Digital Commons Network^™

Six Month Abstinence Heterogeneity In The Best Quit Study., Harold S Javitz, Terry M Bush, Jennifer C Lovejoy, Alula J Torres, Tallie Wetzel, Ken P Wassum, Marcia M Tan, Nabil Alshurafa, Bonnie Spring

Articles, Abstracts, and Reports

BACKGROUND: Understanding the characteristics of smokers who are successful in quitting may help to increase smoking cessation rates.

PURPOSE: To examine heterogeneity in cessation outcome at 6 months following smoking cessation behavioral counseling with or without weight management counseling.

METHODS: 2,540 smokers were recruited from a large quitline provider and then randomized to receive proactive smoking cessation behavioral counseling without or with two versions of weight management counseling. A Classification and Regression Tree (CART) analysis was conducted to identify the individual pretreatment and treatment characteristics of groups of smokers with different quitting success (as measured by point prevalence of self-reported …

Gilteritinib Or Chemotherapy For Relapsed Or Refractory Flt3-Mutated Aml, Alexander E. Perl, Giovanni Martinelli, Jorge E. Cortes, Andreas Neubauer, Ellin Berman, Stefania Paolini, Pau Montesinos, Maria R. Baer, Richard A. Larson, Celalettin Ustun, Francesco Fabbiano, Harry P. Erba, Antonio Di Stasi, Robert Stuart, Rebecca Olin, Margaret Kasner, Fabio Ciceri, Wen-Chien Chou, Nikolai Podoltsev, Christian Recher, Hisayuki Yokoyama, Naoko Hosono, Sung-Soo Yoon, Je-Hwan Lee, Timothy Pardee, Amir T. Fathi, Chaofeng Liu, Nahla Hasabou, Xuan Liu, Erkut Bahceci, Mark J. Levis

Department of Medical Oncology Faculty Papers

BACKGROUND: Patients with relapsed or refractory acute myeloid leukemia (AML) with mutations in the FMS-like tyrosine kinase 3 gene (FLT3) infrequently have a response to salvage chemotherapy. Gilteritinib is an oral, potent, selective FLT3 inhibitor with single-agent activity in relapsed or refractory FLT3-mutated AML.

METHODS: In a phase 3 trial, we randomly assigned adults with relapsed or refractory FLT3-mutated AML in a 2:1 ratio to receive either gilteritinib (at a dose of 120 mg per day) or salvage chemotherapy. The two primary end points were overall survival and the percentage of patients who had complete remission …

Choice Of Conditioning Regimens For Bone Marrow Transplantation In Severe Aplastic Anemia., Nelli Bejanyan, Soyoung Kim, Kyle M. Hebert, Natasha Kekre, Hisham Abdel-Azim, Ibrahim A. Ahmed, Mahmoud Aljurf, Sherif M. Badawy, Amer Beitinjaneh, Jaap Jan Boelens, Miguel Angel Diaz, Christopher C. Dvorak, Shahinaz Gadalla, James Gajewski, Robert Peter Gale, Siddhartha Ganguly, Andrew R. Gennery, Biju George, Usama Gergis, David Gómez-Almaguer, Marta Gonzalez Vicent, Hasan Hashem, Rammurti T. Kamble, Kimberly A. Kasow, Hillard M. Lazarus, Vikram Mathews, Paul J. Orchard, Michael Pulsipher, Olle Ringden, Kirk Schultz, Pierre Teira, Ann E. Woolfrey, Blachy Dávila Saldaña, Bipin Savani, Jacek Winiarski, Jean Yared, Daniel J. Weisdorf, Joseph H. Antin, Mary Eapen

Manuscripts, Articles, Book Chapters and Other Papers

Allogeneic bone marrow transplantation (BMT) is curative therapy for the treatment of patients with severe aplastic anemia (SAA). However, several conditioning regimens can be used for BMT. We evaluated transplant conditioning regimens for BMT in SAA after HLA-matched sibling and unrelated donor BMT. For recipients of HLA-matched sibling donor transplantation (n = 955), fludarabine (Flu)/cyclophosphamide (Cy)/antithymocyte globulin (ATG) or Cy/ATG led to the best survival. The 5-year probabilities of survival with Flu/Cy/ATG, Cy/ATG, Cy ± Flu, and busulfan/Cy were 91%, 91%, 80%, and 84%, respectively (P = .001). For recipients of 8/8 and 7/8 HLA allele-matched unrelated donor transplantation (n …

Adjuvant Chemotherapy And Survival Among Patients 70 Years Of Age And Younger With Node-Negative Breast Cancer And The 21-Gene Recurrence Score Of 26-30, Seho Park, Yunan Han, Ying Liu, Adetunji T Toriola, Lindsay L Peterson, Graham A Colditz, Seung Il Kim, Young Up Cho, Byeong-Woo Park, Yikyung Park

Open Access Publications

BACKGROUND: The benefits of chemotherapy in node-negative, hormone receptor-positive, and human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients with the 21-gene recurrence score (RS) of 18-30, particularly those with RS 26-30, are not known.

METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) data, we retrospectively identified 29,137 breast cancer patients with the 21-gene RS of 18-30 diagnosed between 2004 and 2015. Mortality risks according to the RS and chemotherapy use were compared by the Kaplan-Meier method and Cox's proportional hazards model.

RESULTS: Among the breast cancer patients with the RS 18-30, 21% of them had RS 26-30. …

The Gut-Microbiome In Gulf War Veterans: A Preliminary Report, Patricia A. Janulewicz, Ratanesh K. Seth, Jeffrey M. Carlson, Joy Ajama, Emily Quinn, Timothy Heeren, Nancy Klimas, Steven M. Lasley, Ronnie Horner, Kimberly Sullivan, Saurabh Chatterjee

Faculty Publications

Gulf War Illness (GWI) is a chronic multi-symptom disorder affecting the central nervous system (CNS), immune and gastrointestinal (GI) systems of Gulf War veterans (GWV). We assessed the relationships between GWI, GI symptoms, gut microbiome and inflammatory markers in GWV from the Boston Gulf War Illness Consortium (GWIC). Three groups of GWIC veterans were recruited in this pilot study; GWV without GWI and no gastrointestinal symptoms (controls), GWV with GWI and no gastrointestinal symptoms (GWI-GI), GWV with GWI who reported gastrointestinal symptoms (GW+GI). Here we report on a subset of the first thirteen stool samples analyzed. Results showed significantly different …

Impact Of Combat Experience On Adult Learning For Students Enrolled At Liberty University In Spring 2019, Stephany Dawn Pracht

Doctoral Dissertations and Projects

This dissertation joins an active conversation in the behavioral sciences regarding the challenges of assimilating the adult experienced trauma into the adult education setting. This quantitative study employed a nonexperimental, causal-comparative research design to explore the perceptions of current and former combat-experienced military students about their academic experiences. By exploring the needs in higher education that are concerning and prevalent among those who have experienced active combat, this paper discusses the effects of the combat experience on current and former military members as they seek to acclimate to the academic world. This study was guided by Malcolm Knowles’s idea that …

Phase I, Open-Label, Dose-Escalation Study Of The Safety, Pharmacokinetics, Pharmacodynamics, And Efficacy Of Gsk2879552 In Relapsed/Refractory Sclc, Todd M Bauer, Benjamin Besse, Alex Martinez-Marti, Jose Manuel Trigo, Victor Moreno, Pilar Garrido, Geraldine Ferron-Brady, Yuehui Wu, Jennifer Park, Therese Collingwood, Ryan G Kruger, Helai P Mohammad, Marc S Ballas, Arindam Dhar, Ramaswamy Govindan

Open Access Publications

INTRODUCTION: This first-time-in-humans study assessed the safety, pharmacokinetics (PK), pharmacodynamics (PD), and clinical activity of GSK2879552 in patients with relapsed or refractory SCLC.

METHODS: This phase I, multicenter, open-label study (NCT02034123) enrolled patients (≥18 years old) with relapsed or refractory SCLC (after ≥1 platinum-containing chemotherapy or refusal of standard therapy). Part 1 was a dose-escalation study; Part 2 was a dose-expansion study. Dose escalations were based on safety, PK, and PD. The primary end point (Part 1) was to determine the safety, tolerability, and recommended dose and regimen of GSK2879552. Secondary end points were to characterize PK and PD parameters …

Race And Risk Of Subsequent Aggressive Breast Cancer Following Ductal Carcinoma In Situ, Ying Liu, Robert West, Jason D Weber, Graham A Colditz

Open Access Publications

BACKGROUND: General populations of black women have a higher risk of developing breast cancer negative for both estrogen receptor (ER) and progesterone receptor (PR) in comparison with white counterparts. Racial differences remain unknown in the risk of developing aggressive invasive breast cancer (IBC) that is characterized by negativity for both ER and PR (ER-PR-) or higher 21-gene recurrence scores after ductal carcinoma in situ (DCIS).

METHODS: This study identified 163,892 women (10.5% black, 9.8% Asian, and 8.6% Hispanic) with incident DCIS between 1990 and 2015 from the Surveillance, Epidemiology, and End Results data sets. Cox proportional hazards regression was used …

Vitamin D Status And Risk Of Incident Tuberculosis Disease: A Nested Case-Control Study, Systematic Review, And Individual-Participant Data Meta-Analysis, Omowunmi Aibana, Chuan-Chin Huang, Said Aboud, Alberto Arnedo-Pena, Mercedes C Becerra, Juan Bautista Bellido-Blasco, Ramesh Bhosale, Roger Calderon, Silvia Chiang, Carmen Contreras, Ganmaa Davaasambuu, Wafaie W Fawzi, Molly F Franke, Jerome T Galea, Daniel Garcia-Ferrer, Maria Gil-Fortuño, Barbará Gomila-Sard, Amita Gupta, Nikhil Gupte, Rabia Hussain, Jesus Iborra-Millet, Najeeha T Iqbal, Jose Vicente Juan-Cerdán, Aarti Kinikar, Leonid Lecca, Vidya Mave, Noemi Meseguer-Ferrer, Grace Montepiedra, Ferdinand M Mugusi, Olumuyiwa A Owolabi, Julie Parsonnet, Freddy Roach-Poblete, Maria Angeles Romeu-García, Stephen A Spector, Christopher R Sudfeld, Mark W Tenforde, Toyin O Togun, Rosa Yataco, Zibiao Zhang, Megan B Murray

Faculty, Staff and Student Publications

BACKGROUND: Few studies have evaluated the association between preexisting vitamin D deficiency and incident tuberculosis (TB). We assessed the impact of baseline vitamins D levels on TB disease risk.

METHODS AND FINDINGS: We assessed the association between baseline vitamin D and incident TB in a prospective cohort of 6,751 HIV-negative household contacts of TB patients enrolled between September 1, 2009, and August 29, 2012, in Lima, Peru. We screened for TB disease at 2, 6, and 12 months after enrollment. We defined cases as household contacts who developed TB disease at least 15 days after enrollment of the index patient. …

Blood Leukocyte Dna Methylation Predicts Risk Of Future Myocardial Infarction And Coronary Heart Disease, Golareh Agha, Michael M Mendelson, Cavin K Ward-Caviness, Roby Joehanes, Tianxiao Huan, Rahul Gondalia, Elias Salfati, Jennifer A Brody, Giovanni Fiorito, Jan Bressler, Brian H Chen, Symen Ligthart, Simonetta Guarrera, Elena Colicino, Allan C Just, Simone Wahl, Christian Gieger, Amy R Vandiver, Toshiko Tanaka, Dena G Hernandez, Luke C Pilling, Andrew B Singleton, Carlotta Sacerdote, Vittorio Krogh, Salvatore Panico, Rosario Tumino, Yun Li, Guosheng Zhang, James D Stewart, James S Floyd, Kerri L Wiggins, Jerome I Rotter, Michael Multhaup, Kelly Bakulski, Steven Horvath, Philip S Tsao, Devin M Absher, Pantel Vokonas, Joel Hirschhorn, M Daniele Fallin, Chunyu Liu, Stefania Bandinelli, Eric Boerwinkle, Abbas Dehghan, Joel D Schwartz, Bruce M Psaty, Andrew P Feinberg, Lifang Hou, Luigi Ferrucci, Nona Sotoodehnia, Giuseppe Matullo, Annette Peters, Myriam Fornage, Themistocles L Assimes, Eric A Whitsel, Daniel Levy, Andrea A Baccarelli

Faculty, Staff and Student Publications

BACKGROUND: DNA methylation is implicated in coronary heart disease (CHD), but current evidence is based on small, cross-sectional studies. We examined blood DNA methylation in relation to incident CHD across multiple prospective cohorts.

METHODS: Nine population-based cohorts from the United States and Europe profiled epigenome-wide blood leukocyte DNA methylation using the Illumina Infinium 450k microarray, and prospectively ascertained CHD events including coronary insufficiency/unstable angina, recognized myocardial infarction, coronary revascularization, and coronary death. Cohorts conducted race-specific analyses adjusted for age, sex, smoking, education, body mass index, blood cell type proportions, and technical variables. We conducted fixed-effect meta-analyses across cohorts.

RESULTS: Among …

The Correlation Between Sleep Deprivation And Hypertension In Healthy Adults, Bonnie Keating

All Student-Created Educational Resources

The purpose of this study to investigate the correlation of healthy males between the ages of 18-45 years and blood pressure and if lack of sleep of 6 months or greater can lead to Stage 1 hypertension or worse. Studying sleep deprivation and its effects on healthy people can help identify how important sleep is to maintaining overall health.

"The Traps Started During My Childhood": The Role Of Substance Abuse In Women's Responses To Adverse Childhood Experiences (Aces), Breanna Boppre, Cassandra Boyer

Criminal Justice Faculty Research

The gendered pathways perspective seeks to identify the biological, psychological, and social realities that lead to women’s law-breaking behavior. Prior research in this area demonstrates the link between women’s adverse childhood experiences (ACEs) and involvement in the criminal justice system later in life. The current study fills an important gap in the literature by providing a phenomenological description of the impacts ACEs had upon 19 community supervised women’s lives. Their stories illuminate the need to consider multiple forms of ACEs, from physical and sexual abuse to the death of a loved one. Interviewees’ most prevalent response to ACEs was substance …

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 …

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

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. …

Reducing Aerodynamic Drag By Adopting A Novel Road-Cycling Sprint Position, Paul F. J. Merkes, Paolo Menaspa, Chris R. Abbiss

Research outputs 2014 to 2021

Purpose:

To assess the influence of seated, standing, and forward-standing cycling sprint positions on aerodynamic drag (CdA) and the reproducibility of a field test of CdA calculated in these different positions.

Methods:

A total of 11 recreational male road cyclists rode 250 m in 2 directions at around 25, 32, and 40 km·h.

Results:

A main effect of position showed that the average CdA of the 2 d was lower for the forward-standing position (0.295 [0.059]) compared with both the seated (0.363 [0.071], P = .018) and standing positions (0.372 [0.077], P = .037). Seated and standing positions did …

Autonomic Response In Autism Spectrum Disorder: Relationship To Social And Cognitive Functioning, Michelle A Patriquin, Elizabeth M Hartwig, Bruce H Friedman, Stephen W Porges, Angela Scarpa

Staff and Researcher Publications

Individuals with autism spectrum disorder (ASD) may exhibit chronic autonomic nervous system (ANS) hyperarousal (e.g., lower respiratory sinus arrhythmia and higher heart rate) compared to their typically developing peers, reflecting a chronic biological threat response. The sustained nature of this cardiac threat suggests tonic nervous system perception of threat in safe contexts. Herein, the cardiac literature in adult and child populations with ASD is reviewed and placed within a continuum of functioning in order to inform the relationship between cardiac response and functioning in ASD. Findings from this review support the relationship between chronic autonomic hyperarousal and emotional and behavioral …

The Concentration Of Total Nucleated Cells In Harvested Bone Marrow For Transplantation Has Decreased Over Time., Nicole L. Prokopishyn, Brent R. Logan, Deidre M. Kiefer, Jennifer A. Sees, Pintip Chitphakdithai, Ibrahim A. Ahmed, Paolo N. Anderlini, Amer M. Beitinjaneh, Christopher Bredeson, Jan Cerny, Saurabh Chhabra, Andrew Daly, Miguel Angel Diaz, Nosha Farhadfar, Haydar A. Frangoul, Siddhartha Ganguly, Dennis A. Gastineau, Usama Gergis, Gregory A. Hale, Peiman Hematti, Rammurti T. Kamble, Kimberly A. Kasow, Hillard M. Lazarus, Jane L. Liesveld, Hemant S. Murthy, Maxim Norkin, Richard F. Olsson, Mona Papari, Bipin N. Savani, Jeffrey Szer, Edmund K. Waller, Baldeep Wirk, Jean A. Yared, Michael A. Pulsipher, Nirali N. Shah, Galen E. Switzer, Paul V. O'Donnell, Dennis L. Confer, Bronwen E. Shaw

Manuscripts, Articles, Book Chapters and Other Papers

Bone marrow (BM) is an essential source of hematopoietic stem cell grafts for many allogeneic hematopoietic cell transplant (HCT) recipients, including adult patients (for specific diseases and transplantation strategies) and the majority of pediatric recipient. However, since the advent of granulocyte colony-stimulating factor-mobilized peripheral blood stem cell (PBSC) grafts, there has been a significant decrease in the use of BM in HCT, thought to be due mainly to the increased logistical challenges in harvesting BM compared with PBSCs, as well as generally no significant survival advantage of BM over PBSCs. The decreased frequency of collection has the potential to impact …

Assessment Of Physical Fitness After Bariatric Surgery And Its Association With Protein Intake And Type Of Cholecalciferol Supplementation, Hendrika J M Smelt, Sjaak Pouwels, Alper Celik, Adarsh Gupta, Johannes F Smulders

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Background: Several studies showed that there is a relationship between vitamin and mineral status and muscle strength. In particular this is the case for handgrip strength (HS) and vitamin D deficiency. In bariatric surgery there is a risk of decrease in muscle strength after surgery and also vitamin and mineral deficiencies are not uncommon. The aim of this study is to assess the effect of low vitamin 25 (OH) cholecalciferol levels, high dose cholecalciferol supplementation regime and protein intake on physical fitness, measured using handgrip strength (HS) and the shuttle walk run test (SWRT). Methods: For this retrospective …

An Integrative Cross-Omics Analysis Of Dna Methylation Sites Of Glucose And Insulin Homeostasis, Jun Liu, Elena Carnero-Montoro, Jenny Van Dongen, Samantha Lent, Ivana Nedeljkovic, Symen Ligthart, Pei-Chien Tsai, Tiphaine C. Martin, Pooja R. Mandaviya, Rick Jansen, Marjolein J. Peters, Liesbeth Duijts, Vincent W. V. Jaddoe, Henning Tiemeier, Janine F. Felix, Gonneke Willemsen, Eco J. C. De Geus, Audrey Y. Chu, Daniel Levy, Shih-Jen Hwang, Jan Bressler, Rahul Gondalia, Elias L. Salfati, Christian Herder, Bertha A. Hidalgo, Toshiko Tanaka, Ann Zenobia Moore, Rozenn N. Lemaitre, Min A. Jhun, Jennifer A. Smith, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Despite existing reports on differential DNA methylation in type 2 diabetes (T2D) and obesity, our understanding of its functional relevance remains limited. Here we show the effect of differential methylation in the early phases of T2D pathology by a blood-based epigenome-wide association study of 4808 non-diabetic Europeans in the discovery phase and 11,750 individuals in the replication. We identify CpGs in LETM1, RBM20, IRS2, MAN2A2 and the 1q25.3 region associated with fasting insulin, and in FCRL6, SLAMF1, APOBEC3H and the 15q26.1 region with fasting glucose. In silico cross-omics analyses highlight the role of differential methylation …

Local Challenges And Successes Associated With Transitioning To Sustainable Food System Practices For A West Australian Context: Multi-Sector Stakeholder Perceptions, Ros Sambell, Lesley Andrew, Stephanie Godrich, Justin Wolfgang, Dieter Vandenbroeck, Katie Stubley, Nick Rose, Lenore Newman, Pierre Horwitz, Amanda Devine

Research outputs 2014 to 2021

Large-scale food system practices have diminished soil and water quality and negatively impacted climate change. Yet, numerous opportunities exist to harness food system practices that will ensure better outcomes for human health and ecosystems. The objective of this study was to consider food Production, Processing, Access and Consumption domains, and for each determine the challenges and successes associated with progressing towards a sustainable food system. A workshop engaging 122 participants including producers, consultants, consumers, educators, funders, scientists, media, government and industry representatives, was conducted in Perth, Western Australia. A thematic analysis of statements (Successes (n = 170) or Challenges (n …

Impact Of High Volume Energy Drink Consumption On Electrocardiographic And Blood Pressure Parameters: A Randomized Trial, Sachin A. Shah, Andy H. Szeto, Raechel Farewell, Allen Shek, Dorothy Fan, Kathy N. Quach, Mouchumi Bhattacharyya, Jasmine Elmiari, Winny Chan, Kate O'Dell, Nancy Nguyen, Tracey J. Mcgaughey, Javed M. Nasir, Sanjay Kaul

School of Pharmacy Faculty Articles

Background Energy drinks have been linked to an increase in emergency room visits and deaths. We aim to determine the impact of energy drinks on electrocardiographic and hemodynamic parameters in young healthy volunteers. Methods and Results A randomized, double-masked, placebo-controlled, crossover study was conducted in healthy volunteers. Participants consumed 32 oz of either energy drink A, energy drink B, or placebo within 60 minutes on 3 study days with a 6-day washout period in between. The primary end point of QT c interval and secondary end points of QT interval, PR interval, QRS duration, heart rate, and brachial and central …

Initial Management Of Meningiomas: Analysis Of The National Cancer Database, Catherine R. Garcia, Stacey A. Slone, Monica Chau, Janna H. Neltner, Thomas A. Pittman, John L. Villano

Neurology Faculty Publications

BACKGROUND: Meningiomas are the most common central nervous system tumor. We describe current trends in treatment and survival using the largest cancer dataset in the United States.

METHODS: We analyzed the National Cancer Database from 2004 to 2014, for all patients with diagnosis of meningioma.

RESULTS: 201,765 cases were analyzed. Patients were most commonly White (81.9%) females (73.2%) with a median age of 64 years. Fifty percent of patients were diagnosed by imaging. Patients were reported as grade I (24.9%), grade II (5.0%), grade III (0.7%), or unknown WHO grade (69.4%). Patients diagnosed by imaging were older, received treatment in …

Developmental Expression Of The Cytosolic Sulfotransferases In Human Liver., Sarah Dubaisi, Joseph A. Caruso, R Gaedigk, Carrie A. Vyhlidal, Philip C. Smith, Ronald N. Hines, Thomas A. Kocarek, Melissa Runge-Morris

Manuscripts, Articles, Book Chapters and Other Papers

The liver is the predominant organ of metabolism for many endogenous and foreign chemicals. Cytosolic sulfotransferases (SULTs) catalyze the sulfonation of drugs and other xenobiotics, as well as hormones, neurotransmitters, and sterols, with consequences that include enhanced drug elimination, hormone inactivation, and procarcinogen bioactivation. SULTs are classified into six gene families, but only SULT1 and SULT2 enzymes are expressed in human liver. We characterized the developmental expression patterns of SULT1 and SULT2 mRNAs and proteins in human liver samples using reverse transcription quantitative polymerase chain reaction (RT-qPCR), RNA sequencing, and targeted quantitative proteomics. Using a set of prenatal, infant, and …

Abcb1 Snp Predicts Outcome In Patients With Acute Myeloid Leukemia Treated With Gemtuzumab Ozogamicin: A Report From Children's Oncology Group Aaml0531 Trial., Roya Rafiee, Lata Chauhan, Todd A. Alonzo, Yi-Cheng Wang, Ahlam Elmasry, Michael R. Loken, Jessica Pollard, Richard Aplenc, Susana Raimondi, Betsy A. Hirsch, Irwin D. Bernstein, A S. Gamis, Soheil Meshinchi, Jatinder K. Lamba

Manuscripts, Articles, Book Chapters and Other Papers

Gemtuzumab-ozogamicin (GO), a humanized-anti-CD33 antibody linked with the toxin-calicheamicin-γ is a reemerging and promising drug for AML. Calicheamicin a key element of GO, induces DNA-damage and cell-death once the linked CD33-antibody facilitates its uptake. Calicheamicin efflux by the drug-transporter PgP-1 have been implicated in GO response thus in this study, we evaluated impact of ABCB1-SNPs on GO response. Genomic-DNA samples from 942 patients randomized to receive standard therapy with or without addition of GO (COG-AAML0531) were genotyped for ABCB1-SNPs. Our most interesting results show that for rs1045642, patients with minor-T-allele (CT/TT) had better outcome as compared to patients with CC …

A High-Throughput Screen Indicates Gemcitabine And Jak Inhibitors May Be Useful For Treating Pediatric Aml, Christina D. Drenberg, Anang Shelat, Jinjun Dang, Anitria Cotton, Shelley J. Orwick, Mengyu Li, Jae Yoon Jeon, Qiang Fu, Daelynn R. Buelow, Marissa Pioso, Shuiying Hu, Hiroto Inaba, Raul C. Ribeiro, Jeffrey E. Rubnitz, Tanja A. Gruber, R. Kiplin Guy, Sharyn D. Baker

Pharmaceutical Sciences Faculty Publications

Improvement in survival has been achieved for children and adolescents with AML but is largely attributed to enhanced supportive care as opposed to the development of better treatment regimens. High risk subtypes continue to have poor outcomes with event free survival rates < 40% despite the use of high intensity chemotherapy in combination with hematopoietic stem cell transplant. Here we combine high-throughput screening, intracellular accumulation assays, and in vivo efficacy studies to identify therapeutic strategies for pediatric AML. We report therapeutics not currently used to treat AML, gemcitabine and cabazitaxel, have broad anti-leukemic activity across subtypes and are more effective relative to the AML standard of care, cytarabine, both in vitro and in vivo. JAK inhibitors are selective for acute megakaryoblastic leukemia and significantly prolong survival in multiple preclinical models. Our approach provides advances in the development of treatment strategies for pediatric AML.

Evaluating The Effectiveness And Implementation Of Evidence-Based Treatment: A Multisite Hybrid Design., Jamile A Ashmore, Kirk W Ditterich, Claire C Conley, Melissa R Wright, Peggy S Howland, Kelly L Huggins, Jena Cooreman, Priscilla S Andrews, Donald R Nicholas, Lind Roberts, Larissa Hewitt, Joan N Scales, Jenny K Delap, Christine A Gray, Lynelle A Tyler, Charlotte Collins, Catherine M Whiting, Brittany M Brothers, Marlena M Ryba, Barbara L Andersen

Articles, Abstracts, and Reports

The gap between treatment development and efficacy testing to scaled up implementations of evidence-based treatment (EBT) is an estimated 20 years, and hybrid research designs aim to reduce the gap. One was used for a multisite study in cancer control, testing coprimary aims: (a) determine the feasibility and utility of a flexible EBT implementation strategy and (b) determine the clinical effectiveness of an EBT as implemented by newly trained providers. Therapists from 15 diverse sites implemented the biobehavioral intervention (BBI) for cancer patients (N = 158) as part of standard care. For implementation, therapists determined treatment format, number of …

Whatsapp: A Real-Time Tool To Reduce The Knowledge Gap And Share The Best Clinical Practices In Psoriasis, Luis D Mazzuoccolo, Maria Noel Esposito, Paula C Luna, Sharon Seiref, Mirtha Dominguez, Cristina M Echeverria

Project ECHO Bibliography

BACKGROUND: Psoriasis is a chronic inflammatory disease that affects around 100 million people worldwide. The burden of disease is high, but more recent therapies show promising results. Clinicians need, however, more training in the use of such therapies.

INTRODUCTION: Project ECHO

MATERIALS AND METHODS: One hundred thirty-two dermatologists in Argentina were invited to participate in the WhatsApp discussion group. After 1 year of participation, a follow-up questionnaire was used to assess the effectiveness of the project.

RESULTS: Eighty dermatologists participated. All questions placed in the discussion were answered by a psoriasis specialist, 79% of which were answered within the first …

Splice-Altering Variant In Col11a1 As A Cause Of Nonsyndromic Hearing Loss Dfna37., Kevin T. Booth, James W. Askew, Zohreh Talebizadeh, Patrick L M Huygen, James Eudy, Judith Kenyon, Denise Hoover, Michael S. Hildebrand, Katherine R. Smith, Melanie Bahlo, William J. Kimberling, Richard J H Smith, Hela Azaiez, Shelley D. Smith

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: The aim of this study was to determine the genetic cause of autosomal dominant nonsyndromic hearing loss segregating in a multigenerational family.

METHODS: Clinical examination, genome-wide linkage analysis, and exome sequencing were carried out on the family.

RESULTS: Affected individuals presented with early-onset progressive mild hearing impairment with a fairly flat, gently downsloping or U-shaped audiogram configuration. Detailed clinical examination excluded any additional symptoms. Linkage analysis detected an interval on chromosome 1p21 with a logarithm of the odds (LOD) score of 8.29: designated locus DFNA37. Exome sequencing identified a novel canonical acceptor splice-site variant c.652-2A>C in the COL11A1 …

Effect Of Aging And Predonation Comorbidities On The Related Peripheral Blood Stem Cell Donor Experience: Report From The Related Donor Safety Study., Michael A. Pulsipher, Brent R. Logan, Pintip Chitphakdithai, Deidre M. Kiefer, Marcie L. Riches, J Douglas Rizzo, Paolo Anderlini, Susan F. Leitman, James W. Varni, Hati Kobusingye, Raeanne M. Besser, John P. Miller, Rebecca J. Drexler, Aly Abdel-Mageed, Ibrahim A. Ahmed, Luke P. Akard, Andrew S. Artz, Edward D. Ball, Ruthee-Lu Bayer, Carolyn Bigelow, Brian J. Bolwell, E Randolph Broun, Nancy J. Bunin, David C. Delgado, Katharine Duckworth, Christopher C. Dvorak, Theresa E. Hahn, Ann E. Haight, Parameswaran N. Hari, Brandon M. Hayes-Lattin, David A. Jacobsohn, Ann A. Jakubowski, Kimberly A. Kasow, Hillard M. Lazarus, Jane L. Liesveld, Michael Linenberger, Mark R. Litzow, Walter Longo, Margarida Magalhaes-Silverman, John M. Mccarty, Joseph P. Mcguirk, Shahram Mori, Vinod K. Prasad, Scott D. Rowley, Witold B. Rybka, Indira Sahdev, Jeffrey R. Schriber, George B. Selby, Paul J. Shaughnessy, Shalini Shenoy, Thomas Spitzer, William T. Tse, Joseph P. Uberti, Madhuri Vusirikala, Edmund K. Waller, Daniel J. Weisdorf, Gregory A. Yanik, Willis H. Navarro, Mary M. Horowitz, Galen E. Switzer, Bronwen E. Shaw, Dennis L. Confer

Manuscripts, Articles, Book Chapters and Other Papers

The development of reduced-intensity approaches for allogeneic hematopoietic cell transplantation has resulted in growing numbers of older related donors (RDs) of peripheral blood stem cells (PBSCs). The effects of age on donation efficacy, toxicity, and long-term recovery in RDs are poorly understood. To address this we analyzed hematologic variables, pain, donation-related symptoms, and recovery in 1211 PBSC RDs aged 18 to 79 enrolled in the Related Donor Safety Study. RDs aged > 60 had a lower median CD34+ level before apheresis compared with younger RDs (age > 60, 59 × 106/L; age 41 to 60, 81 × 106/L; age 18 to 40, …