Digital Commons Network^™

Differentiating Among Stages Of Cognitive Impairment In Aging: Version 3 Of The Uniform Data Set (Uds) Neuropsychological Test Battery And Moca Index Scores, Hiroko H Dodge, John C Morris, Et Al

Open Access Publications

Introduction: Federally funded Alzheimer's Disease Centers in the United States have been using a standardized neuropsychological test battery as part of the National Alzheimer's Coordinating Center Uniform Data Set (UDS) since 2005. Version 3 (V3) of the UDS replaced the previous version (V2) in 2015. We compared V2 and V3 neuropsychological tests with respect to their ability to distinguish among the Clinical Dementia Rating (CDR) global scores of 0, 0.5, and 1.

Methods: First, we matched participants receiving V2 tests (V2 cohort) and V3 tests (V3 cohort) in their cognitive functions using tests common to both versions. Then, we compared …

Cerebral Small Vessel Disease Genomics And Its Implications Across The Lifespan, Muralidharan Sargurupremraj, Andrew C. Heath, Pamela A.F. Madden, Et Al.

Open Access Publications

No abstract provided.

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 …

The Current State Of Hiv And Aging: Findings Presented At The 10th International Workshop On Hiv And Aging, Stephanie Shiau, Jane A. O'Halloran, Et Al.

Open Access Publications

No abstract provided.

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 …

Early Socioemotional Competence, Psychopathology, And Latent Class Profiles Of Reparative Prosocial Behaviors From Preschool Through Early Adolescence, Meghan Rose Donohue, Rebecca Tillman, Joan Luby

Open Access Publications

Children who have difficulty using reparative behaviors following transgressions display a wide range of poorer social and emotional outcomes. Despite the importance of reparative skills, no study has charted the developmental trajectory of these behaviors or pinpointed predictors of poorer reparative abilities. To address these gaps in the literature, this study applied growth mixture modeling to parent reports of children's reparative behaviors (N = 230) in a 9-year longitudinal data set spanning from preschool to early adolescence. Three distinct trajectories of reparative behaviors were found: a low-stable, moderate-stable, and high-stable latent class. Poorer emotion understanding, social withdrawal, social rejection, and …

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 …

Cryo-Em Structures Of The Air-Oxidized And Dithionite-Reduced Photosynthetic Alternative Complex Iii From Roseiflexus Castenholzii, Yang Shi, Yueyong Xin, Chao Wang, Robert E Blankenship, Fei Sun, Xiaoling Xu

Open Access Publications

Alternative complex III (ACIII) is a multisubunit quinol:electron acceptor oxidoreductase that couples quinol oxidation with transmembrane proton translocation in both the respiratory and photosynthetic electron transport chains of bacteria. The coupling mechanism, however, is poorly understood. Here, we report the cryo-EM structures of air-oxidized and dithionite-reduced ACIII from the photosynthetic bacterium

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). …

Deciphering The Role Of Innate Immune Nf-ĸb Pathway In Pancreatic Cancer, Namrata Khurana, Paarth B Dodhiawala, Ashenafi Bulle, Kian-Huat Lim

Open Access Publications

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with no effective treatment option. A predominant hallmark of PDAC is the intense fibro-inflammatory stroma which not only physically collapses vasculature but also functionally suppresses anti-tumor immunity. Constitutive and induced activation of the NF-κB transcription factors is a major mechanism that drives inflammation in PDAC. While targeting this pathway is widely supported as a promising therapeutic strategy, clinical success is elusive due to a lack of safe and effective anti-NF-κB pathway therapeutics. Furthermore, the cell type-specific contribution of this pathway, specifically in neoplastic cells, stromal fibroblasts, and immune cells, …

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 …

Neutrophil Swarming Delays The Growth Of Clusters Of Pathogenic Fungi, Alex Hopke, Allison Scherer, Samantha Kreuzburg, Michael S. Abers, Christa S. Zerbe, Mary C. Dinauer, Michael K. Mansour, Daniel Irimia

Open Access Publications

No abstract provided.

Single Cell Transcriptomics Reveals Opioid Usage Evokes Widespread Suppression Of Antiviral Gene Program, Tanya T. Karagiannis, John P. Cleary Jr., Busra Gok, Andrew J. Henderson, Nicholas G. Martin, Masanao Yajima, Elliot C. Nelson, Christine S. Cheng

Open Access Publications

No abstract provided.

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

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Characterization Of Missense Mutations In The Signal Peptide And Propeptide Of Fix In Hemophilia B By A Cell-Based Assay, Wenwen Gao, Yaqi Xu, Hongli Liu, Meng Gao, Qing Cao, Yiyi Wang, Longteng Cui, Rong Huang, Yan Shen, Sanqiang Li, Haiping Yang, Yixiang Chen, Chaokun Li, Haichuan Yu, Weikai Li, Guomin Shen

Open Access Publications

No abstract provided.

Development And Validation Of A Rapid Lateral Flow E1/E2-Antigen Test And Elisa In Patients Infected With Emerging Asian Strain Of Chikungunya Virus In The Americas, Ankita Reddy, Michael S Diamond, Et Al

Open Access Publications

Since its 2013 emergence in the Americas, Chikungunya virus (CHIKV) has posed a serious threat to public health. Early and accurate diagnosis of the disease, though currently lacking in clinics, is integral to enable timely care and epidemiological response. We developed a dual detection system: a CHIKV antigen E1/E2-based enzyme-linked immunosorbent assay (ELISA) and a lateral flow test using high-affinity anti-CHIKV antibodies. The ELISA was validated with 100 PCR-tested acute Chikungunya fever samples from Honduras. The assay had an overall sensitivity and specificity of 51% and 96.67%, respectively, with accuracy reaching 95.45% sensitivity and 92.03% specificity at a cycle threshold …