bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhanced recovery protocol after liver resection
Authors: Savikko J , Ilmakunnas M , Mäkisalo H , Nordin A , Isoniemi H
Published: September 2015

Background

Enhanced recovery protocols (ERPs) accelerate patient recovery and shorten hospital stay by optimization of perioperative care. However, experience with ERPs is still limited in liver surgery.

Methods

The implementation of a multimodal ERP was studied in patients who underwent open and laparoscopic liver surgery. An opioid-sparing pain treatment was chosen together with early mobilization and oral feeding, as well as restricted use of abdominal drains and catheters. Date to discharge, postoperative complications and patient satisfaction were assessed. A historical cohort of patients who underwent liver resection served as a control group.

Results

Some 134 liver resections (126 open, 8 laparoscopic) were performed between April 2013 and March 2014. Operations were carried out mostly for malignant liver tumours. One hundred and six (79·1 per cent) of the 134 patients were discharged by the fifth postoperative day. The median (range) postoperative hospital stay was 4 (2–11) days, compared with 6 (4–16) days for the control group (P < 0·001). Only four patients in the ERP group were readmitted and the 30-day mortality rate was zero.

Conclusion

An ERP for perioperative care after liver surgery was introduced safely and effectively. Discharge within 4 days is achievable with no increase in adverse events and good patient satisfaction.
Synthesis and Hydrogen Gas Sensing Properties of TiO2‐decorated CuO Nanorods
Authors: Park Sunghoon , Kim Soohyun , Kheel Hyejoon , Park Sang Eon , Lee Chongmu
Published: September 2015

Titanium dioxide (TiO2
)‐decorated cupric oxide (CuO) nanorods were fabricated by a facile two‐step process involving thermal oxidation and solvothermal methods. The multiple‐networked TiO2
‐decorated CuO nanorod sensor showed responses of 194–857%, to 0.1–5 ppm of H2
at 300 °C. These responses were 1.5–3.8 times higher than those of the pristine CuO nanorod sensor over the same H2
concentration range. The TiO2
‐decorated CuO nanorod sensor also showed a faster response to H2
gas than the pristine one, even though the former showed somewhat slower recovery than the latter. TiO2
decoration decreased the optimal operation temperature of the CuO nanorod sensor by 100 °C. The origin of the enhanced H2
sensing performance of the TiO2
‐decorated CuO nanorod sensor is discussed.
Mushroom tyrosinase: A model system to combine experimental investigation of enzyme‐catalyzed reactions, data handling using R, and enzyme‐inhibitor structural studies
Authors: Nairn Robert , Cresswell Will , Nairn Jacqueline
Published: September 2015

The activity of mushroom tyrosinase can be measured by monitoring the conversion of phenolic compounds into quinone derivatives using spectrophotometry. This article describes a series of experiments which characterize the functional properties of tyrosinase, the analysis of the resulting data using R to determine the kinetic parameters, and the exploration of the structural properties of tyrosinase–inhibitor complexes. Tyrosinase assay development and subsequent activity measurements, in the presence of varying pH, substrate concentration and inhibitors, offers the opportunity to learn the enzyme characterization skills relevant to a research laboratory setting. Combining the activity studies with an exploration of the nature of the tyrosinase–inhibitor interactions enables a structural understanding of the experimental observations. © 2015 by The International Union of Biochemistry and Molecular Biology, 43(5):370–376, 2015.
A novel approach to extraction of a large thrombus on the intraventricular guide‐wire during transcatheter aortic valve replacement
Authors: Chin Thomas , Priyesh Padmanabhan , Islam Ashequl M.
Published: September 2015

For appropriate patients with severe symptomatic aortic stenosis with a prohibitively high surgical risk, trans‐catheter aortic valve replacement (TAVR) is now established as a viable option. Thrombosis on the intra‐ventricular guide‐wire during TAVR is a recognized complication (Wiper et al., Cardiovasc Revasc Med 2014). There is an obvious potential for embolization with particular concern for stroke in this situation. We describe a case in which a >1cm thrombus was noted on the intra‐ventricular guide‐wire by trans‐esophageal echocardiogram (TEE) during a TAVR procedure. Balloon aortic valvuloplasty was still performed and an Edwards Sapien valve was deployed. After valve deployment a multi‐purpose guiding catheter was advanced with continuous suction. The guide‐wire and thrombus were withdrawn inside the guiding catheter. The guide‐wire and catheter were removed as a single unit, allowing the thrombus to be safely retrieved. We believe that this is a novel technique of aspiration thrombectomy in this potentially hazardous clinical circumstance. As our experience with TAVR increases, so does our experience with the complications. In the PARTNER trial there was a higher rate of neurological events in TAVR patients than those who had open aortic valve replacement (Smith et al. N Engl J Med 2011;364:2187–2198.). This may be related to peri‐procedural formation of thrombus and subsequent embolization. We report a case where a large guide‐wire thrombus identified during TAVR was successfully removed using a novel approach, preventing a potentially major stroke in this high‐risk patient. © 2015 Wiley Periodicals, Inc.
A side‐grooved guiding sheath as an effective treatment strategy for femoro‐popliteal artery lesions
Authors: Yamaguchi Shinichiro , Zen Kan , Kambayashi Daisuke
Published: September 2015

During revascularization for chronic total occlusion (CTO) of the proximal superficial femoral artery (SFA), the guiding sheath may prolapse out of the common femoral artery (CFA) or may not be fully inserted during treatment. Therefore, we have developed a treatment strategy using a novel side‐grooved guiding sheath, whereby a 5.0‐Fr guiding sheath (45 cm long) with a 1.0 mm × 5.0 mm rectangular side‐groove is inserted into the deep femoral artery, the side‐groove is aligned with the bifurcation, and the SFA lesion treatment is performed via the side‐groove. This technique provides good stability and maintains the wire's torque performance, while avoiding sheath prolapse from its position in the CFA. We have successfully treated seven cases of SFA‐CTO with this guiding sheath, and did not observe any increase in complications, procedure time, or amount of contrast media (vs. the conventional procedure). Therefore, our side‐grooved guiding sheath appears to be safe and effective for treating SFA‐CTO, and we hope to perform additional development of this technique. © 2015 Wiley Periodicals, Inc.
A novel drug‐coated scoring balloon for the treatment of coronary in‐stent restenosis: Results from the multi‐center randomized controlled PATENT‐C first in human trial
Authors: Scheller Bruno , Fontaine Tobias , Mangner Norman , Hoffmann Stefan , Bonaventura Klaus , Clever Yvonne P. , Chamie Daniel , Costa Ribamar , Gershony Gary , Kelsch Bettina , Kutschera Maren , Généreux Philippe , Cremers Bodo , Böhm Michael , Speck Ulrich , Abizaid Alexandre
Published: September 2015

Background

Scoring balloons produce excellent acute results in the treatment of in‐stent restenosis (ISR), fibro‐calcific and bifurcation lesions but have not been shown to affect the restenosis rate. A novel paclitaxel‐coated scoring balloon (SB) was developed and tested to overcome this limitation.

Methods and Results

SB were coated with paclitaxel admixed with a specific excipient. Patients at four clinical sites in Germany and one in Brazil with ISR of coronary bare metal stent (BMS) were randomized 1:1 to treatment with either a drug‐coated or uncoated SB. Baseline and 6‐month follow‐up quantitative coronary angiography was performed by an independent blinded core lab and all patients will be evaluated clinically for up to one year. The primary endpoint was angiographic in‐segment late lumen loss (LLL). Secondary endpoints included the rate of clinically driven target lesion revascularization (TLR), composite of major adverse cardiovascular events (MACE), stent thrombosis and other variables. Sixty‐one patients were randomized (28 uncoated and 33 drug‐coated SB); mean age 65 years, males 72%, and presence of diabetes 39%. At 6‐month angiography, in‐segment LLL was 0.48 ± 0.51 mm in the uncoated SB group versus 0.17 ± 0.40 mm in the drug‐coated SB group (P = 0.01; ITT analysis). The rate of binary restenosis was 41% in the uncoated SB group versus 7% in the drug‐coated SB group (P = 0.004). The MACE rate was 32% with the uncoated SB vs. 6% in the drug‐coated SB group (P = 0.016). This difference was primarily due to the reduced need for clinically driven TLR in the coated SB group (3% vs. 32% P = 0.004).

Conclusions

A novel paclitaxel‐coated coronary SB has been developed and successfully used in a first‐in‐human randomized controlled trial [ClinicalTrials.gov Identifier: NCT01495533]. © 2015 Wiley Periodicals, Inc.
Nitrogen‐Doped Carbon Electrocatalysts Decorated with Transition Metals for the Oxygen Reduction Reaction
Authors: Zhou Ruifeng , Jaroniec Mietek , Qiao Shi‐Zhang
Published: September 2015

The high cost of catalysts is the main disadvantage of aqueous fuel cells. In a conventional fuel cell, both the anode and cathode reactions need Pt‐based catalysts to catalyze the respective electrochemical reactions, for example, the oxygen reduction reaction (ORR) on the cathode. As the ORR is very sluggish, more Pt catalyst is needed to balance the anode and cathode currents. In recent years, many alternative catalysts have been explored for the ORR that are mostly based on carbon, which include nonmetal‐decorated carbons and metal‐decorated carbons. Carbons codoped with a transition metal and nitrogen have shown the best ORR performance among all nonprecious metal catalysts, which is comparable to Pt under analogous conditions. We review nitrogen‐doped carbon nanomaterials decorated with transition metals as ORR catalysts, their synthesis, characterization, and performance, with special emphasis on the mechanism and theoretical aspects of the ORR.
Efficient Epoxide Hydrolase Catalyzed Resolutions of (+)‐ and (−)‐cis/trans‐Limonene Oxides
Authors: Ferrandi Erica Elisa , Marchesi Carlotta , Annovazzi Celeste , Riva Sergio , Monti Daniela , Wohlgemuth Roland
Published: September 2015

The synthesis of enantiomerically pure cis‐ and trans‐limonene oxides and their corresponding diols from easily accessible raw materials has been of much interest for a long time. A straightforward one‐step biocatalytic resolution of the (+)‐cis/trans limonene oxide and the (−)‐cis/trans‐limonene oxide has been investigated. Epoxide hydrolases showing complementary stereoselectivity were recombinantly expressed in Escherichia coli, which allowed easy purification. The conditions for the selective epoxide hydrolase catalyzed ring‐opening reactions have been optimized and enabled the preparation of all limonene oxide enantiomers. The described utilization of recombinant epoxide hydrolases for the synthesis of all limonene oxide enantiomers was superior to chemical routes and represents a highly resource‐efficient one‐step preparation.
X‐ray Fluorescence Tomography of Aged Fluid‐Catalytic‐Cracking Catalyst Particles Reveals Insight into Metal Deposition Processes
Authors: Kalirai Sam , Boesenberg Ulrike , Falkenberg Gerald , Meirer Florian , Weckhuysen Bert M.
Published: September 2015

Microprobe X‐ray fluorescence tomography was used to investigate metal poison deposition in individual, intact and industrially deactivated fluid catalytic cracking (FCC) particles at two differing catalytic life‐stages. 3 D multi‐element imaging, at submicron resolution was achieved by using a large‐array Maia fluorescence detector. Our results show that Fe, Ni and Ca have significant concentration at the exterior of the FCC catalyst particle and are highly co‐localized. As concentrations increase as a function of catalytic life‐stage, the deposition profiles of Fe, Ni, and Ca do not change significantly. V has been shown to penetrate deeper into the particle with increasing catalytic age. Although it has been previously suggested that V is responsible for damaging the zeolite components of FCC particles, no spatial correlation was found for V and La, which was used as a marker for the embedded zeolite domains. This suggests that although V is known to be detrimental to zeolites in FCC particles, a preferential interaction does not exist between the two.
Imine Reductase‐Catalyzed Intermolecular Reductive Amination of Aldehydes and Ketones
Authors: Scheller Philipp N. , Lenz Maike , Hammer Stephan C. , Hauer Bernhard , Nestl Bettina M.
Published: September 2015

Imine reductases (IREDs) have emerged as promising biocatalysts for the synthesis of chiral amines. In this study, the asymmetric imine reductase‐catalyzed intermolecular reductive amination with NADPH as the hydrogen source was investigated. A highly chemo‐ and stereoselective imine reductase was applied for the reductive amination by using a panel of carbonyls with different amine nucleophiles. Primary and secondary amine products were generated in moderate to high yields with high enantiomeric excess values. The formation of the imine intermediate was studied between carbonyl substrates and methylamine in aqueous solution in the pH range of 4.0 to 9.0 by 1H NMR spectroscopy. We further measured the kinetics of the reductive amination of benzaldehyde with methylamine. This imine reductase‐catalyzed approach constitutes a powerful and direct method for the synthesis of valuable amines under mild reaction conditions.
Interpersonal and Societal Mattering in Work: A Review and Critique
Authors: Jung Ae‐Kyung
Published: September 2015

The need exists for a comprehensive literature review of the concept of mattering with regard to work. In response, this review examined a theoretical framework of societal and interpersonal mattering, mattering within the work context, and existing psychometric measures of mattering. The author analyzed the research on the current state of mattering at work, identified core frameworks and psychometric issues that have been investigated to date, and suggests the use of a more comprehensive framework for work mattering that illuminates both the relational and social aspects of the work experience. Several promising directions for future research and potential benefits of incorporating work mattering in career counseling practice emerged and are discussed.
Practitioners’ Experiences of Social Media in Career Services
Authors: Kettunen Jaana , Vuorinen Raimo , Sampson James P.
Published: September 2015

This article reports findings from a phenomenographic investigation into career practitioners’ ways of experiencing social media in career services. Focus‐group interviews were conducted with 16 Danish and Finnish career practitioners with experience using social media in career services. Four qualitatively different ways of experiencing social media in career services were identified. Social media in career services was experienced as (a) a means for delivering information, (b) a medium for 1‐to‐1 communication, (c) an interactive working space, and (d) an impetus for paradigm change and reform. The results suggest that models of career intervention and ways of experiencing social media appear to be intertwined. The hierarchical structure of the findings may serve as a tool that enables career practitioners to deepen their ways of experiencing and understanding social media in career services by using the critical aspects that were identified.
The Role of Supervisors' and Supervisees' Mindfulness in Clinical Supervision
Authors: Daniel Laura , Borders L. DiAnne , Willse John
Published: September 2015

The authors explored whether supervisor and supervisee self‐ratings of mindfulness (N = 72 supervision pairs) predicted perceptions of the supervisory relationship and session dynamics. Only supervisor self‐ratings of mindfulness predicted their own ratings of the supervisory relationship and session dynamics.
Probing Operating Electrochemical Interfaces by Photons and Neutrons
Authors: Itkis Daniil M. , Velasco‐Velez Juan Jesus , Knop‐Gericke Axel , Vyalikh Anastasia , Avdeev Mikhail V. , Yashina Lada V.
Published: September 2015

The operation of all electrochemical energy‐related systems, such as supercapacitors, batteries, fuel cells, etc. depends largely on the processes occurring at electrochemical interfaces at which charge separation and chemical reactions occur. Evolution of structure and composition at the interface between electrodes and electrolytes affects all the device′s functional parameters including power and long‐term performance stability. The analytical techniques capable of exploring the interfaces are still very limited, and more often only ex situ studies are performed. This sometimes leads to a loss of important pieces of the puzzle, hindering the development of novel technologies, as in many cases intermediates and electrochemical reaction products cannot be “quenched” for post‐process analyses. Techniques capable of operando probing of electrochemical interfaces by photons and neutrons have become an extensively growing field of research. This review aims at highlighting approaches and developing ideas on the adaptation of photoelectron, X‐ray absorption, vibrational spectroscopy, nuclear magnetic resonance, and X‐ray and neutron reflectometry in electrochemical studies.
Enhanced Photoelectrocatalytic Activity of BiOI Nanoplate–Zinc Oxide Nanorod p–n Heterojunction
Authors: Kuang Pan‐Yong , Ran Jing‐Run , Liu Zhao‐Qing , Wang Hong‐Juan , Li Nan , Su Yu‐Zhi , Jin Yong‐Gang , Qiao Shi‐Zhang
Published: September 2015

The development of highly efficient and robust photocatalysts has attracted great attention for solving the global energy crisis and environmental problems. Herein, we describe the synthesis of a p–n heterostructured photocatalyst, consisting of ZnO nanorod arrays (NRAs) decorated with BiOI nanoplates (NPs), by a facile solvothermal method. The product thus obtained shows high photoelectrochemical water splitting performance and enhanced photoelectrocatalytic activity for pollutant degradation under visible light irradiation. The p‐type BiOI NPs, with a narrow band gap, not only act as a sensitizer to absorb visible light and promote electron transfer to the n‐type ZnO NRAs, but also increase the contact area with organic pollutants. Meanwhile, ZnO NRAs provide a fast electron‐transfer channel, thus resulting in efficient separation of photoinduced electron–hole pairs. Such a p–n heterojunction nanocomposite could serve as a novel and promising catalyst in energy and environmental applications.
Strongly Emissive and Photostable Four‐Coordinate Organoboron N,C Chelates and Their Use in Fluorescence Microscopy
Authors: Pais Vânia F. , Alcaide María M. , López‐Rodríguez Rocío , Collado Daniel , Nájera Francisco , Pérez‐Inestrosa Ezequiel , Álvarez Eleuterio , Lassaletta José M. , Fernández Rosario , Ros Abel , Pischel Uwe
Published: September 2015

Six strongly fluorescent four‐coordinate organoboron N,C chelates containing an aryl isoquinoline skeleton were prepared. Remarkably, the fluorescence quantum yields reach values of up to 0.74 in oxygen‐free toluene. The strong BN interaction was corroborated by the single‐crystal X‐ray analysis of two dyes. The intramolecular charge‐transfer character of the fluorophores was evidenced by solvatochromism studies and time‐dependent DFT calculations at the PCM(toluene)/CAM‐B3LYP/6‐311++G(2d,p)//PCM(toluene)/B3LYP/6‐311G(2d,p) level of theory. The compounds combine high chemical stability with high photostability, especially when equipped with electron‐donating substituents. The strong fluorescence and the large Stokes shifts predestine these compounds for use in confocal fluorescence microscopy. This was demonstrated for the imaging of the N13 mouse microglial cell line. Moreover, significant two‐photon absorption cross sections (up to 61 GM) allow the use of excitation wavelengths in the near‐infrared region (>800 nm).
Fragmentation–Rearrangement of Peptide Backbones Mediated by the Air Pollutant NO2.
Authors: Gamon Luke F. , Nathanael Joses G. , Taggert Bethany I. , Henry Fraser A. , Bogena Jana , Wille Uta
Published: September 2015

The fragmentation–rearrangement of peptide backbones mediated by nitrogen dioxide, NO2., was explored using di‐, tri‐, and tetrapeptides 8–18 as model systems. The reaction, which is initiated through nonradical N‐nitrosation of the peptide bond, shortens the peptide chain by the expulsion of one amino acid moiety with simultaneous fusion of the remaining molecular termini through formation of a new peptide bond. The relative rate of the fragmentation–rearrangement depends on the nature of the amino acids and decreases with increasing steric bulk at the α carbon in the order Gly>Ala>Val. Peptides that possessed consecutive aromatic side chains only gave products that resulted from nitrosation of the sterically less congested N‐terminal amide. Such backbone fragmentation–rearrangement occurs under physiologically relevant conditions and could be an important reaction pathway for peptides, in which sections without readily oxidizable side chains are exposed to the air pollutant NO2.. In addition to NO2.‐induced radical oxidation processes, this outcome shows that ionic reaction pathways, in particular nitrosation, should be factored in when assessing NO2. reactivity in biological systems.
Developing Lithium Chemistry of 1,2‐Dihydropyridines: From Kinetic Intermediates to Isolable Characterized Compounds
Authors: Armstrong David R. , Harris Catriona M. M. , Kennedy Alan R. , Liggat John J. , McLellan Ross , Mulvey Robert E. , Urquhart Matthew D. T. , Robertson Stuart D.
Published: September 2015

Generally considered kinetic intermediates in addition reactions of alkyllithiums to pyridine, 1‐lithio‐2‐alkyl‐1,2‐dihydropyridines have been rarely isolated or characterized. This study develops their “isolated” chemistry. By a unique stoichiometric (that is, 1:1, alkyllithium/pyridine ratios) synthetic approach using tridentate donors we show it is possible to stabilize and hence crystallize monomeric complexes where alkyl is tert‐butyl. Theoretical calculations probing the donor‐free parent tert‐butyl species reveal 12 energetically similar stereoisomers in two distinct cyclotrimeric (LiN)3 conformations. NMR spectroscopy studies (including DOSY spectra) and thermal volatility analysis compare new sec‐butyl and iso‐butyl isomers showing the former is a hexane soluble efficient hydrolithiation agent converting benzophenone to lithium diphenylmethoxide. Emphasizing the criticalness of stoichiometry, reaction of nBuLi/Me6TREN with two equivalents of pyridine results in non‐alkylated 1‐lithio‐1,4‐dihydropyridine⋅Me6TREN and 2‐n‐butylpyridine, implying mechanistically the kinetic 1,2‐n‐butyl intermediate hydrolithiates the second pyridine.
Contractile and Extensible Molecular Figures‐of‐Eight
Authors: Niess Frédéric , Duplan Vincent , Diercks Christian S. , Sauvage Jean‐Pierre
Published: September 2015

Two large rings, 66‐ (m‐66) and 78‐membered (m‐78) rings, each one incorporating two pairs of transition‐metal‐complexing units, have been prepared. The coordinating fragments are alternating bi‐ and tridentate chelating groups, namely, 2,9‐diphenyl‐1,10‐phenanthroline (dpp) and 2,2′,2′,6′′‐terpyridine (terpy) respectively. Both macrocycles form molecular figures‐of‐eight in the presence of FeII, affording a classical bis‐terpy complex as the central core. The larger m‐78 ring can accommodate a four‐coordinate CuI center with the formation of a {Cu(dpp)2}+ central complex and a highly twisted figure‐of‐eight backbone, whereas m‐66 is too small to coordinate CuI. Macrocycle m‐78 thus affords stable complexes with both FeII and CuI; the ligand around the metal changes from (terpy)2 to (dpp)2. This bimodal coordination situation allows for a large amplitude rearrangement of the organic backbone. When coordinated to preferentially octahedrally coordinated FeII or CuII, the height of the molecule along the coordinating axis of the tridentate terpy ligands is only about 11 Å, whereas the height of the molecule along the same vertical axis is several times as large for the tetrahedral CuI complex. Chemically or electrochemically driven contraction and extension motions along a defined axis make this figure‐of‐eight particularly promising as a new class of molecular machine prototype for use as a constitutive element in muscle‐like dynamic systems.
Ruthenium‐Immobilized Periodic Mesoporous Organosilica: Synthesis, Characterization, and Catalytic Application for Selective Oxidation of Alkanes
Authors: Ishito Nobuhiro , Kobayashi Hirokazu , Nakajima Kiyotaka , Maegawa Yoshifumi , Inagaki Shinji , Hara Kenji , Fukuoka Atsushi
Published: September 2015

Periodic mesoporous organosilica (PMO) is a unique material that has a crystal‐like wall structure with coordination sites for metal complexes. A Ru complex, [RuCl2(CO)3]2, is successfully immobilized onto 2,2’‐bipyridine (BPy) units of PMO to form a single‐site catalyst, which has been confirmed by various physicochemical analyses. Using NaClO as an oxidant, the Ru‐immobilized PMO oxidizes the tertiary CH bonds of adamantane to the corresponding alcohols at 57 times faster than the secondary CH bonds, thereby exhibiting remarkably high regioselectivity. Moreover, the catalyst converts cis‐decalin to cis‐9‐decalol in a 63 % yield with complete retention of the substrate stereochemistry. The Ru catalyst can be separated by simple filtration and reused without loss of the original activity and selectivity for the oxidation reactions.
Bifacial Base‐Pairing Behaviors of 5‐Hydroxyuracil DNA Bases through Hydrogen Bonding and Metal Coordination
Authors: Takezawa Yusuke , Nishiyama Kotaro , Mashima Tsukasa , Katahira Masato , Shionoya Mitsuhiko
Published: September 2015

A novel bifacial ligand‐bearing nucleobase, 5‐hydroxyuracil (UOH), which forms both a hydrogen‐bonded base pair (UOH–A) and a metal‐mediated base pair (UOH–M–UOH) has been developed. The UOH–M–UOH base pairs were quantitatively formed in the presence of lanthanide ions such as GdIII when UOH–UOH pairs were consecutively incorporated into DNA duplexes. This result established metal‐assisted duplex stabilization as well as DNA‐templated assembly of lanthanide ions. Notably, a duplex possessing UOH–A base pairs was destabilized by addition of GdIII ions. This observation suggests that the hybridization behaviors of the UOH‐containing DNA strands are altered by metal complexation. Thus, the UOH nucleobase with a bifacial base‐pairing property holds great promise as a component for metal‐responsive DNA materials.
Didecarboxylative Iron‐Catalyzed Bidirectional Aldolization towards Diversity‐Oriented Ketodiol Synthesis
Authors: Quintard Adrien , Rodriguez Jean
Published: September 2015

1,3‐Acetonedicarboxylic acid was selectively activated by Fe(acac)3, providing a synthetic platform for rapid synthesis of keto‐3,3′‐diols. The bidirectional aldol reaction was efficient for challenging aliphatic aldehydes, providing a rapid route to potentially bioactive complex structures.
Synthesis of Aryl Tri‐ and Difluoromethyl Thioethers via a CH‐Thiocyanation/Fluoroalkylation Cascade
Authors: Jouvin Kévin , Matheis Christian , Goossen Lukas J.
Published: September 2015

An AlCl3‐catalyzed CH thiocyanation was discovered and combined with a Langlois‐type trifluoromethylation to afford aryl trifluoromethyl thioethers directly from arenes, N‐thiocyanatosuccinimide (NTS) and Ruppert–Prakash reagent. An analogous combination with a copper‐mediated difluoromethylation gives access to aryl difluoromethyl thioethers. Both processes proceed with exceptional regioselectivity for the most electron‐rich, sterically least hindered position of the arene. The sulfur and fluoroalkyl groups originate from different sources, so that the use of expensive, preformed fluoroalkylthiolation reagents is avoided.
Salicylketoximes That Target Glucose Transporter 1 Restrict Energy Supply to Lung Cancer Cells
Authors: Granchi Carlotta , Qian Yanrong , Lee Hyang Yeon , Paterni Ilaria , Pasero Carolina , Iegre Jessica , Carlson Kathryn E. , Tuccinardi Tiziano , Chen Xiaozhuo , Katzenellenbogen John A. , Hergenrother Paul J. , Minutolo Filippo
Published: September 2015

The glucose transporter GLUT1 is frequently overexpressed in most tumor tissues because rapidly proliferating cancer cells rely primarily on glycolysis, a low‐efficiency metabolic pathway that necessitates a very high rate of glucose consumption. Because blocking GLUT1 is a promising anticancer strategy, we developed a novel class of GLUT1 inhibitors based on the 4‐aryl‐substituted salicylketoxime scaffold. Some of these compounds are efficient inhibitors of glucose uptake in lung cancer cells and have a notable antiproliferative effect. In contrast to their 5‐aryl‐substituted regioisomers, the newly synthesized compounds reported herein do not display significant binding to the estrogen receptors. The inhibition of glucose uptake in cancer cells by these compounds was further observed by fluorescence microscopy imaging using a fluorescent analogue of glucose. Therefore, blocking the ability of tumor cells to take up glucose by means of these small molecules, or by further optimized derivatives, may be a successful approach in the development of novel anticancer drugs.
Association between Th17‐related cytokines and risk of non–small cell lung cancer among patients with or without chronic obstructive pulmonary disease
Authors: Liao Chen , Yu Zu-Bin , Meng Gang , Wang Li , Liu Qing-Yun , Chen Liu-Tong , Feng Shuang-Shuang , Tu Hong-Bo , Li Ya-Fei , Bai Li
Published: September 2015

BACKGROUND

CD4 + T helper 17 (Th17) cells play critical roles in inflammation and tumor development. The involvement of Th17 cells in chronic obstructive pulmonary disease (COPD)‐type inflammation‐associated lung cancer has also been confirmed in animal models. However, to the authors' knowledge, it is unknown whether the role of Th17 cells is different in patients with lung cancer complicated with COPD compared with those without COPD. In the current study, the authors attempted to determine the association between the circulating levels of Th17‐related cytokines and the clinical characteristics of non–small cell lung cancer (NSCLC) in patients with or without COPD.

METHODS

The authors designed a matched case‐control study that included 70 patients with NSCLC with COPD, 148 patients with NSCLC without COPD, and 148 healthy controls. The data regarding the clinicopathological features of these participants were collected. Circulating levels of Th17‐related cytokines, including interleukin (IL) 23 (IL‐23), IL‐17A, IL‐17F, IL‐22, and tumor necrosis factor‐α, were measured.

RESULTS

The circulating levels of IL‐23, IL‐17A, IL‐17F, IL‐22, and tumor necrosis factor‐α were found to be significantly higher in the patients with NSCLC compared with the healthy controls (P<.05). The elevated levels were found to be significantly associated with lung cancer risk (P<.05). However, no significant differences were found between patients with NSCLC with COPD and patients without COPD. It is interesting to note that, among patients with NSCLC without COPD, the levels of these cytokines were consistently higher among patients with stage I to stage IIIA disease compared with those with stage IIIB to stage IV disease (P<.05). In addition, the 5 Th17‐related cytokines demonstrated pairwise correlations, with Spearman rank correlation coefficients of 0.646 to 0.888 (P<.05).

CONCLUSIONS

The results of the current study indicate a clear association between the Th17‐related cytokine profile and the risk of NSCLC complicated by the presence or absence of COPD. Cancer 2015;121:3122‐9. © 2015 American Cancer Society.
Antineoplastic effects of 15(S)‐hydroxyeicosatetraenoic acid and 13‐S‐hydroxyoctadecadienoic acid in non–small cell lung cancer
Authors: Li Ming‐Yue , Yuan Hui-Ling , Ko Fanny W. S. , Wu Bin , Long Xiang , Du Jing , Wu Jun , Ng Calvin S. H. , Wan Innes Y. P. , Mok Tony S. K. , Hui David S. C. , Underwood Malcolm J. , Chen George G.
Published: September 2015

BACKGROUND

Previous studies have shown that the levels of 15‐lipoxygenase 1 (15‐LOX‐1) and 15‐LOX‐2 as well as their metabolites 13‐S‐hydroxyoctadecadienoic acid (13(S)‐HODE) and 15(S)‐hydroxyeicosatetraenoic acid (15(S)‐HETE) are significantly reduced in smokers with non–small cell lung carcinoma (NSCLC). Furthermore, animal model experiments have indicated that the reduction of these molecules occurs before the establishment of cigarette smoking carcinogen–induced lung tumors, and this suggests roles in lung tumorigenesis. However, the functions of these molecules remain unknown in NSCLC.

METHODS

NSCLC cells were treated with exogenous 13(S)‐HODE and 15(S)‐HETE, and then the ways in which they affected cell function were examined. 15‐LOX‐1 and 15‐LOX‐2 were also overexpressed in tumor cells to restore these 2 enzymes to generate endogenous 13(S)‐HODE and 15(S)‐HETE before cell function was assessed.

RESULTS

The application of exogenous 13(S)‐HODE and 15(S)‐HETE significantly enhanced the activity of peroxisome proliferator‐activated receptor γ (PPARγ), inhibited cell proliferation, induced apoptosis, and activated caspases 9 and 3. The overexpression of 15‐LOX‐1 and 15‐LOX‐2 obviously promoted the endogenous levels of 13(S)‐HODE and 15(S)‐HETE, which were demonstrated to be more effective in the inhibition of NSCLC.

CONCLUSIONS

This study has demonstrated that exogenous or endogenous 13(S)‐HODE and 15(S)‐HETE can functionally inhibit NSCLC, likely by activating PPARγ. The restoration of 15‐LOX activity to increase the production of endogenous 15(S)‐HETE and 13(S)‐HODE may offer a novel research direction for molecular targeting treatment of smoking‐related NSCLC. This strategy can potentially avoid side effects associated with the application of synthetic PPARγ ligands. Cancer 2015;121:3130‐45. © 2015 American Cancer Society.
Role of a serum‐based biomarker panel in the early diagnosis of lung cancer for a cohort of high‐risk patients
Authors: Yang Da-Wei , Zhang Yong , Hong Qun-Ying , Hu Jie , Li Chun , Pan Bai-Shen , Wang Qun , Ding Fei-Hong , Ou Jia-Xian , Liu Fang-Lei , Zhang Dan , Zhou Jie-Bai , Song Yuan-Lin , Bai Chun-Xue
Published: September 2015

BACKGROUND

This study applied a combined cancer biomarker panel to clinically identify small cell lung cancer (SCLC) and non–small cell lung cancer (NSCLC) in a high‐risk population.

METHODS

The serum levels of 4 biomarkers (progastrin‐releasing peptide [ProGRP], carcinoembryonic antigen [CEA], squamous cell carcinoma antigen [SCC], and cytokeratin 19 fragment [CYFRA21‐1]) were determined in 153 patients with a high risk of lung cancer (12 with a new diagnosis of SCLC, 52 with NSCLC, and 89 without lung cancer). Information about diagnosis delays was collected through interviews of all participants.

RESULTS

Significantly higher serum levels of ProGRP (P < .0001) were found among the SCLC patients versus the rest of the population. A receiver operating characteristic curve analysis established the cutoff values of ProGRP, CEA, SCC, and CYFRA21‐1 as 300 pg/mL, 7.3 ng/mL, 3 ng/mL, and 6.5 ng/mL, respectively. The sensitivity and specificity of ProGRP in diagnosing SCLC were 75% and 100%, respectively. Among the 14 lung cancer patients with a false‐negative computed tomography (CT) result, the diagnostic panel detected 8 additional cancers.

CONCLUSIONS

This panel increased the diagnostic specificity for high‐risk subjects (those with renal failure being excluded), and auxiliary to a CT scan, it increased the sensitivity for patients with lung cancer. These results might be applied to shorten the diagnosis delay at health care institutions in China. Cancer 2015;121:3113‐21. © 2015 American Cancer Society.
Prevention and management of lung cancer in China
Authors: Hong Qun‐Ying , Wu Guo-Ming , Qian Gui‐Sheng , Hu Cheng‐Ping , Zhou Jian‐Ying , Chen Liang‐An , Li Wei‐Min , Li Shi‐Yue , Wang Kai , Wang Qi , Zhang Xiao‐Ju , Li Jing , Gong Xin , Bai Chun‐Xue ,   on behalf of the Lung Cancer Group of the Chinese Thoracic Society; Chinese Alliance Against Lung Cancer
Published: September 2015

Lung cancer is the leading cause of cancer‐related death worldwide. In China, the incidence of lung cancer has grown rapidly, resulting in a large social and economic burden. Several researchers have devoted their studies to lung cancer and have demonstrated that there are many risk factors for lung cancer in China, including tobacco use, environmental pollution, food, genetics, and chronic obstructive pulmonary disease. However, the lung cancer incidence is still growing rapidly in China, and there is an even higher incidence among the younger generation. One explanation may be the triple‐neglect situation, in which medical policies that neglect prevention, diagnosis, and supportive care have increased patients' mortality and reduced their quality of life. Therefore, it is necessary to enhance the efficiency of prevention and early diagnosis not only by focusing more attention on treatment but also by drawing more attention to supportive care for patients with lung cancer. Cancer 2015;121:3080‐8. © 2015 American Cancer Society.
Implementation of the World Health Organization Framework Convention on Tobacco Control in China: An arduous and long‐term task
Authors: Xiao Dan , Bai Chun-Xue , Chen Zheng-Ming , Wang Chen
Published: September 2015

China is the largest producer and consumer of tobacco in the world. Consequently, the burden of tobacco‐related diseases in China is enormous. Implementation of the World Health Organization Framework Convention on Tobacco Control (WHO FCTC) may lead to a significant reduction in tobacco‐related morbidity and mortality both in China and globally. In this review, the authors summarize the epidemic of tobacco use and the progress made in implementing the WHO FCTC, including the promotion of legislation for smoke‐free public places; smoking‐cessation assistance; labeling of tobacco packaging; enforcement of bans on tobacco advertising, promotion, and sponsorship; increased taxes on tobacco products; increased tobacco prices; improvements in public awareness of the dangers of smoking; and identifying the barriers to implementing effective tobacco‐control measures in China. Since the WHO FCTC officially took effect in China on January 9, 2006, China has taken some important steps, especially in promoting legislation for smoke‐free public places. Because tobacco permeates the fabric of society, business, commerce, and politics in China, commitments and actions from the government are crucial, and implementing the WHO FCTC in China will be an arduous and long‐term task.Cancer2015;121:3061‐8. ©2015 American Cancer Society.
Detection of the Elusive Triazane Molecule (N3H5) in the Gas Phase
Authors: Förstel Marko , Maksyutenko Pavlo , Jones Brant M. , Sun Bing‐Jian , Chen Shih‐Hua , Chang Agnes. H.‐H. , Kaiser Ralf I.
Published: September 2015

We report the detection of triazane (N3H5) in the gas phase. Triazane is a higher order nitrogen hydride of ammonia (NH3) and hydrazine (N2H4) of fundamental importance for the understanding of the stability of single‐bonded chains of nitrogen atoms and a potential key intermediate in hydrogen–nitrogen chemistry. The experimental results along with electronic‐structure calculations reveal that triazane presents a stable molecule with a nitrogen–nitrogen bond length that is a few picometers shorter than that of hydrazine and has a lifetime exceeding 6±2 μs at a sublimation temperature of 170 K. Triazane was synthesized through irradiation of ammonia ice with energetic electrons and was detected in the gas phase upon sublimation of the ice through soft vacuum ultraviolet (VUV) photoionization coupled with a reflectron‐time‐of‐flight mass spectrometer. Isotopic substitution experiments exploiting [D3]‐ammonia ice confirmed the identification through the detection of its fully deuterated counterpart [D5]‐triazane (N3D5).
Ultrafast Photogeneration of a Tetrazolinyl Radical
Authors: Kanal Florian , Schleier Domenik , Nuernberger Patrick
Published: September 2015

Radicals in solution are crucial for many chemical processes. In this work, we unveil the photoreaction sequence leading to radical formation from tetrazolium salts, which are extensively used in enzyme assays and also exhibit a rich photochemistry. Upon UV irradiation, the tetrazolium ion turns into the tetrazolinyl radical via two intermediates on a nanosecond timescale. The solvent's polarity governs the rate of formation, but the reaction pathway towards the tetrazolinyl radical is identical for aqueous and alcoholic solutions, although the final photoproduct distribution differs. These observations provide new insight into the versatile reactivity of tetrazolium salts and ultrafast radical formation in the liquid phase.
Chemical‐Bath‐Deposited Indium Oxide Microcubes for Solar Water Splitting
Authors: Mali Mukund G. , Yoon Hyun , Kim Hayong , Joshi Bhavana , Al‐Deyab Salem S. , Yoon Sam S.
Published: September 2015

We fabricated films of cubic indium oxide (In2O3) by chemical bath deposition (CBD) for solar water splitting. The fabricated films were characterized by X‐ray diffraction analysis, Raman scattering, X‐ray photoelectron spectroscopy, and scanning electron microscopy, and the three‐dimensional microstructure of the In2O3 cubes was elucidated. The CBD deposition time was varied, to study its effect on the growth of the In2O3 microcubes. The optimal deposition time was determined to be 24 h, and the corresponding film exhibited a photocurrent density of 0.55 mA cm−2. Finally, the film stability was tested by illuminating the films with light from an AM 1.5 filter with an intensity of 100 mW cm−2.
Androgen receptor targeting drugs in castration‐resistant prostate cancer and mechanisms of resistance
Authors: Crona DJ , Milowsky MI , Whang YE
Published: September 2015

Reactivated androgen receptor (AR) signaling drives castration‐resistant prostate cancer (CRPC). The novel AR targeting drugs abiraterone and enzalutamide have improved survival of CRPC patients. However, resistance to these agents develops and patients ultimately succumb to CRPC. Potential mechanisms of resistance include the following: 1) Expression of AR splice variants, such as the AR‐V7 isoform, which lacks the ligand‐binding domain; 2) AR missense mutations in the ligand‐binding domain, such as F876L and T877A; and 3) Mutation or overexpression of androgen biosynthetic enzymes or glucocorticoid receptor. Several novel agents may overcome resistance mechanisms. Galeterone acts through multiple mechanisms that include degradation of AR protein and is being evaluated in CRPC patients positive for AR‐V7. EPI‐001 and related compounds inhibit AR splice variants by targeting the N‐terminal transactivation domain of AR. Promising therapies and novel biomarkers, such as AR‐V7, may lead to improved outcomes for CRPC patients.
Monocytes and macrophages in flow: an ESCCA initiative on advanced analyses of monocyte lineage using flow cytometry
Authors: Lambert Claude , Preijers Frank W. M. B. , Yanikkaya Demirel Gulderen , Sack Ulrich
Published: September 2015

In April 2013, a symposium was organized to highlight different aspects of differentiation and activation of the monocyte‐macrophage lineage as analyzed on the flow cytometer. Characterization of this lineage requires knowledge of the maturation process from their progenitors that are present in bone marrow up to the mature monocytic cells in peripheral blood, because each monocytic lineage cell with an aberrant phenotype refers to the corresponding maturation stage. A standardized quantitative analysis will facilitate the monitoring of the pathological processes and the clinical features, such as the outcome of treatment. However, changes in marker expression by variation in intensity, asynchronism, and lineage infidelity must be considered. The dynamics of normal marker expressions in early differentiation stages, e.g. molecules like HLA II, CD64 or CD14, give rise to a hypothesis on their possible role in monocyte ontogeny. Besides their usual role in tissue homeostasis, mature macrophages may also play a similar role in hematopoiesis. This meeting highlighted the large potential of flow cytometric tools available for monitoring of all these aspects in the monocytic and macrophage cell lineage. © 2015 International Clinical Cytometry Society
Multiplexing of receptor occupancy measurements for pharmacodynamic biomarker assessment of biopharmaceuticals
Authors: Vainshtein Inna , Schneider Amy K. , Sun Bo , Schwickart Martin , Roskos Lorin K. , Liang Meina
Published: September 2015

Background

Receptor occupancy (RO) assays measure drug target engagement, and are used as pharmacodynamic (PD) biomarkers. RO assays are commonly performed by flow cytometry and often require multiplexing for assessment of multiple PD biomarkers when specimen volumes are limited. We present multiplexed RO assays for an IGF1R‐EGFR bispecific antibody (Bs‐Ab) and a CTLA4‐Ig recombinant fusion protein to demonstrate key considerations for accurate RO assessment.

Methods

RO in cynomolgus monkeys was determined in whole blood using flow cytometry. Free and total receptors were measured using anti‐receptor fluorescence‐labeled detection reagents, competitive and noncompetitive to drug, respectively.

Results

RO of IGF1R was examined as PD for Bs‐Ab, since IGF1R was expressed on blood cells. Multiplexed measurements of free and total IGF1R showed that IGF1R expression measured by total receptor was highly variable, impacting interpretation of free‐IGF1R. Normalization of free‐over‐total IGF1R measurements compensated for variability of receptor expression allowing for accurate RO assessment. RO of CTLA4‐Ig, a recombinant fusion protein targeting CD80 and CD86 receptors, was multiplexed to simultaneously measure target engagements for both receptors. Both RO methods demonstrated specificity of receptor measurements without cross‐reactivity to each other in multiplexed formats. RO methods were used for evaluation of PD activity of Bs‐Ab and CTLA4‐Ig in cynomolgus monkeys. In both cases, RO results showed dose‐dependent target engagement, corresponding well to the pharmacokinetics.

Conclusions

Multiplexed RO methods allowed accurate assessment of PD activity for Bs‐Ab and CTLA4‐Ig, facilitating development of these biopharmaceuticals from preclinical to clinical stages. © 2015 The Authors Cytometry Part B: Clinical Cytometry Published by Wiley Periodicals, Inc.