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https://www.readbyqxmd.com/read/28817755/measuring-toxic-effects-and-time-to-treatment-failure-for-nivolumab-plus-ipilimumab-in-melanoma
#1
Alexander N Shoushtari, Claire F Friedman, Pedram Navid-Azarbaijani, Michael A Postow, Margaret K Callahan, Parisa Momtaz, Katherine S Panageas, Jedd D Wolchok, Paul B Chapman
Importance: Nivolumab plus ipilimumab (nivo + ipi) is a standard treatment of advanced melanoma. Two randomized trials describe high objective response rates by Response Evaluation Criteria in Solid Tumors. The trials assessed toxic effects using the Common Terminology Criteria for Adverse Events (CTCAE), which may underestimate incidence of clinically significant immune-related adverse events (AEs). Objective: To describe detailed toxic effects and time to treatment failure of patients with melanoma treated with nivo + ipi in a prospective cohort...
August 17, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28812904/pd-catalyzed-regioselective-asymmetric-addition-reaction-of-unprotected-pyrimidines-to-alkoxyallene
#2
Soyeong Kang, Seok Hyeon Jang, Juyeol Lee, Dong-Gil Kim, Mijin Kim, Wook Jeong, Young Ho Rhee
Catalytic asymmetric synthesis of N-heterocyclic glycosides free of protecting and directing groups is reported. The key reaction is highlighted by the atom-efficient and regioselective addition of unprotected pyrimidines to highly functionalized alkoxyallene. Numerous acyclic and cyclic N-heterocyclic glycosides are accessed with minimal formation of organic byproducts. The synthetic utility of the reaction is demonstrated by the first catalytic asymmetric synthesis of anticancer pharmaceutical (-)-Tegafur and stereoselective synthesis of an oxepane nucleoside derivative...
August 16, 2017: Organic Letters
https://www.readbyqxmd.com/read/28809506/stereospecific-palladium-catalyzed-c-h-arylation-of-pyroglutamic-acid-derivatives-at-the-c3-position-enabled-by-8-aminoquinoline-as-a-directing-group
#3
Oscar Verho, Micah Maetani, Bruno Melillo, Jochen Zoller, Stuart L Schreiber
An efficient and stereospecific Pd-catalyzed protocol for the C-H arylation of pyroglutamic acid derivatives that uses 8-aminoquinoline as a directing group is described. The reaction was shown to proceed efficiently with a variety of aryl and heteroaryl iodides bearing different functional groups, giving C3-arylated cis products in good to high yields. Removal of the 8-aminoquinoline unit from these C-H arylation products enables access to synthetically useful cis and trans pyroglutamic acid-based building blocks...
August 15, 2017: Organic Letters
https://www.readbyqxmd.com/read/28806566/volumetric-adsorptive-microsampling-liquid-chromatography-tandem-mass-spectrometry-assay-for-the-simultaneous-quantification-of-four-antibiotics-in-human-blood-method-development-validation-and-comparison-with-dried-blood-spot
#4
Sebastiano Barco, Elio Castagnola, Andrea Moscatelli, James Rudge, Gino Tripodi, Giuliana Cangemi
In this paper we show the development and validation of a volumetric absorptive microsampling (VAMS™)-LC-MS/MS method for the simultaneous quantification of four antibiotics: piperacillin-tazobactam, meropenem, linezolid and ceftazidime in 10μL human blood. The novel VAMS-LC-MS/MS method has been compared with a dried blood spot (DBS)-based method in terms of impact of hematocrit (HCT) on accuracy, reproducibility, recovery and matrix effect. Antibiotics were extracted from VAMS and DBS by protein precipitation with methanol after a re-hydration step at 37°C for 10min...
August 2, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28803148/combustion-derived-nanoparticles-the-neuroenteric-system-cervical-vagus-hyperphosphorylated-alpha-synuclein-and-tau-in-young-mexico-city-residents
#5
Lilian Calderón-Garcidueñas, Rafael Reynoso-Robles, Beatriz Pérez-Guillé, Partha S Mukherjee, Angélica Gónzalez-Maciel
Mexico City (MC) young residents are exposed to high levels of fine particulate matter (PM2.5), have high frontal concentrations of combustion-derived nanoparticles (CDNPs), accumulation of hyperphosphorylated aggregated α-synuclein (α-Syn) and early Parkinson's disease (PD). Swallowed CDNPs have easy access to epithelium and submucosa, damaging gastrointestinal (GI) barrier integrity and accessing the enteric nervous system (ENS). This study is focused on the ENS, vagus nerves and GI barrier in young MC v clean air controls...
August 9, 2017: Environmental Research
https://www.readbyqxmd.com/read/28800388/rapid-access-to-nanographenes-and-fused-heteroaromatics-by-palladium-catalyzed-annulative-%C3%AF-extension-reaction-of-unfunctionalized-aromatics-with-diiodobiaryls
#6
Wataru Matsuoka, Hideto Ito, Kenichiro Itami
Efficient and rapid access to nanographenes and π-extended fused heteroaromatics is important in materials science. Here we report a Pd-catalyzed efficient one-step annulative π-extension (APEX) reaction of PAHs and heteroaromatics, producing various π-extended aromatics. In the presence of a cationic Pd complex, triflic acid, silver pivalate, and diiodobiaryls, diverse unfunctionalized PAHs and heteroaromatics were directly transformed into larger PAHs, nanographenes, and π-extended fused heteroaromatics in a single step...
August 11, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28797473/biomarker-research-to-improve-clinical-outcomes-of-peritoneal-dialysis-consensus-of-the-european-training-and-research-in-peritoneal-dialysis-eutripd-network
#7
REVIEW
Christoph Aufricht, Robert Beelen, Matthias Eberl, Michel Fischbach, Donald Fraser, Achim Jörres, Klaus Kratochwill, Manuel LópezCabrera, Peter Rutherford, Claus-Peter Schmitt, Nicholas Topley, Janusz Witowski
Peritoneal dialysis (PD) therapy substantially requires biomarkers as tools to identify patients who are at the highest risk for PD-related complications and to guide personalized interventions that may improve clinical outcome in the individual patient. In this consensus article, members of the European Training and Research in Peritoneal Dialysis Network (EuTRiPD) review the current status of biomarker research in PD and suggest a selection of biomarkers that can be relevant to the care of PD patients and that are directly accessible in PD effluents...
August 8, 2017: Kidney International
https://www.readbyqxmd.com/read/28792165/acute-stylet-peritoneal-dialysis-in-acute-kidney-injury-the-soul-never-dies
#8
Amith Vijay Leon D'Souza, Nishad Raveendran, Rajendra Singh Tanwar, Piyush Kimmatkar, Pankaj Beniwal, Dhananjai Agarwal, Vinay Vinay
BACKGROUND: Acute Kidney Injury (AKI) has a significant mortality rate. In developing countries, mortality due to AKI is high due to lack of access to dialysis facilities and related cost. The main goal of International Society of Nephrology (ISN) 0 by 25 initiative is to eliminate deaths due to AKI. Peritoneal dialysis is an underutilized modality in such a scenario. The aim of this study was to look into effectiveness of starting Acute stylet Peritoneal Dialysis (PD) in a resource constraint settings...
July 2017: Journal of the Association of Physicians of India
https://www.readbyqxmd.com/read/28777556/metal-organic-framework-templated-chemiresistor-sensing-type-transition-from-p-to-n-using-hollow-metal-oxide-polyhedron-via-galvanic-replacement
#9
Ji-Soo Jang, Won-Tae Koo, Seon-Jin Choi, Il-Doo Kim
Facile synthesis of porous nanobuilding blocks with high surface area and uniform catalyst functionalization has always been regarded as an essential requirement for the development of highly sensitive and selective chemical sensors. Metal-organic frameworks (MOFs) are considered as one of the most ideal templates due to their ability to encapsulate ultra-small catalytic nanoparticles (NPs) in microporous MOF structures in addition to easy removal of the sacrificial MOF scaffold by calcination. Here we introduce a MOFs derived n-type SnO2 (n-SnO2) sensing layer with hollow polyhedron structures, obtained from p-n transition of MOF-templated p-type Co3O4 (p-Co3O4) hollow cubes during galvanic replacement reaction (GRR)...
August 4, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28770395/interventional-nephrology-current-status-and-clinical-impact-in-japan
#10
Masato Ikeda, Hiroyuki Terawaki, Eiichiro Kanda, Maiko Furuya, Yudo Tanno, Masatsugu Nakao, Yukio Maruyama, Masutaka Maeda, Chieko Higuchi, Tsutomu Sakurada, Tomohiro Kaneko, Hiroaki Io, Koji Hashimoto, Atsushi Ueda, Keita Hirano, Naoki Washida, Hiraku Yoshida, Kazuhiro Yoshikawa, Yoshihiro Taniyama, Kenji Harada, Nanae Matsuo, Ichiro Okido, Takashi Yokoo
BACKGROUND: Current status and clinical significance of interventional nephrology has not been reported from Japan. METHODS: Questionnaires were mailed twice to the directors of all 534 Japanese certificated nephrology training institutions in 2014. The main questions were current performance, categorized annual procedure volume and managers of peritoneal dialysis (PD) access, vascular access (VA) surgery, endovascular intervention, and kidney biopsy. Frequencies of nephrologist involvement between high volume center and low volume center and association between the level of nephrologists' involvement to each procedure and annual procedure volume were examined...
August 2, 2017: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/28770387/data-to-decisions-creating-a-culture-of-model-driven-drug-discovery
#11
Frank K Brown, Farida Kopti, Charlie Zhenyu Chang, Scott A Johnson, Meir Glick, Chris L Waller
Merck & Co., Inc., Kenilworth, NJ, USA, is undergoing a transformation in the way that it prosecutes R&D programs. Through the adoption of a "model-driven" culture, enhanced R&D productivity is anticipated, both in the form of decreased attrition at each stage of the process and by providing a rational framework for understanding and learning from the data generated along the way. This new approach focuses on the concept of a "Design Cycle" that makes use of all the data possible, internally and externally, to drive decision-making...
August 2, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28763205/tandem-pd-and-isothiourea-relay-catalysis-enantioselective-synthesis-of-%C3%AE-amino-acid-derivatives-via-allylic-amination-and-2-3-sigmatropic-rearrangement
#12
Stéphanie S M Spoehrle, Thomas H West, James E Taylor, Alexandra M Z Slawin, Andrew D Smith
A tandem relay catalytic protocol using both Pd and isothiourea catalysis has been developed for the enantioselective synthesis of α-amino acid derivatives containing two stereogenic centers from readily accessible N,N-disubstituted glycine aryl esters and allylic phosphates. The optimized process uses a bench-stable succinimide-based Pd-precatalyst (FurCat) to promote Pd-catalyzed allylic ammonium salt generation from the allylic phosphate and the glycine aryl ester. Subsequent in situ enantioselective [2,3]-sigmatropic rearrangement catalyzed by the isothiourea benzotetramisole forms syn-α-amino acid derivatives with high diastereo- and enantioselectivity...
August 1, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28762670/radiological-tenckhoff-catheter-insertion-for-peritoneal-dialysis-a-cost-effective-approach
#13
James Lee, Nigel Mott, Usman Mahmood, John Clouston, Kara Summers, Pauline Nicholas, Pedro Henrique França Gois, Dwarakanathan Ranganathan
INTRODUCTION: Radiological insertion of Tenckhoff catheters can be an alternative option for peritoneal dialysis access creation, as compared to surgical catheter insertion. This study will review the outcomes and complications of radiological Tenckhoff catheter insertion in a metropolitan renal service and compare costs between surgical and radiological insertion. METHODS: Data were collected prospectively for all patients who had a Tenckhoff catheter insertion for peritoneal dialysis (PD) under radiological guidance at our hospital from May 2014 to November 2016...
August 1, 2017: Journal of Medical Imaging and Radiation Oncology
https://www.readbyqxmd.com/read/28753004/palladium-catalyzed-negishi-coupling-of-%C3%AE-cf3-oxiranyl-zincate-access-to-chiral-cf3-substituted-benzylic-tertiary-alcohols
#14
Hu Zhang, Stephen L Buchwald
We report a Pd-catalyzed stereospecific α-arylation of optically pure 2,3-epoxy-1,1,1-trifluoropropane (TFPO). This method allows for the direct and reliable preparation of optically pure 2-CF3-2-(hetero)aryloxiranes, which are precursors to many CF3-substituted tertiary alcohols. The use of continuous-flow methods has allowed the deprotonation of TFPO and subsequent zincation at higher temperature compared to that under traditional batch conditions.
August 10, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28752935/synthesis-of-water-soluble-palladium-nanoparticles-stabilized-by-sulfonated-n-heterocyclic-carbenes
#15
Juan Manuel Asensio, Simon Tricard, Yannick Coppel, Román Andrés, Bruno Chaudret, Ernesto de Jesus
A strategy involving the decomposition of palladium(II) organometallic complexes with sulfonated N-heterocyclic carbene ligands (NHC) leads to the formation of stable and water-soluble Pd nanoparticles. Three different methodologies (thermal decomposition, reduction under ¹³CO atmosphere and reduction with H₂) gave particles with different shapes and sizes, ranging from 1.5 to 7 nm. The structures of the organometallic intermediates and organic decomposition products were elucidated by NMR spectroscopy...
July 28, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28749816/associations-of-rs823128-rs1572931-and-rs823156-polymorphisms-with-reduced-parkinson-s-disease-risks
#16
Ye Bai, Lihong Dong, Xinghua Huang, Shuanglin Zheng, Ping Qiu, Fenghua Lan
The PARK16 locus is considered to play a protective role in Parkinson's disease (PD). However, the epidemiological evidence on the relationships between PARK16 single-nucleotide polymorphisms (rs823128, rs1572931, and rs823156) and PD is inconsistent. Therefore, we carried out a meta-analysis to validate the relationships and performed a bioinformatic analysis to explore putative regulation mechanisms of the single-nucleotide polymorphisms in PD. Through meta-analysis, we confirmed that minor variants of rs823128A>G, rs1572931C>T, and rs823156A>G played protective roles in PD...
July 26, 2017: Neuroreport
https://www.readbyqxmd.com/read/28741842/a-cu-pd-synergistic-dual-catalysis-for-enantioselective-allylic-alkylation-of-aldimine-esters-a-facile-access-to-alpha-alpha-disubstituted-alpha-amino-acids
#17
Chun-Jiang Wang, Liang Wei, Shi-Ming Xu, Qiao Zhu, Chao Che
An unprecedented enantioselective allylic alkylation of readily-available aldimine esters has been developed, which was efficiently catalyzed by a Cu/Pd synergistic dual catalyst. This strategy provides a facile access to nonproteinogenic alpha,alpha-disubstituted alpha-amino acids (alpha-AAs) in high yield with excellent enantioselectivity. The more challenging double allylic allylation of glycinate derived imine esters could also be realized. Furthermore, this methodology was applied for the construction of the key intermediate of PLG peptidomimetics...
July 25, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28732448/synthesis-of-a-bicyclic-azetidine-with-in-vivo-antimalarial-activity-enabled-by-stereospecific-directed-c-sp-3-h-arylation
#18
Micah Maetani, Jochen Zoller, Bruno Melillo, Oscar Verho, Nobutaka Kato, Jun Pu, Eamon Comer, Stuart L Schreiber
The development of new antimalarial therapeutics is necessary to address the increasing resistance to current drugs. Bicyclic azetidines targeting Plasmodium falciparum phenylalanyl-tRNA synthetase comprise one promising new class of antimalarials, especially due to their activities against three stages of the parasite's life cycle, but a lengthy synthetic route to these compounds may affect the feasibility of delivering new therapeutic agents within the cost constraints of antimalarial drugs. Here, we report an efficient synthesis of antimalarial compound BRD3914 (EC50 = 15 nM) that hinges on a Pd-catalyzed, directed C(sp(3))-H arylation of azetidines at the C3 position...
August 16, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28730140/current-advances-in-checkpoint-inhibitors-lessons-from-non-central-nervous-system-cancers-and-potential-for-glioblastoma
#19
REVIEW
Natasha Lakin, Robert Rulach, Stefan Nowicki, Kathreena M Kurian
The adaptive immune system depends on the sequence of antigen presentation, activation, and then inhibition to mount a proportionate response to a threat. Tumors evade the immune response partly by suppressing T-cell activity using immune checkpoints. The use of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death 1 (PD-1), and programmed cell death ligand 1 (PD-L1) antibodies counteract this suppression, thereby enhancing the antitumor activity of the immune system. This approach has proven efficacy in melanoma, renal cancer, and lung cancer...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28727431/pd-catalyzed-iodide-promoted-%C3%AE-arylation-of-ketones-for-the-regioselective-synthesis-of-isocoumarins
#20
Alessandra Casnati, Raimondo Maggi, Giovanni Maestri, Nicola Della Ca', Elena Motti
A variety of isocoumarins have been synthesized directly from 2-halobenzoates and ketones through a palladium-catalyzed α-arylation step followed by an intramolecular cyclization process. The addition of iodide anions to the reaction mixture increased yields and selectivities especially when 2-bromobenzoates were employed. This phosphine-free one-pot synthesis features a high functional group tolerance and gives access to richly decorated isocoumarins. This general methodology was successful in the total synthesis of Xyridin A, an important natural product with antibacterial and antifungal activity...
July 20, 2017: Journal of Organic Chemistry
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