Digital Commons Network^™

Bland Embolization Of Benign Liver Tumors: Review Of The Literature And A Single Center Experience, Daniel Crawford, Sailen Naidu, Indravadan Patel, Grace Knuttinen, Sadeer Alzubaidi, Rahmi Oklu

Open Access Publications

Transarterial embolization has shown promise as a safe, effective, and less invasive treatment modality for benign liver lesions (hemangioma, focal nodular hyperplasia (FNH), and hepatic adenoma (HA)) with fewer complications compared to surgical intervention. There is no consensus regarding the most appropriate embolization material(s) for the treatment of benign liver tumors. The purpose of this study was to review the current literature regarding the transarterial embolization of benign liver tumors and to share our single center experience. This was a non-blinded, retrospective, single-institution review of the bland embolization of benign liver tumors. Clinical data and imaging before and after embolization …

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.

Dosimetric Impact Of Range Uncertainty In Passive Scattering Proton Therapy, Ruirui Liu, Baozhou Sun, Tiezhi Zhang, Jeffery F Williamson, Joseph A O'Sullivan, Tianyu Zhao

Open Access Publications

PURPOSE: The objective of this study was to investigate the dosimetric impact of range uncertainty in a large cohort of patients receiving passive scatter proton therapy.

METHODS: A cohort of 120 patients were reviewed in this study retrospectively, of which 61 were brain, 39 lung, and 20 prostate patients. Range uncertainties of ±3.5% (overshooting and undershooting by 3.5%, respectively) were added and recalculated on the original plans, which had been planned according to our clinical planning protocol while keeping beamlines, apertures, compensators, and dose grids intact. Changes in the coverage on CTV and DVH for critical organs were compared and …

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.

Perlecan In Pericellular Mechanosensory Cell-Matrix Communication, Extracellular Matrix Stabilisation And Mechanoregulation Of Load-Bearing Connective Tissues, Farshid Guilak, Anthony J Hayes, James Melrose

Open Access Publications

In this study, we review mechanoregulatory roles for perlecan in load-bearing connective tissues. Perlecan facilitates the co-acervation of tropoelastin and assembly of elastic microfibrils in translamellar cross-bridges which, together with fibrillin and elastin stabilise the extracellular matrix of the intervertebral disc annulus fibrosus. Pericellular perlecan interacts with collagen VI and XI to define and stabilize this matrix compartment which has a strategic position facilitating two-way cell-matrix communication between the cell and its wider extracellular matrix. Cues from the extracellular matrix are fed through this pericellular matrix back to the chondrocyte, allowing it to perceive and respond to subtle microenvironmental changes …

Cerebral Expression Of Metabotropic Glutamate Receptor Subtype 5 In Idiopathic Autism Spectrum Disorder And Fragile X Syndrome: A Pilot Study, James Robert Brašić, Ayon Nandi, David S Russell, Danna Jennings, Olivier Barret, Samuel D Martin, Keith Slifer, Thomas Sedlak, John P Seibyl, Dean F Wong, Dejan B Budimirovic

Open Access Publications

Multiple lines of evidence suggest that dysfunction of the metabotropic glutamate receptor subtype 5 (mGluR

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 …

Unsupervised Cluster Analysis Of Patients With Recovered Left Ventricular Ejection Fraction Identifies Unique Clinical Phenotypes, Andrew Perry, Francis Loh, Luigi Adamo, Kathleen W. Zhang, Elena Deych, Randi Foraker, Douglas L. Mann

Open Access Publications

BACKGROUND: Patients with heart failure (HF) with recovered ejection fraction (HFrecEF) are a recently identified cohort that are phenotypically and biologically different from HFrEF and HFpEF patients. Whether there are unique phenotypes among HFrecEF patients is not known.

METHODS: We studied all patients at a large medical center, who had an improvement in LVEF from ≤ 35% to ≥ 50% (LVrecEF) between January 1, 2005 and December 31, 2013. We identified a set of 11 clinical variables and then performed unsupervised clustering analyses to identify unique clinical phenotypes among patients with LVrecEF, followed by a Kaplan-Meier analysis to identify differences …

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% …

Blood Leukocytes Recapitulate Diabetogenic Peptide-Mhc-Ii Complexes Displayed In The Pancreatic Islets, Anthony N. Vomund, Cheryl F. Lichti, Orion J. Peterson, Ana Maria Arbelaez, Xiaoxiao Wan, Emil R. Unanue

Open Access Publications

Assessing the self-peptides presented by susceptible major histocompatibility complex (MHC) molecules is crucial for evaluating the pathogenesis and therapeutics of tissue-specific autoimmune diseases. However, direct examination of such MHC-bound peptides displayed in the target organ remains largely impractical. Here, we demonstrate that the blood leukocytes from the nonobese diabetic (NOD) mice presented peptide epitopes to autoreactive CD4 T cells. These peptides were bound to the autoimmune class II MHC molecule (MHC-II) I-Ag7 and originated from insulin B-chain and C-peptide. The presentation required a glucose challenge, which stimulated the release of the insulin peptides from the pancreatic islets. The circulating leukocytes, …

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 …

Unmet Medical Needs And Future Perspectives For Leiomyosarcoma Patients-A Position Paper From The National Leiomyosarcoma Foundation (Nlmsf) And Sarcoma Patients Euronet (Spaen), Bernd Kasper, Brian A Van Tine, Et Al

Open Access Publications

As leiomyosarcoma patients are challenged by the development of metastatic disease, effective systemic therapies are the cornerstone of outcome. However, the overall activity of the currently available conventional systemic treatments and the prognosis of patients with advanced or metastatic disease are still poor, making the treatment of this patient group challenging. Therefore, in a joint effort together with patient networks and organizations, namely Sarcoma Patients EuroNet (SPAEN), the international network of sarcoma patients organizations, and the National LeioMyoSarcoma Foundation (NLMSF) in the United States, we aim to summarize state-of-the-art treatments for leiomyosarcoma patients in order to identify knowledge gaps and …

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, …

Applications Of Ipsc-Derived Beta Cells From Patients With Diabetes, Kristina G. Maxwell, Jeffrey R. Millman

Open Access Publications

No abstract provided.

Mechanisms Of Damage Tolerance And Repair During Dna Replication, Mohamed Elsaid Ashour, Nima Mosammaparast

Open Access Publications

Accurate duplication of chromosomal DNA is essential for the transmission of genetic information. The DNA replication fork encounters template lesions, physical barriers, transcriptional machinery, and topological barriers that challenge the faithful completion of the replication process. The flexibility of replisomes coupled with tolerance and repair mechanisms counteract these replication fork obstacles. The cell possesses several universal mechanisms that may be activated in response to various replication fork impediments, but it has also evolved ways to counter specific obstacles. In this review, we will discuss these general and specific strategies to counteract different forms of replication associated damage to maintain genomic …

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 …

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 …

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 …