bluuebunny/crossref_metadata_2025 huggingface dataset:
A teaching approach from the exhaustive search method to the Needleman–Wunsch algorithm
Authors: Xu Zhongneng , Yang Yayun , Huang Beibei
Published: October 2016

The Needleman–Wunsch algorithm has become one of the core algorithms in bioinformatics; however, this programming requires more suitable explanations for students with different major backgrounds. In supposing sample sequences and using a simple store system, the connection between the exhaustive search method and the Needleman–Wunsch algorithm was analyzed to more thoroughly explain this algorithm. The present study could benefit the teaching and learning of the Needleman–Wunsch algorithm. © 2016 by The International Union of Biochemistry and Molecular Biology, 45(3):194–204, 2017.
PEEK tube‐based online solid‐phase microextraction–high‐performance liquid chromatography for the determination of yohimbine in rat plasma and its application in pharmacokinetics study
Authors: Xiang Xiaowei , Shang Bing , Wang Xiaozheng , Chen Qinhua
Published: October 2016

Yohimbine is a novel compound for the treatment of erectile dysfunction derived from natural products, and pharmacokinetic study is important for its further development as a new medicine. In this work, we developed a novel PEEK tube‐based solid‐phase microextraction (SPME)–HPLC method for analysis of yohimbine in plasma and further for pharmacokinetic study. Poly (AA‐EGDMA) was synthesized inside a PEEK tube as the sorbent for microextraction of yohimbine, and parameters that could influence extraction efficiency were systematically investigated. Under optimum conditions, the PEEK tube‐based SPME method exhibits excellent enrichment efficiency towards yohimbine. By using berberine as internal standard, an online SPME‐HPLC method was developed for analysis of yohimbine in human plasma sample. The method has wide linear range (2–1000 ng/mL) with an R2 of 0.9962; the limit of detection was determined and was as low as 0.1 ng/mL using UV detection. Finally, a pharmacokinetic study of yohimbine was carried out by the online SPME‐HPLC method and the results have been compared with those of reported methods.
Chemical identification and quality evaluation of Lycopus lucidus Turcz by UHPLC‐Q‐TOF‐MS and HPLC‐MS/MS and hierarchical clustering analysis
Authors: Ren Qiang , Ding Lin , Sun Shan‐shan , Wang Hui‐yun , Qu Liang
Published: October 2016

Lycopus lucidus Turcz has been used as a traditional phytomedicine for menstrual disorder, amenorrhea, menstrual cramps, inflammation and cardiovascular diseases. However, there is not enough information about identification and quantification for the chemical constituents of L. lucidus Turcz. In this work, a simple, rapid and sensitive UHPLC‐Q‐TOF‐MS method was developed for characterization and identification of the phytochemical compositions in L. lucidus Turcz in negative ion mode. A total of 37 compounds, including 15 phenolic acids, 12 flavonoids, three triterpenoids and seven organic acids were tentatively characterized and identified by means of the retention time, accurate mass and characteristic fragment ions. Thirteen compounds were reported for the first time in L. lucidus Turcz. Among of them, 11 compounds were further quantified by multiple reactions monitoring. The results showed good performance with respect to linearity (r > 0.9959), repeatability (RSD < 2.6%), intra‐ and inter‐day precision (RSD < 3.2%), recovery (93.1–104.9%), and lower limit of quantification (5–50 ng/mL). Subsequently, the results were analyzed and classified by hierarchical cluster analysis. The research could be applied for identification and quality evaluation for L. lucidus Turcz.
Accumulation of methylglyoxal and d‐lactate in Pb‐induced nephrotoxicity in rats
Authors: Huang Yu‐Shen , Li Yi‐Chieh , Tsai Pei‐Yun , Lin Chia‐En , Chen Chien‐Ming , Chen Shih‐Ming , Lee Jen‐Ai
Published: October 2016

Lead (Pb) is an environmental pollutant associated with several diseases, such as nephrotoxicity. Methylglyoxal (MG) is a reactive dicarbonyl compound formed during glycolysis and reported to increase in kidney damage. Metformin is used as an MG scavenger in the clinic. In this study, we investigated the mechanism of Pb‐induced renal injury and the effect of metformin on Pb‐induced nephrotoxicity. Eighteen Wistar rats were randomly divided into three groups: control, Pb, and Pb + metformin groups. Pb (250 ppm) was administered in drinking water, and 50 mg/kg of metformin was co‐administered orally. After 28 days, the levels of MG and its metabolite d‐lactate in urine, serum and renal tissues were examined. The elevation of renal MG (56.86 ± 17.47 vs 36.40 ± 5.69, p < 0.01) and urinary d‐lactate (0.68 ± 0.28 vs 0.32 ± 0.13, p < 0.01) was observed in Pb‐exposed rats compared with those in control rats. After co‐treatment with metformin, these phenomena were attenuated. In the present study, it was demonstrated for the first time that urinary d‐lactate might serve as the candidate marker for Pb‐induced nephrotoxicity in the clinic, and metformin might be a new therapeutic candidate for Pb poisoning.
Different mechanosensory stimulations of the lower back elicit specific changes in hemodynamics and oxygenation in cortical sensorimotor areas—AfNIRSstudy
Authors: Vrana Andrea , Meier Michael L. , Hotz‐Boendermaker Sabina , Humphreys Barry K. , Scholkmann Felix
Published: October 2016

Background and Objectives

This study aimed at investigating the feasibility of functional near‐infrared spectroscopy (fNIRS) to measure changes in cerebral hemodynamics and oxygenation evoked by painful and nonpainful mechanosensory stimulation on the lower back. The main objectives were to investigate whether cortical activity can be (1) detected using functionalfNIRS, and (2) if it is possible to distinguish between painful and nonpainful pressure as well as a tactile brushing stimulus based on relative changes in oxy‐ and deoxyhemoglobin ([O2Hb] and [HHb]).

Methods

Twenty right‐handed subjects (33.5 ± 10.7 years; range 20–61 years; 8 women) participated in the study. Painful and nonpainful pressure stimulation was exerted with a thumb grip perpendicularly to thespinous processof the lumbar spine. Tactile stimulation was realized by a one‐finger brushing. The supplementary motor area (SMA) and primary somatosensory cortex (S1) were measured bilaterally using a multichannel continuous‐wavefNIRSimaging system.

Results

Characteristic relative changes in [O2Hb] in theSMAand S1 after both pressure stimulations (corrected for multiple comparison) were observed. [HHb] showed only much weaker changes (uncorrected). The brushing stimulus did not reveal any significant changes in [O2Hb] or [HHb].

Conclusion

The results indicate thatfNIRSis sensitive enough to detect varying hemodynamic responses to different types of mechanosensory stimulation. The acquired data will serve as a foundation for further investigations in patients with chronic lower back pain. The future aim is to disentangle possible maladaptive neuroplastic changes in sensorimotor areas during painful and nonpainful lower back stimulations based onfNIRSneuroimaging.
Assessment of feigned cognitive impairment in severe traumatic brain injury patients with the Forced‐choice Graphics Memory Test
Authors: Liu Zilong , Dong Juan , Zhao Xiaohong , Chen Xiaorui , Lippa Sara M. , Caroselli Jerome S. , Fang Xiang
Published: October 2016

Introduction

The Forced‐choice Graphics Memory Test (FGMT) is a newly developed measure to assess feigned cognitive impairment. This study investigated the ability and reliability of FGMT for identification of malingering in patients with traumatic brain injury (TBI).

Methods

The FGMT was administered to 40 healthy volunteers instructed to respond validly (Healthy Control, H‐C), 40 healthy volunteers instructed to feign cognitive impairment (Healthy Malingering, H‐M), 40 severe TBI patients who responded validly (TBI control, TBI‐C), and 30 severe TBI patients who evidenced invalid performance (TBI malingering, TBI‐M).

Results

Both malingering groups (H‐M and TBI‐M) performed much more poorly than the nonmalingering groups (H‐C and TBI‐C). The FGMT overall total score, score on easy items, and score on hard items differed significantly across the four groups. The total score showed the highest classification accuracy in differentiating malingering from nonmalingering. A cutoff of less than 18 (total items) successfully identified 95% of TBI‐C and 93.3% of TBI‐M participants. The FGMT also demonstrated high test–retest reliability and internal consistency. FGMT scores were not affected by TBI patients' education, gender, age, or intelligence.

Conclusion

Our results suggest that the FGMT can be used as a fast and reliable tool for identification of feigned cognitive impairment in patients with TBI.
Hyperbaric oxygen therapy sensitizes nimustine treatment for glioma in mice
Authors: Lu Zhaohui , Ma Jiawei , Liu Bing , Dai Chungang , Xie Tao , Ma Xiaoyu , Li Ming , Dong Jun , Lan Qing , Huang Qiang
Published: October 2016

Nimustine (ACNU) has antitumor activities in patients with malignant glioma. Hyperbaric oxygen (HBO) may enhance the efficacy of certain therapies that are hampered by the hypoxic microenvironment. We examined the combined effects of ACNU and HBO in a GFP transgenic nude mice bearing human glioma model. Mice inoculated with human glioma cells SU3 were randomly divided into the four groups: (A) the control group, (B) the HBOT (HBO therapy) group, (C) the ACNU group, and (D) the HBOT+ACNU group. Tumor size was measured at the indicated time intervals with a caliper; mice were sacrificed 28 days after treatment, and immunohistochemistry staining and western blot analysis were carried out. By the end of the trial, the tumor weights of groups A, B, C, and D were (P < 0.05), 6.03 ± 1.47, 4.13 ± 1.82 (P < 0.05), 2.39 ± 0.25 (P < 0.05), and 1.43 ± 0.38 (P < 0.01), respectively. The expressions of TNF‐α, MMP9, HIF‐α, VEGF, NF‐κB, and IL‐1β were associated with the infiltration of inflammatory cells and the inhibition rate of tumor cells. Hyperbaric oxygen therapy (HBOT) could inhibit glioma cell proliferation and inflammatory cell infiltration, and exert a sensitizing effect on ACNU therapy partially through enhancing oxygen pressure (PO2) in tumor tissues and lower expression levels of HIF‐1α, TNF‐α, IL‐1β, VEGF, MMP9, and NF‐κB.
Pharmacologic activity and pharmacokinetics of metabolites of regorafenib in preclinical models
Authors: Zopf Dieter , Fichtner Iduna , Bhargava Ajay , Steinke Wolfram , Thierauch Karl‐Heinz , Diefenbach Konstanze , Wilhelm Scott , Hafner Frank‐Thorsten , Gerisch Michael
Published: October 2016

Regorafenib is an orally administered inhibitor of protein kinases involved in tumor angiogenesis, oncogenesis, and maintenance of the tumor microenvironment. Phase III studies showed that regorafenib has efficacy in patients with advanced gastrointestinal stromal tumors or treatment‐refractory metastatic colorectal cancer. In clinical studies, steady‐state exposure to the M‐2 and M‐5 metabolites of regorafenib was similar to that of the parent drug; however, the contribution of these metabolites to the overall observed clinical activity of regorafenib cannot be investigated in clinical trials. Therefore, we assessed the pharmacokinetics and pharmacodynamics of regorafenib, M‐2, and M‐5 in vitro and in murine xenograft models. M‐2 and M‐5 showed similar kinase inhibition profiles and comparable potency to regorafenib in a competitive binding assay. Inhibition of key target kinases by all three compounds was confirmed in cell‐based assays. In murine xenograft models, oral regorafenib, M‐2, and M‐5 significantly inhibited tumor growth versus controls. Total peak plasma drug concentrations and exposure to M‐2 and M‐5 in mice after repeated oral dosing with regorafenib 10 mg/kg/day were comparable to those in humans. In vitro studies showed high binding of regorafenib, M‐2, and M‐5 to plasma proteins, with unbound fractions of ~0.6%, ~0.9%, and ~0.4%, respectively, in murine plasma and ~0.5%, ~0.2%, and ~0.05%, respectively, in human plasma. Estimated free plasma concentrations of regorafenib and M‐2, but not M‐5, exceeded the IC50 at human and murine VEGFR2, suggesting that regorafenib and M‐2 are the primary contributors to the pharmacologic activity of regorafenib in vivo.
Terpenoids and More Polar Compounds from the Male Cones of Wollemia nobilis
Authors: Venditti Alessandro , Frezza Claudio , Sciubba Fabio , Foddai Sebastiano , Serafini Mauro , Bianco Armandodoriano
Published: October 2016

The analysis of metabolites contained in the male cones of Wollemia nobilis was investigated for the first time in this study. Several diterpenoids of chemosystematic relevance were recognized for the first time from the genus and/or from the Araucariaceae family, namely isocupressic acid (1), acetyl‐isocupressic acid (2), methyl (E)‐communate (3) and sandaracopimaric acid (4). All these terpenoids are also endowed with interesting biological activities and may play a primary role in the self defence toward herbivores. The presence of a new norlabdane (norlabda‐8(16)‐12‐dien‐14,17‐diol) trivially named as wollemol (5) was also recognized. Norditerpenes are scarcely distributed in Plant Kingdom and in particular in Gymnosperms and this aspect was discussed. The structure of 5 was determined by extensive NMR analysis employing mono‐ and bidimensional experiments. The 7‐4‴‐dimethoxyagathisflavone (6), a biflavonoid already recognized in Araucariaceae and W. nobilis, was also isolated from male cones together with shikimic acid (7), a biogenetic precursor of polyphenolic compounds, besides carbohydrates such as glucose (8) and saccharose (9), and arginine (10) a quite common amino acid.
Substitution of Two Active‐Site Residues Alters C9‐Hydroxylation in a Class II Diterpene Synthase
Authors: Mafu Sibongile , Fischer Emil , Addison J. Bennett , Riberio Barbosana Isabel , Zerbe Philipp
Published: October 2016

Diterpenes form a vast and diverse class of natural products of both ecological and economic importance. Class II diterpene synthase (diTPS) enzymes control the committed biosynthetic reactions underlying diterpene chemical diversity. Homology modelling with site‐directed mutagenesis identified two active‐site residues in the horehound (Marrubium vulgare) class II diTPS peregrinol diphosphate synthase (MvCPS1); residue substitutions abolished the unique MvCPS1‐catalysed water‐capture reaction at C9 and redirected enzyme activity toward formation of an alternative product, halima‐5(10),13‐dienyl diphosphate. These findings contributed new insight into the steric interactions that govern diTPS‐catalysed regiospecific oxygenation reactions and highlight the feasibility of diTPS engineering to provide a broader spectrum of bioactive diterpene natural products.
Incidentally discovered low‐grade appendiceal mucinous neoplasm: a precursor to pseudomyxoma peritonei
Authors: Padmanaban Vennila , Morano William F. , Gleeson Elizabeth , Aggarwal Anshu , Mapow Beth L. , Stein David E. , Bowne Wilbur B.
Published: October 2016

Key Clinical Message

Appendiceal mucoceles (AMs) infrequently arise from an underlying malignancy. Treatment has progressed toward a less aggressive approach over time; they can be managed by appendectomy‐only unless pathology reveals malignancy. The ultimate goal of management is to prevent AM rupture, avoiding the syndrome of pseudomyxoma peritonei.
Visible‐Light‐Controlled Oxidation of Glucose using Titania‐Supported Silver Photocatalysts
Authors: Da Vià Luigi , Recchi Carlo , Davies Thomas E. , Greeves Nicholas , Lopez‐Sanchez Jose A.
Published: October 2016

The visible‐light‐mediated photo‐catalytic selective valorisation of glucose using TiO2‐supported Ag nanoparticles is shown for the first time. The optimisation of the catalyst composition, substrate‐to‐catalyst ratio and reaction medium proved that a near total suppression of the mineralisation pathway could be achieved with a selectivity to partial oxidation products and small‐chain monosaccharides as high as 98 %. The primary products were determined to be gluconic acid, arabinose, erythrose, glyceraldehyde and formic acid. Under UVA light, the selectivity to organics decreases because of the production of CO2 from mineralisation. A reaction mechanism is proposed based on an α‐scission process combined with the Ruff degradation reaction, which explains the presence of the oxidation products, the smaller carbohydrates and formic acid. X‐ray photoelectron spectroscopy, UV/Vis spectroscopy and microscopy studies showed the presence of plasmonic 4 nm particles of silver that were oxidised to silver oxide over the course of the reaction, and recycling studies revealed that this was not detrimental to activity.
Mechanisms for the Reverse Skeletal Isomerization of n‐Butenes to Isobutene over Zeolite Catalysts
Authors: Jo Donghui , Hong Suk Bong
Published: October 2016

The use of 13C‐enriched isobutene in the reverse skeletal isomerization of 1‐butene over zeolite catalysts allowed us to corroborate that the mechanisms for the reverse reaction were essentially the same as those for the forward reaction, regardless of the structure type of the catalyst employed.
Complementary Hydrogen Bonding Modulates Electronic Properties and Controls Self‐Assembly of Donor/Acceptor Semiconductors
Authors: Black H. T. , Yee N. , Zems Y. , Perepichka D. F.
Published: October 2016

A comprehensive investigation of the complementary H‐bonding‐mediated self‐assembly between dipyrrolo[2,3‐b:3′,2′‐e]pyridine (P2P) electron donors and naphthalenediimide/perylenediimide (NDI/PDI) acceptors is reported. The synthesis of parent P2P and several aryl‐substituted derivatives is described, along with their optical, redox, and single‐crystal packing characteristics. The dual functionality of heteroatoms in the P2P/NDI(PDI) assembly, which act as proton donors/acceptors and also contribute to π‐conjugation, leads to H‐bonding‐induced perturbation of electronic levels. Concentration‐dependent NMR and UV/Vis spectroscopic studies revealed a cooperative effect of H‐bonding and π–π stacking interactions. This H‐bonding‐mediated co‐assembly of donor (D) and acceptor (A) components leads to a new charge‐transfer (CT) absorption that can be controlled throughout the visible range. The electronic interactions between D and A were further investigated by time‐dependent DFT, which provided insights into the nature of the CT transition. Electropolymerization of difuryl‐P2P afforded the first conjugated polymer incorporating H‐bonding recognition units in its main chain.
One‐Step Synthesis of Siloxanes from the Direct Process Disilane Residue
Authors: Neumeyer Felix , Auner Norbert
Published: October 2016

The well‐established Müller–Rochow Direct Process for the chloromethylsilane synthesis produces a disilane residue (DPR) consisting of compounds MenSi2Cl6−n (n=1–6) in thousands of tons annually. Technologically, much effort is made to retransfer the disilanes into monosilanes suitable for introduction into the siloxane production chain for increase in economic value. Here, we report on a single step reaction to directly form cyclic, linear, and cage‐like siloxanes upon treatment of the DPR with a 5 m HCl in Et2O solution at about 120 °C for 60 h. For simplification of the Si−Si bond cleavage and aiming on product selectivity the grade of methylation at the silicon backbone is increased to n≥4. Moreover, the HCl/Et2O reagent is also suitable to produce siloxanes from the corresponding monosilanes under comparable conditions.
Highly Selective Halide Receptors Based on Chalcogen, Pnicogen, and Tetrel Bonds
Authors: Scheiner Steve
Published: October 2016

The interactions of halides with a number of bipodal receptors were examined by quantum chemical methods. The receptors were based on a dithieno thiophene framework in which two S atoms can engage in a pair of chalcogen bonds with a halide. These two S atoms were replaced by P and As atoms to compare chalcogen with pnicogen bonding, and by Ge which engages in tetrel bonds with the receptor. Zero, one, and two O atoms were added to the thiophene S atom which is not directly involved in the interaction with the halides. Fluoride bound the most strongly, followed by Cl−, Br−, and I−, respectively. Replacing S by the pnicogen bonds of P strengthened the binding, as did moving down to As in the third row of the periodic table. A further large increment is associated with the switch to the tetrel bonds of Ge. Even though the thiophene S atom is remote from the binding site, each additional O atom added to it raises the binding energy, which can be quite large, as much as 63 kcal mol−1for the Ge⋅⋅⋅F−interaction. The receptors have a pronounced selectivity for F−over the other halides, as high as 27 orders of magnitude. The data suggest that incorporation of tetrel atoms may lead to new and more powerful halide receptors.
Urchinlike ZnS Microspheres Decorated with Nitrogen‐Doped Carbon: A Superior Anode Material for Lithium and Sodium Storage
Authors: Li Junming , Fu Yun , Shi Xiaodong , Xu Zhenming , Zhang Zhian
Published: October 2016

Urchinlike ZnS microspheres decorated with nitrogen‐doped carbon (ZnS@NC) were fabricated by a facile two‐step method in which urchinlike ZnS microspheres were coated with polydopamine and then calcined in an inert gas atmosphere. When employed as the anode material for lithium‐ion batteries and sodium ion batteries, ZnS@NC exhibits a reversible lithium‐storage capacity of 690 mAh g−1 after 100 cycles at 100 mA g−1 and a reversible sodium‐storage capacity of 460 mAh g−1 after 80 cycles at 200 mA g−1.The ZnS@NC electrode shows a high reversible lithium‐storage capacity of 520 mAh g−1 after 200 cycles and a high reversible sodium‐storage capacity of 380 mAh g−1 after 100 cycles even at a current density of 1 A g−1. The superior electrochemical performance could be ascribed to structural merits of the urchinlike ZnS microspheres and synergistic effects between ZnS and polydopamine‐derived nitrogen‐doped carbon. The lithium‐ and sodium‐storage capacities of urchinlike ZnS@NC microspheres are in the top rank in comparison with those reported in other studies.
Real‐time resource efficiency indicators for monitoring and optimization of batch‐processing plants
Authors: Kalliski Marc , Engell Sebastian
Published: October 2016

This paper presents a framework for the definition and calculation of Real‐Time Resource Efficiency Indicators (REIs) for batch processes. The indicators are based on the allocation of resource and energy inputs to the individual batches and recipe operations as the basis for a comprehensive analysis and representation of the overall resource efficiency.

The framework structures REIs into three categories describing (1) the efficiency of key unit operations, (2) the efficiency of the production of an individual batch, and (3) the overall system performance. Indicators from the last two categories can be propagated along the production process and can be aggregated vertically from units to sections and complete production sites. Chemical production processes often involve batch blending and splitting, separation processes, and continuous production steps. The framework allocates the contributions of the continuous steps to the batches and considers merging and splitting of batches. Thus, it yields a reliable and commensurate set of indicators that can be used to monitor and to optimize the resource efficiency of batch processing plants in real‐time in order to support the decision making process in daily operations. To demonstrate the approach, it is applied to a sugar production process that integrates batch and continuously operated unit operations.
Allelopathic Influence of Sesame and Green Gram Intercrops on Cotton in a Replacement Series
Authors: Shah Adnan Noor , Iqbal Javaid , Fahad Shah , Tanveer Mohsin , Yang Guozheng , Khan Ejaz Ahmad , Shahzad Babar , Yousaf Muhammad , Hassan Waseem , Ullah Abid , Bukhari Muhammad Adnan , Salah Akram , Saud Shah , Alharby Hesham
Published: October 2016

Using a mixed culture replacement method, different plant species are planted with different densities per unit area. The benefits of using this method are evident; however, phytotoxic/competitive effects of these different plant species on each other are rarely studied, especially for cotton. Allelopathy is a biological phenomenon that can affect many aspects of plant ecology. A pot experiment was conducted to determine the individual and/or interactive effects of cotton, sesame, and green gram on each other. Sesame, green gram, and cotton were sown in a replacement series in three different combinations: Sesame–cotton (3–0, 2–1, 1–2, 0–3); sesame–green gram (3–0, 2–1, 1–2, 0–3); and cotton–green gram (3–0, 2–1, 1–2, 0–3). The experiment was conducted using a completely randomized design with four replications; results revealed that inclusion of a legume crop (i.e., green gram) significantly improved cotton shoot and root growth and yield, but sowing of sesame with cotton considerably decreased cotton plant performance as compared to green gram. Similarly, sesame plant height was improved by increasing the number of cotton and green gram plants per pot. The effects of sesame and cotton were deleterious for green gram. It was concluded that high‐stature crops (such as the main crop) can be grown with short‐stature leguminous crops as the companion crop.
Multi‐institutional experience of stereotactic body radiotherapy for large (≥5 centimeters) non–small cell lung tumors
Authors: Verma Vivek , Shostrom Valerie K. , Kumar Sameera S. , Zhen Weining , Hallemeier Christopher L. , Braunstein Steve E. , Holland John , Harkenrider Matthew M. , S. Iskhanian Adrian , Neboori Hanmanth J. , Jabbour Salma K. , Attia Albert , Lee Percy , Alite Fiori , Walker Joshua M. , Stahl John M. , Wang Kyle , Bingham Brian S. , Hadzitheodorou Christina , Decker Roy H. , McGarry Ronald C. , Simone Charles B.
Published: October 2016

BACKGROUND

Stereotactic body radiotherapy (SBRT) is the standard of care for patients with nonoperative, early‐stage non–small cell lung cancer (NSCLC) measuring < 5 cm, but its use among patients with tumors measuring ≥5 cm is considerably less defined, with the existing literature limited to small, single‐institution reports. The current multi‐institutional study reported outcomes evaluating the largest such population reported to date.

METHODS

Clinical/treatment characteristics, outcomes, toxicities, and patterns of failure were assessed in patients with primary NSCLC measuring ≥5 cm without evidence of distant/lymph node metastasis who underwent SBRT using ≤5 fractions. Statistics included Kaplan‐Meier survival analyses and univariate/multivariate Cox proportional hazards models.

RESULTS

A total of 92 patients treated from 2004 through 2016 were analyzed from 12 institutions. The median follow‐up was 12 months (15 months in survivors). The median age and tumor size among the patients were 73 years (range, 50‐95 years) and 5.4 cm (range, 5.0‐7.5 cm), respectively. The median dose/fractionation was 50 Gray/5 fractions. The actuarial local control rates at 1 year and 2 years were 95.7% and 73.2%, respectively. The disease‐free survival rate was 72.1% and 53.5%, respectively, at 1 year and 2 years. The 1‐year and 2‐year disease‐specific survival rates were 95.5% and 78.6%, respectively. The median, 1‐year, and 2‐year overall survival rates were 21.4 months, 76.2%, and 46.4%, respectively. On multivariate analysis, lung cancer history and pre‐SBRT positron emission tomography maximum standardized uptake value were found to be associated with overall survival. Posttreatment failures were most commonly distant (33% of all disease recurrences), followed by local (26%) and those occurring elsewhere in the lung (23%). Three patients had isolated local failures. Grade 3 to 4 toxicities included 1 case (1%) and 4 cases (4%) of grade 3 dermatitis and radiation pneumonitis, respectively (toxicities were graded according to the Common Terminology Criteria for Adverse Events [version 4.0]). Grades 2 to 5 radiation pneumonitis occurred in 11% of patients. One patient with a tumor measuring 7.5 cm and a smoking history of 150 pack‐years died of radiation pneumonitis.

CONCLUSIONS

The results of the current study, which is the largest study of patients with NSCLC measuring ≥5 cm reported to date, indicate that SBRT is a safe and efficacious option. Cancer 2017;123:688–696. © 2016 American Cancer Society.
Carbon Nanodots with Sub‐Nanosecond Spontaneous Emission Lifetime
Authors: Liu Cheng‐Wei , Lin Tzu‐Neng , Chang Li‐Yun , Jiang Zh‐Cheng , Shen Ji‐Lin , Chen Po‐Wen , Wang Jyh‐Shyang , Yuan Chi‐Tsu
Published: October 2016

Compared with most mature cadmium‐containing quantum dots (QDs), carbon nanodots (CNDs) are a new class of colloidal nanomaterials that exhibit unique photoluminescence (PL) properties while being nontoxic and easily manufactured using low‐cost precursor materials. However, solid‐state CNDs exhibit poor PL quantum yields (PL‐QYs) and inefficient radiative transition, which significantly hinders their practical use in optoelectronic devices. To address this issue, plasmonic nanoantennas consisting of Au nanorods (Au‐NRs) deposited on a flat Au film with inserted dielectric layers were used to enhance the spontaneous emission of solid‐state CNDs with broad spectral linewidth. Using steady‐state, time‐resolved, and spatial‐resolved PL measurements, we found that after coupling to plasmonic nanogaps (PNGs), the PL emission was significantly enhanced, accompanied by a PL lifetime shortening to the sub‐nanosecond range (≈140 ps). According to the experimental data, the radiative transition is strongly accelerated and can thus overcome the metal loss, leading to a large PL enhancement. Our demonstration can pave the way to the design of eco‐friendly nanoemitters with sub‐nanosecond PL lifetime for promising applications in light‐emitting devices.
An Integrative Bio‐Psycho‐Social Theory of Anorexia Nervosa
Authors: Munro Calum , Randell Louise , Lawrie Stephen M
Published: October 2016

The need for novel approaches to understanding and treating anorexia nervosa (AN) is well recognized. The aim of this paper is to describe an integrative bio‐psycho‐social theory of maintaining factors in AN.

We took a triangulation approach to develop a clinically relevant theory with face validity and internal consistency. We developed theoretical ideas from our clinical practice and reviewed theoretical ideas within the eating disorders and wider bio‐psycho‐social literature. The synthesis of these ideas and concepts into a clinically meaningful framework is described here.

We suggest eight key factors central to understanding the maintenance and treatment resistance of anorexia nervosa: genetic or experiential predisposing factors; dysfunctional feelings processing and regulation systems; excessive vulnerable feelings; ‘feared self’ beliefs; starvation as a maladaptive physiological feelings regulation mechanism; maladaptive psychological coping modes; maladaptive social behaviour; and unmet physical and psychological core needs. Each of these factors serves to maintain the disorder.

The concept of universal physical and psychological core needs can provide an underpinning integrative framework for working with this distinctly physical and psychological disorder. This framework could be used within any treatment model. We suggest that treatments which help address the profound lack of trust, emotional security and self‐acceptance in this patient group will in turn address unmet needs and improve well‐being. Copyright © 2016 John Wiley & Sons, Ltd.

Key Practitioner Message

The concept of unmet physical and psychological needs can be used as an underlying integrative framework for understanding and working with this patient group, alongside any treatment model.

A functional understanding of the neuro‐biological, physiological and psychological mechanisms involved in anorexia nervosa can help patients reduce self‐criticism and shame.

Fears about being or becoming fat, greedy, needy, selfish and unacceptable (‘Feared Self’) drive over‐compensatory self‐depriving behaviour (‘Anorexic Self’).

Psychological treatment for anorexia nervosa should emphasize a focus on feelings and fostering experiences of acceptance and trust.

Treatment for patients with anorexia nervosa needs to be longer than current clinical practice.
Electronic Coupling of Cobalt Nanoparticles to Nitrogen‐Doped Graphene for Oxygen Reduction and Evolution Reactions
Authors: Xu Chaohe , Lu Meihua , Yan Binggong , Zhan Yi , Balaya Palani , Lu Li , Lee Jim Yang
Published: October 2016

The rational design of nonprecious‐metal electrocatalysts with activities comparable to or greater than that of platinum is extremely valuable to the development of high energy density metal–air batteries. Herein, the two‐step preparation of a highly active oxygen electrocatalyst based on ultrasmall cobalt nanoparticles stabilized in a nitrogen‐doped graphene matrix is reported. The catalyst performs as well as the commercial Pt/C catalyst in the oxygen reduction reaction, and better than the Pt/C catalyst in the oxygen evolution reaction. This particular electrocatalyst could significantly lower the overpotentials of oxygen electrochemical reactions in aqueous lithium–air batteries to attain a round‐trip efficiency of about 79.0 % at a current density of 0.1 mA cm−2, thereby surpassing the performance of the commercial Pt/C catalyst. The good performance may be attributed to strong metal–support interactions, maximized by a high dispersion of ultrasmall cobalt nanocrystals in a nitrogen‐doped graphene matrix, which yields electrocatalytic properties greater than the sum of its parts.
Mode dynamics in fourth‐order LC oscillators
Authors: Buonomo Antonio , Lo Schiavo Alessandro
Published: October 2016

We present a complete analysis of single and concurrent modes in fourth‐order LC‐voltage‐controlled oscillators (VCOs), which are increasingly applied in dual‐band communication systems. We give a procedure based on the averaging method that simplifies the derivation of the abridged equations, which are derived without resorting to a change of co‐ordinates. The amplitudes of the oscillatory modes in steady state and in transient are found in explicit form. Conditions for the stability of the single and concurrent modes are derived, which apply to any active one‐port dual‐band LC‐VCO and allow one to predict the nonlinearities ensuring the occurrence of a stable concurrent mode. Numerical and experimental results show a good accuracy of the presented formulas. Copyright © 2016 John Wiley & Sons, Ltd.
Studies on the metabolism of the fentanyl‐derived designer drug butyrfentanyl in human in vitro liver preparations and authentic human samples using liquid chromatography‐high resolution mass spectrometry (LC‐HRMS)
Authors: Steuer Andrea E. , Williner Elena , Staeheli Sandra N. , Kraemer Thomas
Published: October 2016

Increasing numbers of new psychoactive substances (NPS) among them fentanyl derivatives has been reported by the European monitoring centre for drugs and drug addiction (EMCDDA). Butyrfentanyl is a new fentanyl derivative whose potency ratio was found to be seven compared to morphine and 0.13 compared to fentanyl. Several case reports on butyrfentanyl intoxications have been described. Little is known about its pharmacokinetic properties including its metabolism. However, knowledge of metabolism is essential for analytical detection in clinical and forensic toxicology. Therefore, in vitro and in vivo phase I and phase II metabolites of butyrfentanyl were elucidated combining liquid chromatography with a qTOF high resolution mass spectrometer. Human liver microsomes and recombinant cytochrome P450 enzymes (CYP) were used for in vitro assays. Authentic blood and urine samples from a fatal intoxication case were available for in vivo comparison. Butyrfentanyl was shown to undergo extensive metabolism. Six pathways could be postulated with hydroxylation and N‐dealkylation being the major ones in vitro. In vivo, hydroxylation of the butanamide side chain followed by subsequent oxidation to the carboxylic acid represented the major metabolic step in the authentic case. Initial screening experiments with the most relevant CYPs indicated that mainly CYP2D6 and 3A4 were involved in the primary metabolic steps. Altered CYP2D6 and CYP3A4 status might cause a different metabolite pattern, making the inclusion of metabolites of different pathways recommendable when applying targeted screening procedures in clinical and forensic toxicology. Copyright © 2016 John Wiley & Sons, Ltd.
Latitudinal variation in nematode diversity and ecological roles along the Chinese coast
Authors: Wu Jihua , Chen Huili , Zhang Youzheng
Published: October 2016

Aim

To test changes in the phylogenetic relatedness, niche breadth, and life‐history strategies of nematodes along a latitudinal gradient.

Location

Sixteen wetland locations along the Pacific coast of China, from 20°N to 40°N.

Methods

Linear regression was used to relate nematode phylogenetic relatedness (average taxonomic distinctness (AvTD) and average phylogenetic diversity [AvPD]), life‐history group (based on “c‐p” colonizer–persister group classification), and dietary specificity (based on guild classification of feeding selectivity) to latitude.

Results

Wetland nematode taxonomic diversity (richness and Shannon diversity indices) decreased with increasing latitude along the Chinese coast. Phylogenetic diversity indices (AvTDand AvPD) significantly increased with increasing latitude. This indicates that at lower latitudes, species within the nematode community were more closely related. With increasing latitude, the nematode relative richness and abundance decreased for selective deposit feeders but increased for nonselective deposit feeders. The proportion of general opportunists decreased with increasing latitude, but persisters showed the opposite trend. The annual temperature range and thepHof sediments were more important than vegetation type in structuring nematode communities.

Main conclusion

Nematode niche breadth was narrower at lower latitudes with respect to dietary specificity. Higher latitudes with a more variable climate favorroverKlife‐history strategists. Nematode communities at lower latitudes contained more closely related species.
Scaling up movements: from individual space use to population patterns
Authors: Allen Andrew M. , Månsson Johan , Sand Håkan , Malmsten Jonas , Ericsson Göran , Singh Navinder J.
Published: October 2016

Studying multiple individuals from multiple populations would add knowledge about the proportion of different movement strategies (migratory vs. resident) and how space use patterns vary within and across populations. This allows for effective conservation or management of partially migratory animal populations by identifying the appropriate size of management units and temporal interventions. However, this knowledge is often lacking as only a few individuals from a single population are tracked in space and time. To understand the drivers of intraspecific variation in movement patterns across a broad scale, we analyzed the multiannual space use of 307 moose (Alces alces), containing 544 single‐year trajectories, from 10 study areas that are spread over a 1500‐km latitudinal gradient. Using a novel approach, we quantified within‐ and among‐population variation in movement and space use patterns. We identified the movement strategy (migratory, sedentary, nomadic, or dispersal) of moose and computed annual and seasonal home ranges. Individuals demonstrated variable movement strategies from migration to year‐round residence. Summer home ranges were larger in northern study areas, whereas no geographical trends were detected among populations in winter home ranges. Individual‐level traits, such as sex and age, along with factors related to the landscape, such as land use and habitat, explained variation within populations, whereas climatic factors such as temperature and vegetative productivity explained variation among populations. Importantly, the variables that explained individual‐level variation in space use within populations were different for all our populations. We demonstrate the intricate interplay between individual life history and landscape scale variables and how they may determine the observed movement patterns and influence the scale of management.
An Eleven‐Step Synthesis of Galanthamine from Commercially Available Materials
Authors: Nugent Jeremy , Banwell Martin G.
Published: October 2016

Narwedine, an immediate precursor to the therapeutically valuable alkaloid (–)‐galanthamine, has been synthesised by engaging an iodinated isovanillin derivative in an intermolecular Mitsunobu reaction with a 2‐cyclohexen‐1‐ol derivative. The resulting aryl ether participated in an exceptionally efficient intramolecular Heck reaction to give a tetracyclic lactol after the hydrolysis of the primary cyclisation product. This last compound is an advanced intermediate associated with the Magnus synthesis of narwedine and could be elaborated to narwedine itself under reductive amination conditions. As a result, an eleven‐step synthesis of galanthamine has been established.
Direct β‐Selective Cross‐Coupling of Alkenyl Gold Complexes with Alkyl Electrophiles
Authors: Nguyen Julia , Duncan Nicole , Lalic Gojko
Published: October 2016

Alkenyl gold complexes are common intermediates in gold‐catalyzed transformations of allenes and alkynes, and numerous methods for their functionalization have been explored. Particularly valuable are cross‐coupling reactions, which result in the formation of a new C–C bond. Several strategies are known that enable α‐selective cross‐coupling of alkenyl gold complexes with aryl, allyl, or acyl coupling partners. We describe the direct β‐selective cross‐coupling of alkenyl gold complexes with simple alkyl electrophiles. We also describe the effects of the steric and electronic properties of alkenyl gold complexes on the selectivity of the cross‐coupling reaction.
Prescriptions of analgesics during complete disease trajectories in patients who are diagnosed with and die from cancer within the five‐year period 2005–2009
Authors: Fredheim O.M.S. , Brelin S. , Hjermstad M.J. , Loge J.H. , Aass N. , Johannesen T.B. , Skurtveit S.
Published: October 2016

Background

Even though validation studies of the WHO analgesic ladder have indicated that the simple approach of the analgesic ladder can provide adequate pain control in most patients, prevalence studies have documented a high prevalence of pain in cancer patients. Little is known about how analgesics are actually prescribed for cancer pain. The aim of the study was to study prescriptions of analgesics during the entire disease trajectory in patients dying from cancer within five years of diagnosis.

Methods

Complete national data from the Norwegian Cancer Registry, the Norwegian Prescription Database, the Cause of Death Registry and Statistics Norway were used to study prescriptions of analgesics in a complete study population of all patients dying from cancer within five years of diagnosis in Norway from 2005 to 2009.

Results

Of a total of 10,977 subjects who received prescriptions for analgesics between diagnosis and death, 56% started analgesic treatment at step I of the analgesic ladder, 29% started at step II and 14% started at step III. Of the patients starting at step I, 28% continued to step II, 37% bypassed step II and moved directly to step III whereas the remaining 35% remained at step I. Approximately 60% received one or more dispensed prescription of a step III analgesic during the disease trajectory, whereas nearly 20% remained at step I and 20% at step II respectively.

Conclusion

The study indicates that clinicians seem to individually tailor analgesic treatment instead of applying the stepwise approach in the WHO analgesic ladder.

Significance

Complete national data covering the complete disease trajectory in cancer patients dying within five years of diagnosis. The majority of patients do not receive treatment in concordance with the stepwise approach suggested by the WHO analgesic ladder.
Pain expectations in neuropathic pain: Is it best to be optimistic?
Authors: Bostick G.P. , Kamper S.J. , Haanstra T.M. , Dick B.D. , Stitt L.W. , Morley‐Forster P. , Clark A.J. , Lynch M.E. , Gordon A. , Nathan H. , Smyth C. , Ware M.A. , Toth C. , Moulin D.E.
Published: October 2016

Background

Pain expectancy may be an important variable that has been found to influence the effectiveness of treatments for pain. Much of the literature supports a self‐fulfilment perspective where expectations for pain relief predict the actual pain experienced. However, in conditions such as neuropathic pain (NeP) where pain relief is difficult to attain, expectations for pain relief could be unrealistic. The objective of this study was to investigate the relationship between realistic/unrealistic expectations and 6‐month, post‐treatment outcomes.

Methods

We performed a retrospective analysis of a large cohort of patients with NeP (n = 789) attending tertiary care centres to determine the association between unrealistic (both positive and negative) and realistic expectations with outcomes after multidisciplinary treatment. An expectation variable with three categories was calculated: realistic expectations were those whose expected reduction in pain was similar to the observed mean group reduction in pain, while optimistic and pessimistic expectations were those who over‐ or under‐estimated the expected response to treatment, respectively. The association between baseline realistic/unrealistic expectations and 6‐month pain‐related disability, catastrophizing and psychological distress was assessed.

Results

Univariable analyses suggested that realistic expectations were associated with lower levels of disability, catastrophizing and psychological distress, compared to unrealistic expectations. However, after adjustment for baseline symptom severity, multivariable analysis revealed that patients with optimistic expectations had lower levels of disability, than those with realistic expectations. Those with pessimistic expectations had higher levels of catastrophizing and psychological distress at follow‐up.

Conclusions

These findings are largely congruent with the self‐fulfilment perspective to expectations.

Significance

This study defined realistic pain expectations with patient data. Examining the relationship between expectations between pain and disability in a large cohort of patients with neuropathic pain.
Cogasification of Crude Glycerol and Black Liquor Blends: Char Morphology and Gasification Kinetics
Authors: Kirtania Kawnish , Häggström Gustav , Broström Markus , Umeki Kentaro , Furusjö Erik
Published: October 2016

In this study, we assessed the feasibility of black liquor/glycerol blends as a potential gasification feedstock. The char gasification reactivity and kinetics were studied at T=750, 800, 850, and 900 °C for 20 and 40 % blends of glycerol with black liquor. Three qualities of glycerol were used including two industrial‐grade crude glycerols. The gasification rates were similar for all blends; therefore, the alkali‐metal catalysis is also sufficient for the char blends (alkali/C atomic ratio between 0.45 and 0.55). The blends with the most impure glycerol (containing K) had the lowest activation energies (∼120 kJ mol−1) and reaction times for char gasification and, therefore, had fuel properties suitable for gasification. The char particles from different blends showed surface morphologies similar to those of black liquor chars with an even surface distribution of alkali elements. A loss of alkali (mainly K) from the fuel blends during pyrolysis indicated the necessity to perform gas‐phase studies of alkali release. Overall, these results encourage the use of glycerol as a potential gasification feedstock for catalytic‐gasification‐based biorefineries.