bluuebunny/crossref_metadata_2025 huggingface dataset:
Anderson‐Localization and the Mott–Ioffe–Regel Limit in Glassy‐Metallic PEDOT
Authors: Farka Dominik , Coskun Halime , Gasiorowski Jacek , Cobet Christoph , Hingerl Kurt , Uiberlacker Lisa Maria , Hild Sabine , Greunz Theresia , Stifter David , Sariciftci Niyazi Serdar , Menon Reghu , Schoefberger Wolfgang , Mardare Cezarina Cela , Hassel Achim Walter , Schwarzinger Clemens , Scharber Markus Clark , Stadler Philipp
Published: April 2017

Conductive polymers represent a rare case in which free‐carrier absorption is shifted to the far‐infrared—an attractive advantage in light of the requirement of highly transparent conductors across the visible and near‐infrared. Unfortunately, prior approaches to doping these polymers—imperative for high conductance—have consistently led to strong localization arising from fluctuating band alignment among polymer chains. Here, this study overcomes this problem of doping‐induced Anderson localization for the first time in polymers by developing a new conductive polymer synthesis strategy. This study achieves polymerization and doping simultaneously, thereby using an alternative nonmetal oxidant and thereby avoiding the introduction of excess energy that normally arises from exergonic polymerization. The resulting conductive polymer is the first to provide electron coherence in a metallic polymer thin film. The conductivity reaches a remarkable 3300 S cm−1 at 1.8 K and the mean electron scattering length a record 330 Å. This enhancement drives the glassy metal transition in the vicinity of the Mott–Ioffe–Regel (MIR) limit. The new metallic polymer achieves 10−2 Ω−1 figure of merit, making it a contender for transparent conductive contacts previously only accessible using inorganics. The new material offers a uniquely broad transparency window spanning the UV to the mid‐infrared.
Self‐Doped, n‐Type Perylene Diimide Derivatives as Electron Transporting Layers for High‐Efficiency Polymer Solar Cells
Authors: Wang Zhenfeng , Zheng Nannan , Zhang Wenqiang , Yan He , Xie Zengqi , Ma Yuguang , Huang Fei , Cao Yong
Published: April 2017

Perylene diimide (PDI) with high electron affinities are promising candidates for applications in polymer solar cells (PSCs). In addition, the strength of π‐deficient backbones and end‐groups in an n‐type self‐dopable system strongly affects the formed end‐group‐induced electronic interactions. Herein, a series of amine/ammonium functionalized PDIs with excellent alcohol solubility are synthesized and employed as electron transporting layers (ETLs) in PSCs. The electron transfer properties of the resulting PDIs are dramatically tuned by different end‐groups and π‐deficient backbones. Notably, electron transfer is observed directly in solution in self‐doped PDIs for the first time. A significantly enhanced power conversion efficiency of 10.06% is achieved, when applying the PDIs as ETLs in PTB7‐Th:PC71BM‐based PSCs. These results demonstrate the potential of n‐type organic semiconductors with stable n‐type doping capability and facile solution processibility for future applications of energy transition devices.
Feasibility trial for primary stroke prevention in children with sickle cell anemia in Nigeria (SPIN trial)
Authors: Galadanci Najibah A. , Umar Abdullahi Shehu , Vance Leah D. , Musa Tabari Abdulkadir , Ali Shehi , Belonwu Raymond , Salihu Auwal , Amal Galadanci Aisha , Wudil Jibir Binta , Bello‐Manga Halima , Neville Kathleen , Kirkham Fenella J. , Shyr Yu , Phillips Sharon , Covert Brittany V. , Kassim Adetola A. , Jordan Lori C. , Aliyu Muktar H. , DeBaun Michael R.
Published: April 2017

The vast majority of children with sickle cell anemia (SCA) live in Africa, where evidence‐based guidelines for primary stroke prevention are lacking. In Kano, Nigeria, we conducted a feasibility trial to determine the acceptability of hydroxyurea therapy for primary stroke prevention in children with abnormal transcranial Doppler (TCD) measurements. Children with SCA and abnormal non‐imaging TCD measurements (≥200 cm/s) received moderate fixed‐dose hydroxyurea therapy (∼20 mg/kg/day). A comparison group of children with TCD measurements <200 cm/s was followed prospectively. Approximately 88% (330 of 375) of families agreed to be screened, while 87% (29 of 33) of those with abnormal TCD measurements, enrolled in the trial. No participant elected to withdraw from the trial. The average mean corpuscular volume increased from 85.7 fl at baseline to 95.5 fl at 24 months (not all of the children who crossed over had a 24 month visit), demonstrating adherence to hydroxyurea. The comparison group consisted of initially 210 children, of which four developed abnormal TCD measurements, and were started on hydroxyurea. None of the monthly research visits were missed (n = total 603 visits). Two and 10 deaths occurred in the treatment and comparison groups, with mortality rates of 2.69 and 1.81 per 100 patient‐years, respectively (P = .67). Our results provide strong evidence, for high family recruitment, retention, and adherence rates, to undertake the first randomized controlled trial with hydroxyurea therapy for primary stroke prevention in children with SCA living in Africa.
ABO incompatibility in mismatched unrelated donor allogeneic hematopoietic cell transplantation for acute myeloid leukemia: A report from the acute leukemia working party of the EBMT
Authors: Canaani Jonathan , Savani Bipin N. , Labopin Myriam , Michallet Mauricette , Craddock Charles , Socié Gerard , Volin Lisa , Maertens Johan A. , Crawley Charles , Blaise Didier , Ljungman Per T. , Cornelissen Jan , Russell Nigel , Baron Frédéric , Gorin Norbert , Esteve Jordi , Ciceri Fabio , Schmid Christoph , Giebel Sebastian , Mohty Mohamad , Nagler Arnon
Published: April 2017

ABO incompatibility is commonly observed in stem cell transplantation and its impact in this setting has been extensively investigated. HLA‐mismatched unrelated donors (MMURD) are often used as an alternative stem cell source but are associated with increased transplant related complications. Whether ABO incompatibility affects outcome in MMURD transplantation for acute myeloid leukemia (AML) patients is unknown. We evaluated 1,013 AML patients who underwent MMURD transplantation between 2005 and 2014. Engraftment rates were comparable between ABO matched and mismatched patients, as were relapse incidence [34%; 95% confidence interval (CI), 28–39; for ABO matched vs. 36%; 95% CI, 32–40; for ABO mismatched; P = .32], and nonrelapse mortality (28%; 95% CI, 23–33; for ABO matched vs. 25%; 95% CI, 21–29; for ABO mismatched; P = .2). Three year survival was 40% for ABO matched and 43% for ABO mismatched patients (P = .35), Leukemia free survival rates were also comparable between groups (37%; 95% CI, 32–43; for ABO matched vs. 38%; 95% CI, 33–42; for ABO mismatched; P = .87). Incidence of grade II‐IV acute graft versus host disease was marginally lower in patients with major ABO mismatching (Hazard ratio of 0.7, 95% CI, 0.5–1; P = .049]. ABO incompatibility probably has no significant clinical implications in MMURD transplantation.
Chemical and Biological Aspects of Nutritional Immunity—Perspectives for New Anti‐Infectives that Target Iron Uptake Systems
Authors: Bilitewski Ursula , Blodgett Joshua A. V. , Duhme‐Klair Anne‐Kathrin , Dallavalle Sabrina , Laschat Sabine , Routledge Anne , Schobert Rainer
Published: April 2017

Upon bacterial infection, one of the defense mechanisms of the host is the withdrawal of essential metal ions, in particular iron, which leads to “nutritional immunity”. However, bacteria have evolved strategies to overcome iron starvation, for example, by stealing iron from the host or other bacteria through specific iron chelators with high binding affinity. Fortunately, these complex interactions between the host and pathogen that lead to metal homeostasis provide several opportunities for interception and, thus, allow the development of novel antibacterial compounds. This Review focuses on iron, discusses recent highlights, and gives some future perspectives which are relevant in the fight against antibiotic resistance.
Single‐Domain Ferromagnet of Noncentrosymmetric Uniaxial Magnetic Ions and Magnetoelectric Interaction
Authors: Koo Hyun‐Joo , Gordon Elijah E. , Whangbo Myung‐Hwan
Published: April 2017

The feasibility of a single‐domain ferromagnet based on uniaxial magnetic ions was examined. For a noncentrosymmetric uniaxial magnetic ion of magnetic moment μ at a site of local electric dipole moment p, it is unknown to date whether μ prefers to be parallel or antiparallel to μ. The nature of this magnetoelectric interaction was probed in terms of analogical reasoning based on the Rashba effect and density functional theory (DFT) calculations. We show that μ and p prefer an antiparallel arrangement, predict that Fe‐doped CaZnOS is a single‐domain ferromagnet like a bar magnet, and find the probable cause for the ferromagnetism and weak magnetization hysteresis in Fe‐doped hexagonal ZnO and ZnS at very low dopant concentrations.
Identification of a hypertrehalosemic factor in Spodoptera exigua
Authors: Park Youngjin , Kim Yonggyun
Published: April 2017

Trehalose is a major blood sugar in insects with a range of physiological functions, including an energy source and a cryoprotectant. Hemolymph trehalose concentrations are tightly regulated according to physiological conditions. An insulin‐like peptide, SeILP1, downregulates hemolymph trehalose concentrations in Spodoptera exigua. Here, we identified a factor that upregulates hemolymph trehalose concentration in S. exigua. Hemolymph trehalose concentrations were significantly increased after immune challenge or under starvation in a time‐dependent manner. To determine endocrine factors responsible for the upregulation, stress‐associated mediators, such as octopamine, serotonin, or eicosanoids were injected, but they did not upregulate hemolymph trehalose. On the other hand, injection with Schistocerca gregaria adipokinetic hormone (AKH) significantly increased hemolymph trehalose concentration in S. exigua. During upregulation of hemolymph trehalose by AKH injection, trehalose degradation appeared to be inhibited because expression of trehalase and SeILP1 were significantly suppressed while that of trehalose phosphate synthase was not significantly changed. Interrogation of a Spodoptera genome database identified an S. exigua AKH‐like gene and its expression was confirmed. During starvation, its expression concentrations were increased, although RNA interference specific to the AKH‐like hypertrehalosemic factor (SeHTF) gene significantly prevented the upregulation of hemolymph trehalose concentrations during starvation. A synthetic peptide of SeHTF was prepared and injected into S. exigua larvae. At nanomolar concentration, the synthetic SeHTF peptide effectively upregulated hemolymph trehalose concentrations. Here we report a novel hypertrehalosemic factor in S. exigua (SeHTF).
Formulation and Analgesic Effect of Sodium Hyaluronate and Magnesium Sulfate Combination in Rats Following Intra‐articular Injection
Authors: Ho Myoung Jin , Lee Dae Ro , Jung Hyuck Jun , Song Woo Heon , Park Jun Sang , Kang Myung Joo
Published: April 2017

The objective of this study was to formulate hyaluronate (HA) combined with magnesium sulfate (MS) for intra‐articular (IA) injection, to provide rapid and profound analgesia in the treatment of osteoarthritis (OA). The injectable HA/MS combination was optimized with respect to the kinds and amounts of buffering agent (10 mM histidine, pH 7.0) and stabilizer (10 mM sodium citrate), by evaluating changes in the appearance, pH, and intrinsic viscosity at 60°C. Increasing concentrations of sodium citrate significantly inhibited the decline in intrinsic viscosity, denoting the depolymerization of HA, preserving over 91% of initial value. In an efficacy study in iodoacetate‐induced OA rats, treatment with the HA/MS combination (1/2% w/v) significantly reduced joint swelling and pain, compared to the vehicle‐ and HA‐treated groups (p < 0.05) at 7 days postdosing. Thus, IA administration of the combination of HA, a slow‐acting symptom‐modifying agent, with the inorganic analgesic is a potentially effective therapeutic approach for rapid pain relief in the OA knee.
An HPLC method for simultaneous quantitative determination of seven secoiridoid glucosides separated from the roots of Ilex pubescens
Authors: Zhang Yang , Xiong Huan , Bi Jiayi , Zhao Guiyun , Yang Yi , Chen Xue , Li Yuncong , Zhang Chongyu , Zhang Guogang
Published: April 2017

A simple and specific high‐performance liquid chromatographic method has been developed and validated to simultaneously determine seven secoiridoid glucosides for the first time. Three of them were separated from the ethanolic extract of the roots of Ilex pubescens for the first time, namely nuezhenide A, ligusides B and oleonuezhenide. In quantitative analysis, all of the calibration curves showed good linear regression (r > 0.999) within the tested ranges, and the mean recoveries of three different concentrations ranged from 97.6 to 101.2%. The limit of detection and limit of quantification were <4.18 and 11.63 ng mL−1, respectively. The relative standard deviation for repeatability and the precision of seven analytes were <3.4 and 1.9%, respectively. The established method was successfully applied to simultaneous determination of seven secoiridoid glucosides in 11 batches of samples collected from different habitats in China.
A practical approach in bioreactor scale‐up and process transfer using a combination of constant P/V and vvm as the criterion
Authors: Xu Sen , Hoshan Linda , Jiang Rubin , Gupta Balrina , Brodean Eric , O'Neill Kristin , Seamans T. Craig , Bowers John , Chen Hao
Published: April 2017

Bioreactor scale‐up is a critical step in the production of therapeutic proteins such as monoclonal antibodies (MAbs). With the scale‐up criterion such as similar power input per volume or O2 volumetric mass transfer coefficient (
), adequate oxygen supply and cell growth can be largely achieved. However, CO2 stripping in the growth phase is often inadequate. This could cascade down to increased base addition and osmolality, as well as residual lactate increase and compromised production and product quality. Here we describe a practical approach in bioreactor scale‐up and process transfer, where bioreactor information may be limited. We evaluated the sparger
and
(CO2 volumetric mass transfer coefficient) from a range of bioreactor scales (3–2,000 L) with different spargers. Results demonstrated that
for oxygen is not an issue when scaling from small‐scale to large‐scale bioreactors at the same gas flow rate per reactor volume (vvm). Results also showed that sparging CO2 stripping,
, is dominated by the gas throughput. As a result, a combination of a minimum constant vvm air or N2 flow with a similar specific power was used as the general scale‐up criterion. An equation was developed to determine the minimum vvm required for removing CO2 produced from cell respiration. We demonstrated the effectiveness of using such scale‐up criterion with five MAb projects exhibiting different cell growth and metabolic characteristics, scaled from 3 to 2,000 L bioreactors across four sites. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1146–1159, 2017
MiR‐145 inhibits human colorectal cancer cell migration and invasion via PAK4‐dependent pathway
Authors: Sheng Nengquan , Tan Gewen , You Weiqiang , Chen Hongqi , Gong Jianfeng , Chen Di , Zhang Huizhen , Wang Zhigang
Published: April 2017

MicroRNA‐145 (miR‐145), as a tumor‐suppressive miRNA, has been demonstrated down‐regulated in colorectal cancer (CRC) cells, and could inhibit CRC cells growth. However, the molecular pathway in which miR‐145 modulates CRC malignant transformation has not been fully revealed. Here, we reported an intense correlation between the expressions of PAK4 and miR‐145 in human CRC cell lines. Transwell assay verified overexpression of miR‐145, as well as knockdown of PAK4, significantly suppressed cell migration and invasion ability. The impaired migration and invasion ability of SW1116 cells was affected through the down‐regulation of phosphorylation level of LIMK1 and cofilin in a PAK4‐dependent manner. Collectively, we have demonstrated that miR‐145 suppressed CRC migration and invasion through PAK4 pathway, which provides an attractive microRNA‐based therapeutic target for CRC.
Overcoming Linsitinib intrinsic resistance through inhibition of nuclear factor‐κB signaling in esophageal squamous cell carcinoma
Authors: Wu Junzhou , Chen Kaiyan , Zhang Fanrong , Jin Jiaoyue , Zhang Nan , Li Dan , Ying Lisha , Chen Wei , Yu Herbert , Mao Weimin , Su Dan
Published: April 2017

The aim of this study is to evaluate the efficacy of insulin‐like growth factor 1 receptor (IGF‐1R) inhibitor Linsitinib, in esophageal squamous cell carcinoma (ESCC), and to characterize special biomarker to screen Linsitinib‐sensitive patients as well as explore the molecular‐resistant mechanism to Linsitinib in ESCC. Our study evaluated the sensitivity of insulin‐like growth factor 1 receptor (IGF‐1R) inhibitor, Linsitinib in ESCC cells with MTT assay. After Linsitinib treatment, the expressions of downstream signaling molecules and apoptosis pathways were measured by western blot. And the antitumor effect of Linsitinib and JSH‐23, an inhibitor of nuclear factor‐κB transcriptional activity, was analyzed both as single agent and in combination in ESCC. Apoptosis, cell viability, and clonogenic survival analysis were also investigated. The sensitivity of Linsitinib was relatively variable in patient‐derived primary ESCC cells as well as in human commercial cell lines. And the downstream AKT/mTOR and ERK signaling pathways were inhibited by Linsitinib, while phosphorylation level of NF‐κB p65 was obviously activated to reduce apoptosis effect in Linsitinib‐resistant cell lines. Most importantly, blockage of NF‐κB activity by JSH‐23 could sensitize resistant cells to Linsitinib treatment. Results from this study demonstrated that the intrinsic resistance to Linsitinib was predominantly mediated by NF‐κB activation in ESCC. Moreover, combination of Linsitinib and JSH‐23 as therapy provides a novel strategy to overcome resistance to Linsitinib in ESCC.
A Nonbactericidal Zinc‐Complexing Ligand as a Biofilm Inhibitor: Structure‐Guided Contrasting Effects on Staphylococcus aureus Biofilm
Authors: Kapoor Vidushi , Rai Rajanikant , Thiyagarajan Durairaj , Mukherjee Sandipan , Das Gopal , Ramesh Aiyagari
Published: April 2017

Zinc‐complexing ligands are prospective anti‐biofilm agents because of the pivotal role of zinc in the formation of Staphylococcus aureus biofilm. Accordingly, the potential of a thiosemicarbazone (compound C1) and a benzothiazole‐based ligand (compound C4) in the prevention of S. aureus biofilm formation was assessed. Compound C1 displayed a bimodal activity, hindering biofilm formation only at low concentrations and promoting biofilm growth at higher concentrations. In the case of C4, a dose‐dependent inhibition of S. aureus biofilm growth was observed. Atomic force microscopy analysis suggested that at higher concentrations C1 formed globular aggregates, which perhaps formed a substratum that favored adhesion of cells and biofilm formation. In the case of C4, zinc supplementation experiments validated zinc complexation as a plausible mechanism of inhibition of S. aureus biofilm. Interestingly, C4 was nontoxic to cultured HeLa cells and thus has promise as a therapeutic anti‐biofilm agent. The essential understanding of the structure‐driven implications of zinc‐complexing ligands acquired in this study might assist future screening regimes for identification of potent anti‐biofilm agents.
Effect of Fluoride‐Modification on the Phillips Cr/SiO2 Catalyst for Ethylene Polymerization
Authors: Sun Qiaoqiao , Cheng Ruihua , Liu Zhen , He Xuelian , Zhao Ning , Liu Boping
Published: April 2017

In this work, a fluoride‐modified Phillips catalyst was investigated by using combined experimental and computational methods. The addition of fluoride to the Phillips Cr/SiO2 catalyst can increase the activity of the catalyst calcined at a low temperature and the molecular weight of the polyethylene product. DFT calculations were performed to show that the difference of the Gibbs free energy barriers between chain transfer and chain propagation increased after the introduction of the fluoride onto the silica surface, which is in accordance with the increased molecular weight of the polyethylene produced by the fluoride‐modified Phillips Cr/F‐SiO2 catalyst. The computational results also reflect the increase of the activity of the ethylene/1‐hexene copolymerization after the introduction of fluoride, although the modification has little effect on the regioselectivity of the produced ethylene/1‐hexene copolymer. Moreover, copolymers produced by the fluoride‐modified Phillips catalyst with more short‐chain branches (SCBs) in the high‐molecular‐weight fraction and a significant enhancement of the environmental stress crack resistance can be explained from the results of the DFT calculations.
Sequential Reactions of Alkynes on an Iridium(III) Single Site
Authors: Giner Elena A. , Gómez‐Gallego Mar , Merinero Alba D. , Casarrubios Luis , Ramírez de Arellano Carmen , Sierra Miguel A.
Published: April 2017

Sequential insertion of terminal alkynes on IrIII cyclometalated complexes allow the formation of novel metallapolycycles in a controlled and efficient manner. ortho‐Methylarylethynyl derivatives led to an unprecedented cascade combination of three fundamental processes (C−C bond formation, C(sp3)−H activation, and reductive coupling) on a single IrIII center, in a process compatible with functionalized biomolecules and photoactive substrates. The reaction with tert‐butylacetylene led to a [6,5,4]‐polycycle that incorporates an iridacyclobutenylidene in its structure. The sequence is a multicomponent reaction in which the metal not only promotes the different steps but also determines their stereoselectivity. This is an elegant example of the synergy between a metal‐promoting reaction and a symmetry‐defined stereochemistry.
Dawson‐Type Polyoxomolybdate Anions (P2Mo18O626−) Captured by Ionic Liquid on Graphene Oxide as High‐Capacity Anode Material for Lithium‐Ion Batteries
Authors: Hu Jun , Diao Hongling , Luo Wenjing , Song Yu‐Fei
Published: April 2017

The development of advanced anode materials is of significance for the next generation of lithium‐ion batteries (LIBs). Herein, imidazolium‐based ionic liquids (ILs) are grafted covalently on the surface of graphene oxides (GO) through the carboxyl‐amino bond, providing a loading hotbed for the Dawson‐type polyoxometalate (POM) of (NH4)6P2Mo18O62 (denoted as P2Mo18). The as‐prepared GO‐IL‐P2Mo18 nanocomposite is characterized by FTIR and Raman spectroscopy, TGA, SEM, TEM, and XPS. The nanocomposite is used as the anode material for LIBs, and shows a high reversible capacity of 903.9 mAh g−1 with a long cycle life over 1000 cycles. Galvanostatic cycling tests, CV measurements, and AC impedance spectra reveal that the POMs in the GO‐IL‐P2Mo18 nanocomposite give an enhanced specific capacity during the Lithium insertion/extraction process, and the IL provides a favored contact between the electrolyte and the electrode.
Highly Selective Olefin‐Assisted PdII‐Catalyzed Oxidative Alkynylation of Enallenes
Authors: Henry Jeffrey L. , Posevins Daniels , Yang Bin , Qiu Youai , Bäckvall Jan‐E.
Published: April 2017

An olefin‐assisted, palladium‐catalyzed oxidative alkynylation of enallenes for regio‐ and stereoselective synthesis of substituted trienynes has been developed. The reaction shows a broad substrate scope and good tolerance for various functional groups on the allene moiety, including carboxylic acid esters, free hydroxyls, imides, and alkyl groups. Also, a wide range of terminal alkynes with electron‐donating and electron‐withdrawing aryls, heteroaryls, alkyls, trimethylsilyl, and free hydroxyl groups are tolerated.
Rhodium(III)‐Catalyzed Annulative Carbooxygenation of 1,1‐Disubstituted Alkenes Triggered by C−H Activation
Authors: Li Yang , Tang Yuhai , He Xin , Shi Dandan , Wu Jun , Xu Silong
Published: April 2017

A Cp*RhIII‐catalyzed annulative carbooxygenation of challenging 1,1‐disubstituted alkenes triggered by C−H activation of N‐aryloxyacetamides has been established, which affords 2,3‐dihydrobenzofuran derivatives with a quaternary carbon center in good to excellent yields under mild redox‐neutral conditions. An amide group on the alkenes is essential for the process, and may inhibit the β‐H elimination from C(sp3)−Rh species by saturating the rhodium center through coordination. Furthermore, mechanistic insights obtained from control experiments suggest a mechanism involving a RhIII‐RhV‐RhIII catalytic cycle.
Resolution, determination of enantiomeric purity and chiral recognition mechanism of new xanthone derivatives on (S,S)‐whelk‐O1 stationary phase
Authors: Carraro Maria L. , Palmeira Andreia , Tiritan Maria E. , Fernandes Carla , Pinto Madalena M.M.
Published: April 2017

The enantioresolution and determination of the enantiomeric purity of 32 new xanthone derivatives, synthesized in enantiomerically pure form, were investigated on (S,S)‐Whelk‐O1 chiral stationary phase (CSP). Enantioselectivity and resolution (α and RS) with values ranging from 1.41–6.25 and from 1.29–17.20, respectively, were achieved. The elution was in polar organic mode with acetonitrile/methanol (50:50 v/v) as mobile phase and, generally, the (R)‐enantiomer was the first to elute. The enantiomeric excess (ee) for all synthesized xanthone derivatives was higher than 99%. All the enantiomeric pairs were enantioseparated, even those without an aromatic moiety linked to the stereogenic center. Computational studies for molecular docking were carried out to perform a qualitative analysis of the enantioresolution and to explore the chiral recognition mechanisms. The in silico results were consistent with the chromatographic parameters and elution orders. The interactions between the CSP and the xanthone derivatives involved in the chromatographic enantioseparation were elucidated.
Lay health educators and print materials for the promotion of colorectal cancer screening among Korean Americans: A randomized comparative effectiveness study
Authors: Jo Angela M. , Nguyen Tung T. , Stewart Susan , Sung Min J. , Gildengorin Ginny , Tsoh Janice Y. , Tong Elisa K. , Lo Penny , Cuaresma Charlene , Sy Angela , Lam Hy , Wong Ching , Jeong Matthew , Chen Moon S. , Kagawa‐Singer Marjorie
Published: April 2017

BACKGROUND

Colorectal cancer (CRC) is the second most commonly diagnosed cancer among Korean American men and women. Although CRC screening is effective in reducing the burden of this disease, studies have shown that Korean Americans have low screening rates.

METHODS

The authors conducted a 2‐arm cluster randomized controlled trial comparing a brochure (print) with a brochure and lay health educator (LHE) outreach (print + LHE) in increasing CRC screening rates among Korean American individuals. Self‐administered written surveys at baseline and at 6 months assessed knowledge of CRC and its screening, ever screening, and being up to date with screening.

RESULTS

A total of 28 LHEs recruited 348 participants aged 50 to 75 years from their social networks. Significant percentages of participants reported not having health insurance (29.3%) or a usual source of care (35.6%). At 6 months postintervention, the print + LHE participants had a greater increase in knowledge compared with those in the print arm (P = .0013). In multivariable analyses, both groups had significant increases in ever screening (print plus LHE: odds ratio [OR], 1.60 [95% confidence interval (95% CI), 1.26‐2.03] and print: OR, 1.42 [95% CI, 1.10‐1.82]) and being up to date with screening (print plus LHE: OR, 1.63 [95% CI, 1.23‐2.16] and print: OR, 1.40 [95% CI, 1.04‐1.89]). However, these increases did not differ significantly between the study arms. Having insurance and having seen a provider within the past year were found to be positively associated with screening.

CONCLUSIONS

Compared with a brochure, LHE outreach yielded greater increases in knowledge but resulted in similar increases in CRC screening in a Korean American population with barriers to health care access. More work is needed to appropriately address logistical and system barriers in this community. Cancer 2017;123:2705‐15. © 2017 American Cancer Society.
Improved outcomes after successful implementation of a pediatric early warning system (PEWS) in a resource‐limited pediatric oncology hospital
Authors: Agulnik Asya , Mora Robles Lupe Nataly , Forbes Peter W. , Soberanis Vasquez Doris Judith , Mack Ricardo , Antillon‐Klussmann Federico , Kleinman Monica , Rodriguez‐Galindo Carlos
Published: April 2017

BACKGROUND

Hospitalized pediatric oncology patients are at high risk of clinical decline and mortality, particularly in resource‐limited settings. Pediatric early warning systems (PEWS) aid in the early identification of clinical deterioration; however, there are limited data regarding their feasibility or impact in low‐resource settings. This study describes the successful implementation of PEWS at the Unidad Nacional de Oncología Pediátrica (UNOP), a pediatric oncology hospital in Guatemala, resulting in improved inpatient outcomes.

METHODS

A modified PEWS was implemented at UNOP with systems to track errors, transfers to a higher level of care, and high scores. A retrospective cohort study was used to evaluate clinical deterioration events in the year before and after PEWS implementation.

RESULTS

After PEWS implementation at UNOP, there was 100% compliance with PEWS documentation and an error rate of <10%. Implementation resulted in 5 high PEWS per week, with 30% of patients transferring to a higher level of care. Among patients requiring transfer to the pediatric intensive care unit (PICU), 93% had an abnormal PEWS before transfer. The rate of clinical deterioration events decreased after PEWS implementation (9.3 vs 6.5 per 1000‐hospitalpatient‐days, p = .003). Despite an 18% increase in total hospital patient‐days, PICU utilization for inpatient transfers decreased from 1376 to 1088 PICU patient‐days per year (21% decrease; P<.001).

CONCLUSIONS

This study describes the successful implementation of PEWS in a pediatric oncology hospital in Guatemala, resulting in decreased inpatient clinical deterioration events and PICU utilization. This work demonstrates that PEWS is a feasible and effective quality improvement measure to improve hospital care for children with cancer in hospitals with limited resources. Cancer 2017;123:2965–74. © 2017 American Cancer Society.
Regulations and policies regarding e‐cigarettes
Authors: Barraza Leila F. , Weidenaar Kim E. , Cook Livia T. , Logue Andrea R. , Halpern Michael T.
Published: April 2017

Electronic cigarettes (e‐cigarettes) are a growing public health concern because of a dramatic increase in use by adolescents and the uncertainty of potential health impacts. These health concerns and lack of an established federal regulatory scheme have led many local and state governments to address the regulatory void for e‐cigarettes by incorporating them into the statutory definition of tobacco or by passing laws specific to the use of e‐cigarettes. In August 2016, the US Food and Drug Administration issued a final rule deeming e‐cigarettes within their authority; providing uniform requirements like premarket approval applications, Harmful and Potentially Harmful Constituents reporting, and warning labels; and establishing 18 years as a minimum age of purchase. Although the impact on the public's health remains uncertain, regulations and laws governing e‐cigarettes continue to develop. This review highlights the available data regarding safety and public health impacts of e‐cigarettes and details the status of US regulations and policies affecting their sale and use. Cancer 2017;123:3007–14. © 2017 American Cancer Society.
Phase 1 dose‐escalation study of mirvetuximab soravtansine (IMGN853), a folate receptor α‐targeting antibody‐drug conjugate, in patients with solid tumors
Authors: Moore Kathleen N. , Borghaei Hossein , O'Malley David M. , Jeong Woondong , Seward Shelly M. , Bauer Todd M. , Perez Raymond P. , Matulonis Ursula A. , Running Kelli L. , Zhang Xiaoyan , Ponte Jose F. , Ruiz‐Soto Rodrigo , Birrer Michael J.
Published: April 2017

BACKGROUND

Mirvetuximab soravtansine (IMGN853) is an antibody‐drug conjugate that selectively targets folate receptor α (FRα). In this phase 1 dose‐escalation study, the authors investigated IMGN853 in patients with FRα‐positive solid tumors.

METHODS

Patients received IMGN853 on day 1 of a 21‐day cycle (once every 3 weeks dosing), with cycles repeated until patients experienced dose‐limiting toxicity or progression. Dose escalation commenced in single‐patient cohorts for the first 4 planned dose levels and then followed a standard 3 + 3 scheme. The primary objectives were to determine the maximum tolerated dose and the recommended phase 2 dose. Secondary objectives were to determine safety and tolerability, to characterize the pharmacokinetic profile, and to describe preliminary clinical activity.

RESULTS

In total, 44 patients received treatment at doses escalating from 0.15 to 7.0 mg/kg. No meaningful drug accumulation was observed with the dosing regimen of once every 3 weeks. The most common treatment‐related adverse events were fatigue, blurred vision, and diarrhea, the majority of which were grade 1 or 2. The dose‐limiting toxicities observed were grade 3 hypophosphatemia (5.0 mg/kg) and grade 3 punctate keratitis (7.0 mg/kg). Two patients, both of whom were individuals with epithelial ovarian cancer, achieved confirmed tumor responses according to Response Evaluation Criteria in Solid Tumors 1.1, and each was a partial response.

CONCLUSIONS

IMGN853 demonstrated a manageable safety profile and encouraging preliminary clinical activity, particularly in patients with ovarian cancer. The results establish a recommended phase 2 dosing of 6.0 mg/kg (based on adjusted ideal body weight) once every 3 weeks. Cancer 2017. © 2017 American Cancer Society. Cancer 2017;123:3080–7. © 2017 American Cancer Society.
Implementation of Probabilistic Algorithms by Multi‐chromophoric Molecular Networks with Application to Multiple Travelling Pathways
Authors: Fresch Barbara , Remacle Françoise , Levine Raphael D.
Published: April 2017

The implementation of probabilistic algorithms by deterministic hardware is demanding and requires hundreds of instructions to generate a pseudo‐random sequence of numbers. On the contrary, the dynamics at the molecular scale is physically governed by probabilistic laws because of the stochastic nature of thermally activated and quantum processes. By simulating the exciton transfer dynamics in a multi‐chromophoric system, we demonstrate the implementation of a random walk that samples the possible pathways of a traveler through a network and can be probed by time‐resolved fluorescence spectroscopy. The ability of controlling the spatial arrangement of the chromophores allows us to design the “landscape” in which the traveler is moving and therefore to program the molecular device.
Triple‐Doped Monolayer Graphene with Boron, Nitrogen, Aluminum, Silicon, Phosphorus, and Sulfur
Authors: Ullah Saif , Denis Pablo A. , Sato Fernando
Published: April 2017

The structure, stability, electronic properties and chemical reactivity of X/B/N triple‐doped graphene (TDG) systems (X=Al, Si, P, S) are investigated by means of periodic density functional calculations. In the studied TDGs the dopant atoms prefer to be bonded to one another instead of separated. In general, the XNB pattern is preferred, with the exception of sulfur, which favors the SBN motif. The introduction of a third dopant results in a negligible decrease of the cohesive energies with respect to the dual‐doped graphene (DDG) counterparts. Thus, it is expect that these systems can be prepared soon. For SiNB TDG, the introduction of the B dopant reduces the gap opening at the K point and restores the Dirac cones that are destroyed in SiN DDG. On the contrary, for PNB TDG, the bandgap is increased with respect to PN DDG, probably because the introduction of B weakens the PN bonding, and thus the electronic structure is rather similar to that of P‐doped graphene. Finally, with regard to the reactivity of the TDGs, for AlNB, PNB, and SNB the carbon atoms are more reactive than in their AlN, PN, and SN DDG counterparts. On the contrary, the reactivity of SiNB is lower than that of SiN DDG. Therefore, to increase the reactivity of graphene, Al, P, and S should be combined with BN motifs.
Sodium‐glucose cotransporter 2 (SGLT2) inhibitors and fracture risk in patients with type 2 diabetes mellitus: A meta‐analysis
Authors: Ruanpeng Darin , Ungprasert Patompong , Sangtian Jutarat , Harindhanavudhi Tasma
Published: April 2017

Background

Sodium‐glucose cotransporter 2 (SGLT2) inhibitors could potentially alter calcium and phosphate homeostasis and may increase the risk of bone fracture.

Methods

The current meta‐analysis was conducted to investigate the fracture risk among patients with type 2 diabetes mellitus treated with SGLT2 inhibitors. Randomized controlled trials that compared the efficacy of SGLT2 inhibitors to placebo were identified. The risk ratios of fracture among patients who received SGLT2 inhibitors versus placebo were extracted from each study. Pooled risk ratios and 95% confidence intervals were calculated using a random‐effect, Mantel‐Haenszel analysis.

Results

A total of 20 studies with 8286 patients treated with SGLT2 inhibitors were included. The pooled risk ratio of bone fracture in patients receiving SGLT2 inhibitors versus placebo was 0.67 (95% confidence interval, 0.42‐1.07). The pooled risk ratio for canagliflozin, dapagliflozin, and empagliflozin was 0.66 (95% confidence interval, 0.37‐1.19), 0.84 (95% confidence interval, 0.22‐3.18), and 0.57 (95% confidence interval, 0.20‐1.59), respectively.

Conclusions

Increased risk of bone fracture among patients with type 2 diabetes mellitus treated with SGLT2 inhibitors compared with placebo was not observed in this meta‐analysis. However, the results were limited by short duration of treatment/follow‐up and low incidence of the event of interest.
Chiral analysis of amphetamines in hair by liquid chromatography–tandem mass spectrometry: compliance‐monitoring of attention deficit hyperactivity disorder (ADHD) patients under Elvanse® therapy and identification after controlled low‐dose application
Authors: Binz Tina M. , Williner Elena , Strajhar Petra , Dolder Patrick C. , Liechti Matthias E. , Baumgartner Markus R. , Kraemer Thomas , Steuer Andrea E.
Published: April 2017

Amphetamine (AMP) is used as an illicit drug and also for the treatment of attention deficit hyperactivity disorder (ADHD). Respective drugs most often contain the enantiomer (S)‐AMP as active compound or (S)‐AMP is formed from the prodrug lisdexamfetamine (Elvanse®) whereas the illicit drug is usually traded as racemate ((R/S)‐AMP). A differentiation between the use of the medically prescribed drug and the abuse of illicit street amphetamine is of great importance, for example in retrospective consumption monitoring by hair analysis. A liquid chromatography–tandem mass spectrometry (LC–MS/MS) method for the chiral separation and quantitation of (S)‐ and (R)‐AMP in hair was developed. For this purpose, 20 mg hair was extracted and derivatized with N‐(2,4‐dinitro‐5‐fluorophenyl)‐L(S)‐valinamide L(S)‐(DNPV) to yield amphetamine diastereomers. Baseline separation of the resulting diastereomers was achieved on a high‐pressure liquid‐chromatography system (HPLC) coupled to a Sciex QTRAP® 5500 linear ion trap quadrupole mass spectrometer. The method was successfully validated. Analysis of hair samples from nine Elvanse® patients revealed only (S)‐AMP in eight cases; one subject showed both enantiomers indicating a (side‐) consumption of street amphetamine. The analysis of the 16 amphetamine users' samples showed only racemic amphetamine. Furthermore, it could be shown in a controlled study that (S)‐AMP can be detected after administration of even very low doses of lisdexamfetamine and dexamphetamine, which can be of interest in forensic toxicology and especially in drug‐facilitated crime (DFC). The method now enables the retrospective compliance‐monitoring of ADHD patients and the differentiation between medically prescribed intake of (S)‐amphetamine and abuse of illicit street amphetamine.
Differential effect of Incobotulinumtoxin A on pain, neurogenic flare and hyperalgesia in human surrogate models of neurogenic pain
Authors: Diener S.A. , Breimhorst M. , Vogt Th. , Krämer H.H. , Drummond P.D. , Geber C. , Birklein F.
Published: April 2017

Background

The effectiveness of Botulinum‐neurotoxin A (BoNT/A) to treat pain in human pain models is very divergent. This study was conducted to clarify if the pain models or the route of BoNT/A application might be responsible for these divergent findings.

Methods

Sixteen healthy subjects (8 males, mean age 27 ± 5 years) were included in a first set of experiments consisting of three visits: (1) Visit: Quantitative sensory testing (QST) was performed before and after intradermal capsaicin injection (CAPS, 15 μg) on one thigh and electrical current stimulation (ES, 1 Hz) on the contralateral thigh. During stimulation pain and the neurogenic flare response (laser‐Doppler imaging) were assessed. (2) Four weeks later, BoNT/A (Xeomin®, 25 MU) was injected intracutaneously on both sides. (3) Seven days later, the area of BoNT/A application was determined by the iodine‐starch staining and the procedure of the (1) visit was exactly repeated. In consequence of these results, 8 healthy subjects (4 males, mean age 26 ± 3 years) were included into a second set of experiments. The experimental setting was exactly the same with the exception that stimulation frequency of ES was increased to 4 Hz and BoNT/A was injected subcutaneously into the thigh, which was stimulated by capsaicin.

Results

BoNT/A reduced the 1 Hz ES flare size (p < 0.001) and pain ratings (p < 0.01), but had no effect on 4 Hz ES and capsaicin‐induced pain, hyperalgesia, or flare size, regardless of the depth of BoNT/A injection (i.c./s.c). Moreover, i.c. BoNT/A injection significantly increased warm detection and heat pain thresholds in naive skin (WDT, Δ 2.2 °C, p < 0.001; HPT Δ 1.8 °C, p < 0.005).

Conclusion

BoNT/A has a moderate inhibitory effect on peptidergic and thermal C‐fibers in healthy human skin.

Significance

The study demonstrates that BoNT/A (Incobotulinumtoxin A) has differential effects in human pain models: It reduces the neurogenic flare and had a moderate analgesic effects in low frequency but not high frequency current stimulation of cutaneous afferent fibers at C‐fiber strength; BoNT/A had no effect in capsaicin‐induced (CAPS) neurogenic flare or pain, or on hyperalgesia to mechanical or heat stimuli in both pain models. Intracutaneous BoNT/A increases warm and heat pain thresholds on naïve skin.
Treating low back pain with combined cerebral and peripheral electrical stimulation: A randomized, double‐blind, factorial clinical trial
Authors: Hazime F.A. , Baptista A.F. , de Freitas D.G. , Monteiro R.L. , Maretto R.L. , Hasue R.H. , João S.M.A.
Published: April 2017

Background

Recent evidence suggests that chronic low back pain is associated with plastic changes in the brain that can be modified by neuromodulation strategies. This study investigated the efficacy of transcranial direct current stimulation (tDCS) combined simultaneously with peripheral electrical stimulation (PES) for pain relief, disability and global perception in patients with chronic low back pain (CLBP).

Methods

Ninety‐two patients with CLBP were randomized to receive 12 sessions on nonconsecutive days of anodal tDCS (primary motor cortex, M1), 100 Hz sensory PES (lumbar spine), tDCS + PES or sham tDCS + PES. Pain intensity (11‐point numerical rating scale), disability and global perception were applied before treatment and four weeks, three months and six months post randomization.

Results

A two points reduction was achieved only by the tDCS + PES (mean reduction [MR] = −2.6, CI95% = −4.4 to −0.9) and PES alone (MR = −2.2, CI95% = −3.9 to −0.4) compared with the sham group, but not of tDCS alone (MR = −1.7, CI95% = −3.4 to −0.0). In addition to maintaining the analgesic effect for up to three months, tDCS + PES had a higher proportion of respondents in different cutoff points. Global perception was improved at four weeks and maintained three months after treatment only with tDCS + PES. None of the treatments improved disability and the affective aspect of pain consistently with pain reduction.

Conclusion

The results suggest that tDCS + PES and PES alone are effective in relieving CLBP in the short term. However, only tDCS + PES induced a long‐lasting analgesic effect. tDCS alone showed no clinical meaningful pain relief.

Significance

Transcranial direct current stimulation combined simultaneously with PES leads to a significant and clinical pain relief that can last up to three months in chronic low back pain patients.

For this article, a commentary is available at the Wiley Online Library
Engaging with diversity: Framing multiculturalism as a learning opportunity reduces prejudice among high White American identifiers
Authors: Rios Kimberly , Wynn Ashley N.
Published: April 2017

Multiculturalism (i.e., acknowledgment and appreciation of diversity), despite its positive consequences, is often met with resistance among majority group members, particularly those whose race/ethnicity is central to their self‐concept. Building upon findings that multiculturalism lowers White Americans' prejudice when presented as an abstract relative to concrete concept, we tested whether and when even concrete forms of multiculturalism can improve intergroup attitudes. Across two experiments, highly identified White Americans exhibited less racial prejudice when induced to view multiculturalism as a concrete learning opportunity than as a concrete set of policies (Study 1) or a concrete ideology more generally (Study 2). This effect was mediated by high identifiers' increased perceptions that diversity benefits themselves and society as a whole. Implications for prejudice reduction and fostering majority group members' active involvement in diversity‐relevant issues, as well as the applicability of our studies to other cultural contexts, are discussed.
Developing new perspectives on the energy trilemma
Authors: Carrick Alexandra
Published: April 2017

The energy group of SCI (Society of Chemical Industry) was host for an event on 28th March 2017 at SCI Headquarters in London (UK) with a meeting on the important topic of the energy trilemma (sustainable, affordable and secure supply of energy). Alexandra Carrick gives an overview of the event.
Toxicity of silver nanoparticles to Arabidopsis: Inhibition of root gravitropism by interfering with auxin pathway
Authors: Sun Juzhi , Wang Likai , Li Shuang , Yin Liyan , Huang Jin , Chen Chunli
Published: April 2017

Impacts of polyvinylpyrrolidine-coated silver nanoparticles (AgNPs) on root gravitropism in Arabidopsis thaliana were investigated at the physiological, cellular, and molecular levels. Our results showed that AgNPs were taken up by the root and primarily localized at the cell wall and intercellular spaces. Root gravitropism was inhibited by exposure to AgNPs, and the inhibition in root gravitropism caused by exposure to AgNPs exhibited a dose–response relationship. Auxin accumulation was reduced in the root tips because of exposure to AgNPs. However, increased indole-3-acetic acid level could not rescue the inhibition of root gravitropism. Real-time polymerase chain reaction showed significant downregulation of expression of auxin receptor–related genes, which is the TIR1/AFB family of F-box proteins including AFB1, AFB2, AFB3, AFB5, and TIR1. Therefore, the present study suggests that AgNPs have toxicity to the model plant A. thaliana as shown by inhibition of root gravitropism along with a reduction in auxin accumulation and expression of auxin receptors. Environ Toxicol Chem 2017;36:2773–2780. © 2017 SETAC