Digital Commons Network^™

Tlr3 Controls Constitutive Ifn-Β Antiviral Immunity In Human Fibroblasts And Cortical Neurons, Daxing Gao, Michael S Diamond, Et Al

Open Access Publications

Human herpes simplex virus 1 (HSV-1) encephalitis can be caused by inborn errors of the TLR3 pathway, resulting in impairment of CNS cell-intrinsic antiviral immunity. Deficiencies of the TLR3 pathway impair cell-intrinsic immunity to vesicular stomatitis virus (VSV) and HSV-1 in fibroblasts, and to HSV-1 in cortical but not trigeminal neurons. The underlying molecular mechanism is thought to involve impaired IFN-α/β induction by the TLR3 recognition of dsRNA viral intermediates or by-products. However, we show here that human TLR3 controls constitutive levels of IFNB mRNA and secreted bioactive IFN-β protein, and thereby also controls constitutive mRNA levels for IFN-stimulated genes …

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.

Recurrence And Coniglobus Volumetric Resolution Of Subacute And Chronic Subdural Hematoma Post-Middle Meningeal Artery Embolization, Ambooj Tiwari, Adam A Dmytriw, Ryan Bo, Nathan Farkas, Phillip Ye, David S Gordon, Karthikeyan M Arcot, David Turkel-Parrella, Jeffrey Farkas

Open Access Publications

OBJECTIVE: To study the efficacy of middle meningeal artery (MMA) embolization for the treatment of chronic subdural hematoma (SDH) and characterize its post-embolization volumetric resolution.

METHODS: Ten patients diagnosed with 13 cSDH underwent MMA embolization. SDH volumes were measured from time of initial discovery on imaging to pre-operative, post-operative, short-term and long-term follow-up. Time between procedure to obliteration was also measured. Volumetric analysis was done using the coniglobus formula, and recurrence rate as well as resolution timeline was defined using best-fit models.

RESULTS: Out of 10 patients, five were recurrent lesions, three were bilateral and seven unilateral cSDH. Average and …

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.

Inflammatory Signaling Sensitizes Piezo1 Mechanotransduction In Articular Chondrocytes As A Pathogenic Feed-Forward Mechanism In Osteoarthritis, Whasil Lee, Robert J. Nims, Alireza Savadipour, Qiaojuan Zhang, Holly A. Leddy, Fang Liu, Amy L. Mcnulty, Yong Chen, Farshid Guilak, Wolfgang B. Liedtke

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.

A Novel Precision Approach To Overcome The "Addiction Pandemic" By Incorporating Genetic Addiction Risk Severity (Gars) And Dopamine Homeostasis Restoration, Kenneth Blum, Shan Kazmi, Edward J Modestino, Bill William Downs, Debasis Bagchi, David Baron, Thomas Mclaughlin, Richard Green, Rehan Jalali, Panayotis K Thanos, Igor Elman, Rajendra D Badgaiyan, Abdalla Bowirrat, Mark S Gold

Open Access Publications

This article describes a unique therapeutic precision intervention, a formulation of enkephalinase inhibitors, enkephalin, and dopamine-releasing neuronutrients, to induce dopamine homeostasis for detoxification and treatment of individuals genetically predisposed to developing reward deficiency syndrome (RDS). The formulations are based on the results of the addiction risk severity (GARS) test. Based on both neurogenetic and epigenetic evidence, the test evaluates the presence of reward genes and risk alleles. Existing evidence demonstrates that the novel genetic risk testing system can successfully stratify the potential for developing opioid use disorder (OUD) related risks or before initiating opioid analgesic therapy and RDS risk for …

Long, Noncoding Rna Dysregulation In Glioblastoma, Patrick A Desouza, Xuan Qu, Hao Chen, Bhuvic Patel, Christopher A Maher, Albert H Kim

Open Access Publications

Transcription occurs across more than 70% of the human genome and more than half of currently annotated genes produce functional noncoding RNAs. Of these transcripts, the majority-long, noncoding RNAs (lncRNAs)-are greater than 200 nucleotides in length and are necessary for various roles in the cell. It is increasingly appreciated that these lncRNAs are relevant in both health and disease states, with the brain expressing the largest number of lncRNAs compared to other organs. Glioblastoma (GBM) is an aggressive, fatal brain tumor that demonstrates remarkable intratumoral heterogeneity, which has made the development of effective therapies challenging. The cooperation between genetic and …

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.

Universal School Meals And Associations With Student Participation, Attendance, Academic Performance, Diet Quality, Food Security, And Body Mass Index: A Systematic Review, Juliana F W Cohen, Amelie A Hecht, Gabriella M Mcloughlin, Lindsey Turner, Marlene B Schwartz

Open Access Publications

The school environment plays an important role in children's diets and overall health, and policies for universal free school meals have the potential to contribute to positive child health outcomes. This systematic review evaluates studies examining the association between universal free school meals and students' school meal participation rates, diets, attendance, academic performance, and Body Mass Index (BMI), as well as school finances. The search was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA). A search for studies published in economically developed countries published through December 2020 was performed in PubMed, Education Resources Information …

Taking Account Of Asymptomatic Infections: A Modeling Study Of The Covid-19 Outbreak On The Diamond Princess Cruise Ship, Li-Shan Huang, Li Li, Lucia Dunn, Mai He

Open Access Publications

The COVID-19 outbreak on the Diamond Princess (DP) cruise ship has provided empirical data to study the transmission potential of COVID-19 with the presence of pre/asymptomatic cases. We studied the changes in R0 on DP from January 21 to February 19, 2020 based on chain binomial models under two scenarios: no quarantine assuming a random mixing condition, and quarantine of passengers in cabins-passengers may get infected either by an infectious case in a shared cabin or by pre/asymptomatic crew who continued to work. Estimates of R0 at the beginning of the epidemic were 3.27 (95% CI, 3.02-3.54) and 3.78 (95% …

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 …

Variables Associated With Intravenous Rehydration And Hospitalization In Children With Acute Gastroenteritis: A Secondary Analysis Of 2 Randomized Clinical Trials, Naveen Poonai, Philip Tarr, Et Al

Open Access Publications

Importance: Despite guidelines endorsing oral rehydration therapy, intravenous fluids are commonly administered to children with acute gastroenteritis in high-income countries.

Objective: To identify factors associated with intravenous fluid administration and hospitalization in children with acute gastroenteritis.

Design, Setting, and Participants: This study is a planned secondary analysis of the Pediatric Emergency Research Canada (PERC) and Pediatric Emergency Care Applied Research Network (PECARN) probiotic trials. Participants include children aged 3 to 48 months with 3 or more watery stools in 24 hours between November 5, 2013, and April 7, 2017, for the PERC study and July 8, 2014, and June 23, …

Lysis Of Arterial Thrombi By Perfusion Of N,N'-Diacetyl-L-Cystine (Dinac), Dongjune Kim, Susan M. Shea, David N. Ku

Open Access Publications

The search persists for a safe and effective agent to lyse arterial thrombi in the event of acute heart attacks or strokes due to thrombotic occlusion. The culpable thrombi are composed either primarily of platelets and von Willebrand Factor (VWF), or polymerized fibrin, depending on the mechanism of formation. Current thrombolytics were designed to target red fibrin-rich clots, but may be not be efficacious on white VWF-platelet-rich arterial thrombi. We have developed an in vitro system to study the efficacy of known and proposed thrombolytic agents on white clots formed from whole blood in a stenosis with arterial conditions. The …

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 …

Thermoneutrality Alters Gastrointestinal Antigen Passage Patterning And Predisposes To Oral Antigen Sensitization In Mice, Taeko K Noah, Jee-Boong Lee, Christopher A Brown, Amnah Yamani, Sunil Tomar, Varsha Ganesan, Rodney D Newberry, Gary B Huffnagle, Senad Divanovic, Simon P Hogan

Open Access Publications

Food allergy is an emerging epidemic, and the underlying mechanisms are not well defined partly due to the lack of robust adjuvant free experimental models of dietary antigen sensitization. As housing mice at thermoneutrality (Tn) - the temperature of metabolic homeostasis (26-30°C) - has been shown to improve modeling various human diseases involved in inflammation, we tested the impact of Tn housing on an experimental model of food sensitization. Here we demonstrate that WT BALB/c mice housed under standard temperature (18-20°C, Ts) conditions translocated the luminal antigens in the small intestine (SI) across the epithelium

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, …

The Dystonia Coalition: A Multicenter Network For Clinical And Translational Studies, Gamze Kilic-Berkmen, Laura J Wright, Joel S Perlmutter, Cynthia Comella, Mark Hallett, Jan Teller, Sarah Pirio Richardson, David A Peterson, Carlos Cruchaga, Codrin Lungu, H A Jinnah

Open Access Publications

Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal postures, repetitive movements, or both. Research in dystonia has been challenged by several factors. First, dystonia is uncommon. Dystonia is not a single disorder but a family of heterogenous disorders with varied clinical manifestations and different causes. The different subtypes may be seen by providers in different clinical specialties including neurology, ophthalmology, otolaryngology, and others. These issues have made it difficult for any single center to recruit large numbers of subjects with specific types of dystonia for research studies in a timely manner. The Dystonia Coalition …

Neuroskeletal Effects Of Chronic Bioelectric Nerve Stimulation In Health And Diabetes, Alec T Beeve, Ivana Shen, Xiao Zhang, Kristann Magee, Ying Yan, Matthew R Macewan, Erica L Scheller

Open Access Publications

Background/Aims: Bioelectric nerve stimulation (eStim) is an emerging clinical paradigm that can promote nerve regeneration after trauma, including within the context of diabetes. However, its ability to prevent the onset of diabetic peripheral neuropathy (DPN) has not yet been evaluated. Beyond the nerve itself, DPN has emerged as a potential contributor to sarcopenia and bone disease; thus, we hypothesized that eStim could serve as a strategy to simultaneously promote neural and musculoskeletal health in diabetes.

Methods: To address this question, an eStim paradigm pre-optimized to promote nerve regeneration was applied to the sciatic nerve, which directly innervates the tibia and …

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 …

Initial Clinical Experience Of Mr-Guided Radiotherapy For Non-Small Cell Lung Cancer, Cathryn B Crockett, Pamela Samson, Robert Chuter, Michael Dubec, Corinne Faivre-Finn, Olga L Green, Sara L Hackett, Fiona Mcdonald, Clifford Robinson, Anna-Maria Shiarli, Michael W Straza, Joost J C Verhoeff, Maria Werner-Wasik, Gregory Vlacich, David Cobben

Open Access Publications

Curative-intent radiotherapy plays an integral role in the treatment of lung cancer and therefore improving its therapeutic index is vital. MR guided radiotherapy (MRgRT) systems are the latest technological advance which may help with achieving this aim. The majority of MRgRT treatments delivered to date have been stereotactic body radiation therapy (SBRT) based and include the treatment of (ultra-) central tumors. However, there is a move to also implement MRgRT as curative-intent treatment for patients with inoperable locally advanced NSCLC. This paper presents the initial clinical experience of using the two commercially available systems to date: the ViewRay MRIdian and …

Whipworm-Associated Intestinal Microbiome Members Consistent Across Both Human And Mouse Hosts, Bruce A Rosa, Caroline Snowden, John Martin, Kerstin Fischer, Jonah Kupritz, Ethiopia Beshah, Taniawati Supali, Lincoln Gankpala, Peter U Fischer, Joseph F Urban, Makedonka Mitreva

Open Access Publications

The human whipworm

De Novo Synthesis Of Phosphatidylcholine Is Essential For The Promastigote But Not Amastigote Stage In Leishmania Major, Samrat Moitra, Somrita Basu, Mattie Pawlowic, Fong-Fu Hsu, Kai Zhang

Open Access Publications

Phosphatidylcholine (PC) is the most abundant type of phospholipids in eukaryotes constituting ~30% of total lipids in

Sensible Introduction Of Mr-Guided Radiotherapy: A Warm Plea For The Rct, Helena M Verkooijen, Lauren E Henke

Open Access Publications

Magnetic resonance guided radiotherapy (MRgRT) is the newest face of technology within a field long-characterized by continual technologic advance. MRgRT may offer improvement in the therapeutic index of radiation by offering novel planning types, like online adaptation, and improved image guidance, but there is a paucity of randomized data or ongoing randomized controlled trials (RCTs) to demonstrate clinical gains. Strong clinical evidence is needed to confirm the theoretical advantages of MRgRT and for the rapid dissemination of (and reimbursement for) appropriate use. Although some future evidence for MRgRT may come from large registries and non-randomized studies, RCTs should make up …

Neuroscience Of Object Relations In Health And Disorder: A Proposal For An Integrative Model, Dragan M Svrakic, Charles F Zorumski

Open Access Publications

Recent advances in the neuroscience of episodic memory provide a framework to integrate object relations theory, a psychoanalytic model of mind development, with potential neural mechanisms. Object relations are primordial cognitive-affective units of the mind derived from survival- and safety-level experiences with caretakers during phase-sensitive periods of infancy and toddlerhood. Because these are learning experiences, their neural substrate likely involves memory, here affect-enhanced episodic memory. Inaugural object relations are encoded by the hippocampus-amygdala synaptic plasticity, and systems-consolidated by medial prefrontal cortex (mPFC). Self- and object-mental representations, extracted from these early experiences, are at first dichotomized by contradictory affects evoked by …