Digital Commons Network^™

Rheumatoid Meningitis Sine Arthritis., Cathy Lee-Ching, Lawrence C. Kenyon, Matthew Berk, Chantel Park

Department of Medicine Faculty Papers

Rheumatoid meningitis is a rare and very serious extra-articular manifestation of rheumatoid arthritis. We present a case of a 7()year-old female with no history of arthritis who developed stroke-like symptoms, seizures, psychosis and compulsive behavior. Serial brain magnetic resonance images (MRI) over four months demonstrated progressive interhemispheric meningeal thickening. She had mild lymphocytic pleocytosis on the cerebrospinal fluid analysis and serum anti-cyclic citrullinated peptide antibodies resulted positive in high titers. She underwent a brain biopsy showing necrotizing granulomas consistent with rheumatoid meningitis. Her symptoms resolved with treatment with glucocorticoids and cyclophosphamide. She has not been diagnosed with rheumatoid arthritis even …

Social Determinants Of Health And What Mothers Say They Need And Want After Release From Jail., Elisabeth Stelson, Marjie Mogul, Holly Harner, Jeane Ann Grisso, Rosemary Frasso Phd, Msc, Cph

College of Population Health Faculty Papers

Identifying the biopsychosocial needs of mothers who have been released from jail is critical to understanding the best ways to support their health and stability after release. In May through August 2014, we interviewed 15 mothers who had been released from an urban jail about their reentry experiences, and we analyzed transcripts for themes. Eight domains of community reentry emerged through analysis: behavioral health services, education, employment, housing, material resources, medical care, relationships with children, and social support. Participants defined barriers to successful reentry, which paralleled the social determinants of health, and shared suggestions that could be used to mitigate …

Kaposi’S Sarcoma-Associated Herpesvirus Seropositivity Is Associated With Type 2 Diabetes Mellitus: A Case–Control Study In Xinjiang, China, Meng Cui, Qiwen Fang, Jun Zheng, Zhanjun Shu, Yin Chen, Yage Fan, Juan Zhao, Charles Wood, Tiejun Zhang, Yan Zeng

Nebraska Center for Virology: Faculty Publications

Objective: To assess the potential relationship between Kaposi’s sarcoma-associated herpesvirus (KSHV) infection and type 2 diabetes mellitus (DM-2) in Xinjiang, China.

Methods: A case–control study of consecutively included DM-2 patients and normal controls was conducted among the Uygur and Han populations in Xinjiang Uygur Autonomous Region, China. Blood samples were collected and KSHV seroprevalence, antibody titers, and viral load were investigated. Logistic regression analysis and multiple linear regression analysis were applied to explore determinants of the main outcome measures.

Results: A total of 324 patients with DM-2 and 376 normal controls were included. The seroprevalence of KSHV was 49.1% (95% …

Multiple Tumor Suppressors Regulate A Hif-Dependent Negative Feedback Loop Via Isgf3 In Human Clear Cell Renal Cancer., Lili Liao, Zongzhi Z. Liu, Lauren Langbein, Weijia Cai, Eun-Ah Cho, Jie Na, Xiaohua Niu, Wei Jiang, Zhijiu Zhong, Wesley L. Cai, Geetha Jagannathan, Essel Dulaimi, Joseph R. Testa, Robert G. Uzzo, Yuxin Wang, George R. Stark, Jianxin Sun, Stephen C. Peiper, Yaomin Xu, Qin Yan, Haifeng Yang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Whereas VHL inactivation is a primary event in clear cell renal cell carcinoma (ccRCC), the precise mechanism(s) of how this interacts with the secondary mutations in tumor suppressor genes, including PBRM1, KDM5C/JARID1C, SETD2, and/or BAP1, remains unclear. Gene expression analyses reveal that VHL, PBRM1, or KDM5C share a common regulation of interferon response expression signature. Loss of HIF2α, PBRM1, or KDM5C in VHL-/-cells reduces the expression of interferon stimulated gene factor 3 (ISGF3), a transcription factor that regulates the interferon signature. Moreover, loss of SETD2 or BAP1 also reduces the ISGF3 level. Finally, ISGF3 is strongly tumor-suppressive in a xenograft …

Sparse Recurrent Excitatory Connectivity In The Microcircuit Of The Adult Mouse And Human Cortex., Stephanie C Seeman, Luke Campagnola, Pasha A Davoudian, Alex Hoggarth, Travis A Hage, Alice Bosma-Moody, Christopher A Baker, Jung Hoon Lee, Stefan Mihalas, Corinne Teeter, Andrew L Ko, Jeffrey G Ojemann, Ryder P Gwinn, Daniel L Silbergeld, Charles Cobbs, John Phillips, Ed Lein, Gabe Murphy, Christof Koch, Hongkui Zeng, Tim Jarsky

Articles, Abstracts, and Reports

Generating a comprehensive description of cortical networks requires a large-scale, systematic approach. To that end, we have begun a pipeline project using multipatch electrophysiology, supplemented with two-photon optogenetics, to characterize connectivity and synaptic signaling between classes of neurons in adult mouse primary visual cortex (V1) and human cortex. We focus on producing results detailed enough for the generation of computational models and enabling comparison with future studies. Here, we report our examination of intralaminar connectivity within each of several classes of excitatory neurons. We find that connections are sparse but present among all excitatory cell classes and layers we sampled, …

Systemwide Clinical Ultrasound Program Development: An Expert Consensus Model., Robert Strony, Jennifer R. Marin, John Bailitz, Anthony J. Dean, Mike Blaivas, Vivek Tayal, Chris Raio, Rachel Liu, Aimee Woods, Michael Zwank, Matthew Fields, Alyssa Abo, Stan Wu, Tarina Kang, Teresa Liu, Megan Leo, Courtney Smalley, Jerry Chiricolo, Mikaela Chilstrom, Resa E. Lewiss

Department of Emergency Medicine Faculty Papers

Clinical ultrasound (CUS) is integral to the practice of an increasing number of medical specialties. Guidelines are needed to ensure effective CUS utilization across health systems. Such guidelines should address all aspects of CUS within a hospital or health system. These include leadership, training, competency, credentialing, quality assurance and improvement, documentation, archiving, workflow, equipment, and infrastructure issues relating to communication and information technology. To meet this need, a group of CUS subject matter experts, who have been involved in institution- and/or systemwide clinical ultrasound (SWCUS) program development convened. The purpose of this paper was to create a model for SWCUS …

Lateralized Hippocampal Oscillations Underlie Distinct Aspects Of Human Spatial Memory And Navigation., Jonathan Miller, Andrew J. Watrous, Melina Tsitsiklis, Sang Ah Lee, Sameer A. Sheth, Catherine A. Schevon, Elliot H. Smith, Michael R. Sperling, Ashwini Sharan, Ali Akbar Asadi-Pooya, Gregory A. Worrell, Stephen Meisenhelter, Cory S. Inman, Kathryn A. Davis, Bradley Lega, Paul A. Wanda, Sandhitsu R. Das, Joel M. Stein, Richard Gorniak, Joshua Jacobs

Department of Neurology Faculty Papers

The hippocampus plays a vital role in various aspects of cognition including both memory and spatial navigation. To understand electrophysiologically how the hippocampus supports these processes, we recorded intracranial electroencephalographic activity from 46 neurosurgical patients as they performed a spatial memory task. We measure signals from multiple brain regions, including both left and right hippocampi, and we use spectral analysis to identify oscillatory patterns related to memory encoding and navigation. We show that in the left but not right hippocampus, the amplitude of oscillations in the 1-3-Hz "low theta" band increases when viewing subsequently remembered object-location pairs. In contrast, in …

Additive Drug-Specific And Sex-Specific Risks Associated With Co-Use Of Marijuana And Tobacco During Pregnancy: Evidence From 3 Recent Developmental Cohorts (2003-2015)., Suena H Massey, Daniel K Mroczek, David Reiss, Emily S Miller, Jessica A Jakubowski, Eileen K Graham, Shannon M Shisler, Meaghan Mccallum, Marilyn A. Huestis, Jody M Ganiban, Daniel S Shaw, Leslie D Leve, Rina D Eiden, Laura R Stroud, Jenae M Neiderhiser

Institute of Emerging Health Professions Faculty Papers

BACKGROUND: Methodologic challenges related to the concomitant use (co-use) of substances and changes in policy and potency of marijuana contribute to ongoing uncertainty about risks to fetal neurodevelopment associated with prenatal marijuana use. In this study, we examined two biomarkers of fetal neurodevelopmental risk-birth weight and length of gestation-associated with prenatal marijuana use, independent of tobacco (TOB), alcohol (ALC), other drug use (OTH), and socioeconomic risk (SES), in a pooled sample (N = 1191) derived from 3 recent developmental cohorts (2003-2015) with state-of-the-art substance use measures. We examined differential associations by infant sex, and multiplicative effects associated with co-use of …

Targeting Cdk6 And Bcl2 Exploits The "Myb Addiction" Of Ph+ Acute Lymphoblastic Leukemia, Marco De Dominici, Patrizia Porazzi, Angela Rachele Soliera, Samanta A. Mariani, Sankar Addya, Paolo Fortina, Luke F. Peterson, Orietta Spinelli, Alessandro Rambaldi, Giovanni Martinelli, Anna Ferrari, Ilaria Iacobucci, Bruno Calabretta

Department of Cancer Biology Faculty Papers

Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph^þ ALL) is currently treated with BCR-ABL1 tyrosine kinase inhibitors (TKI) in combination with chemotherapy. However, most patients develop resistance to TKI through BCR-ABL1–dependent and –independent mechanisms. Newly developed TKI can target Ph^þ ALL cells with BCR-ABL1–dependent resistance; however, overcoming BCR-ABL1–independent mechanisms of resistance remains challenging because transcription factors, which are difficult to inhibit, are often involved. We show here that (i) the growth of Ph^þ ALL cell lines and primary cells is highly dependent on MYB-mediated transcriptional upregulation of CDK6, cyclin D3, and BCL2, and (ii) restoring their expression in MYB-silenced …

Closed-Loop Stimulation Of Temporal Cortex Rescues Functional Networks And Improves Memory., Youssef Ezzyat, Paul A. Wanda, Deborah F. Levy, Allison Kadel, Ada Aka, Isaac Pedisich, Michael R. Sperling, Ashwini Sharan, Bradley C. Lega, Alexis Burks, Robert E. Gross, Cory S. Inman, Barbara C. Jobst, Mark A. Gorenstein, Kathryn A. Davis, Gregory A. Worrell, Michal T. Kucewicz, Joel M. Stein, Richard Gorniak, Sandhitsu R. Das, Daniel S. Rizzuto, Michael J. Kahana

Department of Neurology Faculty Papers

Memory failures are frustrating and often the result of ineffective encoding. One approach to improving memory outcomes is through direct modulation of brain activity with electrical stimulation. Previous efforts, however, have reported inconsistent effects when using open-loop stimulation and often target the hippocampus and medial temporal lobes. Here we use a closed-loop system to monitor and decode neural activity from direct brain recordings in humans. We apply targeted stimulation to lateral temporal cortex and report that this stimulation rescues periods of poor memory encoding. This system also improves later recall, revealing that the lateral temporal cortex is a reliable target …

Development Of An Objective Assessment Tool For Total Laparoscopic Hysterectomy: A Delphi Method Among Experts And Evaluation On A Virtual Reality Simulator., Sophie Knight, Rajesh Aggarwal, Md, Phd, Frcs, Facs, Aubert Agostini, Anderson Loundou, Stéphane Berdah, Patrice Crochet

Department of Surgery Faculty Papers

INTRODUCTION: Total Laparoscopic hysterectomy (LH) requires an advanced level of operative skills and training. The aim of this study was to develop an objective scale specific for the assessment of technical skills for LH (H-OSATS) and to demonstrate feasibility of use and validity in a virtual reality setting.

MATERIAL AND METHODS: The scale was developed using a hierarchical task analysis and a panel of international experts. A Delphi method obtained consensus among experts on relevant steps that should be included into the H-OSATS scale for assessment of operative performances. Feasibility of use and validity of the scale were evaluated by …

Erk-Mediated Phosphorylation Regulates Sox10 Sumoylation And Targets Expression In Mutant Braf Melanoma., Shujun Han, Yibo Ren, Wangxiao He, Huadong Liu, Zhe Zhi, Xinliang Zhu, Tielin Yang, Yu Rong, Bohan Ma, Timothy J. Purwin, Zhenlin Ouyang, Caixia Li, Xun Wang, Xueqiang Wang, Huizi Yang, Yan Zheng, Andrew E. Aplin, Jiankang Liu, Yongping Shao

Department of Cancer Biology Faculty Papers

In human mutant BRAF melanoma cells, the stemness transcription factor FOXD3 is rapidly induced by inhibition of ERK1/2 signaling and mediates adaptive resistance to RAF inhibitors. However, the mechanism underlying ERK signaling control of FOXD3 expression remains unknown. Here we show that SOX10 is both necessary and sufficient for RAF inhibitor-induced expression of FOXD3 in mutant BRAF melanoma cells. SOX10 activates the transcription of FOXD3 by binding to a regulatory element in FOXD3 promoter. Phosphorylation of SOX10 by ERK inhibits its transcription activity toward multiple target genes by interfering with the sumoylation of SOX10 at K55, which is essential for …

Determination Of An Optimal Response Cut-Off Able To Predict Progression-Free Survival In Patients With Well-Differentiated Advanced Pancreatic Neuroendocrine Tumours Treated With Sunitinib: An Alternative To The Current Recist-Defined Response., Angela Lamarca, Jorge Barriuso, Matthew Kulke, Ivan Borbath, Heinz-Josef Lenz, Jean Luc Raoul, Neal J. Meropol, Catherine Lombard-Bohas, James Posey, Sandrine Faivre, Eric Raymond, Juan W. Valle

Department of Medical Oncology Faculty Papers

BACKGROUND: Sunitinib prolongs progression-free survival (PFS) in patients with advanced pancreatic neuroendocrine tumours (pNET). Response Evaluation Criteria in Solid Tumors (RECIST)-defined partial responses (PR; classically defined as ⩾30% size decrease from baseline) are infrequent.

METHODS: Individual data of pNET patients from the phase II [NCT00056693] and pivotal phase III [NCT00428597] trials of sunitinib were analysed in this investigator-initiated, post hoc study. The primary objective was to determine the optimal RECIST (v.1.0) response cut-off value to identify patients who were progression-free at 11 months (median PFS in phase III trial); and the most informative time-point (highest area under the curve (AUC) …

Overwhelming Research And Clinical Evidence Of Exercise Medicine Efficacy In Cancer Management—Translation Into Practice Is The Challenge Before Us, Robert Newton

Research outputs 2014 to 2021

The paper “Connecting people with cancer to physical activity and exercise programs: a pathway to create accessibility and engagement”1 is very timely. As the authors have convincingly demonstrated, rigorous clinical and research evidence support something of which most medical and allied health professionals are cognizant: the benefit of physical activity and exercise for people with cancer.

Association Of Obstructive Sleep Apnea With Hypertension: A Systematic Review And Meta-Analysis, Haifeng Hou, Yange Zhao, Xiaotong Xue, Jian Ding, Wei Jia Xing, Wei Wang

Research outputs 2014 to 2021

Results: Twenty-six studies with 51 623 participants (28 314 men, 23 309 women; mean age 51.8 years) met inclusion criteria and were included in this study. Among them, six studies showed a significant association between OSA and resistant hypertension (pooled OR = 2.842, 95% CI = 1.703-3.980, P < 0.05). Meanwhile, the combination of 20 original studies on the association of OSA with essential hypertension also presented significant results with the pooled ORs of 1.184 (95% CI = 1.093-1.274, P < 0.05) for mild OSA, 1.316 (95% CI = 1.197-1.433, P < 0.05) for moderate OSA and 1.561 (95% CI = 1.287-1.835, P < 0.05) for severe OSA.

Conclusions: Our findings indicated that OSA is related to an increased risk of resistant hypertension. Mild, moderate and severe OSA are associated essential hypertension, as well a dose-response manner relationship is manifested. The associations are relatively stronger among Caucasians and male OSA patients.

Background: Obstructive sleep apnea (OSA) is a sleep disorder …

Inter-Rater Agreement And Validity Of A Tackling Performance Assessment Scale In Youth American Football, Eric Schussler, Richard J. Jagacinski, Susan E. White, Ajit M. Chaudhari, John A. Buford, James A. Onate

Rehabilitation Sciences Faculty Publications

Background: Long term neurologic injury and concussion have been identified as risks from participation in American football. Altering tackling form has been recommended to reduce the risk of neurologic injury caused by head accelerations when tackling. The purpose of this research is to determine the inter-rater agreement and validity of the Qualitative Youth Tackling System (QYTS), a six-item feedback scale to correct tackling form, when utilized by novice and expert raters.

Hypothesis: Experienced raters will have higher levels of agreement with each other and with motion capture when compared to novice raters. Methods: Both novice and experienced raters viewed video …

Response And Resistance To Paradox-Breaking Braf Inhibitor In Melanomas, Edward J. Hartsough, Curtis H. Kugel, Michael J. Vido, Adam C. Berger, Timothy J. Purwin, Allison F. Goldberg, Michael A. Davies, Matthew J. Schiewer, Karen E. Knudsen, Gideon Bollag, Andrew E. Aplin

Department of Cancer Biology Faculty Papers

FDA-approved BRAF inhibitors produce high response rates and improve overall survival in patients with BRAF V600E/K-mutant melanoma, but are linked to pathologies associated with paradoxical ERK1/2 activation in wild-type BRAF cells. To overcome this limitation, a next-generation paradox-breaking RAF inhibitor (PLX8394) has been designed. Here, we show that by using a quantitative reporter assay, PLX8394 rapidly suppressed ERK1/2 reporter activity and growth of mutant BRAF melanoma xenografts. Ex vivo treatment of xenografts and use of a patient-derived explant system (PDeX) revealed that PLX8394 suppressed ERK1/2 signaling and elicited apoptosis more effectively than the FDA-approved BRAF inhibitor, vemurafenib. Furthermore, PLX8394 was …

Global Mapping Of Transcription Factor Motifs In Human Aging., David Alfego, Ulrich Rodeck, Andres Kriete

Department of Dermatology and Cutaneous Biology Faculty Papers

Biological aging is a complex process dependent on the interplay of cell autonomous and tissue contextual changes which occur in response to cumulative molecular stress and manifest through adaptive transcriptional reprogramming. Here we describe a transcription factor (TF) meta-analysis of gene expression datasets accrued from 18 tissue sites collected at different biological ages and from 7 different in-vitro aging models. In-vitro aging platforms included replicative senescence and an energy restriction model in quiescence (ERiQ), in which ATP was transiently reduced. TF motifs in promoter regions of trimmed sets of target genes were scanned using JASPAR and TRANSFAC. TF signatures established …

Use Of Caudal Epidural Catheter In A Child With Cerebral Palsy With Prior Posterior Spine (T1-Sacrum) Fusion., Divya Dixit, Mary C. Theroux, Kirk W. Dabney, Freeman Miller

Department of Anesthesiology Faculty Papers

No abstract provided.