, Zachary Vesoulis, Jennifer Bogner, John D Corrigan, Philip R O Payne, Fuhai Li

Open Access Publications

OBJECTIVE: Opioid-based analgesia is routinely used in clinical practice for the management of pain and alleviation of suffering at the end of life. It is well-known that opioid-based medications can be highly addictive, promoting not only abuse but also life-threatening overdoses. The scope of opioid-related adverse events (AEs) beyond these well-known effects remains poorly described. This exploratory analysis investigates potential AEs from drug-drug interactions between opioid and nonopioid medications (ODIs).

MATERIALS AND METHODS: In this study, we conduct an initial exploration of the association between ODIs and severe AEs using millions of AE reports available in FDA Adverse Event Reporting …

Glanzmann Thrombasthenia: Genetic Basis And Clinical Correlates, Juliana Perez Botero, Kristy Lee, Brian R. Branchford, Paul F. Bray, Kathleen Freson, Michele P. Lambert, Minjie Luo, Shruthi Mohan, Justyne E Ross, Wolfgang Bergmeier, Jorge Di Paola, Clingen Platelet Disorder Variant Curation Expert Panel

Open Access Publications

Glanzmann thrombasthenia (GT) is an autosomal recessive disorder of platelet aggregation caused by quantitative or qualitative defects in integrins αIIb and β3. These integrins are encoded by the

Incomplete Vesicular Docking Limits Synaptic Strength Under High Release Probability Conditions, Gerardo Malagon, Takafumi Miki, Van Tran, Laura C. Gomez, Alain Marty

Open Access Publications

Central mammalian synapses release synaptic vesicles in dedicated structures called docking/release sites. It has been assumed that when voltage-dependent calcium entry is sufficiently large, synaptic output attains a maximum value of one synaptic vesicle per action potential and per site. Here we use deconvolution to count synaptic vesicle output at single sites (mean site number per synapse: 3.6). When increasing calcium entry with tetraethylammonium in 1.5 mM external calcium concentration, we find that synaptic output saturates at 0.22 vesicle per site, not at 1 vesicle per site. Fitting the results with current models of calcium-dependent exocytosis indicates that the 0.22 …

Unc-4 Acts To Promote Neuronal Identity And Development Of The Take-Off Circuit In The Drosophila Cns, Haluk Lacin, W. Ryan Williamson, Gwyneth M. Card, James B. Skeath, James W. Truman

Open Access Publications

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Development Of A Hybrid Magnetic Resonance/Computed Tomography-Compatible Phantom For Magnetic Resonance Guided Radiotherapy, Min-Joo Kim, Seu-Ran Lee, Kyu-Ho Song, Hyeon-Man Baek, Bo-Young Choe, Tae Suk Suh

Open Access Publications

The purpose of the present study was to develop a hybrid magnetic resonance/computed tomography (MR/CT)-compatible phantom and tissue-equivalent materials for each MR and CT image. Therefore, the essential requirements necessary for the development of a hybrid MR/CT-compatible phantom were determined and the development process is described. A total of 12 different tissue-equivalent materials for each MR and CT image were developed from chemical components. The uniformity of each sample was calculated. The developed phantom was designed to use 14 plugs that contained various tissue-equivalent materials. Measurement using the developed phantom was performed using a 3.0-T scanner with 32 channels and …

Inflammatory Osteolysis Is Regulated By Site-Specific Isgylation Of The Scaffold Protein Nemo, Naga Suresh Adapala, Gaurav Swarnkar, Manoj Arra, Jie Shen, Gabriel Mbalaviele, Ke Ke, Yousef Abu-Amer

Open Access Publications

Inflammatory osteolysis is governed by exacerbated osteoclastogenesis. Ample evidence points to central role of NF-κB in such pathologic responses, yet the precise mechanisms underpinning specificity of these responses remain unclear. We propose that motifs of the scaffold protein IKKγ/NEMO partly facilitate such functions. As proof-of-principle, we used site-specific mutagenesis to examine the role of NEMO in mediating RANKL-induced signaling in mouse bone marrow macrophages, known as osteoclast precursors. We identified lysine (K)270 as a target regulating RANKL signaling as K270A substitution results in exuberant osteoclastogenesis in vitro and murine inflammatory osteolysis in vivo. Mechanistically, we discovered that K270A mutation disrupts …

Long Non-Coding Rna Graslnd Enhances Chondrogenesis Via Suppression Of The Interferon Type Ii Signaling Pathway, Nguyen P.T. Huynh, Catherine C. Gloss, Jeremiah Lorentz, Ruhang Tang, Jonathan M. Brunger, Audrey Mcalinden, Bo Zhang, Farshid Guilak

Open Access Publications

The roles of long noncoding RNAs (lncRNAs) in musculoskeletal development, disease, and regeneration remain poorly understood. Here, we identified the novel lncRNA

Abnormally Increased Carotid Intima Media-Thickness And Elasticity In Patients With Morquio A Disease, Raymond Y Wang, Kyle D Rudser, Donald R Dengel, Nicholas Evanoff, Julia Steinberger, Nina Movsesyan, Robert Garrett, Katherine Christensen, Deborah Boylan, Stephen R Braddock, Marwan Shinawi, Qi Gan, Adriana M Montaño

Open Access Publications

BACKGROUND: Cardiovascular disease frequently causes morbidity and mortality in mucopolysaccharidoses (MPS); however, cardiovascular anatomy and dysfunction in MPS IVA (Morquio A disease) is not well described. Consequently, the study aimed to compare carotid artery structure and elasticity of MPS IVA patients with other MPS patients and healthy control subjects, and quantitate frequency of MPS IVA cardiac structural and functional abnormalities.

METHODS: Prospective, multi-center echocardiogram and carotid ultrasound evaluations of 12 Morquio A patients were compared with other MPS and healthy control subjects. Average differences between groups were adjusted for age, sex, and height with robust variance estimation for confidence intervals …

Genome-Wide Association Study In Two Cohorts From A Multi-Generational Mouse Advanced Intercross Line Highlights The Difficulty Of Replication Due To Study-Specific Heterogeneity, Xinzhu Zhou, Celine L St Pierre, Natalia M Gonzales, Jennifer Zou, Riyan Cheng, Apurva S Chitre, Greta Sokoloff, Abraham A Palmer

Open Access Publications

There has been extensive discussion of the "Replication Crisis" in many fields, including genome-wide association studies (

Defining Stage-Specific Activity Of Potent New Inhibitors Of Cryptosporidium Parvum Growth In Vitro, Lisa J Funkhouser-Jones, Soumya Ravindran, L. David Sibley

Open Access Publications

No abstract provided.

The Struggling Infectious Diseases Fellow: Remediation Challenges And Opportunities, Michael T. Melia, Gerome Escota, Et Al

Open Access Publications

Remediation of struggling learners is a challenge faced by all educators. In recognition of this reality, and in light of contemporary challenges facing infectious diseases (ID) fellowship program directors, the Infectious Diseases Society of America Training Program Directors' Committee focused the 2018 National Fellowship Program Directors' Meeting at IDWeek on "Remediation of the Struggling Fellow." Small group discussions addressed 7 core topics, including feedback and evaluations, performance management and remediation, knowledge deficits, fellow well-being, efficiency and time management, teaching skills, and career development. This manuscript synthesizes those discussions around a competency-based framework to provide program directors and other educators with …

Impaired Tumor Necrosis Factor-Α Secretion By Cd4 T Cells During Respiratory Syncytial Virus Bronchiolitis Associated With Recurrent Wheeze, Maleewan Kitcharoensakkul, Leonard B Bacharier, Huiqing Yin-Declue, Jonathan S Boomer, Geneline Sajol, Marilyn K Leung, Brad Wilson, Kenneth B Schechtman, John P Atkinson, Jonathan M Green, Mario Castro

Open Access Publications

BACKGROUND: Infants with severe respiratory syncytial virus (RSV) bronchiolitis have an increased risk of recurrent wheezing and asthma. We aimed to evaluate the relationships between regulatory T cell (Treg) percentage and cytokine production of in vitro-stimulated CD4+ T cells during acute bronchiolitis and the development of recurrent wheezing in the first 3 years of life.

METHODS: We obtained peripheral blood from 166 infants hospitalized with their first episode of RSV-confirmed bronchiolitis. Granzyme B (GZB) expression, and interleukin-10, interferon-γ, tumor necrosis factor-α (TNF-α), IL-4, and IL-5 production by in vitro anti-CD3/CD28- and anti-CD3/CD46-activated CD4+ T cells, and percentage of peripheral Treg …

Decision-Making Based On 3d Printed Models In Laparoscopic Liver Resections With Intraoperative Ultrasound: A Prospective Observational Study, Jan Witowski, Andrzej Budzyński, Anna Grochowska, David H Ballard, Piotr Major, Mateusz Rubinkiewicz, Adriana Złahoda-Huzior, Tadeusz J Popiela, Mateusz Wierdak, Michał Pędziwiatr

Open Access Publications

OBJECTIVES: The aim of this study was to evaluate impact of 3D printed models on decision-making in context of laparoscopic liver resections (LLR) performed with intraoperative ultrasound (IOUS) guidance.

METHODS: Nineteen patients with liver malignances (74% were colorectal cancer metastases) were prospectively qualified for LLR or radiofrequency ablation in a single center from April 2017 to December 2018. Models were 3DP in all cases based on CT and facilitated optical visualization of tumors' relationships with portal and hepatic veins. Planned surgical extent and its changes were tracked after CT analysis and 3D model inspection, as well as intraoperatively using IOUS. …

The Plasmodium Falciparum Artemisinin Susceptibility-Associated Ap-2 Adaptin Μ Subunit Is Clathrin Independent And Essential For Schizont Maturation, Ryan C Henrici, Rachel L Edwards, Martin Zoltner, Donelly A Van Schalkwyk, Melissa N Hart, Franziska Mohring, Robert W Moon, Stephanie D Nofal, Avnish Patel, Christian Flueck, David A Baker, Audrey R Odom John, Mark C Field, Colin J Sutherland

Open Access Publications

The efficacy of current antimalarial drugs is threatened by reduced susceptibility of

How To Stop The Bleed: First Care Provider Model For Developing Public Trauma Response Beyond Basic Hemorrhage Control, Joshua P Bobko, Dylan J Badin, Leila Danishgar, Kate Bayhan, Kevin J Thompson, William J Harris, R. Todd Baldridge, Gerald R Fortuna

Open Access Publications

INTRODUCTION: Since 2013, the First Care Provider (FCP) model has successfully educated the non-medical population on how to recognize life-threatening injuries and perform interventions recommended by the Committee for Tactical Emergency Casualty Care (C-TECC) and the Hartford Consensus in the disaster setting. Recent programs, such as the federal "Stop The Bleed" campaign, have placed the emphasis of public training on hemorrhage control. However, recent attacks demonstrate that access to wounded, recognition of injury, and rapid evacuation are equally as important as hemorrhage control in minimizing mortality. To date, no training programs have produced a validated study with regard to training …

Neural Mechanisms Of Economic Choices In Mice, Masaru Kuwabara, Ningdong Kang, Timothy E. Holy, Camillo Padoa-Schioppa

Open Access Publications

Economic choices entail computing and comparing subjective values. Evidence from primates indicates that this behavior relies on the orbitofrontal cortex. Conversely, previous work in rodents provided conflicting results. Here we present a mouse model of economic choice behavior, and we show that the lateral orbital (LO) area is intimately related to the decision process. In the experiments, mice chose between different juices offered in variable amounts. Choice patterns closely resembled those measured in primates. Optogenetic inactivation of LO dramatically disrupted choices by inducing erratic changes of relative value and by increasing choice variability. Neuronal recordings revealed that different groups of …

Agonist-Selective Recruitment Of Engineered Protein Probes And Of Grk2 By Opioid Receptors In Living Cells, Miriam Stoeber, Damien Jullié, Joy Li, Soumen Chakraborty, Susruta Majumdar, Nevin A. Lambert, Aashish Manglik, Mark Von Zastrow

Open Access Publications

G protein-coupled receptors (GPCRs) signal through allostery, and it is increasingly clear that chemically distinct agonists can produce different receptor-based effects. It has been proposed that agonists selectively promote receptors to recruit one cellular interacting partner over another, introducing allosteric 'bias' into the signaling system. However, the underlying hypothesis - that different agonists drive GPCRs to engage different cytoplasmic proteins in living cells - remains untested due to the complexity of readouts through which receptor-proximal interactions are typically inferred. We describe a cell-based assay to overcome this challenge, based on GPCR-interacting biosensors that are disconnected from endogenous transduction mechanisms. Focusing …

Cryptococcus Neoformans Chitin Synthase 3 Plays A Critical Role In Dampening Host Inflammatory Responses, Camaron R Hole, Woei C Lam, Rajendra Upadhya, Jennifer K Lodge

Open Access Publications

No abstract provided.

Trpm3_Mir-204: A Complex Locus For Eye Development And Disease, Alan Shiels

Open Access Publications

First discovered in a light-sensitive retinal mutant of Drosophila, the transient receptor potential (TRP) superfamily of non-selective cation channels serve as polymodal cellular sensors that participate in diverse physiological processes across the animal kingdom including the perception of light, temperature, pressure, and pain. TRPM3 belongs to the melastatin sub-family of TRP channels and has been shown to function as a spontaneous calcium channel, with permeability to other cations influenced by alternative splicing and/or non-canonical channel activity. Activators of TRPM3 channels include the neurosteroid pregnenolone sulfate, calmodulin, phosphoinositides, and heat, whereas inhibitors include certain drugs, plant-derived metabolites, and G-protein subunits. Activation …

Spatiotemporal Dynamics Of Multi-Vesicular Release Is Determined By Heterogeneity Of Release Sites Within Central Synapses, Dario Maschi, Vitaly A. Klyachko

Open Access Publications

A synaptic active zone (AZ) can release multiple vesicles in response to an action potential. This multi-vesicular release (MVR) occurs at most synapses, but its spatiotemporal properties are unknown. Nanoscale-resolution detection of individual release events in hippocampal synapses revealed unprecedented heterogeneity among vesicle release sites within a single AZ, with a gradient of release probability decreasing from AZ center to periphery. Parallel to this organization, MVR events preferentially overlap with uni-vesicular release (UVR) events at sites closer to an AZ center. Pairs of fusion events comprising MVR are also not perfectly synchronized, and the earlier event tends to occur closer …

Quantitative Trait Variation In Asd Probands And Toddler Sibling Outcomes At 24 Months, Jessica B Girault, Kelly N Botteron, John N Constantino, Et Al

Open Access Publications

BACKGROUND: Younger siblings of children with autism spectrum disorder (ASD) are at increased likelihood of receiving an ASD diagnosis and exhibiting other developmental concerns. It is unknown how quantitative variation in ASD traits and broader developmental domains in older siblings with ASD (probands) may inform outcomes in their younger siblings.

METHODS: Participants included 385 pairs of toddler siblings and probands from the Infant Brain Imaging Study. ASD probands (mean age 5.5 years, range 1.7 to 15.5 years) were phenotyped using the Autism Diagnostic Interview-Revised (ADI-R), the Social Communication Questionnaire (SCQ), and the Vineland Adaptive Behavior Scales, Second Edition (VABS-II). Siblings …

Prevalence And Family-Related Factors Associated With Suicidal Ideation, Suicide Attempts, And Self-Injury In Children Aged 9 To 10 Years, Danielle C. Deville, Diana Whalen, Florence J. Breslin, Amanda S. Morris, Sahib S. Khalsa, Martin P. Paulus, Deanna M. Barch

Open Access Publications

Importance: Although suicide is a leading cause of death for children in the United States, and the rate of suicide in childhood has steadily increased, little is known about suicidal ideation and behaviors in children.

Objective: To assess the overall prevalence of suicidal ideation, suicide attempts, and nonsuicidal self-injury, as well as family-related factors associated with suicidality and self-injury among preadolescent children.

Design, Setting, and Participants: Cross-sectional study using retrospective analysis of the baseline sample from the Adolescent Brain Cognitive Development (ABCD) study. This multicenter investigation used an epidemiologically informed school-based recruitment strategy, with consideration of the demographic composition of …

2019 Hrs/Ehra/Aphrs/Lahrs Expert Consensus Statement On Catheter Ablation Of Ventricular Arrhythmias: Executive Summary, Edmond M Cronin, Phillip Cuculich, Et Al

Open Access Publications

Ventricular arrhythmias are an important cause of morbidity and mortality and come in a variety of forms, from single premature ventricular complexes to sustained ventricular tachycardia and fibrillation. Rapid developments have taken place over the past decade in our understanding of these arrhythmias and in our ability to diagnose and treat them. The field of catheter ablation has progressed with the development of new methods and tools, and with the publication of large clinical trials. Therefore, global cardiac electrophysiology professional societies undertook to outline recommendations and best practices for these procedures in a document that will update and replace the …