Digital Commons Network^™

Mapping Language Function With Task-Based Vs. Resting-State Functional Mri, Ki Yun Park, John J. Lee, Donna Dierker, Laura M. Marple, Carl D. Hacker, Jarod L. Roland, Daniel S. Marcus, Mikhail Milchenko, Michelle M. Miller-Thomas, Tammie L. Benzinger, Joshua S. Shimony, Abraham Z. Snyder, Eric C. Leuthardt

Open Access Publications

BACKGROUND: Use of functional MRI (fMRI) in pre-surgical planning is a non-invasive method for pre-operative functional mapping for patients with brain tumors, especially tumors located near eloquent cortex. Currently, this practice predominantly involves task-based fMRI (T-fMRI). Resting state fMRI (RS-fMRI) offers an alternative with several methodological advantages. Here, we compare group-level analyses of RS-fMRI vs. T-fMRI as methods for language localization.

PURPOSE: To contrast RS-fMRI vs. T-fMRI as techniques for localization of language function.

METHODS: We analyzed data obtained in 35 patients who had both T-fMRI and RS-fMRI scans during the course of pre-surgical evaluation. The RS-fMRI data were analyzed …

Adherence To Updated Childcare Nutrition Regulations In Colorado, United States, Amy A Eyler, Cheryl R Valko, Katherine A Curoe, Ramya Ramadas, Jamie F Chriqui

Open Access Publications

No abstract provided.

Motile Onchocerca Volvulus Microfilariae In The Anterior Chamber Of The Eye, Michael E Gyasi, Augustine R Hong, Gary J Weil

Open Access Publications

No abstract provided.

A Systematic Review Examining Associations Between Cardiovascular Conditions And Driving Outcomes Among Older Drivers, Ganesh M Babulal, Ramana Kolady, Sarah H Stout, Catherine M Roe

Open Access Publications

There is a vast literature on stroke as a cardiovascular disease and driving outcomes, however little is known about other cardiovascular conditions and driving. The purpose of this review is to examine the literature for studies assessing the effect of non-stroke, vascular conditions on daily driving, reported crash risk and driving decline in older adult drivers as captured by naturalistic methodologies. A systematic review of Embase, Ovid and Scopus Plus examined articles on driving and vascular conditions among older adults. A search yielded 443 articles and, following two screenings, no articles remained that focused on non-stroke, vascular conditions and naturalistic …

Alterations In Plasma Triglycerides And Ceramides: Links With Cardiac Function In Humans With Type 2 Diabetes, Linda R. Peterson, Xuntian Jiang, Ling Chen, Anne C. Goldberg, Marsha S. Farmer, Daniel S. Ory, Jean E. Schaffer

Open Access Publications

No abstract provided.

Gene Therapy For Follistatin Mitigates Systemic Metabolic Inflammation And Post-Traumatic Arthritis In High-Fat Diet-Induced Obesity, Ruhang Tang, Natalia S Harasymowicz, Chia-Lung Wu, Kelsey H Collins, Yun-Rak Choi, Sara J Oswald, Farshid Guilak

Open Access Publications

Obesity-associated inflammation and loss of muscle function play critical roles in the development of osteoarthritis (OA); thus, therapies that target muscle tissue may provide novel approaches to restoring metabolic and biomechanical dysfunction associated with obesity. Follistatin (FST), a protein that binds myostatin and activin, may have the potential to enhance muscle formation while inhibiting inflammation. Here, we hypothesized that adeno-associated virus 9 (AAV9) delivery of FST enhances muscle formation and mitigates metabolic inflammation and knee OA caused by a high-fat diet in mice. AAV-mediated FST delivery exhibited decreased obesity-induced inflammatory adipokines and cytokines systemically and in the joint synovial fluid. …

A Role For Malignant Brain Tumor Domain-Containing Protein 1 In Human Endometrial Stromal Cell Decidualization, Sangappa B Chadchan, Vineet K Maurya, Gwendalyn L Krekeler, Emily S Jungheim, Ramakrishna Kommagani

Open Access Publications

Up to 30% of women experience early miscarriage due to impaired decidualization. For implantation to occur, the uterine endometrial stromal fibroblast-like cells must differentiate into decidual cells, but the genes required for decidualization have not been fully defined. Here, we show that Malignant Brain Tumor Domain-containing Protein 1 (MBTD1), a member of the polycomb group protein family, is critical for human endometrial stromal cell (HESC) decidualization. MBTD1 predominantly localized to HESCs during the secretory phase and the levels were significantly elevated during

Mechanisms Of Action Of Autophagy Modulators Dissected By Quantitative Systems Pharmacology Analysis, Qingya Shi, Fen Pei, Gary A Silverman, Stephen C Pak, David H Perlmutter, Bing Liu, Ivet Bahar

Open Access Publications

Autophagy plays an essential role in cell survival/death and functioning. Modulation of autophagy has been recognized as a promising therapeutic strategy against diseases/disorders associated with uncontrolled growth or accumulation of biomolecular aggregates, organelles, or cells including those caused by cancer, aging, neurodegeneration, and liver diseases such as α1-antitrypsin deficiency. Numerous pharmacological agents that enhance or suppress autophagy have been discovered. However, their molecular mechanisms of action are far from clear. Here, we collected a set of 225 autophagy modulators and carried out a comprehensive quantitative systems pharmacology (QSP) analysis of their targets using both existing databases and predictions made by …

S100a8/A9 Regulates Cd11b Expression And Neutrophil Recruitment During Chronic Tuberculosis, Ninecia R Scott, Rosemary V Swanson, Noor Al-Hammadi, Racquel Domingo-Gonzalez, Shibali Das, Mushtaq Ahmed, Puthayalai Treerat, Shabaana A Khader, Et Al

Open Access Publications

Neutrophil accumulation is associated with lung pathology during active tuberculosis (ATB). However, the molecular mechanism or mechanisms by which neutrophils accumulate in the lung and contribute to TB immunopathology are not fully delineated. Using the well-established mouse model of TB, our new data provide evidence that the alarmin S100A8/A9 mediates neutrophil accumulation during progression to chronic TB. Depletion of neutrophils or S100A8/A9 deficiency resulted in improved Mycobacterium tuberculosis (Mtb) control during chronic but not acute TB. Mechanistically, we demonstrate that, following Mtb infection, S100A8/A9 expression is required for upregulation of the integrin molecule CD11b specifically on neutrophils, mediating their accumulation …

Visible-Light Promoted Atom Transfer Radical Addition-Elimination (Atre) Reaction For The Synthesis Of Fluoroalkylated Alkenes Using Dma As Electron-Donor, Wen-Wen Xu, Le Wang, Ting Mao, Jiwei Gu, Xiao-Fei Li, Chun-Yang He

Open Access Publications

Here, we describe a mild, catalyst-free and operationally-simple strategy for the direct fluoroalkylation of olefins driven by the photochemical activity of an electron donor-acceptor (EDA) complex between DMA and fluoroalkyl iodides. The significant advantages of this photochemical transformation are high efficiency, excellent functional group tolerance, and synthetic simplicity, thus providing a facile route for further application in pharmaceuticals and life sciences.

Effects Of Remote Limb Ischemic Conditioning On Muscle Strength In Healthy Young Adults: A Randomized Controlled Trial, Swati M. Surkar, Marghuretta D. Bland, Anna E. Mattlage, Ling Chen, Jeffrey M. Gidday, Jin-Moo Lee, Tamara Hershey, Catherine E. Lang

Open Access Publications

Remote limb ischemic conditioning (RLIC) is a clinically feasible method in which brief, sub-lethal bouts of ischemia protects remote organs or tissues from subsequent ischemic injury. A single session of RLIC can improve exercise performance and increase muscle activation. The purpose of this study, therefore, was to assess the effects of a brief, two-week protocol of repeated RLIC combined with strength training on strength gain and neural adaptation in healthy young adults. Participants age 18-40 years were randomized to receive either RLIC plus strength training (n = 15) or sham conditioning plus strength training (n = 15). Participants received RLIC …

Photoreceptor Responses To Light In The Pathogenesis Of Diabetic Retinopathy, Shahriyar P Majidi, Rithwick Rajagopal

Open Access Publications

Vision loss, among the most feared complications of diabetes, is primarily caused by diabetic retinopathy, a disease that manifests in well-recognized, characteristic microvascular lesions. The reasons for retinal susceptibility to damage in diabetes are unclear, especially considering that microvascular networks are found in all tissues. However, the unique metabolic demands of retinal neurons could account for their vulnerability in diabetes. Photoreceptors are the first neurons in the visual circuit and are also the most energy-demanding cells of the retina. Here, we review experimental and clinical evidence linking photoreceptors to the development of diabetic retinopathy. We then describe the influence of …

The Immunologic Effect Of Early Intravenous Two And Four Gram Bolus Dosing Of Tranexamic Acid Compared To Placebo In Patients With Severe Traumatic Bleeding (Tampiti): A Randomized, Double-Blind, Placebo-Controlled, Single-Center Trial, Philip C Spinella, Kimberly A Thomas, Isaiah R Turnbull, Anja Fuchs, Kelly Bochicchio, Douglas Schuerer, Stacey Reese, Adrian A Coleoglou Centeno, Christopher B Horn, Jack Baty, Susan M Shea, M Adam Meledeo, Anthony E Pusateri, Jerrold H Levy, Andrew P Cap, Grant V Bochicchio, Tampiti Investigators

Open Access Publications

Background: The hemostatic properties of tranexamic acid (TXA) are well described, but the immunological effects of TXA administration after traumatic injury have not been thoroughly examined. We hypothesized TXA would reduce monocyte activation in bleeding trauma patients with severe injury.

Methods: This was a single center, double-blinded, randomized controlled trial (RCT) comparing placebo to a 2 g or 4 g intravenous TXA bolus dose in trauma patients with severe injury. Fifty patients were randomized into each study group. The primary outcome was a reduction in monocyte activation as measured by human leukocyte antigen-DR isotype (HLA-DR) expression on monocytes 72 h …

Bet Bromodomain Inhibition Attenuates Cardiac Phenotype In Myocyte-Specific Lamin A/C-Deficient Mice, Gaelle Auguste, Leila Rouhi, Scot J Matkovich, Cristian Coarfa, Matthew J Robertson, Grazyna Czernuszewicz, Priyatansh Gurha, Ali J Marian

Open Access Publications

Mutation in the LMNA gene, encoding lamin A/C, causes a diverse group of diseases called laminopathies. Cardiac involvement is the major cause of death and manifests as dilated cardiomyopathy, heart failure, arrhythmias, and sudden death. There is no specific therapy for LMNA-associated cardiomyopathy. We report that deletion of Lmna in cardiomyocytes in mice leads to severe cardiac dysfunction, conduction defect, ventricular arrhythmias, fibrosis, apoptosis, and premature death within 4 weeks. The phenotype is similar to LMNA-associated cardiomyopathy in humans. RNA sequencing, performed before the onset of cardiac dysfunction, led to identification of 2338 differentially expressed genes (DEGs) in Lmna-deleted cardiomyocytes. …

Association Between Use Of Hydrochlorothiazide And Nonmelanoma Skin Cancer: Common Data Model Cohort Study In Asian Population, Seung Min Lee, Kwangsoo Kim, Jihoon Yoon, Sue K Park, Sungji Moon, Sang Eun Lee, Jiseon Oh, Sooyoung Yoo, Kwang-Il Kim, Hyung-Jin Yoon, Hae-Young Lee

Open Access Publications

Although hydrochlorothiazide (HCTZ) has been suggested to increase skin cancer risk in white Westerners, there is scant evidence for the same in Asians. We analyzed the association between the use of hydrochlorothiazide and non-melanoma in the Asian population using the common data model.

METHODS: A retrospective multicenter observational study was conducted using a distributed research network to analyze the effect of HCTZ on skin cancer from 2004 to 2018. We performed Cox regression to evaluate the effects by comparing the use of HCTZ with other antihypertensive drugs. All analyses were re-evaluated using matched data using the propensity score matching (PSM). …

Effects Of Hypoxic And Ischemic Clinical Conditions On The Outcomes Of Acute Ischemic Stroke Patients, Umeshkumar Athiraman, Rene Tempelhoff, Menelaos Karanikolas

Open Access Publications

No abstract provided.

Deficiency Of Peroxiredoxin 2 Exacerbates Angiotensin Ii-Induced Abdominal Aortic Aneurysm, Se-Jin Jeong, Min Ji Cho, Na Young Ko, Sinai Kim, In-Hyuk Jung, Jeong-Ki Min, Sang Hak Lee, Jong-Gil Park, Goo Taeg Oh

Open Access Publications

No abstract provided.

Technical Note: Comparison Of The Internal Target Volume (Itv) Contours And Dose Calculations On 4dct, Average Cbct, And 4dcbct Imaging For Lung Stereotactic Body Radiation Therapy (Sbrt), Michael Dumas, Eric Laugeman, Parag Sevak, Karen C Snyder, Weihua Mao, Indrin J Chetty, Munther Ajlouni, Ning Wen

Open Access Publications

PURPOSE: To investigate the differences between internal target volumes (ITVs) contoured on the simulation 4DCT and daily 4DCBCT images for lung cancer patients treated with stereotactic body radiotherapy (SBRT) and determine the dose delivered on 4D planning technique.

METHODS: For nine patients, 4DCBCTs were acquired before each fraction to assess tumor motion. An ITV was contoured on each phase of the 4DCBCT and a union of the 10 ITVs was used to create a composite ITV. Another ITV was drawn on the average 3DCBCT (avgCBCT) to compare with current clinical practice. The Dice coefficient, Hausdorff distance, and center of mass …

Peptidoglycan Editing Provides Immunity To Acinetobacter Baumannii During Bacterial Warfare, Nguyen-Hung Le, Gisela Di Venanzio, Juvenal Lopez, Seth W Hennon, Mario F Feldman, Et Al

Open Access Publications

Peptidoglycan (PG) is essential in most bacteria. Thus, it is often targeted by various assaults, including interbacterial attacks via the type VI secretion system (T6SS). Here, we report that the Gram-negative bacterium

Direct Neuronal Reprogramming Of Common Marmoset Fibroblasts By Ascl1, Microrna-9/9*, And Microrna-124 Overexpression, Akisa Nemoto, Reona Kobayashi, Sho Yoshimatsu, Yuta Sato, Takahiro Kondo, Andrew S Yoo, Seiji Shiozawa, Hideyuki Okano

Open Access Publications

The common marmoset (

Anellovirus Dynamics Are Associated With Primary Graft Dysfunction In Lung Transplantation, Joshua A. Blatter, Tsuyoshi Takahashi, Brigitte Mittler, Ruben G. Nava, Varun Puri, Daniel Kreisel, David Wang

Open Access Publications

No abstract provided.

Human Plasmacytoid Dendritic Cells And Cutaneous Melanoma, Matilde Monti, Francesca Consoli, Raffaella Vescovi, Mattia Bugatti, William Vermi

Open Access Publications

The prognosis of metastatic melanoma (MM) patients has remained poor for a long time. However, the recent introduction of effective target therapies (BRAF and MEK inhibitors for BRAFV600-mutated MM) and immunotherapies (anti-CTLA-4 and anti-PD-1) has significantly improved the survival of MM patients. Notably, all these responses are highly dependent on the fitness of the host immune system, including the innate compartment. Among immune cells involved in cancer immunity, properly activated plasmacytoid dendritic cells (pDCs) exert an important role, bridging the innate and adaptive immune responses and directly eliminating cancer cells. A distinctive feature of pDCs is the production of high …

Simultaneous Immunization With Omp25 And L7/L12 Provides Protection Against Brucellosis In Mice, Sonal Gupta, Surender Mohan, Vikas Kumar Somani, Somya Aggarwal, Rakesh Bhatnagar

Open Access Publications

Currently used

False-Negative Upper Extremity Ultrasound In The Initial Evaluation Of Patients With Suspected Subclavian Vein Thrombosis Due To Thoracic Outlet Syndrome (Paget-Schroetter Syndrome), Evan R Brownie, Ahmmad A Abuirqeba, J Westley Ohman, Brian G Rubin, Robert W Thompson

Open Access Publications

OBJECTIVE: To assess the utilization and consequences of upper extremity Duplex ultrasound in the initial diagnostic evaluation of patients with suspected subclavian vein (SCV) thrombosis and venous thoracic outlet syndrome (VTOS).

METHODS: A retrospective single-center review was conducted for patients that underwent primary surgical treatment for VTOS between 2008 and 2017, in whom an upper extremity ultrasound had been performed as the initial diagnostic test (n = 214). Clinical and treatment characteristics were compared between patients with positive and false-negative ultrasound studies.

RESULTS: There were 122 men (57%) and 92 women (43%) that had presented with spontaneous idiopathic arm swelling, …

Mirna-Based Rapid Differentiation Of Purified Neurons From Hpscs Advancestowards Quick Screening For Neuronal Disease Phenotypes In Vitro, Mitsuru Ishikawa, Takeshi Aoyama, Shoichiro Shibata, Takefumi Sone, Hiroyuki Miyoshi, Hirotaka Watanabe, Mari Nakamura, Saori Morota, Hiroyuki Uchino, Andrew S Yoo, Hideyuki Okano

Open Access Publications

Obtaining differentiated cells with high physiological functions by an efficient, but simple and rapid differentiation method is crucial for modeling neuronal diseases in vitro using human pluripotent stem cells (hPSCs). Currently, methods involving the transient expression of one or a couple of transcription factors have been established as techniques for inducing neuronal differentiation in a rapid, single step. It has also been reported that microRNAs can function as reprogramming effectors for directly reprogramming human dermal fibroblasts to neurons. In this study, we tested the effect of adding neuronal microRNAs, miRNA-9/9*, and miR-124 (miR-9/9*-124), for the neuronal induction method of hPSCs …

Racial And Ethnic Differences In Parental Decision-Making Roles In Pediatric Oncology, Bryan A. Sisk, Tammy I. Kang, Jennifer W. Mack

Open Access Publications

No abstract provided.

Using Practice Effects For Targeted Trials Or Sub-Group Analysis In Alzheimer's Disease: How Practice Effects Predict Change Over Time, Guoqiao Wang, Richard E. Kennedy, Terry E. Goldberg, Mackenzie E. Fowler, Gary R. Cutter, Lon S. Schneider

Open Access Publications

OBJECTIVE: To describe the presence of practice effects in persons with Alzheimer disease (AD) or mild cognitive impairment (MCI) and to evaluate how practice effects affect cognitive progression and the outcome of clinical trials.

METHODS: Using data from a meta-database consisting of 18 studies including participants from the Alzheimer disease Cooperative Study (ADCS) and the Alzheimer Disease Neuroimaging Initiative (ADNI) with ADAS-Cog11 as the primary outcome, we defined practice effects based on the improvement in the first two ADAS-Cog11 scores and then estimated the presence of practice effects and compared the cognitive progression between participants with and without practice effects. …

Randomized, Double-Blind, Placebo-Controlled, Flexible-Dose Titration Study Of Methylphenidate Hydrochloride Extended-Release Capsules (Aptensio Xr) In Preschool Children With Attention-Deficit/Hyperactivity Disorder, Ann C. Childress, Scott H. Kollins, Henry C. Foehl, Jeffrey H. Newcorn, Greg Mattingly, Robert J. Kupper, Akwete L. Adjei

Open Access Publications

No abstract provided.

Composite Measure Of Physiological Dysregulation As A Predictor Of Mortality: The Long Life Family Study, Konstantin G Arbeev, Olivia Bagley, Svetlana V Ukraintseva, Hongzhe Duan, Alexander M Kulminski, Eric Stallard, Deqing Wu, Kaare Christensen, Mary F Feitosa, Bharat Thyagarajan, Joseph M Zmuda, Anatoliy I Yashin

Open Access Publications

Biological aging results in changes in an organism that accumulate over age in a complex fashion across different regulatory systems, and their cumulative effect manifests in increased physiological dysregulation (PD) and declining robustness and resilience that increase risks of health disorders and death. Several composite measures involving multiple biomarkers that capture complex effects of aging have been proposed. We applied one such approach, the Mahalanobis distance (D

Pharmacological Inhibition Of Ataxia-Telangiectasia Mutated Exacerbates Acute Kidney Injury By Activating P53 Signaling In Mice, Masahiro Uehara, Tetsuro Kusaba, Tomoharu Ida, Kunihiro Nakai, Tomohiro Nakata, Aya Tomita, Noriko Watanabe-Uehara, Kisho Ikeda, Takashi Kitani, Noriyuki Yamashita, Yuhei Kirita, Satoaki Matoba, Benjamin D. Humphreys, Keiichi Tamagaki

Open Access Publications

No abstract provided.