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The Gender Lens On Adhd: A Critical Assessment Of Diagnostic Patterns And Pitfalls, Taylor Funkhouser

BUHealth

Within the realm of neurodevelopmental disorders, attention deficit hyperactivity disorder (ADHD) is one of the most prevalent. However, research uncovers a major discrepancy between the diagnostic rates of men vs women, which points to the potential underdiagnosis and misdiagnosis in females compared to their male counterparts. This phenomenon raises concerns towards the impact this has on women, such has their mental and physical health. It begs the question, why does this discrepancy occur? To understand the answer to this question, it is important to look at the standard process and procedures involved with diagnosing a person with ADHD and compare …

Incidence And Types Of Cardiac Arrhythmias In The Peri-Ictal Period In Patients Having A Generalized Convulsive Seizure, Laura Vilella, Christina Y Miyake, Ganne Chaitanya, Johnson P Hampson, Shirin Jamal Omidi, Manuela Ochoa-Urrea, Blanca Talavera, Oscar Mancera, Norma J Hupp, Jaison S Hampson, M R Sandhya Rani, Nuria Lacuey, Shiqiang Tao, Rup K Sainju, Daniel Friedman, Maromi Nei, Catherine A Scott, Brian Gehlbach, Stephan U Schuele, Jennifer A Ogren, Ronald M Harper, Beate Diehl, Lisa M Bateman, Orrin Devinsky, George B Richerson, Guo-Qiang Zhang, Samden D Lhatoo

Faculty, Staff and Students Publications

Background and objectives: Generalized convulsive seizures (GCSs) are the main risk factor of sudden unexpected death in epilepsy (SUDEP), which is likely due to peri-ictal cardiorespiratory dysfunction. The incidence of GCS-induced cardiac arrhythmias, their relationship to seizure severity markers, and their role in SUDEP physiopathology are unknown. The aim of this study was to analyze the incidence of seizure-induced cardiac arrhythmias, their association with electroclinical features and seizure severity biomarkers, as well as their specific occurrences in SUDEP cases.

Methods: This is an observational, prospective, multicenter study of patients with epilepsy aged 18 years and older with recorded GCS during …

Ai-Assisted Segmentation Tool For Brain Tumor Mr Image Analysis, Myungeun Lee, Jong Hyo Kim, Wookjin Choi, Ki Hong Lee

Department of Radiation Oncology Faculty Papers

TumorPrism3D software was developed to segment brain tumors with a straightforward and user-friendly graphical interface applied to two- and three-dimensional brain magnetic resonance (MR) images. The MR images of 185 patients (103 males, 82 females) with glioblastoma multiforme were downloaded from The Cancer Imaging Archive (TCIA) to test the tumor segmentation performance of this software. Regions of interest (ROIs) corresponding to contrast-enhancing lesions, necrotic portions, and non-enhancing T2 high signal intensity components were segmented for each tumor. TumorPrism3D demonstrated high accuracy in segmenting all three tumor components in cases of glioblastoma multiforme. They achieved a better Dice similarity coefficient (DSC) …

Contributions Of Brain Microstructures And Metabolism To Visual Field Loss Patterns In Glaucoma Using Archetypal And Information Gain Analyses, Yueyin Pang, Ji Won Bang, Anisha Kasi, Jeremy Li, Carlos Parra, Els Fieremans, Gadi Wollstein, Joel S. Schuman, Mengyu Wang, Kevin C Chan

Wills Eye Hospital Papers

PURPOSE: To investigate the contributions of the microstructural and metabolic brain environment to glaucoma and their association with visual field (VF) loss patterns by using advanced diffusion magnetic resonance imaging (dMRI), proton magnetic resonance spectroscopy (MRS), and clinical ophthalmic measures.

METHODS: Sixty-nine glaucoma and healthy subjects underwent dMRI and/or MRS at 3 Tesla. Ophthalmic data were collected from VF perimetry and optical coherence tomography. dMRI parameters of microstructural integrity in the optic radiation and MRS-derived neurochemical levels in the visual cortex were compared among early glaucoma, advanced glaucoma, and healthy controls. Multivariate regression was used to correlate neuroimaging metrics with …

Predictors Of Aneurysm Obliteration In Patients Treated With The Web Device: Results Of A Multicenter Retrospective Study, Panagiotis Mastorakos, Kareem El Naamani, Nimer Adeeb, Mathews Lan, James Castiglione, Omaditya Khanna, Ritam Ghosh, Jose Danilo Bengzon Diestro, Mahmoud Dibas, Rachel M Mclellan, Oktay Algin, Sherief Ghozy, Nicole M Cancelliere, Assala Aslan, Hugo H Cuellar-Saenz, Sovann V Lay, Adrien Guenego, Leonardo Renieri, Joseph Carnevale, Guillaume Saliou, Eimad Shotar, Kevin Premat, Markus Möhlenbruch, Michael Kral, Justin E Vranic, Charlotte Chung, Mohamed M Salem, Ivan Lylyk, Paul M Foreman, Jay A Vachhani, Hamza Shaikh, Vedran Župančić, Muhammad U Hafeez, Joshua Catapano, Muhammad Waqas, Vincent M Tutino, Mohamed K Ibrahim, Marwa A Mohammed, James D Rabinov, Yifan Ren, Clemens M Schirmer, Mariangela Piano, Maria Bres Bullrich, Michael Mayich, Anna L Kühn, Caterina Michelozzi, Stéphanie Elens, Robert M Starke, Ameer E Hassan, Mark Ogilvie, Anh Nguyen, Jesse Jones, Waleed Brinjikji, Marios Psychogios, Christian Ulfert, Julian Spears, Brian T Jankowitz, Jan-Karl Burkhardt, Ricardo A Domingo, Thien Huynh, Rabih G Tawk, Boris Lubicz, Marie T Nawka, Pietro Panni, Ajit S Puri, Guglielmo Pero, Erez Nossek, Eytan Raz, Monika Killer-Oberpfalzer, M Ozgur Ozates, Giyas Ayberk, Robert W Regenhardt, Christoph J Griessenauer, Hamed Asadi, Adnan Siddiqui, Andrew F Ducruet, Felipe C Albuquerque, Nirav J Patel, Christopher J Stapleton, Peter Kan, Vladimir Kalousek, Pedro Lylyk, Srikanth Boddu, Jared Knopman, Mohammad A Aziz-Sultan, Frédéric Clarençon, Nicola Limbucci, Mario Zanaty, Juan Carlos Martinez-Gutierrez, Sunil Sheth, Gary Spiegel, Rawad Abbas, Abdelaziz Amllay, Stavropoula I Tjoumakaris, Michael R Gooch, Nabeel A Herial, Robert H Rosenwasser, Hekmat Zarzour, Richard F Schmidt, Vitor Mendes Pereira, Aman B Patel, Pascal M Jabbour, Adam A Dmytriw

Faculty, Staff and Student Publications

Background and purpose: Despite the numerous studies evaluating the occlusion rates of aneurysms following WEB embolization, there are limited studies identifying predictors of occlusion. Our purpose was to identify predictors of aneurysm occlusion and the need for retreatment.

Materials and methods: This is a review of a prospectively maintained database across 30 academic institutions. We included patients with previously untreated cerebral aneurysms embolized using the WEB who had available intraprocedural data and long-term follow-up.

Results: We studied 763 patients with a mean age of 59.9 (SD, 11.7) years. Complete aneurysm occlusion was observed in 212/726 (29.2%) cases, and contrast stasis …

Broadcasters, Receivers, Functional Groups Of Metabolites, And The Link To Heart Failure By Revealing Metabolomic Network Connectivity, Azam Yazdani, Raul Mendez-Giraldez, Akram Yazdani, Rui-Sheng Wang, Daniel J Schaid, Sek Won Kong, M Reza Hadi, Ahmad Samiei, Esmat Samiei, Clemens Wittenbecher, Jessica Lasky-Su, Clary B Clish, Jochen D Muehlschlegel, Francesco Marotta, Joseph Loscalzo, Samia Mora, Daniel I Chasman, Martin G Larson, Sarah H Elsea

Faculty, Staff and Students Publications

Background and objective: Blood-based small molecule metabolites offer easy accessibility and hold significant potential for insights into health processes, the impact of lifestyle, and genetic variation on disease, enabling precise risk prevention. In a prospective study with records of heart failure (HF) incidence, we present metabolite profiling data from individuals without HF at baseline.

Methods: We uncovered the interconnectivity of metabolites using data-driven and causal networks augmented with polygenic factors. Exploring the networks, we identified metabolite broadcasters, receivers, mediators, and subnetworks corresponding to functional classes of metabolites, and provided insights into the link between metabolomic architecture and regulation in health. …

Dissociation Of Reading And Naming In Ventral Occipitotemporal Cortex, Oscar Woolnough, Nitin Tandon

Faculty, Staff and Student Publications

Lesions in the language-dominant ventral occipitotemporal cortex (vOTC) can result in selective impairment of either reading or naming, resulting in alexia or anomia. Yet, functional imaging studies that show differential activation for naming and reading do not reveal activity exclusively tuned to one of these inputs. To resolve this dissonance in the functional architecture of the vOTC, we used focused stimulation to the vOTC in 49 adult patients during reading and naming, and generated a population-level, probabilistic map to evaluate if reading and naming are clearly dissociable within individuals. Language mapping (50 Hz, 2829 stimulations) was performed during passage reading …

Cell-Specific Single Viral Vector Crispr/Cas9 Editing And Genetically Encoded Tool Delivery In The Central And Peripheral Nervous Systems, Jamie C Moffa, India N Bland, Jessica R Tooley, Vani Kalyanaraman, Monique Heitmeier, Meaghan C Creed, Bryan A Copits

2020-Current year OA Pubs

CRISPR/Cas9 gene editing represents an exciting avenue to study genes of unknown function and can be combined with genetically encoded tools such as fluorescent proteins, channelrhodopsins, DREADDs, and various biosensors to more deeply probe the function of these genes in different cell types. However, current strategies to also manipulate or visualize edited cells are challenging due to the large size of Cas9 proteins and the limited packaging capacity of adeno-associated viruses (AAVs). To overcome these constraints, we developed an alternative gene editing strategy using a single AAV vector and mouse lines that express Cre-dependent Cas9 to achieve efficient cell-type specific …

Ai Driven Analysis Of Mri To Measure Health And Disease Progression In Fshd, Lara Riem, Olivia Ducharme, Matthew Cousins, Xue Feng, Allison Kenney, Jacob Morris, Stephen J Tapscott, Rabi Tawil, Jeff Statland, Dennis Shaw, Leo Wang, Michaela Walker, Leann Lewis, Michael A Jacobs, Doris G Leung, Seth D Friedman, Silvia S Blemker

Faculty, Staff and Student Publications

Facioscapulohumeral muscular dystrophy (FSHD) affects roughly 1 in 7500 individuals. While at the population level there is a general pattern of affected muscles, there is substantial heterogeneity in muscle expression across- and within-patients. There can also be substantial variation in the pattern of fat and water signal intensity within a single muscle. While quantifying individual muscles across their full length using magnetic resonance imaging (MRI) represents the optimal approach to follow disease progression and evaluate therapeutic response, the ability to automate this process has been limited. The goal of this work was to develop and optimize an artificial intelligence-based image …

Reverse Phase Proteomic Array Profiling Of Asparagine Synthetase Expression In Newly Diagnosed Acute Myeloid Leukemia, Nisha Narayanan, Jennifer Marvin-Peek, Mohamad K Abouelnaaj, Dhabya Majid, Bofei Wang, Brandon D Brown, Yihua Qiu, Steven M Kornblau, Hussein A Abbas

Faculty, Staff and Student Publications

Asparaginase-based therapy is a cornerstone in acute lymphoblastic leukemia (ALL) treatment, capitalizing on the methylation status of the asparagine synthetase (ASNS) gene, which renders ALL cells reliant on extracellular asparagine. Contrastingly, ASNS expression in acute myeloid leukemia (AML) has not been thoroughly investigated, despite studies suggesting that AML with chromosome 7/7q deletions might have reduced ASNS levels. Here, we leverage reverse phase protein arrays to measure ASNS expression in 810 AML patients and assess its impact on outcomes. We find that AML with inv(16) has the lowest overall ASNS expression. While AML with deletion 7/7q had ASNS levels slightly lower …

Hur Controls Glutaminase Rna Metabolism, Douglas Adamoski, Larissa M Dos Reis, Ana Carolina Paschoalini Mafra, Felipe Corrêa-Da-Silva, Pedro Manoel Mendes De Moraes-Vieira, Ioana Berindan-Neagoe, George A Calin, Sandra Martha Gomes Dias

Faculty, Staff and Student Publications

Glutaminase (GLS) is directly related to cell growth and tumor progression, making it a target for cancer treatment. The RNA-binding protein HuR (encoded by the ELAVL1 gene) influences mRNA stability and alternative splicing. Overexpression of ELAVL1 is common in several cancers, including breast cancer. Here we show that HuR regulates GLS mRNA alternative splicing and isoform translation/stability in breast cancer. Elevated ELAVL1 expression correlates with high levels of the glutaminase isoforms C (GAC) and kidney-type (KGA), which are associated with poor patient prognosis. Knocking down ELAVL1 reduces KGA and increases GAC levels, enhances glutamine anaplerosis into the TCA cycle, and …

Task And Stimulus Coding In The Multiple-Demand Network, Sneha Shashidhara, Moataz Assem, Matthew F Glasser, John Duncan

2020-Current year OA Pubs

In the human brain, a multiple-demand (MD) network plays a key role in cognitive control, with core components in lateral frontal, dorsomedial frontal and lateral parietal cortex, and multivariate activity patterns that discriminate the contents of many cognitive activities. In prefrontal cortex of the behaving monkey, different cognitive operations are associated with very different patterns of neural activity, while details of a particular stimulus are encoded as small variations on these basic patterns (Sigala et al, 2008). Here, using the advanced fMRI methods of the Human Connectome Project and their 360-region cortical parcellation, we searched for a similar result in …

O-Glcnacylation Of Mitf Regulates Its Activity And Cdk4/6 Inhibitor Resistance In Breast Cancer, Yi Zhang, Shuyan Zhou, Yan Kai, Ya-Qin Zhang, Changmin Peng, Zhuqing Li, Muhammad Jameel Mughal, Belmar Julie, Xiaoyan Zheng, Junfeng Ma, Cynthia X Ma, Min Shen, Matthew D Hall, Shunqiang Li, Wenge Zhu

2020-Current year OA Pubs

Cyclin-dependent kinases 4 and 6 (CDK4/6) play a pivotal role in cell cycle and cancer development. Targeting CDK4/6 has demonstrated promising effects against breast cancer. However, resistance to CDK4/6 inhibitors (CDK4/6i), such as palbociclib, remains a substantial challenge in clinical settings. Using high-throughput combinatorial drug screening and genomic sequencing, we find that the microphthalmia-associated transcription factor (MITF) is activated via O-GlcNAcylation by O-GlcNAc transferase (OGT) in palbociclib-resistant breast cancer cells and tumors. Mechanistically, O-GlcNAcylation of MITF at Serine 49 enhances its interaction with importin α/β, thus promoting its translocation to nuclei, where it suppresses palbociclib-induced senescence. Inhibition of MITF or …

Loss Of The Dna Repair Gene Rnase H2 Identifies A Unique Subset Of Ddr-Deficient Leiomyosarcomas, Michael S Nakazawa, Ian M Silverman, Victoria Rimkunas, Artur Veloso, Dominik Glodzik, Adrienne Johnson, Toshiro K Ohsumi, Shreyaskumar R Patel, Anthony P Conley, Christina L Roland, Pamela T Soliman, Hannah C Beird, Chia-Chin Wu, Davis R Ingram, Rossana Lazcano, Dawon Song, Khalida M Wani, Alexander J Lazar, Timothy A Yap, Wei-Lien Wang, J Andrew Livingston

Faculty, Staff and Student Publications

Targeting the DNA damage response (DDR) pathway is an emerging therapeutic approach for leiomyosarcoma (LMS), and loss of RNase H2, a DDR pathway member, is a potentially actionable alteration for DDR-targeted treatments. Therefore, we designed a protein- and genomic-based RNase H2 screening assay to determine its prevalence and prognostic significance. Using a selective RNase H2 antibody on a pan-tumor microarray (TMA), RNase H2 loss was more common in LMS (11.5%, 9/78) than across all tumors (3.8%, 32/843). In a separate LMS cohort, RNase H2 deficiency was confirmed in uterine LMS (U-LMS, 21%, 23/108) and soft-tissue LMS (ST-LMS; 30%, 39/102). In …

Reliable Detection Of Generalized Convulsive Seizures Using An Off-The-Shelf Digital Watch: A Multisite Phase 2 Study, Yash Shashank Vakilna, Xiaojin Li, Jaison S Hampson, Yan Huang, John C Mosher, Yuri Dabaghian, Xi Luo, Blanca Talavera, Sandipan Pati, Masel Todd, Ryan Hays, Charles Akos Szabo, Guo-Qiang Zhang, Samden D Lhatoo

Faculty, Staff and Student Publications

Objective: The aim of this study was to develop a machine learning algorithm using an off-the-shelf digital watch, the Samsung watch (SM-R800), and evaluate its effectiveness for the detection of generalized convulsive seizures (GCS) in persons with epilepsy.

Methods: This multisite epilepsy monitoring unit (EMU) phase 2 study included 36 adult patients. Each patient wore a Samsung watch that contained accelerometer, gyroscope, and photoplethysmographic sensors. Sixty-eight time and frequency domain features were extracted from the sensor data and were used to train a random forest algorithm. A testing framework was developed that would better reflect the EMU setting, consisting of …

Early And Late Complications Of Mandibulectomy Free Flap Reconstruction: Does The Selective Use Of Soft Tissue Only Flaps Reduce Complications?, Dylan B Mcbee, Michael J Dileo, Caroline C Keehn, Andrew T Huang, Angela D Haskins, David J Hernandez

Faculty, Staff and Students Publications

Purpose: This study aims to evaluate the factors most associated with early and late complications following microvascular free tissue transfer (MVFTT) after mandibulectomy.

Methods: A retrospective review of patients undergoing MVFTT after segmental mandibulectomy from September 2016 to February 2021 was performed across a single academic institution. Surgical variables were collected, including the location of the resultant mandibular defect (anterior vs posterior) and flap type (osseous or non-osseous). The primary outcome variables included postoperative complications (early, < 90 days; and late, >90 days) and the patients' functional status (return to oral intake). Descriptive statistics, chi-square test, Fischer's exact test, and 2-sample t tests were used …

Alcohol Milestones And Internalizing, Externalizing, And Executive Function: Longitudinal And Polygenic Score Associations, Sarah E Paul, David A A Baranger, Joshua J Jackson, Aaron J Gorelik, Alexander S Hatoum, Michael Strube, Andrey P Anokhin, Arpana Agrawal, Kathleen K Bucholz, Ryan Bogdan, Et Al.

2020-Current year OA Pubs

BACKGROUND: Although the link between alcohol involvement and behavioral phenotypes (e.g. impulsivity, negative affect, executive function [EF]) is well-established, the directionality of these associations, specificity to stages of alcohol involvement, and extent of shared genetic liability remain unclear. We estimate longitudinal associations between transitions among alcohol milestones, behavioral phenotypes, and indices of genetic risk.

METHODS: Data came from the Collaborative Study on the Genetics of Alcoholism (

RESULTS: Externalizing phenotypes (e.g. conduct disorder symptoms) were associated with future initiation and drinking problems (hazard ratio (HR)⩾1.16). Internalizing (e.g. social anxiety) was associated with hazards for progression from first drink to severe …

In Vivo Validation Of Late-Onset Alzheimer's Disease Genetic Risk Factors., Michael Sasner, Christoph Preuss, Ravi S Pandey, Asli Uyar, Dylan Garceau, Kevin P Kotredes, Harriet M. Jackson, Adrian L Oblak, Peter Bor-Chian Lin, Bridget Perkins, Disha Soni, Cindy Ingraham, Audrey Lee-Gosselin, Bruce T Lamb, Gareth R Howell, Gregory W. Carter

Faculty Research 2024

INTRODUCTION: Genome-wide association studies have identified over 70 genetic loci associated with late-onset Alzheimer's disease (LOAD), but few candidate polymorphisms have been functionally assessed for disease relevance and mechanism of action.

METHODS: Candidate genetic risk variants were informatically prioritized and individually engineered into a LOAD-sensitized mouse model that carries the AD risk variants APOE ε4/ε4 and Trem2*R47H. The potential disease relevance of each model was assessed by comparing brain transcriptomes measured with the Nanostring Mouse AD Panel at 4 and 12 months of age with human study cohorts.

RESULTS: We created new models for 11 coding and loss-of-function risk variants. …

Assessment Of Neurovascular Uncoupling: Apoe Status Is A Key Driver Of Early Metabolic And Vascular Dysfunction., Kristen D. Onos, Peter B Lin, Ravi S Pandey, Scott A Persohn, Charles P Burton, Ethan W Miner, Kierra Eldridge, Jonathan Nyandu Kanyinda, Kate E Foley, Gregory W. Carter, Gareth R Howell, Paul R Territo

Faculty Research 2024

BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia worldwide, with apolipoprotein Eε4 (APOEε4) being the strongest genetic risk factor. Current clinical diagnostic imaging focuses on amyloid and tau; however, new methods are needed for earlier detection.

METHODS: PET imaging was used to assess metabolism-perfusion in both sexes of aging C57BL/6J, and hAPOE mice, and were verified by transcriptomics, and immunopathology.

RESULTS: All hAPOE strains showed AD phenotype progression by 8 months, with females exhibiting the regional changes, which correlated with GO-term enrichments for glucose metabolism, perfusion, and immunity. Uncoupling analysis revealed APOEε4/ε4 exhibited significant Type-1 uncoupling (↓ …

Lexical Access In Women With The Fmr1 Premutation, Nadia Sabeh Ayon

Theses and Dissertations

Background: Emergent research indicates that women carrying the FMR1 premutation (FXpm) may encounter difficulties in language skills, including increased dysfluencies, a reduction in the quantity and diversity of words produced, and increased word retrieval errors with age (Sterling et al., 2013; Bredin-Oja et al., 2021). Objectives: The present study aims to assess semantic and phonological lexical access skills in FXpm women as well as to examine the impact of cognitive load (time pressure) on lexical access.

Methods: Forty-two FXpm women and 25 control women, aged 26-65 years (M=46.22, age-matched: p=.115), participated. The Network Production Task (Oomen & Postma, 2001), featuring …

Wide-Field Optical Coherence Tomography Imaging Improves Rate Of Change Detection In Progressing Glaucomatous Eyes Compared With Standard-Field Imaging, Christopher Bowd, Akram Belghith, Jasmin Rezapour, Jost B. Jonas, Leslie Hyman, Robert N. Weinreb, Linda M. Zangwill

Wills Eye Hospital Papers

PURPOSE: To compare rates of retinal nerve fiber layer change over time in healthy, eyes with nonprogressing glaucoma and eyes with progressing glaucoma using single wide-field (SWF) and optic nerve head (ONH) cube scan optical coherence tomography (OCT) images.

METHODS: Forty-five eyes of 25 healthy individuals and 263 eyes of 161 glaucoma patients from the Diagnostic Innovations in Glaucoma Study were included. All eyes underwent 24-2 visual field testing and OCT (Spectralis SD-OCT) ONH and macular imaging. SWF images (up to 43° × 28°) were created by stitching together ONH cube scans centered on the optic disc and macular cube …

Understanding The Genetic Complexity Of Puberty Timing Across The Allele Frequency Spectrum, Katherine A Kentistou, Lena R Kaisinger, Stasa Stankovic, Marc Vaudel, Edson Mendes De Oliveira, Andrea Messina, Robin G Walters, Xiaoxi Liu, Alexander S Busch, Hannes Helgason, Deborah J Thompson, Federico Santoni, Konstantin M Petricek, Yassine Zouaghi, Isabel Huang-Doran, Daniel F Gudbjartsson, Eirik Bratland, Kuang Lin, Eugene J Gardner, Yajie Zhao, Raina Y Jia, Chikashi Terao, Marjorie J Riggan, Manjeet K Bolla, Mojgan Yazdanpanah, Nahid Yazdanpanah, Jonathan P Bradfield, Linda Broer, Archie Campbell, Daniel I Chasman, Diana L Cousminer, Nora Franceschini, Lude H Franke, Giorgia Girotto, Chunyan He, Marjo-Riitta Järvelin, Peter K Joshi, Yoichiro Kamatani, Robert Karlsson, Jian'an Luan, Kathryn L Lunetta, Reedik Mägi, Massimo Mangino, Sarah E Medland, Christa Meisinger, Raymond Noordam, Teresa Nutile, Maria Pina Concas, Ozren Polašek, Eleonora Porcu, Susan M Ring, Cinzia Sala, Albert V Smith, Toshiko Tanaka, Peter J Van Der Most, Veronique Vitart, Carol A Wang, Gonneke Willemsen, Marek Zygmunt, Thomas U Ahearn, Irene L Andrulis, Hoda Anton-Culver, Antonis C Antoniou, Paul L Auer, Catriona L K Barnes, Matthias W Beckmann, Amy Berrington De Gonzalez, Natalia V Bogdanova, Stig E Bojesen, Hermann Brenner, Julie E Buring, Federico Canzian, Jenny Chang-Claude, Fergus J Couch, Angela Cox, Laura Crisponi, Kamila Czene, Mary B Daly, Ellen W Demerath, Joe Dennis, Peter Devilee, Immaculata De Vivo, Thilo Dörk, Alison M Dunning, Miriam Dwek, Johan G Eriksson, Peter A Fasching, Lindsay Fernandez-Rhodes, Liana Ferreli, Olivia Fletcher, Manuela Gago-Dominguez, Montserrat García-Closas, José A García-Sáenz, Anna González-Neira, Harald Grallert, Pascal Guénel, Christopher A Haiman, Per Hall, Ute Hamann, Hakon Hakonarson, Roger J Hart, Martha Hickey, Maartje J Hooning, Reiner Hoppe, John L Hopper, Jouke-Jan Hottenga, Frank B Hu, Hanna Huebner, David J Hunter, Helena Jernström, Esther M John, David Karasik, Elza K Khusnutdinova, Vessela N Kristensen, James V Lacey, Diether Lambrechts, Lenore J Launer, Penelope A Lind, Annika Lindblom, Patrik K E Magnusson, Arto Mannermaa, Mark I Mccarthy, Thomas Meitinger, Cristina Menni, Kyriaki Michailidou, Iona Y Millwood, Roger L Milne, Grant W Montgomery, Heli Nevanlinna, Ilja M Nolte, Dale R Nyholt, Nadia Obi, Katie M O'Brien, Kenneth Offit, Albertine J Oldehinkel, Sisse R Ostrowski, Aarno Palotie, Ole B Pedersen, Annette Peters, Giulia Pianigiani, Dijana Plaseska-Karanfilska, Anneli Pouta, Alfred Pozarickij, Paolo Radice, Gad Rennert, Frits R Rosendaal, Daniela Ruggiero, Emmanouil Saloustros, Dale P Sandler, Sabine Schipf, Carsten O Schmidt, Marjanka K Schmidt, Kerrin Small, Beatrice Spedicati, Meir Stampfer, Jennifer Stone, Rulla M Tamimi, Lauren R Teras, Emmi Tikkanen, Constance Turman, Celine M Vachon, Qin Wang, Robert Winqvist, Alicja Wolk, Babette S Zemel, Wei Zheng, Ko W Van Dijk, Behrooz Z Alizadeh, Stefania Bandinelli, Eric Boerwinkle, Dorret I Boomsma, Marina Ciullo, Georgia Chenevix-Trench, Francesco Cucca, Tõnu Esko, Christian Gieger, Struan F A Grant, Vilmundur Gudnason, Caroline Hayward, Ivana Kolčić, Peter Kraft, Deborah A Lawlor, Nicholas G Martin, Ellen A Nøhr, Nancy L Pedersen, Craig E Pennell, Paul M Ridker, Antonietta Robino, Harold Snieder, Ulla Sovio, Tim D Spector, Doris Stöckl, Cathie Sudlow, Nic J Timpson, Daniela Toniolo, André Uitterlinden, Sheila Ulivi, Henry Völzke, Nicholas J Wareham, Elisabeth Widen, James F Wilson, Lifelines Cohort Study, Danish Blood Donor Study, Ovarian Cancer Association Consortium, Breast Cancer Association Consortium, Biobank Japan Project, China Kadoorie Biobank Collaborative Group, Paul D P Pharoah, Liming Li, Douglas F Easton, Pål R Njølstad, Patrick Sulem, Joanne M Murabito, Anna Murray, Despoina Manousaki, Anders Juul, Christian Erikstrup, Kari Stefansson, Momoko Horikoshi, Zhengming Chen, I Sadaf Farooqi, Nelly Pitteloud, Stefan Johansson, Felix R Day, John R B Perry, Ken K Ong

Faculty, Staff and Student Publications

Pubertal timing varies considerably and is associated with later health outcomes. We performed multi-ancestry genetic analyses on ~800,000 women, identifying 1,080 signals for age at menarche. Collectively, these explained 11% of trait variance in an independent sample. Women at the top and bottom 1% of polygenic risk exhibited ~11 and ~14-fold higher risks of delayed and precocious puberty, respectively. We identified several genes harboring rare loss-of-function variants in ~200,000 women, including variants in ZNF483, which abolished the impact of polygenic risk. Variant-to-gene mapping approaches and mouse gonadotropin-releasing hormone neuron RNA sequencing implicated 665 genes, including an uncharacterized G-protein-coupled receptor, GPR83, …

High Throughput Plasma Proteomics And Risk Of Heart Failure And Frailty In Late Life, Diego Ramonfaur, Leo F Buckley, Victoria Arthur, Yimin Yang, Brian L Claggett, Chiadi E Ndumele, Keenan A Walker, Thomas Austin, Michelle C Odden, James S Floyd, Sandra Sanders-Van Wijk, Joyce Njoroge, Jorge R Kizer, Dalane Kitzman, Suma H Konety, Jennifer Schrack, Fangyu Liu, B Gwen Windham, Priya Palta, Josef Coresh, Bing Yu, Amil M Shah

Faculty, Staff and Student Publications

Importance: Heart failure (HF) and frailty frequently coexist and may share a common pathobiology, although the underlying mechanisms remain unclear. Understanding these mechanisms may provide guidance for preventing and treating both conditions.

Objective: To identify shared pathways between incident HF and frailty in late life using large-scale proteomics.

Design, setting, and participants: In this cohort study, 4877 aptamers (Somascan v4) were measured among participants in the community-based longitudinal Atherosclerosis Risk In Communities (ARIC) cohort study at visit 3 (V3; 1993-1995; n = 10 638) and at visit 5 (V5; 2011-2013; n = 3908). Analyses were externally replicated among 3189 participants …

A Cytomics-On-A-Chip Platform And Diagnostic Model Stratifies Risk For Oral Lichenoid Conditions, Michael P Mcrae, Kritika Srinivasan Rajsri, A Ross Kerr, Nadarajah Vigneswaran, Spencer W Redding, Malvin Janal, Stella K Kang, Leena Palomo, Nicolaos J Christodoulides, Meena Singh, Jeffery Johnston, John T Mcdevitt

Faculty, Staff and Student Publications

Objective: A small fraction of oral lichenoid conditions (OLC) have potential for malignant transformation. Distinguishing OLCs from other oral potentially malignant disorders (OPMDs) can help prevent unnecessary concern or testing, but accurate identification by nonexpert clinicians is challenging due to overlapping clinical features. In this study, the authors developed a 'cytomics-on-a-chip' tool and integrated predictive model for aiding the identification of OLCs.

Study design: All study subjects underwent both scalpel biopsy for histopathology and brush cytology. A predictive model and OLC Index comprising clinical, demographic, and cytologic features was generated to discriminate between subjects with lichenoid (OLC+) (N = 94) …

The Role Of Occipital Condyle And Atlas Anomalies On Occipital Cervical Fusion Outcomes In Chiari Malformation Type I With Syringomyelia: A Study From The Park-Reeves Syringomyelia Research Consortium, Alexander T Yahanda, Joyce Koueik, Laurie L Ackerman, P David Adelson, Gregory W Albert, Philipp R Aldana, Tord D Alden, Richard C E Anderson, David F Bauer, Tammy Bethel-Anderson, Karin Bierbrauer, Douglas L Brockmeyer, Joshua J Chern, Daniel E Couture, David J Daniels, Brian J Dlouhy, Susan R Durham, Richard G Ellenbogen, Ramin Eskandari, Herbert E Fuchs, Gerald A Grant, Patrick C Graupman, Stephanie Greene, Jeffrey P Greenfield, Naina L Gross, Daniel J Guillaume, Todd C Hankinson, Gregory G Heuer, Mark Iantosca, Bermans J Iskandar, Eric M Jackson, George I Jallo, James M Johnston, Bruce A Kaufman, Robert F Keating, Nickalus R Khan, Mark D Krieger, Jeffrey R Leonard, Cormac O Maher, Francesco T Mangano, Jonathan Martin, J Gordon Mccomb, Sean D Mcevoy, Thanda Meehan, Arnold H Menezes, Michael S Muhlbauer, Brent R O'Neill, Greg Olavarria, John Ragheb, Nathan R Selden, Manish N Shah, Chevis N Shannon, Joshua S Shimony, Matthew D Smyth, Scellig S D Stone, Jennifer M Strahle, Mandeep S Tamber, James C Torner, Gerald F Tuite, Elizabeth C Tyler-Kabara, Scott D Wait, John C Wellons, William E Whitehead, Tae Sung Park, David D Limbrick, Raheel Ahmed

Faculty, Staff and Student Publications

Objective: Congenital anomalies of the atlanto-occipital articulation may be present in patients with Chiari malformation type I (CM-I). However, it is unclear how these anomalies affect the biomechanical stability of the craniovertebral junction (CVJ) and whether they are associated with an increased incidence of occipitocervical fusion (OCF) following posterior fossa decompression (PFD). The objective of this study was to determine the prevalence of condylar hypoplasia and atlas anomalies in children with CM-I and syringomyelia. The authors also investigated the predictive contribution of these anomalies to the occurrence of OCF following PFD (PFD+OCF).

Methods: The authors analyzed the prevalence of condylar …

Endovascular Versus Medical Therapy In Posterior Cerebral Artery Stroke: Role Of Baseline Nihss Score And Occlusion Site, Davide Strambo, Patrik Michel, Thanh N Nguyen, Mohamad Abdalkader, Muhammad M Qureshi, Daniel Strbian, Christian Herweh, Markus A Möhlenbruch, Silja Räty, Marta Olivé-Gadea, Marc Ribo, Marios Psychogios, Urs Fischer, Anh Nguyen, Joji B Kuramatsu, David Haupenthal, Martin Köhrmann, Cornelius Deuschl, Jordi Kühne Escolà, Jelle Demeestere, Robin Lemmens, Lieselotte Vandewalle, Shadi Yaghi, Liqi Shu, Volker Puetz, Daniel P O Kaiser, Johannes Kaesmacher, Adnan Mujanovic, Dominique Cornelius Marterstock, Tobias Engelhorn, Manuel Requena, Hormuzdiyar H Dasenbrock, Piers Klein, Diogo C Haussen, Mahmoud H Mohammaden, Hend Abdelhamid, Lorena Souza Viana, Bruno Cunha, Isabel Fragata, Michele Romoli, Francesco Diana, Wei Hu, Chao Zhang, Pekka Virtanen, Riikka Lauha, Jessica Jesser, Judith Clark, Stavros Matsoukas, Johanna T Fifi, Sunil A Sheth, Sergio Salazar-Marioni, João Pedro Marto, João Nuno Ramos, Milena Miszczuk, Christoph Riegler, Sven Poli, Khouloud Poli, Ashutosh P Jadhav, Shashvat M Desai, Volker Maus, Maximilian Kaeder, Adnan H Siddiqui, Andre Monteiro, Hesham E Masoud, Neil Suryadareva, Maxim Mokin, Shail Thanki, Kemal Alpay, Pauli Ylikotila, James E Siegler, Italo Linfante, Guilherme Dabus, Negar Asdaghi, Vasu Saini, Christian H Nolte, Eberhard Siebert, Bettina L Serrallach, Charlotte S Weyland, Uta Hanning, Lukas Meyer, Anne Berberich, Peter A Ringleb, Raul G Nogueira, Simon Nagel

Faculty, Staff and Student Publications

Background: Acute ischemic stroke with isolated posterior cerebral artery occlusion (iPCAO) lacks management evidence from randomized trials. We aimed to evaluate whether the association between endovascular treatment (EVT) and outcomes in iPCAO acute ischemic stroke is modified by initial stroke severity (baseline National Institutes of Health Stroke Scale [NIHSS]) and arterial occlusion site.

Methods: Based on the multicenter, retrospective, case-control study of consecutive iPCAO acute ischemic stroke patients (PLATO study [Posterior Cerebral Artery Occlusion Stroke]), we assessed the heterogeneity of EVT outcomes compared with medical management (MM) for iPCAO, according to baseline NIHSS score (≤6 versus >6) and occlusion site …

The Beneficial Role Of Sunitinib In Tumor Immune Surveillance By Regulating Tumor Pd-L1, Vivian L Rose, Anaga Ajoy, Craig A Johnston, Gloria R Gogola, Pranav J Parikh

Faculty, Staff and Student Publications

Importance: There is a need for a pediatric hand function test that can be used to objectively assess movement quality. We have developed a toy-based test, the Bead Maze Hand Function (BMHF) test, to quantify how well a child performs an activity. This is achieved by assessing the control of forces applied while drawing a bead over wires of different complexity.

Objective: To study the psychometric properties of the BMHF test and understand the influence of age and task complexity on test measures.

Design: A cross-sectional, observational study performed in a single visit.

Setting: Clinical research laboratory.

Participants: Twenty-three participants …

Liver Disease And Transplantation In Telomere Biology Disorders: An International Multicenter Cohort, Yunzu Michele Wang, Steven K Brennan, Sakil Kulkarni, Et Al.

2020-Current year OA Pubs

BACKGROUND: Patients with telomere biology disorders (TBD) develop hepatic disease, including hepatitis, cirrhosis, and hepatopulmonary syndrome. No specific treatment exists for TBD-related liver disease, and the role of liver transplantation (LT) remains controversial. Our study objectives were to describe the clinical characteristics, management, and outcomes in patients with TBD-related liver disease, and their LT outcomes.

METHODS: Data from 83 patients with TBD-associated liver disease were obtained from 17 participating centers in the Clinical Care Consortium of Telomere-Associated Ailments and by self-report for our retrospective, multicenter, international cohort study.

RESULTS: Group A ("Advanced") included 40 patients with advanced liver disease. Of …

Momelotinib Vs. Ruxolitinib In Myelofibrosis Patient Subgroups By Baseline Hemoglobin Levels In The Simplify-1 Trial, Vikas Gupta, Stephen Oh, Et Al.

2020-Current year OA Pubs

A key hallmark of myelofibrosis is anemia, which ranges from mild to severe based on hemoglobin levels. To more clearly define outcomes with the Janus kinase (JAK) 1/JAK2/activin A receptor type 1 inhibitor momelotinib by anemia severity, we performed a descriptive post hoc exploratory analysis of the double-blind, randomized, phase 3 SIMPLIFY-1 study (NCT01969838;

Impact Of Lifetime Stressor Exposure On Neuroenergetics In Schizophrenia Spectrum Disorders, Joshua Chiappelli, Anya Savransky, Yizhou Ma, Si Gao, Mark D Kvarta, Peter Kochunov, George M Slavich, L Elliot Hong

Faculty, Staff and Student Publications

N-acetylasparate and lactate are two prominent brain metabolites closely related to mitochondrial functioning. Prior research revealing lower levels of NAA and higher levels of lactate in the cerebral cortex of patients with schizophrenia suggest possible abnormalities in the energy supply pathway necessary for brain function. Given that stress and adversity are a strong risk factor for a variety of mental health problems, including psychotic disorders, we investigated the hypothesis that stress contributes to abnormal neuroenergetics in patients with schizophrenia. To test this hypothesis, we used the Stress and Adversity Inventory (STRAIN) to comprehensively assess the lifetime stressor exposure profiles of …