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Michael karin

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https://www.readbyqxmd.com/read/29779975/design-and-synthesis-of-a-series-of-bioavailable-fatty-acid-synthase-fasn-kr-domain-inhibitors-for-cancer-therapy
#1
Tianbao Lu, Carsten Schubert, Maxwell D Cummings, Gilles Bignan, Peter J Connolly, Karine Smans, Donald Ludovici, Michael H Parker, Christophe Meyer, Christian Rocaboy, Richard Alexander, Bruce Grasberger, Sabine De Breucker, Norbert Esser, Erwin Fraiponts, Ron Gilissen, Boudewijn Janssens, Danielle Peeters, Luc Van Nuffel, Peter Vermeulen, James Bischoff, Lieven Meerpoel
We designed and synthesized a new series of fatty acid synthase (FASN) inhibitors with potential utility for the treatment of cancer. Extensive SAR studies led to highly active FASN inhibitors with good cellular activity and oral bioavailability, exemplified by compound 34. Compound 34 is a potent inhibitor of human FASN (IC50  = 28 nM) that effectively inhibits proliferation of A2780 ovarian cells (IC50  = 13 nM) in lipid-reduced serum (LRS). This cellular activity can be rescued by addition of palmitate, consistent with an on-target effect...
May 8, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29778638/the-impact-of-dysphagia-on-mortality-of-nursing-home-residents-results-from-the-nutritionday-project
#2
Rainer Wirth, Maryam Pourhassan, Melanie Streicher, Michael Hiesmayr, Karin Schindler, Cornel Christian Sieber, Dorothee Volkert
OBJECTIVES: Dysphagia is a frequent finding in nursing home residents. The aim of this study is to evaluate the association of dysphagia and mortality in nursing home residents and identify further risk factors for mortality in residents with dysphagia. DESIGN: One-day, annually repeated cross-sectional study, evaluating the nutritional situation of nursing home residents with 6-month mortality as outcome. SETTING: 191 nursing homes from 14 countries in Europe and the United States participating in the nutritionDay study between 2007 and 2012...
May 16, 2018: Journal of the American Medical Directors Association
https://www.readbyqxmd.com/read/29773792/mxb-is-an-interferon-induced-restriction-factor-of-human-herpesviruses
#3
Michel Crameri, Michael Bauer, Nicole Caduff, Raphael Walker, Fiona Steiner, Francesca D Franzoso, Cornelia Gujer, Karin Boucke, Talissa Kucera, Andrea Zbinden, Christian Münz, Cornel Fraefel, Urs F Greber, Jovan Pavlovic
The type I interferon (IFN) system plays an important role in controlling herpesvirus infections, but it is unclear which IFN-mediated effectors interfere with herpesvirus replication. Here we report that human myxovirus resistance protein B (MxB, also designated Mx2) is a potent human herpesvirus restriction factor in the context of IFN. We demonstrate that ectopic MxB expression restricts a range of herpesviruses from the Alphaherpesvirinae and Gammaherpesvirinae, including herpes simplex virus 1 and 2 (HSV-1 and HSV-2), and Kaposi's sarcoma-associated herpesvirus (KSHV)...
May 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29768139/canakinumab-for-the-treatment-of-autoinflammatory-recurrent-fever-syndromes
#4
Fabrizio De Benedetti, Marco Gattorno, Jordi Anton, Eldad Ben-Chetrit, Joost Frenkel, Hal M Hoffman, Isabelle Koné-Paut, Helen J Lachmann, Seza Ozen, Anna Simon, Andrew Zeft, Inmaculada Calvo Penades, Michel Moutschen, Pierre Quartier, Ozgur Kasapcopur, Anna Shcherbina, Michael Hofer, Philip J Hashkes, Jeroen Van der Hilst, Ryoki Hara, Segundo Bujan-Rivas, Tamas Constantin, Ahmet Gul, Avi Livneh, Paul Brogan, Marco Cattalini, Laura Obici, Karine Lheritier, Antonio Speziale, Guido Junge
BACKGROUND: Familial Mediterranean fever, mevalonate kinase deficiency (also known as the hyperimmunoglobulinemia D syndrome), and the tumor necrosis factor receptor-associated periodic syndrome (TRAPS) are monogenic autoinflammatory diseases characterized by recurrent fever flares. METHODS: We randomly assigned patients with genetically confirmed colchicine-resistant familial Mediterranean fever, mevalonate kinase deficiency, or TRAPS at the time of a flare to receive 150 mg of canakinumab subcutaneously or placebo every 4 weeks...
May 17, 2018: New England Journal of Medicine
https://www.readbyqxmd.com/read/29760786/ultrasound-criteria-for-risk-stratification-of-thyroid-nodules-in-the-previously-iodine-deficient-area-of-austria-a-single-centre-retrospective-analysis
#5
Christina Tugendsam, Veronika Petz, Wolfgang Buchinger, Brigitta Schmoll-Hauer, Iris Pia Schenk, Karin Rudolph, Michael Krebs, Georg Zettinig
Background: We aimed to study the validity of six published ultrasound criteria for risk stratification of thyroid nodules in the former severely iodine deficient population of Austria. Methods: Retrospective, single centre, observer blinded study design. All patients with a history of thyroidectomy due to nodules seen in the centre between 2004 and 2014 with preoperative in-house sonography and documented postoperative histology were analyzed ( n  = 195). A board of five experienced thyroidologists evaluated the images of 45 papillary carcinomas, 8 follicular carcinomas, and 142 benign nodules regarding the following criteria: mild hypoechogenicity, marked hypoechogenicity, microlobulated or irregular margins, microcalcifications, taller than wide shape, missing thin halo...
2018: Thyroid Research
https://www.readbyqxmd.com/read/29760400/sex-related-differences-in-vision-are-heterogeneous
#6
Albulena Shaqiri, Maya Roinishvili, Lukasz Grzeczkowski, Eka Chkonia, Karin Pilz, Christine Mohr, Andreas Brand, Marina Kunchulia, Michael H Herzog
Despite well-established sex differences for cognition, audition, and somatosensation, few studies have investigated whether there are also sex differences in visual perception. We report the results of fifteen perceptual measures (such as visual acuity, visual backward masking, contrast detection threshold or motion detection) for a cohort of over 800 participants. On six of the fifteen tests, males significantly outperformed females. On no test did females significantly outperform males. Given this heterogeneity of the sex effects, it is unlikely that the sex differences are due to any single mechanism...
May 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29760101/design-of-an-allosterically-modulated-doxycycline-and-doxorubicin-drug-binding-protein
#7
Karin Schmidt, Bernd R Gardill, Alina Kern, Peter Kirchweger, Michael Börsch, Yves A Muller
The allosteric interplay between distant functional sites present in a single protein provides for one of the most important regulatory mechanisms in biological systems. While the design of ligand-binding sites into proteins remains challenging, this holds even truer for the coupling of a newly engineered binding site to an allosteric mechanism that regulates the ligand affinity. Here it is shown how computational design algorithms enabled the introduction of doxycycline- and doxorubicin-binding sites into the serine proteinase inhibitor (serpin) family member α1-antichymotrypsin...
May 14, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29755376/relation-between-mathematical-performance-math-anxiety-and-affective-priming-in-children-with-and-without-developmental-dyscalculia
#8
Karin Kucian, Isabelle Zuber, Juliane Kohn, Nadine Poltz, Anne Wyschkon, Günter Esser, Michael von Aster
Many children show negative emotions related to mathematics and some even develop mathematics anxiety. The present study focused on the relation between negative emotions and arithmetical performance in children with and without developmental dyscalculia (DD) using an affective priming task. Previous findings suggested that arithmetic performance is influenced if an affective prime precedes the presentation of an arithmetic problem. In children with DD specifically, responses to arithmetic operations are supposed to be facilitated by both negative and mathematics-related primes (= negative math priming effect )...
2018: Frontiers in Psychology
https://www.readbyqxmd.com/read/29754439/exploring-psychological-mechanisms-of-clinical-response-to-an-internet-delivered-psychological-pain-management-program
#9
Milena Gandy, Eyal Karin, Michael Jones, Sarah McDonald, Louise Sharpe, Nick Titov, Blake Farran Dear
BACKGROUND: The evidence for Internet-delivered pain management programs for chronic pain is growing, but there is little empirical understanding of how they effect change. Understanding mechanisms of clinical response to these programs could inform their effective development and delivery. METHODS: A large sample (n = 396) from a previous randomised controlled trial of a validated internet-delivered psychological pain management program, the Pain Course, was used to examine the influence of three potential psychological mechanisms (pain acceptance, pain self-efficacy, fear of movement/re-injury) on treatment-related change in disability, depression, anxiety and average pain...
May 13, 2018: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/29748586/the-gut-liver-axis-and-the-intersection-with-the-microbiome
#10
REVIEW
Anupriya Tripathi, Justine Debelius, David A Brenner, Michael Karin, Rohit Loomba, Bernd Schnabl, Rob Knight
In the past decade, an exciting realization has been that diverse liver diseases - ranging from nonalcoholic steatohepatitis, alcoholic steatohepatitis and cirrhosis to hepatocellular carcinoma - fall along a spectrum. Work on the biology of the gut-liver axis has assisted in understanding the basic biology of both alcoholic fatty liver disease and nonalcoholic fatty liver disease (NAFLD). Of immense importance is the advancement in understanding the role of the microbiome, driven by high-throughput DNA sequencing and improved computational techniques that enable the complexity of the microbiome to be interrogated, together with improved experimental designs...
May 10, 2018: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/29743675/137-ancient-human-genomes-from-across-the-eurasian-steppes
#11
Peter de Barros Damgaard, Nina Marchi, Simon Rasmussen, Michaël Peyrot, Gabriel Renaud, Thorfinn Korneliussen, J Víctor Moreno-Mayar, Mikkel Winther Pedersen, Amy Goldberg, Emma Usmanova, Nurbol Baimukhanov, Valeriy Loman, Lotte Hedeager, Anders Gorm Pedersen, Kasper Nielsen, Gennady Afanasiev, Kunbolot Akmatov, Almaz Aldashev, Ashyk Alpaslan, Gabit Baimbetov, Vladimir I Bazaliiskii, Arman Beisenov, Bazartseren Boldbaatar, Bazartseren Boldgiv, Choduraa Dorzhu, Sturla Ellingvag, Diimaajav Erdenebaatar, Rana Dajani, Evgeniy Dmitriev, Valeriy Evdokimov, Karin M Frei, Andrey Gromov, Alexander Goryachev, Hakon Hakonarson, Tatyana Hegay, Zaruhi Khachatryan, Ruslan Khaskhanov, Egor Kitov, Alina Kolbina, Tabaldiev Kubatbek, Alexey Kukushkin, Igor Kukushkin, Nina Lau, Ashot Margaryan, Inga Merkyte, Ilya V Mertz, Viktor K Mertz, Enkhbayar Mijiddorj, Vyacheslav Moiyesev, Gulmira Mukhtarova, Bekmukhanbet Nurmukhanbetov, Z Orozbekova, Irina Panyushkina, Karol Pieta, Václav Smrčka, Irina Shevnina, Andrey Logvin, Karl-Göran Sjögren, Tereza Štolcová, Kadicha Tashbaeva, Alexander Tkachev, Turaly Tulegenov, Dmitriy Voyakin, Levon Yepiskoposyan, Sainbileg Undrakhbold, Victor Varfolomeev, Andrzej Weber, Nikolay Kradin, Morten E Allentoft, Ludovic Orlando, Rasmus Nielsen, Martin Sikora, Evelyne Heyer, Kristian Kristiansen, Eske Willerslev
For thousands of years the Eurasian steppes have been a centre of human migrations and cultural change. Here we sequence the genomes of 137 ancient humans (about 1× average coverage), covering a period of 4,000 years, to understand the population history of the Eurasian steppes after the Bronze Age migrations. We find that the genetics of the Scythian groups that dominated the Eurasian steppes throughout the Iron Age were highly structured, with diverse origins comprising Late Bronze Age herders, European farmers and southern Siberian hunter-gatherers...
May 9, 2018: Nature
https://www.readbyqxmd.com/read/29743205/preclinical-development-of-a-bispecific-antibody-that-safely-and-effectively-targets-cd19-and-cd47-for-the-treatment-of-b-cell-lymphoma-and-leukemia
#12
Vanessa Buatois, Zoë Johnson, Susana Salgado-Pires, Anne Papaïoannou, Eric Hatterer, Xavier Chauchet, Françoise Richard, Leticia Barba, Bruno Daubeuf, Laura Cons, Lucile Broyer, Matilde D'Asaro, Thomas Matthes, Simon LeGallou, Thierry Fest, Karin Tarte, Robert K Clarke Hinojosa, Eulàlia Genescà Ferrer, José María Ribera, Aditi Dey, Katharine Bailey, Adele K Fielding, Linda Eissenberg, Julie Ritchey, Michael Rettig, John F DiPersio, Marie H Kosco-Vilbois, Krzysztof Masternak, Nicolas Fischer, Limin Shang, Walter G Ferlin
CD47, a ubiquitously expressed innate immune checkpoint receptor that serves as a universal "don't eat me" signal of phagocytosis, is often up-regulated by hematological and solid cancers to evade immune surveillance. Development of CD47-targeted modalities is hindered by the ubiquitous expression of the target, often leading to rapid drug elimination and hemotoxicity including anemia. To overcome such liabilities, we have developed a fully human bispecific antibody, NI-1701, designed to co-engage CD47 and CD19 selectively on B cells...
May 9, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29742528/prophylactic-mesh-for-the-prevention-of-parastomal-hernias-need-for-a-deep-dive
#13
Christoffer Odensten, Karin Strigård, Jörgen Rutegård, Michael Dahlberg, Ulrika Ståhle, Ulf Gunnarson, Pia Näsvall
No abstract text is available yet for this article.
May 8, 2018: Annals of Surgery
https://www.readbyqxmd.com/read/29741699/reply-regarding-business-travelers
#14
Lin H Chen, Karin Leder, Patricia Schlagenhauf, Michael Libman, Jay Keystone, Marc Mendelson, Philippe Gautret, Eli Schwartz, Marc Shaw, Sue MacDonald, Anne McCarthy, Bradley A Connor, Davidson H Hamer, Mary E Wilson
No abstract text is available yet for this article.
January 1, 2018: Journal of Travel Medicine
https://www.readbyqxmd.com/read/29741150/comparison-of-the-pharmacokinetics-and-ex-vivo-antimalarial-activities-of-artesunate-amodiaquine-and-artemisinin-piperaquine-in-healthy-volunteers-for-preselection-malaria-therapy
#15
Nguyen Ngoc Quang, Marina Chavchich, Chu Xuan Anh, Geoffrey W Birrell, Karin van Breda, Thomas Travers, Kerryn Rowcliffe, Michael D Edstein
The pharmacokinetics (PK) and ex vivo activity (pharmacodynamics [PD]) of two artemisinin combination therapies (ACTs) (artemisinin-piperaquine [ARN-PPQ] [Artequick® ] and artesunate-amodiaquine [ARS-AQ] [Coarsucam™ ]) in healthy Vietnamese volunteers were compared following 3-day courses of the ACTs for the preselection of the drugs for falciparum malaria therapy. For PK analysis, serial plasma samples were collected from two separate groups of 22 volunteers after ACT administration. Of these volunteers, ex vivo activity was assessed in plasma samples from seven volunteers who received both ACTs...
May 7, 2018: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/29732651/supporting-carers-of-children-and-adolescents-with-eating-disorders-in-austria-succeat-study-protocol-for-a-randomised-controlled-trial
#16
Claudia Franta, Julia Philipp, Karin Waldherr, Stefanie Truttmann, Elisabeth Merl, Gabriele Schöfbeck, Doris Koubek, Clarissa Laczkovics, Hartmut Imgart, Annika Zanko, Michael Zeiler, Janet Treasure, Andreas Karwautz, Gudrun Wagner
Supporting Carers of Children and Adolescents with Eating Disorders in Austria (SUCCEAT) is an intervention for carers of children and adolescents with anorexia nervosa and atypical anorexia nervosa. This paper describes the study protocol for a randomised controlled trial including the process and economic evaluation. Carers are randomly allocated to one of the 2 SUCCEAT intervention formats, either 8 weekly 2-hr workshop sessions (n = 48) or web-based modules (n = 48), and compared with a nonrandomised control group (n = 48)...
May 6, 2018: European Eating Disorders Review: the Journal of the Eating Disorders Association
https://www.readbyqxmd.com/read/29727617/genome-wide-control-of-heterochromatin-replication-by-the-telomere-capping-protein-trf2
#17
Aaron Mendez-Bermudez, Liudmyla Lototska, Serge Bauwens, Marie-Josèphe Giraud-Panis, Olivier Croce, Karine Jamet, Agurtzane Irizar, Macarena Mowinckel, Stephane Koundrioukoff, Nicolas Nottet, Genevieve Almouzni, Mare-Paule Teulade-Fichou, Michael Schertzer, Mylène Perderiset, Arturo Londoño-Vallejo, Michelle Debatisse, Eric Gilson, Jing Ye
Hard-to-replicate regions of chromosomes (e.g., pericentromeres, centromeres, and telomeres) impede replication fork progression, eventually leading, in the event of replication stress, to chromosome fragility, aging, and cancer. Our knowledge of the mechanisms controlling the stability of these regions is essentially limited to telomeres, where fragility is counteracted by the shelterin proteins. Here we show that the shelterin subunit TRF2 ensures progression of the replication fork through pericentromeric heterochromatin, but not centromeric chromatin...
May 3, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29724424/acr-appropriateness-criteria-%C3%A2-suspected-thoracic-aortic-aneurysm
#18
Shelby J Bennett, Karin E Dill, Michael Hanley, Osmanuddin Ahmed, Benoit Desjardins, Kenneth L Gage, Michael Ginsburg, Ali Khoynezhad, Isabel B Oliva, Michael L Steigner, Richard Strax, Nupur Verma, Frank J Rybicki
Although the incidence of thoracic aortic aneurysm is on the rise, initial imaging diagnosis can present a challenge for many clinicians. Providers are faced with many imaging choices as part of the initial workup. Considering level of invasiveness, relative radiation level, and quality of associated diagnostic data, CT angiography and MR angiography are believed to be the most appropriate options for radiological diagnosis of suspected thoracic aortic aneurysm. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel...
May 2018: Journal of the American College of Radiology: JACR
https://www.readbyqxmd.com/read/29720733/adding-dasatinib-to-intensive-treatment-in-core-binding-factor-acute-myeloid-leukemia-results-of-the-amlsg-11-08-trial
#19
Peter Paschka, Richard F Schlenk, Daniela Weber, Axel Benner, Lars Bullinger, Michael Heuser, Verena I Gaidzik, Felicitas Thol, Mridul Agrawal, Veronica Teleanu, Michael Lübbert, Walter Fiedler, Markus Radsak, Jürgen Krauter, Heinz-A Horst, Richard Greil, Karin Mayer, Andrea Kündgen, Uwe Martens, Gerhard Heil, Helmut R Salih, Bernd Hertenstein, Carsten Schwänen, Gerald Wulf, Elisabeth Lange, Michael Pfreundschuh, Mark Ringhoffer, Michael Girschikofsky, Thomas Heinicke, Doris Kraemer, Gudrun Göhring, Arnold Ganser, Konstanze Döhner, Hartmut Döhner
In this phase Ib/IIa study (ClinicalTrials.gov Identifier: NCT00850382) of the German-Austrian AML Study Group (AMLSG) the multikinase inhibitor dasatinib was added to intensive induction and consolidation chemotherapy and administered as single agent for 1-year maintenance in first-line treatment of adult patients with core-binding factor (CBF) acute myeloid leukemia (AML). The primary combined end point in this study was safety and feasibility, and included the rates of early (ED) and hypoplastic (HD) deaths, pleural/pericardial effusion 3°/4° and liver toxicity 3°/4°, and the rate of refractory disease...
April 17, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29720585/de-novo-activating-mutations-drive-clonal-evolution-and-enhance-clonal-fitness-in-kmt2a-rearranged-leukemia
#20
Axel Hyrenius-Wittsten, Mattias Pilheden, Helena Sturesson, Jenny Hansson, Michael P Walsh, Guangchun Song, Julhash U Kazi, Jian Liu, Ramprasad Ramakrishan, Cristian Garcia-Ruiz, Stephanie Nance, Pankaj Gupta, Jinghui Zhang, Lars Rönnstrand, Anne Hultquist, James R Downing, Karin Lindkvist-Petersson, Kajsa Paulsson, Marcus Järås, Tanja A Gruber, Jing Ma, Anna K Hagström-Andersson
Activating signaling mutations are common in acute leukemia with KMT2A (previously MLL) rearrangements (KMT2A-R). These mutations are often subclonal and their biological impact remains unclear. Using a retroviral acute myeloid mouse leukemia model, we demonstrate that FLT3 ITD , FLT3 N676K , and NRAS G12D accelerate KMT2A-MLLT3 leukemia onset. Further, also subclonal FLT3 N676K mutations accelerate disease, possibly by providing stimulatory factors. Herein, we show that one such factor, MIF, promotes survival of mouse KMT2A-MLLT3 leukemia initiating cells...
May 2, 2018: Nature Communications
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