Digital Commons Network^™

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.

An Endogenous Peptide Marker Differentiates Sod1 Stability And Facilitates Pharmacodynamic Monitoring In Sod1 Amyotrophic Lateral Sclerosis, Ilya Gertsman, Joanne Wuu, Melissa Mcalonis-Downes, Majid Ghassemian, Karen Ling, Frank Rigo, Frank Bennett, Michael Benatar, Timothy M. Miller, Sandrine Da Cruz

Open Access Publications

The discovery of novel biomarkers has emerged as a critical need for therapeutic development in amyotrophic lateral sclerosis (ALS). For some subsets of ALS, such as the genetic superoxide dismutase 1 (SOD1) form, exciting new treatment strategies, such as antisense oligonucleotide-mediated (ASO-mediated) SOD1 silencing, are being tested in clinical trials, so the identification of pharmacodynamic biomarkers for therapeutic monitoring is essential. We identify increased levels of a 7-amino acid endogenous peptide of SOD1 in cerebrospinal fluid (CSF) of human SOD1 mutation carriers but not in other neurological cases or nondiseased controls. Levels of peptide elevation vary based on the specific …

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 …

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 …

Commonly Integrated Epigenetic Modifications Of Differentially Expressed Genes Lead To Adaptive Resistance In Cancer., Abdullah Al Emran, Diego M Marzese, Dinoop R Menon, Heinz Hammerlindl, Farzana Ahmed, Erika Richtig, Pascal Duijf, Dave Hoon, Helmut Schaider

Articles, Abstracts, and Reports

Aim: To investigate the integrated epigenetic regulation of acquired drug resistance in cancer. Materials & methods: Our gene expression data of five induced drug-tolerant cell models, one resistant cell line and one publicly available drug-resistant dataset were integrated to identify common differentially expressed genes and pathways. ChIP-seq and DNA methylation by HM450K beadchip were used to study the epigenetic profile of differential expressed genes. Results & conclusion: Integrated transcriptomic analysis identified a common 'viral mimicry' related gene signature in induced drug-tolerant cells and the resistant state. Analysis of the epigenetic regulation revealed a common set of down-regulated genes, which are …

Reaching The End Of The Line: Urinary Tract Infections, Kevin O Tamadonfar, Natalie S Omattage, Caitlin N Spaulding, Scott J Hultgren

Open Access Publications

Urinary tract infections (UTIs) cause a substantial health care burden. UTIs (i) are most often caused by uropathogenic

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 …

High-Density Diffuse Optical Tomography For Imaging Human Brain Function, Muriah D Wheelock, Joseph P Culver, Adam T Eggebrecht

Open Access Publications

This review describes the unique opportunities and challenges for noninvasive optical mapping of human brain function. Diffuse optical methods offer safe, portable, and radiation free alternatives to traditional technologies like positron emission tomography or functional magnetic resonance imaging (fMRI). Recent developments in high-density diffuse optical tomography (HD-DOT) have demonstrated capabilities for mapping human cortical brain function over an extended field of view with image quality approaching that of fMRI. In this review, we cover fundamental principles of the diffusion of near infrared light in biological tissue. We discuss the challenges involved in the HD-DOT system design and implementation that must …

How To Conduct Clinical Trials In Children: A Tutorial., Valentina Shakhnovich, Christoph P. Hornik, Gregory L. Kearns, Jaylene Weigel, Susan M. Abdel-Rahman

Manuscripts, Articles, Book Chapters and Other Papers

Despite a growing interest in, and commitment to, implementing pediatric clinical trials, approximately one in every five trials in children fails because of inappropriate study design, suboptimal experiment planning, or inadequate participant enrollment. This tutorial, presented from the perspectives of seasoned pediatric investigators, an experienced research coordinator, and an established pediatric clinical trials network, is designed to provide practical guidance for successfully implementing pediatric clinical trials at an academic center or another comparable institution.

Pharmacogene Variation Consortium Gene Introduction: Nudt15., Jun J. Yang, Michelle Whirl-Carrillo, Stuart A. Scott, Amy J. Turner, Matthias Schwab, Yoichi Tanaka, Guilherme Suarez-Kurtz, Elke Schaeffeler, Teri E. Klein, Neil A. Miller, Andrea Gaedigk

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

Stimulation Of Heat Shock Protein 90 Chaperone Function Through Binding Of A Novobiocin Analog Ku-32, Bhaskar K. Chatterjee, Abhilash Jayaraj, Vinay Kumar, Brian Blagg, Rachel E. Davis, B Jayaram, Shashank Deep, Tapan K. Chaudhuri

Faculty Publications

Heat shock protein 90 (Hsp90) is a eukaryotic chaperone responsible for the folding and functional activation of numerous client proteins, many of which are oncoproteins. Thus, Hsp90 inhibition has been intensely pursued, resulting in the development of many potential Hsp90 inhibitors, not all of which are well-characterized. Hsp90 inhibitors not only abrogate its chaperone functions, but also could help us gain insight into the structure-function relationship of this chaperone. Here, using biochemical and cell-based assays along with isothermal titration calorimetry, we investigate KU-32, a derivative of the Hsp90 inhibitor novobiocin (NB), for its ability to modulate Hsp90 chaperone function. Although …

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 …

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 …

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. …

Transcriptional Regulation Factors Of The Human Mitochondrial Aspartate/Glutamate Carrier Gene, Isoform 2 (Slc25a13): Usf1 As Basal Factor And Foxa2 As Activator In Liver Cells, Paolo Convertini, Simona Todisco, Francesco De Santis, Ilaria Pappalardo, Dominga Iacobazzi, Maria Antonietta Castiglione Morelli, Yvonne N. Fondufe-Mittendorf, Giuseppe Martelli, Ferdinando Palmieri, Vittoria Infantino

Molecular and Cellular Biochemistry Faculty Publications

Mitochondrial carriers catalyse the translocation of numerous metabolites across the inner mitochondrial membrane, playing a key role in different cell functions. For this reason, mitochondrial carrier gene expression needs tight regulation. The human SLC25A13 gene, encoding for the mitochondrial aspartate/glutamate carrier isoform 2 (AGC2), catalyses the electrogenic exchange of aspartate for glutamate plus a proton, thus taking part in many metabolic processes including the malate-aspartate shuttle. By the luciferase (LUC) activity of promoter deletion constructs we identified the putative promoter region, comprising the proximal promoter (−442 bp/−19 bp), as well as an enhancer region (−968 bp/−768 bp). Furthermore, with different …

An Obligatory Role For Club Cells In Preventing Obliterative Bronchiolitis In Lung Transplants, Zhiyi Liu, Fuyi Liao, Davide Scozzi, Yuka Furuya, Kaitlyn N Pugh, Ramsey Hachem, Delphine L Chen, Marlene Cano, Jonathan M Green, Alexander S Krupnick, Daniel Kreisel, Anne Karina T Perl, Howard J Huang, Steven L Brody, Andrew E Gelman

Open Access Publications

Obliterative bronchiolitis (OB) is a poorly understood airway disease characterized by the generation of fibrotic bronchiolar occlusions. In the lung transplant setting, OB is a pathological manifestation of bronchiolitis obliterans syndrome (BOS), which is a major impediment to long-term recipient survival. Club cells play a key role in bronchiolar epithelial repair, but whether they promote lung transplant tolerance through preventing OB remains unclear. We determined if OB occurs in mouse orthotopic lung transplants following conditional transgene-targeted club cell depletion. In syngeneic lung transplants club cell depletion leads to transient epithelial injury followed by rapid club cell-mediated repair. In contrast, allogeneic …

Extracellular Vesicles As Biological Shuttles For Targeted Therapies., Stefania Raimondo, Gianluca Giavaresi, Aurelio Lorico, Riccardo Alessandro

College of Osteopathic Medicine (TUN) Publications and Research

The development of effective nanosystems for drug delivery represents a key challenge for the improvement of most current anticancer therapies. Recent progress in the understanding of structure and function of extracellular vesicles (EVs)-specialized membrane-bound nanocarriers for intercellular communication-suggests that they might also serve as optimal delivery systems of therapeutics. In addition to carrying proteins, lipids, DNA and different forms of RNAs, EVs can be engineered to deliver specific bioactive molecules to target cells. Exploitation of their molecular composition and physical properties, together with improvement in bio-techniques to modify their content are critical issues to target them to specific cells/tissues/organs. Here, …

Gasdermin Pores Permeabilize Mitochondria To Augment Caspase-3 Activation During Apoptosis And Inflammasome Activation., Corey Rogers, Dan A. Erkes, Alexandria Nardone, Andrew E. Aplin, Teresa Fernandes-Alnemri, Emad S. Alnemri

Department of Biochemistry and Molecular Biology Faculty Papers

Gasdermin E (GSDME/DFNA5) cleavage by caspase-3 liberates the GSDME-N domain, which mediates pyroptosis by forming pores in the plasma membrane. Here we show that GSDME-N also permeabilizes the mitochondrial membrane, releasing cytochrome c and activating the apoptosome. Cytochrome c release and caspase-3 activation in response to intrinsic and extrinsic apoptotic stimuli are significantly reduced in GSDME-deficient cells comparing with wild type cells. GSDME deficiency also accelerates cell growth in culture and in a mouse model of melanoma. Phosphomimetic mutation of the highly conserved phosphorylatable Thr6 residue of GSDME, inhibits its pore-forming activity, thus uncovering a potential mechanism by which GSDME …

Incorporating Pathway Information Into Feature Selection Towards Better Performed Gene Signatures, Suyan Tian, Chi Wang, Bing Wang

Biostatistics Faculty Publications

To analyze gene expression data with sophisticated grouping structures and to extract hidden patterns from such data, feature selection is of critical importance. It is well known that genes do not function in isolation but rather work together within various metabolic, regulatory, and signaling pathways. If the biological knowledge contained within these pathways is taken into account, the resulting method is a pathway-based algorithm. Studies have demonstrated that a pathway-based method usually outperforms its gene-based counterpart in which no biological knowledge is considered. In this article, a pathway-based feature selection is firstly divided into three major categories, namely, pathway-level selection, …

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 …

Astct Consensus Grading For Cytokine Release Syndrome And Neurologic Toxicity Associated With Immune Effector Cells, Daniel W Lee, Armin Ghobadi, John F Dipersio, Et Al

Open Access Publications

Chimeric antigen receptor (CAR) T cell therapy is rapidly emerging as one of the most promising therapies for hematologic malignancies. Two CAR T products were recently approved in the United States and Europe for the treatment ofpatients up to age 25years with relapsed or refractory B cell acute lymphoblastic leukemia and/or adults with large B cell lymphoma. Many more CAR T products, as well as other immunotherapies, including various immune cell- and bi-specific antibody-based approaches that function by activation of immune effector cells, are in clinical development for both hematologic and solid tumor malignancies. These therapies are associated with unique …

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, …

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 …