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Sequence Specificity Despite Intrinsic Disorder: How A Disease-Associated Val/Met Polymorphism Rearranges Tertiary Interactions In A Long Disordered Protein, Ruchi Lohia, Reza Salari, Grace Brannigan Oct 2019

Sequence Specificity Despite Intrinsic Disorder: How A Disease-Associated Val/Met Polymorphism Rearranges Tertiary Interactions In A Long Disordered Protein, Ruchi Lohia, Reza Salari, Grace Brannigan

Open Access Publications

The role of electrostatic interactions and mutations that change charge states in intrinsically disordered proteins (IDPs) is well-established, but many disease-associated mutations in IDPs are charge-neutral. The Val66Met single nucleotide polymorphism (SNP) in precursor brain-derived neurotrophic factor (BDNF) is one of the earliest SNPs to be associated with neuropsychiatric disorders, and the underlying molecular mechanism is unknown. Here we report on over 250 μs of fully-atomistic, explicit solvent, temperature replica-exchange molecular dynamics (MD) simulations of the 91 residue BDNF prodomain, for both the V66 and M66 sequence. The simulations were able to correctly reproduce the location of both local and …


Which Components Of Processing Speed Are Affected In Adhd Subtypes?, Michelle Y Kibby, Sarah A Vadnais, Audreyana C Jagger-Rickels Oct 2019

Which Components Of Processing Speed Are Affected In Adhd Subtypes?, Michelle Y Kibby, Sarah A Vadnais, Audreyana C Jagger-Rickels

Publications

The term "processing speed" (PS) encompasses many components including perceptual, cognitive and output speed. Despite evidence for reduced PS in Attention-Deficit/Hyperactivity Disorder (ADHD), little is known about which component(s) is most impacted in ADHD, or how it may vary by subtypes. Participants included 151 children, ages 8-12 years, with ADHD Predominantly Inattentive Type, ADHD Combined Type and typically developing controls using DSM-IV criteria. All children completed four measures of processing speed: Symbol Search, Coding, Decision Speed, and simple reaction time. We found children with ADHD-PI and ADHD-C had slower perceptual and psychomotor/incidental learning speed than controls and that ADHD-PI had …


Multiple Sclerosis Outcomes After Cancer Immunotherapy, Catherine R. Garcia, Rani Jayswal, Val R. Adams, Lowell B. Anthony, John L. Villano Oct 2019

Multiple Sclerosis Outcomes After Cancer Immunotherapy, Catherine R. Garcia, Rani Jayswal, Val R. Adams, Lowell B. Anthony, John L. Villano

Markey Cancer Center Faculty Publications

INTRODUCTION: Neurological immune-related adverse events are a rare but potentially deadly complication after immune checkpoint inhibitor (ICI) treatment. As multiple sclerosis (MS) is an immune-mediated disease, it is unknown how ICI treatment may affect outcomes.

METHODS: We analyzed the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database for pembrolizumab, atezolizumab, nivolumab, ipilimumab, avelumab, and durvalumab 2 years prior their FDA approval until December 31, 2017, to include all cases with confirmed diagnosis/relapse of MS. We also included cases reported in the literature and a patient from our institution.

RESULTS: We identified 14 cases of MS …


Energy Balance Related Lifestyle Factors And Risk Of Endometrial And Colorectal Cancer Among Individuals With Lynch Syndrome: A Systematic Review, Adriana M Coletta, Susan K Peterson, Leticia A Gatus, Kate J Krause, Susan M Schembre, Susan C Gilchrist, Mala Pande, Eduardo Vilar, Y Nancy You, Miguel A Rodriguez-Bigas, Larkin L Strong, Patrick M Lynch, Karen H Lu, Karen Basen-Engquist Oct 2019

Energy Balance Related Lifestyle Factors And Risk Of Endometrial And Colorectal Cancer Among Individuals With Lynch Syndrome: A Systematic Review, Adriana M Coletta, Susan K Peterson, Leticia A Gatus, Kate J Krause, Susan M Schembre, Susan C Gilchrist, Mala Pande, Eduardo Vilar, Y Nancy You, Miguel A Rodriguez-Bigas, Larkin L Strong, Patrick M Lynch, Karen H Lu, Karen Basen-Engquist

Faculty, Staff and Student Publications

Lifestyle factors related to energy balance, such as excess body weight, poor diet, and physical inactivity, are associated with risk of sporadic endometrial cancer (EC) and colorectal cancer (CRC). There are limited data on energy balance-related lifestyle factors and EC or CRC risk among individuals with lynch syndrome, who are at extraordinarily higher risk of developing EC or CRC. We conducted a systematic review of evidence related to weight status, weight change, dietary habits, and physical activity on EC and CRC risk among individuals with lynch syndrome. Findings are reported narratively. We searched Medline, EMBASE, CENTRAL, PubMed, and clinicaltrials.gov up …


Socioemotional Selectivity And Psychological Health In Amyotrophic Lateral Sclerosis Patients And Caregivers: A Longitudinal, Dyadic Analysis, Suzanne C. Segerstrom, Edward J. Kasarskis, David W. Fardo, Philip M. Westgate Oct 2019

Socioemotional Selectivity And Psychological Health In Amyotrophic Lateral Sclerosis Patients And Caregivers: A Longitudinal, Dyadic Analysis, Suzanne C. Segerstrom, Edward J. Kasarskis, David W. Fardo, Philip M. Westgate

Psychology Faculty Publications

Objective: Socioemotional selectivity theory predicts that as the end of life approaches, goals and resources that provide immediate, hedonic reward become more important than those that provide delayed rewards. This study tested whether these goal domains differentially affected psychological health in the context of marital dyads in which one partner had been diagnosed with amyotrophic lateral sclerosis (ALS), a life-limiting disease.

Design: ALS patients (N = 102) being treated in three multidisciplinary clinics and their spouses (N = 100) reported their loneliness, financial worry and psychological health every 3 months for up to 18 months.

Main …


Tic Suppression In Children With Recent-Onset Tics Predicts 1-Year Tic Outcome, Soyoung Kim, Deanna J Greene, Amy Robichaux-Viehoever, Emily C Bihun, Jonathan M Koller, Haley Acevedo, Bradley L Schlaggar, Kevin J Black Oct 2019

Tic Suppression In Children With Recent-Onset Tics Predicts 1-Year Tic Outcome, Soyoung Kim, Deanna J Greene, Amy Robichaux-Viehoever, Emily C Bihun, Jonathan M Koller, Haley Acevedo, Bradley L Schlaggar, Kevin J Black

Open Access Publications

Successful voluntary tic suppression is a key component of the behavioral interventions that are used to treat tic disorders. This study aimed to examine tic suppression in children with recent-onset tics and determine whether the capacity to suppress tics predicts future tic severity. We tested 45 children (30 male, mean age 7.74 years) with recent-onset tics (mean 3.47 months prior to the first study visit; baseline) and re-examined each child at the 12-month anniversary of the first recognized tic (follow-up). At the baseline visit, children performed a tic suppression task with several conditions: tic freely, inhibit tics given a verbal …


Inhibition Of 4-Aminobutyrate Aminotransferase Protects Against Injury-Induced Osteoarthritis In Mice, Jie Shen, Cuicui Wang, Jun Ying, Taotao Xu, Audrey Mcalinden, Regis J. O'Keefe Sep 2019

Inhibition Of 4-Aminobutyrate Aminotransferase Protects Against Injury-Induced Osteoarthritis In Mice, Jie Shen, Cuicui Wang, Jun Ying, Taotao Xu, Audrey Mcalinden, Regis J. O'Keefe

Open Access Publications

Recently we demonstrated that ablation of the DNA methyltransferase enzyme, Dnmt3b, resulted in catabolism and progression of osteoarthritis (OA) in murine articular cartilage through a mechanism involving increased mitochondrial respiration. In this study, we identify 4-aminobutyrate aminotransferase (Abat) as a downstream target of Dnmt3b. Abat is an enzyme that metabolizes γ-aminobutyric acid to succinate, a key intermediate in the tricarboxylic acid cycle. We show that Dnmt3b binds to the Abat promoter, increases methylation of a conserved CpG sequence just upstream of the transcriptional start site, and inhibits Abat expression. Dnmt3b deletion in articular chondrocytes results in reduced methylation of the …


Related And Unrelated Donor Transplantation For Β-Thalassemia Major: Results Of An International Survey., Chunfu Li, Vikram Mathews, Soyoung Kim, Biju George, Kyle Hebert, Hua Jiang, Changgang Li, Yiping Zhu, Daniel A. Keesler, Jaap Jan Boelens, Christopher C. Dvorak, Rajni Agarwal, Jeffery J. Auletta, Rakesh K. Goyal, Rabi Hanna, Kimberly Kasow, Shalini Shenoy, Angela R. Smith, Mark C. Walters, Mary Eapen Sep 2019

Related And Unrelated Donor Transplantation For Β-Thalassemia Major: Results Of An International Survey., Chunfu Li, Vikram Mathews, Soyoung Kim, Biju George, Kyle Hebert, Hua Jiang, Changgang Li, Yiping Zhu, Daniel A. Keesler, Jaap Jan Boelens, Christopher C. Dvorak, Rajni Agarwal, Jeffery J. Auletta, Rakesh K. Goyal, Rabi Hanna, Kimberly Kasow, Shalini Shenoy, Angela R. Smith, Mark C. Walters, Mary Eapen

Manuscripts, Articles, Book Chapters and Other Papers

We studied 1110 patients with β-thalassemia major aged ≤25 years who received transplants with grafts from HLA-matched related (n = 677; 61%), HLA-mismatched related (n = 78; 7%), HLA-matched unrelated (n = 252; 23%), and HLA-mismatched unrelated (n = 103; 9%) donors between 2000 and 2016. Ninety percent of transplants were performed in the last decade. Eight-five percent of patients received ≥20 transfusions and 88% were inadequately chelated. All patients received myeloablative-conditioning regimen. Overall and event-free survival were highest for patients aged ≤6 years and after HLA-matched related and HLA-matched unrelated donor transplantation. The 5-year probabilities of overall survival for …


Satb2 Versus Cdx2: A Battle Royale For Diagnostic Supremacy In Mucinous Tumors, Stefan M. Brettfeld, Benjamin D. Ramos, Ryan S. Berry, David R. Martin, Joshua A. Hanson Sep 2019

Satb2 Versus Cdx2: A Battle Royale For Diagnostic Supremacy In Mucinous Tumors, Stefan M. Brettfeld, Benjamin D. Ramos, Ryan S. Berry, David R. Martin, Joshua A. Hanson

Pathology Research and Scholarship

CONTEXT.—: Metastatic mucinous tumors present a diagnostic challenge for pathologists as tumor histomorphology is often nonspecific and optimal immunoprofiles are still under investigation.

OBJECTIVE.—: To present a head-to-head comparison of special AT-rich sequence-binding protein 2 (SATB2) and caudal type homeobox 2 (CDX2) expression in a diverse array of primary mucinous tumors.

DESIGN.—: SATB2 and CDX2 immunohistochemical stains were performed on whole sections from 44 mucinous colorectal carcinomas and 175 noncolorectal mucinous tumors. A nuclear scoring system measuring intensity (0-3+) and percentage staining (0 =

RESULTS.—: SATB2 demonstrated acceptable accuracy at low to moderate expression levels (H-scores of 1-4). With these …


Perceived Barriers Related To Testing, Management And Treatment Of Hcv Infection Among Physicians Prescribing Opioid Agonist Therapy: The C-Scope Study, Alain H. Litwin, Martine Drolet, Chizoba Nwankwo, Martha Torrens, Andrej Kastelic, Stephan Walcher, Lorenzo Somaini, Emily Mulvihill, Jochen Ertl, Jason Grebely Sep 2019

Perceived Barriers Related To Testing, Management And Treatment Of Hcv Infection Among Physicians Prescribing Opioid Agonist Therapy: The C-Scope Study, Alain H. Litwin, Martine Drolet, Chizoba Nwankwo, Martha Torrens, Andrej Kastelic, Stephan Walcher, Lorenzo Somaini, Emily Mulvihill, Jochen Ertl, Jason Grebely

Project ECHO Bibliography

The aim of this analysis was to evaluate perceived barriers related to HCV testing, management and treatment among physicians practicing in clinics offering opioid agonist treatment (OAT). C-SCOPE was a study consisting of a self-administered survey among physicians practicing at clinics providing OAT in Australia, Canada, Europe and the United States between April and May 2017. A 5-point Likert scale (1 = not a barrier, 3 = moderate barrier, 5 = extreme barrier) was used to measure responses to perceived barriers for HCV testing, evaluation and treatment across the domains of the health system, clinic and patient. Among the 203 …


Low-Cost, High-Resolution Imaging For Detecting Cervical Precancer In Medically-Underserved Areas Of Texas, Sonia G Parra, Ana M Rodriguez, Katelin D Cherry, Richard A Schwarz, Rose M Gowen, Laura B Guerra, Andrea M Milbourne, Paul A Toscano, Susan P Fisher-Hoch, Kathleen M Schmeler, Rebecca R Richards-Kortum Sep 2019

Low-Cost, High-Resolution Imaging For Detecting Cervical Precancer In Medically-Underserved Areas Of Texas, Sonia G Parra, Ana M Rodriguez, Katelin D Cherry, Richard A Schwarz, Rose M Gowen, Laura B Guerra, Andrea M Milbourne, Paul A Toscano, Susan P Fisher-Hoch, Kathleen M Schmeler, Rebecca R Richards-Kortum

Faculty, Staff and Student Publications

OBJECTIVE: Cervical cancer rates in the United States have declined since the 1940's, however, cervical cancer incidence remains elevated in medically-underserved areas, especially in the Rio Grande Valley (RGV) along the Texas-Mexico border. High-resolution microendoscopy (HRME) is a low-cost, in vivo imaging technique that can identify high-grade precancerous cervical lesions (CIN2+) at the point-of-care. The goal of this study was to evaluate the performance of HRME in medically-underserved areas in Texas, comparing results to a tertiary academic medical center.

METHODS: HRME was evaluated in five different outpatient clinical settings, two in Houston and three in the RGV, with medical providers …


Low-Cost, High-Resolution Imaging For Detecting Cervical Precancer In Medically-Underserved Areas Of Texas, Sonia G Parra, Ana M Rodriguez, Katelin D Cherry, Richard A Schwarz, Rose M Gowen, Laura B Guerra, Andrea M Milbourne, Paul A Toscano, Susan P Fisher-Hoch, Kathleen M Schmeler, Rebecca R Richards-Kortum Sep 2019

Low-Cost, High-Resolution Imaging For Detecting Cervical Precancer In Medically-Underserved Areas Of Texas, Sonia G Parra, Ana M Rodriguez, Katelin D Cherry, Richard A Schwarz, Rose M Gowen, Laura B Guerra, Andrea M Milbourne, Paul A Toscano, Susan P Fisher-Hoch, Kathleen M Schmeler, Rebecca R Richards-Kortum

Faculty, Staff and Student Publications

OBJECTIVE: Cervical cancer rates in the United States have declined since the 1940's, however, cervical cancer incidence remains elevated in medically-underserved areas, especially in the Rio Grande Valley (RGV) along the Texas-Mexico border. High-resolution microendoscopy (HRME) is a low-cost, in vivo imaging technique that can identify high-grade precancerous cervical lesions (CIN2+) at the point-of-care. The goal of this study was to evaluate the performance of HRME in medically-underserved areas in Texas, comparing results to a tertiary academic medical center.

METHODS: HRME was evaluated in five different outpatient clinical settings, two in Houston and three in the RGV, with medical providers …


Childhood Obesity In The State Of Missouri: A Review For Providers To Counsel And Treat Patients., Usman Hasnie, Matthew Lindquist, Brooke Sweeney, Sarah Hampl, Betty M. Drees Sep 2019

Childhood Obesity In The State Of Missouri: A Review For Providers To Counsel And Treat Patients., Usman Hasnie, Matthew Lindquist, Brooke Sweeney, Sarah Hampl, Betty M. Drees

Manuscripts, Articles, Book Chapters and Other Papers

Childhood obesity is a common disease both nationally and in the state of Missouri. Obesity in childhood is often under-recognized and is difficult to treat. Screening, accurate diagnosis, and counseling is imperative to proper management. Common barriers to treatment include a lack of accurate identification and a lack of awareness of needed and available treatments of this disease in the pediatric setting. This review article highlights behavioral measures as well as pharmacologic and surgical therapies for obesity in children. This review is intended as guidance for providers to properly counsel and treat patients with this disease.


Apples To Apples? Neural Correlates Of Emotion Regulation Differences Between High- And Low-Risk Adolescents, Michael T Perino, João F Guassi Moreira, Ethan M Mccormick, Eva H Telzer Aug 2019

Apples To Apples? Neural Correlates Of Emotion Regulation Differences Between High- And Low-Risk Adolescents, Michael T Perino, João F Guassi Moreira, Ethan M Mccormick, Eva H Telzer

2010-2019 OA Pubs

Adolescence has been noted as a period of increased risk taking. The literature on normative neurodevelopment implicates aberrant activation of affective and regulatory regions as key to inhibitory failures. However, many of these studies have not included adolescents engaging in high rates of risky behavior, making generalizations to the most at-risk populations potentially problematic. We conducted a comparative study of nondelinquent community (n = 24, mean age = 15.8 years, 12 female) and delinquent adolescents (n = 24, mean age = 16.2 years, 12 female) who completed a cognitive control task during functional magnetic resonance imaging, where behavioral inhibition was …


Best Practices For Bioinformatic Characterization Of Neoantigens For Clinical Utility, Megan M Richters, Huiming Xia, Katie M Campbell, William E Gillanders, Obi L Griffith, Malachi Griffith Aug 2019

Best Practices For Bioinformatic Characterization Of Neoantigens For Clinical Utility, Megan M Richters, Huiming Xia, Katie M Campbell, William E Gillanders, Obi L Griffith, Malachi Griffith

Open Access Publications

Neoantigens are newly formed peptides created from somatic mutations that are capable of inducing tumor-specific T cell recognition. Recently, researchers and clinicians have leveraged next generation sequencing technologies to identify neoantigens and to create personalized immunotherapies for cancer treatment. To create a personalized cancer vaccine, neoantigens must be computationally predicted from matched tumor-normal sequencing data, and then ranked according to their predicted capability in stimulating a T cell response. This candidate neoantigen prediction process involves multiple steps, including somatic mutation identification, HLA typing, peptide processing, and peptide-MHC binding prediction. The general workflow has been utilized for many preclinical and clinical …


Designing High-Quality Implementation Research: Development, Application, Feasibility And Preliminary Evaluation Of The Implementation Science Research Development (Impres) Tool And Guide, Louise Hull, Lucy Goulding, Zarnie Khadjesari, Rachel E. Davis, Andy Healey, Ioannis Bakolis, Nick Sevdalis Aug 2019

Designing High-Quality Implementation Research: Development, Application, Feasibility And Preliminary Evaluation Of The Implementation Science Research Development (Impres) Tool And Guide, Louise Hull, Lucy Goulding, Zarnie Khadjesari, Rachel E. Davis, Andy Healey, Ioannis Bakolis, Nick Sevdalis

Faculty Publications

BACKGROUND: Designing implementation research can be a complex and daunting task, especially for applied health researchers who have not received specialist training in implementation science. We developed the Implementation Science Research Development (ImpRes) tool and supplementary guide to address this challenge and provide researchers with a systematic approach to designing implementation research. METHODS: A multi-method and multi-stage approach was employed. An international, multidisciplinary expert panel engaged in an iterative brainstorming and consensus-building process to generate core domains of the ImpRes tool, representing core implementation science principles and concepts that researchers should consider when designing implementation research. Simultaneously, an iterative process …


Cancer Cell Population Growth Kinetics At Low Densities Deviate From The Exponential Growth Model And Suggest An Allee Effect., Kaitlyn E Johnson, Grant Howard, William Mo, Michael K Strasser, Ernesto A B F Lima, Sui Huang, Amy Brock Aug 2019

Cancer Cell Population Growth Kinetics At Low Densities Deviate From The Exponential Growth Model And Suggest An Allee Effect., Kaitlyn E Johnson, Grant Howard, William Mo, Michael K Strasser, Ernesto A B F Lima, Sui Huang, Amy Brock

Articles, Abstracts, and Reports

Most models of cancer cell population expansion assume exponential growth kinetics at low cell densities, with deviations to account for observed slowing of growth rate only at higher densities due to limited resources such as space and nutrients. However, recent preclinical and clinical observations of tumor initiation or recurrence indicate the presence of tumor growth kinetics in which growth rates scale positively with cell numbers. These observations are analogous to the cooperative behavior of species in an ecosystem described by the ecological principle of the Allee effect. In preclinical and clinical models, however, tumor growth data are limited by the …


Behavior Change Interventions Delivered Through Interpersonal Communication, Agricultural Activities, Community Mobilization, And Mass Media Increase Complementary Feeding Practices And Reduce Child Stunting In Ethiopia, Sunny S. Kim, Phuong Hong Nguyen, Yisehac Yohannes, Yewelsew Abebe, Manisha Tharaney, Elizabeth Drummond, Edward A. Frongillo Jr., Marie T. Ruel, Purnima Menon Aug 2019

Behavior Change Interventions Delivered Through Interpersonal Communication, Agricultural Activities, Community Mobilization, And Mass Media Increase Complementary Feeding Practices And Reduce Child Stunting In Ethiopia, Sunny S. Kim, Phuong Hong Nguyen, Yisehac Yohannes, Yewelsew Abebe, Manisha Tharaney, Elizabeth Drummond, Edward A. Frongillo Jr., Marie T. Ruel, Purnima Menon

Faculty Publications

BACKGROUND: Appropriate infant and young child feeding practices are critical for optimal child growth and development, but in Ethiopia, complementary feeding (CF) practices are very poor. Alive & Thrive (A&T) provided intensive behavior change interventions through 4 platforms: interpersonal communication (IPC), nutrition-sensitive agricultural activities (AG), community mobilization (CM), and mass media (MM).

OBJECTIVES: The aim of this study was to evaluate the impact of A&T intensive compared with nonintensive interventions (standard nutrition counseling and agricultural extension service and less intensive CM and MM) on CF practices and knowledge and child anthropometric outcomes.

METHODS: We used a cluster-randomized …


2019 Hrs/Ehra/Aphrs/Lahrs Expert Consensus Statement On Catheter Ablation Of Ventricular Arrhythmias, Edmond M Cronin, Phillip Cuculich, Et Al. Aug 2019

2019 Hrs/Ehra/Aphrs/Lahrs Expert Consensus Statement On Catheter Ablation Of Ventricular Arrhythmias, Edmond M Cronin, Phillip Cuculich, Et Al.

2010-2019 OA Pubs

Ventricular arrhythmias are an important cause of morbidity and mortality and come in a variety of forms, from single premature ventricular complexes to sustained ventricular tachycardia and fibrillation. Rapid developments have taken place over the past decade in our understanding of these arrhythmias and in our ability to diagnose and treat them. The field of catheter ablation has progressed with the development of new methods and tools, and with the publication of large clinical trials. Therefore, global cardiac electrophysiology professional societies undertook to outline recommendations and best practices for these procedures in a document that will update and replace the …


Visualization Of Cardiac Implantable Electronic Device Data For Older Adults Using Participatory Design., Ryan Ahmed, Tammy Toscos Phd, Romisa Rohani Ghahari, Richard J Holden, Elizabeth Martin, Shauna Wagner, Carly Daley, Amanda Coupe, Michael Mirro Md Aug 2019

Visualization Of Cardiac Implantable Electronic Device Data For Older Adults Using Participatory Design., Ryan Ahmed, Tammy Toscos Phd, Romisa Rohani Ghahari, Richard J Holden, Elizabeth Martin, Shauna Wagner, Carly Daley, Amanda Coupe, Michael Mirro Md

Health Services and Informatics Research

Patients with heart failure (HF) are commonly implanted with cardiac resynchronization therapy (CRT) devices as part of their treatment. Presently, they cannot directly access the remote monitoring (RM) data generated from these devices, representing a missed opportunity for increased knowledge and engagement in care. However, electronic health data sharing can create information overload issues for both clinicians and patients, and some older patients may not be comfortable using the technology (i.e., computers and smartphones) necessary to access this data. To mitigate these problems, patients can be directly involved in the creation of data visualization tailored to their preferences and needs, …


Measurement Repeatability Of 18 F-Fdg Pet/Ct Versus 18 F-Fdg Pet/Mri In Solid Tumors Of The Pelvis, Tyler J Fraum, Kathryn J Fowler, John P Crandall, Richard A Laforest, Amber Salter, Hongyu An, Michael A Jacobs, Perry W Grigsby, Farrokh Dehdashti, Richard L Wahl Aug 2019

Measurement Repeatability Of 18 F-Fdg Pet/Ct Versus 18 F-Fdg Pet/Mri In Solid Tumors Of The Pelvis, Tyler J Fraum, Kathryn J Fowler, John P Crandall, Richard A Laforest, Amber Salter, Hongyu An, Michael A Jacobs, Perry W Grigsby, Farrokh Dehdashti, Richard L Wahl

Open Access Publications

Knowledge of the within-subject variability of


Customized Methylc-Capture Sequencing To Evaluate Variation In The Human Sperm Dna Methylome Representative Of Altered Folate Metabolism., Donovan Chan, Xiaojian Shao, Marie-Charlotte Dumargne, Mahmoud Aarabi, Marie-Michelle Simon, Tony Kwan, Janice L. Bailey, Bernard Robaire, Sarah Kimmins, Maria C. San Gabriel, Armand Zini, Clifford Librach, Sergey Moskovtsev, Elin Grundberg, Guillaume Bourque, T Pastinen, Jacquetta M. Trasler Aug 2019

Customized Methylc-Capture Sequencing To Evaluate Variation In The Human Sperm Dna Methylome Representative Of Altered Folate Metabolism., Donovan Chan, Xiaojian Shao, Marie-Charlotte Dumargne, Mahmoud Aarabi, Marie-Michelle Simon, Tony Kwan, Janice L. Bailey, Bernard Robaire, Sarah Kimmins, Maria C. San Gabriel, Armand Zini, Clifford Librach, Sergey Moskovtsev, Elin Grundberg, Guillaume Bourque, T Pastinen, Jacquetta M. Trasler

Manuscripts, Articles, Book Chapters and Other Papers

Background: The sperm DNA methylation landscape is unique and critical for offspring health. If gamete-derived DNA methylation escapes reprograming in early embryos, epigenetic defects in sperm may be transmitted to the next generation. Current techniques to assess sperm DNA methylation show bias toward CpG-dense regions and do not target areas of dynamic methylation, those predicted to be environmentally sensitive and tunable regulatory elements.

Objectives: Our goal was to assess variation in human sperm DNA methylation and design a targeted capture panel to interrogate the human sperm methylome.

Methods: To characterize variation in sperm DNA methylation, we performed whole genome bisulfite …


Rheumatoid Arthritis-Relevant Dna Methylation Changes Identified In Acpa-Positive Asymptomatic Individuals Using Methylome Capture Sequencing., Xiaojian Shao, Marie Hudson, Ines Colmegna, Celia M T Greenwood, Marvin J. Fritzler, Philip Awadalla, T Pastinen, Sasha Bernatsky Jul 2019

Rheumatoid Arthritis-Relevant Dna Methylation Changes Identified In Acpa-Positive Asymptomatic Individuals Using Methylome Capture Sequencing., Xiaojian Shao, Marie Hudson, Ines Colmegna, Celia M T Greenwood, Marvin J. Fritzler, Philip Awadalla, T Pastinen, Sasha Bernatsky

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: To compare DNA methylation in subjects positive vs negative for anti-citrullinated protein antibodies (ACPA), a key serological marker of rheumatoid arthritis (RA) risk.

METHODS: With banked serum from a random subset (N = 3600) of a large general population cohort, we identified ACPA-positive samples and compared them to age- and sex-matched ACPA-negative controls. We used a custom-designed methylome panel to conduct targeted bisulfite sequencing of 5 million CpGs located in regulatory or hypomethylated regions of DNA from whole blood (red blood cell lysed). Using binomial regression models, we investigated the differentially methylated regions (DMRs) between ACPA-positive vs ACPA-negative subjects. …


Comparison Of The Use Of Wireless Capsule Endoscopy With Magnetic Resonance Enterography In Children With Inflammatory Bowel Disease., Nadia Mazen Hijaz, Thomas M. Attard, Jennifer Colombo, Neil J. Mardis, Craig A. Friesen Jul 2019

Comparison Of The Use Of Wireless Capsule Endoscopy With Magnetic Resonance Enterography In Children With Inflammatory Bowel Disease., Nadia Mazen Hijaz, Thomas M. Attard, Jennifer Colombo, Neil J. Mardis, Craig A. Friesen

Manuscripts, Articles, Book Chapters and Other Papers

Background: Magnetic resonance enterography (MRE) and wireless capsule endoscopy (WCE) are equally accepted modalities for noninvasive screening of small bowel involvement (SBI) in children with Crohn's disease (CD) and indeterminate colitis (IC) albeit there is a paucity of data comparing the two and thereby guiding the clinician in selecting the ideal diagnostic approach. Therefore, the goal of this study is to provide additional evidence for capsule endoscopy role in the evaluation of established Crohn's disease exacerbation compared to MRE in relation to Pediatric Crohn's Disease Activity Index (PCDAI), and histological indices.

Aim: To prospectively compare the findings of MRE and …


Demographic, Clinical, And Treatment Characteristics Of The Juvenile Primary Fibromyalgia Syndrome Cohort Enrolled In The Childhood Arthritis And Rheumatology Research Alliance Legacy Registry., Jennifer E. Weiss, Kenneth N. Schikler, Alexis D. Boneparth, Mark Connelly, Carra Registry Investigators Jul 2019

Demographic, Clinical, And Treatment Characteristics Of The Juvenile Primary Fibromyalgia Syndrome Cohort Enrolled In The Childhood Arthritis And Rheumatology Research Alliance Legacy Registry., Jennifer E. Weiss, Kenneth N. Schikler, Alexis D. Boneparth, Mark Connelly, Carra Registry Investigators

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: To describe the demographic, clinical, and treatment characteristics of youth diagnosed with juvenile primary fibromyalgia syndrome (JPFS) who are seen in pediatric rheumatology clinics.

METHODS: Information on demographics, symptoms, functioning, and treatments recommended and tried were obtained on patients with JPFS as part of a multi-site patient registry (the Childhood Arthritis and Rheumatology Research Alliance Legacy Registry). Data were summarized using descriptive statistics. In a subset of patients completing registry follow-up visits, changes in symptoms, pain, and functioning were evaluated using growth modeling.

RESULTS: Of the 201 patients with JPFS enrolled in the registry, most were Caucasian/White (85%), non-Hispanic …


Relationship Between Duration And Extent Of Oedema And Visual Acuity Outcome With Ranibizumab In Diabetic Macular Oedema: A Post Hoc Analysis Of Protocol I Data, Srinivas R Sadda, Joanna Campbell, Pravin U Dugel, Nancy M Holekamp, Szilárd Kiss, Anat Loewenstein, Albert J Augustin, Vanessa Shih, Xiaoshu Xu, Charles C Wykoff, Scott M Whitcup Jul 2019

Relationship Between Duration And Extent Of Oedema And Visual Acuity Outcome With Ranibizumab In Diabetic Macular Oedema: A Post Hoc Analysis Of Protocol I Data, Srinivas R Sadda, Joanna Campbell, Pravin U Dugel, Nancy M Holekamp, Szilárd Kiss, Anat Loewenstein, Albert J Augustin, Vanessa Shih, Xiaoshu Xu, Charles C Wykoff, Scott M Whitcup

Open Access Publications

BACKGROUND/OBJECTIVES: This post hoc analysis explores the relationship between residual oedema exposure after ranibizumab treatment initiation and long-term visual acuity outcome in eyes with centre-involved diabetic macular oedema (DMO).

SUBJECTS/METHODS: Eyes randomised to the ranibizumab + prompt or deferred laser treatment arms in the Protocol I trial and with observed central retinal thickness (CRT) readings at baseline and ≥1 follow-up visits (n = 367) were stratified by 1) oedema duration (number of study visits with CRT ≥ 250 µm during the first 52 weeks of ranibizumab treatment); and 2) oedema extent (amount of excess CRT [≥ 250 µm] at each …


Effects Of Microbiota-Directed Foods In Gnotobiotic Animals And Undernourished Children, Jeanette L Gehrig, Siddarth Venkatesh, Hao-Wei Chang, Matthew C Hibberd, Vanderlene L Kung, Jiye Cheng, Robert Y Chen, Sathish Subramanian, Carrie A Cowardin, Martin F Meier, David O'Donnell, Michael Talcott, Larry D Spears, Clay F Semenkovich, Christopher Sawyer, Richard D Head, Michael J Barratt, Jeffrey I Gordon, Et Al Jul 2019

Effects Of Microbiota-Directed Foods In Gnotobiotic Animals And Undernourished Children, Jeanette L Gehrig, Siddarth Venkatesh, Hao-Wei Chang, Matthew C Hibberd, Vanderlene L Kung, Jiye Cheng, Robert Y Chen, Sathish Subramanian, Carrie A Cowardin, Martin F Meier, David O'Donnell, Michael Talcott, Larry D Spears, Clay F Semenkovich, Christopher Sawyer, Richard D Head, Michael J Barratt, Jeffrey I Gordon, Et Al

Open Access Publications

To examine the contributions of impaired gut microbial community development to childhood undernutrition, we combined metabolomic and proteomic analyses of plasma samples with metagenomic analyses of fecal samples to characterize the biological state of Bangladeshi children with severe acute malnutrition (SAM) as they transitioned, after standard treatment, to moderate acute malnutrition (MAM) with persistent microbiota immaturity. Host and microbial effects of microbiota-directed complementary food (MDCF) prototypes targeting weaning-phase bacterial taxa underrepresented in SAM and MAM microbiota were characterized in gnotobiotic mice and gnotobiotic piglets colonized with age- and growth-discriminatory bacteria. A randomized, double-blind controlled feeding study identified a lead MDCF …


A Sparse Covarying Unit That Describes Healthy And Impaired Human Gut Microbiota Development, Arjun S Raman, Jeanette L Gehrig, Siddarth Venkatesh, Hao-Wei Chang, Matthew C Hibberd, Sathish Subramanian, Michael J Barratt, Jeffrey I Gordon, Et Al Jul 2019

A Sparse Covarying Unit That Describes Healthy And Impaired Human Gut Microbiota Development, Arjun S Raman, Jeanette L Gehrig, Siddarth Venkatesh, Hao-Wei Chang, Matthew C Hibberd, Sathish Subramanian, Michael J Barratt, Jeffrey I Gordon, Et Al

Open Access Publications

Characterizing the organization of the human gut microbiota is a formidable challenge given the number of possible interactions between its components. Using a statistical approach initially applied to financial markets, we measured temporally conserved covariance among bacterial taxa in the microbiota of healthy members of a Bangladeshi birth cohort sampled from 1 to 60 months of age. The results revealed an "ecogroup" of 15 covarying bacterial taxa that provide a concise description of microbiota development in healthy children from this and other low-income countries, and a means for monitoring community repair in undernourished children treated with therapeutic foods. Features of …


Development And Initial Psychometric Evaluation Of The Computer-Based Prostate Cancer Screening Decision Aid Acceptance Scale For African-American Men, Otis L. Owens, Nikki R. Wooten, Abbas S. Tavakoli Jul 2019

Development And Initial Psychometric Evaluation Of The Computer-Based Prostate Cancer Screening Decision Aid Acceptance Scale For African-American Men, Otis L. Owens, Nikki R. Wooten, Abbas S. Tavakoli

Faculty Publications

BACKGROUND:

To reliably evaluate the acceptance and use of computer-based prostate cancer decision aids (CBDAs) for African-American men, culturally relevant measures are needed. This study describes the development and initial psychometric evaluation of the 24-item Computer-Based Prostate Cancer Screening Decision Aid Acceptance Scale among 357 African-American men.

METHODS:

Exploratory factor analysis (EFA) with maximum likelihood estimation and polychoric correlations followed by Promax and Varimax rotations. RESULTS: EFA yielded three factors: Technology Use Expectancy and Intention (16 items), Technology Use Anxiety (5 items), and Technology Use Self-Efficacy (3 items) with good to excellent internal consistency reliability at .95, .90, and .85, …


New Insights Into Dna Methylation Signatures: Smarca2 Variants In Nicolaides-Baraitser Syndrome., Eric Chater-Diehl, Resham Ejaz, Cheryl Cytrynbaum, Michelle T. Siu, Andrei Turinsky, Sanaa Choufani, Sarah J. Goodman, Omar Abdul-Rahman, Melanie Bedford, Naghmeh Dorrani, Kendra Engleman, Josue Flores-Daboub, David Genevieve, Roberto Mendoza-Londono, Wendy Meschino, Laurence Perrin, Nicole Safina, Sharron Townshend, Stephen W. Scherer, Evdokia Anagnostou, Amelie Piton, Matthew Deardorff, Michael Brudno, David Chitayat, Rosanna Weksberg Jul 2019

New Insights Into Dna Methylation Signatures: Smarca2 Variants In Nicolaides-Baraitser Syndrome., Eric Chater-Diehl, Resham Ejaz, Cheryl Cytrynbaum, Michelle T. Siu, Andrei Turinsky, Sanaa Choufani, Sarah J. Goodman, Omar Abdul-Rahman, Melanie Bedford, Naghmeh Dorrani, Kendra Engleman, Josue Flores-Daboub, David Genevieve, Roberto Mendoza-Londono, Wendy Meschino, Laurence Perrin, Nicole Safina, Sharron Townshend, Stephen W. Scherer, Evdokia Anagnostou, Amelie Piton, Matthew Deardorff, Michael Brudno, David Chitayat, Rosanna Weksberg

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Nicolaides-Baraitser syndrome (NCBRS) is a neurodevelopmental disorder caused by pathogenic sequence variants in SMARCA2 which encodes the catalytic component of the chromatin remodeling BAF complex. Pathogenic variants in genes that encode epigenetic regulators have been associated with genome-wide changes in DNA methylation (DNAm) in affected individuals termed DNAm signatures.

METHODS: Genome-wide DNAm was assessed in whole-blood samples from the individuals with pathogenic SMARCA2 variants and NCBRS diagnosis (n = 8) compared to neurotypical controls (n = 23) using the Illumina MethylationEPIC array. Differential methylated CpGs between groups (DNAm signature) were identified and used to generate a model enabling classification …