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https://www.readbyqxmd.com/read/28337327/discovery-of-potent-selective-and-structurally-novel-dot1l-inhibitors-by-a-fragment-linking-approach
#1
Henrik Möbitz, Rainer Machauer, Philipp Holzer, Andrea Vaupel, Frédéric Stauffer, Christian Ragot, Giorgio Caravatti, Clemens Scheufler, Cesar Fernandez, Ulrich Hommel, Ralph Tiedt, Kim S Beyer, Chao Chen, Hugh Zhu, Christoph Gaul
Misdirected catalytic activity of histone methyltransferase Dot1L is believed to be causative for a subset of highly aggressive acute leukemias. Targeting the catalytic domain of Dot1L represents a potential therapeutic approach for these leukemias. In the context of a comprehensive Dot1L hit finding strategy, a knowledge-based virtual screen of the Dot1L SAM binding pocket led to the discovery of 2, a non-nucleoside fragment mimicking key interactions of SAM bound to Dot1L. Fragment linking of 2 and 3, an induced back pocket binder identified in earlier studies, followed by careful ligand optimization led to the identification of 7, a highly potent, selective and structurally novel Dot1L inhibitor...
March 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28325979/an-endangered-west-african-rattan-palm-eremospatha-dransfieldii
#2
Ariane Cosiaux, Lauren M Gardiner, Doudjo N Ouattara, Fred W Stauffer, Bonaventure Sonké, Thomas L P Couvreur
No abstract text is available yet for this article.
2017: Biodiversity Data Journal
https://www.readbyqxmd.com/read/28317459/outcome-of-peripheral-t-cell-lymphoma-in-first-complete-remission-a-danish-swedish-population-based-study
#3
Henrik Cederleuf, Lasse Hjort Jakobsen, Fredrik Ellin, Peter de Nully Brown, Thomas Stauffer Larsen, Martin Bøgsted, Thomas Relander, Mats Jerkeman, Tarec Christoffer El-Galaly
In the present study, we investigate the outcome of 109 Danish and 123 Swedish patients with nodal PTCL in first complete remission (CR), and examine the impact of imaging-based follow-up (FU) strategies. The patients were selected by the following criteria: (a) newly diagnosed nodal PTCL from 2007 to 2012, (b) age ≥18 years, and (c) CR after CHOP or CHOEP therapy. FU guidelines in Sweden included symptom assessment, clinical examinations and blood tests at 3-4-month intervals for 2 years. FU strategies in Denmark was similar but included routine imaging, usually every 6 months for 2 years...
March 20, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28298620/refractory-cardiogenic-shock-from-right-ventricular-infarction-successfully-managed-with-inhaled-epoprostenol
#4
Natalie Held, Nathaniel Little, Mori J Krantz, Brian L Stauffer
BACKGROUND Recognition and appropriate management of right ventricular (RV) infarction is essential, as RV injury increases mortality and substantially alters management during acute coronary syndrome. We report a case of RV infarction presenting with new right bundle branch block (RBBB), and therapeutic use of inhaled epoprostenol to reduce RV afterload and augment cardiac output during refractory cardiogenic shock. CASE REPORT A 53-year-old male presented to our institution in ventricular fibrillation with subsequent development of RBBB in the setting of proximal right coronary artery occlusion...
March 16, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/28251250/quality-assurance-guidelines-for-superficial-hyperthermia-clinical-trials-ii-%C3%A2-technical-requirements-for-heating-devices
#5
REVIEW
Hana Dobšíček Trefná, Johannes Crezee, Manfred Schmidt, Dietmar Marder, Ulf Lamprecht, Michael Ehmann, Jacek Nadobny, Josefin Hartmann, Nicolleta Lomax, Sultan Abdel-Rahman, Sergio Curto, Akke Bakker, Mark D Hurwitz, Chris J Diederich, Paul R Stauffer, Gerard C Van Rhoon
Quality assurance (QA) guidelines are essential to provide uniform execution of clinical trials with uniform quality hyperthermia treatments. This document outlines the requirements for appropriate QA of all current superficial heating equipment including electromagnetic (radiative and capacitive), ultrasound, and infrared heating techniques. Detailed instructions are provided how to characterize and document the performance of these hyperthermia applicators in order to apply reproducible hyperthermia treatments of uniform high quality...
March 1, 2017: Strahlentherapie und Onkologie: Organ der Deutschen Röntgengesellschaft ... [et Al]
https://www.readbyqxmd.com/read/28247063/misfolded-sod1-is-not-a-primary-component-of-sporadic-als
#6
Sandrine Da Cruz, Anh Bui, Shahram Saberi, Sandra K Lee, Jennifer Stauffer, Melissa McAlonis-Downes, Derek Schulte, Donald P Pizzo, Philippe A Parone, Don W Cleveland, John Ravits
A common feature of inherited and sporadic ALS is accumulation of abnormal proteinaceous inclusions in motor neurons and glia. SOD1 is the major protein component accumulating in patients with SOD1 mutations, as well as in mutant SOD1 mouse models. ALS-linked mutations of SOD1 have been shown to increase its propensity to misfold and/or aggregate. Antibodies specific for monomeric or misfolded SOD1 have detected misfolded SOD1 accumulating predominantly in spinal cord motor neurons of ALS patients with SOD1 mutations...
February 28, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28214485/outcome-of-peripheral-venous-reconstructions-during-tumor-resection
#7
Philip Y Sun, Mark D Fleming, Kendall Stauffer, Manju Kalra, Gustavo Oderich, Thomas Bower, Peter Gloviczki, Randall R DeMartino
OBJECTIVE: Peripheral venous reconstruction surgery may be necessary for appropriate oncologic resection; however, the operative approach and surgical outcomes are not well described. We report our experience with these complex reconstructions to identify best practice. METHODS: We retrospectively reviewed all adult patients who underwent peripheral vein reconstruction for tumor resection at Mayo Clinic, Rochester (2000-2015). Patients were classified into three subgroups by the location: iliac (IL), lower extremity (LE), and upper extremity (UE)...
March 2017: Journal of Vascular Surgery. Venous and Lymphatic Disorders
https://www.readbyqxmd.com/read/28168958/standardization-and-streamlining-of-a-pancreas-surgery-practice-improves-outcomes-and-resource-utilization-a-single-institution-s-20-year-experience
#8
John A Stauffer, Edwin O Onkendi, Michael B Wallace, Massimo Raimondo, Timothy A Woodward, Frank J Lukens, Horacio J Asbun
BACKGROUND: In the past two decades, pancreas surgery (PS) has undergone significant advances in operative techniques and with a focus on multidisciplinary high-volume practices. METHODS: A review of patients undergoing PS from 3/1995-2/2015 was conducted; dividing patients into group A (1995-2005) and group B (2005-2015) for a detailed comparison. Effect of surgeon volume in group B was determined. RESULTS: A total of 1001 patients underwent PS (group A: 259; group B: 742)...
January 30, 2017: American Journal of Surgery
https://www.readbyqxmd.com/read/28130338/exosomes-from-pediatric-dilated-cardiomyopathy-patients-modulate-a-pathological-response-in-cardiomyocytes
#9
Xuan Jiang, Juliana Sucharov, Brian L Stauffer, Shelley D Miyamoto, Carmen C Sucharov
Stimulation of the renin-angiotensin-aldosterone system (RAAS) and β-adrenergic receptors plays an important role in adult heart failure (HF). Despite the demonstrated benefits of RAAS inhibition and β-adrenergic receptor blockade in adult HF patients, no substantial improvement in survival rate has been observed in children with HF. This suggests that the underlying disease mechanism is uniquely regulated in pediatric HF. Here, we show that treatment of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and neonatal rat ventricular myocytes (NRVMs) with serum from pediatric dilated cardiomyopathy (DCM) patients induces pathologic changes in gene expression, which occurs independently of the RAAS and adrenergic systems, suggesting that serum circulating factors play an important role in cardiac remodeling...
January 27, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28119418/nucleoid-and-cytoplasmic-localization-of-small-rnas-in-escherichia-coli
#10
Huanjie Sheng, Weston T Stauffer, Razika Hussein, Chris Lin, Han N Lim
Bacterial small RNAs (sRNAs) regulate protein production by binding to mRNAs and altering their translation and degradation. sRNAs are smaller than most mRNAs but larger than many proteins. Therefore it is uncertain whether sRNAs can enter the nucleoid to target nascent mRNAs. Here, we investigate the intracellular localization of sRNAs transcribed from plasmids in Escherichia coli using RNA fluorescent in-situ hybridization. We found that sRNAs (GlmZ, OxyS, RyhB and SgrS) have equal preference for the nucleoid and cytoplasm, and no preferential localization at the cell membrane...
January 23, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28095160/minimal-loss-of-lifetime-for-patients-with-diffuse-large-b-cell-lymphoma-in-remission-and-event-free-24-months-after-treatment-a-danish-population-based-study
#11
Lasse Hjort Jakobsen, Martin Bøgsted, Peter de Nully Brown, Bente Arboe, Judit Jørgensen, Thomas Stauffer Larsen, Maja Bech Juul, Lene Schurmann, Linda Højberg, Olav Jonas Bergmann, Therese Lassen, Pär Lars Josefsson, Paw Jensen, Hans Erik Johnsen, Tarec Christoffer El-Galaly
Purpose The general outlook for patients with diffuse large B-cell lymphoma (DLBCL) in first remission is important information for patients and for planning post-treatment follow-up. The purpose of this study was to evaluate the survival of patients with DLBCL in remission compared with a matched general population. Methods A total of 1,621 patients from the Danish Lymphoma Registry who were newly diagnosed with DLBCL between 2003 and 2011 were included in this study. All patients were ≥ 16 years of age at diagnosis and had achieved complete remission or complete remission unconfirmed after first-line rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or R-CHOP-like therapy...
March 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28092686/epigenomic-reprogramming-during-pancreatic-cancer-progression-links-anabolic-glucose-metabolism-to-distant-metastasis
#12
Oliver G McDonald, Xin Li, Tyler Saunders, Rakel Tryggvadottir, Samantha J Mentch, Marc O Warmoes, Anna E Word, Alessandro Carrer, Tal H Salz, Sonoko Natsume, Kimberly M Stauffer, Alvin Makohon-Moore, Yi Zhong, Hao Wu, Kathryn E Wellen, Jason W Locasale, Christine A Iacobuzio-Donahue, Andrew P Feinberg
During the progression of pancreatic ductal adenocarcinoma (PDAC), heterogeneous subclonal populations emerge that drive primary tumor growth, regional spread, distant metastasis, and patient death. However, the genetics of metastases largely reflects that of the primary tumor in untreated patients, and PDAC driver mutations are shared by all subclones. This raises the possibility that an epigenetic process might operate during metastasis. Here we report large-scale reprogramming of chromatin modifications during the natural evolution of distant metastasis...
March 2017: Nature Genetics
https://www.readbyqxmd.com/read/28081082/seedless-velocimetry-at-100%C3%A2-%C3%A2-khz-with-picosecond-laser-electronic-excitation-tagging
#13
Naibo Jiang, Jason G Mance, Mikhail N Slipchenko, Josef J Felver, Hans U Stauffer, Tongxun Yi, Paul M Danehy, Sukesh Roy
Picosecond-laser electronic-excitation tagging (PLEET), a seedless picosecond-laser-based velocimetry technique, is demonstrated in non-reactive flows at a repetition rate of 100 kHz with a 1064 nm, 100 ps burst-mode laser. The fluorescence lifetime of the PLEET signal was measured in nitrogen, and the laser heating effects were analyzed. PLEET experiments with a free jet of nitrogen show the ability to measure multi-point flow velocity fluctuations at a 100 kHz detection rate or higher. Both spectral and dynamic mode decomposition analyses of velocity on a Ma=0...
January 15, 2017: Optics Letters
https://www.readbyqxmd.com/read/28049386/quality-assurance-guidelines-for-superficial-hyperthermia-clinical-trials-i-clinical-requirements
#14
Hana Dobšíček Trefná, Hans Crezee, Manfred Schmidt, Dietmar Marder, Ulf Lamprecht, Michael Ehmann, Josefin Hartmann, Jacek Nadobny, Johanna Gellermann, Netteke van Holthe, Pirus Ghadjar, Nicoletta Lomax, Sultan Abdel-Rahman, Christoph Bert, Akke Bakker, Mark D Hurwitz, Chris J Diederich, Paul R Stauffer, Gerard C van Rhoon
Quality assurance guidelines are essential to provide uniform execution of clinical trials and treatment in the application of hyperthermia. This document provides definitions for a good hyperthermia treatment and identifies the clinical conditions where a certain hyperthermia system can or cannot adequately heat the tumour volume. It also provides brief description of the characteristics and performance of the current electromagnetic (radiative and capacitive), ultrasound and infra-red heating techniques. This information helps to select the appropriate heating technique for the specific tumour location and size, and appropriate settings of the water bolus and thermometry...
January 31, 2017: International Journal of Hyperthermia
https://www.readbyqxmd.com/read/28040280/management-and-outcome-of-patients-with-acute-myocardial-infarction-presenting-with-pacemaker-rhythm
#15
Noemi Bertel, Fabienne Witassek, Milo Puhan, Paul Erne, Hans Rickli, Barbara Naegeli, Giovanni Pedrazzini, Jean-Christophe Stauffer, Dragana Radovanovic
BACKGROUND: Diagnosis of acute myocardial infarction (MI) is challenging in pacemaker patients. Little is known about this patient group. METHODS: Patients with MI enrolled in the Swiss national AMIS Plus registry between January 2005 and December 2015 were analyzed. All patients with either paced ventricular rhythm or sinus rhythm with intrinsic ventricular conduction (IVC) were included in this study. Outcomes using crude data and propensity score matching were compared between patients with pacemaker rhythm and patients with IVC...
March 1, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28028089/wolbachia-in-parasitoids-attacking-native-european-and-introduced-eastern-cherry-fruit-flies-in-europe
#16
Hannes Schuler, Peter Kern, Wolfgang Arthofer, Heidrun Vogt, Maximilian Fischer, Christian Stauffer, Markus Riegler
The eastern cherry fruit fly, Rhagoletis cingulata Loew (Diptera: Tephritidae), is an economically important pest of cherries in North America. In 1983 it was first reported in Europe where it shares its ecological niche with the native European cherry fruit fly, Rhagoletis cerasi L. (Diptera: Tephritidae). Their coexistence in Europe led to the recent horizontal transmission of the Wolbachia strain wCer1 from R. cerasi to R. cingulata Horizontal Wolbachia transmission is mediated by either sharing of ecological niches or by interacting species such as parasitoids...
December 2016: Environmental Entomology
https://www.readbyqxmd.com/read/28027588/integrating-multiple-data-sources-in-species-distribution-modeling-a-framework-for-data-fusion
#17
Krishna Pacifici, Brian J Reich, David A W Miller, Beth Gardner, Glenn Stauffer, Susheela Singh, Alexa McKerrow, Jaime A Collazo
The last decade has seen a dramatic increase in the use of species distribution models (SDMs) to characterize patterns of species' occurrence and abundance. Efforts to parameterize SDMs often create a tension between the quality and quantity of data available to fit models. Estimation methods that integrate both standardized and non-standardized data types offer a potential solution to the trade-off between data quality and quantity. Recently several authors have developed approaches for jointly modeling two sources of data (one of high quality and one of lesser quality)...
December 27, 2016: Ecology
https://www.readbyqxmd.com/read/28024327/simple-synthesis-of-nanocrystalline-tin-sulfide-n-doped-reduced-graphene-oxide-composites-as-lithium-ion-battery-anodes
#18
Duck Hyun Youn, Shannon K Stauffer, Penghao Xiao, Hunmin Park, Yejin Nam, Andrei Dolocan, Graeme Henkelman, Adam Heller, C Buddie Mullins
Composites of nitrogen-doped reduced graphene oxide (NRGO) and nanocrystalline tin sulfides were synthesized, and their performance as lithium ion battery anodes was evaluated. Following the first cycle the composite consisted of Li2S/LixSn/NRGO. The conductive NRGO cushions the stress associated with the expansion of lithiation of Sn, and the noncycling Li2S increases the residual Coulombic capacity of the cycled anode because (a) Sn domains in the composite formed of unsupported SnS2 expand only by 63% while those in the composite formed of unsupported SnS expand by 91% and (b) Li percolates rapidly at the boundary between the Li2S and LixSn nanodomains...
December 27, 2016: ACS Nano
https://www.readbyqxmd.com/read/28018428/pancreatic-surgery-in-the-older-population-a-single-institution-s-experience-over-two-decades
#19
Bhaumik Brahmbhatt, Abhishek Bhurwal, Frank J Lukens, Mauricia A Buchanan, John A Stauffer, Horacio J Asbun
Objectives. Surgery is the most effective treatment for pancreatic cancer. However, present literature varies on outcomes of curative pancreatic resection in the elderly. The objective of the study was to evaluate age as an independent risk factor for 90-day mortality and complications after pancreatic resection. Methods. Nine hundred twenty-nine consecutive patients underwent 934 pancreatic resections between March 1995 and July 2014 in a tertiary care center. Primary analyses focused on outcomes in terms of 90-day mortality and postoperative complications after pancreatic resection in these two age groups...
2016: Current Gerontology and Geriatrics Research
https://www.readbyqxmd.com/read/28004807/expert-consensus-document-mitochondrial-function-as-a-therapeutic-target-in-heart-failure
#20
REVIEW
David A Brown, Justin B Perry, Mitchell E Allen, Hani N Sabbah, Brian L Stauffer, Saame Raza Shaikh, John G F Cleland, Wilson S Colucci, Javed Butler, Adriaan A Voors, Stefan D Anker, Bertram Pitt, Burkert Pieske, Gerasimos Filippatos, Stephen J Greene, Mihai Gheorghiade
Heart failure is a pressing worldwide public-health problem with millions of patients having worsening heart failure. Despite all the available therapies, the condition carries a very poor prognosis. Existing therapies provide symptomatic and clinical benefit, but do not fully address molecular abnormalities that occur in cardiomyocytes. This shortcoming is particularly important given that most patients with heart failure have viable dysfunctional myocardium, in which an improvement or normalization of function might be possible...
April 2017: Nature Reviews. Cardiology
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