Digital Commons Network^™

Development And Implementation Of An Electronic Clinical Dementia Rating And Financial Capacity Instrument-Short Form, Taylor Howell, John C Morris, Krista L Moulder, Connie Mayo, Maria Carroll, Yan Li, Et Al

2020-Current year OA Pubs

Introduction: To address the need for remote assessments of cognitive decline and dementia, we developed and administered electronic versions of the Clinical Dementia Rating (CDR®) and the Financial Capacity Instrument-Short Form (FCI-SF) (F-CAP

Methods: The CDR and FCI-SF were adapted for remote, unsupervised, online use based on item response analysis of the standard instruments. Participants completed the eCDR and eFCI first in clinic, and then at home within 2 weeks.

Results: Of the 243 enrolled participants, 179 (73%) cognitively unimpaired (CU), 50 (21%) with mild cognitive impairment (MCI) or dementia, and 14 (6%) with an unknown diagnosis, 84% and 85% …

Challenges And Progress In Research, Diagnostics, And Therapeutics In Alzheimer's Disease And Related Dementias, Nikolay V Dokholyan, Richard C Mohs, Randall J Bateman

2020-Current year OA Pubs

The health, well-being, and financial security of Americans are greatly impacted by Alzheimer's disease. The forecast paints an upward trajectory with the number of Americans suffering from Alzheimer's disease and related dementia. To discuss the Alzheimer's crisis, The Senate Committee on Finance, Subcommittee on Health Care, held a hearing titled, "The Alzheimer's Crisis: Examining, Testing, and Treatment Pipelines and Fiscal Implications," on December 16, 2020. Here, we summarize and expand on the discussion of the panel and its review of recent progress, ongoing challenges associated with Alzheimer's disease, and potential initiatives that promise to speed progress in developing treatments and …

Stigma Towards Mental Illness And Help-Seeking Behaviors Among Adult And Child Psychiatrists In Hungary: A Cross-Sectional Study, Dorottya Őri, Péter Szocsics, Tamás Molnár, Fanni Virág Ralovich, Zsolt Huszár, Ágnes Bene, Sándor Rózsa, Zsuzsa Győrffy, György Purebl

2020-Current year OA Pubs

OBJECTIVE: Stigma towards people with mental health problems is a growing issue across the world, to which healthcare providers might contribute. The aim of the present study was to explore psychiatrists' attitudes towards their patients and link them to psychosocial and professional factors.

METHODS: An online questionnaire was used to approach the in- and outpatient psychiatric services across Hungary. A total of 211 trainees and specialists in adult and child psychiatry participated in our study. Their overall stigmatizing attitudes were measured, with focus on attitude, disclosure and help-seeking, and social distance dimensions by using the self-report Opening Minds Stigma Scale …

Effect Of Acute Postsurgical Pain Trajectories On 30-Day And 1-Year Pain, Saria S Awadalla, Victoria Winslow, Michael S. Avidan, Simon Haroutounian, Thomas G. Kannampallil

2020-Current year OA Pubs

Untreated pain after surgery leads to poor patient satisfaction, longer hospital length of stay, lower health-related quality of life, and non-compliance with rehabilitation regimens. The aim of this study is to characterize the structure of acute pain trajectories during the postsurgical hospitalization period and quantify their association with pain at 30-days and 1-year after surgery. This cohort study included 2106 adult (≥18 years) surgical patients who consented to participate in the SATISFY-SOS registry (February 1, 2015 to September 30, 2017). Patients were excluded if they did not undergo invasive surgeries, were classified as outpatients, failed to complete follow up assessments …

Adverse Events Related To Ultrasound-Guided Regional Anesthesia Performed By Emergency Physicians: Systematic Review Protocol, Sean P. Stickles, Deborah Shipley Kane, Chadd K. Kraus, Robert J. Strony, Enyo A. Ablordeppey, Michelle M. Doering, Daniel Theodoro, Jacques Simon Lee, Christopher R. Carpenter

2020-Current year OA Pubs

The use of ultrasound-guided regional anesthesia for pain management has become increasingly prevalent in Emergency Medicine, with studies noting excellent pain control while sparing opioid use. However, the use of ultrasound-guided regional anesthesia may be hampered by concern about risks for patient harm. This systematic review protocol describes our approach to evaluate the incidence of adverse events from the use of ultrasound-guided regional anesthesia by Emergency Physicians as described in the literature. This project will also seek to document the scope of ultrasound-guided regional anesthesia applications being performed in Emergency Medicine literature, and potentially serve as a framework for future …

Cdc20 Regulates Sensitivity To Chemotherapy And Radiation In Glioblastoma Stem Cells, Diane D. Mao, Ryan T. Cleary, Amit Gujar, Tatenda Mahlokozera, Albert H. Kim

2020-Current year OA Pubs

Glioblastoma stem cells (GSCs) are an important subpopulation in glioblastoma, implicated in tumor growth, tumor recurrence, and radiation resistance. Understanding the cellular mechanisms for chemo- and radiation resistance could lead to the development of new therapeutic strategies. Here, we demonstrate that CDC20 promotes resistance to chemotherapy and radiation therapy. CDC20 knockdown does not increase TMZ- and radiation-induced DNA damage, or alter DNA damage repair, but rather promotes cell death through accumulation of the pro-apoptotic protein, Bim. Our results identify a CDC20 signaling pathway that regulates chemo- and radiosensitivity in GSCs, with the potential for CDC20-targeted therapeutic strategies in the treatment …

The Association Of Prescription Opioid Use With Suicide Attempts: An Analysis Of Statewide Medical Claims Data, Chongliang Luo, Kun Chen, Riddhi Doshi, Nathaniel Rickles, Yong Chen, Harold Schwartz, Robert H. Aseltine

2020-Current year OA Pubs

BACKGROUND: Suicides and opioid overdose deaths are among the most pressing public health concerns in the US. However direct evidence for the association between opioid use and suicidal behavior is limited. The objective of this article is to examine the association between frequency and dose of prescription opioid use and subsequent suicide attempts.

METHODS AND FINDINGS: This retrospective cohort study analyzed 4 years of statewide medical claims data from the Connecticut All-Payer Claims Database. Commercially insured adult patients in Connecticut (n = 842,773) who had any medical claims beginning in January 2012 were followed through December 2015. The primary outcome …

Comparative Analysis Of Dcas9-Vp64 Variants And Multiplexed Guide Rnas Mediating Crispr Activation, Kohei Omachi, Jeffrey H. Miner

2020-Current year OA Pubs

CRISPR/Cas9-mediated transcriptional activation (CRISPRa) is a powerful tool for investigating complex biological phenomena. Although CRISPRa approaches based on the VP64 transcriptional activator have been widely studied in both cultured cells and in animal models and exhibit great versatility for various cell types and developmental stages in vivo, different dCas9-VP64 versions have not been rigorously compared. Here, we compared different dCas9-VP64 constructs in identical contexts, including the cell lines used and the transfection conditions, for their ability to activate endogenous and exogenous genes. Moreover, we investigated the optimal approach for VP64 addition to VP64- and p300-based constructs. We found that MS2-MCP-scaffolded …

Internalization Of Appearance Ideals And Not Religiosity Indirectly Impacts The Relationship Between Acculturation And Disordered Eating Risk In South And Southeast Asian Women Living In The United States, Sonakshi Negi, Erik M Benau, Megan Strowger, Anne Claire Grammer, C Alix Timko

2020-Current year OA Pubs

Objective: Studies that examine disordered eating in samples of Asian individuals living in the United States frequently combine all individuals of Asian descent into a single group, which can obscure important differences between groups and their experiences of acculturation. The goal of the present study was to establish the relation of acculturation, internalization of appearance ideals, and religiosity as predicting body dissatisfaction and disordered eating in women of South and Southeast Asian (SSEA) descent.

Method: Women of SSEA descent (

Results: Direct paths from acculturation to both body dissatisfaction and disordered eating were not significant. Thin ideal internalization completely accounted …

Unique Molecular Identifier-Based High-Resolution Hla Typing And Transcript Quantitation Using Long-Read Sequencing, Caleb Cornaby, Maureen C Montgomery, Chang Liu, Eric T Weimer

2020-Current year OA Pubs

HLA typing provides essential results for stem cell and solid organ transplants, as well as providing diagnostic benefits for various rheumatology, gastroenterology, neurology, and infectious diseases. It is becoming increasingly clear that understanding the expression of patient HLA transcripts can provide additional benefits for many of these same patient groups. Our study cohort was evaluated using a long-read RNA sequencing methodology to provide rapid HLA genotyping results and normalized HLA transcript expression. Our assay used NGSEngine to determine the HLA genotyping result and normalized mRNA transcript expression using Athlon2. The assay demonstrated an excellent concordance rate of 99.7%. Similar to …

Preeclampsia Is Associated With Reduced Isg15 Levels Impairing Extravillous Trophoblast Invasion, Asli Ozmen, Anthony O Odibo, Et Al

2020-Current year OA Pubs

Among several interleukin (IL)-6 family members, only IL-6 and IL-11 require a gp130 protein homodimer for intracellular signaling due to lack of intracellular signaling domain in the IL-6 receptor (IL-6R) and IL-11R. We previously reported enhanced decidual IL-6 and IL-11 levels at the maternal-fetal interface with significantly higher peri-membranous IL-6 immunostaining in adjacent interstitial trophoblasts in preeclampsia (PE) vs. gestational age (GA)-matched controls. This led us to hypothesize that competitive binding of these cytokines to the gp130 impairs extravillous trophoblast (EVT) differentiation, proliferation and/or invasion. Using global microarray analysis, the current study identified inhibition of interferon-stimulated gene 15 (

Molecular Heterogeneity In Pediatric Malignant Rhabdoid Tumors In Patients With Multi-Organ Involvement, Katherine E Miller, Margaret Shatara, Et Al

2020-Current year OA Pubs

Rhabdoid tumors (RTs) of the brain (atypical teratoid/rhabdoid tumor; AT/RT) and extracranial sites (most often the kidney; RTK) are malignant tumors predominantly occurring in children, frequently those with

Glutathione S-Transferase Alpha 4 Promotes Proliferation And Chemoresistance In Colorectal Cancer Cells, Zhanhu Zhang, Lili Xu, Lin Huang, Tianqi Li, Jane Y Wang, Chunhua Ma, Xiaoyun Bian, Xiaoyan Ren, Haibo Li, Xingmin Wang

2020-Current year OA Pubs

Glutathione

Efficient T Cell Migration And Activation Require L-Plastin, Hemant Joshi, Sharon Celeste Morley

2020-Current year OA Pubs

Rapid re-organization of the actin cytoskeleton supports T-cell trafficking towards immune sites and interaction with antigen presenting cells (APCs). F-actin rearrangement enables T-cell trafficking by stabilizing adhesion to vascular endothelial cells and promoting transendothelial migration. T-cell/APC immune synapse (IS) maturation also relies upon f-actin-anchored LFA-1:ICAM-1 ligation. Therefore, efficient T-cell responses require tight regulation of f-actin dynamics. In this review, we summarize how the actin-bundling protein L-plastin (LPL) regulates T-cell activation and migration. LPL enhances f-actin polymerization and also directly binds to the β2 chain of the integrin LFA-1 to support intercellular adhesion and IS formation in human and murine T …

Beta-Adrenergic Antagonist Tolerance In Amyloid Cardiomyopathy, Stuart Ramsell, Carlos Arias Bermudez, Cyril Ayuk Mbeng Takem Baiyee, Brandon Rodgers, Samir Parikh, Salem Almaani, Nidhi Sharma, Samantha Lorusso, Miriam Freimer, Elyse Redder, Naresh Bumma, Ajay Vallkati, Yvonne Efebera, Rami Kahwash, Courtney M Campbell

2020-Current year OA Pubs

Background: Beta-adrenergic antagonists or blockers (BB) are a cornerstone of cardiac therapy for multiple indications. However, BB are considered relatively contraindicated in amyloid cardiomyopathy due to poor tolerance. This intolerance is hypothesized to be due to concomitant neuropathy and significant restrictive cardiomyopathy. This study analyzes the incidence and characteristics of BB tolerance in patients with amyloid cardiomyopathy.

Methods: Through a single-center retrospective chart review, patients with amyloid cardiomyopathy, confirmed by endomyocardial biopsy or technetium-99 pyrophosphate scan, were identified and clinical data was collected. Statistical methods included Chi-square test and two sample

Results: Of 135 cardiac amyloidosis patients, 27 patients (20.0%) …

Combining Empirical Knowledge, In Silico Molecular Docking And Admet Profiling To Identify Therapeutic Phytochemicals From Brucea Antidysentrica For Acute Myeloid Leukemia, Lemessa Etana Bultum, Gemechu Bekele Tolossa, Doheon Lee

2020-Current year OA Pubs

Acute myeloid leukemia (AML) is one of the deadly cancers. Chemotherapy is the first-line treatment and the only curative intervention is stem cell transplantation which are intolerable for aged and comorbid patients. Therefore, finding complementary treatment is still an active research area. For this, empirical knowledge driven search for therapeutic agents have been carried out by long and arduous wet lab processes. Nonetheless, currently there is an accumulated bioinformatics data about natural products that enabled the use of efficient and cost effective in silico methods to find drug candidates. In this work, therefore, we set out to computationally investigate the …

Checkpoint Blockade-Induced Cd8+ T Cell Differentiation In Head And Neck Cancer Responders, Liye Zhou, Paul Zolkind, Obi Griffith, Et Al

2020-Current year OA Pubs

BACKGROUND: Immune checkpoint blockade (ICB) response in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) is limited to 15%-20% of patients and underpinnings of resistance remain undefined.

METHODS: Starting with an anti-PD1 sensitive murine HNSCC cell line, we generated an isogenic anti-PD1 resistant model. Mass cytometry was used to delineate tumor microenvironments of both sensitive parental murine oral carcinoma (MOC1) and resistant MOC1esc1 tumors. To examine heterogeneity and clonal dynamics of tumor infiltrating lymphocytes (TILs), we applied paired single-cell RNA and TCR sequencing in three HNSCC models.

RESULTS: Anti-PD1 resistant MOC1esc1 line displayed a conserved cell intrinsic immune evasion signature. …

Subtyping Of Common Complex Diseases And Disorders By Integrating Heterogeneous Data. Identifying Clusters Among Women With Lower Urinary Tract Symptoms In The Lurn Study, Victor P. Andreev, H Henry Lai, Et Al

2020-Current year OA Pubs

We present a methodology for subtyping of persons with a common clinical symptom complex by integrating heterogeneous continuous and categorical data. We illustrate it by clustering women with lower urinary tract symptoms (LUTS), who represent a heterogeneous cohort with overlapping symptoms and multifactorial etiology. Data collected in the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN), a multi-center observational study, included self-reported urinary and non-urinary symptoms, bladder diaries, and physical examination data for 545 women. Heterogeneity in these multidimensional data required thorough and non-trivial preprocessing, including scaling by controls and weighting to mitigate data redundancy, while the various data …

Phase I Clinical Trial Evaluating The Safety And Efficacy Of Adp-A2m10 Spear T Cells In Patients With Mage-A10+ Advanced Non-Small Cell Lung Cancer, George R Blumenschein, Siddhartha Devarakonda, Ramaswamy Govindan, Et Al

2020-Current year OA Pubs

BACKGROUND: ADP-A2M10 specific peptide enhanced affinity receptor (SPEAR) T cells (ADP-A2M10) are genetically engineered autologous T cells that express a high-affinity melanoma-associated antigen A10 (MAGE-A10)-specific T-cell receptor (TCR) targeting MAGE-A10

METHODS: Eligible patients were HLA-A*02 positive with advanced NSCLC expressing MAGE-A10. Patients underwent apheresis; T cells were isolated, transduced with a lentiviral vector containing the TCR targeting MAGE-A10, and expanded. Patients underwent lymphodepletion with varying doses/schedules of fludarabine and cyclophosphamide prior to receiving ADP-A2M10. ADP-A2M10 were administered at 0.08-0.12×10

RESULTS: Eleven patients (male, n=6; female, n=5) with NSCLC (adenocarcinoma, n=8; squamous cell carcinoma, n=3) were treated. Five, three, and three …

Episodic Memories Among Irritable Bowel Syndrome (Ibs) Patients: An Important Aspect Of The Ibs Symptom Experience, Gregory S Sayuk, Carol S North, David E Pollio, Britt M Gott, David H Alpers

2020-Current year OA Pubs

Objective: Some IBS patients possess detailed memories of the events surrounding their bowel symptom onset ("episodic memories"). In this exploratory study we sought to: (1) examine memory relationship with gastrointestinal (GI) symptom severity, extraintestinal symptoms, and mood; (2) qualitatively explore memory valence and content in IBS patients with or without episodic memories.

Methods: Referral IBS patients

Results: 14/29 (48.3%) of IBS subjects endorsed episodic memories of IBS symptom onset, often GI infections/enteritis (35.7%). Recall of the exact year (69%) and month (60%) of symptom onset were common. Episodic memories were associated with greater IBS symptom severity/bother, higher anxiety/depression, and poorer …

Case Report: A Novel Eif2b3 Pathogenic Variant In Central Nervous System Hypomyelination/Vanishing White Matter, Parith Wongkittichote, Soe Soe Mar, Robert C Mckinstry, Hoanh Nguyen

2020-Current year OA Pubs

Leukodystrophies are a group of heterogeneous disorders affecting brain myelin. Among those, childhood ataxia with central nervous system hypomyelination/vanishing white matter (CACH/VWM) is one of the more common inherited leukodystrophies. Pathogenic variants in one of the genes encoding five subunits of EIF2B are associated with CACH/VWM. Herein, we presented a case of CACH/VWM who developed ataxia following a minor head injury. Brain magnetic resonance imaging showed extensive white matter signal abnormality. Diagnosis of CACH/VWM was confirmed by the presence of compound heterozygous variants in

Maternal Perceptions About Sensory Interventions In The Neonatal Intensive Care Unit: An Exploratory Qualitative Study, Julia Lisle, Kylie Buma, Joan Smith, Marinthea Richter, Prutha Satpute, Roberta Pineda

2020-Current year OA Pubs

Background: Mothers play an important role in providing positive sensory experiences to their infants during NICU hospitalization. However, little is known regarding maternal perceptions about sensory-based interventions in the NICU. Further, understanding maternal perceptions was an important part of the process during development of the Supporting and Enhancing NICU Sensory Experiences (SENSE) program.

Methods: Twenty mothers of very preterm infants were interviewed after NICU discharge and asked open-ended questions about sensory-based interventions they performed in the NICU and probed about their perceptions related to the development of a sensory-based guideline and the use of volunteers to provide sensory-based interventions when …

Predictors Of Lung Adenocarcinoma With Leptomeningeal Metastases: A 2022 Targeted-Therapy-Assisted Molgpa Model, Milan Zhang, Jiayi Tong, Weifeng Ma, Chongliang Luo, Huiqin Liu, Yushu Jiang, Lingzhi Qin, Xiaojuan Wang, Lipin Yuan, Jiewen Zhang, Fuhua Peng, Yong Chen, Wei Li, Ying Jiang

2020-Current year OA Pubs

Objective: To explore prognostic indicators of lung adenocarcinoma with leptomeningeal metastases (LM) and provide an updated graded prognostic assessment model integrated with molecular alterations (molGPA).

Methods: A cohort of 162 patients was enrolled from 202 patients with lung adenocarcinoma and LM. By randomly splitting data into the training (80%) and validation (20%) sets, the Cox regression and random survival forest methods were used on the training set to identify statistically significant variables and construct a prognostic model. The C-index of the model was calculated and compared with that of previous molGPA models.

Results: The Cox regression and random forest models …

Associations Of Polymorphisms In The Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha Gene With Subsequent Coronary Heart Disease: An Individual-Level Meta-Analysis, Tessa Schillemans, Sharon Cresci, Et Al

2020-Current year OA Pubs

No abstract provided.

Exploring The Role Of Low-Density Neutrophils During Mycobacterium Tuberculosis Infection, Ananda N Rankin, Skyler V Hendrix, Sumanta K Naik, Christina L Stallings

2020-Current year OA Pubs

Tuberculosis (TB) is caused by infection with the bacterium

Cilia Action In Islets: Lessons From Mouse Models, Jung Hoon Cho, Jing W Hughes

2020-Current year OA Pubs

Primary cilia as a signaling organelle have garnered recent attention as a regulator of pancreatic islet function. These rod-like sensors exist on all major islet endocrine cell types and transduce a variety of external cues, while dysregulation of cilia function contributes to the development of diabetes. The complex role of islet primary cilia has been examined using genetic deletion targeting various components of cilia. In this review, we summarize experimental models for the study of islet cilia and current understanding of mechanisms of cilia regulation of islet hormone secretion. Consensus from these studies shows that pancreatic cilia perturbation can cause …

A Polygenic Risk Score Based On A Cardioembolic Stroke Multitrait Analysis Improves A Clinical Prediction Model For This Stroke Subtype, Jara Cárcel-Márquez, Laura Ibañez, Laura Heitsch, Rajat Dhar, Carlos Cruchaga, Jin-Moo Lee, Et Al

2020-Current year OA Pubs

Background: Occult atrial fibrillation (AF) is one of the major causes of embolic stroke of undetermined source (ESUS). Knowing the underlying etiology of an ESUS will reduce stroke recurrence and/or unnecessary use of anticoagulants. Understanding cardioembolic strokes (CES), whose main cause is AF, will provide tools to select patients who would benefit from anticoagulants among those with ESUS or AF. We aimed to discover novel loci associated with CES and create a polygenetic risk score (PRS) for a more efficient CES risk stratification.

Methods: Multitrait analysis of GWAS (MTAG) was performed with MEGASTROKE-CES cohort (

Results: We found and replicated …

Uric Acid Predicts Recovery Of Left Ventricular Function And Adverse Events In Heart Failure With Reduced Ejection Fraction: Potential Mechanistic Insight From Network Analyses, Xiqiang Wang, Xiude Fan, Qihui Wu, Jing Liu, Linyan Wei, Dandan Yang, Xiang Bu, Xiaoxiang Liu, Aiqun Ma, Tomohiro Hayashi, Gongchang Guan, Yu Xiang, Shuang Shi, Junkui Wang, Jiansong Fang

2020-Current year OA Pubs

Background and Aims: Heart failure with reduced ejection fraction (HFrEF) still carries a high risk for a sustained decrease in left ventricular ejection fraction (LVEF) even with the optimal medical therapy. Currently, there is no effective tool to stratify these patients according to their recovery potential. We tested the hypothesis that uric acid (UA) could predict recovery of LVEF and prognosis of HFrEF patients and attempted to explore mechanistic relationship between hyperuricemia and HFrEF.

Methods: HFrEF patients with hyperuricemia were selected from the National Inpatient Sample (NIS) 2016-2018 database and our Xianyang prospective cohort study. Demographics, cardiac risk factors, and …

A Callosal Biomarker Of Behavioral Intervention Outcomes For Autism Spectrum Disorder? A Case-Control Feasibility Study With Diffusion Tensor Imaging, Javier Virues-Ortega, Nicole S. Mckay, Jessica C. Mccormack, Nerea Lopez, Rosalie Liu, Ian Kirk

2020-Current year OA Pubs

Tentative results from feasibility analyses are critical for planning future randomized control trials (RCTs) in the emerging field of neural biomarkers of behavioral interventions. The current feasibility study used MRI-derived diffusion imaging data to investigate whether it would be possible to identify neural biomarkers of a behavioral intervention among people diagnosed with autism spectrum disorder (ASD). The corpus callosum has been linked to cognitive processing and callosal abnormalities have been previously found in people diagnosed with ASD. We used a case-control design to evaluate the association between the type of intervention people diagnosed with ASD had previously received and their …

The Role Of Neutrophil Extracellular Traps In Acute Lung Injury, Davide Scozzi, Fuyi Liao, Alexander S Krupnick, Daniel Kreisel, Andrew E Gelman

2020-Current year OA Pubs

Acute lung injury (ALI) is a heterogeneous inflammatory condition associated with high morbidity and mortality. Neutrophils play a key role in the development of different forms of ALI, and the release of neutrophil extracellular traps (NETs) is emerging as a common pathogenic mechanism. NETs are essential in controlling pathogens, and their defective release or increased degradation leads to a higher risk of infection. However, NETs also contain several pro-inflammatory and cytotoxic molecules than can exacerbate thromboinflammation and lung tissue injury. To reduce NET-mediated lung damage and inflammation, DNase is frequently used in preclinical models of ALI due to its capability …