bluuebunny/crossref_metadata_2025 huggingface dataset:
Survival analysis of the CEAwatch multicentre clustered randomized trial
Authors: Verberne C J , Zhan Z , van den Heuvel E R , Oppers F , de Jong A M , Grossmann I , Klaase J M , de Bock G H , Wiggers T
Published: April 2017

Background

The CEAwatch randomized trial showed that follow-up with intensive carcinoembryonic antigen (CEA) monitoring (CEAwatch protocol) was better than care as usual (CAU) for early postoperative detection of colorectal cancer recurrence. The aim of this study was to calculate overall survival (OS) and disease-specific survival (DSS).

Methods

For all patients with recurrence, OS and DSS were compared between patients detected by the CEAwatch protocol versus CAU, and by the method of detection of recurrence, using Cox regression models.

Results

Some 238 patients with recurrence were analysed (7·5 per cent); a total of 108 recurrences were detected by CEA blood test, 64 (55·2 per cent) within the CEAwatch protocol and 44 (41·9 per cent) in the CAU group (P = 0·007). Only 16 recurrences (13·8 per cent) were detected by patient self-report in the CEAwatch group, compared with 33 (31·4 per cent) in the CAU group. There was no significant improvement in either OS or DSS with the CEAwatch protocol compared with CAU : hazard ratio 0·73 (95 per cent 0·46 to 1·17) and 0·78 (0·48 to 1·28) respectively. There were no differences in survival when recurrence was detected by CT versus CEA measurement, but both of these methods yielded better survival outcomes than detection by patient self-report.

Conclusion

There was no direct survival benefit in favour of the intensive programme, but the CEAwatch protocol led to a higher proportion of recurrences being detected by CEA -based blood test and reduced the number detected by patient self-report. This is important because detection of recurrence by blood test was associated with significantly better survival than patient self-report, indirectly supporting use of the CEAwatch protocol.
Business Model Innovation for Sustainability: Towards a Unified Perspective for Creation of Sustainable Business Models
Authors: Evans Steve , Vladimirova Doroteya , Holgado Maria , Van Fossen Kirsten , Yang Miying , Silva Elisabete A. , Barlow Claire Y.
Published: April 2017

Business model innovation has seen a recent surge in academic research and business practice. Changes to business models are recognized as a fundamental approach to realize innovations for sustainability. However, little is known about the successful adoption of sustainable business models (SBMs). The purpose of this paper is to develop a unified theoretical perspective for understanding business model innovations that lead to better organizational economic, environmental and social performance. The paper examines bodies of literature on business model innovation, sustainability innovation, networks theory, stakeholder theory and product–service systems. We develop five propositions that support the creation of SBMs in a unified perspective, which lays a foundation to support organizations in investigating and experimenting with alternative new business models. This article contributes to the emerging field of SBMs, which embed economic, environmental and social flows of value that are created, delivered and captured in a value network. It highlights gaps for addressing the challenges of business model innovation for sustainability and suggests avenues for future research. © 2017 The Authors. Business Strategy and the Environment published by ERP Environment and John Wiley & Sons Ltd
Nanoparticles for bone tissue engineering
Authors: Vieira Sílvia , Vial Stephanie , Reis Rui L. , Oliveira J. Miguel
Published: April 2017

Tissue engineering (TE) envisions the creation of functional substitutes for damaged tissues through integrated solutions, where medical, biological, and engineering principles are combined. Bone regeneration is one of the areas in which designing a model that mimics all tissue properties is still a challenge. The hierarchical structure and high vascularization of bone hampers a TE approach, especially in large bone defects. Nanotechnology can open up a new era for TE, allowing the creation of nanostructures that are comparable in size to those appearing in natural bone. Therefore, nanoengineered systems are now able to more closely mimic the structures observed in naturally occurring systems, and it is also possible to combine several approaches ‐ such as drug delivery and cell labeling ‐ within a single system. This review aims to cover the most recent developments on the use of different nanoparticles for bone TE, with emphasis on their application for scaffolds improvement; drug and gene delivery carriers, and labeling techniques. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:590–611, 2017
Evaluation of green solvents: Oil extraction from oleaginous yeast Lipomyces starkeyi using cyclopentyl methyl ether (CPME)
Authors: Probst Kyle V. , Wales Michael D. , Rezac Mary E. , Vadlani Praveen V.
Published: April 2017

Cyclopentyl methyl ether (CPME) was evaluated for extracting oil or triacylglycerol (TAG) from wet cells of the oleaginous yeast Lipomyces starkeyi. CPME is a greener alternative to chloroform as a potential solvent for oil recovery. A monophasic system of CPME and biphasic system of CPME:water (1:0.7) performed poorly having the lowest TAG extraction efficiency and TAG selectivity compared to other monophasic systems of hexane and chloroform and the biphasic Bligh and Dyer method (chloroform:methanol:water). Biphasic systems of CPME:water:alcohol (methanol/ethanol/1‐propanol) were tested and methanol achieved the best oil extraction efficiency compared to ethanol and 1‐propanol. Different biphasic systems of CPME:methanol:water were tested, the best TAG extraction efficiency and TAG selectivity achieved was 9.9 mg/mL and 64.6%, respectively, using a starting ratio of 1:1.7:0.6 and a final ratio of 1:1:0.8 (CPME:methanol:water). Similar results were achieved for the Bligh and Dyer method (TAG extraction efficiency of 10.2 mg/mL and TAG selectivity of 66.0%) indicating that the biphasic CPME system was comparable. The fatty acid profile remained constant across all the solvent systems tested indicating that choice of solvent was not specific for any certain fatty acid. This study was able to demonstrate that CPME could be used as an alternative solvent for the extraction of oil from the wet biomass of oleaginous yeast. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1096–1103, 2017
StrandAdvantage test for early‐line and advanced‐stage treatment decisions in solid tumors
Authors: Sen Manimala , Katragadda Shanmukh , Ravichandran Aarthi , Deshpande Gouri , Parulekar Minothi , Nayanala Swetha , Vittal Vikram , Shen Weiming , Phooi Nee Yong Melanie , Jacob Jemima , Parchuru Sravanthi , Dhanuskodi Kalpana , Eyring Kenneth , Agrawal Pooja , Agarwal Smita , Shanmugam Ashwini , Gupta Satish , Vishwanath Divya , Kumari Kiran , Hariharan Arun K. , Balaji Sai A. , Liang Qiaoling , Robolledo Belen , Gauribidanur Raghavendrachar Vijayashree , Oomer Farooque Mohammed , Buresh Cary J. , Ramamoorthy Preveen , Bahadur Urvashi , Subramanian Kalyanasundaram , Hariharan Ramesh , Veeramachaneni Vamsi , Sankaran Satish , Gupta Vaijayanti
Published: April 2017

Comprehensive genetic profiling of tumors using next‐generation sequencing (NGS) is gaining acceptance for guiding treatment decisions in cancer care. We designed a cancer profiling test combining both deep sequencing and immunohistochemistry (IHC) of relevant cancer targets to aid therapy choices in both standard‐of‐care (SOC) and advanced‐stage treatments for solid tumors. The SOC report is provided in a short turnaround time for four tumors, namely lung, breast, colon, and melanoma, followed by an investigational report. For other tumor types, an investigational report is provided. The NGS assay reports single‐nucleotide variants (SNVs), copy number variations (CNVs), and translocations in 152 cancer‐related genes. The tissue‐specific IHC tests include routine and less common markers associated with drugs used in SOC settings. We describe the standardization, validation, and clinical utility of the StrandAdvantage test (SA test) using more than 250 solid tumor formalin‐fixed paraffin‐embedded (FFPE) samples and control cell line samples. The NGS test showed high reproducibility and accuracy of >99%. The test provided relevant clinical information for SOC treatment as well as more information related to investigational options and clinical trials for >95% of advanced‐stage patients. In conclusion, the SA test comprising a robust and accurate NGS assay combined with clinically relevant IHC tests can detect somatic changes of clinical significance for strategic cancer management in all the stages.
The prognostic value of simultaneous tumor and serum RAS/RAF mutations in localized colon cancer
Authors: Thomsen Caroline Emilie B. , Appelt Ane Lindegaard , Andersen Rikke Fredslund , Lindebjerg Jan , Jensen Lars Henrik , Jakobsen Anders
Published: April 2017

The impact of RAS/RAF mutations in localized colon cancer needs clarification. Based on analysis of tumor‐specific DNA, this study aimed at elucidating the prognostic influence of mutational status in tumor and serum using an extended panel of mutations.

The study retrospectively included 294 patients with curatively resected stage I–III adenocarcinoma of the colon. Mutations in tumor and serum were determined at time of surgery. Analyses were performed with droplet digital PCR technology. Hazard ratio (HR) for the association between mutational status and survival was estimated in multivariate analysis taking known prognostic factors into account.

Mutational status in tumor did not on its own have significant prognostic impact (P = 0.22). Patients with a RAS mutation simultaneously in tumor and serum had a significantly worse prognosis, overall survival (OS) (HR = 2.30, 95% CI = 1.27–4.15, P = 0.0057), and disease‐free survival (DFS) (HR = 2.18, 95%CI = 1.26–3.77, P = 0.0053). BRAF mutation in the serum and proficient mismatch repair (pMMR) protein in tumor also indicated significantly worse prognosis, OS (HR = 3.45, 95% CI = 1.52–7.85, P = 0.0032) and DFS (HR = 3.61, 95% CI = 1.70–7.67, P = 0.0008). In conclusion, RAS mutations in serum, and BRAF mutation in serum combined with pMMR in tumor were strong independent prognostic factors in patients with RAS/RAF mutated tumors.
Cancer risk in patients with hepatitis C virus infection: a population‐based study in Sweden
Authors: Liu Xiangdong , Chen Yanqing , Wang Youxin , Dong Xiaohua , Wang Junming , Tang Jianhua , Sundquist Kristina , Sundquist Jan , Ji Jianguang
Published: April 2017

Increased risks of certain cancers have been observed in patients with hepatitis C virus (HCV) infection. However, data on other cancer sites/types are lacking. We analyzed systematically the risk of developing 35 common cancers in patients with HCV infection using a nationwide Swedish database. Patients with HCV infection were identified from the Swedish Hospital Inpatient and Outpatient Register and Primary Health Care Database, and followed until the diagnosis of cancer. Standardized incidence ratios (SIRs) were calculated for subsequent 35 common cancer sites/types between 1990 and 2010 in patients with HCV infection in Sweden. Increased risks were recorded for six cancers. The highest SIR was seen for liver cancer (36.67; 95% CI: 33.20–40.40). The decreased risk was for prostate cancer (0.73; 95% CI: 0.59–0.90) and melanoma (0.50; 95% CI: 0.30–0.79). A significant sex‐difference for cancer was observed only for liver cancer (40.72; 95% CI: 36.36–45.45 for men and 27.21; 95% CI: 21.90–33.41 for women). Also, increased SIRs were noted only for liver cancer during the entire period of follow‐up. HCV infection was associated with an increased incidence of liver cancer and additionally five other types of cancer. Active surveillance of other cancers may be needed in order to be diagnosed at an earlier stage.
New Resorcinol Derivatives from a Sponge‐Derived Fungus Hansfordia sinuosae
Authors: Wu Zehong , Li Yuan , Liu Dong , Ma Min , Chen Jianliang , Lin Wenhan
Published: April 2017

Ten new resorcinol derivatives named hansfordiols A – J (1 – 10) were isolated from the fermentation broth of the sponge‐derived fungus Hansfordia sinuosae. High resolution electron ionization mass spectrometry, FT‐IR spectroscopy, and NMR techniques were used to elucidate the structures of these compounds, and the absolute configurations were established by the modified Mosher's method and their specific optical rotation. The structures of compounds 8 – 10 were featured with various chlorination at aromatic rings. Their antioxidant activities on ABTS, cytotoxicity on the HCT‐8, Bel‐7402, BGC‐823, A549, and A2780 cell lines, and antibacterial activities were evaluated.
Adult criminality among former residential school adolescents
Authors: Manninen Marko , Suvisaari Jaana , Marola Niko , Aaltonen Mikko
Published: April 2017

Background

There is evidence from around the world that disruptive behaviour during adolescence is associated with increased risk of later criminality. Outcomes for young people placed in the Finnish residential school because of severe conduct problems are not known.

Aims

Our aims were to investigate criminality after leaving a residential school placement during adolescence, and to compare trends in criminality between four successive graduate cohorts (1991, 1996, 2001 and 2006).

Methods

We used official records to study complete national cohort of all 861 people who had been resident in the Finnish residential school system on the last day of each of the years 1991, 1996, 2001 and 2006. They were compared with 4255 matched general population controls. The follow‐up time was up to 20 years.

Results

Two‐thirds (66%) of all residential school graduates (N = 566: 448/78% men, 118/41% women) had at least one criminal conviction in adulthood, a 13‐fold elevation over the general population rate. The most prevalent crime categories were violence (N = 409, 48%: 331/58% men, 78/27% women) and property crimes (N = 405: 47%: 346/60% men, 51/21% women). The risk of violent crime was 18 times that among controls; 13 of residential school males (2.3%) had a homicide conviction. Once adult, the risk of offending decreased with age. There was a significant trend for improvement in offending rates between the earliest and latest residential school cohorts.

Conclusions

The risk of committing crimes after a residential school placement is sufficiently elevated that alternative strategies, perhaps particularly longer‐term post‐release supervision and aftercare, should be considered. Indications of lower crime rates in later cohorts suggest that some positive changes to the school regime and/or aftercare may have been made already. Copyright © 2017 John Wiley & Sons, Ltd.
Dynamics of Bulk Oxygen in the Selective Oxidation of Acrolein
Authors: Heid Maurice , Knoche Stefan , Gora Niklas , Ohlig Dominik , Drochner Alfons , Etzold Bastian J. M. , Vogel Herbert
Published: April 2017

The gas‐phase oxidation of acrolein to acrylic acid on a hydrothermally prepared mixed oxide catalyst was investigated by steady‐state isotopic transient kinetic analysis (SSIKTA) as well as different types of concentration‐programmed techniques (CPR‐pulse, CPO) under in situ or process‐relevant conditions. Balancing the amounts of active oxygen gives an overview of the quantities of participating bulk oxygen species. The dynamics of bulk oxygen lead to re‐oxidation processes on the catalyst surface and thus influence the selectivity pattern of the network of acrolein oxidation. Furthermore, the bulk dynamics are activated by temperature.
Synthesis and Catalysis of Redox‐Active Bis(imino)acenaphthene (BIAN) Iron Complexes
Authors: Villa Matteo , Miesel Dominique , Hildebrandt Alexander , Ragaini Fabio , Schaarschmidt Dieter , Jacobi von Wangelin Axel
Published: April 2017

Reactions of various substituted bis(imino)acenaphthenes (R‐BIANs) with FeCl2(thf)1.5 afforded the tetrahedral complexes (R‐BIAN)FeCl2 (2) from bulky α‐diimines and the octahedral complexes [Fe(R‐BIAN)3][FeCl4]2 (3) from less bulky ligands. The driving force for the formation of complexes 3 is the high ligand‐field stabilization of the low‐spin FeII center. The two sets of complexes exhibit distinct charge‐transfer band intensities and redox activities. (R‐BIAN)FeCl2 complexes showed reversible ligand‐centered reductions at −0.9 V (vs. FcH/FcH+; FcH: ferrocene); further reduction led to decomposition. Irreversible oxidations were observed at 0.2 and 0.4 V, associated with a reduction at −0.4 V, as well as a ligand‐centered redox event at 1.0 V. First applications of the Fe(BIAN) complexes to hydrogenations of alkenes indicated good catalytic activity under mild conditions.
Mechanistic Insights into the Catalytic Hydrolysis of Ammonia Borane with Proton‐Responsive Iridium Complexes: an Experimental and Theoretical Study
Authors: Wang Wan‐Hui , Tang Hui‐Peng , Lu Wen‐Duo , Li Yang , Bao Ming , Himeda Yuichiro
Published: April 2017

For the homogeneous catalytic hydrolysis of ammonia borane (AB), a series of water‐soluble proton‐responsive iridium complexes bearing hydroxyl groups were utilized. Among the examined catalysts, [Cp*Ir(6,6′‐(OH)2‐bpy)(OH2)]SO4 exhibited the best catalytic performance in AB aqueous solution. Results obtained from experimental and theoretical studies revealed that hydrolysis of AB is assisted by synergistic effects between the pendent hydroxyl groups and the metal center.
Highly Stable Intermetallic FeSn2‐Graphite Composite Anode for Sodium‐Ion Batteries
Authors: Edison Eldho , Ling Wong Chui , Aravindan Vanchiappan , Madhavi Srinivasan
Published: April 2017

The development of anodes with high capacity, long cycle life and good rate capability is essential to expedite the commercialization of sodium‐ion batteries for practical applications, including grid storage and electric vehicles (EV). Herein, we report the facile solvothermal synthesis of nanostructured iron distannide (FeSn2) intermetallic particles as an alloy‐type anode and the improvement of its cycle life by fabricating FeSn2‐graphite composites by a ball‐milling process. The influence of graphite concentration on the sodium storage properties is studied. The composite anode delivered over 400 mAh g−1 sodiation capacity over 200 cycles at a specific current of 100 mA g−1. In addition, the composite anode exhibited excellent rate performance at higher current rates. This result would certainly pave the way for the development of high‐performance anodes that would realize low‐cost sodium‐ion batteries with a longer calendar life.
Au Nanochains Anchored on 3D Polyaniline/Reduced Graphene Oxide Nanocomposites as a High‐Performance Catalyst for Ethanol Electrooxidation
Authors: Zhang Ke , Shi Yuting , Li Shumin , Wang Caiqin , Yan Bo , Xu Hui , Wang Jin , Guo Jun , Du Yukou
Published: April 2017

A nanocomposite containing Au, polyaniline (PANI) and reduced graphene oxide (RGO) has been synthesized by a two‐step method. The PANI can intermix with graphene to build a three‐dimensional (3D) structure, which is beneficial for uniform dispersion of Au networks with a mean diameter of 5.6 nm. In addition to its role as the support of Au, the presence of PANI is also favorable for avoiding the heavy agglomeration of graphene when the reduction occurs. Additionally, the introduction of graphene can not only boost the connections with PANI, but also accelerate the electron transfer between the electrolyte solution and catalysts. Electrochemical tests indicate that the Au/PANI/RGO hybrid exhibits high catalytic activity and stability for ethanol electrooxidation in alkaline conditions. The superior performance can be ascribed to the uniform dispersion of the Au nanocatalyst on the PANI/RGO support with a particular 3D structure, resulting in an increase of the electrochemically active surface area together with a synergic effect between the PANI, graphene and Au.
Peroxotantalate‐Based Ionic Liquid Catalyzed Epoxidation of Allylic Alcohols with Hydrogen Peroxide
Authors: Ma Wenbao , Chen Chen , Kong Kang , Dong Qifeng , Li Kun , Yuan Mingming , Li Difan , Hou Zhenshan
Published: April 2017

The efficient and environmentally benign epoxidation of allylic alcohols has been attained by using new kinds of monomeric peroxotantalate anion‐functionalized ionic liquids (ILs=[P4,4,4,n]3[Ta(O)3(η‐O2)], P4,4,4,n=quaternary phosphonium cation, n=4, 8, and 14), which have been developed and their structures determined accordingly. This work revealed the parent anions of the ILs underwent structural transformation in the presence of H2O2. The formed active species exhibited excellent catalytic activity, with a turnover frequency for [P4,4,4,4]3[Ta(O)3(η‐O2)] of up to 285 h−1, and satisfactory recyclability in the epoxidation of various allylic alcohols under very mild conditions by using only one equivalent of hydrogen peroxide as an oxidant. NMR studies showed the reaction was facilitated through a hydrogen‐bonding mechanism, in which the peroxo group (O–O) of the peroxotantalate anion served as the hydrogen‐bond acceptor and hydroxyl group in the allylic alcohols served as the hydrogen‐bond donor. This work demonstrates that simple monomeric peroxotantalates can catalyze epoxidation of allylic alcohols efficiently.
Mechanistic Aspects in the Formation, Growth and Surface Functionalization of Metal Oxide Nanoparticles in Organic Solvents
Authors: Deshmukh Rupali , Niederberger Markus
Published: April 2017

The synthesis of metal oxide nanoparticles in organic solvents, so‐called nonaqueous (or nonhydrolytic) processes represent powerful alternatives to aqueous approaches and have become an independent research field. 10 Years ago, when we published our first review on organic reaction pathways in nonaqueous sol–gel approaches, the number of examples was relatively limited. Nowadays, it is almost impossible to provide an exhaustive overview. Here we review the development of the last few years, without neglecting pioneering examples, which help to follow the historical development. The importance of a profound understanding of mechanistic aspects of nanoparticle crystallization and formation mechanisms can't be overestimated, when it comes to the design of rational synthesis concepts under minimization of trial‐and‐error experiments. The main reason for the progress in mechanistic understanding lies in the availability of characterization tools that make it possible to monitor chemical reactions from the dissolution of the precursor to the nucleation and growth of the nanoparticles, by ex situ methods involving sampling after different reaction times, but more and more also by in situ studies. After a short introduction to experimental aspects of nonaqueous sol–gel routes to metal oxide nanoparticles, we provide an overview of the main and basic organic reaction pathways in these approaches. Afterwards, we summarize the main characterization methods to study formation mechanisms, and then we discuss in great depth the chemical formation mechanisms of many different types of metal oxide nanoparticles. The review concludes with a paragraph on selected crystallization mechanisms reported for nonaqueous systems and a few illustrative examples of nonaqueous sol–gel concepts applied to surface chemistry.
Why DNA Is a More Effective Scaffold than RNA in Nucleic Acid‐Based Asymmetric Catalysis—Supramolecular Control of Cooperative Effects
Authors: Marek Jasmin J. , Hennecke Ulrich
Published: April 2017

Nucleic acids can form efficient hybrid catalysts for asymmetric catalysis upon binding of low‐molecular‐weight metal complexes. Up to now DNA has been the preferred nucleic acid component, while RNA was largely ignored. It is shown that despite RNA′s successful use in ribozymes, RNA is less suited for use in hybrid catalysts for asymmetric catalysis. A common dimethyl bipyridine copper complex does not form highly active and enantioselective hybrid catalysts with RNA due to the absence of synergistic effects between the copper complex and dsRNA.
Simultaneous Triple Imaging with Two PARASHIFT Probes: Encoding Anatomical, pH and Temperature Information using Magnetic Resonance Shift Imaging
Authors: Finney Katie‐Louise N. A. , Harnden Alice C. , Rogers Nicola J. , Senanayake P. Kanthi , Blamire Andrew M. , O'Hogain Dara , Parker David
Published: April 2017

The chemical shift of paramagnetically shifted resonances in lanthanide(III) complexes encodes information about temperature and has also been made to report pH in parallel, through introduction of a single phosphonate group adjacent to the reporter tert‐butyl resonance. The enhanced sensitivity of this new probe has allowed the simultaneous triple imaging of the water signal and the shifted tert‐butyl signals of thulium and dysprosium complexes of a common ligand, separated by over 160 ppm. In parallel spectral imaging experiments, the temperature and pH dependence of the frequency of the Tm and Dy signals has been deconvoluted, allowing the pH and temperature in the liver, kidney and bladder to be measured.
Modulating the Bonding Properties of N‐Heterocyclic Carbenes (NHCs): A Systematic Charge‐Displacement Analysis
Authors: Gaggioli Carlo Alberto , Bistoni Giovanni , Ciancaleoni Gianluca , Tarantelli Francesco , Belpassi Leonardo , Belanzoni Paola
Published: April 2017

In view of their intensive use as ligands in many reactions catalyzed by transition‐metal complexes, modulation of the bonding properties of N‐heterocyclic carbenes (NHCs) on a rational basis is highly desirable, which should enable optimization of current applications or even promote new functions. In this paper, we provide a quantitative analysis of the chemical bond between a metal fragment AuCl and a series of 29 different NHCs in [(NHC)AuCl] complexes. NHCs electronic properties are modified through: i) variation of the groups attached to the NHC nitrogen atoms or backbone; ii) change of unsaturation/size of the NHC ring; iii) inclusion of paracyclophane moieties; or iv) heteroatom substitution on the NHC ring. For evaluating the donation and back‐donation components of the Dewar–Chatt–Duncanson (DCD) model in the NHC−AuCl bond, we apply the charge‐displacement (CD) analysis within the NOCV (natural orbitals for chemical valence) framework, a methodology that avoids the constraint of using symmetrized structures. We show that modulation of the NHC bonding properties requires substantial modification of their structure, such as, for instance, insertion of two ketone groups into the NHC backbone (which enhances the π back‐donation bond component and introduces an effective electronic communication within the NHC ring) or replacement of a nitrogen atom in the ring with an sp3 or sp2 carbon atom (which increases and decreases the π back‐donation bond component, respectively). We extend our investigation by quantitatively comparing the NHC electronic structures for a subset of 13 NHCs in [(NHC)PPh] adducts, the 31P NMR chemical shift values of which are experimentally available. The latter have been considered as a suitable tool for measuring the NHCs π acceptor properties [Bertrand et al., Angew. Chem. Int. Ed. 2013, 52, 2939–2943]. We show that information obtained using the metal fragment can be transferred to the PPh moiety and vice versa. However, the 31P NMR chemical shift values only qualitatively correlate with the π acceptor properties of the NHCs, with the stronger π acidic carbenes as the most outliners.
Building Block Dependent Morphology Modulation of Cage Nanoparticles and Recognition of Nitroaromatics
Authors: Acharyya Koushik , Chowdhury Aniket , Mondal Bijnaneswar , Chakraborty Shubhadip , Mukherjee Partha Sarathi
Published: April 2017

Morphology of nanomaterials has a strong impact on their chemical/physical properties, and controlled synthesis of such materials with desirable morphology is a major challenge. This article presents the role of a building block in the morphology of organic cage particles. In this context, three organic cages (A3X2, B3X2, and C3X2) were devised from triphenylamine‐based dialdehydes (A–C) and a flexible triamine (X) by utilizing dynamic imine chemistry. All of the synthesized cages were characterized by various spectroscopic techniques, which suggested the formation of [3+2] assembled architectures. Though the cages are isostructural, structural variation in the aldehyde building blocks imparted by the incorporation of phenyl moieties into the triphenylamine core produces morphologically diverse cage particles, as indicated by SEM. The synthesized cages were found to be fluorescent; the reduced analogue of cage A3X2 (A3X2r) was tested to explore its use as a chemosensor for the detection of nitroaromatic explosives. The experimental findings suggest high selectivity and sensitivity of A3X2r towards picric acid (PA) among the various nitroaromatics tested. A theoretical investigation of fluorescence quenching suggested that formation of a ground‐state charge‐transfer complex with a resonance energy‐transfer (RET) process could be the main reason behind such selectivity of the cage towards PA.
Switching Thin Films of Azobenzene‐Containing Metal–Organic Frameworks with Visible Light
Authors: Müller Kai , Knebel Alexander , Zhao Fangli , Bléger David , Caro Jürgen , Heinke Lars
Published: April 2017

Stimuli‐responsive molecules change their properties when exposed to external signals, such as light, and enable the preparation of smart materials. UV light, which often destroys organic materials, is typically required for activating the desired response of photoswitchable compounds, significantly limiting the potential applications of light‐operated smart materials. Herein, we present the first metal–organic framework (MOF), which enables reversible modulation of key properties upon irradiation with visible light only. The fluorinated azobenzene side groups in the MOF structure can be reversibly switched between the trans and cis state by green and violet light, avoiding UV light. It was demonstrated that the uptake of guest molecules by these MOF films can be switched in a fully remote‐controlled way. The membrane separation of hydrogen/hydrocarbon mixtures was investigated. The light‐induced changes of the MOF pore size result in the switching of the permeation and of the selection factor.
Rhodium‐Catalyzed Stereospecific C−H Amination for the Construction of Spiroaminal Cores: Reactivity Difference between Nitrenoid and Carbenoid Species against Amide Functionality
Authors: Kono Masato , Harada Shingo , Nemoto Tetsuhiro
Published: April 2017

Metal nitrenoids and metal carbenoids exhibit similar reactivity for insertion into a C−H bond and a C=C double bond. These reactions have attracted the attention of organic chemists due to their unusual bond‐forming ability, but the reactivity difference between these chemical species has not been studied. In this paper, we examined the reactivity difference using the corresponding Rh nitrenoid and Rh carbenoid precursors. The Rh nitrenoid inserted into an intramolecular C(sp3)−H bond adjacent to an amide nitrogen, affording functionalized spiroaminals that are ubiquitous in natural products, while the Rh carbenoid inserted into an amide C−N bond. The totally different reactivity was rationalized by the relatively low energy barrier for the C−H insertion reaction of the Rh nitrenoid. Computational analysis suggests that the origin of the discrepancy is the electrophilicity of the coordinating atoms to the Rh complex.
One‐Step Synthesis of MIL‐53(Al)/Boehmite Composites
Authors: Schwegler Johannes , Fischer Marcus , Paula Carolin , Schulz Peter S. , Hartmann Martin
Published: April 2017

[EMIM][Hbdc] and [EMIM]2[bdc] were synthesized and successfully used in a one‐step synthesis procedure of MIL‐53(Al)/boehmite composites with unusual properties. The breathing effect typically observed for MIL‐53(Al) is not found and scanning electron microscopy confirms the presence of MIL‐53 nanoparticles in a boehmite matrix. The completely different characteristics of this MIL‐53 samples in comparison to hydrothermally synthesized MIL‐53(Al) clearly demonstrate the tremendous influence of variations of the reagents used for the syntheses of metal‐organic framework materials.
Design of Dividing‐Wall Columns by Mixed‐Integer Nonlinear Programming Optimization
Authors: Franke Meik B.
Published: April 2017

Dividing‐wall columns (DWCs) offer an interesting alternative to conventional distillation towers. Savings of up to 30 % in both energy and capital cost are reported. While these high savings are realistic in some applications, DWCs offer less or no advantage at all in other applications. In any case, it is important to make a fair comparison between the conventional system and the DWC based on an optimized process design. Mixed‐integer nonlinear programming (MINLP), especially the presented modified Generalized Benders Decomposition approach, could be the tool to make this comparison, as shown here.
Biological Evaluation of Dipyrromethanes in Cancer Cell Lines: Antiproliferative and Pro‐apoptotic Properties
Authors: Jorda Radek , Lopes Susana M. M. , Řezníčková Eva , Kryštof Vladimír , Pinho e Melo Teresa M. V. D.
Published: April 2017

Functionalized dipyrromethanes were synthesized by hetero‐Diels–Alder reactions of nitroso‐ and azoalkenes and screened for their in vitro activity as anticancer agents. The studied dipyrromethanes were tested against leukemia and lymphoma cell lines, and showed GI50 values in the mid‐micromolar range. The pro‐apoptotic activities of two candidates, (E)‐1‐(2′‐ethoxycarbonylhydrazono‐1′‐benzyl‐1H‐tetrazol‐5‐yl)‐5,5′‐diethyldipyrromethane and (E)‐1‐(2′‐p‐nitrophenyl‐2′‐hydroxyiminoethyl)‐5‐phenyldipyrromethane, and their effects on the cell cycle are described. The latter compound was found to decrease the S‐phase cell population in a dose‐dependent manner and to irreversibly block cells in the G2/M phase.
Tumor volume doubling time of pulmonary metastases predicts overall survival and can guide the initiation of multikinase inhibitor therapy in patients with metastatic, follicular cell‐derived thyroid carcinoma
Authors: Sabra Mona M. , Sherman Eric J. , Tuttle R. Michael
Published: April 2017

BACKGROUND

The current study was conducted to better characterize the association between overall survival (OS) from metastatic thyroid cancer and the rate of structural disease progression.

METHODS

In this retrospective study, the average tumor volume doubling time (midDT) of 2 dominant lung metastases was used to group patients into 6 clinically relevant cohorts. OS was calculated from the time of metastasis diagnosis and from the time the pulmonary lesions crossed over the 1‐cm diameter threshold.

RESULTS

The tumor growth rate was remarkably constant in lung metastases from thyroid cancer over a median follow‐up of 8.5 years (median correlation coefficient, 0.92; coefficient of determination, 0.85). Patients with a midDT ≤1 year were found to have worse OS compared with those with a higher midDT (log‐rank P = .01). The 5‐year OS rate from the 1‐cm diameter time point was 20% for patients with a midDT ≤1 year (15 patients), 50% for patients with a midDT of 1 to 2 years (19 patients), 53% for patients with a midDT of 2 to 3 years (9 patients), 80% for patients with a midDT of 3 to 4 years (6 patients), and 80% for patients with a midDT of ≥4 years or who were negative (12 patients). Within the group of patients with a midDT ≤1 year, the 2‐year OS rate from the 1‐cm diameter point was 88% in the patients treated with multikinase inhibitors (8 patients) versus 43% in the nontreated group (7 patients) (P = .13).

CONCLUSIONS

The midDT of lung metastases appears to be a good prognostic indicator of OS in patients with metastatic thyroid cancer. Unlike the thyroglobulin DT, the midDT alone can be used to predict eligibility for multikinase inhibitor therapy. Cancer 2017;123:2955–64. © 2017 American Cancer Society.
Effects of patient‐centered communication on anxiety, negative affect, and trust in the physician in delivering a cancer diagnosis: A randomized, experimental study
Authors: Zwingmann Jelena , Baile Walter F. , Schmier Johann W. , Bernhard Jürg , Keller Monika
Published: April 2017

BACKGROUND

When bad news about a cancer diagnosis is being delivered, patient‐centered communication (PCC) has been considered important for patients' adjustment and well‐being. However, few studies have explored how interpersonal skills might help cancer patients cope with anxiety and distress during bad‐news encounters.

METHODS

A prospective, experimental design was used to investigate the impact of the physician communication style during a bad‐news encounter. Ninety‐eight cancer patients and 92 unaffected subjects of both sexes were randomly assigned to view a video of a clinician delivering a first cancer diagnosis with either an enhanced patient‐centered communication (E‐PCC) style or a low patient‐centered communication (L‐PCC) style. Participants rated state anxiety and negative affect before and immediately after the video exposure, whereas trust in the physician was rated after the video exposure only. Main and interaction effects were analyzed with generalized linear models.

RESULTS

Viewing the disclosure of a cancer diagnosis resulted in a substantial increase in state anxiety and negative affect among all participants. This emotional response was moderated by the physician's communication style: Participants viewing an oncologist displaying an E‐PCC style were significantly less anxious than those watching an oncologist displaying an L‐PCC style. They also reported significantly higher trust in the physician.

CONCLUSIONS

Under a threatening, anxiety‐provoking disclosure of bad news, a short sequence of empathic PCC influences subjects' psychological state, insofar that they report feeling less anxious and more trustful of the oncologist. Video exposure appears to be a valuable method for investigating the impact of a physician's communication style during critical encounters. Cancer 2017;123:3167–75. © 2017 American Cancer Society.
The impact of the omission or inadequate dosing of radiotherapy in extranodal natural killer T‐cell lymphoma, nasal type, in the United States
Authors: Vargo John A. , Patel Arisha , Glaser Scott M. , Balasubramani Goundappa K. , Farah Rafic J. , Marks Stanley M. , Beriwal Sushil
Published: April 2017

BACKGROUND

Extranodal natural killer T‐cell lymphoma, nasal‐type (NKTCL), is a rare malignancy in Western populations and is thus challenging for standardization of care and a prospective study. This study was aimed at defining patterns of care for NKTCL in the context of radiotherapy (RT) use and dose selection in the United States.

METHODS

Six hundred forty‐two stage I‐II NKTCL patients from 1998 to 2012 were identified from the National Cancer Data Base. Binary logistic regression analyses were performed to identify sociodemographic, treatment, and tumor characteristics predictive of the treatment selection and RT dose. Overall survival (OS) analyses were completed with the Kaplan‐Meier and Cox multivariate methods, including a propensity score adjustment for a potential indication bias.

RESULTS

Of the 642 included NKTCL patients, 70% were at stage I, 79% were white, and 66% were ≤ 60 years old. Fifty‐five percent received chemotherapy plus RT, 19% received RT alone, and 27% received chemotherapy alone. The median RT dose was 50 Gy (interquartile range, 43.2‐54 Gy), 37% received < 45 Gy, and 43% received < 50 Gy. A multivariate survival analysis showed improved OS in comparison with chemotherapy alone for RT alone at ≥50 Gy (hazard ratio [HR], 0.41; 95% confidence interval [CI], 0.23‐0.70; P < .01), for chemotherapy plus RT at <50 Gy (HR, 0.55, 95% CI, 0.36‐0.86; P < .01), and for chemotherapy plus RT at ≥50 Gy (HR, 0.41; 95% CI, 0.27‐0.63; P < .01).

CONCLUSIONS

Stage I‐II NKTCL patients in the United States commonly receive chemotherapy alone or suboptimal‐dose RT. The omission of RT or the use of suboptimal RT is negatively associated with OS. Efforts to continue improving evidenced‐based management are warranted. Cancer 2017;123:3176–85. © 2017 American Cancer Society.
p16/Ki‐67 dual labeling and urinary cytology results according to the New Paris System for Reporting Urinary Cytology: Impact of extended follow‐up
Authors: Piaton Eric , Advenier Anne‐Sophie , Carré Christian , Decaussin‐Petrucci Myriam , Mège‐Lechevallier Florence , Hutin Karine , Nennig Cindy , Colombel Marc , Ruffion Alain
Published: April 2017

BACKGROUND

Overexpression of p16INK4a has been identified in urothelial malignancies both cytologically and histologically. In addition, p16/Ki‐67 dual labeling has been shown to identify high‐grade urothelial cancer cells and some progression cases within a 12‐month delay. The Paris System for Reporting Urinary Cytology (TPS) was published in late 2015. Its aim is to clarify the criteria for diagnosing or, conversely, excluding high‐grade urothelial carcinoma (HGUC).

METHODS

Dual labeling was performed on archived ThinPrep‐based Papanicolaou slides. A total of 208 samples (negative for high‐grade urothelial carcinoma [NHGUC], 59; consistent with low‐grade urothelial neoplasia [LGUN], 24; atypical urothelial cells [AUC], 15; and suspicious for or showing HGUC, 110) were analyzed for p16/Ki‐67 after reclassification according to TPS. We assessed the oncologic status of the patients with cystoscopy, urinary cytology, histology, and prolonged 36‐month follow‐up data.

RESULTS

The sensitivity of p16/Ki‐67 for life‐threatening lesions was not different from that of urinary cytology (82.8% vs 83.6%; P = 1). However, among patients with samples classified as NHGUC and AUC, disease‐free survival was significantly shorter for dual‐labeled cases versus cases with negative dual labeling (P < .0001). The same tendency was observed in patients with histologically proven LGUN (P < .0001). As for specificity in patients with negative cystoscopy and cytology combined, prolonged follow‐up showed 90% overall survival at 24 months.

CONCLUSIONS

A long‐term evaluation of p16/Ki‐67 dual labeling may identify HGUC and progression in cases with negative/low‐grade urinary cytology results, and there are potential implications for the clinical management of patients after the conservative treatment of non–muscle‐invasive urothelial carcinoma. Cancer Cytopathol 2017;125:552–62. © 2017 American Cancer Society.
Fluorescent Proteins for Flow Cytometry
Authors: Hawley Teresa S. , Hawley Robert G. , Telford William G.
Published: April 2017

Fluorescent proteins have become standard tools for cell and molecular biologists. The color palette of fluorescent proteins spans the ultraviolet, visible, and near‐infrared spectrum. Utility of fluorescent proteins has been greatly facilitated by the availability of compact and affordable solid state lasers capable of providing various excitation wavelengths. In theory, the plethora of fluorescent proteins and lasers make it easy to detect multiple fluorescent proteins simultaneously. However, in practice, heavy spectral overlap due to broad excitation and emission spectra presents a challenge. In conventional flow cytometry, careful selection of excitation wavelengths and detection filters is necessary. Spectral flow cytometry, an emerging methodology that is not confined by the “one color, one detector” paradigm, shows promise in the facile detection of multiple fluorescent proteins. This chapter provides a synopsis of fluorescent protein development, a list of commonly used fluorescent proteins, some practical considerations and strategies for detection, and examples of applications. © 2017 by John Wiley & Sons, Inc.
High‐Throughput Particle Uptake Analysis by Imaging Flow Cytometry
Authors: Smirnov Asya , Solga Michael D. , Lannigan Joanne , Criss Alison K.
Published: April 2017

Quantifying the efficiency of particle uptake by host cells is important in the fields of infectious diseases, autoimmunity, cancer, developmental biology, and drug delivery. Here we present a protocol for high‐throughput analysis of particle uptake by imaging flow cytometry, using the bacterium Neisseria gonorrhoeae attached to and internalized by neutrophils as an example. Cells are exposed to fluorescently labeled bacteria, fixed, and stained with a bacteria‐specific antibody of a different fluorophore. Thus, in the absence of a permeabilizing agent, extracellular bacteria are double‐labeled with two fluorophores while intracellular bacteria remain single‐labeled. A spot count algorithm is used to determine the number of single‐ and double‐labeled bacteria in individual cells, to calculate the percent of cells associated with bacteria, percent of cells with internalized bacteria, and percent of cell‐associated bacteria that are internalized. These analyses quantify bacterial association and internalization across thousands of cells and can be applied to diverse experimental systems. © 2017 by John Wiley & Sons, Inc.
Method to Detect the Cellular Source of Over‐Activated NADPH Oxidases Using NAD(P)H Fluorescence Lifetime Imaging
Authors: Bremer Daniel , Leben Ruth , Mothes Ronja , Radbruch Helena , Niesner Raluca
Published: April 2017

Fluorescence‐lifetime imaging microscopy (FLIM) is a technique to generate images, in which the contrast is obtained by the excited‐state lifetime of fluorescent molecules instead of their intensity and emission spectrum. The ubiquitous coenzymes NADH and NADPH, hereafter NAD(P)H, in cells show a short fluorescence lifetime ≈︀400 psec in the free‐state and a longer fluorescence lifetime when bound to enzymes. The fluorescence lifetime of NAD(P)H in this state depends on the binding‐site on the specific enzyme. In the case of NADPH bound to members of the NADPH oxidases family we measured a fluorescence lifetime of 3650 psec as compared to enzymes typically active in cells, in which case fluorescence lifetimes of ∼2000 psec are measured. Here we present a robust protocol based on NAD(P)H fluorescence lifetime imaging in isolated cells to distinguish between normally active enzymes and NADPH oxidases, mainly responsible for oxidative stress. © 2017 by John Wiley & Sons, Inc.
Mapping Transposon Insertions in Bacterial Genomes by Arbitrarily Primed PCR
Authors: Saavedra José T. , Schwartzman Julia A. , Gilmore Michael S.
Published: April 2017

Transposons can be used to easily generate and label the location of mutations throughout bacterial and other genomes. Transposon insertion mutants may be screened for a phenotype as individual isolates, or by selection applied to a pool of thousands of mutants. Identifying the location of a transposon insertion is critical for connecting phenotype to the genetic lesion. In this unit, we present an easy and detailed approach for mapping transposon insertion sites using arbitrarily‐primed PCR (AP‐PCR). Two rounds of PCR are used to (1) amplify DNA spanning the transposon insertion junction, and (2) increase the specific yield of transposon insertion junction fragments for sequence analysis. The resulting sequence is mapped to a bacterial genome to identify the site of transposon insertion. In this protocol, AP‐PCR as it is routinely used to map sites of transposon insertion within Staphylococcus aureus, is used to illustrate the principle. Guidelines are provided for adapting this protocol for mapping insertions in other bacterial genomes. Mapping transposon insertions using this method is typically achieved in 2 to 3 days if starting from a culture of the transposon insertion mutant. © 2017 by John Wiley & Sons, Inc.