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Consensus Subtypes Of Hepatocellular Carcinoma Associated With Clinical Outcomes And Genomic Phenotypes, Sung Hwan Lee, Sun Young Yim, Yun Seong Jeong, Qi-Xiang Li, Sang-Hee Kang, Bo Hwa Sohn, Shwetha V Kumar, Ji-Hyun Shin, You Rhee Choi, Jae-Jun Shim, Hayeon Kim, Ji Hoon Kim, Shin Kim, Sheng Guo, Randy L Johnson, Ahmed Kaseb, Koo Jeong Kang, Yun Shin Chun, Hee Jin Jang, Byoung Gill Lee, Hyun Goo Woo, Min Jin Ha, Rehan Akbani, Lewis R Roberts, David A Wheeler, Ju-Seog Lee Dec 2022

Consensus Subtypes Of Hepatocellular Carcinoma Associated With Clinical Outcomes And Genomic Phenotypes, Sung Hwan Lee, Sun Young Yim, Yun Seong Jeong, Qi-Xiang Li, Sang-Hee Kang, Bo Hwa Sohn, Shwetha V Kumar, Ji-Hyun Shin, You Rhee Choi, Jae-Jun Shim, Hayeon Kim, Ji Hoon Kim, Shin Kim, Sheng Guo, Randy L Johnson, Ahmed Kaseb, Koo Jeong Kang, Yun Shin Chun, Hee Jin Jang, Byoung Gill Lee, Hyun Goo Woo, Min Jin Ha, Rehan Akbani, Lewis R Roberts, David A Wheeler, Ju-Seog Lee

Faculty, Staff and Student Publications

BACKGROUND AND AIMS: Although many studies revealed transcriptomic subtypes of HCC, concordance of the subtypes are not fully examined. We aim to examine a consensus of transcriptomic subtypes and correlate them with clinical outcomes.

APPROACH AND RESULTS: By integrating 16 previously established genomic signatures for HCC subtypes, we identified five clinically and molecularly distinct consensus subtypes. STM (STeM) is characterized by high stem cell features, vascular invasion, and poor prognosis. CIN (Chromosomal INstability) has moderate stem cell features, but high genomic instability and low immune activity. IMH (IMmune High) is characterized by high immune activity. BCM (Beta-Catenin with high Male …


Cerebrovascular Reactivity Mapping Using Resting-State Functional Mri In Patients With Gliomas, Mei-Yu Yeh, Henry S Chen, Ping Hou, Vinodh A Kumar, Jason M Johnson, Kyle R Noll, Sujit S Prabhu, Sherise D Ferguson, Donald F Schomer, Hsu-Hsia Peng, Ho-Ling Liu Dec 2022

Cerebrovascular Reactivity Mapping Using Resting-State Functional Mri In Patients With Gliomas, Mei-Yu Yeh, Henry S Chen, Ping Hou, Vinodh A Kumar, Jason M Johnson, Kyle R Noll, Sujit S Prabhu, Sherise D Ferguson, Donald F Schomer, Hsu-Hsia Peng, Ho-Ling Liu

Faculty, Staff and Student Publications

Background: Recently, a data-driven regression analysis method was developed to utilize the resting-state (rs) blood oxygenation level-dependent signal for cerebrovascular reactivity (CVR) mapping (rs-CVR), which was previously optimized by comparing with the CO2 inhalation-based method in health subjects and patients with neurovascular diseases.

Purpose: To investigate the agreement of rs-CVR and the CVR mapping with breath-hold MRI (bh-CVR) in patients with gliomas.

Study type: Retrospective.

Population: Twenty-five patients (12 males, 13 females; mean age ± SD, 48 ± 13 years) with gliomas.

Field strength/sequence: Dynamic T2*-weighted gradient-echo echo-planar imaging during a breath-hold paradigm and during the rs on a 3-T …


Standards For Evaluating Neonatal Growth Outcomes Using Individualized Pathological Growth Potential Realization Indices, Russell L Deter, Wesley Lee, Roberto Romero Dec 2022

Standards For Evaluating Neonatal Growth Outcomes Using Individualized Pathological Growth Potential Realization Indices, Russell L Deter, Wesley Lee, Roberto Romero

Faculty, Staff and Students Publications

OBJECTIVE: Provide standards for detecting neonatal growth abnormalities with the average pathological Growth Potential Realization Index (av. pGPRI).

METHODS: Individualized Growth Assessment (IGA) evaluations of 117 neonates with normal growth outcomes were carried out using measurements of WT, HC, AC, ThC and CHL. Growth Potential Realization Index (GPRI) values for each parameter were calculated from predicted and actual birth measurements, the former obtained using Rossavik size models derived from the second-trimester growth potential estimates. Subtraction of either the upper and lower boundaries of GPRI reference ranges from these GPRI measurements gave + pGPRI and - pGPRI measurements. GPRI's within their …


Avpcancerfree: Impact Of A Digital Behavior Change Intervention On Parental Hpv Vaccine –Related Perceptions And Behaviors, Ross Shegog, Lara S Savas, C Mary Healy, Erica L Frost, Sharon P Coan, Efrat K Gabay, Sharice M Preston, Stanley W Spinner, Mathew Wilbur, Elisabeth Becker, Travis Teague, Sally W Vernon Nov 2022

Avpcancerfree: Impact Of A Digital Behavior Change Intervention On Parental Hpv Vaccine –Related Perceptions And Behaviors, Ross Shegog, Lara S Savas, C Mary Healy, Erica L Frost, Sharon P Coan, Efrat K Gabay, Sharice M Preston, Stanley W Spinner, Mathew Wilbur, Elisabeth Becker, Travis Teague, Sally W Vernon

Faculty, Staff and Student Publications

Parent hesitancy contributes to reduced HPV vaccination rates. The HPVcancerfree app (HPVCF) was designed to assist parents in making evidence-based decisions regarding HPV vaccination. This study examined if parents of vaccine-eligible youth (11-12 yrs.) who use HPVCF in addition to usual care demonstrate significantly more positive intentions and attitudes toward HPV vaccination and greater HPV vaccination rates compared to those not using HPVCF. Clinics (n = 51) within a large urban pediatric network were randomly assigned to treatment (HPVCF + usual care) or comparison (usual care only) conditions in a RCT conducted between September 2017 and February 2019. Parents completed …


Hdac2 In Primary Sensory Neurons Constitutively Restrains Chronic Pain By Repressing Α2Δ-1 Expression And Associated Nmda Receptor Activity, Jixiang Zhang, Shao-Rui Chen, Meng-Hua Zhou, Daozhong Jin, Hong Chen, Li Wang, Ronald A Depinho, Hui-Lin Pan Nov 2022

Hdac2 In Primary Sensory Neurons Constitutively Restrains Chronic Pain By Repressing Α2Δ-1 Expression And Associated Nmda Receptor Activity, Jixiang Zhang, Shao-Rui Chen, Meng-Hua Zhou, Daozhong Jin, Hong Chen, Li Wang, Ronald A Depinho, Hui-Lin Pan

Faculty, Staff and Student Publications

α2δ-1 (encoded by the Cacna2d1 gene) is a newly discovered NMDA receptor-interacting protein and is the therapeutic target of gabapentinoids (e.g., gabapentin and pregabalin) frequently used for treating patients with neuropathic pain. Nerve injury causes sustained α2δ-1 upregulation in the dorsal root ganglion (DRG), which promotes NMDA receptor synaptic trafficking and activation in the spinal dorsal horn, a hallmark of chronic neuropathic pain. However, little is known about how nerve injury initiates and maintains the high expression level of α2δ-1 to sustain chronic pain. Here, we show that nerve injury caused histone hyperacetylation and diminished enrichment of histone deacetylase-2 (HDAC2), …


Synaptic Development In Diverse Olfactory Neuron Classes Uses Distinct Temporal And Activity-Related Programs, Michael A. Aimino, Alison T. Depew, Lucas Restrepo, Timothy J. Mosca Nov 2022

Synaptic Development In Diverse Olfactory Neuron Classes Uses Distinct Temporal And Activity-Related Programs, Michael A. Aimino, Alison T. Depew, Lucas Restrepo, Timothy J. Mosca

Farber Institute for Neuroscience Faculty Papers

Developing neurons must meet core molecular, cellular, and temporal requirements to ensure the correct formation of synapses, resulting in functional circuits. However, because of the vast diversity in neuronal class and function, it is unclear whether or not all neurons use the same organizational mechanisms to form synaptic connections and achieve functional and morphologic maturation. Moreover, it remains unknown whether neurons united in a common goal and comprising the same sensory circuit develop on similar timescales and use identical molecular approaches to ensure the formation of the correct number of synapses. To begin to answer these questions, we took advantage …


Using Genomic Variation To Distinguish Ovarian High-Grade Serous Carcinoma From Benign Fallopian Tubes, Jesus Gonzalez-Bosquet, Nicholas D Cardillo, Henry D Reyes, Brian J Smith, Kimberly K Leslie, David P Bender, Michael J Goodheart, Eric J Devor Nov 2022

Using Genomic Variation To Distinguish Ovarian High-Grade Serous Carcinoma From Benign Fallopian Tubes, Jesus Gonzalez-Bosquet, Nicholas D Cardillo, Henry D Reyes, Brian J Smith, Kimberly K Leslie, David P Bender, Michael J Goodheart, Eric J Devor

Department of Obstetrics and Gynecology Faculty Papers

The preoperative diagnosis of pelvic masses has been elusive to date. Methods for characterization such as CA-125 have had limited specificity. We hypothesize that genomic variation can be used to create prediction models which accurately distinguish high grade serous ovarian cancer (HGSC) from benign tissue.

Methods: In this retrospective, pilot study, we extracted DNA and RNA from HGSC specimens and from benign fallopian tubes. Then, we performed whole exome sequencing and RNA sequencing, and identified single nucleotide variants (SNV), copy number variants (CNV) and structural variants (SV). We used these variants to create prediction models to distinguish cancer from benign …


Premature Ovarian Insufficiency In Clpb Deficiency: Transcriptomic, Proteomic And Phenotypic Insights, Elena J Tucker, Julia T Warren, Et Al. Nov 2022

Premature Ovarian Insufficiency In Clpb Deficiency: Transcriptomic, Proteomic And Phenotypic Insights, Elena J Tucker, Julia T Warren, Et Al.

2020-Current year OA Pubs

CONTEXT: Premature ovarian insufficiency (POI) is a common form of female infertility that usually presents as an isolated condition but can be part of various genetic syndromes. Early diagnosis and treatment of POI can minimize comorbidity and improve health outcomes.

OBJECTIVE: We aimed to determine the genetic cause of syndromic POI, intellectual disability, neutropenia, and cataracts.

METHODS: We performed whole-exome sequencing (WES) followed by functional validation via RT-PCR, RNAseq, and quantitative proteomics, as well as clinical update of previously reported patients with variants in the caseinolytic peptidase B (CLPB) gene.

RESULTS: We identified causative variants in CLPB, encoding a mitochondrial …


Effect Of Selective Decontamination Of The Digestive Tract On Hospital Mortality In Critically Ill Patients Receiving Mechanical Ventilation: A Randomized Clinical Trial, The Suddicu Investigators For The Australian And New Zealand Intensive Care Society Clinical Trials Group, John A Myburgh, Ian M Seppelt, Fiona Goodman, Laurent Billot, Maryam Correa, Joshua S Davis, Anthony C Gordon, Naomi E Hammond, Jon Iredell, Qiang Li, Sharon Micallef, Jennene Miller, Jayanthi Mysore, Colman Taylor, Paul J Young, Brian H Cuthbertson, Simon R Finfer Nov 2022

Effect Of Selective Decontamination Of The Digestive Tract On Hospital Mortality In Critically Ill Patients Receiving Mechanical Ventilation: A Randomized Clinical Trial, The Suddicu Investigators For The Australian And New Zealand Intensive Care Society Clinical Trials Group, John A Myburgh, Ian M Seppelt, Fiona Goodman, Laurent Billot, Maryam Correa, Joshua S Davis, Anthony C Gordon, Naomi E Hammond, Jon Iredell, Qiang Li, Sharon Micallef, Jennene Miller, Jayanthi Mysore, Colman Taylor, Paul J Young, Brian H Cuthbertson, Simon R Finfer

Faculty, Staff and Student Publications

IMPORTANCE: Whether selective decontamination of the digestive tract (SDD) reduces mortality in critically ill patients remains uncertain.

OBJECTIVE: To determine whether SDD reduces in-hospital mortality in critically ill adults.

DESIGN, SETTING, AND PARTICIPANTS: A cluster, crossover, randomized clinical trial that recruited 5982 mechanically ventilated adults from 19 intensive care units (ICUs) in Australia between April 2018 and May 2021 (final follow-up, August 2021). A contemporaneous ecological assessment recruited 8599 patients from participating ICUs between May 2017 and August 2021.

INTERVENTIONS: ICUs were randomly assigned to adopt or not adopt a SDD strategy for 2 alternating 12-month periods, separated by a …


Molecular Subclasses Of Clear Cell Ovarian Carcinoma And Their Impact On Disease Behavior And Outcomes, Kelly L Bolton, Irenaeus C C Chan, Brian J Wiley, Et Al. Nov 2022

Molecular Subclasses Of Clear Cell Ovarian Carcinoma And Their Impact On Disease Behavior And Outcomes, Kelly L Bolton, Irenaeus C C Chan, Brian J Wiley, Et Al.

2020-Current year OA Pubs

PURPOSE: To identify molecular subclasses of clear cell ovarian carcinoma (CCOC) and assess their impact on clinical presentation and outcomes.

EXPERIMENTAL DESIGN: We profiled 421 primary CCOCs that passed quality control using a targeted deep sequencing panel of 163 putative CCOC driver genes and whole transcriptome sequencing of 211 of these tumors. Molecularly defined subgroups were identified and tested for association with clinical characteristics and overall survival.

RESULTS: We detected a putative somatic driver mutation in at least one candidate gene in 95% (401/421) of CCOC tumors including ARID1A (in 49% of tumors), PIK3CA (49%), TERT (20%), and TP53 (16%). …


Increased Circulating Cortisol After Vaginal Birth Is Associated With Increased Fgf19 Secretion In Neonatal Pigs, Caitlin Vonderohe, Gregory Guthrie, Barbara Stoll, Valeria Melendez Hebib, Harry Dawson, Douglas Burrin Nov 2022

Increased Circulating Cortisol After Vaginal Birth Is Associated With Increased Fgf19 Secretion In Neonatal Pigs, Caitlin Vonderohe, Gregory Guthrie, Barbara Stoll, Valeria Melendez Hebib, Harry Dawson, Douglas Burrin

Children’s Nutrition Research Center Staff Publications

The influence of birth modality (scheduled cesarean or spontaneous vaginal) on the development of the newborn has been a source of controversy in neonatology. The impact of cesarean vs vaginal birth on the development of bile acid and fibroblast growth factor 19 (FGF19) signaling is unknown. Our aim was to determine the effect of birth modality and gestational age (preterm vs term) on plasma hormone levels, bile acid pool distribution, expression of genes in the bile acid-FXR-FGF19 pathway, and plasma levels of FGF19 at birth and on day 3 of life in neonatal pigs. Four sows underwent cesarean delivery on …


Copy Number Variants Are Ovarian Cancer Risk Alleles At Known And Novel Risk Loci, Amber A Devries, Joe Dennis, Jonathan P Tyrer, Pei-Chen Peng, Simon G Coetzee, Alberto L Reyes, Jasmine T Plummer, Brian D Davis, Stephanie S Chen, Felipe Segato Dezem, Katja K H Aben, Hoda Anton-Culver, Natalia N Antonenkova, Matthias W Beckmann, Alicia Beeghly-Fadiel, Andrew Berchuck, Natalia V Bogdanova, Nadja Bogdanova-Markov, James D Brenton, Ralf Butzow, Ian Campbell, Jenny Chang-Claude, Georgia Chenevix-Trench, Linda S Cook, Anna Defazio, Jennifer A Doherty, Thilo Dörk, Diana M Eccles, A Heather Eliassen, Peter A Fasching, Renée T Fortner, Graham G Giles, Ellen L Goode, Marc T Goodman, Jacek Gronwald, Opal Study Group, Aocs Group, Niclas Håkansson, Michelle A T Hildebrandt, Chad Huff, David G Huntsman, Allan Jensen, Siddhartha Kar, Beth Y Karlan, Elza K Khusnutdinova, Lambertus A Kiemeney, Susanne K Kjaer, Jolanta Kupryjanczyk, Marilyne Labrie, Diether Lambrechts, Nhu D Le, Jan Lubiński, Taymaa May, Usha Menon, Roger L Milne, Francesmary Modugno, Alvaro N Monteiro, Kirsten B Moysich, Kunle Odunsi, Håkan Olsson, Celeste L Pearce, Tanja Pejovic, Susan J Ramus, Elio Riboli, Marjorie J Riggan, Isabelle Romieu, Dale P Sandler, Joellen M Schildkraut, V Wendy Setiawan, Weiva Sieh, Honglin Song, Rebecca Sutphen, Kathryn L Terry, Pamela J Thompson, Linda Titus, Shelley S Tworoger, Els Van Nieuwenhuysen, Digna Velez Edwards, Penelope M Webb, Nicolas Wentzensen, Alice S Whittemore, Alicja Wolk, Anna H Wu, Argyrios Ziogas, Matthew L Freedman, Kate Lawrenson, Paul D P Pharoah, Douglas F Easton, Simon A Gayther, Michelle R Jones Nov 2022

Copy Number Variants Are Ovarian Cancer Risk Alleles At Known And Novel Risk Loci, Amber A Devries, Joe Dennis, Jonathan P Tyrer, Pei-Chen Peng, Simon G Coetzee, Alberto L Reyes, Jasmine T Plummer, Brian D Davis, Stephanie S Chen, Felipe Segato Dezem, Katja K H Aben, Hoda Anton-Culver, Natalia N Antonenkova, Matthias W Beckmann, Alicia Beeghly-Fadiel, Andrew Berchuck, Natalia V Bogdanova, Nadja Bogdanova-Markov, James D Brenton, Ralf Butzow, Ian Campbell, Jenny Chang-Claude, Georgia Chenevix-Trench, Linda S Cook, Anna Defazio, Jennifer A Doherty, Thilo Dörk, Diana M Eccles, A Heather Eliassen, Peter A Fasching, Renée T Fortner, Graham G Giles, Ellen L Goode, Marc T Goodman, Jacek Gronwald, Opal Study Group, Aocs Group, Niclas Håkansson, Michelle A T Hildebrandt, Chad Huff, David G Huntsman, Allan Jensen, Siddhartha Kar, Beth Y Karlan, Elza K Khusnutdinova, Lambertus A Kiemeney, Susanne K Kjaer, Jolanta Kupryjanczyk, Marilyne Labrie, Diether Lambrechts, Nhu D Le, Jan Lubiński, Taymaa May, Usha Menon, Roger L Milne, Francesmary Modugno, Alvaro N Monteiro, Kirsten B Moysich, Kunle Odunsi, Håkan Olsson, Celeste L Pearce, Tanja Pejovic, Susan J Ramus, Elio Riboli, Marjorie J Riggan, Isabelle Romieu, Dale P Sandler, Joellen M Schildkraut, V Wendy Setiawan, Weiva Sieh, Honglin Song, Rebecca Sutphen, Kathryn L Terry, Pamela J Thompson, Linda Titus, Shelley S Tworoger, Els Van Nieuwenhuysen, Digna Velez Edwards, Penelope M Webb, Nicolas Wentzensen, Alice S Whittemore, Alicja Wolk, Anna H Wu, Argyrios Ziogas, Matthew L Freedman, Kate Lawrenson, Paul D P Pharoah, Douglas F Easton, Simon A Gayther, Michelle R Jones

Faculty, Staff and Student Publications

BACKGROUND: Known risk alleles for epithelial ovarian cancer (EOC) account for approximately 40% of the heritability for EOC. Copy number variants (CNVs) have not been investigated as EOC risk alleles in a large population cohort.

METHODS: Single nucleotide polymorphism array data from 13 071 EOC cases and 17 306 controls of White European ancestry were used to identify CNVs associated with EOC risk using a rare admixture maximum likelihood test for gene burden and a by-probe ratio test. We performed enrichment analysis of CNVs at known EOC risk loci and functional biofeatures in ovarian cancer-related cell types.

RESULTS: We identified …


Tumor Suppressor Dear1 Regulates Mammary Epithelial Cell Fate And Predicts Early Onset And Metastasis In Triple Negative Breast Cancer, Uyen Q Le, Nanyue Chen, Seetharaman Balasenthil, Eugene Lurie, Fei Yang, Suyu Liu, Laura Rubin, Luisa Maren Solis Soto, Maria Gabriela Raso, Harsh Batra, Aysegul A Sahin, Ignacio I Wistuba, Ann Mcneill Killary Nov 2022

Tumor Suppressor Dear1 Regulates Mammary Epithelial Cell Fate And Predicts Early Onset And Metastasis In Triple Negative Breast Cancer, Uyen Q Le, Nanyue Chen, Seetharaman Balasenthil, Eugene Lurie, Fei Yang, Suyu Liu, Laura Rubin, Luisa Maren Solis Soto, Maria Gabriela Raso, Harsh Batra, Aysegul A Sahin, Ignacio I Wistuba, Ann Mcneill Killary

Faculty, Staff and Student Publications

Triple negative breast cancer (TNBC) is a disease of poor prognosis, with the majority classified as the basal-like subtype associated with epithelial-mesenchymal transition and metastasis. Because basal breast cancers originate from proliferative luminal progenitor-like cells upon dysregulation of proper luminal differentiation, genes regulating luminal-basal transition are critical to elucidate novel therapeutic targets to improve TNBC outcomes. Herein we demonstrate that the tumor suppressor DEAR1/TRIM62 is a critical regulator of luminal cell fate. DEAR1 loss in human mammary epithelial cells results in significantly enhanced mammosphere formation that is accelerated in the presence of TGF-β/SMAD3 signaling. Mammospheres formed following DEAR1 loss are …


Liquefied Petroleum Gas Or Biomass For Cooking And Effects On Birth Weight, Thomas F Clasen, Lindsay J Underhill, Et Al. Nov 2022

Liquefied Petroleum Gas Or Biomass For Cooking And Effects On Birth Weight, Thomas F Clasen, Lindsay J Underhill, Et Al.

2020-Current year OA Pubs

BACKGROUND: Exposure during pregnancy to household air pollution caused by the burning of solid biomass fuel is associated with adverse health outcomes, including low birth weight. Whether the replacement of a biomass cookstove with a liquefied petroleum gas (LPG) cookstove would result in an increase in birth weight is unclear.

METHODS: We performed a randomized, controlled trial involving pregnant women (18 to <35 years of age and at 9 to <20 weeks' gestation as confirmed on ultrasonography) in Guatemala, India, Peru, and Rwanda. The women were assigned in a 1:1 ratio to use a free LPG cookstove and fuel (intervention group) or to continue using a biomass cookstove (control group). Birth weight, one of four prespecified primary outcomes, was the primary outcome for this report; data for the other three outcomes are not yet available. Birth weight was measured within 24 hours after birth. In addition, 24-hour personal exposures to fine particulate matter (particles with a diameter of ≤2.5 μm [PM

RESULTS: A total of 3200 women underwent randomization; 1593 were assigned to the intervention group, and 1607 to the control group. Uptake of the intervention was nearly complete, with traditional biomass cookstoves being used at a median rate …


A Randomized Pilot Study Of Oncology Massage To Treat Chemotherapy-Induced Peripheral Neuropathy, Gabriel Lopez, Cathy Eng, Michael Overman, David Ramirez, Wenli Liu, Curtiss Beinhorn, Pamela Sumler, Sarah Prinsloo, Yisheng Li, Minxing Chen, Eduardo Bruera, Lorenzo Cohen Nov 2022

A Randomized Pilot Study Of Oncology Massage To Treat Chemotherapy-Induced Peripheral Neuropathy, Gabriel Lopez, Cathy Eng, Michael Overman, David Ramirez, Wenli Liu, Curtiss Beinhorn, Pamela Sumler, Sarah Prinsloo, Yisheng Li, Minxing Chen, Eduardo Bruera, Lorenzo Cohen

Faculty, Staff and Student Publications

This pilot randomized controlled trial investigated massage therapy for symptomatic relief of chemotherapy-induced peripheral neuropathy (CIPN) to determine the ideal weekly frequency and number of weeks of providing massage. We evaluated the feasibility and initial efficacy of a Swedish massage protocol to treat lower extremity (LE) CIPN. Inclusion criteria: LE neuropathy attributed to oxaliplatin, paclitaxel, or docetaxel, with no other attributable causes; ≥ 6 months since last chemotherapy; self-reported neuropathy score ≥ 3, 0-10 scale; age ≥ 18. Participant randomization (2:2:1:1) to one of four groups: LE (2) or head/neck/shoulder (control; 1) massage 3 times (3X) a week for 4 …


Omics Analyses Of A Somatic Trp53r245w/+ Breast Cancer Model Identify Cooperating Driver Events Activating Pi3k/Akt/Mtor Signaling, Xiaojie Yu, Yun Zhang, Shunbin Xiong, Joy M Mcdaniel, Chang Sun, Gilda P Chau, Jovanka Gencel-Augusto, Dhruv Chachad, Rhiannon L Morrissey, Xiayu Rao, Jing Wang, Guillermina Lozano Nov 2022

Omics Analyses Of A Somatic Trp53r245w/+ Breast Cancer Model Identify Cooperating Driver Events Activating Pi3k/Akt/Mtor Signaling, Xiaojie Yu, Yun Zhang, Shunbin Xiong, Joy M Mcdaniel, Chang Sun, Gilda P Chau, Jovanka Gencel-Augusto, Dhruv Chachad, Rhiannon L Morrissey, Xiayu Rao, Jing Wang, Guillermina Lozano

Faculty, Staff and Student Publications

Alterations of the tumor suppressor


Perceptions And Concerns Regarding Covid-19 Vaccination In A Military Base Population, Samuel R. Theis, Peter C. Li, Devin Kelly, Thad Ocampo, Andrew Berglund, Damien Morgan, Ronald J. Markert, Evan Fisher, Kathryn Burtson Nov 2022

Perceptions And Concerns Regarding Covid-19 Vaccination In A Military Base Population, Samuel R. Theis, Peter C. Li, Devin Kelly, Thad Ocampo, Andrew Berglund, Damien Morgan, Ronald J. Markert, Evan Fisher, Kathryn Burtson

Internal Medicine Faculty Publications

Introduction: Safe and effective vaccines against severe acute respiratory syndrome-associated coronavirus 2 are essential tools in the fight against the coronavirus disease 2019 (COVID-19) pandemic. However, hesitancy to vaccination is a major barrier to achieving herd immunity, particularly among a population working on a military base. To better understand the perceptions and concerns of these individuals, a voluntary survey was conducted. Materials and methods: An interactive, online survey was constructed and disseminated to individuals associated with Wright-Patterson Air Force Base (WPAFB) in Dayton, OH. Survey participation was voluntary with responses collected over the initial weeks in which WPAFB began to …


Accounting For The Growth Of Observation Stays In The Assessment Of Medicare's Hospital Readmissions Reduction Program, Amber K Sabbatini, Karen E Joynt-Maddox, Joshua M Liao, Anirban Basu, Canada Parrish, William Kreuter, Brad Wright Nov 2022

Accounting For The Growth Of Observation Stays In The Assessment Of Medicare's Hospital Readmissions Reduction Program, Amber K Sabbatini, Karen E Joynt-Maddox, Joshua M Liao, Anirban Basu, Canada Parrish, William Kreuter, Brad Wright

2020-Current year OA Pubs

IMPORTANCE: Decreases in 30-day readmissions following the implementation of the Medicare Hospital Readmissions Reduction Program (HRRP) have occurred against the backdrop of increasing hospital observation stay use, yet observation stays are not captured in readmission measures.

OBJECTIVE: To examine whether the HRRP was associated with decreases in 30-day readmissions after accounting for observation stays.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included a 20% sample of inpatient admissions and observation stays among Medicare fee-for-service beneficiaries from January 1, 2009, to December 31, 2015. Data analysis was performed from November 2021 to June 2022. A differences-in-differences analysis assessed changes in …


Assessing Urinary Phenol And Paraben Mixtures In Pregnant Women With And Without Gestational Diabetes Mellitus: A Case-Control Study, Wei-Jen Chen, Candace Robledo, Erin M Davis, Jean R Goodman, Chao Xu, Jooyeon Hwang, Amanda E Janitz, Tabitha Garwe, Antonia M Calafat, Jennifer D Peck Nov 2022

Assessing Urinary Phenol And Paraben Mixtures In Pregnant Women With And Without Gestational Diabetes Mellitus: A Case-Control Study, Wei-Jen Chen, Candace Robledo, Erin M Davis, Jean R Goodman, Chao Xu, Jooyeon Hwang, Amanda E Janitz, Tabitha Garwe, Antonia M Calafat, Jennifer D Peck

Faculty, Staff and Student Publications

Prior studies have identified the associations between environmental phenol and paraben exposures and increased risk of gestational diabetes mellitus (GDM), but no study addressed these exposures as mixtures. As methods have emerged to better assess exposures to multiple chemicals, our study aimed to apply Bayesian kernel machine regression (BKMR) to evaluate the association between phenol and paraben mixtures and GDM. This study included 64 GDM cases and 237 obstetric patient controls from the University of Oklahoma Medical Center. Mid-pregnancy spot urine samples were collected to quantify concentrations of bisphenol A (BPA), benzophenone-3, triclosan, 2,4-dichlorophenol, 2,5-dichlorophenol, butylparaben, methylparaben, and propylparaben. Multivariable …


Identification Of Novel Susceptibility Methylation Loci For Pancreatic Cancer In A Two-Phase Epigenome-Wide Association Study, Ziqiao Wang, Yue Lu, Myriam Fornage, Li Jiao, Jianjun Shen, Donghui Li, Peng Wei Nov 2022

Identification Of Novel Susceptibility Methylation Loci For Pancreatic Cancer In A Two-Phase Epigenome-Wide Association Study, Ziqiao Wang, Yue Lu, Myriam Fornage, Li Jiao, Jianjun Shen, Donghui Li, Peng Wei

Faculty, Staff and Student Publications

The role of DNA methylation and its interplay with gene expression in the susceptibility to pancreatic cancer (PanC) remains largely unexplored. To fill in this gap, we conducted an integrative two-phase epigenome-wide association study (EWAS) of PanC using genomic DNA from 44 cases and 556 controls (20 local controls and 536 public controls in the Framingham Heart Study) in phase 1 and 23 cases and 22 controls in phase 2. We validated the findings using pre-diagnostic blood samples from 13 cases and 26 controls in the Women's Health Initiative (WHI) Study. We further examined gene expression in peripheral leukocytes of …


Risk Factors For Community-Acquired Bacterial Infection Among Young Infants In South Asia: A Longitudinal Cohort Study With Nested Case-Control Analysis, Nicholas E Connor, Mohammad Shahidul Islam, Luke C Mullany, Nong Shang, Zulfiqar A Bhutta, Anita K M Zaidi, Sajid Soofi, Imran Nisar, Pinaki Panigrahi, Kalpana Panigrahi, Radhanath Satpathy, Anuradha Bose, Rita Isaac, Abdullah H Baqui, Dipak K Mitra, Qazi Sadeq-Ur Rahman, Tanvir Hossain, Stephanie J Schrag, Jonas M Winchell, Melissa L Arvay, Maureen H Diaz, Jessica L Waller, Martin W Weber, Davidson H Hamer, Patricia Hibberd, A S M Nawshad Uddin Ahmed, Maksuda Islam, Mohammad Belal Hossain, Shamim A Qazi, Shams El Arifeen, Gary L Darmstadt, Samir K Saha Nov 2022

Risk Factors For Community-Acquired Bacterial Infection Among Young Infants In South Asia: A Longitudinal Cohort Study With Nested Case-Control Analysis, Nicholas E Connor, Mohammad Shahidul Islam, Luke C Mullany, Nong Shang, Zulfiqar A Bhutta, Anita K M Zaidi, Sajid Soofi, Imran Nisar, Pinaki Panigrahi, Kalpana Panigrahi, Radhanath Satpathy, Anuradha Bose, Rita Isaac, Abdullah H Baqui, Dipak K Mitra, Qazi Sadeq-Ur Rahman, Tanvir Hossain, Stephanie J Schrag, Jonas M Winchell, Melissa L Arvay, Maureen H Diaz, Jessica L Waller, Martin W Weber, Davidson H Hamer, Patricia Hibberd, A S M Nawshad Uddin Ahmed, Maksuda Islam, Mohammad Belal Hossain, Shamim A Qazi, Shams El Arifeen, Gary L Darmstadt, Samir K Saha

Faculty, Staff and Student Publications

OBJECTIVE: Risk factors predisposing infants to community-acquired bacterial infections during the first 2 months of life are poorly understood in South Asia. Identifying risk factors for infection could lead to improved preventive measures and antibiotic stewardship.

METHODS: Five sites in Bangladesh, India and Pakistan enrolled mother-child pairs via population-based pregnancy surveillance by community health workers. Medical, sociodemographic and epidemiological risk factor data were collected. Young infants aged 0-59 days with signs of possible serious bacterial infection (pSBI) and age-matched controls provided blood and respiratory specimens that were analysed by blood culture and real-time PCR. These tests were used to build …


A Blood-Based Metabolite Panel For Distinguishing Ovarian Cancer From Benign Pelvic Masses, Ehsan Irajizad, Chae Y Han, Joseph Celestino, Ranran Wu, Eunice Murage, Rachelle Spencer, Jennifer B Dennison, Jody Vykoukal, James P Long, Kim Anh Do, Charles Drescher, Karen Lu, Zhen Lu, Robert C Bast, Sam Hanash, Johannes F Fahrmann Nov 2022

A Blood-Based Metabolite Panel For Distinguishing Ovarian Cancer From Benign Pelvic Masses, Ehsan Irajizad, Chae Y Han, Joseph Celestino, Ranran Wu, Eunice Murage, Rachelle Spencer, Jennifer B Dennison, Jody Vykoukal, James P Long, Kim Anh Do, Charles Drescher, Karen Lu, Zhen Lu, Robert C Bast, Sam Hanash, Johannes F Fahrmann

Faculty, Staff and Student Publications

PURPOSE: To assess the contributions of circulating metabolites for improving upon the performance of the risk of ovarian malignancy algorithm (ROMA) for risk prediction of ovarian cancer among women with ovarian cysts.

EXPERIMENTAL DESIGN: Metabolomic profiling was performed on an initial set of sera from 101 serous and nonserous ovarian cancer cases and 134 individuals with benign pelvic masses (BPM). Using a deep learning model, a panel consisting of seven cancer-related metabolites [diacetylspermine, diacetylspermidine, N-(3-acetamidopropyl)pyrrolidin-2-one, N-acetylneuraminate, N-acetyl-mannosamine, N-acetyl-lactosamine, and hydroxyisobutyric acid] was developed for distinguishing early-stage ovarian cancer from BPM. The performance of the metabolite panel was evaluated in an …


Investigation Of Murine Host Sex As A Biological Variable In Epithelial Barrier Function And Muscle Contractility In Human Intestinal Organoids, Brooke T Beanland, Eoin P Mcneill, David J Sequeira, Hasen Xue, Noah F Shroyer, Allison L Speer Nov 2022

Investigation Of Murine Host Sex As A Biological Variable In Epithelial Barrier Function And Muscle Contractility In Human Intestinal Organoids, Brooke T Beanland, Eoin P Mcneill, David J Sequeira, Hasen Xue, Noah F Shroyer, Allison L Speer

Faculty, Staff and Student Publications

Intestinal failure (IF) occurs when intestinal surface area or function is not sufficient to support digestion and nutrient absorption. Human intestinal organoid (HIO)-derived tissue-engineered intestine is a potential cure for IF. Research to date has demonstrated successful HIO transplantation (tHIO) into mice with significant in vivo maturation. An area lacking in the literature is exploration of murine host sex as a biological variable (SABV) in tHIO function. In this study, we investigate murine host SABV in tHIO epithelial barrier function and muscle contractility. HIOs were generated in vitro and transplanted into nonobese diabetic, severe combined immunodeficiency gamma chain deficient male …


Venous Sinus Stenting For Low Pressure Gradient Stenoses In Idiopathic Intracranial Hypertension, Mehmet Enes Inam, Juan Carlos Martinez-Gutierrez, Matthew J Kole, Francisco Sanchez, Elvira Lekka, Van Thi Thanh Truong, Victor Lopez-Rivera, Faheem G Sheriff, Laura A Zima, Claudia Pedroza, Rosa Tang, Ore-Ofe Adesina, Allison Engstrom, Sunil A Sheth, Peng Roc Chen Nov 2022

Venous Sinus Stenting For Low Pressure Gradient Stenoses In Idiopathic Intracranial Hypertension, Mehmet Enes Inam, Juan Carlos Martinez-Gutierrez, Matthew J Kole, Francisco Sanchez, Elvira Lekka, Van Thi Thanh Truong, Victor Lopez-Rivera, Faheem G Sheriff, Laura A Zima, Claudia Pedroza, Rosa Tang, Ore-Ofe Adesina, Allison Engstrom, Sunil A Sheth, Peng Roc Chen

Faculty, Staff and Student Publications

BACKGROUND: Medically refractory idiopathic intracranial hypertension (IIH) is frequently treated with venous sinus stenosis stenting with high success rates. Patient selection has been driven almost exclusively by identification of supraphysiological venous pressure gradients across stenotic regions based on theoretical assessment of likelihood of response.

OBJECTIVE: To explore the possibility of benefit in low venous pressure gradient patients.

METHODS: Using a single-center, prospectively maintained registry of patients with IIH undergoing venous stenting, we defined treatment groups by gradient pressures of ≤4, 5 to 8, and >8 mmHg based on the most frequently previously published thresholds for stenting. Baseline demographics, clinical, and …


Outcome Prediction In Newborn Infants: Past, Present, And Future, Vivek V Shukla, Matthew A Rysavy, Abhik Das, Jon E Tyson, Edward F Bell, Namasivayam Ambalavanan, Waldemar A Carlo Nov 2022

Outcome Prediction In Newborn Infants: Past, Present, And Future, Vivek V Shukla, Matthew A Rysavy, Abhik Das, Jon E Tyson, Edward F Bell, Namasivayam Ambalavanan, Waldemar A Carlo

Faculty, Staff and Student Publications

The perinatal and neonatal periods are the periods of considerable organ development and maturation. Perinatal and neonatal illnesses can result in mortality and morbidities that burden families and the healthcare system. Outcome prediction is essential for informing perinatal and intensive care management, prognosis, and post-discharge interventions. The Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NRN) research databases include hospital and neurodevelopment follow-up outcomes of infants with various underlying diseases and conditions receiving intensive care, providing a unique opportunity to assess outcome risk prediction. The NRN has developed outcome risk prediction tools for use …


Brain Structure In Acutely Underweight And Partially Weight-Restored Individuals With Anorexia Nervosa: A Coordinated Analysis By The Enigma Eating Disorders Working Group, Esther Walton, Fabio Bernardoni, Victoria-Luise Batury, Klaas Bahnsen, Sara Larivière, Giovanni Abbate-Daga, Susana Andres-Perpiña, Lasse Bang, Amanda Bischoff-Grethe, Samantha J Brooks, Iain C Campbell, Giammarco Cascino, Josefina Castro-Fornieles, Enrico Collantoni, Federico D'Agata, Brigitte Dahmen, Unna N Danner, Angela Favaro, Jamie D Feusner, Guido K W Frank, Hans-Christoph Friederich, John L Graner, Beate Herpertz-Dahlmann, Andreas Hess, Stefanie Horndasch, Allan S Kaplan, Lisa-Katrin Kaufmann, Walter H Kaye, Sahib S Khalsa, Kevin S Labar, Luca Lavagnino, Luisa Lazaro, Renzo Manara, Amy E Miles, Gabriella F Milos, Alessio Maria Monteleone, Palmiero Monteleone, Benson Mwangi, Owen O'Daly, Jose Pariente, Julie Roesch, Ulrike H Schmidt, Jochen Seitz, Megan E Shott, Joe J Simon, Paul A M Smeets, Christian K Tamnes, Elena Tenconi, Sophia I Thomopoulos, Annemarie A Van Elburg, Aristotle N Voineskos, Georg G Von Polier, Christina E Wierenga, Nancy L Zucker, Neda Jahanshad, Joseph A King, Paul M Thompson, Laura A Berner, Stefan Ehrlich Nov 2022

Brain Structure In Acutely Underweight And Partially Weight-Restored Individuals With Anorexia Nervosa: A Coordinated Analysis By The Enigma Eating Disorders Working Group, Esther Walton, Fabio Bernardoni, Victoria-Luise Batury, Klaas Bahnsen, Sara Larivière, Giovanni Abbate-Daga, Susana Andres-Perpiña, Lasse Bang, Amanda Bischoff-Grethe, Samantha J Brooks, Iain C Campbell, Giammarco Cascino, Josefina Castro-Fornieles, Enrico Collantoni, Federico D'Agata, Brigitte Dahmen, Unna N Danner, Angela Favaro, Jamie D Feusner, Guido K W Frank, Hans-Christoph Friederich, John L Graner, Beate Herpertz-Dahlmann, Andreas Hess, Stefanie Horndasch, Allan S Kaplan, Lisa-Katrin Kaufmann, Walter H Kaye, Sahib S Khalsa, Kevin S Labar, Luca Lavagnino, Luisa Lazaro, Renzo Manara, Amy E Miles, Gabriella F Milos, Alessio Maria Monteleone, Palmiero Monteleone, Benson Mwangi, Owen O'Daly, Jose Pariente, Julie Roesch, Ulrike H Schmidt, Jochen Seitz, Megan E Shott, Joe J Simon, Paul A M Smeets, Christian K Tamnes, Elena Tenconi, Sophia I Thomopoulos, Annemarie A Van Elburg, Aristotle N Voineskos, Georg G Von Polier, Christina E Wierenga, Nancy L Zucker, Neda Jahanshad, Joseph A King, Paul M Thompson, Laura A Berner, Stefan Ehrlich

Faculty, Staff and Student Publications

Background: The pattern of structural brain abnormalities in anorexia nervosa (AN) is still not well understood. While several studies report substantial deficits in gray matter volume and cortical thickness in acutely underweight patients, others find no differences, or even increases in patients compared with healthy control subjects. Recent weight regain before scanning may explain some of this heterogeneity. To clarify the extent, magnitude, and dependencies of gray matter changes in AN, we conducted a prospective, coordinated meta-analysis of multicenter neuroimaging data.

Methods: We analyzed T1-weighted structural magnetic resonance imaging scans assessed with standardized methods from 685 female patients with AN …


Does Attention-Deficit/Hyperactivity Disorder Increase The Risk Of Minor Blunt Head Trauma In Children?, Murat Pakyurek, Mohamed Badawy, Irma T Ugalde, Paul Ishimine, Pradip P Chaudhari, Kevan Mccarten-Gibbs, Ozra Nobari, Nathan Kuppermann, James F Holmes Nov 2022

Does Attention-Deficit/Hyperactivity Disorder Increase The Risk Of Minor Blunt Head Trauma In Children?, Murat Pakyurek, Mohamed Badawy, Irma T Ugalde, Paul Ishimine, Pradip P Chaudhari, Kevan Mccarten-Gibbs, Ozra Nobari, Nathan Kuppermann, James F Holmes

Faculty, Staff and Student Publications

PROBLEM: It is unclear if attention-deficit hyperactivity disorder (ADHD) increases the risk of head trauma in children.

METHODS: We conducted a multicenter prospective observational study of children with minor blunt head trauma. Guardians were queried, and medical records were reviewed as to whether the patient had previously been diagnosed with ADHD. Enrolled patients were categorized based on their mechanism of injury, with a comparison of those with motor vehicle collision (MVC) versus non-MVC mechanisms.

FINDINGS: A total of 3410 (84%) enrolled children had ADHD status available, and 274 (8.0%; 95% confidence interval, CI: 7.1, 9.0%) had been diagnosed with ADHD. …


Challenges And Lessons Learned From The Rapid Operationalization Of A Prospective Cohort To Study The Natural History And Neurodevelopmental Outcomes Of Postnatal Zika Virus Infection Among Infants And Children In Rural Guatemala, Alejandra Paniagua-Avila, Daniel Olson, Amy Connery, D Mirella Calvimontes, Guillermo A Bolanos, Molly M Lamb, Desiree Bauer, Aida Ralda, Neudy Rojop, Eduardo Barrios, Andrea Chacon, Melissa Gomez, Paola Arroyave, Sara Hernandez, Maria Alejandra Martinez, Saskia Bunge-Montes, Alison Colbert, Kareen Arias, Garret Brazeale, Andrea Holliday, Kay M Tomashek, Hana M El Sahly, Wendy Keitel, Flor M Munoz, Edwin J Asturias Nov 2022

Challenges And Lessons Learned From The Rapid Operationalization Of A Prospective Cohort To Study The Natural History And Neurodevelopmental Outcomes Of Postnatal Zika Virus Infection Among Infants And Children In Rural Guatemala, Alejandra Paniagua-Avila, Daniel Olson, Amy Connery, D Mirella Calvimontes, Guillermo A Bolanos, Molly M Lamb, Desiree Bauer, Aida Ralda, Neudy Rojop, Eduardo Barrios, Andrea Chacon, Melissa Gomez, Paola Arroyave, Sara Hernandez, Maria Alejandra Martinez, Saskia Bunge-Montes, Alison Colbert, Kareen Arias, Garret Brazeale, Andrea Holliday, Kay M Tomashek, Hana M El Sahly, Wendy Keitel, Flor M Munoz, Edwin J Asturias

Center for Medical Ethics and Health Policy Staff Publications

During the course of the 2015-2017 outbreak of Zika virus (ZIKV) in the Americas, the emerging virus was recognized as a congenital infection that could damage the developing brain. As the Latin American ZIKV outbreak advanced, the scientific and public health community questioned if this newly recognized neurotropic flavivirus could affect the developing brain of infants and young children infected after birth. We report here the study design, methods and the challenges and lessons learned from the rapid operationalization of a prospective natural history cohort study aimed at evaluating the potential neurological and neurodevelopmental effects of postnatal ZIKV infection in …


Sars-Cov-2 Mrna Vaccination Causes Prolonged Increased Cortical Thickening And Vascularity In Ipsilateral Axillary Lymph Nodes, Sharlene A Teefey, William D Middleton, Jackson S Turner, Ali H Ellebedy, Teresa Suessen, Michael Wallendorf, Jane A O'Halloran, Rachel Presti Nov 2022

Sars-Cov-2 Mrna Vaccination Causes Prolonged Increased Cortical Thickening And Vascularity In Ipsilateral Axillary Lymph Nodes, Sharlene A Teefey, William D Middleton, Jackson S Turner, Ali H Ellebedy, Teresa Suessen, Michael Wallendorf, Jane A O'Halloran, Rachel Presti

2020-Current year OA Pubs

OBJECTIVES: To describe the serial grey-scale and color Doppler appearance of ipsilateral axillary lymphadenopathy in response to the Pfizer-BioNTech Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) messenger RNA (mRNA) vaccine over 24 to 28 weeks.

METHODS: The data for this study were collected during an observational study to determine whether mRNA vaccination induced a germinal center B cell reaction in blood and draining axillary lymph nodes. The current study evaluated the serial color Doppler and grey-scale sonographic appearance of these lymph nodes. Ten participants who each underwent 6 sonograms and FNAs over 24 to 28 weeks were included in the study. …


Ovarian Steroid Cell Tumors, Not Otherwise Specified: Analysis Of Nine Cases With A Literature Review, Mengyan Lin, Kechun Bao, Lingjia Lu, Shuhang Xu, Yun Liang, Xiaodong Cheng, Fenfen Wang Nov 2022

Ovarian Steroid Cell Tumors, Not Otherwise Specified: Analysis Of Nine Cases With A Literature Review, Mengyan Lin, Kechun Bao, Lingjia Lu, Shuhang Xu, Yun Liang, Xiaodong Cheng, Fenfen Wang

Faculty, Staff and Student Publications

BACKGROUND: Ovarian steroid cell tumors (SCTs), not otherwise specified (NOS), are rare, with few large studies. The purpose of this study was to analyze the clinical features, prognosis, and treatment choices for these patients of different age groups.

METHODS: This was a retrospective study. We identified nine cases of ovarian steroid cell tumor, not otherwise specified, confirmed by post-operative histopathological examination, and analyzed clinical features, surgical procedures, and follow up outcomes. We also reviewed cases reports of ovarian steroid cell tumors, not otherwise specified.

RESULTS: A total of nine cases were included. The age range was 9-68 years (mean, 41.89 …