Digital Commons Network^™

Image-Based Multiplex Immune Profiling Of Cancer Tissues: Translational Implications A Report Of The International Immuno-Oncology Biomarker Working Group On Breast Cancer, Chowdhury Arif Jahangir, David B Page, Glenn Broeckx, Claudia A Gonzalez, Caoimbhe Burke, Clodagh Murphy, Jorge S Reis-Filho, Amy Ly, Paul W Harms, Rajarsi R Gupta, Michael Vieth, Akira I Hida, Mohamed Kahila, Zuzana Kos, Paul J Van Diest, Sara Verbandt, Jeppe Thagaard, Reena Khiroya, Khalid Abduljabbar, Gabriela Acosta Haab, Balazs Acs, Sylvia Adams, Jonas S Almeida, Isabel Alvarado-Cabrero, Farid Azmoudeh-Ardalan, Sunil Badve, Nurkhairul Bariyah Baharun, Enrique R Bellolio, Vydehi Bheemaraju, Kim Rm Blenman, Luciana Botinelly Mendonça Fujimoto, Octavio Burgues, Alexandros Chardas, Maggie Chon U Cheang, Francesco Ciompi, Lee Ad Cooper, An Coosemans, Germán Corredor, Flavio Luis Dantas Portela, Frederik Deman, Sandra Demaria, Sarah N Dudgeon, Mahmoud Elghazawy, Claudio Fernandez-Martín, Susan Fineberg, Stephen B Fox, Jennifer M Giltnane, Sacha Gnjatic, Paula I Gonzalez-Ericsson, Anita Grigoriadis, Niels Halama, Matthew G Hanna, Aparna Harbhajanka, Steven N Hart, Johan Hartman, Stephen Hewitt, Hugo M Horlings, Zaheed Husain, Sheeba Irshad, Emiel Am Janssen, Tatsuki R Kataoka, Kosuke Kawaguchi, Andrey I Khramtsov, Umay Kiraz, Pawan Kirtani, Liudmila L Kodach, Konstanty Korski, Guray Akturk, Ely Scott, Anikó Kovács, Anne-Vibeke Laenkholm, Corinna Lang-Schwarz, Denis Larsimont, Jochen K Lennerz, Marvin Lerousseau, Xiaoxian Li, Anant Madabhushi, Sai K Maley, Vidya Manur Narasimhamurthy, Douglas K Marks, Elizabeth S Mcdonald, Ravi Mehrotra, Stefan Michiels, Durga Kharidehal, Fayyaz Ul Amir Afsar Minhas, Shachi Mittal, David A Moore, Shamim Mushtaq, Hussain Nighat, Thomas Papathomas, Frederique Penault-Llorca, Rashindrie D Perera, Christopher J Pinard, Juan Carlos Pinto-Cardenas, Giancarlo Pruneri, Lajos Pusztai, Nasir Mahmood Rajpoot, Bernardo Leon Rapoport, Tilman T Rau, Joana M Ribeiro, David Rimm, Anne Vincent-Salomon, Joel Saltz, Shahin Sayed, Evangelos Hytopoulos, Sarah Mahon, Kalliopi P Siziopikou, Christos Sotiriou, Albrecht Stenzinger, Maher A Sughayer, Daniel Sur, Fraser Symmans, Sunao Tanaka, Timothy Taxter, Sabine Tejpar, Jonas Teuwen, E Aubrey Thompson, Trine Tramm, William T Tran, Jeroen Van Der Laak, Gregory E Verghese, Giuseppe Viale, Noorul Wahab, Thomas Walter, Yannick Waumans, Hannah Y Wen, Wentao Yang, Yinyin Yuan, John Bartlett, Sibylle Loibl, Carsten Denkert, Peter Savas, Sherene Loi, Elisabeth Specht Stovgaard, Roberto Salgado, William M Gallagher, Arman Rahman

Faculty, Staff and Student Publications

Recent advances in the field of immuno-oncology have brought transformative changes in the management of cancer patients. The immune profile of tumours has been found to have key value in predicting disease prognosis and treatment response in various cancers. Multiplex immunohistochemistry and immunofluorescence have emerged as potent tools for the simultaneous detection of multiple protein biomarkers in a single tissue section, thereby expanding opportunities for molecular and immune profiling while preserving tissue samples. By establishing the phenotype of individual tumour cells when distributed within a mixed cell population, the identification of clinically relevant biomarkers with high-throughput multiplex immunophenotyping of tumour …

Desirability Of Outcome Ranking For Obstetrical Trials: Illustration And Application To The Arrive Trial, Grecio J Sandoval, William A Grobman, Scott R Evans, Madeline M Rice, Rebecca G Clifton, Suneet P Chauhan, Maged M Costantine, Kelly S Gibson, Monica Longo, Torri D Metz, Emily S Miller, Samuel Parry, Uma M Reddy, Dwight J Rouse, Hyagriv N Simhan, John M Thorp, Alan T N Tita, George R Saade

Faculty, Staff and Student Publications

BACKGROUND: In randomized trials, 1 primary outcome is typically chosen to evaluate the consequences of an intervention, whereas other important outcomes are relegated to secondary outcomes. This issue is amplified for many obstetrical trials in which an intervention may have consequences for both the pregnant person and the child. In contrast, desirability of outcome ranking, a paradigm shift for the design and analysis of clinical trials based on patient-centric evaluation, allows multiple outcomes-including from >1 individual-to be considered concurrently.

OBJECTIVE: This study aimed to describe desirability of outcome ranking methodology tailored to obstetrical trials and to apply the methodology to …

The Hyphal-Specific Toxin Candidalysin Promotes Fungal Gut Commensalism, Shen-Huan Liang, Shabnam Sircaik, Joseph Dainis, Pallavi Kakade, Swathi Penumutchu, Liam D Mcdonough, Ying-Han Chen, Corey Frazer, Tim B Schille, Stefanie Allert, Osama Elshafee, Maria Hänel, Selene Mogavero, Shipra Vaishnava, Ken Cadwell, Peter Belenky, J Christian Perez, Bernhard Hube, Iuliana V Ene, Richard J Bennett

Faculty, Staff and Student Publications

The fungus Candida albicans frequently colonizes the human gastrointestinal tract, from which it can disseminate to cause systemic disease. This polymorphic species can transition between growing as single-celled yeast and as multicellular hyphae to adapt to its environment. The current dogma of C. albicans commensalism is that the yeast form is optimal for gut colonization, whereas hyphal cells are detrimental to colonization but critical for virulence

Watching The Fall Of Roe V Wade: Media Exposure Relates To Us Women's Alcohol Use Intentions, Stacy M Post, Mary C Jobe, Arianne N Malekzadeh, Katarina E Aubuchon, Rebecca K Hoffman, Michelle L Stock, Lisa Bowleg

Faculty, Staff and Student Publications

OBJECTIVE: The Supreme Court of the United States’ decision in Dobbs v. Jackson Women’s Health Organization in June 2022 overturned Roe v. Wade and ended federal protection of abortion rights. Given the drastic policy changes as a result of the ruling and high exposure to media related to abortion, women opposed to the decision may have experienced distress, which could trigger maladaptive coping strategies, such as alcohol use. The present research examined how consuming abortion-related media in the weeks following the Dobbs decision impacted alcohol use intentions among women of reproductive age residing in the 13 “trigger law” states that …

Artificial Intelligence-Based Radiotherapy Contouring And Planning To Improve Global Access To Cancer Care, Laurence E Court, Ajay Aggarwal, Anuja Jhingran, Komeela Naidoo, Tucker Netherton, Adenike Olanrewaju, Christine Peterson, Jeannette Parkes, Hannah Simonds, Christoph Trauernicht, Lifei Zhang, Beth M Beadle, Radiation Planning Assistant Consortium Collaborators, Affiliations Expand

Faculty, Staff and Student Publications

PURPOSE: Increased automation has been identified as one approach to improving global cancer care. The Radiation Planning Assistant (RPA) is a web-based tool offering automated radiotherapy (RT) contouring and planning to low-resource clinics. In this study, the RPA workflow and clinical acceptability were assessed by physicians around the world.

METHODS: The RPA output for 75 cases was reviewed by at least three physicians; 31 radiation oncologists at 16 institutions in six countries on five continents reviewed RPA contours and plans for clinical acceptability using a 5-point Likert scale.

RESULTS: For cervical cancer, RPA plans using bony landmarks were scored as …

Normative Modelling Of Brain Morphometry Across The Lifespan With Centilebrain: Algorithm Benchmarking And Model Optimisation, Ruiyang Ge, Yuetong Yu, Yi Xuan Qi, Yu-Nan Fan, Shiyu Chen, Chuntong Gao, Shalaila S Haas, Faye New, Dorret I Boomsma, Henry Brodaty, Rachel M Brouwer, Randy Buckner, Xavier Caseras, Fabrice Crivello, Eveline A Crone, Susanne Erk, Simon E Fisher, Barbara Franke, David C Glahn, Udo Dannlowski, Dominik Grotegerd, Oliver Gruber, Hilleke E Hulshoff Pol, Gunter Schumann, Christian K Tamnes, Henrik Walter, Lara M Wierenga, Neda Jahanshad, Paul M Thompson, Sophia Frangou, Enigma Lifespan Working Group

Faculty, Staff and Student Publications

The value of normative models in research and clinical practice relies on their robustness and a systematic comparison of different modelling algorithms and parameters; however, this has not been done to date. We aimed to identify the optimal approach for normative modelling of brain morphometric data through systematic empirical benchmarking, by quantifying the accuracy of different algorithms and identifying parameters that optimised model performance. We developed this framework with regional morphometric data from 37 407 healthy individuals (53% female and 47% male; aged 3-90 years) from 87 datasets from Europe, Australia, the USA, South Africa, and east Asia following a …

Heterozygous Loss-Of-Function Variants In Dock4 Cause Neurodevelopmental Delay And Microcephaly., Charlotte Herbst, Viktoria Bothe, Meret Wegler, Susanne Axer-Schaefer, Séverine Audebert-Bellanger, Jozef Gecz, Benjamin Cogne, Hagit Baris Feldman, Anselm H C Horn, Anna C E Hurst, Melissa A. Kelly, Michael C. Kruer, Alina Kurolap, Annie Laquerriere, Megan Li, Paul R. Mark, Markus Morawski, Mathilde Nizon, Tomi Pastinen, Tilman Polster, Pascale Saugier-Veber, Jang Sesong, Heinrich Sticht, Jens T. Stieler, Isabelle Thiffault, Clare L. Van Eyk, Pascale Marcorelles, Myriam Vezain-Mouchard, Rami Abou Jamra, Henry Oppermann

Manuscripts, Articles, Book Chapters and Other Papers

Neurons form the basic anatomical and functional structure of the nervous system, and defects in neuronal differentiation or formation of neurites are associated with various psychiatric and neurodevelopmental disorders. Dynamic changes in the cytoskeleton are essential for this process, which is, inter alia, controlled by the dedicator of cytokinesis 4 (DOCK4) through the activation of RAC1. Here, we clinically describe 7 individuals (6 males and one female) with variants in DOCK4 and overlapping phenotype of mild to severe global developmental delay. Additional symptoms include coordination or gait abnormalities, microcephaly, nonspecific brain malformations, hypotonia and seizures. Four individuals carry missense variants …

Mechanisms Of Sleep Disturbances In Long-Term Cancer Survivors: A Childhood Cancer Survivor Study Report, Lauren C Daniel, Huiqi Wang, Tara M Brinkman, Kathy Ruble, Eric S Zhou, Oxana Palesh, Robyn Stremler, Rebecca Howell, Daniel A Mulrooney, Valerie M Crabtree, Sogol Mostoufi-Moab, Kevin Oeffinger, Joseph Neglia, Yutaka Yasui, Gregory T Armstrong, Kevin Krull

Faculty, Staff and Student Publications

Background: Sleep problems following childhood cancer treatment may persist into adulthood, exacerbating cancer-related late effects and putting survivors at risk for poor physical and psychosocial functioning. This study examines sleep in long-term survivors and their siblings to identify risk factors and disease correlates.

Methods: Childhood cancer survivors (≥5 years from diagnosis; n = 12 340; 51.5% female; mean [SD] age = 39.4 [9.6] years) and siblings (n = 2395; 57.1% female; age = 44.6 [10.5] years) participating in the Childhood Cancer Survivor Study completed the Pittsburgh Sleep Quality Index (PSQI). Multivariable Poisson-error generalized estimating equation compared prevalence of binary sleep …

Energetic Trade-Offs In Migration Decision-Making, Reproductive Effort And Subsequent Parental Care In A Long-Distance Migratory Bird, Alexander R Schindler, Anthony D Fox, Christopher K Wikle, Bart M Ballard, Alyn J Walsh, Seán B A Kelly, Lei Cao, Larry R Griffin, Mitch D Weegman

Faculty, Staff and Student Publications

Migratory species trade-off long-distance movement with survival and reproduction, but the spatio-temporal scales at which these decisions occur are relatively unknown. Technological and statistical advances allow fine-scale study of animal decision-making, improving our understanding of possible causes and therefore conservation management. We quantified effects of reproductive preparation during spring migration on subsequent breeding outcomes, breeding outcomes on autumn migration characteristics and autumn migration characteristics on subsequent parental survival in Greenland white-fronted geese (

Epigenome-Wide Association Study Identifies Neonatal Dna Methylation Associated With Two-Year Attention Problems In Children Born Very Preterm., Marie Camerota, Barry M. Lester, Francisco Xavier Castellanos, Brian S. Carter, Jennifer Check, Jennifer Helderman, Julie A. Hofheimer, Elisabeth C. Mcgowan, Charles R. Neal, Steven L. Pastyrnak, Lynne M. Smith, Thomas Michael O'Shea, Carmen J. Marsit, Todd M. Everson

Manuscripts, Articles, Book Chapters and Other Papers

Prior research has identified epigenetic predictors of attention problems in school-aged children but has not yet investigated these in young children, or children at elevated risk of attention problems due to preterm birth. The current study evaluated epigenome-wide associations between neonatal DNA methylation and attention problems at age 2 years in children born very preterm. Participants included 441 children from the Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI) Study, a multi-site study of infants born < 30 weeks gestational age. DNA methylation was measured from buccal swabs collected at NICU discharge using the Illumina MethylationEPIC Bead Array. Attention problems were assessed at 2 years of adjusted age using the attention problems subscale of the Child Behavior Checklist (CBCL). After adjustment for multiple testing, DNA methylation at 33 CpG sites was associated with child attention problems. Differentially methylated CpG sites were located in genes previously linked to physical and mental health, including several genes associated with ADHD in prior epigenome-wide and genome-wide association studies. Several CpG sites were located in genes previously linked to exposure to prenatal risk factors in the NOVI sample. Neonatal epigenetics measured at NICU discharge could be useful in identifying preterm children at risk for long-term attention problems and related psychiatric disorders, who could benefit from early prevention and intervention efforts.

Estrogen Signaling In The Dorsal Raphe Regulates Binge-Like Drinking In Mice, Valeria C Torres Irizarry, Bing Feng, Xiaohua Yang, Nirali Patel, Sarah Schaul, Lucas Ibrahimi, Hui Ye, Pei Luo, Leslie Carrillo-Sáenz, Penghua Lai, Maya Kota, Devin Dixit, Chunmei Wang, Amy W Lasek, Yanlin He, Pingwen Xu

Faculty, Staff and Students Publications

Estrogens promote binge alcohol drinking and contribute to sex differences in alcohol use disorder. However, the mechanisms are largely unknown. This study aims to test if estrogens act on 5-hydroxytryptamine neurons in the dorsal raphe nucleus (5-HTDRN) to promote binge drinking. We found that female mice drank more alcohol than male mice in chronic drinking in the dark (DID) tests. This sex difference was associated with distinct alterations in mRNA expression of estrogen receptor α (ERα) and 5-HT-related genes in the DRN, suggesting a potential role of estrogen/ERs/5-HT signaling. In supporting this view, 5-HTDRN neurons from naïve male mice had …

Racial Discrimination, Knowledge, And Health Outcomes: The Mediating Role Of Hepatitis B-Related Stigma Among Patients With Chronic Hepatitis B, Julia G. Katcher, Ann C. Klassen, Hie-Won Hann, Mimi Chang, Hee-Soon Juon

Department of Medical Oncology Faculty Papers

It is well described in current literature that Hepatitis B virus (HBV) affects Asian Americans more than any other racial group in the United States and that there is a stigma attached to this condition. The effects of stigma can be lasting, penetrating physiologically and psychologically, yet few studies have focused on the consequences of this phenomenon. The purpose of this study was to examine the mediating role of stigma in the effect of racial discrimination and knowledge (of HBV sequelae) on health status of Korean Americans with chronic hepatitis B (CHB). Three hundred sixty-five CHB patients were recruited and …

Multivalent Cytomegalovirus Glycoprotein B Nucleoside Modified Mrna Vaccines Did Not Demonstrate A Greater Antibody Breadth, Hsuan-Yuan Wang, Leike Li, Cody S Nelson, Richard Barfield, Sarah Valencia, Cliburn Chan, Hiromi Muramatsu, Paulo J C Lin, Norbert Pardi, Zhiqiang An, Drew Weissman, Sallie R Permar

Faculty, Staff and Student Publications

Human cytomegalovirus (HCMV) remains the most common congenital infection and infectious complication in immunocompromised patients. The most successful HCMV vaccine to date, an HCMV glycoprotein B (gB) subunit vaccine adjuvanted with MF59, achieved 50% efficacy against primary HCMV infection. A previous study demonstrated that gB/MF59 vaccinees were less frequently infected with HCMV gB genotype strains most similar to the vaccine strain than strains encoding genetically distinct gB genotypes, suggesting strain-specific immunity accounted for the limited efficacy. To determine whether vaccination with multiple HCMV gB genotypes could increase the breadth of anti-HCMV gB humoral and cellular responses, we immunized 18 female …

Inhibition Of Csf1r And Kit With Pexidartinib Reduces Inflammatory Signaling And Cell Viability In Endometriosis, Timothy N Dunn, Dominique I Cope, Suni Tang, Tirupataiah Sirupangi, Sydney E Parks, Zian Liao, Fei Yuan, Chad J Creighton, Ramya P Masand, Linda Alpuing Radilla, Xiaoming Guan, Laura Detti, Diana Monsivais, Martin M Matzuk

Faculty, Staff and Students Publications

Endometriosis is a common and debilitating disease, affecting ∼170 million women worldwide. Affected patients have limited therapeutic options such as hormonal suppression or surgical excision of the lesions, though therapies are often not completely curative. Targeting receptor tyrosine kinases (RTKs) could provide a nonhormonal treatment option for endometriosis. We determined that 2 RTKs, macrophage-colony stimulating factor 1 receptor (CSF1R) and mast/stem cell growth factor receptor KIT (KIT), are overexpressed in endometriotic lesions and could be novel nonhormonal therapeutic targets for endometriosis. The kinase activity of CSF1R and KIT is suppressed by pexidartinib, a small molecule inhibitor that was recently approved …

Novel Ancestry-Specific Primary Open-Angle Glaucoma Loci And Shared Biology With Vascular Mechanisms And Cell Proliferation, Valeria Lo Faro, Arjun Bhattacharya, Wei Zhou, Dan Zhou, Ying Wang, Kristi Läll, Masahiro Kanai, Esteban Lopera-Maya, Peter Straub, Priyanka Pawar, Ran Tao, Xue Zhong, Shinichi Namba, Global Biobank Meta-Analysis Initiative, Serena Sanna, Ilja M Nolte, Yukinori Okada, Nathan Ingold, Stuart Macgregor, Harold Snieder, Ida Surakka, Jonathan Shortt, Chris Gignoux, Nicholas Rafaels, Kristy Crooks, Anurag Verma, Shefali S Verma, Lindsay Guare, Daniel J Rader, Cristen Willer, Alicia R Martin, Milam A Brantley, Eric R Gamazon, Nomdo M Jansonius, Karen Joos, Nancy J Cox, Jibril Hirbo

Faculty, Staff and Student Publications

Primary open-angle glaucoma (POAG), a leading cause of irreversible blindness globally, shows disparity in prevalence and manifestations across ancestries. We perform meta-analysis across 15 biobanks (of the Global Biobank Meta-analysis Initiative) (n = 1,487,441: cases = 26,848) and merge with previous multi-ancestry studies, with the combined dataset representing the largest and most diverse POAG study to date (n = 1,478,037: cases = 46,325) and identify 17 novel significant loci, 5 of which were ancestry specific. Gene-enrichment and transcriptome-wide association analyses implicate vascular and cancer genes, a fifth of which are primary ciliary related. We perform an extensive statistical analysis of …

Sodium Oligomannate Alters Gut Microbiota, Reduces Cerebral Amyloidosis And Reactive Microglia In A Sex-Specific Manner, Megan E Bosch, Choonghee Lee, Aishwarya Nambiar, Samira Parhizkar, Marie L Laury, David M Holtzman, Et Al.

2020-Current year OA Pubs

It has recently become well-established that there is a connection between Alzheimer's disease pathology and gut microbiome dysbiosis. We have previously demonstrated that antibiotic-mediated gut microbiota perturbations lead to attenuation of Aβ deposition, phosphorylated tau accumulation, and disease-associated glial cell phenotypes in a sex-dependent manner. In this regard, we were intrigued by the finding that a marine-derived oligosaccharide, GV-971, was reported to alter gut microbiota and reduce Aβ amyloidosis in the 5XFAD mouse model that were treated at a point when Aβ burden was near plateau levels. Utilizing comparable methodologies, but with distinct technical and temporal features, we now report …

Neoadjuvant Trebananib Plus Paclitaxel-Based Chemotherapy For Stage Ii/Iii Breast Cancer In The Adaptively Randomized I-Spy2 Trial-Efficacy And Biomarker Discovery, Kathy S Albain, Christina Yau, Emanuel F Petricoin, Denise M Wolf, Julie E Lang, A Jo Chien, Tufia Haddad, Andres Forero-Torres, Anne M Wallace, Henry Kaplan, Lajos Pusztai, David Euhus, Rita Nanda, Anthony D Elias, Amy S Clark, Constantine Godellas, Judy C Boughey, Claudine Isaacs, Debu Tripathy, Janice Lu, Rachel L Yung, Rosa I Gallagher, Julia D Wulfkuhle, Lamorna Brown-Swigart, Gregor Krings, Yunn Yi Chen, David A Potter, Erica Stringer-Reasor, Sarah Blair, Smita M Asare, Amy Wilson, Gillian L Hirst, Ruby Singhrao, Meredith Buxton, Julia L Clennell, Ashish Sanil, Scott Berry, Adam L Asare, Jeffrey B Matthews, Angela M Demichele, Nola M Hylton, Michelle Melisko, Jane Perlmutter, Hope S Rugo, W Fraser Symmans, Laura J Van't Veer, Douglas Yee, Donald A Berry, Laura J Esserman

Faculty, Staff and Student Publications

Purpose: The neutralizing peptibody trebananib prevents angiopoietin-1 and angiopoietin-2 from binding with Tie2 receptors, inhibiting angiogenesis and proliferation. Trebananib was combined with paclitaxel±trastuzumab in the I-SPY2 breast cancer trial.

Patients and methods: I-SPY2, a phase II neoadjuvant trial, adaptively randomizes patients with high-risk, early-stage breast cancer to one of several experimental therapies or control based on receptor subtypes as defined by hormone receptor (HR) and HER2 status and MammaPrint risk (MP1, MP2). The primary endpoint is pathologic complete response (pCR). A therapy "graduates" if/when it achieves 85% Bayesian probability of success in a phase III trial within a given subtype. …

High Resolution Spatial Profiling Of Kidney Injury And Repair Using Rna Hybridization-Based In Situ Sequencing, Haojia Wu, Eryn E Dixon, Qiao Xuanyuan, Juanru Guo, Yasuhiro Yoshimura, Chitnis Debashish, Anezka Niesnerova, Hao Xu, Morgane Rouault, Benjamin D Humphreys

2020-Current year OA Pubs

Emerging spatially resolved transcriptomics technologies allow for the measurement of gene expression in situ at cellular resolution. We apply direct RNA hybridization-based in situ sequencing (dRNA HybISS, Cartana part of 10xGenomics) to compare male and female healthy mouse kidneys and the male kidney injury and repair timecourse. A pre-selected panel of 200 genes is used to identify cell state dynamics patterns during injury and repair. We develop a new computational pipeline, CellScopes, for the rapid analysis, multi-omic integration and visualization of spatially resolved transcriptomic datasets. The resulting dataset allows us to resolve 13 kidney cell types within distinct kidney niches, …

Secretory Leukocyte Protease Inhibitor Protects Against Severe Urinary Tract Infection In Mice, Anne L Rosen, Michael A Lint, Dayne H Voelker, Nicole M Gilbert, Christopher P Tomera, Jesús Santiago-Borges, Meghan A Wallace, Thomas J Hannan, Carey-Ann D Burnham, Scott J Hultgren, Andrew L Kau

2020-Current year OA Pubs

Millions suffer from urinary tract infections (UTIs) worldwide every year with women accounting for the majority of cases. Uropathogenic

Frequency Specific Optogenetic Stimulation Of The Locus Coeruleus Induces Task-Relevant Plasticity In The Motor Cortex, Ching-Tzu Tseng, Hailey F Welch, Ashley L Gi, Erica Mina Kang, Tanushree Mamidi, Sahiti Pydimarri, Kritika Ramesh, Alfredo Sandoval, Jonathan E Ploski, Catherine A Thorn

Faculty, Staff and Student Publications

The locus ceruleus (LC) is the primary source of neocortical noradrenaline, which is known to be involved in diverse brain functions including sensory perception, attention, and learning. Previous studies have shown that LC stimulation paired with sensory experience can induce task-dependent plasticity in the sensory neocortex and in the hippocampus. However, it remains unknown whether LC activation similarly impacts neural representations in the agranular motor cortical regions that are responsible for movement planning and production. In this study, we test whether optogenetic stimulation of the LC paired with motor performance is sufficient to induce task-relevant plasticity in the somatotopic cortical …

Pediatric Spinal Ependymoma With Chromothripsis Of Chromosome 6: A Case Report And Review Of The Literature., Keela R. Scott, Melissa Gener, Elena Repnikova

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Ependymomas are the third most common central nervous system tumor in the pediatric population; however, spinal ependymomas in children are rare. Ependymomas affecting the spinal cord most frequently occur in adults of 20-40 years of age. The current World Health Organization classification system for ependymomas is now composed of ten different entities based on histopathology, location, and molecular studies, with evidence that the new classification system more accurately predicts clinical outcomes.

CASE PRESENTATION: We present the case of a 16-year-old Caucasian female patient with a history of type 2 neurofibromatosis with multiple schwannomas, meningioma, and spinal ependymoma. Chromosome analysis …

Sex-Dependent Effects Of Chronic Circadian Disruption In Aβpp/Ps1 Mice., Jesse Britz, Emmanuel Ojo, Nazmul Haque, Asmita Dhukhwa, Erin R Hascup, Kevin N Hascup, Shelley A Tischkau

Articles

BACKGROUND: Chronic disruption of the circadian timing system, often reflected as a loss of restful sleep, also includes myriad other pathophysiological effects.

OBJECTIVE: The current study examined how chronic circadian disruption (CD) could contribute to pathology and rate of progression in the AβPP/PS1 mouse model of Alzheimer's disease (AD).

METHODS: A chronic CD was imposed until animals reached 6 or 12 months of age in AβPP/PS1 and C57BL/6J control mice. Home cage activity was monitored for a period of 3-4 weeks prior to the endpoint along with a single timepoint measure of glucose sensitivity. To assess long term effects of …

Impact Of An Integrated Health, Nutrition, And Early Child Stimulation And Responsive Care Intervention Package Delivered To Preterm Or Term Small For Gestational Age Babies During Infancy On Growth And Neurodevelopment: Study Protocol Of An Individually Randomized Controlled Trial In India (Small Babies Trial), Ranadip Chowdhury, Rukman Manapurath, Ingvild Fossgard Sandøy, Ravi Prakash Upadhyay, Neeta Dhabhai, Saijuddin Shaikh, Harish Chellani, Tarun Shankar Choudhary, Abhinav Jain, Jose Martines, Nita Bhandari, Tor A Strand, Sunita Taneja

Faculty, Staff and Student Publications

BACKGROUND: Preterm and term small for gestational age (SGA) babies are at high risk of experiencing malnutrition and impaired neurodevelopment. Standalone interventions have modest and sometimes inconsistent effects on growth and neurodevelopment in these babies. For greater impact, intervention may be needed in multiple domains-health, nutrition, and psychosocial care and support. Therefore, the combined effects of an integrated intervention package for preterm and term SGA on growth and neurodevelopment are worth investigating.

METHODS: An individually randomized controlled trial is being conducted in urban and peri-urban low to middle-socioeconomic neighborhoods in South Delhi, India. Infants are randomized (1:1) into two strata …

Development And Validation Of The American Heart Association's Prevent Equations, Sadiya S Khan, Kunihiro Matsushita, Yingying Sang, Shoshana H Ballew, Morgan E Grams, Aditya Surapaneni, Michael J Blaha, April P Carson, Alexander R Chang, Elizabeth Ciemins, Alan S Go, Orlando M Gutierrez, Shih-Jen Hwang, Simerjot K Jassal, Csaba P Kovesdy, Donald M Lloyd-Jones, Michael G Shlipak, Latha P Palaniappan, Laurence Sperling, Salim S Virani, Katherine Tuttle, Ian J Neeland, Sheryl L Chow, Janani Rangaswami, Michael J Pencina, Chiadi E Ndumele, Josef Coresh, Chronic Kidney Disease Prognosis Consortium And The American Heart Association Cardiovascular-Kidney-Metabolic Science Advisory Group

Faculty, Staff and Students Publications

BACKGROUND: Multivariable equations are recommended by primary prevention guidelines to assess absolute risk of cardiovascular disease (CVD). However, current equations have several limitations. Therefore, we developed and validated the American Heart Association Predicting Risk of CVD EVENTs (PREVENT) equations among US adults 30 to 79 years of age without known CVD.

METHODS: The derivation sample included individual-level participant data from 25 data sets (N=3 281 919) between 1992 and 2017. The primary outcome was CVD (atherosclerotic CVD and heart failure). Predictors included traditional risk factors (smoking status, systolic blood pressure, cholesterol, antihypertensive or statin use, and diabetes) and estimated glomerular …

The Novel Phosphatase Nudt5 Is A Critical Regulator Of Triple-Negative Breast Cancer Growth, Jing Qian, Yanxia Ma, William M Tahaney, Cassandra L Moyer, Amanda Lanier, Jamal Hill, Darian Coleman, Negar Koupaei, Susan G Hilsenbeck, Michelle I Savage, Brent D G Page, Abhijit Mazumdar, Powel H Brown

Faculty, Staff and Student Publications

BACKGROUND: The most aggressive form of breast cancer is triple-negative breast cancer (TNBC), which lacks expression of the estrogen receptor (ER) and progesterone receptor (PR), and does not have overexpression of the human epidermal growth factor receptor 2 (HER2). Treatment options for women with TNBC tumors are limited, unlike those with ER-positive tumors that can be treated with hormone therapy, or those with HER2-positive tumors that can be treated with anti-HER2 therapy. Therefore, we have sought to identify novel targeted therapies for TNBC. In this study, we investigated the potential of a novel phosphatase, NUDT5, as a potential therapeutic target …

Hospital-Level Nicu Capacity, Utilization, And 30-Day Outcomes In Texas, David C Goodman, Patrick Stuchlik, Cecilia Ganduglia-Cazaban, Jon E Tyson, Joanna Leyenaar, Elenir B C Avritscher, Mathew Rysavy, Kanekal S Gautham, David Lynch, Therese A Stukel

Faculty, Staff and Student Publications

IMPORTANCE: Risk-adjusted neonatal intensive care unit (NICU) utilization and outcomes vary markedly across regions and hospitals. The causes of this variation are poorly understood.

OBJECTIVE: To assess the association of hospital-level NICU bed capacity with utilization and outcomes in newborn cohorts with differing levels of health risk.

DESIGN, SETTING, AND PARTICIPANTS: This population-based retrospective cohort study included all Medicaid-insured live births in Texas from 2010 to 2014 using linked vital records and maternal and newborn claims data. Participants were Medicaid-insured singleton live births (LBs) with birth weights of at least 400 g and gestational ages between 22 and 44 weeks. …

Viral Dnaemia And Dna Virus Seropositivity And Mortality In Pediatric Sepsis, Stephanie S Cabler, Gregory A Storch, Andrew H Walton, John C Lin, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Sepsis is a leading cause of pediatric mortality. Little attention has been paid to the association between viral DNA and mortality in children and adolescents with sepsis.

OBJECTIVE: To assess the association of the presence of viral DNA with sepsis-related mortality in a large multicenter study.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study compares pediatric patients with and without plasma cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus 1 (HSV-1), human herpesvirus 6 (HHV-6), parvovirus B19 (B19V), BK polyomavirus (BKPyV), human adenovirus (HAdV), and torque teno virus (TTV) DNAemia detected by quantitative real-time polymerase chain reaction or plasma IgG …

Evaluation Of A Tiered Opioid Prescription Algorithm In An Eras Pathway: Exploring Opportunities For Further Refinement, M Sol Basabe, Tina S Suki, Mark F Munsell, Maria D Iniesta, Juan E Garcia Lopez, Robert Tyler Hillman, Katherine Cain, Sarah Huepenbecker, Gabriel Mena, Jolyn S Taylor, Pedro T Ramirez, Larissa A Meyer

Faculty, Staff and Student Publications

Background: Opioid over-prescription is wasteful and contributes to the opioid crisis. We implemented a personalized tiered discharge opioid protocol and education on opioid disposal to minimize over-prescription.

Objective: To evaluate the intervention by investigating opioid use post-discharge for women undergoing abdomino-pelvic surgery, and patient adherence to opioid disposal education.

Methods: We analyzed post-discharge opioid consumption among 558 patients. Eligible patients included those who underwent elective gynecologic surgery, were not taking scheduled opioids pre-operatively, and received discharge opioids according to a tiered prescribing algorithm. A survey assessing discharge opioid consumption and disposal safety knowledge was distributed on post-discharge day 21. Over-prescription …

Gestational Diabetes Augments Group B Streptococcus Infection By Disrupting Maternal Immunity And The Vaginal Microbiota, Vicki Mercado-Evans, Marlyd E Mejia, Jacob J Zulk, Samantha Ottinger, Zainab A Hameed, Camille Serchejian, Madelynn G Marunde, Clare M Robertson, Mallory B Ballard, Simone H Ruano, Natalia Korotkova, Anthony R Flores, Kathleen A Pennington, Kathryn A Patras

Faculty, Staff and Student Publications

Group B Streptococcus (GBS) is a pervasive perinatal pathogen, yet factors driving GBS dissemination in utero are poorly defined. Gestational diabetes mellitus (GDM), a complication marked by dysregulated immunity and maternal microbial dysbiosis, increases risk for GBS perinatal disease. Using a murine GDM model of GBS colonization and perinatal transmission, we find that GDM mice display greater GBS in utero dissemination and subsequently worse neonatal outcomes. Dual-RNA sequencing reveals differential GBS adaptation to the GDM reproductive tract, including a putative glycosyltransferase (yfhO), and altered host responses. GDM immune disruptions include reduced uterine natural killer cell activation, impaired recruitment to placentae, …

Prenatal Exposure To Maternal Disadvantage-Related Inflammatory Biomarkers: Associations With Neonatal White Matter Microstructure, Ashley F P Sanders, Brian Tirado, Nicole A Seider, Regina L Triplett, Rachel E Lean, Jeffrey J Neil, J Philip Miller, Rebecca Tillman, Tara A Smyser, Deanna M Barch, Joan L Luby, Cynthia E Rogers, Christopher D Smyser, Barbara B Warner, Et Al.

2020-Current year OA Pubs

Prenatal exposure to heightened maternal inflammation has been associated with adverse neurodevelopmental outcomes, including atypical brain maturation and psychiatric illness. In mothers experiencing socioeconomic disadvantage, immune activation can be a product of the chronic stress inherent to such environmental hardship. While growing preclinical and clinical evidence has shown links between altered neonatal brain development and increased inflammatory states in utero, the potential mechanism by which socioeconomic disadvantage differentially impacts neural-immune crosstalk remains unclear. In the current study, we investigated associations between socioeconomic disadvantage, gestational inflammation, and neonatal white matter microstructure in 320 mother-infant dyads over-sampled for poverty. We analyzed maternal …