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https://www.readbyqxmd.com/read/29057301/uncovering-a-novel-pathway-for-p16-silencing-therapeutic-implications-for-lung-cancer
#1
C Gamell, T Gulati, B Solomon, S Haupt, Y Haupt
A key step during onset of most cases of non-small cell lung cancer (NSCLC) is the loss of the tumor suppressor p16(INK4a) (best known as p16), commonly due to promoter hypermethylation. We recently reported a novel regulatory pathway involving E6-associated protein and cell division control protein 6, which provides a methylation-independent mechanism for p16 silencing in patients with a particularly aggressive form of NSCLC.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/28966548/genome-wide-linkage-and-association-analysis-of-primary-open-angle-glaucoma-endophenotypes-in-the-norfolk-island-isolate
#2
Elizabeth Matovinovic, Pik Fang Kho, Rodney A Lea, Miles C Benton, David A Eccles, Larisa M Haupt, Alex W Hewitt, Justin C Sherwin, David A Mackey, Lyn R Griffiths
PURPOSE: Primary open-angle glaucoma (POAG) refers to a group of heterogeneous diseases involving optic nerve damage. Two well-established risk factors for POAG are elevated intraocular pressure (IOP) and a thinner central corneal thickness (CCT). These endophenotypes exhibit a high degree of heritability across populations. Large-scale genome-wide association studies (GWASs) of outbred populations have robustly implicated several susceptibility gene variants for both IOP and CCT. Despite this progress, a substantial amount of genetic variance remains unexplained...
2017: Molecular Vision
https://www.readbyqxmd.com/read/28954302/risk-of-subsequent-bone-cancers-among-69%C3%A2-460-five-year-survivors-of-childhood-and-adolescent-cancer-in-europe
#3
Miranda M Fidler, Raoul C Reulen, David L Winter, Rodrigue S Allodji, Francesca Bagnasco, Edit Bárdi, Andrea Bautz, Chloe J Bright, Julianne Byrne, Elizabeth A M Feijen, Stanislaw Garwicz, Desiree Grabow, Thorgerdur Gudmundsdottir, Joyeeta Guha, Nadia Haddy, Momcilo Jankovic, Peter Kaatsch, Melanie Kaiser, Rahel Kuonen, Helena Linge, Milena Maule, Franco Merletti, Hilde Øfstaas, Cecile M Ronckers, Roderick Skinner, Jop Teepen, Monica Terenziani, Giao Vu-Bezin, Finn Wesenberg, Thomas Wiebe, Zsuzsanna Jakab, Riccardo Haupt, Päivi Lähteenmäki, Lorna Zadravec Zaletel, Claudia E Kuehni, Jeanette F Winther, Florent de Vathaire, Leontien C Kremer, Lars Hjorth, Michael M Hawkins
Introduction: We investigate the risks of subsequent primary bone cancers after childhood and adolescent cancer in 12 European countries. For the first time, we satisfactorily address the risks beyond 40 years from diagnosis and beyond 40 years of age among all survivors. Methods: This largest-ever assembled cohort comprises 69 460 five-year survivors of cancer diagnosed before age 20 years. Standardized incidence ratios, absolute excess risks, and multivariable-adjusted relative risks and relative excess risks were calculated...
February 1, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28940721/a-comparative-in-vitro-study-of-different-techniques-for-removal-of-fibre-posts-from-root-canals
#4
Franziska Haupt, Jana Pfitzner, Michael Hülsmann
This study evaluates the effectiveness of different techniques to remove fibre posts from root filled teeth in vitro. One hundred and fifty-three extracted single-rooted teeth were decoronated, root-canal treated and divided into three groups (n = 51). Post spaces were prepared for different types of fibre posts: glass fibre, quartz fibre, carbon fibre. Each group was divided into three subgroups with regard to the post removal technique (n = 17): SonicFlex Endo, long-shaft round bur, DT-Post removal kit. Residual material, loss of dentine, working time and procedural errors were assessed using computed tomography...
September 20, 2017: Australian Endodontic Journal: the Journal of the Australian Society of Endodontology Inc
https://www.readbyqxmd.com/read/28925362/generation-of-a-klf15-homozygous-knockout-human-embryonic-stem-cell-line-using-paired-crispr-cas9n-and-human-cardiomyocytes-derivation
#5
Claudia Noack, Luis Peter Haupt, Wolfram-Hubertus Zimmermann, Katrin Streckfuss-Bömeke, Laura Cecilia Zelarayán
Krueppel-like factor 15 (KLF15) is abundantly expressed in liver, kidney, and muscle, including myocardium. In the adult heart KLF15 is important to maintain homeostasis and to repress hypertrophic remodeling. We generated a homozygous hESC KLF15 knockout (KO) line using paired CRISPR/Cas9n. KLF15-KO cells maintained full pluripotency and differentiation potential as well as genomic integrity. We demonstrated that KLF15-KO cells can be differentiated into morphologically normal cardiomyocytes turning them into a valuable tool for studying human KLF15-mediated mechanisms resulting in human cardiac dysfunction...
August 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28906153/investigational-drugs-in-phase-ii-clinical-trials-for-the-treatment-of-neuroblastoma
#6
Loredana Amoroso, Riccardo Haupt, Alberto Garaventa, Mirco Ponzoni
Neuroblastoma (NB) is an embryonal tumor originating from undifferentiated neural crest cell, highly heterogeneous ranging from spontaneous regression to progression despite multimodal treatments. Approximately, 20% of patients are refractory to frontline therapy and 50% will relapse/progress after an initial response. The overall five year survival for high-risk neuroblastoma ranges from 35-45%. Despite enhanced understanding of NB biology and the addition of myeloablative chemotherapy, isotretinoin and immunotherapy, survival for high risk NB remains less than 50%...
November 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28900272/from-malaria-to-cancer-computational-drug-repositioning-of-amodiaquine-using-plip-interaction-patterns
#7
Sebastian Salentin, Melissa F Adasme, Jörg C Heinrich, V Joachim Haupt, Simone Daminelli, Yixin Zhang, Michael Schroeder
Drug repositioning identifies new indications for known drugs. Here we report repositioning of the malaria drug amodiaquine as a potential anti-cancer agent. While most repositioning efforts emerge through serendipity, we have devised a computational approach, which exploits interaction patterns shared between compounds. As a test case, we took the anti-viral drug brivudine (BVDU), which also has anti-cancer activity, and defined ten interaction patterns using our tool PLIP. These patterns characterise BVDU's interaction with its target s...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28888202/iron-accumulation-in-senescent-cells-is-coupled-with-impaired-ferritinophagy-and-inhibition-of-ferroptosis
#8
Shashank Masaldan, Sharnel A S Clatworthy, Cristina Gamell, Peter M Meggyesy, Antonia-Tonia Rigopoulos, Sue Haupt, Ygal Haupt, Delphine Denoyer, Paul A Adlard, Ashley I Bush, Michael A Cater
Cellular senescence is characterised by the irreversible arrest of proliferation, a pro-inflammatory secretory phenotype and evasion of programmed cell death mechanisms. We report that senescence alters cellular iron acquisition and storage and also impedes iron-mediated cell death pathways. Senescent cells, regardless of stimuli (irradiation, replicative or oncogenic), accumulate vast amounts of intracellular iron (up to 30-fold) with concomitant changes in the levels of iron homeostasis proteins. For instance, ferritin (iron storage) levels provided a robust biomarker of cellular senescence, for associated iron accumulation and for resistance to iron-induced toxicity...
September 1, 2017: Redox Biology
https://www.readbyqxmd.com/read/28886907/final-efficacy-immunogenicity-and-safety-analyses-of-a-nine-valent-human-papillomavirus-vaccine-in-women-aged-16-26-years-a-randomised-double-blind-trial
#9
Warner K Huh, Elmar A Joura, Anna R Giuliano, Ole-Erik Iversen, Rosires Pereira de Andrade, Kevin A Ault, Deborah Bartholomew, Ramon M Cestero, Edison N Fedrizzi, Angelica L Hirschberg, Marie-Hélène Mayrand, Angela Maria Ruiz-Sternberg, Jack T Stapleton, Dorothy J Wiley, Alex Ferenczy, Robert Kurman, Brigitte M Ronnett, Mark H Stoler, Jack Cuzick, Suzanne M Garland, Susanne K Kjaer, Oliver M Bautista, Richard Haupt, Erin Moeller, Michael Ritter, Christine C Roberts, Christine Shields, Alain Luxembourg
BACKGROUND: Primary analyses of a study in young women aged 16-26 years showed efficacy of the nine-valent human papillomavirus (9vHPV; HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58) vaccine against infections and disease related to HPV 31, 33, 45, 52, and 58, and non-inferior HPV 6, 11, 16, and 18 antibody responses when compared with quadrivalent HPV (qHPV; HPV 6, 11, 16, and 18) vaccine. We aimed to report efficacy of the 9vHPV vaccine for up to 6 years following first administration and antibody responses over 5 years...
September 5, 2017: Lancet
https://www.readbyqxmd.com/read/28857192/moisture-content-of-root-canal-dentine-affects-detection-of-microcracks-using-micro-computed-tomography
#10
T Rödig, C Müller, M Hoch, F Haupt, X Schulz, A Wiegand, M Rizk
AIM: To evaluate the effect of moisture content in root canal dentine on detection of microcracks using micro-computed tomography. METHODOLOGY: Ten roots with and without craze lines or cracks (each n = 5) were selected and scanned six times with different moisture conditions of root dentine using a micro-CT scanner at a high resolution of 10.5 μm. Scanning conditions were as follows: 1. after 30 d wet storage, 2. after 2 h dry time, 3. after 48 h wet storage, 4...
August 30, 2017: International Endodontic Journal
https://www.readbyqxmd.com/read/28844201/bivalirudin-versus-heparin-monotherapy-in-myocardial-infarction
#11
RANDOMIZED CONTROLLED TRIAL
David Erlinge, Elmir Omerovic, Ole Fröbert, Rikard Linder, Mikael Danielewicz, Mehmet Hamid, Eva Swahn, Loghman Henareh, Henrik Wagner, Peter Hårdhammar, Iwar Sjögren, Jason Stewart, Per Grimfjärd, Jens Jensen, Mikael Aasa, Lotta Robertsson, Pontus Lindroos, Jan Haupt, Helena Wikström, Anders Ulvenstam, Pallonji Bhiladvala, Bo Lindvall, Anders Lundin, Tim Tödt, Dan Ioanes, Truls Råmunddal, Thomas Kellerth, Leszek Zagozdzon, Matthias Götberg, Jonas Andersson, Oskar Angerås, Ollie Östlund, Bo Lagerqvist, Claes Held, Lars Wallentin, Fredrik Scherstén, Peter Eriksson, Sasha Koul, Stefan James
BACKGROUND: The comparative efficacy of various anticoagulation strategies has not been clearly established in patients with acute myocardial infarction who are undergoing percutaneous coronary intervention (PCI) according to current practice, which includes the use of radial-artery access for PCI and administration of potent P2Y12 inhibitors without the planned use of glycoprotein IIb/IIIa inhibitors. METHODS: In this multicenter, randomized, registry-based, open-label clinical trial, we enrolled patients with either ST-segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) who were undergoing PCI and receiving treatment with a potent P2Y12 inhibitor (ticagrelor, prasugrel, or cangrelor) without the planned use of glycoprotein IIb/IIIa inhibitors...
September 21, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28835619/the-zero-effect-voxel-based-lesion-symptom-mapping-of-number-transcoding-errors-following-stroke
#12
Marleen Haupt, Céline R Gillebert, Nele Demeyere
Zero represents a special case in our numerical system because it is not represented on a semantic level. Former research has shown that this can lead to specific impairments when transcoding numerals from dictation to written digits. Even though, number processing is considered to be dominated by the left hemisphere, studies have indicated that both left as well as right hemispheric stroke patients commit errors when transcoding numerals including zeros. Here, for the first time, a large sample of subacute stroke patients (N = 667) was assessed without being preselected based on the location of their lesion, or a specific impairment in transcoding zero...
August 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28833726/performance-of-1-3-%C3%AE-d-glucan-for-diagnosing-invasive-fungal-diseases-in-children
#13
Carmelina Calitri, Ilaria Caviglia, Giuliana Cangemi, Elisa Furfaro, Roberto Bandettini, Francesca Fioredda, Loredana Amoroso, Maura Faraci, Francesco M Risso, Girolamo Mattioli, Andrea Moscatelli, Riccardo Haupt, Elio Castagnola
Plasma 1,3-β-D-glucan (BDG) is indicated as a tool for early diagnosis of invasive fungal diseases (IFD). However, data on its diagnostic value are scarce in children. Therefore, definition of BDG test performance in paediatrics is needed. BDG was evaluated in children admitted to "Istituto Giannina Gaslini," Genoa, Italy, who developed clinical conditions at risk for IFD. Results were analysed for sensitivity, specificity, predictive values, likelihood ratios, accuracy, informedness and probability of missing one case by a negative test...
August 17, 2017: Mycoses
https://www.readbyqxmd.com/read/28831512/-advance-directive-of-probands-in-pharmaceutical-research-a-medical-ethics-discussion
#14
REVIEW
M Haupt, F Jessen, H Fangerau
In the fourth Act on the amendment of pharmaceutical legal and other regulations in November 2016, the legislature has designated the proband advance directive based on the instrument of patient advance directive to enable group beneficial research with persons not capable of giving consent. This article describes the existing conditional need for group beneficial research and presents the problem of the decisive instrument for advance directives at the center of the considerations. The features of the proband advance directive concluded by the legislature stand in opposition to a successful implementation, particularly due to the necessary concrete clarification content far in advance for informed research participants...
August 22, 2017: Der Nervenarzt
https://www.readbyqxmd.com/read/28820525/the-content-validity-of-a-chemotherapy-induced-peripheral-neuropathy-patient-reported-outcome-measure
#15
Ellen M Lavoie Smith, Rylie Haupt, James P Kelly, Deborah Lee, Grace Kanzawa-Lee, Robert Knoerl, Celia Bridges, Paola Alberti, Nusara Prasertsri, Clare Donohoe
PURPOSE/OBJECTIVES: To test the content validity of a 16-item version of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy (QLQ-CIPN20). 
. RESEARCH APPROACH: Cross-sectional, prospective, qualitative design. 
. SETTING: Six outpatient oncology clinics within the University of Michigan Health System's comprehensive cancer center in Ann Arbor. 
...
September 1, 2017: Oncology Nursing Forum
https://www.readbyqxmd.com/read/28814507/systematic-gene-tagging-using-crispr-cas9-in-human-stem-cells-to-illuminate-cell-organization
#16
Brock Roberts, Amanda Haupt, Andrew Tucker, Tanya Grancharova, Joy Arakaki, Margaret A Fuqua, Angelique Nelson, Caroline Hookway, Susan A Ludmann, Irina A Mueller, Ruian Yang, Rick Horwitz, Susanne M Rafelski, Ruwanthi N Gunawardane
We present a CRISPR/Cas9 genome-editing strategy to systematically tag endogenous proteins with fluorescent tags in human induced pluripotent stem cells (hiPSC). To date, we have generated multiple hiPSC lines with monoallelic green fluorescent protein tags labeling 10 proteins representing major cellular structures. The tagged proteins include alpha tubulin, beta actin, desmoplakin, fibrillarin, nuclear lamin B1, nonmuscle myosin heavy chain IIB, paxillin, Sec61 beta, tight junction protein ZO1, and Tom20...
October 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28771610/the-impact-of-thyroid-hormones-on-patients-with-hepatocellular-carcinoma
#17
Matthias Pinter, Lukas Haupt, Florian Hucke, Simona Bota, Theresa Bucsics, Michael Trauner, Markus Peck-Radosavljevic, Wolfgang Sieghart
BACKGROUND & AIMS: Hypothyroidism has recently been proposed as predisposing factor for HCC development. However, the role of thyroid hormones (TH) in established HCC is largely unclear. We investigated the impact of TH on clinical characteristics and prognosis of HCC patients. METHODS: Of 838 patients diagnosed with nonsurgical HCC at the Division of Gastroenterology and Hepatology/Medical University of Vienna between 1992 and 2012, 667 patients fulfilled the inclusion criteria...
2017: PloS One
https://www.readbyqxmd.com/read/28743750/serum-amyloid-a-forms-stable-oligomers-that-disrupt-vesicles-at-lysosomal-ph-and-contribute-to-the-pathogenesis-of-reactive-amyloidosis
#18
Shobini Jayaraman, Donald L Gantz, Christian Haupt, Olga Gursky
Serum amyloid A (SAA) is an acute-phase plasma protein that functions in innate immunity and lipid homeostasis. SAA is a protein precursor of reactive AA amyloidosis, the major complication of chronic inflammation and one of the most common human systemic amyloid diseases worldwide. Most circulating SAA is protected from proteolysis and misfolding by binding to plasma high-density lipoproteins. However, unbound soluble SAA is intrinsically disordered and is either rapidly degraded or forms amyloid in a lysosome-initiated process...
August 8, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28733641/influence-of-c-terminal-truncation-of-murine-serum-amyloid-a-on-fibril-structure
#19
Matthies Rennegarbe, Inga Lenter, Angelika Schierhorn, Romy Sawilla, Christian Haupt
Amyloid A (AA) amyloidosis is a systemic protein misfolding disease affecting humans and other vertebrates. While the protein precursor in humans and mice is the acute-phase reactant serum amyloid A (SAA) 1.1, the deposited fibrils consist mainly of C-terminally truncated SAA fragments, termed AA proteins. For yet unknown reasons, phenotypic variations in the AA amyloid distribution pattern are clearly associated with specific AA proteins. Here we describe a bacterial expression system and chromatographic strategies to obtain significant amounts of C-terminally truncated fragments of murine SAA1...
July 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28700675/occupation-with-grain-crops-is-associated-with-lower-type-1-diabetes-incidence-registry-based-case-control-study
#20
Martin Haupt-Jorgensen, Erik Nielsen, Kåre Engkilde, Mia Lerche, Jesper Larsen, Karsten Buschard
Intranasal administration of gliadin prevents autoimmune diabetes in non-obese diabetic mice. The current study was designed to investigate if bakers are intranasally exposed to gluten during work and whether occupation as baker is inversely associated with type 1 diabetes. Gliadin was measured in nasal swabs from eight bakers and butchers. The odds ratio of type 1 diabetes in selected profession groups was analysed in a registry-based case-control study with data from 1980 to 2010 derived from Statistics Denmark...
2017: PloS One
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