Digital Commons Network^™

Characterization Of Additive Gene-Environment Interactions For Colorectal Cancer Risk, Claire E Thomas, Yi Lin, Michelle Kim, Eric S Kawaguchi, Conghui Qu, Caroline Y Um, Brigid M Lynch, Bethany Van Guelpen, Kostas Tsilidis, Robert Carreras-Torres, Franzel J B Van Duijnhoven, Lori C Sakoda, Peter T Campbell, Yu Tian, Jenny Chang-Claude, Stéphane Bézieau, Arif Budiarto, Julie R Palmer, Polly A Newcomb, Graham Casey, Loic Le Marchandz, Marios Giannakis, Christopher I Li, Andrea Gsur, Christina Newton, Mireia Obón-Santacana, Victor Moreno, Pavel Vodicka, Hermann Brenner, Michael Hoffmeister, Andrew J Pellatt, Robert E Schoen, Niki Dimou, Neil Murphy, Marc J Gunter, Sergi Castellví-Bel, Jane C Figueiredo, Andrew T Chan, Mingyang Song, Li Li, D Timothy Bishop, Stephen B Gruber, James W Baurley, Stephanie A Bien, David V Conti, Jeroen R Huyghe, Anshul Kundaje, Yu-Ru Su, Jun Wang, Temitope O Keku, Michael O Woods, Sonja I Berndt, Stephen J Chanock, Catherine M Tangen, Alicja Wolk, Andrea Burnett-Hartman, Anna H Wu, Emily White, Matthew A Devall, Virginia Díez-Obrero, David A Drew, Edward Giovannucci, Akihisa Hidaka, Andre E Kim, Juan Pablo Lewinger, John Morrison, Jennifer Ose, Nikos Papadimitriou, Bens Pardamean, Anita R Peoples, Edward A Ruiz-Narvaez, Anna Shcherbina, Mariana C Stern, Xuechen Chen, Duncan C Thomas, Elizabeth A Platz, W James Gauderman, Ulrike Peters, Li Hsu

Faculty, Staff and Student Publications

Background: Colorectal cancer (CRC) is a common, fatal cancer. Identifying subgroups who may benefit more from intervention is of critical public health importance. Previous studies have assessed multiplicative interaction between genetic risk scores and environmental factors, but few have assessed additive interaction, the relevant public health measure.

Methods: Using resources from CRC consortia, including 45,247 CRC cases and 52,671 controls, we assessed multiplicative and additive interaction (relative excess risk due to interaction, RERI) using logistic regression between 13 harmonized environmental factors and genetic risk score, including 141 variants associated with CRC risk.

Results: There was no evidence of multiplicative interaction …

Exploring The Role Of Reward Functioning In The Overlap Of Post-Traumatic Stress And Cocaine Use Disorder, Kate Hull, Hanaan Bing-Canar, Krista Miloslavich, Christopher Holden, Aneet Ahluwalia, Scott D Lane, Joy M Schmitz, Margaret C Wardle

Faculty, Staff and Student Publications

Background: Posttraumatic stress disorder (PTSD) symptoms are common in people with cocaine use disorder (CUD), and even sub-threshold PSTD symptoms result in worse treatment outcomes. Difficulties with reward functioning may drive this comorbidity. Impairments in reward functioning are prominent in both PTSD and CUD and contribute to development of substance use problems after trauma. There are three distinct reward processes that may be involved in the PTSD/CUD overlap: consummatory reward (ability to experience pleasure), motivational reward (willingness to exert effort for rewards), and reward learning (adapting behavior based on reward history). Here we test whether impairments in these reward functions …

Exposure Therapy Consortium: Outcomes Of The Proof-Of-Principle Study, Jasper A J Smits, Jonathan S Abramowitz, Rebecca A Anderson, Joanna J Arch, Daniel Badeja, Snir Barzilay, Amanda N Belanger, Thomas Borchert, Emma Bryant, Alane S Burger, Laura J Dixon, Christina D Dutcher, Hayley E Fitzgerald, Bronwyn M Graham, Anke Haberkamp, Stefan G Hofmann, Jürgen Hoyer, Jonathan D Huppert, David Johnson, Baraa Q Kabha, Alex Kirk, Jürgen Margraf, Peter M Mcevoy, Bryan Mcspadden, Jill Newby, Michael W Otto, Santiago Papini, E Marie Parsons, Andre Pittig, Roxana Pittig, Winfried Rief, Svenja Schaumburg, Kiara R Timpano, Lena Waltemate, Andre Wannemüller, Cornelia Weise, Exposure Therapy Consortium

Faculty, Staff and Student Publications

Background: This paper reports on the outcomes of a proof-of-principle study for the Exposure Therapy Consortium, a global network of researchers and clinicians who work to improve the effectiveness and uptake of exposure therapy. The study aimed to test the feasibility of the consortium's big-team science approach and test the hypothesis that adding post-exposure processing focused on enhancing threat reappraisal would enhance the efficacy of a one-session large-group interoceptive exposure therapy protocol for reducing anxiety sensitivity.

Methods: The study involved a multi-site cluster-randomized controlled trial comparing exposure with post-processing (ENHANCED), exposure without post-processing (STANDARD), and a stress management intervention (CONTROL) …

Long-Term Follow-Up Of A Phase 2 Study Of All-Trans Retinoic Acid, Arsenic Trioxide, And Gemtuzumab Ozogamicin In Acute Promyelocytic Leukemia, Wei-Ying Jen, Jennifer Marvin-Peek, Hagop M Kantarjian, Yesid Alvarado, Gautam Borthakur, Elias Jabbour, William Wierda, Tapan M Kadia, Naval G Daver, Courtney D Dinardo, Nicholas J Short, Nitin Jain, Alessandra Ferrajoli, Steven Kornblau, Musa Yilmaz, Maro Ohanian, David Mccue, Jan Burger, Danielle Hammond, Keyur Patel, Ghayas C Issa, Naveen Pemmaraju, Koji Sasaki, Abhishek Maiti, Hussein A Abbas, Kelly Chien, Koichi Takahashi, Fadi Haddad, Prithviraj Bose, Lucia Masarova, Guillermo Montalban-Bravo, Mahesh Swaminathan, Mark Brandt, Sherry Pierce, Guillermo Garcia-Manero, Farhad Ravandi

Faculty, Staff and Student Publications

Background: All-trans retinoic acid (ATRA) and arsenic trioxide (ATO) combinations have produced excellent outcomes in patients with standard-risk acute promyelocytic leukemia (APL). Herein, the authors update their long-term results with the regimen of ATO-ATRA and gemtuzumab ozogamicin (GO) in standard-risk and high-risk APL.

Methods: This was a phase 2 trial of patients with newly diagnosed APL. Induction comprised ATRA 45 mg/m2 and ATO 0.15 mg/kg daily. GO 6-9 mg/m2 was added for high-risk patients and for standard-risk patients who developed leukocytosis >10 × 109/L. Consolidation consisted of four courses of ATO-ATRA, with GO for patients who had PML::RARA persistence.

Results: …

Prevalence Of Carotid Ultrasound Screening In Survivors Of Childhood Cancer: A Report From The Childhood Cancer Survivor Study, Yolanda Bryce, Jillian A Whitton, Kayla L Stratton, Wendy M Leisenring, Eric J Chow, Gregory Armstrong, Brent Weil, Bryan Dieffenbach, Rebecca M Howell, Kevin C Oeffinger, Paul C Nathan, Emily S Tonorezos

Faculty, Staff and Student Publications

Introduction: Many childhood cancer survivors are at risk for cardiovascular disease and stroke. The North American Children's Oncology Group long-term follow-up guidelines recommend carotid ultrasound in cancer survivors 10 years after neck radiation therapy (RT) ≥40 Gy. The use of carotid ultrasound in this population has not been described.

Methods: Survivors of childhood cancer diagnosed 1970-1999 (N = 8693) and siblings (N = 1989) enrolled in the Childhood Cancer Survivor Study were asked if they had ever had a carotid ultrasound. Prevalence of carotid ultrasound was evaluated. Prevalence ratios (PR) and 95% confidence intervals (CIs) were evaluated in multivariate Poisson …

Novel Use And Value Of Contrast-Enhanced Susceptibility-Weighted Imaging Morphologic And Radiomic Features In Predicting Extremity Soft Tissue Undifferentiated Pleomorphic Sarcoma Treatment Response, Raul F Valenzuela, Elvis De Jesus Duran Sierra, Mathew A Canjirathinkal, Behrang Amini, Ken-Pin Hwang, Jingfei Ma, Keila E Torres, R Jason Stafford, Wei-Lien Wang, Robert S Benjamin, Andrew J Bishop, John E Madewell, William A Murphy, Colleen M Costelloe

Faculty, Staff and Student Publications

Purpose: Undifferentiated pleomorphic sarcomas (UPSs) demonstrate therapy-induced hemosiderin deposition, granulation tissue formation, fibrosis, and calcification. We aimed to determine the treatment-assessment value of morphologic tumoral hemorrhage patterns and first- and high-order radiomic features extracted from contrast-enhanced susceptibility-weighted imaging (CE-SWI).

Materials and methods: This retrospective institutional review board-authorized study included 33 patients with extremity UPS with magnetic resonance imaging and resection performed from February 2021 to May 2023. Volumetric tumor segmentation was obtained at baseline, postsystemic chemotherapy (PC), and postradiation therapy (PRT). The pathology-assessed treatment effect (PATE) in surgical specimens separated patients into responders (R; ≥90%, n = 16), partial responders …

Knowledge-Based Planning For Fully Automated Radiation Therapy Treatment Planning Of 10 Different Cancer Sites, Christine V Chung, Meena S Khan, Adenike Olanrewaju, Mary Pham, Quyen T Nguyen, Tina Patel, Prajnan Das, Michael S O'Reilly, Valerie K Reed, Anuja Jhingran, Hannah Simonds, Ethan B Ludmir, Karen E Hoffman, Komeela Naidoo, Jeannette Parkes, Ajay Aggarwal, Lauren L Mayo, Shalin J Shah, Chad Tang, Beth M Beadle, Julie Wetter, Gary Walker, Simon Hughes, Vinod Mullassery, Stephen Skett, Christopher Thomas, Lifei Zhang, Son Nguyen, Raymond P Mumme, Raphael J Douglas, Hana Baroudi, Laurence E Court

Faculty, Staff and Student Publications

Purpose: Radiation treatment planning is highly complex and can have significant inter- and intra-planner inconsistency, as well as variability in planning time and plan quality. Knowledge-based planning (KBP) is a tool that can be used to efficiently produce high-quality, consistent, clinically acceptable plans, independent of planner skills and experience. In this study, we created and validated multiple clinically acceptable and fully automatable KBP models, with the goal of creating VMAT plans without user intervention.

Methods: Ten KBP models were configured using high quality clinical plans from a single institution. They were then honed to be part of a fully automatable …

Characterizing Spatial Immune Architecture In Metastatic Melanoma Using High-Dimensional Multiplex Imaging, Joel Eliason, Santhoshi Krishnan, Yasunari Fukuda, Matias A Bustos, Dan Winkowski, Sungnam Cho, Akshay Basi, Regan Baird, Elizabeth A Grimm, Michael A Davies, Dave S B Hoon, Arvind Rao, Jared K Burks, Suhendan Ekmekcioglu

Faculty, Staff and Student Publications

Introduction: Immune checkpoint inhibitors (ICIs) have significantly improved survival for patients with metastatic melanoma, yet many experienceresistance due to immunosuppressive mechanisms within the tumor immune microenvironment (TIME). Understanding how the spatial architecture of immune and inflammatory components changes across disease stages may reveal novel prognostic biomarkers and therapeutic targets.

Methods: We performed high-dimensional spatial profiling of two melanoma tissue microarrays (TMAs), representing Stage III (n = 157) and Stage IV (n = 248) metastatic tumors. Using imaging mass cytometry (IMC) and multiplex immunofluorescence (mIF), we characterized the phenotypic, functional, and spatial properties of the TIME. Cellular neighborhoods were …

Epidemiology Of Patient Record Duplication, Onur Sahin, Audrey Zhao, Reuben Joseph Applegate, Todd R Johnson, Elmer V Bernstam

Faculty, Staff and Student Publications

Objectives: Duplicate patient records can increase costs and medical errors. We assessed the association between demographic factors, comorbidities, health care usage, and duplicate electronic health records.

Methods: We analyzed the association between duplicate patient records and multiple demographic variables (race, Hispanic ethnicity, sex, and age) as well as the Charlson Comorbidity Index (CCI), number of diagnoses, and number of health care encounters. The study population included 3,018,413 patients seen at a large urban academic medical center with at least one recorded diagnosis. Duplication of patient medical records was determined by using a previously validated enterprise Master Person Index.

Results: Unknown …

18 Kda Translocator Protein (Tspo) Is Upregulated In Rat Brain After Peripheral Nerve Injury And Downregulated By Diroximel Fumarate, Rafael A Cazuza, Sever M Zagrai, Anamaria R Grieco, Thomas D Avery, Andrew D Abell, Hsiao-Ying Wey, Marco L Loggia, Peter M Grace

Faculty, Staff and Student Publications

Neuroimmune signaling is a key process underlying neuropathic pain. Clinical studies have demonstrated that 18 kDa translocator protein (TSPO), a putative marker of neuroinflammation, is upregulated in discrete brain regions of patients with chronic pain. However, no preclinical studies have investigated TSPO dynamics in the brain in the context of neuropathic pain and in response to analgesic treatments. We used positron emission tomography-computed tomography (PET-CT) and [18F]-PBR06 radioligand to measure TSPO levels in the brain across time after chronic constriction injury (CCI) of the sciatic nerve in both male and female rats. Up to 10 weeks post-CCI, TSPO expression was …

High-Grade B-Cell Lymphoma Not Otherwise Specified, With Diffuse Large B-Cell Lymphoma Gene Expression Signatures: Genomic Analysis And Potential Therapeutics, Waseem Lone, Alyssa Bouska, Tyler A Herek, Catalina Amador, Joo Song, Alexander M Xu, Dylan Jochum, Issa Ismail Issa, Dennis D Weisenburger, Xuan Zhang, Sharath Kumar Bhagavathi, Tayla B Heavican-Foral, Sunandini Sharma, Ab Rauf Shah, Abdul Rouf Mir, Aisha Ahmad Alkhinji, Dalia El-Gamal, Bhavana J Dave, Keenan Hartert, Jiayu Yu, Mallick Saumyaranjan, Timothy C Greiner, Julie Vose, Timothy W Mckeithan, Kai Fu, Michael Green, Chengfeng Bi, Akil Merchant, Wing C Chan, Javeed Iqbal

Faculty, Staff and Student Publications

High-grade B-cell lymphoma not otherwise specified (HGBCL, NOS) has overlapping morphological and genetic features with diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL), leading to uncertainty in its diagnosis and clinical management. Using functional genomic approaches, we previously characterized HGBCL and NOS, that demonstrate gene expression profiling (GEP), and genetic signatures similar to BL. Herein, we characterize distinct HGBCL, NOS, cohort (n = 55) in adults (n = 45) and in children (n = 10), and compared the GEP, genomic DNA copy number (CN), and mutational spectrum with de novo DLBCL (n = 85) and BL (n = 52). …

Plasma Dna Methylation-Based Biomarkers For Mpnst Detection In Patients With Neurofibromatosis Type 1, Katarzyna Tomczak, Manishkumar S Patel, Angela D Bhalla, Christine B Peterson, Sharon M Landers, S Carson Callahan, Di Zhang, Justin Wong, Jace P Landry, Alexander J Lazar, J Andrew Livingston, B Ashleigh Guadagnolo, Heather G Lyu, Heather Lillemoe, Christina L Roland, Emily Z Keung, Christopher P Scally, Kelly K Hunt, Ian E Mccutcheon, John M Slopis, Jian Gu, Paul Scheet, Liang Wang, Kunal Rai, Keila E Torres

Faculty, Staff and Student Publications

Malignant peripheral nerve sheath tumor (MPNST) development is characterized by an altered DNA methylation landscape, which presents a promising area for developing MPNST-specific biomarkers for screening patients with NF1. Genome-wide DNA methylation profiling of a cohort of 13 patients with MPNST (29 samples of tumor and adjacent neurofibroma tissues) and of NF1-MPNST cell lines was performed to identify and validate candidate MPNST-specific CpG sites (CpGs). A logistic regression prediction model was constructed to select MPNST-specific CpGs distinct from adjacent neurofibromas and normal tissues. To test if hypermethylation at selected CpGs can also be detected in plasma from patients with MPNST, …

What Time Is It? It Is 8 And 1/2 Time: A Rare Case Of Ischemic Stroke Consistent With Eight-And-A-Half Syndrome, Jessica Daza, Marcelo Bedoya-Sommerkamp, Eunbee Cho, Celia Daza, Francisco Gomez, Fatimah Bello, Jia Lin

Faculty, Staff and Student Publications

Eight-and-a-half syndrome is a rare neuro-ophthalmic syndrome characterized by conjugate horizontal gaze palsy, ipsilateral internuclear ophthalmoplegia, and ipsilateral facial nerve palsy. It results from a lesion affecting the paramedian pontine reticular formation, the medial longitudinal fasciculus, and the abducens nucleus of the same side, at the level of the lower pons. We present a case of a 49-year-old man with 2-week diplopia and 3-day right-sided facial droop, drooling, and dysarthria. CT angiography of the head and neck revealed atherosclerotic disease, with decreased caliber of the basilar artery at the level of the pons. Brain MRI showed a subacute ischemic lesion …

Trends In Contacts Made By Immigrants To The National Domestic Violence Hotline, Before And During The Covid-19 Pandemic, Sarah Treves-Kagan, Vi D Le, Liris S Berra, Colleen M Ray, Yanet Ruvalcaba, Leila Wood, Denise V D'Angelo, Tatiana M Vera, Lianne Fuino Estefan

Faculty, Staff and Student Publications

Objectives: Immigrants in the United States are more likely than nonimmigrants to experience risk factors for intimate partner violence (IPV) and problems in getting support. The COVID-19 pandemic and recent incidents of xenophobia and anti-immigrant sentiment may have exacerbated exposure to IPV risk factors. We examined immigrant experiences of IPV before and during the COVID-19 pandemic.

Methods: This study identified changes in characteristics of abuse, services used, referrals, and barriers to services among those who contacted the National Domestic Violence Hotline (NDVH) and identified as immigrants, reported immigration status as a concern, needed immigration support, and/or identified immigration status as …

Semi-Automated Virtual Endoscopy Of The Frontal Recess, Ali Jafar, William Yao, Martin Citardi

Faculty, Staff and Student Publications

Introduction: Virtual endoscopy (VE) is the computer-based reprocessing of diagnostic imaging to simulate endoscopy of an anatomic region of interest. VE of the Frontal Sinus Outflow Tract (FSOT) may assist surgical planning and education.

Method: VE was performed on 16 normal sinus computed tomography (CT) scans for a total of 32 sides using the "path-to-target" tool on the TruDi surgical navigation system (ver. 2.3; Acclarent, Irving, CA, USA). To aid orientation during VE, planning points were placed on the middle turbinate, ethmoidal bulla, and skull base. The VE representation of anatomy and FSOT accuracy was manually confirmed by reviewing the …

Administration Of Anti-Gfap Antibodies Increases Cgrp Expression And Increases Pain Hypersensitivity In Spinal Cord Injured Animals, Georgene W Hergenroeder, Samuel T Molina, Juan J Herrera

Faculty, Staff and Student Publications

Background: Spinal cord injury (SCI) results in a multitude of cellular and pathological changes including neuronal loss, axonal damage, gliosis, and loss of motor and sensory function. In 40%-70% of patients, SCI can also trigger the development of neuropathic pain. Our previous study demonstrated that SCI patients who developed autoantibodies to glial fibrillary acidic protein (GFAP) were at increased risk for the subsequent development of neuropathic pain. However, whether GFAP autoantibodies (GFAPab) contribute to the development of neuropathic pain after SCI had yet to be examined.

Objective: Using a mid-thoracic contusion model of SCI in male Sprague-Dawley rats, we examined …

How Different Is Invasive Coronary Physiology In The Left Anterior Descending Artery?, Nils P Johnson, K Lance Gould

Faculty, Staff and Student Publications

Given the large amount of myocardium supplied by the left anterior descending (LAD) artery, it understandably receives additional scrutiny during coronary angiography. However, these same features make the interpretation of pressure wire physiology more nuanced to avoid overtreatment. This review provides case examples to underpin an extensive literature review supporting the argument that a "positive" fractional flow reserve (FFR) in the LAD needs to be approached with caution. A large hyperemic gradient, or low FFR, can arise from either a severe and focal lesion in conjunction with low flow or diffuse disease coupled with intact or normal flow. Separating these …

Vagally Mediated Heart Rate Variability Modulates The Association Between The Perceived Workload And The Stroop Effect On Behavioral Performance, Xiao Yang, Michael Gazzanigo, Fang Fang, Spencer House

Psychology Faculty Publications

Vagally mediated heart rate variability (vmHRV) reflects top-down cognitive processes involved in emotion-cognition integration. Using cognitive control can be effortful and increase negative affect. However, this intrinsic affective component of cognitive control has not been well studied, and the role of vmHRV in the association between subjective experience in using cognitive control and behavioral performance remains unknown. The current study aimed to examine the relationship of vmHRV with cognitive control and perceived workload in a cognitive task. Eighty-one participants performed the Stroop interference task. Participants rated subjective workload using the NASA Task Load Index (NASA-TLX) scale for congruent and incongruent …

Three-Dimensional Deep Learning Normal Tissue Complication Probability Model To Predict Late Xerostomia In Patients With Head And Neck Cancer, Hung Chu, Suzanne P M De Vette, Hendrike Neh, Nanna M Sijtsema, Roel J H M Steenbakkers, Amy Moreno, Johannes A Langendijk, Peter M A Van Ooijen, Clifton D Fuller, Lisanne V Van Dijk

Faculty, Staff and Student Publications

Purpose: Conventional normal tissue complication probability (NTCP) models for patients with head and neck cancer are typically based on single-value variables, which, for radiation-induced xerostomia, are baseline xerostomia and mean salivary gland doses. This study aimed to improve the prediction of late xerostomia by using 3-dimensional information from radiation dose distributions, computed tomography imaging, organ-at-risk segmentations, and clinical variables with deep learning (DL).

Methods and materials: An international cohort of 1208 patients with head and neck cancer from 2 institutes was used to train and twice validate DL models (deep convolutional neural network, EfficientNet-v2, and ResNet) with 3-dimensional dose distribution, …

A Serum Biomarker Panel And Miniarray Detection System For Tracking Disease Activity And Flare Risk In Lupus Nephritis, Chenling Tang, Gongjun Tan, Aygun Teymur, Jiechang Guo, Arturo Haces-Garcia, Weihang Zhu, Richard Williams, Jing Ning, Ramesh Saxena, Tianfu Wu

Faculty, Staff and Student Publications

Introduction: Lupus nephritis (LN) leads to end stage renal disease (ESRD), and early diagnosis and disease monitoring of LN could significantly reduce the risk. however, there is not such a system clinically. In this study we aim to develop a biomarker-panel based point-of-care system for LN.

Methods: Immunoassay screening combined with genomic expression databases and machine learning techniques was used to identify a biomarker panel of LN. A quantitative biomarker-panel mini-array (BPMA) system was developed and the sensitivity, specificity, reproducibility, and stability of the were examined. The performance of BPMA in disease monitoring was validated with machine models using a …

Integrating Multi-Omics Data To Uncover Prostate Tissue Dna Methylation Biomarkers And Target Genes For Prostate Cancer Risk, Shuai Liu, Jingjing Zhu, Dylan Green, Hua Zhong, Quan Long, Chong Wu, Liang Wang, Youping Deng, Lang Wu

Faculty, Staff and Student Publications

Previous studies have indicated that specific CpG sites may be linked to the risk of prostate cancer (PCa) by regulating the expression of PCa target genes. However, most existing studies aim to identify DNA methylation (DNAm) biomarkers through blood tissue genetic instruments, which impedes the identification of relevant biomarkers in prostate tissue. To identify PCa risk-associated CpG sites in prostate tissue, we established genetic prediction models of DNAm levels using data from normal prostate samples in the GTEx (N = 108) and assessed associations between genetically predicted DNAm in prostate and PCa risk by studying 122,188 cases and 604,640 controls. …

Sex And Apoe Ε4 Allele Differences In Longitudinal White Matter Microstructure In Multiple Cohorts Of Aging And Alzheimer's Disease, Amalia Peterson, Aditi Sathe, Dimitrios Zaras, Yisu Yang, Alaina Durant, Kacie D Deters, Niranjana Shashikumar, Kimberly R Pechman, Michael E Kim, Chenyu Gao, Nazirah Mohd Khairi, Zhiyuan Li, Tianyuan Yao, Yuankai Huo, Logan Dumitrescu, Katherine A Gifford, Jo Ellen Wilson, Francis E Cambronero, Shannon L Risacher, Lori L Beason-Held, Yang An, Konstantinos Arfanakis, Guray Erus, Christos Davatzikos, Duygu Tosun, Arthur W Toga, Paul M Thompson, Elizabeth C Mormino, Mohamad Habes, Di Wang, Panpan Zhang, Kurt Schilling, Marilyn Albert, Walter Kukull, Sarah A Biber, Bennett A Landman, Sterling C Johnson, Julie Schneider, Lisa L Barnes, David A Bennett, Angela L Jefferson, Susan M Resnick, Andrew J Saykin, Timothy J Hohman, Derek B Archer

Faculty, Staff and Student Publications

Introduction: The effects of sex and apolipoprotein E (APOE)-Alzheimer's disease (AD) risk factors-on white matter microstructure are not well characterized.

Methods: Diffusion magnetic resonance imaging data from nine well-established longitudinal cohorts of aging were free water (FW)-corrected and harmonized. This dataset included 4741 participants (age = 73.06 ± 9.75) with 9671 imaging sessions over time. FW and FW-corrected fractional anisotropy (FAFWcorr) were used to assess differences in white matter microstructure by sex and APOE ε4 carrier status.

Results: Sex differences in FAFWcorr in projection tracts and APOE ε4 differences in FW limbic and occipital transcallosal tracts were most pronounced.

Discussion: …

Examining Low-Income Caregivers' Knowledge And Comprehension Of The Dental Caries Process, Melissa Sullivan, Denise C. Mckinney, Deanne Shuman, Qi Zhang

Dental Hygiene Faculty Publications

Purpose Dental caries among young children remains a public health concern in the United States (US). Children of caregivers with low oral health literacy (OHL) tend to have greater unmet dental needs and poorer oral health status. The purpose of this study was to examine the understanding of pediatric dental terms associated with the dental caries process among low-income caregivers.

Methods This study included 14 caregivers with children enrolled in a Special Supplemental Nutrition Program for Women, Infants and Children (WIC) in the Southeastern US. Through structured phone interviews, the validated Oral Health Literacy Inventory for Parents (OH-LIP) was used …

Multiplex Lateral Flow Test Sensitivity And Specificity In Detecting Influenza A, B And Sars-Cov-2 In Adult Patients In A Uk Emergency Department, Rahul Batra, Edward Blandford, Raghavendran Kulasegaran-Shylini, Matthias E Futschik, Abbie Bown, Matthew Catton, Hermione Conti-Frith, Alexandra Alexandridou, Rebecca Gill, Clara Milroy, Sean Harper, Holly Gettings, Maryann Noronha, Hooi-Ling Harrison, Sam Douthwaite, Gaia Nebbia, Paul E Klapper, Sarah Tunkel, Richard Vipond, Susan Hopkins, Tom Fowler

School of Biomedical Sciences

BACKGROUND: Rapid identification of individuals with acute respiratory infections is crucial for preventing nosocomial infections. For rapid diagnosis, especially in EDs, lateral flow devices (LFDs) are a convenient, inexpensive option with a rapid turnaround. Several 'multiplex' LFDs (M-LFDs) now exist, testing for multiple pathogens from a single swab sample. We evaluated the real-world performance of M-LFD versus PCR testing in detecting influenza A, B and SARS-CoV-2) in the ED setting.

METHODS: After preliminary evaluation of an M-LFD (SureScreen) with laboratory-grown virus and PCR-negative clinical samples, it was evaluated in a real-world setting at the ED of St Thomas' Hospital (London, …

Longitudinal Host Transcriptional Responses To Sars-Cov-2 Infection In Adults With Extremely High Viral Load, Vasanthi Avadhanula, Chad J Creighton, Laura Ferlic-Stark, Divya Nagaraj, Yiqun Zhang, Richard Sucgang, Erin G Nicholson, Anubama Rajan, Vipin Kumar Menon, Harshavardhan Doddapaneni, Donna Marie Muzny, Ginger A Metcalf, Sara Joan Javornik Cregeen, Kristi Louise Hoffman, Richard A Gibbs, Joseph F Petrosino, Pedro A Piedra

Faculty, Staff and Students Publications

Current understanding of viral dynamics of SARS-CoV-2 and host responses driving the pathogenic mechanisms in COVID-19 is rapidly evolving. Here, we conducted a longitudinal study to investigate gene expression patterns during acute SARS-CoV-2 illness. Cases included SARS-CoV-2 infected individuals with extremely high viral loads early in their illness, individuals having low SARS-CoV-2 viral loads early in their infection, and individuals testing negative for SARS-CoV-2. We could identify widespread transcriptional host responses to SARS-CoV-2 infection that were initially most strongly manifested in patients with extremely high initial viral loads, then attenuating within the patient over time as viral loads decreased. Genes …

Goldenbraid20 E Coli: A Comprehensive And Characterized Toolkit For Enterics, Matthew B Cooke, Kobie T Welch, Laura D Ramirez, Alice X Wen, David C Marciano, Christophe Herman

Faculty, Staff and Students Publications

Modular cloning systems streamline laboratory workflows by consolidating genetic 'parts' into reusable and modular collections, enabling researchers to fast-track strain construction. The GoldenBraid 2.0 modular cloning system utilizes the cutting property of type IIS restriction enzymes to create defined genetic 'grammars', which facilitate the reuse of standardized genetic parts and assembly of genetic parts in the right order. Here, we present a GoldenBraid 2.0 toolkit of genetic parts designed to accelerate cloning in the model bacterium

Association Between Parathyroid Hormone Concentration And Incident Atrial Fibrillation In Older Persons With Kidney Failure Initiating Dialysis, Pascale Khairallah, Sai Liu, Maria E Montez-Rath, Kevin F Erickson, Tara I Chang, Wolfgang C Winkelmayer

Faculty, Staff and Students Publications

Introduction: Atrial fibrillation (AF) is common in persons with kidney failure on hemodialysis. In the general population, higher intact parathyroid hormone (iPTH) levels were found to be associated with presence of AF. Whether iPTH associates with AF in patients on hemodialysis is unknown.

Methods: Using merged USRDS-DaVita data (2006-2011), we selected persons aged 67+ years who initiated hemodialysis and survived 120 days. Eligible persons had continuous Medicare A + B coverage from 2 years prior to kidney failure and no diagnosis of AF. Sociodemographic, comorbidity, and clinical information were abstracted from Medicare forms, billing claims, and electronic health records. iPTH …

Mutations In Retinal Cyclic Nucleotide-Gated Channels Identified In Familial Cases Of Inherited Retinal Dystrophies From Pakistan, Zainab Akhtar, Kiran Afshan, Yumei Li, Sumaira Altaf, Aleesha Asghar, Ume Sughra, Wajid Ali Khan, Haiba Kaul, Rui Chen, Sabika Firasat

Faculty, Staff and Students Publications

Purpose: Cyclic nucleotide-gated (CNG) channels are ligand-gated ion channels that transduce light signals into electrical signals in the retinal photoreceptors. Pathogenic variants in CNG channel genes are reported to cause inherited retinal dystrophies (IRDs). The current study used targeted panel sequencing to describe the mutational spectrum of CNG channel genes in familial cases of IRDs from eight consanguineous Pakistani families.

Methods: The current study included consanguineous Pakistani families with at least two affected members. DNA was extracted from whole blood samples by the phenol-chloroform method. Two affected members from each family were initially analyzed using targeted panel sequencing of 344 …

Recombinant Human Alpha-N-Acetylglucosamine-6-Sulfatase Delivered To Sanfilippo D Mice With Repeated Intracerebroventricular Injections Corrects Cns Pathology, Grant L. Austin, Feng Wang, Steven Q. Le, Alexander Sorensen, Shan Li, Lai C. Foong, Srikanth Singamsetty, Jill Wood, Tsui-Fen Chou, Patricia I. Dickson

2020-Current year OA Pubs

Mucopolysaccharidosis type IIID (MPS IIID; Sanfilippo D) is caused by biallelic pathogenic variants in N-acetylglucosamine-6-sulfatase (GNS), which participates in catabolism of heparan sulfate (HS) glycosaminoglycans. Characterization of MPS IIID disease at a cellular level has not been robustly achieved. We used unbiased quantitative proteomics to establish a cellular phenotype for MPS IIID mice. Recombinant human GNS (rhGNS), a variant of which previously demonstrated single dose efficacy in MPS IIID human fibroblasts and in MPS IIID neonatal mice, was used to establish a repeat dosing schedule to treat MPS IIID mice. Adult Gns KO mice or heterozygous carriers were treated via …

Hypertriglyceridemia In New-Onset Type 1 Pediatric Diabetes, Colleen A Macke, Iman Al-Gadi, Nidhi Bansal, Sarah K Lyons, Aikaterini A Nella

Faculty, Staff and Students Publications

Hypertriglyceridemia (HTG) in the setting of newly diagnosed diabetes is common in both adult and pediatric populations, as insulin deficiency promotes lipolysis and impairs triglyceride (TG) clearance. Severe HTG (defined as TG levels above 1000 mg/dL) in pediatric patients with new-onset type 1 diabetes mellitus (T1D) is rare; the true incidence and sequela of this phenomenon have not been well characterized. We present a single-center experience on severe HTG in pediatric patients with new-onset T1D between 2013 and 2022 and summarize the cases previously reported in the literature. Our cases display variability in their presentation and in their association with …