Medicine and Health Sciences Commons^™

Naturalistic Assessment Of Reaction Time Variability In Older Adults At Risk For Alzheimer's Disease, Matthew S Welhaf, Hannah Wilks, Andrew J Aschenbrenner, David A Balota, Suzanne E Schindler, Tammie L S Benzinger, Brian A Gordon, Carlos Cruchaga, Chengjie Xiong, John C Morris, Jason Hassenstab

2020-Current year OA Pubs

OBJECTIVE: Maintaining attention underlies many aspects of cognition and becomes compromised early in neurodegenerative diseases like Alzheimer's disease (AD). The consistency of maintaining attention can be measured with reaction time (RT) variability. Previous work has focused on measuring such fluctuations during in-clinic testing, but recent developments in remote, smartphone-based cognitive assessments can allow one to test if these fluctuations in attention are evident in naturalistic settings and if they are sensitive to traditional clinical and cognitive markers of AD.

METHOD: Three hundred and seventy older adults (aged 75.8 +/- 5.8 years) completed a week of remote daily testing on the …

Migraine Headache In Patients With Spontaneous Coronary Artery Dissection: A Report Of The Iscad Registry, Bryan J Wells, Kathryn Lindley, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Spontaneous coronary artery dissection (SCAD) is a nonatherosclerotic cause of myocardial infarction. Migraine headache has been reported to be common among patients with SCAD, but the degree of migraine-related disability has not been quantified.

METHODS: Clinical data and headache variables were obtained from the baseline assessment of the prospective, multicenter iSCAD Registry. Migraine-related disability was quantified using the self-reported Migraine Disability Assessment (MIDAS). Demographic, clinical, psychosocial, and medical characteristics from data entry forms were compared between patients with and without migraine.

RESULTS: Of the 773 patients with available data, 46% reported previous or current migraines. Those with migraines were …

Inherited C-Terminal Trex1 Variants Disrupt Homology-Directed Repair To Cause Senescence And Dna Damage Phenotypes In Drosophila, Mice, And Humans, Samuel D Chauvin, Fang R Zhao, W Alexander Stinson, Wei Qian, Prabhakar S Andhey, Maxim N Artyomov, Elisha D O Roberson, Jonathan J Miner, Et Al.

2020-Current year OA Pubs

Age-related microangiopathy, also known as small vessel disease (SVD), causes damage to the brain, retina, liver, and kidney. Based on the DNA damage theory of aging, we reasoned that genomic instability may underlie an SVD caused by dominant C-terminal variants in TREX1, the most abundant 3'-5' DNA exonuclease in mammals. C-terminal TREX1 variants cause an adult-onset SVD known as retinal vasculopathy with cerebral leukoencephalopathy (RVCL or RVCL-S). In RVCL, an aberrant, C-terminally truncated TREX1 mislocalizes to the nucleus due to deletion of its ER-anchoring domain. Since RVCL pathology mimics that of radiation injury, we reasoned that nuclear TREX1 would cause …

Safety Of Non-Cuffed Tunneled Central Venous Catheters In Adults With Cystic Fibrosis, Arshan Dehbozorgi, Badr Jandali, Robert Turner, Aaron Rohr, Brandon Custer, Kate Young, Carissa Walter, Lauren Clark, Yanming Li, Deepika Polineni, Joel Mermis

2020-Current year OA Pubs

BACKGROUND: Peripherally inserted central catheters (PICCs) are the most common route of intravenous (I.V.) access for treatment of cystic fibrosis (CF) pulmonary exacerbations, but repeated PICC placement can result in upper extremity peripheral venous stenosis. Once peripheral stenosis develops, a non-cuffed tunneled central venous catheter (NcTCVC) is an alternative route for IV access. While these are regularly used at some CF centers, the safety and complication rate compared to PICCs in adults with CF has not been reported. This study aims to describe the safety of NcTCVCs in adults with CF.

METHODS: A retrospective cohort study was performed at a …

Efficacy And Safety Of A Four-Drug, Quarter-Dose Treatment For Hypertension: The Quartet Usa Randomized Trial, Mark D Huffman, Et Al.

2020-Current year OA Pubs

New approaches are needed to lower blood pressure (BP) given persistently low control rates. QUARTET USA sought to evaluate the effect of four-drug, quarter-dose BP lowering combination in patients with hypertension. QUARTET USA was a randomized (1:1), double-blinded trial conducted in federally qualified health centers among adults with hypertension. Participants received either a quadpill of candesartan 2 mg, amlodipine 1.25 mg, indapamide 0.625 mg, and bisoprolol 2.5 mg or candesartan 8 mg for 12 weeks. If BP was >130/>80 mm Hg at 6 weeks in either arm, then participants received open label add-on amlodipine 5 mg. The primary outcome …

Influence Of Eat, Sleep, And Console On Infants Pharmacologically Treated For Opioid Withdrawal: A Post Hoc Subgroup Analysis Of The Esc-Now Randomized Clinical Trial., Lori A. Devlin, Zhuopei Hu, Stephanie L. Merhar, Songthip T. Ounpraseuth, Alan E. Simon, Jeannette Y. Lee, Abhik Das, Margaret M. Crawford, Rachel G. Greenberg, P Brian Smith, Rosemary D. Higgins, Michele C. Walsh, Ward Rice, David A. Paul, Jessie R. Maxwell, Camille M. Fung, Tanner Wright, Julie Ross, Jennifer M. Mcallister, Moira Crowley, Sophie K. Shaikh, Lori Christ, Jaime Brown, Julie Riccio, Kara Wong Ramsey, Erica F. Braswell, Lauren Tucker, Karen Mcalmon, Krishna Dummula, Julie Weiner, Jessica R. White, Sarah Newman, Jessica N. Snowden, Leslie W. Young, Eunice Kennedy Shriver Nichd Neonatal Research Network And Nih Environmental Influences On Child Health Outcomes (Echo) Program Institutional Development Award States Pediatric Clinical Trials Network

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: The function-based eat, sleep, console (ESC) care approach substantially reduces the proportion of infants who receive pharmacologic treatment for neonatal opioid withdrawal syndrome (NOWS). This reduction has led to concerns for increased postnatal opioid exposure in infants who receive pharmacologic treatment. However, the effect of the ESC care approach on hospital outcomes for infants pharmacologically treated for NOWS is currently unknown.

OBJECTIVE: To evaluate differences in opioid exposure and total length of hospital stay (LOS) for pharmacologically treated infants managed with the ESC care approach vs usual care with the Finnegan tool.

DESIGN, SETTING, AND PARTICIPANTS: This post hoc …

Molecular Classification And Biomarkers Of Outcome With Immunotherapy In Extensive-Stage Small-Cell Lung Cancer: Analyses Of The Caspian Phase 3 Study, Mingchao Xie, Miljenka Vuko, Jaime Rodriguez-Canales, Johannes Zimmermann, Markus Schick, Cathy O'Brien, Luis Paz-Ares, Jonathan W Goldman, Marina Chiara Garassino, Carl M Gay, John V Heymach, Haiyi Jiang, J Carl Barrett, Ross A Stewart, Zhongwu Lai, Lauren A Byers, Charles M Rudin, Yashaswi Shrestha

Student and Faculty Publications

BACKGROUND: We explored potential predictive biomarkers of immunotherapy response in patients with extensive-stage small-cell lung cancer (ES-SCLC) treated with durvalumab (D) + tremelimumab (T) + etoposide-platinum (EP), D + EP, or EP in the randomized phase 3 CASPIAN trial.

METHODS: 805 treatment-naïve patients with ES-SCLC were randomized (1:1:1) to receive D + T + EP, D + EP, or EP. The primary endpoint was overall survival (OS). Patients were required to provide an archived tumor tissue block (or ≥ 15 newly cut unstained slides) at screening, if these samples existed. After assessment for programmed cell death ligand-1 expression and tissue …

Propofol Enhancement Of Slow Wave Sleep To Target The Nexus Of Geriatric Depression And Cognitive Dysfunction: Protocol For A Phase I Open Label Trial, Rachel Lynn Rios, Michael Green, S Kendall Smith, Mohammadmehdi Kafashan, Shinung Ching, Nuri B Farber, Nan Lin, Brendan P Lucey, Charles F Reynolds, Eric J Lenze, Ben Julian Agustin Palanca, Swiped Study Team

2020-Current year OA Pubs

INTRODUCTION: Late-life treatment-resistant depression (LL-TRD) is common and increases risk for accelerated ageing and cognitive decline. Impaired sleep is common in LL-TRD and is a risk factor for cognitive decline. Slow wave sleep (SWS) has been implicated in key processes including synaptic plasticity and memory. A deficiency in SWS may be a core component of depression pathophysiology. The anaesthetic propofol can induce electroencephalographic (EEG) slow waves that resemble SWS. Propofol may enhance SWS and oral antidepressant therapy, but relationships are unclear. We hypothesise that propofol infusions will enhance SWS and improve depression in older adults with LL-TRD. This hypothesis has …

Early Outcomes Of Mr-Guided Sbrt For Patients With Recurrent Pancreatic Adenocarcinoma, Spencer Poiset, Sophia Shah, Louis Cappelli, Rani Anné, Karen Mooney, Maria Werner-Wasik, Talya Laufer, James Posey, Daniel Lin, Atrayee Mallick, Harish Lavu, Babar Bashir, Charles Yeo, Adam Mueller

Kimmel Cancer Center Faculty Papers

BACKGROUND: Local treatment options for locally recurrent pancreatic adenocarcinoma (LR-PAC) are limited, with median survival time (MST) of 9-13 months (mos) following recurrence. MRI-guided stereotactic body radiation therapy (MRgSBRT) provides the ability to dose escalate while sparing normal tissue. Here we report on the early outcomes of MRgSBRT for LR-PAC.

METHODS: Patients with prior resection of pancreatic adenocarcinoma with local recurrence treated with MRgSBRT at a single tertiary referral center from 5-2021 to 2-2023 were identified from our prospective database. MRgSBRT was delivered to 40-50 Gy in 4-5 fractions with target and OAR delineation per institutional standards. Endpoints included local …

Vascular Risk Profile And Changes Of Arterial Hypertension After Surgical Revascularization In Adult Moyamoya Patients, Patrick Haas, Lucas Moritz Wiggenhauser, Jonas Tellermann, Helene Hurth, Daniel Feucht, Marcos Tatagiba, Nadia Khan, Constantin Roder

Student and Faculty Publications

Moyamoya disease (MMD) is a rare stenoocclusive cerebral vasculopathy often treated by neurosurgical revascularization using extracranial-intracranial bypasses to prevent ischemic or hemorrhagic events. Little is known about the vascular risk profile of adult MMD patients compared to the general population. We therefore analyzed 133 adult MMD patients and compared them with data from more than 22,000 patients from the German Health Update database. Patients with MMD showed an age- and sex-adjusted increased prevalence of arterial hypertension, especially in women between 30 and 44 years and in patients of both sexes between 45 and 64 years. Diabetes mellitus was diagnosed significantly …

Loss Of Lpar6 And Cab39l Dysregulates The Basal-To-Luminal Urothelial Differentiation Program, Contributing To Bladder Carcinogenesis, Sangkyou Lee, Jolanta Bondaruk, Yishan Wang, Huiqin Chen, June Goo Lee, Tadeusz Majewski, Rachel D Mullen, David Cogdell, Jiansong Chen, Ziqiao Wang, Hui Yao, Pawel Kus, Joon Jeong, Ilkyun Lee, Woonyoung Choi, Neema Navai, Charles Guo, Colin Dinney, Keith Baggerly, Cathy Mendelsohn, David Mcconkey, Richard R Behringer, Marek Kimmel, Peng Wei, Bogdan Czerniak

Student and Faculty Publications

We describe a strategy that combines histologic and molecular mapping that permits interrogation of the chronology of changes associated with cancer development on a whole-organ scale. Using this approach, we present the sequence of alterations around RB1 in the development of bladder cancer. We show that RB1 is not involved in initial expansion of the preneoplastic clone. Instead, we found a set of contiguous genes that we term "forerunner" genes whose silencing is associated with the development of plaque-like field effects initiating carcinogenesis. Specifically, we identified five candidate forerunner genes (ITM2B, LPAR6, MLNR, CAB39L, and ARL11) mapping near RB1. Two …

A Multicenter Study Of Venetoclax-Based Treatment For Patients With Richter Transformation Of Chronic Lymphocytic Leukemia, Paul J Hampel, Mahesh Swaminathan, Kerry A Rogers, Erin M Parry, Jan A Burger, Matthew S Davids, Wei Ding, Alessandra Ferrajoli, Jonathan M Hyak, Nitin Jain, Saad S Kenderian, Yucai Wang, William G Wierda, Jennifer A Woyach, Sameer A Parikh, Philip A Thompson

Student and Faculty Publications

Patients with chronic lymphocytic leukemia (CLL) who develop Richter transformation (RT) have a poor prognosis when treated with chemoimmunotherapy regimens used for de novo diffuse large B-cell lymphoma. Venetoclax, a BCL2 inhibitor, has single-agent efficacy in patients with RT and is potentially synergistic with chemoimmunotherapy. In this multicenter, retrospective study, we evaluated 62 patients with RT who received venetoclax-based treatment outside of a clinical trial, in combination with a Bruton tyrosine kinase inhibitor (BTKi; n=28), rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) (n=13), or intensive chemoimmunotherapy other than R-CHOP (n=21). The best overall and complete response rates were 36%/25%, 54%/46%, and …

Nivolumab Plus Brentuximab Vedotin For Relapsed/Refractory Peripheral T-Cell Lymphoma And Cutaneous T-Cell Lymphoma, Pier Luigi Zinzani, Neha Mehta-Shah, Et Al.

2020-Current year OA Pubs

No abstract provided.

Human Neutralizing Antibodies Target A Conserved Lateral Patch On H7n9 Hemagglutinin Head, Manxue Jia, Hanjun Zhao, Nicholas C Morano, Hong Lu, Yin-Ming Lui, Haijuan Du, Jordan E Becker, Kwok-Yung Yuen, David D Ho, Peter D Kwong, Lawrence Shapiro, Kelvin Kai-Wang To, Xueling Wu

Faculty and Staff Publications

Avian influenza A virus H7N9 causes severe human infections with >30% fatality. Currently, there is no H7N9-specific prevention or treatment for humans. Here, from a 2013 H7N9 convalescent case in Hong Kong, we isolate four hemagglutinin (HA)-reactive monoclonal antibodies (mAbs), with three directed to the globular head domain (HA1) and one to the stalk domain (HA2). Two clonally related HA1-directed mAbs, H7.HK1 and H7.HK2, potently neutralize H7N9 and protect female mice from lethal H7N9/AH1 challenge. Cryo-EM structures reveal that H7.HK1 and H7.HK2 bind to a β14-centered surface and disrupt the 220-loop that makes hydrophobic contacts with sialic acid on an …

Fetal Brain-Derived Exosomal Mirnas From Maternal Blood: Potential Diagnostic Biomarkers For Fetal Alcohol Spectrum Disorders (Fasds), Nune Darbinian, Monica Hampe, Diana Martirosyan, Ahsun Bajwa, Armine Darbinyan, Nana Merabova, Gabriel Tatevosian, Laura Goetzl, Shohreh Amini, Michael E Selzer

Student and Faculty Publications

Fetal alcohol spectrum disorders (FASDs) are leading causes of neurodevelopmental disability but cannot be diagnosed early in utero. Because several microRNAs (miRNAs) are implicated in other neurological and neurodevelopmental disorders, the effects of EtOH exposure on the expression of these miRNAs and their target genes and pathways were assessed. In women who drank alcohol (EtOH) during pregnancy and non-drinking controls, matched individually for fetal sex and gestational age, the levels of miRNAs in fetal brain-derived exosomes (FB-Es) isolated from the mothers’ serum correlated well with the contents of the corresponding fetal brain tissues obtained after voluntary pregnancy termination. In six …

Brain Cell-Type Shifts In Alzheimer’S Disease, Autism, And Schizophrenia Interrogated Using Methylomics And Genetics, Chloe X Yap, Daniel D Vo, Matthew G Heffel, Arjun Bhattacharya, Cindy Wen, Yuanhao Yang, Kathryn E Kemper, Jian Zeng, Zhili Zheng, Zhihong Zhu, Eilis Hannon, Dorothea Seiler Vellame, Alice Franklin, Christa Caggiano, Brie Wamsley, Daniel H Geschwind, Noah Zaitlen, Alexander Gusev, Bogdan Pasaniuc, Jonathan Mill, Chongyuan Luo, Michael J Gandal

Student and Faculty Publications

Few neuropsychiatric disorders have replicable biomarkers, prompting high-resolution and large-scale molecular studies. However, we still lack consensus on a more foundational question: whether quantitative shifts in cell types-the functional unit of life-contribute to neuropsychiatric disorders. Leveraging advances in human brain single-cell methylomics, we deconvolve seven major cell types using bulk DNA methylation profiling across 1270 postmortem brains, including from individuals diagnosed with Alzheimer's disease, schizophrenia, and autism. We observe and replicate cell-type compositional shifts for Alzheimer's disease (endothelial cell loss), autism (increased microglia), and schizophrenia (decreased oligodendrocytes), and find age- and sex-related changes. Multiple layers of evidence indicate that endothelial …

Biobank-Wide Association Scan Identifies Risk Factors For Late-Onset Alzheimer's Disease And Endophenotypes, Donghui Yan, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

Rich data from large biobanks, coupled with increasingly accessible association statistics from genome-wide association studies (GWAS), provide great opportunities to dissect the complex relationships among human traits and diseases. We introduce BADGERS, a powerful method to perform polygenic score-based biobank-wide association scans. Compared to traditional approaches, BADGERS uses GWAS summary statistics as input and does not require multiple traits to be measured in the same cohort. We applied BADGERS to two independent datasets for late-onset Alzheimer's disease (AD; n=61,212). Among 1738 traits in the UK biobank, we identified 48 significant associations for AD. Family history, high cholesterol, and numerous traits …

Improved Pediatric Icu Mortality Prediction For Respiratory Diseases: Machine Learning And Data Subdivision Insights, Johayra Prithula, Muhammad E H Chowdhury, Muhammad Salman Khan, Khalid Al-Ansari, Susu M Zughaier, Khandaker Reajul Islam, Abdulrahman Alqahtani

Student and Faculty Publications

The growing concern of pediatric mortality demands heightened preparedness in clinical settings, especially within intensive care units (ICUs). As respiratory-related admissions account for a substantial portion of pediatric illnesses, there is a pressing need to predict ICU mortality in these cases. This study based on data from 1188 patients, addresses this imperative using machine learning techniques and investigating different class balancing methods for pediatric ICU mortality prediction. This study employs the publicly accessible "Paediatric Intensive Care database" to train, validate, and test a machine learning model for predicting pediatric patient mortality. Features were ranked using three machine learning feature selection …

Accessibility, Relevance, And Impact Of A Symptom Monitoring Tool For Home Hospice Care: Theory Elaboration And Qualitative Assessment, Karla T Washington, Debra Parker Oliver, Allison K Donehower, Patrick White, Jacquelyn J Benson, Patrick G Lyons, George Demiris

2020-Current year OA Pubs

BACKGROUND: Early users found Engagement and Visualization to Improve Symptoms in Oncology Care (ENVISION), a web-based application designed to improve home management of hospice patients' symptoms and support patients' and family caregivers' well-being, to be generally useful and easy to use. However, they also raised concerns about potential challenges users with limited technological proficiency might experience.

OBJECTIVE: We sought to concurrently accomplish two interrelated study aims: (1) to develop a conceptual framework of digital inclusivity for health information systems and (2) to apply the framework in evaluating the digital inclusivity of the ENVISION application.

METHODS: We engaged ENVISION users (N=34) …

The Influence Of Vitamin D Levels On Dental Caries: A Retrospective Study Of The United States Population, Man Hung, Himani Patel, Samantha Lee, Justin Nguyen, Amir Mohajeri

Student and Faculty Publications

(1) Background: This study examines vitamin D’s impact on dental caries to inform prevention strategies, given its critical role in bone and calcium regulation, vital for dental health. (2) Methods: Data from 18,683 participants of the National Health and Nutrition Examination Survey (NHANES) 2011–2016 were analyzed. NHANES collects U.S. population data through interviews, physical exams, and tests, including vitamin D levels and dental health assessed using both the decayed, missing, and filled teeth (DMFT) index and the presence of untreated dental caries. Vitamin D levels were measured according to serum 25(OH)D concentrations, and the analyses adjusted for confounders such as …

Sustained Response To Atogepant In Episodic Migraine: Post Hoc Analyses Of A 12-Week Randomized Trial And A 52-Week Long-Term Safety Trial, Richard Lipton, Stephanie J. Nahas, Patricia Pozo-Rosich, Tanya Bilchik, Peter Mcallister, Michelle Finnegan, Yingyi Liu, Natty Chalermpalanupap, Brett Dabruzzo, David Dodick

Department of Neurology Faculty Papers

BACKGROUND: Atogepant is an oral calcitonin gene-related peptide receptor antagonist approved for the preventive treatment of migraine in adults. These analyses evaluated the proportions of clinical trial participants who experienced sustained responses to atogepant over 12 or 52 weeks of treatment.

METHODS: These were post hoc analyses of ADVANCE, a 12-week, double-blind, randomized trial of atogepant 10, 30, and 60 mg once daily vs. placebo for the preventive treatment of episodic migraine, and a separate open-label long-term safety (LTS) trial of atogepant 60 mg once daily over 52 weeks. The 60 mg dose of atogepant was used to detect safety …

Graded Decisions In The Human Brain, Tao Xie, Markus Adamek, Hohyun Cho, Matthew A Adamo, Anthony L Ritaccio, Jon T Willie, Peter Brunner, Jan Kubanek

2020-Current year OA Pubs

Decision-makers objectively commit to a definitive choice, yet at the subjective level, human decisions appear to be associated with a degree of uncertainty. Whether decisions are definitive (i.e., concluding in all-or-none choices), or whether the underlying representations are graded, remains unclear. To answer this question, we recorded intracranial neural signals directly from the brain while human subjects made perceptual decisions. The recordings revealed that broadband gamma activity reflecting each individual's decision-making process, ramped up gradually while being graded by the accumulated decision evidence. Crucially, this grading effect persisted throughout the decision process without ever reaching a definite bound at the …

Il-2-Free Tumor-Infiltrating Lymphocyte Therapy With Pd-1 Blockade Demonstrates Potent Efficacy In Advanced Gynecologic Cancer, Jing Guo, Chunyan Wang, Ning Luo, Yuliang Wu, Wei Huang, Jihui Zhu, Weihui Shi, Jinye Ding, Yao Ge, Chunhong Liu, Zhen Lu, Robert C Bast, Guihai Ai, Weihong Yang, Rui Wang, Caixia Li, Rong Chen, Shupeng Liu, Huajun Jin, Binghui Zhao, Zhongping Cheng

Student and Faculty Publications

BACKGROUND: Tumor-infiltrating lymphocyte (TIL) therapy has been restricted by intensive lymphodepletion and high-dose intravenous interleukin-2 (IL-2) administration. To address these limitations, we conducted preclinical and clinical studies to evaluate the safety, antitumor activity, and pharmacokinetics of an innovative modified regimen in patients with advanced gynecologic cancer.

METHODS: Patient-derived xenografts (PDX) were established from a local recurrent cervical cancer patient. TILs were expanded ex vivo from minced tumors without feeder cells in the modified TIL therapy regimen. Patients underwent low-dose cyclophosphamide lymphodepletion followed by TIL infusion without intravenous IL-2. The primary endpoint was safety; the secondary endpoints included objective response rate, …

Gilteritinib As Post-Transplant Maintenance For Aml With Internal Tandem Duplication Mutation Of Flt3, Mark J Levis, Geoffrey L Uy, Et Al.

2020-Current year OA Pubs

PURPOSE: Allogeneic hematopoietic cell transplantation (HCT) improves outcomes for patients with AML harboring an internal tandem duplication mutation of

METHODS: Adults with

RESULTS: Three hundred fifty-six participants were randomly assigned post-HCT to receive gilteritinib or placebo. Although RFS was higher in the gilteritinib arm, the difference was not statistically significant (hazard ratio [HR], 0.679 [95% CI, 0.459 to 1.005]; two-sided

CONCLUSION: Although the overall improvement in RFS was not statistically significant, RFS was higher for participants with detectable

Common Single-Base Insertions In The Vntr Of The Carboxyl Ester Lipase (Cel) Gene Are Benign And Also Likely To Arise Somatically In The Exocrine Pancreas, Ranveig S Brekke, Anny Gravdal, Khadija El Jellas, Grace E Curry, Jianguo Lin, Steven J Wilhelm, Solrun J Steine, Eric Mas, Stefan Johansson, Mark E Lowe, Bente B Johansson, Xunjun Xiao, Karianne Fjeld, Anders Molven

2020-Current year OA Pubs

The CEL gene encodes carboxyl ester lipase, a pancreatic digestive enzyme. CEL is extremely polymorphic due to a variable number tandem repeat (VNTR) located in the last exon. Single-base deletions within this VNTR cause the inherited disorder MODY8, whereas little is known about VNTR single-base insertions in pancreatic disease. We therefore mapped CEL insertion variants (CEL-INS) in 200 Norwegian patients with pancreatic neoplastic disorders. Twenty-eight samples (14.0%) carried CEL-INS alleles. Most common were insertions in repeat 9 (9.5%), which always associated with a VNTR length of 13 repeats. The combined INS allele frequency (0.078) was similar to that observed in …

The Long-Term Effects Of Blood Urea Nitrogen Levels On Cardiovascular Disease And All-Cause Mortality In Diabetes: A Prospective Cohort Study, Hongfang Liu, Xiaoqin Xin, Jinghui Gan, Jungao Huang

Student and Faculty Publications

BACKGROUND: The long-term effects of blood urea nitrogen(BUN) in patients with diabetes remain unknown. Current studies reporting the target BUN level in patients with diabetes are also limited. Hence, this prospective study aimed to explore the relationship of BUN with all-cause and cardiovascular mortalities in patients with diabetes.

METHODS: In total, 10,507 participants with diabetes from the National Health and Nutrition Examination Survey (1999-2018) were enrolled. The causes and numbers of deaths were determined based on the National Death Index mortality data from the date of NHANES interview until follow-up (December 31, 2019). Multivariate Cox proportional hazard regression models were …

A Multi-Institutional Meningioma Mri Dataset For Automated Multi-Sequence Image Segmentation, Dominic Labella, Omaditya Khanna, Shan Mcburney-Lin, Ryan Mclean, Pierre Nedelec, Arif Rashid, Nourel Hoda Tahon, Talissa Altes, Ujjwal Baid, Radhika Bhalerao, Yaseen Dhemesh, Scott Floyd, Devon Godfrey, Fathi Hilal, Anastasia Janas, Anahita Kazerooni, Collin Kent, John Kirkpatrick, Florian Kofler, Kevin Leu, Nazanin Maleki, Bjoern Menze, Maxence Pajot, Zachary Reitman, Jeffrey Rudie, Rachit Saluja, Yury Velichko, Chunhao Wang, Pranav Warman, Nico Sollmann, David Diffley, Khanak Nandolia, Daniel Warren, Ali Hussain, John Pascal Fehringer, Yulia Bronstein, Lisa Deptula, Evan Stein, Mahsa Taherzadeh, Eduardo Portela De Oliveira, Aoife Haughey, Marinos Kontzialis, Luca Saba, Benjamin Turner, Melanie Brüßeler, Shehbaz Ansari, Athanasios Gkampenis, David Maximilian Weiss, Aya Mansour, Islam Shawali, Nikolay Yordanov, Joel Stein, Roula Hourani, Mohammed Yahya Moshebah, Ahmed Magdy Abouelatta, Tanvir Rizvi, Klara Willms, Dann Martin, Abdullah Okar, Gennaro D'Anna, Ahmed Taha, Yasaman Sharifi, Shahriar Faghani, Dominic Kite, Marco Pinho, Muhammad Ammar Haider, Michelle Alonso-Basanta, Javier Villanueva-Meyer, Andreas Rauschecker, Ayman Nada, Mariam Aboian, Adam Flanders, Spyridon Bakas, Evan Calabrese

Department of Radiology Faculty Papers

Meningiomas are the most common primary intracranial tumors and can be associated with significant morbidity and mortality. Radiologists, neurosurgeons, neuro-oncologists, and radiation oncologists rely on brain MRI for diagnosis, treatment planning, and longitudinal treatment monitoring. However, automated, objective, and quantitative tools for non-invasive assessment of meningiomas on multi-sequence MR images are not available. Here we present the BraTS Pre-operative Meningioma Dataset, as the largest multi-institutional expert annotated multilabel meningioma multi-sequence MR image dataset to date. This dataset includes 1,141 multi-sequence MR images from six sites, each with four structural MRI sequences (T2-, T2/FLAIR-, pre-contrast T1-, and post-contrast T1-weighted) accompanied by …

Seasonality, Clinical Characteristics, And Outcomes Of Respiratory Syncytial Virus Disease By Subtype Among Children Aged <5 Years: New Vaccine Surveillance Network, United States, 2016-2020., Ariana P. Toepfer, Justin Z. Amarin, Andrew J. Spieker, Laura S. Stewart, Mary Allen Staat, Elizabeth P. Schlaudecker, Geoffrey A. Weinberg, Peter G. Szilagyi, Janet A. Englund, Eileen J. Klein, Marian G. Michaels, John V. Williams, Rangaraj Selvarangan, Christopher J. Harrison, Joana Y. Lively, Pedro A. Piedra, Vasanthi Avadhanula, Brian Rha, James Chappell, Meredith Mcmorrow, Heidi Moline, Natasha B. Halasa

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of acute respiratory illnesses in children. RSV can be broadly categorized into 2 major subtypes: A and B. RSV subtypes have been known to cocirculate with variability in different regions of the world. Clinical associations with viral subtype have been studied among children with conflicting findings such that no conclusive relationships between RSV subtype and severity have been established.

METHODS: During 2016-2020, children aged/guardian interviews, chart reviews, and collection of midturbinate nasal plus/minus throat swabs for RSV (RSV-A, RSV-B, and untyped) using reverse transcription polymerase chain reaction.

RESULTS: Among 6398 RSV-positive …

Third-Party Fecal Microbiota Transplantation For High-Risk Treatment-Naïve Acute Gvhd Of The Lower Gi Tract, Zachariah Defilipp, Ashish V Damania, Haesook T Kim, Chia-Chi Chang, Areej El-Jawahri, Steven L Mcafee, Aj S Bottoms, Vesselina Toncheva, Melissa M Smith, Maria Dolaher, Lindsey Perry, Meghan White, Brittany Diana, Sheila Connolly, Bimalangshu R Dey, Matthew J Frigault, Richard A Newcomb, Paul V O'Donnell, Thomas R Spitzer, Michael K Mansour, Daniela Weber, Nadim J Ajami, Elizabeth Hohmann, Robert R Jenq, Yi-Bin Chen

Student and Faculty Publications

Disruption of the intestinal microbiome is observed with acute graft-versus-host disease (GVHD) of the lower gastrointestinal (LGI) tract, and fecal microbiota transplantation (FMT) has successfully cured steroid-refractory cases. In this open-label, single-arm, pilot study, third-party, single-donor FMT was administered in combination with systemic corticosteroids to participants with high-risk acute LGI GVHD, with a focus on treatment-naïve cases. Participants were scheduled to receive 1 induction dose (15 capsules per day for 2 consecutive days), followed by 3 weekly maintenance doses, consisting of 15 capsules per dose. The primary end point of the study was feasibility, which would be achieved if ≥80% …

Common Variation In A Long Non-Coding Rna Gene Modulates Variation Of Circulating Tgf-Β2 Levels In Metastatic Colorectal Cancer Patients (Alliance), Julia Quintanilha, Alexander Sibley, Yingmiao Liu, Donna Niedzwiecki, Susan Halabi, Layne Rogers, Bert O'Neil, Hedy Kindler, William Kelly, Alan Venook, Howard Mcleod, Mark Ratain, Andrew Nixon, Federico Innocenti, Kouros Owzar

Department of Medical Oncology Faculty Papers

BACKGROUND: Herein, we report results from a genome-wide study conducted to identify protein quantitative trait loci (pQTL) for circulating angiogenic and inflammatory protein markers in patients with metastatic colorectal cancer (mCRC). The study was conducted using genotype, protein marker, and baseline clinical and demographic data from CALGB/SWOG 80405 (Alliance), a randomized phase III study designed to assess outcomes of adding VEGF or EGFR inhibitors to systemic chemotherapy in mCRC patients. Germline DNA derived from blood was genotyped on whole-genome array platforms. The abundance of protein markers was quantified using a multiplex enzyme-linked immunosorbent assay from plasma derived from peripheral venous …