Digital Commons Network^™

Tumor Heterogeneity As A Predictor Of Response To Neoadjuvant Chemotherapy In Locally Advanced Rectal Cancer, Alissa Greenbaum, David R. Martin, Thèrése Bocklage, Ji-Hyun Lee, Scott A. Ness, Ashwani Rajput

Pathology Research and Scholarship

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) is the standard of care for locally advanced adenocarcinoma of the rectum, but it is currently unknown which patients have disease that will respond. This study tested the correlation between response to nCRT and intratumoral heterogeneity using next-generation sequencing assays.

PATIENTS AND METHODS: DNA was extracted from formalin-fixed, paraffin-embedded biopsy samples from a cohort of patients with locally advanced rectal adenocarcinoma (T3/4 or N1/2 disease) who received nCRT. High read-depth sequencing of > 400 cancer-relevant genes was performed. Tumor mutations and variant allele frequencies were used to calculate mutant-allele tumor heterogeneity (MATH) scores as measures of intratumoral …

Downregulation Of Cenpf Remodels Prostate Cancer Cells And Alters Cellular Metabolism., Muhammad Shahid, Minhyung Kim, Min Young Lee, Austin Yeon, Sungyong You, Hyung L Kim, Jayoung Kim

Articles, Abstracts, and Reports

Metabolic alterations in prostate cancer (PC) are associated with progression and aggressiveness. However, the underlying mechanisms behind PC metabolic functions are unknown. The authors' group recently reported on the important role of centromere protein F (CENPF), a protein associated with the centromere-kinetochore complex and chromosomal segregation during mitosis, in PC MRI visibility. This study focuses on discerning the role of CENPF in metabolic perturbation in human PC3 cells. A series of bioinformatics analyses shows that CENPF is one gene that is strongly associated with aggressive PC and that its expression is positively correlated with metastasis. By identifying and reconstructing the …

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 …

The Man With 2 Hearts: 25 Years From Heterotopic To Orthotopic Heart Transplantation, Elizabeth L Godfrey, Michael L Kueht, Abbas Rana, O H Frazier

The Texas Heart Institute Journal

Substantial technological advances in mechanical circulatory support have caused a shift in the management of end-stage heart failure. From the 1970s through the 1990s, heterotopic heart transplantation was routinely performed in patients in whom orthotopic transplantation was likely to fail. Heterotopic heart transplantation is now performed less often because modern mechanical circulatory assist devices are routinely used as bridges to orthotopic transplantation; regardless, the operation has helped numerous patients who would not otherwise have received adequate allografts. We describe the case of a man with idiopathic nonischemic cardiomyopathy who, at age 17, was given an ABO- and size-matched heterotopic allograft …

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 …

High Fat Diet Alters Gut Microbiota But Not Spatial Working Memory In Early Middle-Aged Sprague Dawley Rats, Nikita Girish Deshpande, Juhi Saxena, Tristan G. Pesaresi, Casey Dylan Carrell, Grayson Breneman Ashby, Min-Ken Liao, Linnea Ruth Freeman

Open Access Fund Publications

As the global population ages, and rates of dementia rise, understanding lifestyle factors that play a role in the development and acceleration of cognitive decline is vital to creating therapies and recommendations to improve quality of later life. Obesity has been shown to increase risk for dementia. However, the specific mechanisms for obesity-induced cognitive decline remain unclear. One potential contributor to diet-induced cognitive changes is neuroinflammation. Furthermore, a source of diet-induced inflammation to potentially increase neuroinflammation is via gut dysbiosis. We hypothesized that a high fat diet would cause gut microbe dysbiosis, and subsequently: neuroinflammation and cognitive decline. Using 7-month …

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 Trauma-Informed Art Therapy Approach For Boys With Sexualized Problematic Behaviors: A Group Method, Rebecca Cyr

Expressive Therapies Capstone Theses

Treatment of sexualized problematic behaviors (SPB) in children and adolescents is a clinically significant issue that has little research to support the fundamental need for treatment. Sexualized problematic behaviors (SPB) can be an indication of a child’s own complex trauma and sexual abuse history. Using a relational, trauma-informed, and developmental approach to treatment in combination with art therapy, children demonstrating SPB can learn how to better express themselves, respect themselves and others, and heal a fragmented sense of self. Developmentally, these children and adolescents are in the stage where identity formation is the main task. Therefore, this series of art …

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.

Comparison Of Methods Used To Estimate The Global Burden Of Disease Related To Undernutrition And Suboptimal Breastfeeding, Alexander C. Mclain, Edward A. Frongillo Jr., Sonja Y. Hess, Ellen G. Piwoz

Faculty Publications

The Global Burden of Disease study (GBD) is an ambitious effort to estimate the disease burden attributable to various risk factors. The results from the GBD are used around the world to monitor the UN established Sustainable Development Goals, set health policies and research strategies, among others. The GBD along with other studies, such as those from the Maternal Child Epidemiology Estimation Group and the Lancet Breastfeeding Series Group, produce estimates of the nutrition-related global burden of disease that exhibit considerable differences. These differences are difficult to reconcile due to the estimation methods, which in recent years have substantially increased …

Perspective: Challenges In Use Of Adolescent Anthropometry For Understanding The Burden Of Malnutrition, Alison Tumilowicz, Ty Beal, Lynnette M. Neufeld, Edward A. Frongillo Jr.

Faculty Publications

Improving nutritional status during adolescence is an opportunity to improve the lives of this generation and the next. Estimating the burden of malnutrition at a population level is fundamental to targeting interventions and measuring progress over time, and for adolescents, we usually depend on survey data and the 2007 WHO Growth Reference to do so. There is substantial risk of misguided conclusions regarding adolescent prevalence estimates, however, when underlying methodological limitations of the indicators and reference are not adequately considered. We use national prevalence estimates among girls and young women 10-22 y of age from the 2014 State of Food …

"Notjustgirls": Exploring Male-Related Eating Disordered Content Across Social Media Platforms, Jessica Pater, Lauren Reining, Andrew D. Miller, Tammy Toscos Phd, Elizabeth D. Mynatt

Mirro Center Articles

ABSTRACT: Eating disorders (EDs) are a worldwide public health concern that impact approximately 10% of the U.S. population. Our previous research characterized these behaviors across online spaces. These characterizations have used clinical terminology, and their lexical variants, to identify ED content online. However, previous HCI research on EDs (including our own) suffers from a lack of gender and cultural diversity. In this paper, we designed a follow-up study of online ED characterizations, extending our previous methodologies to focus specifically on male/masculine-related content. We highlight the similarities and differences found in the terminology utilized and media archetypes associated with the social …

Diagnosing Growth In Low-Grade Gliomas With And Without Longitudinal Volume Measurements: A Retrospective Observational Study., Hassan M Fathallah-Shaykh, Andrew Deatkine, Elizabeth Coffee, Elias Khayat, Asim K Bag, Xiaosi Han, Paula Province Warren, Markus Bredel, John Fiveash, James Markert, Nidhal Carla Bouaynaya, Louis B Nabors

Henry M. Rowan College of Engineering Departmental Research

BACKGROUND: Low-grade gliomas cause significant neurological morbidity by brain invasion. There is no universally accepted objective technique available for detection of enlargement of low-grade gliomas in the clinical setting; subjective evaluation by clinicians using visual comparison of longitudinal radiological studies is the gold standard. The aim of this study is to determine whether a computer-assisted diagnosis (CAD) method helps physicians detect earlier growth of low-grade gliomas.

METHODS AND FINDINGS: We reviewed 165 patients diagnosed with grade 2 gliomas, seen at the University of Alabama at Birmingham clinics from 1 July 2017 to 14 May 2018. MRI scans were collected during …

Tdp-43 Proteinopathy In Aging: Associations With Risk-Associated Gene Variants And With Brain Parenchymal Thyroid Hormone Levels, Peter T. Nelson, Zsombor Gal, Wang-Xia Wang, Dana M. Niedowicz, Sergey C. Artiushin, Samuel Wycoff, Angela Wei, Gregory A. Jicha, David W. Fardo

Pathology and Laboratory Medicine Faculty Publications

TDP-43 proteinopathy is very prevalent among the elderly (affecting at least 25% of individuals over 85 years of age) and is associated with substantial cognitive impairment. Risk factors implicated in age-related TDP-43 proteinopathy include commonly inherited gene variants, comorbid Alzheimer's disease pathology, and thyroid hormone dysfunction. To test parameters that are associated with aging-related TDP-43 pathology, we performed exploratory analyses of pathologic, genetic, and biochemical data derived from research volunteers in the University of Kentucky Alzheimer's Disease Center autopsy cohort (n = 136 subjects). Digital pathologic methods were used to discriminate and quantify both neuritic and intracytoplasmic TDP-43 pathology …

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 …

Systemic Antibiotic Therapy Reduces Circulating Inflammatory Dendritic Cells And Treg-Th17 Plasticity In Periodontitis, Mythilypriya Rajendran, Stephen Looney, Nagendra Singh, Mahmoud Elashiry, Mohamed M Meghil, Ahmed R El-Awady, Omnia Tawfik, Cristiano Susin, Roger M Arce, Christopher W Cutler

Faculty, Staff and Student Publications

Periodontitis (PD) is a common dysbiotic inflammatory disease that leads to local bone deterioration and tooth loss. PD patients experience low-grade bacteremias with oral microbes implicated in the risk of heart disease, cancer, and kidney failure. Although Th17 effectors are vital to fighting infection, functional imbalance of Th17 effectors and regulatory T cells (Tregs) promote inflammatory diseases. In this study, we investigated, in a small pilot randomized clinical trial, whether expansion of inflammatory blood myeloid dendritic cells (DCs) and conversion of Tregs to Th17 cells could be modulated with antibiotics (AB) as part of initial therapy in PD patients. PD …

Genome-Wide Association Study In Finnish Twins Highlights The Connection Between Nicotine Addiction And Neurotrophin Signaling Pathway, Jenni Hällfors, Teemu Palviainen, Ida Surakka, Richa Gupta, Jadwiga Buchwald, Anu Raevuori, Samuli Ripatti, Tellervo Korhonen, Pekka Jousilahti, Pamela A F Madden, Jaakko Kaprio, Anu Loukola

Open Access Publications

The heritability of nicotine dependence based on family studies is substantial. Nevertheless, knowledge of the underlying genetic architecture remains meager. Our aim was to identify novel genetic variants responsible for interindividual differences in smoking behavior. We performed a genome-wide association study on 1715 ever smokers ascertained from the population-based Finnish Twin Cohort enriched for heavy smoking. Data imputation used the 1000 Genomes Phase I reference panel together with a whole genome sequence-based Finnish reference panel. We analyzed three measures of nicotine addiction-smoking quantity, nicotine dependence and nicotine withdrawal. We annotated all genome-wide significant SNPs for their functional potential. First, we …

Experiences Of Lgbtq Male Students Of Color In A Predominantly White Environment, Alberto Gonzalez

Ursidae: The Undergraduate Research Journal at the University of Northern Colorado

The limited literature on Lesbian, Gay, Bisexual, Transgender, and Queer people of color (LGBTQ-PoC) tends to focus on heterosexism in ethnic/racial communities and racism in white LGBTQ communities. This qualitative study, informed by Intersectionality, and Narrative Inquiry, expands on how to create spaces that are more inclusive for LGBTQ students of color on college campuses. This study documents and analyzes the stories of LGBTQ male college students of color regarding their academic and social interactions, and challenges encountered while navigating a predominantly white environment. Data was collected using semi-structured individual interviews. Questions focused on how participants’ identities developed, where they …

Epigenome-Wide Analysis Identifies Genes And Pathways Linked To Neurobehavioral Variation In Preterm Infants., Todd M. Everson, Carmen J. Marsit, T Michael O'Shea, Amber Burt, Karen Hermetz, Brian S. Carter, Jennifer Helderman, Julie A. Hofheimer, Elisabeth C. Mcgowan, Charles R. Neal, Steven L. Pastyrnak, Lynne M. Smith, Antoine Soliman, Sheri A. Dellagrotta, Lynne M. Dansereau, James F. Padbury, Barry M. Lester

Manuscripts, Articles, Book Chapters and Other Papers

Neonatal molecular biomarkers of neurobehavioral responses (measures of brain-behavior relationships), when combined with neurobehavioral performance measures, could lead to better predictions of long-term developmental outcomes. To this end, we examined whether variability in buccal cell DNA methylation (DNAm) associated with neurobehavioral profiles in a cohort of infants born less than 30 weeks postmenstrual age (PMA) and participating in the Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI) Study (N = 536). We tested whether epigenetic age, age acceleration, or DNAm levels at individual loci differed between infants based on their NICU Network Neurobehavioral Scale (NNNS) profile classifications. We adjusted …

Ucp1 Expression-Associated Gene Signatures Of Human Epicardial Adipose Tissue., Kanta Chechi, Jinchu Vijay, Pierre Voisine, Patrick Mathieu, Yohan Bossé, Andre Tchernof, Elin Grundberg, Denis Richard

Manuscripts, Articles, Book Chapters and Other Papers

Multiple reports of uncoupling protein 1 (UCP1) expression have established its presence in human epicardial adipose tissue (eAT). Its functional relevance to eAT, however, remains largely unknown. In a recent study, we reported that adrenergic stimulation of eAT was associated with downregulation of secreted proteins involved in oxidative stress-related and immune-related pathways. Here, we explored the UCP1-associated features of human eAT using next-generation deep sequencing. Paired biopsies of eAT, mediastinal adipose tissue (mAT), and subcutaneous adipose tissue (sAT) obtained from cardiac surgery patients, with specific criteria of high and low expression of UCP1 in eAT, were subjected to RNA sequencing. …

Down Syndrome Mouse Models Have An Abnormal Enteric Nervous System, Ellen M Schill, Christina M Wright, Alisha Jamil, Jonathan M Lacombe, Randall J Roper, Robert O Heuckeroth

Open Access Publications

Children with trisomy 21 (Down syndrome [DS]) have a 130-fold increased incidence of Hirschsprung Disease (HSCR), a developmental defect where the enteric nervous system (ENS) is missing from distal bowel (i.e., distal bowel is aganglionic). Treatment for HSCR is surgical resection of aganglionic bowel, but many children have bowel problems after surgery. Post-surgical problems like enterocolitis and soiling are especially common in children with DS. To determine how trisomy 21 affects ENS development, we evaluated the ENS in two DS mouse models, Ts65Dn and Tc1. These mice are trisomic for many chromosome 21 homologous genes, including Dscam and Dyrk1a, which …

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 …

Comparison Of Nylon-Flocked Swab And Dacron Swab Cytology For Anal Hsil Detection In Transgender Women And Gay, Bisexual, And Other Men Who Have Sex With Men, Dorothy J. Wiley, Hilary K. Hsu, Martha A. Ganser, Jenny Brook, David A. Elashoff, Stephen A. Young, Nancy E. Joste, Ronald Mitsuyasu, Teresa M. Darragh, David H. Morris, Otoniel M. Martínez-Maza, Roger Detels, Jian Yu Rao, Robert K. Bolan, Eric T. Shigeno, Ernesto Rodriguez, Matthrew G. Moran

Pathology Research and Scholarship

BACKGROUND: An anal histological high-grade squamous intraepithelial lesion (hHSIL) is an anal cancer precursor. Experts recommend Dacron swab anal cytology as a primary screen for anal hHSILs, especially among human immunodeficiency virus-infected and -uninfected men who have sex with men (MSM). Studies have shown that Dacron cytology inaccurately predicts anal hHSILs and results in unnecessary diagnostic procedures. Nylon-flocked (NF) swabs have been shown to trap pathogens and cells well. Thus, this study compared test characteristics of anal cytology using NF and Dacron swab collection protocols to predict anal hHSILs.

METHODS: A single-visit, randomized clinical trial compared NF and Dacron swab …

A Clinician's Guide To Next Generation Imaging In Patients With Advanced Prostate Cancer (Radar Iii)., E. David Crawford, Phillip J. Koo, Neal Shore, Susan F. Slovin, Raoul S. Concepcion, Stephen J. Freedland, Leonard G. Gomella, Lawrence Karsh, Thomas E. Keane, Paul Maroni, David Penson, Daniel P. Petrylak, Ashley Ross, Vlad Mouraviev, Robert E. Reiter, Chaitanya Divgi, Evan Y. Yu

Department of Urology Faculty Papers

PURPOSE: The advanced prostate cancer therapeutic landscape has changed dramatically in the last several years, resulting in improved overall survival of patients with castration naïve and castration resistant disease. The evolution and development of novel next generation imaging techniques will affect diagnostic and therapeutic decision making. Clinicians must navigate when and which next generation imaging techniques to use and how to adjust treatment strategies based on the results, often in the absence of correlative therapeutic data. Therefore, guidance is needed based on best available information and current clinical experience.

MATERIALS AND METHODS: The RADAR (Radiographic Assessments for Detection of Advanced …

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, …

Conditional Deletion Of Des1 In The Mouse Retina Does Not Impair The Visual Cycle In Cones, Philip D Kiser, Alexander V Kolesnikov, Jianying Z Kiser, Zhiqian Dong, Bhagirath Chaurasia, Liping Wang, Scott A Summers, Thanh Hoang, Seth Blackshaw, Neal S Peachey, Vladimir J Kefalov, Krzysztof Palczewski

Open Access Publications

Cone photoreceptors are essential for vision under moderate to high illuminance and allow color discrimination. Their fast dark adaptation rate and resistance to saturation are believed to depend in part on an intraretinal visual cycle that supplies 11- cis-retinaldehyde to cone opsins. Candidate enzymes of this pathway have been reported, but their physiologic contribution to cone photoresponses remains unknown. Here, we evaluate the role of a candidate retinol isomerase of this pathway, sphingolipid δ4 desaturase 1 (Des1). Single-cell RNA sequencing analysis revealed Des1 expression not only in Müller glia but also throughout the retina and in the retinal pigment epithelium. …

Skin Cancer Precursor Immunotherapy For Squamous Cell Carcinoma Prevention, Abby R Rosenberg, Mary Tabacchi, Kenneth H Ngo, Michael Wallendorf, Ilana S Rosman, Lynn A Cornelius, Shadmehr Demehri

Open Access Publications

BACKGROUND: Topical calcipotriol plus 5-fluorouracil (5-FU) combination is an effective immunotherapy against actinic keratosis (AK), which is a precursor to squamous cell carcinoma (SCC). However, the long-term effectiveness of calcipotriol plus 5-FU treatment for SCC prevention is unknown.

METHODS: We performed a blinded prospective cohort study on participants of a randomized double-blind clinical trial in which a 4-day course of topical calcipotriol plus 5-FU combination was compared to Vaseline plus 5-FU (control) for AK treatment. SCC and basal cell carcinoma (BCC) incidences were assessed at 1, 2, and 3 years after trial. Tissues were analyzed for calcipotriol plus 5-FU-induced T …

Factors Associated With Condom Use With Non-Commercial Partners Among Sexually-Active Transgender Women In Cambodia: Findings From A National Survey Using Respondent-Driven Sampling., Siyan Yi, Amelia Plant, Sovannary Tuot, Phalkun Mun, Srean Chhim, Navy Chann, Pheak Chhoun, Carinne M. Brody

BACKGROUND: Globally, the prevalence of HIV among transgender women is much higher than that of the general adult population. This can be explained by the persistently low rate of consistent condom use among this population. This study was therefore conducted to explore factors associated with consistent condom use among sexually-active transgender women in Cambodia, specifically with their non-commercial partners.

METHODS: Data used for this study were collected as part of the National Integrated Biological and Behavioral Survey 2016. Participants were recruited from the capital city of Phnom Penh and 12 other provinces with high burden of HIV using the Respondent-Driven …

Buparlisib In Patients With Recurrent Glioblastoma Harboring Phosphatidylinositol 3-Kinase Pathway Activation: An Open-Label, Multicenter, Multi-Arm, Phase Ii Trial., Patrick Y Wen, Mehdi Touat, Brian M Alexander, Ingo K Mellinghoff, Shakti Ramkissoon, Christine S Mccluskey, Kristine Pelton, Sam Haidar, Sankha S Basu, Sarah C Gaffey, Loreal E Brown, Juan Emmanuel Martinez-Ledesma, Shaofang Wu, Jungwoo Kim, Wei Wei, Mi-Ae Park, Jason T Huse, John G Kuhn, Mikael L Rinne, Howard Colman, Nathalie Y R Agar, Antonio M Omuro, Lisa M Deangelis, Mark R Gilbert, John F De Groot, Timothy F Cloughesy, Andrew S Chi, Thomas M Roberts, Jean J Zhao, Eudocia Q Lee, Lakshmi Nayak, James R Heath, Laura L Horky, Tracy T Batchelor, Rameen Beroukhim, Susan M Chang, Azra H Ligon, Ian F Dunn, Dimpy Koul, Geoffrey S Young, Michael D Prados, David A Reardon, W K Alfred Yung, Keith L Ligon

Articles, Abstracts, and Reports

PURPOSE: Phosphatidylinositol 3-kinase (PI3K) signaling is highly active in glioblastomas. We assessed pharmacokinetics, pharmacodynamics, and efficacy of the pan-PI3K inhibitor buparlisib in patients with recurrent glioblastoma with PI3K pathway activation.

METHODS: This study was a multicenter, open-label, multi-arm, phase II trial in patients with PI3K pathway-activated glioblastoma at first or second recurrence. In cohort 1, patients scheduled for re-operation after progression received buparlisib for 7 to 13 days before surgery to evaluate brain penetration and modulation of the PI3K pathway in resected tumor tissue. In cohort 2, patients not eligible for re-operation received buparlisib until progression or unacceptable toxicity. Once …