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Reshma Jagsi, Kent A Griffith, Jennifer R Bellon, Wendy A Woodward, Janet K Horton, Alice Ho, Felix Y Feng, Corey Speers, Beth Overmoyer, Michael Sabel, Anne F Schott, Lori Pierce
Purpose Locoregional control for inflammatory breast cancers and chest wall recurrences is suboptimal, which has motivated interest in radiosensitization to intensify therapy. Preclinical studies have suggested a favorable therapeutic index when poly (ADP-ribose) polymerase inhibitors are used as radiosensitizers; clinical investigation is necessary to establish appropriate dosing and confirm safety. Patients and Methods We conducted a multi-institutional phase I study of veliparib and concurrent radiotherapy (RT) to the chest wall and regional lymph nodes in 30 patients with inflammatory or locally recurrent breast cancer after complete surgical resection...
March 20, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Nikhil Satchidanand, Timothy J Servoss, Ranjit Singh, Angela M Bosinski, Penny Tirpak, Linda L Horton, Bruce J Naughton
BACKGROUND: Early, data-driven discussion surrounding palliative care can improve care delivery and patient experience. OBJECTIVE: To develop a 30-day mortality prediction tool for older patients in intensive care unit (ICU) with pneumonia that will initiate palliative care earlier in hospital course. DESIGN: Retrospective Electronic Health Record (EHR) review. SETTING: Four urban and suburban hospitals in a Western New York hospital system...
January 1, 2018: American Journal of Hospice & Palliative Care
Yingfeng Deng, Zhao V Wang, Ruth Gordillo, Yi Zhu, Aktar Ali, Chen Zhang, Xiaoding Wang, Mengle Shao, Zhuzhen Zhang, Puneeth Iyengar, Rana K Gupta, Jay D Horton, Joseph A Hill, Philipp E Scherer
OBJECTIVE: The spliced transcription factor Xbp1 (Xbp1s), a transducer of the unfolded protein response (UPR), regulates lipolysis. Lipolysis is stimulated by fasting when uridine synthesis is also activated in adipocytes. METHODS: Here we have examined the regulatory role Xbp1s in stimulation of uridine biosynthesis in adipocytes and triglyceride mobilization using inducible mouse models. RESULTS: Xbp1s is a key molecule involved in adipocyte uridine biosynthesis and release by activation of carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, dihydroorotase (CAD), the rate-limiting enzyme for UMP biosynthesis...
March 2, 2018: Molecular Metabolism
Anamika Patel, Peng Yang, Matthew Tinkham, Mihika Pradhan, Ming-An Sun, Yixuan Wang, Don Hoang, Gernot Wolf, John R Horton, Xing Zhang, Todd Macfarlan, Xiaodong Cheng
Tandem zinc finger (ZF) proteins are the largest and most rapidly diverging family of DNA-binding transcription regulators in mammals. ZFP568 represses a transcript of placental-specific insulin like growth factor 2 (Igf2-P0) in mice. ZFP568 binds a 24-base pair sequence-specific element upstream of Igf2-P0 via the eleven-ZF array. Both DNA and protein conformations deviate from the conventional one finger-three bases recognition, with individual ZFs contacting 2, 3, or 4 bases and recognizing thymine on the opposite strand...
March 13, 2018: Cell
Keith Martin, Zoë Mullan, Richard Horton
No abstract text is available yet for this article.
March 2018: Lancet Global Health
Susan Horton, Richard Sullivan, John Flanigan, Kenneth A Fleming, Modupe A Kuti, Lai Meng Looi, Sanjay A Pai, Mark Lawler
Modern, affordable pathology and laboratory medicine (PALM) systems are essential to achieve the 2030 Sustainable Development Goals for health in low-income and middle-income countries (LMICs). In this last in a Series of three papers about PALM in LMICs, we discuss the policy environment and emphasise three crucial high-level actions that are needed to deliver universal health coverage. First, nations need national strategic laboratory plans; second, these plans require adequate financing for implementation; and last, pathologists themselves need to take on leadership roles to advocate for the centrality of PALM to achieve the Sustainable Development Goals for health...
March 14, 2018: Lancet
Sabine Kleinert, Richard Horton
No abstract text is available yet for this article.
March 14, 2018: Lancet
Alejandro A Gru, Jinah Kim, Melissa Pulitzer, Joan Guitart, Maxime Battistella, Gary S Wood, Lorenzo Cerroni, Werner Kempf, Rein Willemze, Joya Pawade, Christiane Querfeld, Andras Schaffer, Laura Pincus, Michael Tetzlaff, Madeleine Duvic, Julia Scarisbrick, Pierluigi Porcu, Aaron R Mangold, David J Dicaudio, Michi Shinohara, Eric K Hong, Bethany Horton, Youn H Kim
This pathology PILOT study aims to define the role and feasibility of centralized pathology review in a cohort of 75 patients from different centers in the United States and Europe using digital slide scanning. The pathologic material from 75 patients who had been diagnosed with mycosis fungoides/Sézary syndrome and were clinically staged as IIb or above was retrieved from 11 participating centers. Each pathology reviewer was provided with the pathologic diagnosis (by the referring pathologist), and the following list of histopathologic criteria (presence or absence) from the initial report: epidermotropism, folliculotropism (FT), large cell transformation, syringotropism, and granulomas...
March 14, 2018: American Journal of Surgical Pathology
John R Horton, Xu Liu, Lizhen Wu, Kai Zhang, John Shanks, Xing Zhang, Ganesha Rai, Bryan T Mott, Daniel J Jansen, Stephen C Kales, Mark J Henderson, Katherine Pohida, Yuhong Fang, Xin Hu, Ajit Jadhav, David J Maloney, Matthew D Hall, Anton Simeonov, Haian Fu, Paula M Vertino, Qin Yan, Xiaodong Cheng
Isomers of chiral drugs can exhibit marked differences in biological activities. We studied the binding and inhibitory activities of 12 compounds against KDM5A. Among them are two pairs of enantiomers representing two distinct inhibitor chemotypes, namely (R)- and (S)-2-((2-chlorophenyl)(2-(piperidin-1-yl)ethoxy)methyl)-1H-pyrrolo[3,2-b]pyridine-7-carboxylic acid (compounds N51 and N52) and (R)- and (S)-N-(1-(3-isopropyl-1H-pyrazole-5-carbonyl)pyrrolidin-3-yl)cyclopropane-carboxamide (compounds N54 and N55)...
March 14, 2018: Journal of Medicinal Chemistry
Richard Horton
No abstract text is available yet for this article.
March 10, 2018: Lancet
Philippa Howlett, Jane K Cleal, Huihai Wu, Nikunj Shah, Alex Horton, Nick Curzen, Michael Mahmoudi
Objective: MicroRNAs (miRNAs) may serve as potential biomarkers in a variety of pathologies. The aim of this study was to determine whether miRNAs could serve as blood-based markers of isolated coronary artery calcification (CAC) defined as CAC in the absence of an underlying metabolic abnormality. Methods: 24 age-matched and sex-matched patients who had been referred for elective CT coronary calcium score and angiography as part of investigation for cardiac chest pain were recruited...
2018: Open Heart
Penny C Szklarski, Garrett S Booth
No abstract text is available yet for this article.
March 2018: Transfusion
Ana C Blanchard, Ashley M Rooney, Yvonne Yau, Yu Zhang, Patrick J Stapleton, Eric Horton, Michelle Klingel, Sanja Stanojevic, Felix Ratjen, Bryan Coburn, Valerie Waters
BACKGROUND: Infection with Pseudomonas aeruginosa (Pa) with a chronic phenotype is associated with antibiotic eradication therapy (AET) failure. Our objective was to determine whether higher levels of Pa (detected using qPCR) prior to culture positivity were associated with AET failure in pediatric CF patients. METHODS: Pa-specific qPCR was performed on stored sputa prior to culture positivity in pediatric CF patients with new-onset culture-positive Pa infections undergoing AET with a 28-day course of tobramycin-inhaled solution (TIS)...
March 7, 2018: Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society
Amanda K Doughty, Brian J Horton, Nguyen T D Huyen, C Rowdy Ballagh, Ross Corkrey, Geoff N Hinch
We investigated how individuality and lameness altered social organisation by assessing food-directed movement patterns in sheep. One hundred and ninety-six mature Merino ewes were walked in 16 different runs around a 1.1 km track following a food source. Flock position and lameness, were measured and temperament was assessed using an Isolation Box Test. The mean value for the correlations of position between a run and the run preceding it was r = 0.55 ± SEM 0.03. All correlations between runs were positive (r = 0...
March 7, 2018: Behavioural Processes
Jerome Soquet, Roberto Chiletti, Stephen Horton, Igor E Konstantinov, Johann Brink, Christian P Brizard, Warwick Butt, Yves d'Udekem
BACKGROUND: In 2011 we reported unfavourable outcomes of second-run extracorporeal life support (ECLS) in children. We wanted to investigate whether this previous report affected our strategy and modified our long-term outcomes. METHODS: Between 1988 and 2015, 31 patients underwent a second-run ECLS. Median age at the time of first support was 9days (0-16 years). Median length of support for the first and second runs were 4.7days (0.1-10) and 3.6days (0.5-8.7) respectively, with an interval of 1...
February 13, 2018: Heart, Lung & Circulation
Yassan Abdolazimi, Sooyeon Lee, Haixia Xu, Paul Allegretti, Timothy M Horton, Benjamin Yeh, Hannah P Moeller, Robert J Nichols, David McCutcheon, Aryaman Shalizi, Mark Smith, Neali A Armstrong, Justin P Annes
Pharmacologic expansion of endogenous β-cells is a promising therapeutic strategy for diabetes. To elucidate the molecular pathways that control β-cell growth we screened ∼2,400 bioactive compounds for rat β-cell replication-modulating activity. Numerous hit compounds impaired or promoted rat β-cell replication, including CC-401, an advanced clinical candidate previously characterized as a c-Jun N-terminal kinase (JNK) inhibitor. Surprisingly, CC-401 induced rodent (in vitro and in vivo) and human (in vitro) β-cell replication via dual specificity tyrosine-phosphorylation-regulated kinases (DYRK1A/B) inhibition...
March 5, 2018: Endocrinology
Richard Horton
No abstract text is available yet for this article.
March 3, 2018: Lancet
Krzysztof Gomułka, Joanna Radzik-Zając, Urszula Zaleska-Dorobisz, Bernard Panaszek
No abstract text is available yet for this article.
October 2017: Postȩpy Dermatologii i Alergologii
Richard Suu-Ire, Lineke Begeman, Ashley C Banyard, Andrew C Breed, Christian Drosten, Elisa Eggerbauer, Conrad M Freuling, Louise Gibson, Hooman Goharriz, Daniel L Horton, Daisy Jennings, Ivan V Kuzmin, Denise Marston, Yaa Ntiamoa-Baidu, Silke Riesle Sbarbaro, David Selden, Emma L Wise, Thijs Kuiken, Anthony R Fooks, Thomas Müller, James L N Wood, Andrew A Cunningham
Rabies is a fatal neurologic disease caused by lyssavirus infection. People are infected through contact with infected animals. The relative increase of human rabies acquired from bats calls for a better understanding of lyssavirus infections in their natural hosts. So far, there is no experimental model that mimics natural lyssavirus infection in the reservoir bat species. Lagos bat virus is a lyssavirus that is endemic in straw-colored fruit bats (Eidolon helvum) in Africa. Here we compared the susceptibility of these bats to three strains of Lagos bat virus (from Senegal, Nigeria, and Ghana) by intracranial inoculation...
March 5, 2018: PLoS Neglected Tropical Diseases
M Susan Caswell, Rhona M Hanning
OBJECTIVE: Unhealthy dietary behaviours are prevalent among adolescents. This might relate, in part, to obesogenic environments, including recreation food facilities. The REFRESH Study (Recreation Environment and Food Research: Experiences from Hockey) aimed to explore, from the perspectives of adolescent ice hockey players and parents, broad social and physical environmental influences on adolescent food behaviours associated with hockey participation. DESIGN: Players used photovoice to describe their food experiences in relation to ice hockey...
March 1, 2018: Public Health Nutrition
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