Digital Commons Network^™

Leishmania Guyanensis Suppressed Inducible Nitric Oxide Synthase Provoked By Its Viral Endosymbiont, Dmitry Kopelyanskiy, Chantal Desponds, Florence Prevel, Matteo Rossi, Romain Migliorini, Tiia Snäkä, Remzi Onur Eren, Stéphanie Claudinot, Lon-Fye Lye, Manolis Pasparakis, Stephen M Beverley, Nicolas Fasel

2020-Current year OA Pubs

Inducible nitric oxide synthase (iNOS) is essential to the production of nitric oxide (NO), an efficient effector molecule against intracellular human pathogens such as

Avoid Or Embrace? Practice Effects In Alzheimer's Disease Prevention Trials, Andrew J Aschenbrenner, Jason Hassenstab, Guoqiao Wang, Yan Li, Chengjie Xiong, Eric Mcdade, David B Clifford, Randall J Bateman, Et Al.

2020-Current year OA Pubs

Demonstrating a slowing in the rate of cognitive decline is a common outcome measure in clinical trials in Alzheimer's disease (AD). Selection of cognitive endpoints typically includes modeling candidate outcome measures in the many, richly phenotyped observational cohort studies available. An important part of choosing cognitive endpoints is a consideration of improvements in performance due to repeated cognitive testing (termed "practice effects"). As primary and secondary AD prevention trials are comprised predominantly of cognitively unimpaired participants, practice effects may be substantial and may have considerable impact on detecting cognitive change. The extent to which practice effects in AD prevention trials …

Automated Measurement Of Net Water Uptake From Baseline And Follow-Up Cts In Patients With Large Vessel Occlusion Stroke, Atul Kumar, Yasheng Chen, Aaron Corbin, Ali Hamzehloo, Amin Abedini, Zeynep Vardar, Grace Carey, Kunal Bhatia, Laura Heitsch, Jamal J Derakhshan, Jin-Moo Lee, Rajat Dhar

2020-Current year OA Pubs

Quantifying the extent and evolution of cerebral edema developing after stroke is an important but challenging goal. Lesional net water uptake (NWU) is a promising CT-based biomarker of edema, but its measurement requires manually delineating infarcted tissue and mirrored regions in the contralateral hemisphere. We implement an imaging pipeline capable of automatically segmenting the infarct region and calculating NWU from both baseline and follow-up CTs of large-vessel occlusion (LVO) patients. Infarct core is extracted from CT perfusion images using a deconvolution algorithm while infarcts on follow-up CTs were segmented from non-contrast CT (NCCT) using a deep-learning algorithm. These infarct masks …

Elevated Axonal Protein Markers Following Repetitive Blast Exposure In Military Personnel, Rany Vorn, Rosanne Naunheim, Chen Lai, Chelsea Wagner, Jessica M Gill

2020-Current year OA Pubs

Blast exposures that occur during training are common in military personnel; however, the biomarkers that relate to these subtle injuries is not well understood. Therefore, the purpose of this study is to identify the acute biomarkers related to blast injury in a cohort of military personnel exposure to blast-related training. Thirty-four military personnel who participated in the training program were included in this study. Blood samples were collected before and after repetitive blast-related training on days 2 (

Crispr-Cas9 Knock-In Of T513m And G41s Mutations In The Murine Β-Galactosyl-Ceramidase Gene Re-Capitulates Early-Onset And Adult-Onset Forms Of Krabbe Disease, Rima Rebiai, Emily Rue, Steve Zaldua, Duc Nguyen, Giuseppe Scesa, Martin Jastrzebski, Robert Foster, Bin Wang, Xuntian Jiang, Leon Tai, Scott T Brady, Richard Van Breemen, Maria I Givogri, Mark S Sands, Ernesto R Bongarzone

2020-Current year OA Pubs

Krabbe Disease (KD) is a lysosomal storage disorder characterized by the genetic deficiency of the lysosomal enzyme β-galactosyl-ceramidase (GALC). Deficit or a reduction in the activity of the GALC enzyme has been correlated with the progressive accumulation of the sphingolipid metabolite psychosine, which leads to local disruption in lipid raft architecture, diffuse demyelination, astrogliosis, and globoid cell formation. The

Use Of Implementation Mapping With Community-Based Participatory Research: Development Of Implementation Strategies Of A New Goal Setting And Goal Management Intervention System, Eunyoung Kang, Erin R Foster

2020-Current year OA Pubs

AIMS: This study aims to identify implementation determinants, mechanisms of action, implementation strategies, and implementation outcome evaluation plans for a new theory-based rehabilitation goal setting and goal management intervention system, called MyGoals, using Implementation Mapping with community-based participatory research principles.

METHODS: We completed Implementation Mapping tasks 1 to 4 as a planning team consisting of MyGoals target implementers (occupational therapists (OTs), MyGoals intervention target clients (adults with chronic conditions), and the research team. We are currently conducting mapping task 5. These processes were guided by the Consolidated Framework for Implementation Research, social cognitive theory, the taxonomy of behavior change methods, …

Cryogel Scaffold-Mediated Delivery Of Adipose-Derived Stem Cells Promotes Healing In Murine Model Of Atrophic Non-Union, Katherine R Hixon, Dakota B Katz, Jennifer A Mckenzie, Anna N Miller, Farshid Guilak, Matthew J Silva

2020-Current year OA Pubs

Non-union is defined as the permanent failure of a bone to heal and occurs clinically in 5% of fractures. Atrophic non-unions, characterized by absent/minimal callus formation, are poorly understood and difficult to treat. We recently demonstrated a novel murine model of atrophic non-union in the 3.6Col1A1-tk (Col1-tk) mouse, wherein dosing with the nucleoside analog ganciclovir (GCV) was used to deplete proliferating osteoprogenitor cells, leading to a radiographic and biomechanical non-union after the mid-shaft femur fracture. Using this Col1-tk atrophic non-union model, we hypothesized that the scaffold-mediated lentiviral delivery of doxycycline-inducible BMP-2 transgenes would induce osteogenesis at the fracture site. Cryogel …

Hdl Composition, Heart Failure, And Its Comorbidities, Ahmed Diab, Carla Valenzuela Ripoll, Zhen Guo, Ali Javaheri

2020-Current year OA Pubs

Although research on high-density lipoprotein (HDL) has historically focused on atherosclerotic coronary disease, there exists untapped potential of HDL biology for the treatment of heart failure. Anti-oxidant, anti-inflammatory, and endothelial protective properties of HDL could impact heart failure pathogenesis. HDL-associated proteins such as apolipoprotein A-I and M may have significant therapeutic effects on the myocardium, in part by modulating signal transduction pathways and sphingosine-1-phosphate biology. Furthermore, because heart failure is a complex syndrome characterized by multiple comorbidities, there are complex interactions between heart failure, its comorbidities, and lipoprotein homeostatic mechanisms. In this review, we will discuss the effects of heart …

Plasma Neurofilament Light Chain Levels Are Elevated In Children And Young Adults With Wolfram Syndrome, Sarah A Eisenstein, Raveena S Boodram, Courtney L Sutphen, Heather M Lugar, Brian A Gordon, Bess A Marshall, Fumihiko Urano, Anne M Fagan, Tamara Hershey

2020-Current year OA Pubs

Wolfram syndrome is a rare disease caused by pathogenic variants in the

Differential Sphingosine-1-Phosphate Receptor-1 Protein Expression In The Dorsolateral Prefrontal Cortex Between Schizophrenia Type 1 And Type 2, Ganesh B Chand, Hao Jiang, J Philip Miller, C Harker Rhodes, Zhude Tu, Dean Foster Wong

2020-Current year OA Pubs

Understanding the etiology and treatment approaches in schizophrenia is challenged in part by the heterogeneity of this disorder. One encouraging progress is the growing evidence that there are subtypes of schizophrenia. Recent

Modification Of Neurogenic Colonic Motor Behaviours By Chemogenetic Ablation Of Calretinin Neurons, Jing Feng, Tim J Hibberd, Jialie Luo, Pu Yang, Zili Xie, Lee Travis, Nick J Spencer, Hongzhen Hu

2020-Current year OA Pubs

How the enteric nervous system determines the pacing and propagation direction of neurogenic contractions along the colon remains largely unknown. We used a chemogenetic strategy to ablate enteric neurons expressing calretinin (CAL). Mice expressing human diphtheria toxin receptor (DTR) in CAL neurons were generated by crossing

The Temporal Relationship Between Local School Closure And Increased Incidence Of Pediatric Diabetic Ketoacidosis, Casey K Mccluskey, Janine E Zee-Cheng, Margaret J Klein, Matthew C Scanlon, Alexandre T Rotta, Kenneth E Remy, Christopher L Carroll, Steven L Shein

2020-Current year OA Pubs

IMPORTANCE: The incidence of pediatric diabetic ketoacidosis (DKA) increased early in the COVID-19 pandemic, but the relative contribution of behavioral changes and viral-related pathophysiology are unknown.

OBJECTIVE: To evaluate the relationship between school closure date and onset of increased DKA to help clarify the etiology of the increased incidence.

DESIGN: A multi-center, quality-controlled Pediatric Intensive Care Unit (PICU) database was used to identify the number of admissions to a participating PICU with DKA on each calendar day from 60 days before local school closure to 90 days after, and compared to baseline data from the same periods in 2018-2019. Interrupted …

Is It Possible To Separate The Graft-Versus-Leukemia (Gvl) Effect Against B Cell Acute Lymphoblastic Leukemia From Graft-Versus-Host Disease (Gvhd) After Hematopoietic Cell Transplant?, Jacob Rozmus, Sima T Bhatt, Nataliya Prokopenko Buxbaum, Geoffrey D E Cuvelier, Amanda M Li, Carrie L Kitko, Kirk R Schultz

2020-Current year OA Pubs

Hematopoietic cell transplant is a curative therapy for many pediatric patients with high risk acute lymphoblastic leukemia. Its therapeutic mechanism is primarily based on the generation of an alloreactive graft-versus-leukemia effect that can eliminate residual leukemia cells thus preventing relapse. However its efficacy is diminished by the concurrent emergence of harmful graft-versus-host disease disease which affects healthly tissue leading to significant morbidity and mortality. The purpose of this review is to describe the interventions that have been trialed in order to augment the beneficial graft-versus leukemia effect post-hematopoietic cell transplant while limiting the harmful consequences of graft-versus-host disease. This includes …

Glial Dysfunction And Its Contribution To The Pathogenesis Of The Neuronal Ceroid Lipofuscinoses, Keigo Takahashi, Hemanth R Nelvagal, Jenny Lange, Jonathan D Cooper

2020-Current year OA Pubs

While significant efforts have been made in developing pre-clinical treatments for the neuronal ceroid lipofuscinoses (NCLs), many challenges still remain to bring children with NCLs a cure. Devising effective therapeutic strategies for the NCLs will require a better understanding of pathophysiology, but little is known about the mechanisms by which loss of lysosomal proteins causes such devastating neurodegeneration. Research into glial cells including astrocytes, microglia, and oligodendrocytes have revealed many of their critical functions in brain homeostasis and potential contributions to neurodegenerative diseases. Genetically modified mouse models have served as a useful platform to define the disease progression in the …

Case Report: "Primary Immunodeficiency"-Severe Autoimmune Enteropathy In A Pediatric Heart Transplant Recipient Treated With Abatacept And Alemtuzumab, Elizaveta Kalaidina, Elizabeth C Utterson, Deepa Mokshagundam, Mai He, Shalini Shenoy, Megan A Cooper

2020-Current year OA Pubs

Disorders of immune dysregulation following heart transplantation in children have been reported; however, the management of such disorders remains uncertain and challenging. In this case report, we describe a clinical course of a child with severe autoimmune enteropathy after a heart transplant in infancy and detail a treatment approach with abatacept and alemtuzumab. A 21-month-old girl with a medical history of congenital dilated cardiomyopathy and heart transplantation at 2 months was evaluated for chronic hematochezia. The patient underwent an extensive workup, including endoscopic biopsy which showed crypt apoptosis, similar to that seen with graft-versus-host disease (GVHD). Results of her immune …

Low Cancer Incidence In Naked Mole-Rats May Be Related To Their Inability To Express The Warburg Effect, Pedro Freire Jorge, Matthew L Goodwin, Maurits H Renes, Maarten W Nijsten, Matthew Pamenter

2020-Current year OA Pubs

Metabolic flexibility in mammals enables stressed tissues to generate additional ATP by converting large amounts of glucose into lactic acid; however, this process can cause transient local or systemic acidosis. Certain mammals are adapted to extreme environments and are capable of enhanced metabolic flexibility as a specialized adaptation to challenging habitat niches. For example, naked mole-rats (NMRs) are a fossorial and hypoxia-tolerant mammal whose metabolic responses to environmental stressors markedly differ from most other mammals. When exposed to hypoxia, NMRs exhibit robust hypometabolism but develop minimal acidosis. Furthermore, and despite a very long lifespan relative to other rodents, NMRs have …

Efficacy Of Laser Interstitial Thermal Therapy (Litt) For Newly Diagnosed And Recurrent Idh Wild-Type Glioblastoma, John F De Groot, Albert H Kim, Et Al.

2020-Current year OA Pubs

BACKGROUND: Treatment options for unresectable new and recurrent glioblastoma remain limited. Laser ablation has demonstrated safety as a surgical approach to treating primary brain tumors. The LAANTERN prospective multicenter registry (NCT02392078) data were analyzed to determine clinical outcomes for patients with new and recurrent

METHODS: Demographics, intraprocedural data, adverse events, KPS, health economics, and survival data were prospectively collected and then analyzed on

RESULTS: A total of 29 new and 60 recurrent

CONCLUSIONS: Laser ablation is a viable option for patients with new and recurrent glioblastoma. Median OS for

Leptomeningeal Disease And Tumor Dissemination In A Murine Diffuse Intrinsic Pontine Glioma Model: Implications For The Study Of The Tumor-Cerebrospinal Fluid-Ependymal Microenvironment, Shelei Pan, Dezhuang Ye, Yimei Yue, Lihua Yang, Christopher P Pacia, Dakota Defreitas, Prabagaran Esakky, Sonika Dahiya, David D Limbrick, Joshua B Rubin, Hong Chen, Jennifer M Strahle

2020-Current year OA Pubs

BACKGROUND: Leptomeningeal disease and hydrocephalus are present in up to 30% of patients with diffuse intrinsic pontine glioma (DIPG), however there are no animal models of cerebrospinal fluid (CSF) dissemination. As the tumor-CSF-ependymal microenvironment may play an important role in tumor pathogenesis, we identified characteristics of the Nestin-tumor virus A (Nestin-Tva) genetically engineered mouse model that make it ideal to study the interaction of tumor cells with the CSF and its associated pathways with implications for the development of treatment approaches to address CSF dissemination in DIPG.

METHODS: A Nestin-Tva model of DIPG utilizing the 3 most common DIPG genetic …

Prospective Biomarker Study In Newly Diagnosed Glioblastoma: Cyto-C Clinical Trial, Corinne E Griguer, Milan G Chheda, Et Al.

2020-Current year OA Pubs

BACKGROUND: Glioblastoma (GBM) has a 5-year survival rate of 3%-5%. GBM treatment includes maximal resection followed by radiotherapy with concomitant and adjuvant temozolomide (TMZ). Cytochrome C oxidase (CcO) is a mitochondrial enzyme involved in the mechanism of resistance to TMZ. In a prior retrospective trial, CcO activity in GBMs inversely correlated with clinical outcome. The current Cyto-C study was designed to prospectively evaluate and validate the prognostic value of tumor CcO activity in patients with newly diagnosed primary GBM, and compared to the known prognostic value of

METHODS: This multi-institutional, blinded, prospective biomarker study enrolled 152 patients with newly diagnosed …

Multivariate Analysis Of Associations Between Clinical Sequencing And Outcome In Glioblastoma, Peter H Yang, Yu Tao, Jingqin Luo, Mounica Paturu, Hsiang-Chih Lu, Shakti Ramkissoon, Jonathan W Heusel, Eric C Leuthardt, Michael R Chicoine, Joshua L Dowling, Gavin P Dunn, Eric Duncavage, Sonika Dahiya, Arindam R Chattherjee, Albert H Kim

2020-Current year OA Pubs

BACKGROUND: Many factors impact survival in patients with glioblastoma, including age, Karnofsky Performance Status, postoperative chemoradiation,

METHODS: We utilized a widely available diagnostic platform (FoundationOne CDx) to perform high-throughput next-generation sequencing on 185 patients with newly diagnosed glioblastoma in our tertiary care center. We performed multivariate analysis to control for clinical parameters with known impact on survival to elucidate the independent prognostic value of prevalent mutant genes and the independent impact of gross total resection.

RESULTS: When controlling for factors with known prognostic significance including

CONCLUSIONS: This study verifies the independent prognostic value of several mutant genes in glioblastoma. Six …

Immune Deconvolution And Temporal Mapping Identifies Stromal Targets And Developmental Intervals For Abrogating Murine Low-Grade Optic Glioma Formation, Amanda De Andrade Costa, Jit Chatterjee, Olivia Cobb, Elizabeth Cordell, Astoria Chao, Suzanne Schaeffer, Andrea Goldstein, Sonika Dahiya, David H Gutmann

2020-Current year OA Pubs

BACKGROUND: Brain tumor formation and progression are dictated by cooperative interactions between neoplastic and non-neoplastic cells. This stromal dependence is nicely illustrated by tumors arising in the Neurofibromatosis type 1 (NF1) cancer predisposition syndrome, where children develop low-grade optic pathway gliomas (OPGs). Using several authenticated

METHODS: A combination of bulk and single-cell RNA mouse optic nerve sequencing, immunohistochemistry, T cell assays, and pharmacologic and antibody-mediated inhibition methods were used in these experiments.

RESULTS: We show that T cells and microglia are the main non-neoplastic immune cell populations in both murine and human LGGs. Moreover, we demonstrate that CD8

CONCLUSIONS: Collectively, …

Mitochondrial Fitness And Cancer Risk, Andrew V. Kossenkov, Andrew Milcarek, Faiyaz Notta, Gun-Ho Jang, Julie M. Wilson, Steven Gallinger, Daniel Cui Zhou, Li Ding, Jagadish C. Ghosh, Michela Perego, Annamaria Morotti, Marco Locatelli, Marie E. Robert, Valentina Vaira, Dario C. Altieri

2020-Current year OA Pubs

Changes in metabolism are a hallmark of cancer, but molecular signatures of altered bioenergetics to aid in clinical decision-making do not currently exist. We recently identified a group of human tumors with constitutively reduced expression of the mitochondrial structural protein, Mic60, also called mitofilin or inner membrane mitochondrial protein (IMMT). These Mic60-low tumors exhibit severe loss of mitochondrial fitness, paradoxically accompanied by increased metastatic propensity and upregulation of a unique transcriptome of Interferon (IFN) signaling and Senescence-Associated Secretory Phenotype (SASP). Here, we show that an optimized, 11-gene signature of Mic60-low tumors is differentially expressed in multiple malignancies, compared to normal …

Children With Supratentorial Midline Pilocytic Astrocytomas Exhibit Multiple Progressions And Acquisition Of Neurologic Deficits Over Time, Nicole M Brossier, Jennifer M Strahle, Samuel J Cler, Michael Wallendorf, David H Gutmann

2020-Current year OA Pubs

No abstract provided.

The Impact Of A Virtual Orthopaedic Surgery Symposium On Medical Students: Increasing Awareness And Knowledge Of The Field, Theodore Quan, Alex Gu, Amil R. Agarwal, Simone A. Bernstein, Alisa Malyavko, William N. Levine, Lisa K. Cannada, Medical Student Orthopedic Society

2020-Current year OA Pubs

UNLABELLED: Orthopaedic surgery has become an increasingly popular field of residency training for medical students. Many institutions offer elective time to explore areas of interest through clinical rotations and research; however, most of these opportunities are reserved for senior medical students. The purpose of this study was to evaluate the impact of a dedicated medical student orthopaedic surgery symposium to increase awareness about the field and to assess students' interest and knowledge of orthopaedic surgery before and after the symposium.

METHODS: Medical students were invited to submit orthopaedic surgery-related research to a free, 1-day virtual symposium held in April 2022. …

Employment Status For “Essential Workers”: The Case For Gig Worker Parity, Miriam A. Cherry

All Faculty Scholarship

This Article explores what I call the “essential worker paradox”: During the pandemic, gig workers have been recognized as providing critical and important services. At the same time, the law has yet to recognize gig workers fully and to commit to providing them with the same basic protections as employees. The Article argues that the stark difference in treatment between gig workers and regular employees has long created unfairness. While views of gig work as a side hustle or work driven by customer convenience may have prevailed in the past, now the meal delivery driver and the on-demand grocery shopper …

Developing Standards For Gender-Responsive Human Rights Due Diligence, Constance Z. Wagner, Nancy Kaymar Stafford

All Faculty Scholarship

This article addresses the current state of gender-responsive human rights due diligence (GR-HRDD) standards and advocates for greater attention to be paid to women’s human rights in the due diligence process. The 2011 United Nations Guiding Principles on Business and Human Rights (UNGPs) created a global framework for recognizing, preventing, and addressing the risk of adverse impacts of human rights violations linked to business activities. The responsibility of businesses to respect human rights under the UNGPs includes implementing a human rights due diligence process. Although the UNGPs do not provide guidance on the process for integrating women’s rights into human …

Acknowledging The Racist Roots Of Disinvestment And Abandonment: How Local Government Can Set The Stage For Change, Dana M. Malkus

All Faculty Scholarship

Disinvestment and associated property abandonment are defining features of many post-industrial legacy cities. While the reasons are varied and complex, racist law and policy are at the root. Though abandoned properties negatively affect an entire city, their effects usually disproportionately fall on neighborhoods of color. Law and policy have been major drivers of how such neighborhoods look and feel today. Because law and policy have been part of the problem, they are also a necessary part of the solution.

This kind of large-scale, multi-disciplinary problem is beyond the ability of a single institution or sector to address. Stakeholders such as …

Block Rewards, Carried Interests, And Other Valuation Quandaries In Taxing Compensation, Henry M. Ordower

All Faculty Scholarship

In this article, Ordower contextualizes block rewards litigation with historical failures to tax compensation income paid in kind. Tax fairness principles demand current taxation of the noneconomically diluting block rewards’ market value.

Fix Or Fox: Where Do We Go From Here?, Marsha Griggs

All Faculty Scholarship

Recently the National Conference of Bar Examiners (“NCBE”) announced that it will make sample questions from its proposed NextGen Bar Exam publicly available. NCBE is the entity that creates and sells all the questions used on the Uniform Bar Exam adopted in Kansas, Missouri, and thirty-six other states. In theory, the NextGen Exam is being developed in response to mounting critique that the bar exam is not a true measure of competence to practice law and claims that the exam disadvantages applicants based on socioeconomic status and race. But is the NextGen prototype a fix or a fox in the …

Book Review Of Shaping The Bar: The Future Of Attorney Licensing, Marsha Griggs, Andrea A. Curcio

All Faculty Scholarship

In Shaping the Bar: The Future of Attorney Licensing, Professor Joan Howarth issues a clarion call to the academy, the legal community, and the judiciary to reform the way we license lawyers in the United States. In this book Howarth identifies the current crisis in law licensing, the history of racism that created this crisis, and the tools available to address it. Shaping the Bar challenges our entrenched notions of professional identity, and it forces us to confront vulnerabilities in attorney self-regulation. It does so in a manner that will stir even those not immersed in the current debate about …