Digital Commons Network^™

Coronavirus Disease-19 And Cardiovascular Disease: A Risk Factor Or A Risk Marker?, Jing Liu, Salim S Virani, Mahboob Alam, Ali E Denktas, Ihab Hamzeh, Umair Khalid

Faculty, Staff and Students Publications

Severe acute respiratory syndrome coronavirus-2 causes the clinical syndrome of coronavirus disease of 2019 (COVID-19) which has become a global pandemic resulting in significant morbidity and mortality. While the virus primarily affects the respiratory system, it also causes a wide variety of complex cardiac manifestations such as acute myopericarditis, acute coronary syndrome, congested heart failure, cardiogenic shock and cardiac arrhythmias. There are numerous proposed mechanisms of cardiac injury, including direct cellular injury, pro-inflammatory cytokine storm, myocardial oxygen-demand mismatch, and systemic inflammation causing multi-organ failure. Additionally, medications commonly used to treat COVID-19 patients have various cardiovascular side effects. We aim to …

Coronavirus Disease-19 And Cardiovascular Disease: A Risk Factor Or A Risk Marker?, Jing Liu, Salim S Virani, Mahboob Alam, Ali E Denktas, Ihab Hamzeh, Umair Khalid

Faculty, Staff and Students Publications

Severe acute respiratory syndrome coronavirus-2 causes the clinical syndrome of coronavirus disease of 2019 (COVID-19) which has become a global pandemic resulting in significant morbidity and mortality. While the virus primarily affects the respiratory system, it also causes a wide variety of complex cardiac manifestations such as acute myopericarditis, acute coronary syndrome, congested heart failure, cardiogenic shock and cardiac arrhythmias. There are numerous proposed mechanisms of cardiac injury, including direct cellular injury, pro-inflammatory cytokine storm, myocardial oxygen-demand mismatch, and systemic inflammation causing multi-organ failure. Additionally, medications commonly used to treat COVID-19 patients have various cardiovascular side effects. We aim to …

Temporal Changes And Institutional Variation In Use Of Percutaneous Coronary Intervention For St-Elevation Myocardial Infarction With Multivessel Coronary Artery Disease In The United States: An Ncdr Research To Practice Project, Eric A Secemsky, Neel Butala, Aishwarya Raja, Rohan Khera, Yongfei Wang, Jeptha P Curtis, Thomas M Maddox, Salim S Virani, Ehrin J Armstrong, Kendrick A Shunk, Ralph G Brindis, Deepak Bhatt, Robert W Yeh

Faculty, Staff and Students Publications

IMPORTANCE: After disparate results from observational and small randomized studies, the COMPLETE trial demonstrated superiority of multivessel (MV) percutaneous coronary intervention (PCI) over culprit-only PCI for ST-elevation myocardial infarction (STEMI).

OBJECTIVE: To describe temporal trends and institutional variation of MV PCI use for STEMI in the United States to inform how new evidence may influence clinical practice.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included STEMI admissions involving MV disease from 1598 institutions in the National Cardiovascular Data Registry CathPCI Registry from the third quarter of 2009 to the first quarter of 2018. An MV PCI was defined as a …

Type 2 Diabetes Subgroups, Risk For Complications, And Differential Effects Due To An Intensive Lifestyle Intervention, Michael P Bancks, Haiying Chen, Ashok Balasubramanyam, Alain G Bertoni, Mark A Espeland, Steven E Kahn, Scott Pilla, Elizabeth Vaughan, Lynne E Wagenknecht

Faculty, Staff and Students Publications

OBJECTIVE: We reevaluated the Action for Health in Diabetes (Look AHEAD) intervention, incorporating diabetes subgroups, to identify whether intensive lifestyle intervention (ILI) is associated with differential risk for cardiovascular disease (CVD) by diabetes subgroup.

RESEARCH DESIGN AND METHODS: In the Look AHEAD trial, 5,145 participants, aged 45-76 years, with type 2 diabetes (T2D) and overweight or obesity were randomly assigned to 10 years of ILI or a control condition of diabetes support and education. The ILI focused on weight loss through decreased caloric intake and increased physical activity. To characterize diabetes subgroups, we applied k-means clustering to data on age …

Exercise-Induced Alterations In Phospholipid Hydrolysis, Airway Surfactant, And Eicosanoids And Their Role In Airway Hyperresponsiveness In Asthma, Ryan C Murphy, Ying Lai, James D Nolin, Robier A Aguillon Prada, Arindam Chakrabarti, Michael V Novotny, Michael C Seeds, William A Altemeier, Michael H Gelb, Robert Duncan Hite, Teal S Hallstrand

Faculty, Staff and Student Publications

The mechanisms responsible for driving endogenous airway hyperresponsiveness (AHR) in the form of exercise-induced bronchoconstriction (EIB) are not fully understood. We examined alterations in airway phospholipid hydrolysis, surfactant degradation, and lipid mediator release in relation to AHR severity and changes induced by exercise challenge. Paired induced sputum (

Global Trends In Norovirus Genotype Distribution Among Children With Acute Gastroenteritis., Jennifer L. Cannon, Joseph Bonifacio, Filemon Bucardo, Javier Buesa, Leesa Bruggink, Martin Chi-Wai Chan, Tulio M. Fumian, Sidhartha Giri, Mark D. Gonzalez, Joanne Hewitt, Jih-Hui Lin, Janet Mans, Christian Muñoz, Chao-Yang Pan, Xiao-Li Pang, Corinna Pietsch, Mustafiz Rahman, Naomi Sakon, Rangaraj Selvarangan, Hannah Browne, Leslie Barclay, Jan Vinjé

Manuscripts, Articles, Book Chapters and Other Papers

Noroviruses are a leading cause of acute gastroenteritis (AGE) among adults and children worldwide. NoroSurv is a global network for norovirus strain surveillance among children(genotype and polymerase type) and uploaded 1,325 dual-typed sequences to the NoroSurv web portal during 2016-2020. More than 50% of submitted sequences were GII.4 Sydney[P16] or GII.4 Sydney[P31] strains. Other common strains included GII.2[P16], GII.3[P12], GII.6[P7], and GI.3[P3] viruses. In total, 22 genotypes and 36 dual types, including GII.3 and GII.20 viruses with rarely reported polymerase types, were detected, reflecting high strain diversity. Surveillance data captured in NoroSurv enables the monitoring of trends in norovirus strains …

The Impact Of Erythropoietin On Short- And Long-Term Kidney-Related Outcomes In Neonates Of Extremely Low Gestational Age. Results Of A Multicenter, Double-Blind, Placebo-Controlled Randomized Clinical Trial, David J. Askenazi, Patrick J. Heagerty, Robert H. Schmicker, Patrick Brophy, Sandra E. Juul, Stuart L. Goldstein, Sangeeta Hingorani, Jean Lowe, Penut Trial Consortium

Pediatrics Research and Scholarship

OBJECTIVE: To evaluate whether extremely low gestational age neonates (ELGANs) randomized to erythropoietin have better or worse kidney-related outcomes during hospitalization and at 22-26 months of corrected gestational age (cGA) compared with those randomized to placebo.

STUDY DESIGN: We performed an ancillary study to a multicenter double-blind, placebo-controlled randomized clinical trial of erythropoietin in ELGANs.

RESULTS: The prevalence of severe (stage 2 or 3) acute kidney injury (AKI) was 18.2%. We did not find a statistically significant difference between those randomized to erythropoietin vs placebo for in-hospital primary (severe AKI) or secondary outcomes (any AKI and serum creatinine/cystatin C values …

Highly Accurate Chip-Based Resequencing Of Sars-Cov-2 Clinical Samples, Kendall Hoff, Xun Ding, Lucas Carter, John Duque, Ju-Yu Lin, Samantha Dung, Priyanka Singh, Jiayi Sun, Filip Crnogorac, Radha Swaminathan, Emily N. Alden, Xuechen Zhu, Ryota Shimada, Marijan Posavi, Noah Hull, Darrell L. Dinwiddie, Adam M. Halasz, Glenn Mcgall, Wei Zhou, Jeremy S. Edwards

Pediatrics Research and Scholarship

SARS-CoV-2 has infected over 128 million people worldwide, and until a vaccine is developed and widely disseminated, vigilant testing and contact tracing are the most effective ways to slow the spread of COVID-19. Typical clinical testing only confirms the presence or absence of the virus, but rather, a simple and rapid testing procedure that sequences the entire genome would be impactful and allow for tracing the spread of the virus and variants, as well as the appearance of new variants. However, traditional short read sequencing methods are time consuming and expensive. Herein, we describe a tiled genome array that we …

In Men With Obesity, T2dm Is Associated With Poor Trabecular Microarchitecture And Bone Strength And Low Bone Turnover, Francesca Vigevano, Giulia Gregori, Georgia Colleluori, Rui Chen, Vimlin Autemrongsawat, Nicola Napoli, Clifford Qualls, Dennis T Villareal, Reina Armamento-Villareal

Faculty, Staff and Students Publications

INTRODUCTION: Obesity and type 2 Diabetes (T2D) are both associated with greater bone mineral density (BMD) but increased risk of fractures. The effect of the combination of both conditions on bone metabolism, microarchitecture, and strength in the obese population remains unknown.

METHODS: Data from 112 obese men were collected. Bone turnover and biochemical markers were measured by enzyme-linked immunosorbent assay, body composition and BMD at all sites were assessed by dual energy X-ray absorptiometry, whereas bone microarchitecture and strength (stiffness and failure load) were measured by high-resolution peripheral computed tomography. Data were compared among metabolically healthy obese (MHO) and metabolically …

A Microbiota-Directed Food Intervention For Undernourished Children, Robert Y Chen, Matthew C Hibberd, Arjun S Raman, Daniel Webber, Cyrus Zhou, Vinaik Sundaresan, Kazi Ahsan, Martin F Meier, Michael J Barratt, Jeffrey I Gordon, Et Al

Open Access Publications

BACKGROUND: More than 30 million children worldwide have moderate acute malnutrition. Current treatments have limited effectiveness, and much remains unknown about the pathogenesis of this condition. Children with moderate acute malnutrition have perturbed development of their gut microbiota.

METHODS: In this study, we provided a microbiota-directed complementary food prototype (MDCF-2) or a ready-to-use supplementary food (RUSF) to 123 slum-dwelling Bangladeshi children with moderate acute malnutrition between the ages of 12 months and 18 months. The supplementation was given twice daily for 3 months, followed by 1 month of monitoring. We obtained weight-for-length, weight-for-age, and length-for-age z scores and mid-upper-arm circumference …

Hybrid Diffusion Imaging Reveals Altered White Matter Tract Integrity And Associations With Symptoms And Cognitive Dysfunction In Chronic Traumatic Brain Injury., Jennifer Muller, Devon Middleton, M. Alizadeh, George Zabrecky, Nancy Wintering, Anthony J. Bazzan, Ji Lang, Chengyuan Wu, Daniel A. Monti, Qianhong Wu, Andrew B. Newberg, Feroze B. Mohamed

Department of Radiology Faculty Papers

The detection and association of in vivo biomarkers in white matter (WM) pathology after acute and chronic mild traumatic brain injury (mTBI) are needed to improve care and develop therapies. In this study, we used the diffusion MRI method of hybrid diffusion imaging (HYDI)to detect white matter alterations in patients with chronic TBI (cTBI). 40 patients with cTBI presenting symptoms at least three months post injury, and 17 healthy controls underwent magnetic resonance HYDI. cTBI patients were assessed with a battery of neuropsychological tests. A voxel-wise statistical analysis within the white matter skeleton was performed to study between group differences …

Evolution Of Genetic Networks For Human Creativity, I Zwir, C Del-Val, C R Cloninger, Et Al

Open Access Publications

The genetic basis for the emergence of creativity in modern humans remains a mystery despite sequencing the genomes of chimpanzees and Neanderthals, our closest hominid relatives. Data-driven methods allowed us to uncover networks of genes distinguishing the three major systems of modern human personality and adaptability: emotional reactivity, self-control, and self-awareness. Now we have identified which of these genes are present in chimpanzees and Neanderthals. We replicated our findings in separate analyses of three high-coverage genomes of Neanderthals. We found that Neanderthals had nearly the same genes for emotional reactivity as chimpanzees, and they were intermediate between modern humans and …

Genetic And Non-Genetic Factors Affecting The Expression Of Covid-19-Relevant Genes In The Large Airway Epithelium, Silva Kasela, Victor E Ortega, Molly Martorella, Suresh Garudadri, Jenna Nguyen, Elizabeth Ampleford, Anu Pasanen, Srilaxmi Nerella, Kristina L Buschur, Igor Z Barjaktarevic, R Graham Barr, Eugene R Bleecker, Russell P Bowler, Alejandro P Comellas, Christopher B Cooper, David J Couper, Gerard J Criner, Jeffrey L Curtis, Meilan K Han, Nadia N Hansel, Eric A Hoffman, Robert J Kaner, Jerry A Krishnan, Fernando J Martinez, Merry-Lynn N Mcdonald, Deborah A Meyers, Robert Paine, Stephen P Peters, Mario Castro, Loren C Denlinger, Serpil C Erzurum, John V Fahy, Elliot Israel, Nizar N Jarjour, Bruce D Levy, Xingnan Li, Wendy C Moore, Sally E Wenzel, Charles Langelier, Prescott G Woodruff, Tuuli Lappalainen, Stephanie A Christenson

Faculty, Staff and Student Publications

BACKGROUND: The large airway epithelial barrier provides one of the first lines of defense against respiratory viruses, including SARS-CoV-2 that causes COVID-19. Substantial inter-individual variability in individual disease courses is hypothesized to be partially mediated by the differential regulation of the genes that interact with the SARS-CoV-2 virus or are involved in the subsequent host response. Here, we comprehensively investigated non-genetic and genetic factors influencing COVID-19-relevant bronchial epithelial gene expression.

METHODS: We analyzed RNA-sequencing data from bronchial epithelial brushings obtained from uninfected individuals. We related ACE2 gene expression to host and environmental factors in the SPIROMICS cohort of smokers with …

Dorsal Anterior Cingulate Cortex Encodes The Integrated Incentive Motivational Value Of Cognitive Task Performance, Debbie M Yee, Jennifer L Crawford, Bidhan Lamichhane, Todd S Braver

2020-Current year OA Pubs

Humans can seamlessly combine value signals from diverse motivational incentives, yet it is not well understood how these signals are "bundled" in the brain to modulate cognitive control. The dorsal ACC (dACC) is theorized to integrate motivational value dimensions in the service of goal-directed action, although this hypothesis has yet to receive rigorous confirmation. In the present study, we examined the role of human dACC in motivational incentive integration. Healthy young adult men and women were scanned with fMRI while engaged in an experimental paradigm that quantifies the combined effects of liquid (e.g., juice, neutral, saltwater) and monetary incentives on …

Proteogenomic And Metabolomic Characterization Of Human Glioblastoma, Liang-Bo Wang, Alla Karpova, Marina A Gritsenko, Jennifer E Kyle, Song Cao, Yize Li, Dmitry Rykunov, Antonio Colaprico, Joseph H Rothstein, Runyu Hong, Vasileios Stathias, Macintosh Cornwell, Francesca Petralia, Yige Wu, Boris Reva, Karsten Krug, Pietro Pugliese, Emily Kawaler, Lindsey K Olsen, Wen-Wei Liang, Xiaoyu Song, Yongchao Dou, Michael C Wendl, Wagma Caravan, Wenke Liu, Daniel Cui Zhou, Jiayi Ji, Chia-Feng Tsai, Vladislav A Petyuk, Jamie Moon, Weiping Ma, Rosalie K Chu, Karl K Weitz, Ronald J Moore, Matthew E Monroe, Rui Zhao, Xiaolu Yang, Seungyeul Yoo, Azra Krek, Alexis Demopoulos, Houxiang Zhu, Matthew A Wyczalkowski, Joshua F Mcmichael, Brittany L Henderson, Caleb M Lindgren, Hannah Boekweg, Shuangjia Lu, Jessika Baral, Lijun Yao, Kelly G Stratton, Lisa M Bramer, Erika Zink, Sneha P Couvillion, Kent J Bloodsworth, Shankha Satpathy, Weiva Sieh, Simina M Boca, Stephan Schürer, Feng Chen, Maciej Wiznerowicz, Karen A Ketchum, Emily S Boja, Christopher R Kinsinger, Ana I Robles, Tara Hiltke, Mathangi Thiagarajan, Alexey I Nesvizhskii, Bing Zhang, D R Mani, Michele Ceccarelli, Xi S Chen, Sandra L Cottingham, Qing Kay Li, Albert H Kim, David Fenyö, Kelly V Ruggles, Henry Rodriguez, Mehdi Mesri, Samuel H Payne, Adam C Resnick, Pei Wang, Richard D Smith, Antonio Iavarone, Milan G Chheda, Jill S Barnholtz-Sloan, Karin D Rodland, Tao Liu, Li Ding, Clinical Proteomic Tumor Analysis Consortium

Faculty, Staff and Students Publications

Glioblastoma (GBM) is the most aggressive nervous system cancer. Understanding its molecular pathogenesis is crucial to improving diagnosis and treatment. Integrated analysis of genomic, proteomic, post-translational modification and metabolomic data on 99 treatment-naive GBMs provides insights to GBM biology. We identify key phosphorylation events (e.g., phosphorylated PTPN11 and PLCG1) as potential switches mediating oncogenic pathway activation, as well as potential targets for EGFR-, TP53-, and RB1-altered tumors. Immune subtypes with distinct immune cell types are discovered using bulk omics methodologies, validated by snRNA-seq, and correlated with specific expression and histone acetylation patterns. Histone H2B acetylation in classical-like and immune-low GBM …

Functional Interpretation Of Atad3a Variants In Neuro-Mitochondrial Phenotypes, Zheng Yie Yap, Yo Han Park, Saskia B Wortmann, Adam C Gunning, Shlomit Ezer, Sukyeong Lee, Lita Duraine, Ekkehard Wilichowski, Kate Wilson, Johannes A Mayr, Matias Wagner, Hong Li, Usha Kini, Emily Davis Black, Kristin G Monaghan, James R Lupski, Sian Ellard, Dominik S Westphal, Tamar Harel, Wan Hee Yoon

Faculty, Staff and Students Publications

BACKGROUND: ATPase family AAA-domain containing protein 3A (ATAD3A) is a nuclear-encoded mitochondrial membrane-anchored protein involved in diverse processes including mitochondrial dynamics, mitochondrial DNA organization, and cholesterol metabolism. Biallelic deletions (null), recessive missense variants (hypomorph), and heterozygous missense variants or duplications (antimorph) in ATAD3A lead to neurological syndromes in humans.

METHODS: To expand the mutational spectrum of ATAD3A variants and to provide functional interpretation of missense alleles in trans to deletion alleles, we performed exome sequencing for identification of single nucleotide variants (SNVs) and copy number variants (CNVs) in ATAD3A in individuals with neurological and mitochondrial phenotypes. A Drosophila Atad3a Gal4 …

Pfmfr3: A Multidrug-Resistant Modulator In Plasmodium Falciparum, Frances Rocamora, Purva Gupta, Eva S Istvan, Madeline R Luth, Emma F Carpenter, Krittikorn Kümpornsin, Erika Sasaki, Jaeson Calla, Nimisha Mittal, Krypton Carolino, Edward Owen, Manuel Llinás, Sabine Ottilie, Daniel E Goldberg, Marcus C S Lee, Elizabeth A Winzeler

2020-Current year OA Pubs

In malaria, chemical genetics is a powerful method for assigning function to uncharacterized genes. MMV085203 and GNF-Pf-3600 are two structurally related napthoquinone phenotypic screening hits that kill both blood- and sexual-stage

Obstructive Sleep Apnea And Dementia-Common Gene Associations Through Network-Based Identification Of Common Driver Genes, Hyun-Hwan Jeong, Arvind Chandrakantan, Adam C Adler

Faculty, Staff and Students Publications

BACKGROUND: Obstructive Sleep Apnea (OSA) occurs in 7% of the adult population. The relationship between neurodegenerative diseases such as dementia and sleep disorders have long attracted clinical attention; however, no comprehensive data exists elucidating common gene expression between the two diseases. The objective of this study was to (1) demonstrate the practicability and feasibility of utilizing a systems biology approach called network-based identification of common driver genes (NICD) to identify common genomic features between two associated diseases and (2) utilize this approach to identify genes associated with both OSA and dementia.

METHODS: This study utilized 2 public databases (PCNet, DisGeNET) …

Noninvasive Hemoglobin Level Prediction In A Mobile Phone Environment: State Of The Art Review And Recommendations., Kamrul Hasan Md, Masanul Aziz Md, Ishrak Islam Zarif Md, Mahmudul Hasan, Mma Hashem, Shion Guha Phd, Richard R Love, Sheikh Ahamed

Health Services and Informatics Research

BACKGROUND: There is worldwide demand for an affordable hemoglobin measurement solution, which is a particularly urgent need in developing countries. The smartphone, which is the most penetrated device in both rich and resource-constrained areas, would be a suitable choice to build this solution. Consideration of a smartphone-based hemoglobin measurement tool is compelling because of the possibilities for an affordable, portable, and reliable point-of-care tool by leveraging the camera capacity, computing power, and lighting sources of the smartphone. However, several smartphone-based hemoglobin measurement techniques have encountered significant challenges with respect to data collection methods, sensor selection, signal analysis processes, and machine-learning …

The Structure, Function And Evolution Of A Complete Human Chromosome 8, Glennis A Logsdon, Milinn Kremitzki, Tina A Graves-Lindsay, Et Al

Open Access Publications

The complete assembly of each human chromosome is essential for understanding human biology and evolution

Dietary Intake Is Associated With Neuropsychological Impairment In Women With Hiv, Leah H. Rubin, Deborah R. Gustafson, Lakshmi Warrior, Lila Sheira, Kathryn C. Fitzgerald, Raha Dastgheyb, Kathleen M. Weber, Phyllis C. Tien, Audrey French, Amanda B. Spence, Anjali Sharma, Dionna W. Williams, Cory J. White, Eric C. Seaberg, Edward A. Frongillo Jr., Sheri D. Weiser

Faculty Publications

Background

Diet is a modifiable risk factor that may influence cognition in people with HIV.

Objectives

We examined the association between dietary intake and cognition in women with HIV (WWH) and HIV-seronegative women.

Methods

An 18-item dietary National Cancer Institute screener was completed by 729 WWH and 346 HIV-seronegative Women's Interagency HIV Study participants. Daily intake frequencies of processed meats, sweet beverages, fish, whole milk, and vegetables were calculated. Participants completed biennial neuropsychological (NP) testing. NP domains included attention/working memory, executive function, processing speed, memory, learning, fluency, and motor function. NP impairment was defined as demographically adjusted T-scores (mean = …

Reducing Patient Risk For Suicidal Behaviors With A Safety Bundle Of Best Practices With Non-Psychiatric Patients, Olayemi Akindele

Student Scholarly Projects

Practice Problem: Suicide is a public health condition that affects people globally. The increased suicidal behaviors of patients in a medical-surgical unit demanded an effective screening protocol to identify high-risk patients.

PICOT: In patients 18 years and older on a medical-surgical unit, does the implementation of the Columbia Suicide Severity Rating Scale (C-SSRS) tool and application of a Safety Bundle of Best Practices (SBBP) increase early identification of suicide risk with decreased patient self-harm behaviors, compared to the current standard practice of no assessment tool or safety bundle of best practices within 12 weeks?

Evidence: Ten studies served as evidence …

Rev-Erb In Gabaergic Neurons Controls Diurnal Hepatic Insulin Sensitivity, Guolian Ding, Xin Li, Xinguo Hou, Wenjun Zhou, Yingyun Gong, Fuqiang Liu, Yanlin He, Jia Song, Jing Wang, Paul Basil, Wenbo Li, Sichong Qian, Pradip Saha, Jinbang Wang, Chen Cui, Tingting Yang, Kexin Zou, Younghun Han, Christopher I Amos, Yong Xu, Li Chen, Zheng Sun

Faculty, Staff and Students Publications

Systemic insulin sensitivity shows diurnal rhythm with a peak at wakening1,2. The molecular mechanism underlying such a temporal pattern is unclear. Here we demonstrate that nuclear receptors Rev-erbα/β in the GABAergic neurons in the suprachiasmatic nucleus (SCNGABA) control the diurnal rhythm of insulin-mediated suppression of hepatic glucose production in mice, without affecting diurnal eating or locomotor behaviors under the regular light-dark cycles. Rev-erb regulates the rhythmic expression of genes involved in neurotransmission in the SCN and modulates the oscillatory firing activity of SCNGABA neurons. Chemogenetic stimulation of SCNGABA neurons at wakening causes glucose intolerance, while restoration …

Patient Satisfaction With Noise, Robert W. Kentner Ii

Student Scholarly Projects

Practice Problem: Noise on hospital units can interfere with patient rest, timely recovery, and statisfacton with care. Improvements in the reduction of hospital noise levels lead to improved patient satisfaction and improved rest. Patients were surveyed on their satisfaction with noise during the day and at night.

PICOT: In Acute Care Patients (P), does the implementation of a noise reduction program (I) compared to no noise reduction program (C), affect patient satisfaction with noise (O) over a six-week period (T)?

Evidence: Studies show that many hospitals have noise levels that exceed the World Health Organization’s recommended standards for noise …

Automated Software-Assisted Diagnosis Of Esophageal Squamous Cell Neoplasia Using High-Resolution Microendoscopy, Mimi C Tan, Sheena Bhushan, Timothy Quang, Richard Schwarz, Kalpesh H Patel, Xinying Yu, Zhengqi Li, Guiqi Wang, Fan Zhang, Xueshan Wang, Hong Xu, Rebecca R Richards-Kortum, Sharmila Anandasabapathy

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: High-resolution microendoscopy (HRME) is an optical biopsy technology that provides subcellular imaging of esophageal mucosa but requires expert interpretation of these histopathology-like images. We compared endoscopists with an automated software algorithm for detection of esophageal squamous cell neoplasia (ESCN) and evaluated the endoscopists' accuracy with and without input from the software algorithm.

METHODS: Thirteen endoscopists (6 experts, 7 novices) were trained and tested on 218 post-hoc HRME images from 130 consecutive patients undergoing ESCN screening/surveillance. The automated software algorithm interpreted all images as neoplastic (high-grade dysplasia, ESCN) or non-neoplastic. All endoscopists provided their interpretation (neoplastic or non-neoplastic) …

A Millifluidic Perfusion Cassette For Studying The Pathogenesis Of Enteric Infections Using Ex-Vivo Organoids, Reid L Wilson, Sarah A Hewes, Anubama Rajan, Shih-Ching Lin, Carolyn Bomidi, Takanori Iida, Mary K Estes, Anthony W Maresso, K Jane Grande-Allen

Faculty, Staff and Students Publications

To generate physiologically-relevant experimental models, the study of enteric diarrheal diseases is turning increasingly to advanced in vitro models that combine ex vivo, stem cell-derived "organoid" cell lines with bioengineered culture environments that expose them to mechanical stimuli, such as fluid flow. However, such approaches require considerable technical expertise with both microfabrication and organoid culture, and are, therefore, inaccessible to many researchers. For this reason, we have developed a perfusion system that is simple to fabricate, operate, and maintain. Its dimensions approximate the volume and cell culture area of traditional 96-well plates and allow the incorporation of fastidious primary, stem …

Quantitative Endophenotypes As An Alternative Approach To Understanding Genetic Risk In Neurodegenerative Diseases, Fabiana H G Farias, Bruno A Benitez, Carlos Cruchaga

2020-Current year OA Pubs

Endophenotypes, as measurable intermediate features of human diseases, reflect underlying molecular mechanisms. The use of quantitative endophenotypes in genetic studies has improved our understanding of pathophysiological changes associated with diseases. The main advantage of the quantitative endophenotypes approach to study human diseases over a classic case-control study design is the inferred biological context that can enable the development of effective disease-modifying treatments. Here, we summarize recent progress on biomarkers for neurodegenerative diseases, including cerebrospinal fluid and blood-based, neuroimaging, neuropathological, and clinical studies. This review focuses on how endophenotypic studies have successfully linked genetic modifiers to disease risk, disease onset, or …

Myocardial T1 And T2 Mapping By Magnetic Resonance In Patients With Immune Checkpoint Inhibitor-Associated Myocarditis., Paaladinesh Thavendiranathan, Lili Zhang, Amna Zafar, Zsofia D Drobni, Syed S Mahmood, Marcella Cabral, Magid Awadalla, Anju Nohria, Daniel A Zlotoff, Franck Thuny, Lucie M Heinzerling, Ana Barac, Ryan J Sullivan, Carol L Chen, Dipti Gupta, Michael C Kirchberger, Sarah E Hartmann, Jonathan W Weinsaft, Hannah K Gilman, Muhammad A. Rizvi Md, Bojan Kovacina, Caroline Michel, Gagan Sahni, Ana González-Mansilla, Antonio Calles, Francisco Fernández-Avilés, Michael Mahmoudi, Kerry L Reynolds, Sarju Ganatra, Juan José Gavira, Nahikari Salterain González, Manuel García De Yébenes Castro, Raymond Y Kwong, Michael Jerosch-Herold, Otavio R Coelho-Filho, Jonathan Afilalo, Eduardo Zataraín-Nicolás, A John Baksi, Bernd J Wintersperger, Oscar Calvillo-Arguelles, Stephane Ederhy, Eric H Yang, Alexander R Lyon, Michael G Fradley, Tomas G Neilan

Hematology-Medical Oncology Division

BACKGROUND: Myocarditis is a potentially fatal complication of immune checkpoint inhibitor (ICI) therapy. Data on the utility of cardiovascular magnetic resonance (CMR) T1 and T2 mapping in ICI myocarditis are limited.

OBJECTIVES: This study sought to assess the value of CMR T1 and T2 mapping in patients with ICI myocarditis.

METHODS: In this retrospective study from an international registry of patients with ICI myocarditis, clinical and CMR findings (including T1 and T2 maps) were collected. Abnormal T1 and T2 were defined as 2 SD above site (vendor/field strength specific) reference values and a z-score was calculated for each patient. Major …

Functional Connectivity Within Glioblastoma Impacts Overall Survival, Andy G S Daniel, Ki Yun Park, Jarod L Roland, Donna Dierker, James Gross, Joseph B Humphries, Carl D Hacker, Abraham Z Snyder, Joshua S Shimony, Eric C Leuthardt

2020-Current year OA Pubs

BACKGROUND: Glioblastoma (GBM; World Health Organization grade IV) assumes a variable appearance on MRI owing to heterogeneous proliferation and infiltration of its cells. As a result, the neurovascular units responsible for functional connectivity (FC) may exist within gross tumor boundaries, albeit with altered magnitude. Therefore, we hypothesize that the strength of FC within GBMs is predictive of overall survival.

METHODS: We used predefined FC regions of interest (ROIs) in de novo GBM patients to characterize the presence of within-tumor FC observable via resting-state functional MRI and its relationship to survival outcomes.

RESULTS: Fifty-seven GBM patients (mean age, 57.8 ± 13.9 …

Myd88 L265p Elicits Mutation-Specific Ubiquitination To Drive Nf-Κb Activation And Lymphomagenesis, Xinfang Yu, Wei Li, Qipan Deng, Haidan Liu, Xu Wang, Hui Hu, Ya Cao, Zijun Y Xu-Monette, Ling Li, Mingzhi Zhang, Zhongxin Lu, Ken H Young, Yong Li

Faculty, Staff and Students Publications

Myeloid differentiation primary response protein 88 (MYD88) is a critical universal adapter that transduces signaling from Toll-like and interleukin receptors to downstream nuclear factor-κB (NF-κB). MYD88L265P (leucine changed to proline at position 265) is a gain-of-function mutation that occurs frequently in B-cell malignancies such as Waldenstrom macroglobulinemia. In this study, E3 ligase RING finger protein family 138 (RNF138) catalyzed K63-linked nonproteolytic polyubiquitination of MYD88L265P, resulting in enhanced recruitment of interleukin-1 receptor-associated kinases and elevated NF-κB activation. However, RNF138 had little effect on wild-type MYD88 (MYD88WT). With either RNF138 knockdown or mutation on MYD88 ubiquitination sites, MYD88L265P did not constitutively activate …