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Kelly D Moynihan, Cary F Opel, Gregory L Szeto, Alice Tzeng, Eric F Zhu, Jesse M Engreitz, Robert T Williams, Kavya Rakhra, Michael H Zhang, Adrienne M Rothschilds, Sudha Kumari, Ryan L Kelly, Byron H Kwan, Wuhbet Abraham, Kevin Hu, Naveen K Mehta, Monique J Kauke, Heikyung Suh, Jennifer R Cochran, Douglas A Lauffenburger, K Dane Wittrup, Darrell J Irvine
Checkpoint blockade with antibodies specific for cytotoxic T lymphocyte-associated protein (CTLA)-4 or programmed cell death 1 (PDCD1; also known as PD-1) elicits durable tumor regression in metastatic cancer, but these dramatic responses are confined to a minority of patients. This suboptimal outcome is probably due in part to the complex network of immunosuppressive pathways present in advanced tumors, which are unlikely to be overcome by intervention at a single signaling checkpoint. Here we describe a combination immunotherapy that recruits a variety of innate and adaptive immune cells to eliminate large tumor burdens in syngeneic tumor models and a genetically engineered mouse model of melanoma; to our knowledge tumors of this size have not previously been curable by treatments relying on endogenous immunity...
October 24, 2016: Nature Medicine
Jack Kit-Chung Ng, Bonnie Ching-Ha Kwan, Kai-Ming Chow, Phyllis Mei-Shan Cheng, Man-Ching Law, Wing-Fai Pang, Chi-Bon Leung, Philip Kam-Tao Li, Cheuk-Chun Szeto
BACKGROUND/AIMS: Previous studies showed that frailty is prevalent in both pre-dialysis and dialysis patients. However, the prevalence and prognostic implication of frailty in Chinese peritoneal dialysis (PD) patients remain unknown. METHODS: We used a validated questionnaire to determine the Frailty Score of 193 unselected prevalent PD patients. All patients were then followed for 2 years for their need of hospitalization and mortality. RESULTS: Amongst the 193 patients, 134 (69...
October 24, 2016: Kidney & Blood Pressure Research
Stéphane Cadot, Olivier Renault, Mathieu Frégnaux, Denis Rouchon, Emmanuel Nolot, Kai Szeto, Chloé Thieuleux, Laurent Veyre, Hanako Okuno, François Martin, Elsje Alessandra Quadrelli
The lack of scalable-methods for the growth of 2D MoS2 crystals, an identified emerging material with applications ranging from electronics to energy storage, is a current bottleneck against its large-scale deployment. We report here a two-step ALD route with new organometallic precursors, Mo(NMe2)4 and 1,2-ethanedithiol (HS(CH2)2SH) which consists in the layer-by-layer deposition of an amorphous surface Mo(iv) thiolate at 50 °C, followed by a subsequent annealing at higher temperature leading to ultra-thin MoS2 nanocrystals (∼20 nm-large) in the 1-2 monolayer range...
October 20, 2016: Nanoscale
Yim Tong Szeto, Kam Shing Wong, Andrea Han, Sok Cheon Pak, Wouter Kalle
AIM: The aim of this clinical study is to provide scientific evidence for supporting traditional Chinese application and usage to the patients. For this purpose, we tested the ability if Panax ginseng extract to lower oxidative damage to nuclear DNA in human lymphocytes by comparing the effect of cooked Chinese turnip on this effect. MATERIALS AND METHODS: Seven healthy subjects (4 males and 3 females from 37 to 60 years) participated two occasions which were at least 2 weeks apart...
September 2016: Journal of Intercultural Ethnopharmacology
Jacob T Gutsche, Mark E Mikkelsen, Fenton H McCarthy, Todd A Miano, William J Vernick, Harish Ramakrishna, Prakash A Patel, Yianni Augoustides, Wilson Y Szeto, Nimesh D Desai, Meghan B Lane-Fall, Matthew L Williams
When clinicians consider extracorporeal life support (ECLS) for acute respiratory distress syndrome (ARDS) patients with hemodynamic instability, both veno-arterial (VA) and veno-venous (VV) ECLS are therapeutic possibilities. We analyzed 17 patients with ARDS on inotropic or vasopressor support requiring ECLS for refractory hypoxemia. After implementing VV ECLS, pressor requirements (based on norepinephrine equivalents) were significantly lower in all patients (P = .0001 for overall comparison across time points)...
October 4, 2016: Anesthesia and Analgesia
Chengyuan Tang, Juan Cai, Zheng Dong
Lipid accumulation in renal cells has been implicated in the pathogenesis of obesity-related kidney disease, but the underlying mechanism is poorly understood. Szeto et al. now unravel a central role of mitochondrial dysfunction in a high fat diet-induced glomerulopathy and proximal tubular injury. Moreover, they demonstrate the renoprotective effect of SS31, a mitochondria-targeted antioxidant, in related models. Targeting mitochondria may offer a novel strategy for the therapy of obesity-related kidney disease...
November 2016: Kidney International
Simon K H Szeto, Tommy C Y Chan, Raymond L M Wong, Alex L K Ng, Emmy Y M Li, Vishal Jhanji
PURPOSE: To investigate the prevalence of ocular manifestations and visual outcomes in patients with herpes zoster ophthalmicus (HZO). METHODS: Consecutive cases diagnosed with HZO who attended 2 hospitals between July 1, 2011, and June 30, 2015, were retrospectively reviewed. Patient demographics, clinical presentations, and management were reviewed. The logistic regression model was used to estimate the odds ratio of visual loss with ocular manifestations. RESULTS: A total of 259 patients were included...
October 12, 2016: Cornea
I-Min A Chen, Victor M Markowitz, Ken Chu, Krishna Palaniappan, Ernest Szeto, Manoj Pillay, Anna Ratner, Jinghua Huang, Evan Andersen, Marcel Huntemann, Neha Varghese, Michalis Hadjithomas, Kristin Tennessen, Torben Nielsen, Natalia N Ivanova, Nikos C Kyrpides
The Integrated Microbial Genomes with Microbiome Samples (IMG/M: system contains annotated DNA and RNA sequence data of (i) archaeal, bacterial, eukaryotic and viral genomes from cultured organisms, (ii) single cell genomes (SCG) and genomes from metagenomes (GFM) from uncultured archaea, bacteria and viruses and (iii) metagenomes from environmental, host associated and engineered microbiome samples. Sequence data are generated by DOE's Joint Genome Institute (JGI), submitted by individual scientists, or collected from public sequence data archives...
October 13, 2016: Nucleic Acids Research
Adam S Darwich, Alison Margolskee, Xavier Pepin, Leon Aarons, Aleksandra Galetin, Amin Rostami-Hodjegan, Sara Carlert, Maria Hammarberg, Constanze Hilgendorf, Pernilla Johansson, Eva Karlsson, Dónal Murphy, Christer Tannergren, Helena Thörn, Mohammed Yasin, Florent Mazuir, Olivier Nicolas, Sergej Ramusovic, Christine Xu, Shriram M Pathak, Timo Korjamo, Johanna Laru, Jussi Malkki, Sari Pappinen, Johanna Tuunainen, Jennifer Dressman, Simone Hansmann, Edmund Kostewicz, Handan He, Tycho Heimbach, Fan Wu, Carolin Hoft, Yan Pang, Michael B Bolger, Eva Huehn, Viera Lukacova, James M Mullin, Ke X Szeto, Chester Costales, Jian Lin, Mark McAllister, Sweta Modi, Charles Rotter, Manthena Varma, Mei Wong, Amitava Mitra, Jan Bevernage, Jeike Biewenga, Achiel Van Peer, Richard Lloyd, Carole Shardlow, Peter Langguth, Irina Mishenzon, Mai Anh Nguyen, Jonathan Brown, Hans Lennernäs, Bertil Abrahamsson
Three Physiologically Based Pharmacokinetic software packages (GI-Sim, Simcyp® Simulator, and GastroPlus™) were evaluated as part of the Innovative Medicine Initiative Oral Biopharmaceutics Tools project (OrBiTo) during a blinded "bottom-up" anticipation of human pharmacokinetics. After data analysis of the predicted vs. measured pharmacokinetics parameters, it was found that oral bioavailability (Foral) was underpredicted for compounds with low permeability, suggesting improper estimates of intestinal surface area, colonic absorption and/or lack of intestinal transporter information...
September 28, 2016: European Journal of Pharmaceutical Sciences
V H Lee, T W Lam, S C Ng, M H Szeto, K O Lam, T W Leung
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
Zichen Wang, Caroline D Monteiro, Kathleen M Jagodnik, Nicolas F Fernandez, Gregory W Gundersen, Andrew D Rouillard, Sherry L Jenkins, Axel S Feldmann, Kevin S Hu, Michael G McDermott, Qiaonan Duan, Neil R Clark, Matthew R Jones, Yan Kou, Troy Goff, Holly Woodland, Fabio M R Amaral, Gregory L Szeto, Oliver Fuchs, Sophia M Schüssler-Fiorenza Rose, Shvetank Sharma, Uwe Schwartz, Xabier Bengoetxea Bausela, Maciej Szymkiewicz, Vasileios Maroulis, Anton Salykin, Carolina M Barra, Candice D Kruth, Nicholas J Bongio, Vaibhav Mathur, Radmila D Todoric, Udi E Rubin, Apostolos Malatras, Carl T Fulp, John A Galindo, Ruta Motiejunaite, Christoph Jüschke, Philip C Dishuck, Katharina Lahl, Mohieddin Jafari, Sara Aibar, Apostolos Zaravinos, Linda H Steenhuizen, Lindsey R Allison, Pablo Gamallo, Fernando de Andres Segura, Tyler Dae Devlin, Vicente Pérez-García, Avi Ma'ayan
Gene expression data are accumulating exponentially in public repositories. Reanalysis and integration of themed collections from these studies may provide new insights, but requires further human curation. Here we report a crowdsourcing project to annotate and reanalyse a large number of gene expression profiles from Gene Expression Omnibus (GEO). Through a massive open online course on Coursera, over 70 participants from over 25 countries identify and annotate 2,460 single-gene perturbation signatures, 839 disease versus normal signatures, and 906 drug perturbation signatures...
September 26, 2016: Nature Communications
Prashanth Vallabhajosyula, Jean Paul Gottret, Rohan Menon, Ibrahim Sultan, Zara Abbas, Mary Siki, Matthew Kramer, Aaron Pulsipher, Suveeksha Naidu, Alberto Pochettino, Kariana Milewski, Wilson Y Szeto, Joseph E Bavaria
BACKGROUND: In acute DeBakey I aortic dissection presenting with malperfusion syndromes, we assessed whether standard open repair with concomitant antegrade stent grafting (thoracic endovascular aneurysm repair; TEVAR) of the descending thoracic aorta (DTA) improves outcomes compared with standard repair alone. METHODS: From 2005 to 2012, 277 patients with acute DeBakey I dissection underwent emergent operation. Of these, 104 patients (37%) presenting with end-organ malperfusion were divided into those undergoing standard distal repair entailing transverse hemiarch replacement (Standard group, n = 65) versus standard repair with concomitant DTA TEVAR during circulatory arrest (TEVAR group, n = 39)...
September 22, 2016: Annals of Thoracic Surgery
George J Arnaoutakis, Wilson Y Szeto
No abstract text is available yet for this article.
August 28, 2016: Journal of Thoracic and Cardiovascular Surgery
Robert Kupp, Lior Shtayer, An-Chi Tien, Emily Szeto, Nader Sanai, David H Rowitch, Shwetal Mehta
The basic helix-loop-helix (bHLH) transcription factor OLIG2 is a master regulator of oligodendroglial fate decisions and tumorigenic competence of glioma stem-like cells (GSCs). However, the molecular mechanisms underlying dysregulation of OLIG2 function during gliomagenesis remains poorly understood. Here, we show that OLIG2 modulates growth factor signaling in two distinct populations of GSCs, characterized by expression of either the epidermal growth factor receptor (EGFR) or platelet-derived growth factor receptor alpha (PDGFRα)...
September 13, 2016: Cell Reports
Cherif Larabi, Kai C Szeto, Yassine Bouhoute, Marc O Charlin, Nicolas Merle, Aimery De Mallmann, Regis M Gauvin, Laurent Delevoye, Mostafa Taoufik
Ring opening metathesis polymerization (ROMP) of bicyclo[2.2.1]hept-2-ene (norbornene) is carried out over silica-supported catalysts based on tungsten complexes bearing an oxo ligand (1: [(SiO)W(O)(CH2 SiMe3 )3 , 2: [(SiO)W(O)(CHCMe2 Ph)(dAdPO)], dAdPO  2,6 diadamantyl-4-methylphenoxide, 3: [(SiO)2 W(O)(CH2 SiMe3 )2 ]). The evaluation of the catalytic activities of the aforementioned materials in ROMP indicates that at low reaction time (0.5 min), the highest polymer yield is obtained with catalyst 2...
September 12, 2016: Macromolecular Rapid Communications
Vinod H Thourani, Jessica Forcillo, Nirat Beohar, Darshan Doshi, Rupa Parvataneni, Girma M Ayele, Ajay J Kirtane, Vasilis Babaliaros, Susheel Kodali, Chandan Devireddy, Wilson Szeto, Howard C Herrmann, Raj Makkar, Gorav Ailawadi, Scott Lim, Hersh S Maniar, Alan Zajarias, Rakesh Suri, E Murat Tuzcu, Samir Kapadia, Lars Svensson, Jose Condado, Hanna A Jensen, Michael J Mack, Martin B Leon
BACKGROUND: Although preoperative renal dysfunction (RD) is associated with increased mortality and morbidity after surgical aortic valve replacement, its impact on clinical outcomes after transcatheter aortic valve replacement (TAVR) is less defined. METHODS: TAVR patients in the PARTNER (Placement of Aortic Transcatheter Valves) trial with a calculable glomerular filtration rate (GFR) using the Modification of Diet in Renal Disease equation were included. Patients were divided into three groups: GFR >60 mL/min (none/mild RD), GFR 31 to 60 mL/min (moderate RD), and GFR ≤30 mL/min (severe RD)...
October 2016: Annals of Thoracic Surgery
Alessandro Gallo, Anthony Fong, Kai C Szeto, Julia Rieb, Laurent Delevoye, Régis M Gauvin, Mostafa Taoufik, Baron Peters, Susannah L Scott
Extensive chlorination of γ-Al2O3 results in the formation of highly Lewis acidic surface domains depleted in surface hydroxyl groups. Adsorption of methyltrioxorhenium (MTO) onto these chlorinated domains serves to activate it as a low temperature, heterogeneous olefin metathesis catalyst and confers both high activity and high stability. Characterization of the catalyst reveals that the immobilized MTO undergoes partial ligand exchange with the surface, whereby some Re sites acquire a chloride ligand from the modified alumina while donating an oxo ligand to the support...
October 5, 2016: Journal of the American Chemical Society
Matthew L Williams, Joseph E Bavaria, Michael A Acker, Nimesh D Desai, Prashanth Vallabhajosyula, W Clark Hargrove, Pavan Atluri, Wilson Y Szeto
BACKGROUND: When valve replacement is required in patients with end-stage renal disease (ESRD), it is not clear if mechanical or bioprosthetic valve selection is better. We compared outcomes between ESRD patients who underwent either mechanical or biologic valve replacements at our institution. METHODS: All patients with ESRD who underwent either mitral or aortic valve replacement from 2002 to 2014 at our institution were reviewed (n = 215; mechanical = 64, biological = 151)...
August 17, 2016: Annals of Thoracic Surgery
Harish Ramakrishna, Prakash A Patel, Jacob T Gutsche, Prashanth Vallabhajosyula, Wilson Y Szeto, Emily MacKay, Jared W Feinman, Ronak Shah, Elizabeth Zhou, Stuart J Weiss, John G Augoustides
No abstract text is available yet for this article.
April 16, 2016: Journal of Cardiothoracic and Vascular Anesthesia
Amin Morteza Najarian, Bryan Szeto, Ushula M Tefashe, Richard L McCreery
Large area molecular junctions were fabricated on electron-beam deposited carbon (eC) surfaces with molecular layers in the range of 2-5.5 nm between conducting, amorphous carbon contacts. Incorporating eC as an interconnect between Au and the molecular layer improves substrate roughness, prevents electromigration and uses well-known electrochemistry to form a covalent C-C bond to the molecular layer. Au/eC/anthraquinone/eC/Au junctions were fabricated on Si/SiOx with high yield and reproducibility and were unchanged by 10(7) current-voltage cycles and temperatures between 80 and 450 K...
September 27, 2016: ACS Nano
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