bluuebunny/crossref_metadata_2025 huggingface dataset:
Determinants of pro‐environmental behavior and environmentally conscious consumer behavior: An empirical investigation from emerging market
Authors: Kautish Pradeep , Sharma Rajesh
Published: July 2019

Given the due importance of environmentally conscious consumer behavior (ECCB) and willingness to be environmentally friendly (WEF), the aim of this paper is to study the relationships between the determinants of pro‐environmental behavior (e.g., perceived behavioral control, environmental knowledge, environmental concern, and perceived environmental consequences), with ECCB and WEF. The proposed theoretical model is grounded in marketing literature, extends the theory of planned behavior, and empirically tested in the Indian market. A survey with questionnaire was administered to gather data from 510 respondents from the state capital of the country. Structural equation modeling was used to test the hypotheses; the results confirm adequate support for the theory of planned behavior and proposed theoretical model. In addition, ECCB found to be significantly influenced by the consumers' environmental knowledge, and perceived environmental consequences, and environmental concern was significantly related to WEF. The study implies that green marketers should direct their marketing efforts towards integrating these four pro‐environmental behavior determinants in order to facilitate the ECCB and WEF for green products. For promoting the ECCB, green marketers should strengthen environmental knowledge and perceived environmental consequences to target consumers, and for augmenting the WEF, they should improve the environment concern among consumers. This study contributes to the mainstream literature by ascertaining the distinctive impact of the four noteworthy determinants of pro‐environmental behavior on ECCB and WEF in emerging markets.
Biogenic synthesis of silver nanoparticles using Brazilian propolis
Authors: Barbosa Valcilaine T. , Souza Joyelanne K. C. , Alvino Valter , Meneghetti Mario R. , Florez‐Rodriguez Pedro P. , Moreira Rui E. , Paulino Gustavo V. B. , Landell Melissa F. , Basílio‐Júnior Irinaldo D. , do Nascimento Ticiano G. , Grillo Luciano A. M. , Dornelas Camila B.
Published: July 2019

Biological methods have been used to synthesize silver nanoparticles through materials such as bacteria, fungi, plants, and propolis due to their reducing properties, stabilizer role and environmentally friendly characteristic. Considering the antimicrobial activity of propolis as well as the broad‐spectrum antibacterial effects of silver nanoparticles, this study aim to describe the use of Brazilian propolis to synthesize silver nanoparticles (AgNP‐P) and investigate its antimicrobial activity. The synthesis was optimized by factorial design, choosing the best conditions for smaller size particles. AgNP‐P demonstrated a maximum absorbance at 412 nm in ultraviolet‐visible spectra, which indicated a spherical format and its formation. Dynamic light scattering demonstrated a hydrodynamic size of 109 nm and polydispersity index less than 0.3, showing a good size distribution and stability. After its purification via centrifugation, microscopy analysis corroborates the format and showed the presence of propolis around silver nanoparticle. X‐ray diffraction peaks were attributed to the main planes of the metallic silver crystalline structure; meanwhile infrared spectroscopy demonstrated the main groups responsible for silver reduction, represented by ∼22% of AgNP‐P indicates by thermal analysis. Our product revealed an important antimicrobial activity indicating a synergism between propolis and silver nanoparticles as expected and promising to be an effective antimicrobial product to be used in infections.
Educational guidance process integrating opinion mining
Authors: Lazib Samia , Bouarab‐Dahmani Farida , Haddadi Lynda
Published: July 2019

Opinion mining is a fast‐developing field of study with numerous applications. It raises economic and political interests, especially in decision‐making processes. In this paper, we are interested in educational opinion mining. We propose an educational guidance process that aims to improve university orientation after the secondary school cycle. Unlike the ordinary orientation processes, our process integrates the opinions of pupil, parents, and teachers, collected periodically. These opinions ​​are treated to sort out the studies’ domains in a positive polarity order. An orientation score is then calculated based on these opinions, the student's aptitudes and the continuous evaluation marks to guide pupils toward the most favourable discipline. The experimentations conducted on a sample of pupils (300) give a better convergence to the pupils’ explicit choices using our proposal with a κ coefficient of 0.71, against 0.29 using only marks.
Three‐year follow‐up results from phase II studies of nivolumab in Japanese patients with previously treated advanced non‐small cell lung cancer: Pooled analysis of ONO‐4538‐05 and ONO‐4538‐06 studies
Authors: Horinouchi Hidehito , Nishio Makoto , Hida Toyoaki , Nakagawa Kazuhiko , Sakai Hiroshi , Nogami Naoyuki , Atagi Shinji , Takahashi Toshiaki , Saka Hideo , Takenoyama Mitsuhiro , Katakami Nobuyuki , Tanaka Hiroshi , Takeda Koji , Satouchi Miyako , Isobe Hiroshi , Maemondo Makoto , Goto Koichi , Hirashima Tomonori , Minato Koichi , Sumiyoshi Naoki , Tamura Tomohide
Published: July 2019

Background

Nivolumab is a programmed cell death 1 (PD‐1) receptor inhibitor antibody that enhances immune system antitumor activity. It is associated with longer overall survival (OS) than the standard treatment of docetaxel in patients with previously treated advanced squamous (SQ) and non‐squamous (non‐SQ) non‐small cell lung cancer (NSCLC). We previously conducted two phase II studies of nivolumab in Japanese patients with SQ (ONO‐4538‐05) and non‐SQ (ONO‐4538‐06) NSCLC, showing overall response rates (ORRs) (95% CI) of 25.7% (14.2‐42.1) and 22.4% (14.5‐32.9), respectively, with acceptable toxicity. In this analysis, we more precisely estimated the long‐term safety and efficacy in patients with SQ and non‐SQ NSCLC by pooling data from these two trials.

Methods

SQ (N = 35) and non‐SQ (N = 76) NSCLC patients received nivolumab (3 mg/kg, every 2 weeks) until progression or discontinuation. OS was estimated using the Kaplan–Meier method. A pooled analysis of SQ and non‐SQ patients was also performed.

Results

In SQ NSCLC patients, the median OS (95% CI) was 16.3 months (12.4‐25.2), and the estimated 1‐year, 2‐year, and 3‐year survival rates were 71.4% (53.4‐83.5), 37.1% (21.6‐52.7), and 20.0% (8.8‐34.4), respectively. In non‐SQ NSCLC patients, median OS was 17.1 months (13.3‐23.0), and the estimated 1‐, 2‐, and 3‐year survival rates were 68.0% (56.2‐77.3), 37.4% (26.5‐48.1), and 31.9% (21.7‐42.5), respectively. When SQ NSCLC and non‐SQ NSCLC data were pooled, the median OS was 17.1 months (14.2‐20.6), and the estimated 1‐, 2‐, and 3‐year survival rates were 69.1% (59.6‐76.8), 37.3% (28.3‐46.2), and 28.1% (20.0‐36.7), respectively. Twenty (76.9%) of 26 responders lived for 3 or more years. Nivolumab was well tolerated and no new safety signals were found.

Conclusion

Treatment with nivolumab improved long‐term survival and was well tolerated in patients with SQ and non‐SQ NSCLC.

Trial registration

JapicCTI‐132072; JapicCTI‐132073.
Nivolumab‐induced celiac‐like enteropathy in patient with metastatic renal cell carcinoma: Case report and review of the literature
Authors: Duval Lucie , Habes Sarah , Chatellier Thierry , Guerzider Pascale , Bossard Céline , Masliah Claude , Archambeaud Isabelle , Touchefeu Yann , Matysiak‐Budnik Tamara
Published: July 2019

Nivolumab may induce severe celiac‐like enteropathy, that may appear very rapidly, after only two injections of nivolumab, and may be successfully treated with corticosteroids. This observation underlines the importance of histological analysis of duodenal biopsies and the necessity to rule out a real celiac disease in patients with nivolumab‐induced diarrhea.
Development of Highly Selective Support for CO Hydrogenation to Light Olefins with Partially Passivated Iron Catalysts
Authors: Xing Yu , Jia Gaopeng , Liu Zhenxin , Fang Shaoming , Zhao Chenxi , Guo Xuehui , Suib Steven L.
Published: July 2019

The front cover artwork for Issue 14/2019 is provided by researchers from Yu Xing, Zhenxin Liu and co‐workers at the Zhengzhou University of Light Industry (P. R. China) and the University of Connecticut (USA). The image shows that light olefins (ethylene, propylene and butylene) may be selectively generated through conversion of syngas over an iron catalyst with a partially passivated Al–O–Zn support. See the Full Paper itself at https://doi.org/10.1002/cctc.201900023.
The Charm of Small Conferences
Authors: Kraume Matthias
Published: July 2019

No abstract.
A new incipient fault monitoring method based on modified principal component analysis
Authors: Yang Yinghua , Wang Xiulong , Liu Xiaozhi
Published: July 2019

A novel multivariate statistical process monitoring (MSPM) method based on modified principal component analysis (PCA) is proposed to solve the low detection rate problem of incipient fault. In this modified PCA, on the basis of normal PCA model, the columns of loading matrix are reordered by mutual information between different statistic component matrices and training data. Then, instead of cumulative percent variance criterion, the principal component subspace is selected according to the largest mutual information. The selected PC subspace can maximally reflect fault characteristics into a new statistical index. Besides, a detection index based on the sliding average control chart statistic is proposed, which eliminates the effect of noise by proper averaging of the most recent samples, greatly improving the ability and accuracy of fault detection. The case study of a numerical simulation and Tennessee Eastman process shows that the proposed method can effectively detect incipient fault.
Polystyrene‐Supported Palladium (Pd@PS)‐Catalyzed Carbonylative Annulation of Aryl Iodides Using Oxalic Acid as a Sustainable CO Source for the Synthesis of 2‐Aryl Quinazolinones
Authors: Ram Shankar , Shaifali  , Chauhan Arvind Singh , Sheetal  , Sharma Ajay Kumar , Das Pralay
Published: July 2019

An efficient and convenient strategy for the synthesis of diversely substituted quinazolinones from o‐carbamoyl/cyano aniline and aryl iodides using oxalic acid as a CO source under polystyrene supported palladium (Pd@PS) nanoparticles (NPs) catalyzed conditions has been developed. In this study, oxalic acid has been employed as safe, economic, environmentally benign, sustainable and bench‐stable, solid CO surrogate under Double‐Layer‐Vial (DLV) system for the synthesis of 2‐aryl quinazolinones. This methodology does not require any special high‐pressure equipment like autoclaves, microwaves, etc. Moreover, a simple procedure for catalyst preparation, catalyst recyclability, easy handling of reaction, additive and base‐free generation of CO, excellent to good yields and vast substrate scope are the additional features of developed protocol.
Reversible C=C Bond Activation by an Intramolecularly Coordinated Antimony(I) Compound
Authors: Kořenková Monika , Hejda Martin , Erben Milan , Jirásko Robert , Jambor Roman , Růžička Aleš , Rychagova Elena , Ketkov Sergey , Dostál Libor
Published: July 2019

The reaction of N,C,N‐chelated stibinidene ArSb (1) (Ar=C6H3‐2,6‐(CH=NtBu)2) with selected N‐alkyl/aryl‐maleimides RN(C(O)CH)2(R=Me,tBu, Ph) gave the addition products with bridged bicyclic [2.2.1] structure containing an antimony atom at the bridgehead position, fused with a 6‐membered benzene and a 5‐membered N‐alkyl/aryl‐pyrrolidine ring. These compounds were completely characterized. More importantly, additional studies showed that these reactions are reversible in solution, thereby representing an unprecedented reversible activation of a C=C bond by an antimony(I) compound.
Double Phosphinoboration of CO2: A Facile Route to Diphospha‐Ureas
Authors: LaFortune James H. W. , Qu Zheng‐Wang , Bamford Karlee L. , Trofimova Alina , Westcott Stephen A. , Stephan Douglas W.
Published: July 2019

The reactions of CO2 with a series of phosphinoboranes, including R2PBpin (R=Ph, tBu; pin=pinacol), R2PBMes2 (R=Ph, tBu; Mes=2,4,6‐Me3‐C6H2), and R2PBcat (R=Ph, tBu, Mes; cat=catechol) are described. Although R2PBpin and R2PBMes2 afford products of the form R2PCO2Bpin (R=Ph 1, tBu 4) and R2PCO2BMes2 (R=Ph 2, tBu 3), respectively, R2PBcat lead to further reaction affording the diphospha‐ureas, (R2P)2CO (R=Ph 5, tBu 6, Mes 7), together with O(Bcat)2. Computational studies provide insight into the mechanism, revealing an intermediate derived from double phosphinoboration of CO2.
Prediction of bubble terminal velocity in surfactant aqueous solutions
Authors: Zheng Kaixin , Li Chen , Yan Xiaokang , Zhang Haijun , Wang Lijun
Published: July 2019

Bubble terminal velocity has a significant effect on gas holdup, residence time, and efficiency of the interface transfer. Surfactant is often required to generate small and stable bubbles in gas‐liquid two‐phase devices. In this paper, bubble terminal velocities were obtained for different surfactant aqueous solutions using high‐speed CCD (charged couple device) system and digital image analysis technology. Experimental results showed that available correlations were not able to accurately predict terminal velocity of bubbles rising in surfactant aqueous solutions. Thus, a new correlation is proposed based on experimental data and it provides an accurate approximation of bubble terminal velocity. The average relative error for the proposed correlation is determined to be 7.2% in MIBC aqueous solutions, 4.5% in OP‐10 aqueous solutions, and 4.6% in 2‐octanol aqueous solutions. The proposed correlation agrees well with experiment data from literate within ranges of the Morton number, Mo, the bubble Reynolds number, Re, and the Eötvös number, Eo: 3.29 × 10−11<Mo<4.29, 0.08<Re<1062, 0.04<Eo<91.16.
Rhodium‐Catalyzed Defluorinative Vinylation of gem‐Difluoroalkenes for the Synthesis of 2‐Fluoro‐1,3‐dienes
Authors: Song Shengjin , Liu Huan , Wang Lu , Zhu Chuan , Loh Teck‐Peng , Feng Chao
Published: July 2019

Summary of main observation and conclusion

Herein, we present a strategy for the formation of 2‐fluoro‐1,3‐diene derivatives via rhodium‐catalyzed direct C(sp2)—C(sp2) cross‐coupling of gem‐difluoroalkenes and acrylamides. By merging Rh(III)‐catalyzed C(sp2)–H bond activation and nucleophilic addition/F‐elimination of gem‐difluoroalkene, an efficient defluorinative vinylation reaction is uncovered, which leads to the generation of 2‐fluoro‐1,3‐dienes in moderate to good yields with excellent stereoselectivity under mild conditions. Preliminary mechanistic study suggests unique effects of fluorine substituents which allow the reactivity profile not observed with the congeners bearing heavier halides.
Provocative questions in osteosarcoma basic and translational biology: A report from the Children's Oncology Group
Authors: Roberts Ryan D. , Lizardo Michael M. , Reed Damon R. , Hingorani Pooja , Glover Jason , Allen‐Rhoades Wendy , Fan Timothy , Khanna Chand , Sweet‐Cordero E. Alejandro , Cash Thomas , Bishop Michael W. , Hegde Meenakshi , Sertil Aparna R. , Koelsche Christian , Mirabello Lisa , Malkin David , Sorensen Poul H. , Meltzer Paul S. , Janeway Katherine A. , Gorlick Richard , Crompton Brian D.
Published: July 2019

Patients who are diagnosed with osteosarcoma (OS) today receive the same therapy that patients have received over the last 4 decades. Extensive efforts to identify more effective or less toxic regimens have proved disappointing. As we enter a postgenomic era in which we now recognize OS not as a cancer of mutations but as one defined by p53 loss, chromosomal complexity, copy number alteration, and profound heterogeneity, emerging threads of discovery leave many hopeful that an improving understanding of biology will drive discoveries that improve clinical care. Under the organization of the Bone Tumor Biology Committee of the Children's Oncology Group, a team of clinicians and scientists sought to define the state of the science and to identify questions that, if answered, have the greatest potential to drive fundamental clinical advances. Having discussed these questions in a series of meetings, each led by invited experts, we distilled these conversations into a series of seven Provocative Questions. These include questions about the molecular events that trigger oncogenesis, the genomic and epigenomic drivers of disease, the biology of lung metastasis, research models that best predict clinical outcomes, and processes for translating findings into clinical trials. Here, we briefly present each Provocative Question, review the current scientific evidence, note the immediate opportunities, and speculate on the impact that answered questions might have on the field. We do so with an intent to provide a framework around which investigators can build programs and collaborations to tackle the hardest problems and to establish research priorities for those developing policies and providing funding.
Site of extranodal metastasis impacts survival in patients with testicular germ cell tumors
Authors: Patel Hiten D. , Singla Nirmish , Ghandour Rashed A. , Freifeld Yuval , Cheaib Joseph G. , Woldu Solomon L. , Pierorazio Phillip M. , Bagrodia Aditya
Published: July 2019

Background

Using a large, nationally representative, population‐based cancer registry, this study systematically evaluated the impact of the location and burden of extranodal testicular germ cell tumor (TGCT) metastases on survival.

Methods

Men with stage III TGCTs captured by the Surveillance, Epidemiology, and End Results registry from 2010 to 2015 with distant extranodal metastases were identified. Clinicopathologic information was collected, and patients were subdivided according to the specific organ site or sites of metastatic involvement (lung, liver, bone, and/or brain). Kaplan‐Meier analysis and multivariable Cox regression were used to evaluate cancer‐specific survival (CSS), and model performance was assessed with Harrell's C statistic.

Results

Nine hundred sixty‐nine patients with stage III TGCTs were included with predominantly nonseminomatous histology (84%). Most patients (91%) had pulmonary metastases, whereas 20%, 10%, and 10% had liver, bone, and brain metastases, respectively. Over a median follow‐up of 21 months, 19% of these men died of TGCTs. When they were grouped by the primary site of metastasis, patients with more than 1 extrapulmonary metastasis exhibited the worst CSS (hazard ratio [HR] vs isolated pulmonary involvement, 4.27; 95% confidence interval [CI], 2.60‐7.00; P < .01). Among patients with isolated extrapulmonary involvement, those with brain metastases had the poorest survival (HR, 3.24; 95% CI, 1.98‐5.28; P < .01), and they were followed by patients with liver (HR, 2.29; 95% CI, 1.56‐3.35; P < .01) and bone metastases (HR, 1.97; 95% CI, 1.11‐3.50; P = .02). Harrell's C statistic (multivariable) was 0.71.

Conclusions

The site of metastatic involvement affects survival outcomes for patients with TGCTs, and this may reflect both the aggressive biology and the challenging treatment of these tumors. Further incorporation of organotropism into current prognostic models for metastatic TGCTs warrants attention.
Functional Metal Oxides in Perovskite Solar Cells
Authors: Wang Jintao , Liu Yunfei , Chen Xiaotian , Chen Chen , Chen Ping , Wang Zhaokui , Duan Yu
Published: July 2019

As extremely important inorganic materials, metal oxides play an irreplaceable role in solid perovskite solar cells. In this review, the preparation methods of metal oxides, their effects on the perovskite optoelectronic devices incorporated with the energy level compatibility of perovskite materials are provided. Finally, the possible reactions between interfaces during growth progress as well as passivation mechanism of some metal oxides to perovskite materials are discussed. The physical, chemical, and electrical properties of functional metal oxides endow the enhancement of the efficiency and stability of perovskite photovoltaic devices.
Fundamental Properties of Transition‐Metals‐Adsorbed Graphene
Authors: Tran Ngoc Thanh Thuy , Nguyen Duy Khanh , Lin Shih‐Yang , Gumbs Godfrey , Lin Ming‐Fa
Published: July 2019

The revealing properties of transition metal (T)‐doped graphene systems are investigated with the use of the first‐principles method. The detailed calculations cover the bond length, position and height of adatoms, binding energy, atom‐dominated band structure, adatom‐induced free carrier density as well as energy gap, spin‐density distributions, spatial charge distribution, and atom‐, orbital‐ and spin‐projected density‐of‐states (DOS). The magnetic configurations are clearly identified from the total magnetic moments, spin‐split energy bands, spin‐density distributions and spin‐decomposed DOS. Moreover, the single‐ or multi‐orbital hybridizations in T−C, T−T, and C−C bonds can be accurately deduced from the careful analyses of the above‐mentioned physical quantities. They are responsible for the optimal geometric structure, the unusual electronic properties, as well as the diverse magnetic properties. All the doped systems are metals except for the low‐concentration Ni‐doped ones with semiconducting behavior. In contrast, ferromagnetism is exhibited in various Fe/Co‐concentrations but only under high Ni‐concentrations. Our theoretical predictions are compared with available experimental data, and potential applications are also discussed.
Quantitative Prediction of CYP3A4‐ and CYP3A5‐Mediated Drug Interactions
Authors: Guo Yingying , Lucksiri Aroonrut , Dickinson Gemma L. , Vuppalanchi Raj K. , Hilligoss Janna K. , Hall Stephen D.
Published: July 2019

We verified a physiologically‐based pharmacokinetic (PBPK) model to predict cytochrome P450 3A4/5‐mediated drug‐drug interactions (DDIs). A midazolam (MDZ)–ketoconazole (KTZ) interaction study in 24 subjects selected by CYP3A5 genotype, and liquid chromatography and mass spectroscopy quantification of CYP3A4/5 abundance from independently acquired and genotyped human liver (n = 136) and small intestinal (N = 12) samples, were conducted. The observed CYP3A5 genetic effect on MDZ systemic and oral clearance was successfully replicated by a mechanistic framework incorporating the proteomics‐informed CYP3A abundance and optimized small intestinal CYP3A4 abundance based on MDZ intestinal availability (FG) of 0.44. Furthermore, combined with a modified KTZ PBPK model, this framework recapitulated the observed geometric mean ratio of MDZ area under the curve (AUCR) following 200 or 400 mg KTZ, which was, respectively, 2.7–3.4 and 3.9–4.7‐fold in intravenous administration and 11.4–13.4 and 17.0–19.7‐fold in oral administration, with AUCR numerically lower (P > 0.05) in CYP3A5 expressers than nonexpressers. In conclusion, the developed mechanistic framework supports dynamic prediction of CYP3A‐mediated DDIs in study planning by bridging DDIs between CYP3A5 expressers and nonexpressers.
Autoimmune Effects of Lung Cancer Immunotherapy Revealed by Data‐Driven Analysis on a Nationwide Cohort
Authors: Yang Shihao , Yu Kun‐Hsing , Palmer Nathan , Fox Kathe , Kou S. C. , Kohane Isaac S.
Published: July 2019

The autoimmune adverse effects of lung cancer immunotherapy are not fully understood at the population level. Using observational data from commercial health insurance claims, we compared autoimmune diseases risk of immune checkpoint inhibitors (including pembrolizumab and nivolumab) and that of chemotherapy using the matching method. By 6 months after treatment initialization, the cumulative incidence of new autoimmune diseases among patients receiving immunotherapy was 13.13% (95% confidence interval (CI), 10.79–15.50%) and that of the matched chemotherapy patients was 6.65% (95% CI, 5.79–7.50%), constituting a hazard ratio (HR) of 1.97 (95% CI, 1.58–2.48). Both pembrolizumab (HR = 2.06 (95% CI, 1.20–3.65), P = 0.0032) and nivolumab (HR = 1.76 (95% CI, 1.39–2.24), P < 0.0001) were associated with higher risks of developing autoimmune diseases, especially for hypothyroidism (P < 0.0001). Our findings suggest the need to monitor autoimmune side effects of immunotherapy.
Formation and Activation of Zr/Hf Bis(phenolate‐ether) Precatalysts
Authors: Cuthbert Eric N. T. , Busico Vincenzo , Herbert David E. , Budzelaar Peter H. M.
Published: July 2019

Zr and Hf complexes of bis(phenolate‐ether) (“O4”) ligands feature high activity, stereoselectivity and molecular weight capability for propene polymerization at high temperature. Here we report a simplified ligand synthesis and several new examples of O4 ligands. The formation of precatalysts LMR2 (M = Zr, Hf; R = Bn, Me) from LH2 and MR4 was found to be accompanied in some cases by the formation of dimers (µ‐L)2[MR2]2, and X‐ray structures of two such dimers have been determined. Treatment of LMMe2 with [Ph3C]+[B(C6F5)4]– produces fairly clean cationic species LMMe+ which were studied by 1H NMR. 2D ROESY data, in particular, suggest that for “smaller” O4 ligands the LMMe+ cation reversibly rearranges from the active (fac/fac) form to a presumably inactive fac/mer or mer/mer form; more bulky substituents appear to suppress this rearrangement. Implications for polymerization catalysis are discussed.
Dinuclear and Trinuclear Complexes of Copper(I) and Silver(I) Supported by a Highly Fluorinated Pyrazolate [3,5‐(CF3)2Pz]– and N‐Heterocycles
Authors: Dias H. V. Rasika , Diyabalanage Himashinie , Jayaratna Naleen B. , Shaw Daniel , Hettiarachchi Champika V. , Parasar Devaborniny
Published: July 2019

The chemistry of trinuclear silver(I) and copper(I) pyrazolates with aromatic, bidentate N‐heterocycles, 2,2′‐bipyridine, 6,6′‐dimethyl‐2,2′‐bipyridine, 1,10‐phenanthroline, 2,9‐dimethyl‐1,10‐phenanthroline, and 1,8‐naphthyridine are presented. These N‐donor ligands react readily with {[3,5‐(CF3)2Pz]Ag}3 and {[3,5‐(CF3)2Pz]Cu}3 providing mixed‐ligand complexes with all nitrogen coordination spheres at metal in high yield. The fluorinated pyrazolate acts as a bridging ligand in these complexes. The bipyridine and phenanthroline systems with donor lone pairs at an acute angle serve as bidentate chelators for copper and silver providing dinuclear complexes. They feature planar, boat or chair shaped Ag2N4 or Cu2N4 cores and four‐coordinate, tetrahedral metal sites. The 1,8‐naphthyridine that has donor nitrogen lone pairs at a parallel orientation affords trinuclear copper and silver complexes with two‐ and three‐coordinate metal centers. It uses only one of its lone pairs effectively in these adducts for metal ion coordination. In addition, 1,8‐naphthyridine moieties of these copper and silver complexes show intermolecular π–π stacking. Results presented here show the effects of donor nitrogen lone‐pair orientations of the bidentate N‐heterocycles on the structures of the products resulting from their chemistry with {[3,5‐(CF3)2Pz]Ag}3 and {[3,5‐(CF3)2Pz]Cu}3.
Acid‐Catalyzed Intramolecular Imination / Nucleophilic Trapping of 4‐Aminobutanal Derivatives: One‐Pot Access to 2‐(Pyrazolyl)pyrrolidines
Authors: Smolobochkin Andrey V. , Rizbayeva Tanzilya S. , Gazizov Almir S. , Voronina Julia K. , Dobrynin Alexey B. , Gildebrant Anastasiya V. , Strelnik Anna G. , Sazykin Ivan S. , Burilov Alexander R. , Pudovik Michail A. , Sazykina Marina A.
Published: July 2019

A first successful synthesis of 2‐(pyrazolyl)pyrrolidines is reported starting from readily available reagents. A wide variety of N‐substituted 2‐(pyrazolyl)pyrrolidines are obtained with up to 96 % yield. The influence of the obtained compounds on biofilm formation by V. aquamarinus DSM 26054 and A. calcoaceticus VKPM B–10353 have been studied. Some of the tested compounds were found to suppress the growth of bacterial biofilms at nanomolar concentrations and thus are promising candidates for further studies.
Robust and Scalable Approach to 1,3‐Disubstituted Pyridylcyclobutanes
Authors: Demchuk Oleksandr P. , Hryshchuk Oleksandr V. , Vashchenko Bohdan V. , Radchenko Dmytro S. , Kovtunenko Volodymyr O. , Komarov Igor V. , Grygorenko Oleksandr O.
Published: July 2019

An approach to all isomeric 3‐pyridylcyclobutane‐derived building blocks, i.e. ketones, alcohols and amines, is described. Synthesis of the title compounds relied on the five‐step reaction sequence including alkylation of isomeric pyridyl acetonitriles with 1,3‐dibromo‐2,2‐dimethoxypropane. Hydrolysis, decarboxylation and removal of the ketal moiety led to the key 3‐pyridylcyclobutanones (obtained on up to 120 g scale in a single run), which were transformed into the corresponding alcohols and amines with high diastereoselectivity. The title cyclobutanone derivatives were used to synthesize three isomeric nicotine analogues, as well as for parallel synthesis of a small lead‐like compound library via reductive amination.
APC mutational patterns in gastric adenocarcinoma are enriched for missense variants with associated decreased survival
Authors: Rubinstein Jill C. , Khan Sajid A. , Christison‐Lagay Emily R. , Cha Charles
Published: July 2019

Adenomatous polyposis coli (APC) mutations are causally associated with familial adenomatous polyposis (FAP) and are recurrent somatic events across numerous tumor types, including gastric adenocarcinoma. Severity of disease in FAP correlates with specific APC mutations, but the impact of given mutations on phenotype in gastric cancer is not well studied. Sequencing data from the Genomic Data Commons (GDC) demonstrate an APC mutational pattern in gastric cancer that differs dramatically from that seen in colon cancer. Exome sequencing data from APC‐mutant colon and gastric adenocarcinomas in GDC was filtered for single nucleotide variants (SNVs) using MuTect2 Variant Aggregation and Masking pipeline, Somatic Aggregation Workflow. APC mutations were found in 57/441 gastric (12.9%) and 309/433 colon adenocarcinomas (71.4%). There was a significant difference in the proportion of stopgain, frameshift, and missense mutations between tumor types(P < .00001). Colon tumors were predominated by frameshift and stopgains, comprising 47.7% and 35.7%, respectively. In contrast, 47.1% of gastric mutations were missense. Gastric tumors harboring missense mutations showed decreased overall survival relative to other mutational subtypes(P = .008). In the gastric samples, 25.9% of frameshift and stopgain mutations are in the 3′ portion of the gene, compared to 1.4% of colon samples. APC mutations demonstrate different distributions in gastric and colon adenocarcinoma, with a shift toward missense variants in gastric tumors and worse survival in gastric tumors harboring them. As different mutations confer variable degrees of protein dysfunction and resultant clinical manifestation, expanded investigation of specific mutational patterns will prove integral to future‐risk stratification strategies.
The clinical and economic burden among caregivers of patients with Alzheimer's disease in Canada
Authors: Szabo Shelagh , Lakzadeh Pardis , Cline Stephanie , Palma dos Reis Rodrigo , Petrella Robert
Published: July 2019

Objective

To estimate the clinical and direct medical economic burden among Alzheimer disease (AD) caregivers using real‐world, longitudinal patient‐level data in Canada.

Methods/Design

This retrospective observational study assessed the clinical and direct medical economic burden among individuals who cohabitate with AD patients (“AD caregiver cohort”) compared with older adults who were cohabiting with another adult without dementia (“comparison cohort”) using real‐world data from the Southwestern Ontario database, a representative Canadian electronic health record (EHR) longitudinal EHR.

Results

The AD caregiver cohort (n = 2749; mild AD: n = 2254, moderate AD: n = 302, and severe AD, n = 193) had a similar or higher level of clinical and economic burden than the comparison cohort (n = 12 152). The overall AD cohort and caregivers of patients with mild AD had a similar clinical burden to the comparison cohort. Those caregiving for more severely affected AD patients had an increased risk of comorbidities and required more medication, physician attention, and hospital encounters compared with caregivers of less severe AD patients and the comparison cohort. Mean annual costs were higher among the AD caregiver cohort than the comparison cohort, and those caregiving for moderate and severe AD patients incurred the highest costs. Overall mortality was higher in the AD caregiver cohort compared with the comparison cohort.

Conclusions

Caregivers of patients with mild AD had a similar clinical and direct economic burden to older adults who were not dementia caregivers, whereas the burden among caregivers of moderate and severe AD patients was much greater.
Phase II trial with axitinib in recurrent and/or metastatic salivary gland cancers of the upper aerodigestive tract
Authors: Locati Laura D. , Cavalieri Stefano , Bergamini Cristiana , Resteghini Carlo , Alfieri Salvatore , Calareso Giuseppina , Bossi Paolo , Perrone Federica , Tamborini Elena , Quattrone Pasquale , Granata Roberta , Galbiati Donata , Platini Francesca , Orlandi Ester , Mariani Luigi , Licitra Lisa
Published: July 2019

Background

Patients with prognosis recurrent/metastatic (R/M) salivary gland carcinomas (SGCs) are poor. Activity of axitinib was demonstrated in adenoid cystic carcinoma (ACC). We tested axitinib in a larger cohort of R/M SGCs including non‐ACC.

Methods

Axitinib was administered at 10 mg daily (dose escalation allowed) until progression or unacceptable toxicity. Null hypothesis would be rejected if more than 3 of 26 responses were observed.

Results

Twenty‐six patients (50% were male; 6 ACC, 20 non‐ACC) were treated. Response rate was 8% (2 partial responses), 13 stable disease (>6 months in 7 patients) and 11 disease progression. Median progression‐free survival and overall survival were 5.5 and 26.2 months, respectively. All patients had at least one adverse event: stomatitis (69%), fatigue (58%) and hypertension (54%) were the most frequent.

Conclusions

This trial did not meet its primary endpoint hence axitinib should not be considered for further investigations in SGCs. Safety profile was in line with the scientific literature.
Network slicing security: Challenges and directions
Authors: Cunha Vitor A. , da Silva Eduardo , de Carvalho Marcio B. , Corujo Daniel , Barraca Joao P. , Gomes Diogo , Granville Lisandro Z. , Aguiar Rui L.
Published: July 2019

Network slicing emerges as a key technology in next generation networks, boosted by the integration of software‐defined networking and network functions virtualization. However, while allowing resource sharing among multiple tenants, such networks must also ensure the security requirements needed for the scenarios they are employed. This letter presents the leading security challenges on the use of network slices at the packet core, the solutions that academy and industry are proposing to address them, pointing out some directions that should be considered.
HIV, antiretroviral therapy and non‐communicable diseases in sub‐Saharan Africa: empirical evidence from 44 countries over the period 2000 to 2016
Authors: Coetzee Lelani , Bogler Lisa , De Neve Jan‐Walter , Bärnighausen Till , Geldsetzer Pascal , Vollmer Sebastian
Published: July 2019

Introduction

The HIV‐infected population is growing due to the increased accessibility of antiretroviral therapy (ART) that extends the lifespan of people living with HIV (PLHIV). We aimed to assess whether national HIV prevalence and ART use are associated with an increased prevalence of cardiovascular risk factors.

Methods

Using country‐level data, we analysed the effect of HIV prevalence and use of ART on cardiovascular risk factors in 44 countries in sub‐Saharan Africa between 2000 and 2016. We used fixed‐effects estimation to quantify the effect of HIV and ART on the prevalence of diabetes, mean body mass index, the prevalence of overweight, obesity and hypertension, and mean systolic blood pressure. The models were adjusted for calendar time, the age structure of the population, income and education.

Results

Diabetes prevalence among PLHIV was 5.8 percentage points higher (95% confidence interval (CI) 1.8 pp to 9.8 pp) compared to individuals without HIV. People receiving ART had a 4.6 percentage point higher prevalence (95% CI 2.6 pp to 6.6 pp). The prevalence of obesity was increased by 14.7 percentage points (95% CI 2.5 pp to 26.9 pp) for PLHIV. Receiving ART was associated with an increased obesity prevalence by 14.0 percentage points (95% CI 4.8 pp to 23.2 pp), whereas it had no significant association with the prevalence of overweight. The population aged 40 to 59 had a significantly higher prevalence of diabetes, overweight and obesity. HIV prevalence and ART use had no significant association with the prevalence of hypertension.

Conclusions

An ageing HIV‐infected population on ART is associated with a significant increase in the prevalence of diabetes and obesity in sub‐Saharan Africa. The increasing prevalence of these cardiovascular risk factors emphasizes the need for comprehensive healthcare programmes that screen and treat both HIV and non‐communicable diseases to decrease the associated morbidity and mortality rates.
Leukocyte‐ and platelet‐rich fibrin is an effective membrane for lateral ridge augmentation: An in vivo study using a canine model with surgically created defects
Authors: Lee Jun‐Beom , Lee Jung‐Tae , Hwang Sukhyun , Choi Jung‐Yoo , Rhyu In‐Chul , Yeo In‐Sung L.
Published: July 2019

Background

Leukocyte‐ and platelet‐rich fibrin (L‐PRF) has been suggested to enhance bone healing and the effects of L‐PRF need to be evaluated in lateral residual alveolar bone augmentation. This in vivo study aimed to analyze the effects of L‐PRF as a membrane on bone regeneration in lateral residual alveolar augmentation.

Methods

Eight mongrel dogs were used; the mandibular premolars were extracted and then three lateral ridge defects were surgically created on each side of the arch. After 4 weeks, guided bone ridge augmentation was performed in each defect with the following treatment groups: N+D (nonresorbable membrane with deproteinized bovine bone mineral [DBBM]), N+B (nonresorbable membrane with β‐tricalcium phosphate [β‐TCP]), R+D (resorbable membrane with DBBM), R+B (resorbable membrane with β‐TCP), and P+D (L‐PRF with DBBM), and P+B (L‐PRF and β‐TCP). Following 4 weeks of bone healing, the new bone amount for each group was measured by light microscopy (primary outcome) and microcomputed tomography (micro‐CT) (secondary outcome). The mean values were compared at the 0.05 significance level.

Results

The P+D group showed the most newly formed bone in histology and in micro‐CT analyses. L‐PRF was more effective in bone regeneration when compared to nonresorbable and resorbable barrier membranes. Additionally, this study indicated DBBM was the more favorable osseous graft material for bone regeneration than β‐TCP when barrier membranes are used.

Conclusion

From the results of this in vivo study using surgically created defects, L‐PRF plays an effective role as a barrier membrane for lateral ridge augmentation. L‐PRF may be an excellent barrier membrane in place of other nonresorbable and resorbable membranes.
revtools: An R package to support article screening for evidence synthesis
Authors: Westgate Martin J.
Published: July 2019

The field of evidence synthesis is growing rapidly, with a corresponding increase in the number of software tools and workflows to support the construction of systematic reviews, systematic maps, and meta‐analyses. Despite much progress, however, a number of problems remain, including slow integration of new statistical or methodological approaches into user‐friendly software, low prevalence of open‐source software, and poor integration among distinct software tools. These issues hinder the utility and transparency of new methods to the research community. Here, I present revtools, an R package to support article screening during evidence synthesis projects. It provides tools for the import and deduplication of bibliographic data, screening of articles by title or abstract, and visualization of article content using topic models. The software is entirely open‐source and combines command‐line scripting for experienced programmers with custom‐built user interfaces for casual users, with further methods to support article screening to be added over time. revtools provides free access to novel methods in an open‐source environment and represents a valuable step in expanding the capacity of R to support evidence synthesis projects.
Surfactant Crystals as Stimulable Foam Stabilizers: Tuning Stability with Counterions
Authors: Zhang Li , Wang Haiting , Zheng Bin , Du Huiling , Salonen Anniina
Published: July 2019

The demands on foam stability are variable and changing, which is why design of foams that are both ultrastable and stimulable is important. We study foams stabilized using surfactant particles made through precipitation of sodium dodecyl sulfate with alkali chlorides. We have previously shown that depending on the concentrations of surfactant and salt, the foams can be ultrastable or age like common surfactant foams. We now show that the adsorption of surfactant crystals changes with the type of salt added and how the crystals are made, as well as the surfactant concentration. We see differences in foam stability if the crystals are made prior to foaming or if they are formed concomitantly with foaming. The adsorption of the crystals is improved if the crystals are made during generation, possibly because of their smaller size. The foams destabilize when heated above the Krafft boundary. We show that through tuning the surfactant concentration and salt type or concentration, we can modulate the melting temperature, and hence the destruction temperature of foam between 22 and 50 °C. Precipitated surfactant particles are versatile alternatives to stabilize ultrastable and stimulable foams.
Orange peels: from by‐product to resource through lactic acid fermentation
Authors: Ricci Annalisa , Diaz Ana Belen , Caro Ildefonso , Bernini Valentina , Galaverna Gianni , Lazzi Camilla , Blandino Ana
Published: July 2019

BACKGROUND

Considering the large amounts of by‐products derived from orange processing, which are generally discarded, the present study aimed to explore the feasibility of using orange peel for lactic acid production in solid state fermentation.

RESULTS

Different species of lactic acid bacteria were employed, singly and in co‐culture, to evaluate their ability to ferment orange peel and produce lactic acid. Among the single cultures tested, Lactobacillus casei 2246 was the most efficient strain, reaching the highest concentration of lactic acid (209.65 g kg−1) and yield (0.88 g g−1). The use of Lactobacillus plantarum 285 and Lactobacillus paracasei 4186 in co‐culture produced a comparable amount of lactic acid, showing a better performance than the same strains in single cultures.

CONCLUSION

Orange peels represent a suitable raw material for solid state fermentation employing lactic acid bacteria. Lactic acid was obtained that consumed the most of sugars available, leading to high yields. Despite all the strains tested showing the same growth ability, different peculiarities in lactic acid production were revealed, dependent on the species/strains, suggesting the relevance of strain selection. © 2019 Society of Chemical Industry
Safety and quality issues in summer squashes using handheld portable NIRS sensors for real‐time decision making and for on‐vine monitoring
Authors: Entrenas José‐Antonio , Pérez‐Marín Dolores , Torres Irina , Garrido‐Varo Ana , Sánchez María‐Teresa
Published: July 2019

BACKGROUND

Portable handheld near infrared spectroscopy (NIRS) instruments currently present enormous advantages in terms of size, weight, and robustness. They also provide fast, precise information that can be obtained in situ, and they represent a viable option for controlling vegetable safety and quality during the growth period. The aim of this research was to evaluate three handheld portable NIRS instruments for in situ and real‐time analysis of intact summer squashes. Traditional methods were used to analyze 221 summer squashes, and this work was used to develop calibration models for morphological, safety, and quality parameters. The longitudinal distribution of nitrate content in summer squashes weighing over 400 g was also studied, and the evolution of this parameter during the harvest period was tracked to determine which summer squashes and which zones of the vegetables (peduncle, equatorial, or stylar) could be earmarked for baby‐food production.

RESULTS

The robustness of the calibration models confirmed the expectations raised by NIRS technology for morphological, safety, and quality control of individual summer squashes, and the models developed with the MicroNIR‐1700 instrument were those that provided more accuracy and precision, being the peduncle zone the part with higher nitrate content.

CONCLUSIONS

It is in the peduncle zone, therefore, where measurements of this parameter must be carried out to decide on the destination of the harvested product. Summer squashes picked at the end of the harvest are those that must be used for baby‐food production. © 2019 Society of Chemical Industry
Management of arteriovenous malformation of the ear: A protocol for resection and reconstruction
Authors: Vilela Chagas Ferreira Marina , Goldenberg Dov Charles , Kharmandayan Vania , Gemperli Rolf
Published: July 2019

Objective

Arteriovenous malformations (AVM) of the ear show unique features. Progressive growth or inadequate management of AVMs may lead to bleeding, infection, cartilage exposure, and ultimately loss of structure. Total ear amputation is an alternative; however, due to the structural complexity of the ear, reconstruction is technically challenging. This study presents a treatment algorithm based on a clinical series, with treatment options including resection and immediate and late reconstruction.

Methods

Between 2004 and 2018, 12 patients with auricular AVMs were treated with AVM resection and ear reconstruction at our hospital. Among these 12 patients, seven were women, and patients’ ages ranged between 4 and 34 years. Parameters considered before resection and reconstruction were compromised ear extension (partial, total, or extra‐auricular involvement), thickness (cutaneous and cartilaginous), symptoms (bleeding, infection, ulceration, and/or cartilage exposure), and preoperative embolization. Total resection of AVMs was planned as the first step in all cases, followed by primary closure. AVM resection was categorized into a partial or total procedure, resulting in partial or total ear defects. Reconstruction was categorized as immediate or delayed.

Results

Preoperative embolization was performed in 10 patients. AVMs were totally removed, resulting in seven total ear amputations. In six of these patients, total ear reconstruction was performed 6 months later, and all patients were recurrence‐free. Only one patient did not undergo ear reconstruction. Regrowth was not observed in any reconstructed ear.

Conclusion

Treatment of ear AVMs requires a planned approach to achieve favorable clinical outcomes and for concomitant safe and definitive reconstruction.

Level of Evidence

4

Laryngoscope, 130:1322–1326, 2020