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Richard Axel

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https://www.readbyqxmd.com/read/29330256/osteoprotegerin-is-associated-with-major-bleeding-but-not-with-cardiovascular-outcomes-in-patients-with-acute-coronary-syndromes-insights-from-the-plato-platelet-inhibition-and-patient-outcomes-trial
#1
Thor Ueland, Axel Åkerblom, Tatevik Ghukasyan, Annika E Michelsen, Pål Aukrust, Richard C Becker, Maria Bertilsson, Anders Himmelmann, Stefan K James, Agneta Siegbahn, Robert F Storey, Frederic Kontny, Lars Wallentin
BACKGROUND: Elevated levels of osteoprotegerin, a secreted tumor necrosis factor-related molecule, might be associated with adverse outcomes in patients with coronary artery disease. We measured plasma osteoprotegerin concentrations on hospital admission, at discharge, and at 1 and 6 months after discharge in a predefined subset (n=5135) of patients with acute coronary syndromes in the PLATO (Platelet Inhibition and Patient Outcomes) trial. METHODS AND RESULTS: The associations between osteoprotegerin and the composite end point of cardiovascular death, nonprocedural spontaneous myocardial infarction or stroke, and non-coronary artery bypass grafting major bleeding during 1 year of follow-up were assessed by Cox proportional hazards models...
January 12, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29301099/from-maps-to-multi-dimensional-network-mechanisms-of-mental-disorders
#2
REVIEW
Urs Braun, Axel Schaefer, Richard F Betzel, Heike Tost, Andreas Meyer-Lindenberg, Danielle S Bassett
The development of advanced neuroimaging techniques and their deployment in large cohorts has enabled an assessment of functional and structural brain network architecture at an unprecedented level of detail. Across many temporal and spatial scales, network neuroscience has emerged as a central focus of intellectual efforts, seeking meaningful descriptions of brain networks and explanatory sets of network features that underlie circuit function in health and dysfunction in disease. However, the tools of network science commonly deployed provide insight into brain function at a fundamentally descriptive level, often failing to identify (patho-)physiological mechanisms that link system-level phenomena to the multiple hierarchies of brain function...
January 3, 2018: Neuron
https://www.readbyqxmd.com/read/29300976/integrating-new-approaches-to-atrial-fibrillation-management-the-6th-afnet-ehra-consensus-conference
#3
Dipak Kotecha, Günter Breithardt, A John Camm, Gregory Y H Lip, Ulrich Schotten, Anders Ahlsson, David Arnar, Dan Atar, Angelo Auricchio, Jeroen Bax, Stefano Benussi, Carina Blomstrom-Lundqvist, Martin Borggrefe, Giuseppe Boriani, Axel Brandes, Hugh Calkins, Barbara Casadei, Manuel Castellá, Winnie Chua, Harry Crijns, Dobromir Dobrev, Larissa Fabritz, Martin Feuring, Ben Freedman, Andrea Gerth, Andreas Goette, Eduard Guasch, Doreen Haase, Stephane Hatem, Karl Georg Haeusler, Hein Heidbuchel, Jeroen Hendriks, Craig Hunter, Stefan Kääb, Stefanie Kespohl, Ulf Landmesser, Deirdre A Lane, Thorsten Lewalter, Lluís Mont, Michael Nabauer, Jens C Nielsen, Michael Oeff, Jonas Oldgren, Ali Oto, Laurent Pison, Tatjana Potpara, Ursula Ravens, Isabelle Richard-Lordereau, Michiel Rienstra, Irina Savelieva, Renate Schnabel, Moritz F Sinner, Philipp Sommer, Sakis Themistoclakis, Isabelle C Van Gelder, Panagiotis E Vardas, Atul Verma, Reza Wakili, Evelyn Weber, David Werring, Stephan Willems, André Ziegler, Gerhard Hindricks, Paulus Kirchhof
There are major challenges ahead for clinicians treating patients with atrial fibrillation (AF). The population with AF is expected to expand considerably and yet, apart from anticoagulation, therapies used in AF have not been shown to consistently impact on mortality or reduce adverse cardiovascular events. New approaches to AF management, including the use of novel technologies and structured, integrated care, have the potential to enhance clinical phenotyping or result in better treatment selection and stratified therapy...
January 2, 2018: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/29277560/long-term-efficacy-and-safety-of-stem-cell-therapy-cx601-for-complex-perianal-fistulas-in-patients-with-crohn-s-disease
#4
Julián Panés, Damián García-Olmo, Gert Van Assche, Jean Frederic Colombel, Walter Reinisch, Daniel C Baumgart, Axel Dignass, Maria Nachury, Marc Ferrante, Lili Kazemi-Shirazi, Jean C Grimaud, Fernando de la Portilla, Eran Goldin, Marie Paule Richard, Mary Carmen Diez, Ignacio Tagarro, Anne Leselbaum, Silvio Danese
BACKGROUND & AIMS: Therapies for perianal fistulas in patients with Crohn's disease (CD) are often ineffective in producing long-term healing. We performed a randomized placebo-controlled trial to determine the long-term efficacy and safety of a single local administration of allogeneic expanded adipose-derived stem cells (Cx601) in patients with CD and perianal fistulas. METHODS: We performed a double-blind study at 49 hospitals in Europe and Israel, comprising 212 patients with CD and treatment-refractory, draining, complex perianal fistulas...
December 22, 2017: Gastroenterology
https://www.readbyqxmd.com/read/29259276/long-term-carbon-sink-in-borneo-s-forests-halted-by-drought-and-vulnerable-to-edge-effects
#5
Lan Qie, Simon L Lewis, Martin J P Sullivan, Gabriela Lopez-Gonzalez, Georgia C Pickavance, Terry Sunderland, Peter Ashton, Wannes Hubau, Kamariah Abu Salim, Shin-Ichiro Aiba, Lindsay F Banin, Nicholas Berry, Francis Q Brearley, David F R P Burslem, Martin Dančák, Stuart J Davies, Gabriella Fredriksson, Keith C Hamer, Radim Hédl, Lip Khoon Kho, Kanehiro Kitayama, Haruni Krisnawati, Stanislav Lhota, Yadvinder Malhi, Colin Maycock, Faizah Metali, Edi Mirmanto, Laszlo Nagy, Reuben Nilus, Robert Ong, Colin A Pendry, Axel Dalberg Poulsen, Richard B Primack, Ervan Rutishauser, Ismayadi Samsoedin, Bernaulus Saragih, Plinio Sist, J W Ferry Slik, Rahayu Sukmaria Sukri, Martin Svátek, Sylvester Tan, Aiyen Tjoa, Mark van Nieuwstadt, Ronald R E Vernimmen, Ishak Yassir, Petra Susan Kidd, Muhammad Fitriadi, Nur Khalish Hafizhah Ideris, Rafizah Mat Serudin, Layla Syaznie Abdullah Lim, Muhammad Shahruney Saparudin, Oliver L Phillips
Less than half of anthropogenic carbon dioxide emissions remain in the atmosphere. While carbon balance models imply large carbon uptake in tropical forests, direct on-the-ground observations are still lacking in Southeast Asia. Here, using long-term plot monitoring records of up to half a century, we find that intact forests in Borneo gained 0.43 Mg C ha-1 per year (95% CI 0.14-0.72, mean period 1988-2010) above-ground live biomass. These results closely match those from African and Amazonian plot networks, suggesting that the world's remaining intact tropical forests are now en masse out-of-equilibrium...
December 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/29249692/%C3%AE-2-adrenergic-neurotrophin-feedforward-loop-promotes-pancreatic-cancer
#6
Bernhard W Renz, Ryota Takahashi, Takayuki Tanaka, Marina Macchini, Yoku Hayakawa, Zahra Dantes, H Carlo Maurer, Xiaowei Chen, Zhengyu Jiang, C Benedikt Westphalen, Matthias Ilmer, Giovanni Valenti, Sarajo K Mohanta, Andreas J R Habenicht, Moritz Middelhoff, Timothy Chu, Karan Nagar, Yagnesh Tailor, Riccardo Casadei, Mariacristina Di Marco, Axel Kleespies, Richard A Friedman, Helen Remotti, Maximilian Reichert, Daniel L Worthley, Jens Neumann, Jens Werner, Alina C Iuga, Kenneth P Olive, Timothy C Wang
Catecholamines stimulate epithelial proliferation, but the role of sympathetic nerve signaling in pancreatic ductal adenocarcinoma (PDAC) is poorly understood. Catecholamines promoted ADRB2-dependent PDAC development, nerve growth factor (NGF) secretion, and pancreatic nerve density. Pancreatic Ngf overexpression accelerated tumor development in LSL-Kras+/G12D;Pdx1-Cre (KC) mice. ADRB2 blockade together with gemcitabine reduced NGF expression and nerve density, and increased survival of LSL-Kras+/G12D;LSL-Trp53+/R172H;Pdx1-Cre (KPC) mice...
December 1, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29235213/models-meet-data-challenges-and-opportunities-in-implementing-land-management-in-earth-system-models
#7
REVIEW
Julia Pongratz, Han Dolman, Axel Don, Karl-Heinz Erb, Richard Fuchs, Martin Herold, Chris Jones, Tobias Kuemmerle, Sebastiaan Luyssaert, Patrick Meyfroidt, Kim Naudts
As the applications of Earth system models (ESMs) move from general climate projections toward questions of mitigation and adaptation, the inclusion of land management practices in these models becomes crucial. We carried out a survey among modeling groups to show an evolution from models able only to deal with land-cover change to more sophisticated approaches that allow also for the partial integration of land management changes. For the longer term a comprehensive land management representation can be anticipated for all major models...
December 13, 2017: Global Change Biology
https://www.readbyqxmd.com/read/29227286/drug-perturbation-based-stratification-of-blood-cancer
#8
Sascha Dietrich, Małgorzata Oleś, Junyan Lu, Leopold Sellner, Simon Anders, Britta Velten, Bian Wu, Jennifer Hüllein, Michelle da Silva Liberio, Tatjana Walther, Lena Wagner, Sophie Rabe, Sonja Ghidelli-Disse, Marcus Bantscheff, Andrzej K Oleś, Mikołaj Słabicki, Andreas Mock, Christopher C Oakes, Shihui Wang, Sina Oppermann, Marina Lukas, Vladislav Kim, Martin Sill, Axel Benner, Anna Jauch, Lesley Ann Sutton, Emma Young, Richard Rosenquist, Xiyang Liu, Alexander Jethwa, Kwang Seok Lee, Joe Lewis, Kerstin Putzker, Christoph Lutz, Davide Rossi, Andriy Mokhir, Thomas Oellerich, Katja Zirlik, Marco Herling, Florence Nguyen-Khac, Christoph Plass, Emma Andersson, Satu Mustjoki, Christof von Kalle, Anthony D Ho, Manfred Hensel, Jan Dürig, Ingo Ringshausen, Marc Zapatka, Wolfgang Huber, Thorsten Zenz
As new generations of targeted therapies emerge and tumor genome sequencing discovers increasingly comprehensive mutation repertoires, the functional relationships of mutations to tumor phenotypes remain largely unknown. Here, we measured ex vivo sensitivity of 246 blood cancers to 63 drugs alongside genome, transcriptome, and DNA methylome analysis to understand determinants of drug response. We assembled a primary blood cancer cell encyclopedia data set that revealed disease-specific sensitivities for each cancer...
December 11, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29216349/developing-a-standard-set-of-patient-centred-outcomes-for-inflammatory-bowel-disease-an-international-cross-disciplinary-consensus
#9
Andrew H Kim, Charlotte Roberts, Brian G Feagan, Rupa Banerjee, Willem Bemelman, Keith Bodger, Marc Derieppe, Axel Dignass, Richard Driscoll, Ray Fitzpatrick, Janette Gaarentstroom-Lunt, Peter D Higgins, Paulo Gustavo Kotze, Jillian Meissner, Marian O'Connor, Zhi-Hua Ran, Corey A Siegel, Helen Terry, Welmoed K van Deen, C Janneke van der Woude, Alandra Weaver, Suk-Kyun Yang, Bruce E Sands, Séverine Vermeire, Simon Pl Travis
Background and Aims: Success in delivering value-based healthcare involves measuring outcomes that matter most to patients. Our aim was to develop a minimum Standard Set of patient-centred outcome measures for inflammatory bowel disease (IBD), for use in different healthcare settings. Methods: An international working group (n=25) representing patients, patient associations, gastroenterologists, surgeons, specialist nurses, IBD registries and patient-reported outcome measure (PROM) methodologists participated in a series of teleconferences incorporating a modified Delphi process...
December 5, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/29188306/epidemiology-biology-and-therapy-of-merkel-cell-carcinoma-conclusions-from-the-eu-project-immomec
#10
REVIEW
Jürgen C Becker, Andreas Stang, Axel Zur Hausen, Nicole Fischer, James A DeCaprio, Richard W Tothill, Rikke Lyngaa, Ulla Kring Hansen, Cathrin Ritter, Paul Nghiem, Christopher K Bichakjian, Selma Ugurel, David Schrama
Merkel cell carcinoma (MCC) is a highly aggressive, often lethal neuroendocrine cancer. Its carcinogenesis may be either caused by the clonal integration of the Merkel cell polyomavirus into the host genome or by UV-induced mutations. Notably, virally-encoded oncoproteins and UV-induced mutations affect comparable signaling pathways such as RB restriction of cell cycle progression or p53 inactivation. Despite its low incidence, MCC recently received much attention based on its exquisite immunogenicity and the resulting major success of immune modulating therapies...
November 30, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29173394/outcome-after-heart-transplantation-from-donation-after-circulatory-determined-death-donors
#11
Simon Messer, Aravinda Page, Richard Axell, Marius Berman, Jules Hernández-Sánchez, Simon Colah, Barbora Parizkova, Kamen Valchanov, John Dunning, Evgeny Pavlushkov, Sendhil K Balasubramanian, Jayan Parameshwar, Yasir Abu Omar, Martin Goddard, Stephen Pettit, Clive Lewis, Anna Kydd, David Jenkins, Christopher J Watson, Catherine Sudarshan, Pedro Catarino, Marie Findlay, Ayyaz Ali, Steven Tsui, Stephen R Large
BACKGROUND: The requirement for heart transplantation is increasing, vastly outgrowing the supply of hearts available from donation after brain death (DBD) donors. Transplanting hearts after donation after circulatory-determined death (DCD) may be a viable additive alternative to DBD donors. This study compared outcomes from the largest single-center experience of DCD heart transplantation against matched DBD heart transplants. METHODS: DCD hearts were retrieved using normothermic regional perfusion (NRP) or direct procurement and perfusion (DPP)...
December 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/29129353/impact-of-lymph-node-dissection-at-the-time-of-radical-nephrectomy-with-tumor-thrombectomy-on-oncological-outcomes-results-from-the-international-renal-cell-carcinoma-venous-thrombus-consortium-ircc-vtc
#12
Derya Tilki, Thenappan Chandrasekar, Umberto Capitanio, Gaetano Ciancio, Siamak Daneshmand, Paolo Gontero, Javier Gonzalez, Axel Haferkamp, Markus Hohenfellner, William C Huang, Estefania Linares Espinós, Adam Lorentz, Juan I Martinez-Salamanca, Viraj A Master, James M McKiernan, Francesco Montorsi, Giacomo Novara, Sascha Pahernik, Juan Palou, Raj S Pruthi, Oscar Rodriguez-Faba, Paul Russo, Douglas S Scherr, Shahrokh F Shariat, Martin Spahn, Carlo Terrone, Cesar Vera-Donoso, Richard Zigeuner, John A Libertino, Christopher P Evans
OBJECTIVES: To study the effect of lymph node dissection (LND) at the time of nephrectomy and tumor thrombectomy on oncological outcomes in patients with renal cell carcinoma (RCC) and tumor thrombus. PATIENTS AND METHODS: The records of 1,978 patients with RCC and tumor thrombus who underwent radical nephrectomy and tumor thrombectomy from 1985 to 2014 at 24 centers were analyzed. None of the patients had distant metastases. Extent and pathologic results of LND were compared with respect to cancer-specific survival (CSS)...
November 9, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/29103759/the-incidence-and-management-of-non-head-and-neck-incidentalomas-for-the-head-and-neck-surgeon
#13
REVIEW
Axel Sahovaler, David H Yeh, Deric Morrison, Sandrine de Ribaupierre, Jonathan Izawa, Adam Power, Richard Inculet, Neil Parry, David A Palma, Mark Landis, Andrew Leung, Kevin Fung, S Danielle MacNeil, John Yoo, Anthony C Nichols
No abstract text is available yet for this article.
November 2017: Oral Oncology
https://www.readbyqxmd.com/read/29069604/duct-and-acinar-derived-pancreatic-ductal-adenocarcinomas-show-distinct-tumor-progression-and-marker-expression
#14
Rute M M Ferreira, Rocio Sancho, Hendrik A Messal, Emma Nye, Bradley Spencer-Dene, Richard K Stone, Gordon Stamp, Ian Rosewell, Alberto Quaglia, Axel Behrens
The cell of origin of pancreatic ductal adenocarcinoma (PDAC) has been controversial. Here, we show that identical oncogenic drivers trigger PDAC originating from both ductal and acinar cells with similar histology but with distinct pathophysiology and marker expression dependent on cell of origin. Whereas acinar-derived tumors exhibited low AGR2 expression and were preceded by pancreatic intraepithelial neoplasias (PanINs), duct-derived tumors displayed high AGR2 and developed independently of a PanIN stage via non-mucinous lesions...
October 24, 2017: Cell Reports
https://www.readbyqxmd.com/read/28940816/clinical-impact-of-kmt2c-and-spry4-expression-levels-in-intensively-treated-younger-adult-acute-myeloid-leukemia-patients
#15
Sabine Kayser, Maximilian Feszler, Julia Krzykalla, Matthias Schick, Michael Kramer, Axel Benner, Felicitas Thol, Uwe Platzbecker, Carsten Müller-Tidow, Anthony D Ho, Gerhard Ehninger, Michael Heuser, Richard F Schlenk, Christian Thiede, Christoph Röllig, Alwin Krämer
OBJECTIVE: To evaluate the prognostic impact of gene expression levels (ELs) of two tumor suppressor genes, sprouty 4 (SPRY4, located on 5q) and lysine methyltransferase 2C (KMT2C, located on 7q) in correlation with clinical characteristics and genetic abnormalities assessed at initial diagnosis in acute myeloid leukemia (AML). METHOD: Gene expression levels were measured on cDNA by RT-qPCR from diagnostic bone marrow samples of 275 intensively treated adult AML patients (median age, 48 years)...
September 22, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28934212/outcome-of-papillary-versus-clear-cell-renal-cell-carcinoma-varies-significantly-in-non-metastatic-disease
#16
MULTICENTER STUDY
Nina Wagener, Dominic Edelmann, Axel Benner, Richard Zigeuner, Hendrik Borgmann, Ingmar Wolff, Laura M Krabbe, Mireia Musquera, Paolo Dell'Oglio, Umberto Capitanio, Tobias Klatte, Luca Cindolo, Matthias May, Sabine D Brookman-May
Renal cell carcinoma (RCC) comprises a heterogenous group of tumors. Traditionally, papillary RCC (pRCC) is associated with a favorable outcome compared to clear cell RCC (ccRCC), while other series report equivalent or worse prognosis. In this paper we comparatively evaluate outcome of pRCC versus ccRCC in two large multi-institutional databases (cohort study), including distribution of pRCC subtypes 1 and 2. Retrospective data of 1,943 surgically treated pRCC patients from 17 European/ North American centers between 1984-2015 were compared to 5,600 ccRCC patients from a database comprising 11 European/ North American centers (1984-2011)...
2017: PloS One
https://www.readbyqxmd.com/read/28891408/adjuvant-dabrafenib-plus-trametinib-in-stage-iii-braf-mutated-melanoma
#17
RANDOMIZED CONTROLLED TRIAL
Georgina V Long, Axel Hauschild, Mario Santinami, Victoria Atkinson, Mario Mandalà, Vanna Chiarion-Sileni, James Larkin, Marta Nyakas, Caroline Dutriaux, Andrew Haydon, Caroline Robert, Laurent Mortier, Jacob Schachter, Dirk Schadendorf, Thierry Lesimple, Ruth Plummer, Ran Ji, Pingkuan Zhang, Bijoyesh Mookerjee, Jeff Legos, Richard Kefford, Reinhard Dummer, John M Kirkwood
BACKGROUND: Combination therapy with the BRAF inhibitor dabrafenib plus the MEK inhibitor trametinib improved survival in patients with advanced melanoma with BRAF V600 mutations. We sought to determine whether adjuvant dabrafenib plus trametinib would improve outcomes in patients with resected, stage III melanoma with BRAF V600 mutations. METHODS: In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned 870 patients with completely resected, stage III melanoma with BRAF V600E or V600K mutations to receive oral dabrafenib at a dose of 150 mg twice daily plus trametinib at a dose of 2 mg once daily (combination therapy, 438 patients) or two matched placebo tablets (432 patients) for 12 months...
November 9, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28857842/relapsed-refractory-acute-myeloid-leukemia-any-progress
#18
Richard F Schlenk, Carsten Müller-Tidow, Axel Benner, Meinhard Kieser
PURPOSE OF REVIEW: Aim of this review was to focus on prognostic and predictive factors, standard and new treatment approaches, and on statistical considerations for future clinical trials in patients with relapsed/refractory acute myeloid leukemia (r/r-AML). RECENT FINDINGS: New prognostic molecular markers were identified in r/r-AML, FLT3-ITD, mutated IDH1, and biallelic CEBPA mutations. Intensive combination chemotherapy including gemtuzumab ozogamicin emerged as an effective salvage therapy in refractory AML...
November 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28772123/molecular-mechanisms-of-synaptic-vesicle-priming-by-munc13-and-munc18
#19
Ying Lai, Ucheor B Choi, Jeremy Leitz, Hong Jun Rhee, Choongku Lee, Bekir Altas, Minglei Zhao, Richard A Pfuetzner, Austin L Wang, Nils Brose, JeongSeop Rhee, Axel T Brunger
Munc13 catalyzes the transit of syntaxin from a closed complex with Munc18 into the ternary SNARE complex. Here we report a new function of Munc13, independent of Munc18: it promotes the proper syntaxin/synaptobrevin subconfiguration during assembly of the ternary SNARE complex. In cooperation with Munc18, Munc13 additionally ensures the proper syntaxin/SNAP-25 subconfiguration. In a reconstituted fusion assay with SNAREs, complexin, and synaptotagmin, inclusion of both Munc13 and Munc18 quadruples the Ca(2+)-triggered amplitude and achieves Ca(2+) sensitivity at near-physiological concentrations...
August 2, 2017: Neuron
https://www.readbyqxmd.com/read/28741377/renal-cell-carcinoma-alternative-nephron-sparing-treatment-options-for-small-renal-masses-a-systematic-review
#20
Fieke M Prins, Linda G W Kerkmeijer, Anne A Pronk, Evert-Jan P A Vonken, Richard P Meijer, Axel Bex, Maurits M Barendrecht
BACKGROUND: The standard treatment of T1 renal cell carcinoma (RCC) is (partial) nephrectomy. For patients where surgery is not the treatment of choice, for example in the elderly, in case of severe comorbidity, inoperability, or refusal of surgery, alternative treatment options are available. These treatment options include active surveillance (AS), radiofrequency ablation (RFA), cryoablation (CA), microwave ablation (MWA), or stereotactic body radiotherapy (SBRT). In the present overview, the efficacy, safety, and outcome of these different options are summarized, particularly focusing on recent developments...
October 2017: Journal of Endourology
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