bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis and characterization of silica‐coated magnetite nanoparticles modified with bis(pyrazolyl) triazine ruthenium(II) complex and the application of these nanoparticles as a highly efficient catalyst for the hydrogen transfer reduction of ketones
Authors: Mobinikhaledi Akbar , Moghanian Hassan , Ajerloo Bahram , Dousti Fatemeh
Published: December 2019

We present a facile and efficient method for modifying the surface of silica‐coated Fe3O4 magnetic nanoparticles (MNPs) with bis(pyrazolyl) triazine ruthenium(II) complex [MNPs@BPT–Ru (II)]. Field emission‐scanning electron microscopy, thermogravimetric/derivative thermogravimetry analysis, X‐ray powder diffraction, Fourier‐transform infrared spectroscopy, vibrating sample magnetometry, and energy‐dispersive X‐ray spectrometry analyses were employed for characterizing the structure of these nanoparticles. MNPs@BPT–Ru(II) nanoparticles proved to be a magnetic, reusable, and heterogeneous catalyst for the hydrogen transfer reduction of ketone derivatives. In addition, highly pure products were obtained with excellent yields in relatively short times in the presence of this catalyst. A comparison of this catalyst with those previously used for the hydrogen transfer reactions proved the uniqueness of MNPs@BPT–Ru(II) nanoparticle which is due to its inherent magnetic properties and large surface area. The presented method also had other advantages such as simple reaction conditions, eco‐friendliness, high recovery ability, easy work‐up, and low cost.
Valorization of mixed radish seed oil and Prunus armeniaca L. oil as a promising feedstock for biodiesel production: Evaluation and analysis of biodiesels
Authors: Fadhil Abdelrahman B. , Nayyef Akram W. , Sedeeq Saba H.
Published: December 2019

A blend of radish oil (RO) and apricot kernel oil (AKO) was transesterified with methanol, ethanol, and their equivalent mixture, to yield methylic biodiesel (MBD), ethylic biodiesel (EBD), and methylic/ethylic biodiesel (MEBD), respectively with the refining of the so‐developed fuels through adsorption onto the activated carbon prepared by ZnCl2 activation of apricot shells. The best conversion of RO–AKO blend to MBD (96.12 ± 1.25%) and MEBD (94.23 ± 2.22) was attained at KOH concentration, 0.75% w/w of oil, alcohol/oil molar ratio, 6/1, mixing intensity, 600 rpm, reaction temperature, 60°C, and 45‐min reaction period, whereas the best conditions that produced the highest yield of EBD (95.19 ± 2.0 %) were KOH concentration, 1.0 KOH % w/w of oil, ethanol/oil molar ratio, 8/1, mixing intensity, 600 rpm, reaction temperature, 65°C, and 75‐min reaction period. The Fourier‐transform infrared spectroscopy and 1H nuclear magnetic resonance confirmed formation of the alkyl esters from the RO–AKO blend. The quality of MBD, EBD, and MEBD obtained from the RO–AKO blend was evaluated and found comparable with the American Society for Testing and Materials (ASTM) D6751 standards. Additionally, blending of MEBD with petrodiesel was possible, and properties of the blends were in accordance with those established by ASTM D7467‐17. The methanolysis of the RO–AKO mixture followed the pseudo‐first‐order kinetics with activation energy of 27.27 kJ mol−1. In conclusion, the RO–AKO mixture could be low‐cost feedstock for biodiesel production. Moreover, apricot shells could be exploited as a priceless and suitable adsorbent for the adsorption of impurities found in the crude alkyl esters for its high surface area.
Anatomy and Flight Performance of the Early Enantiornithine Bird Protopteryx fengningensis: Information from New Specimens of the Early Cretaceous Huajiying Formation of China
Authors: Chiappe Luis M. , Di Liu , Serrano Francisco J. , Yuguang Zhang , Meng Qingjin
Published: December 2019

The Early Cretaceous (∼131 Million Years Ago) Protopteryx fengningensis is one of the oldest and most primitive enantiornithine birds; however, knowledge of its anatomy has largely been limited to the succinct description of two specimens (holotype and paratype). This study describes two new specimens of P. fengningensis preserving most of the skeleton and plumage, and it therefore adds significantly to understanding the morphology of this important species and the character evolution of enantiornithine birds. The well‐preserved plumage of these specimens also affords a quantitative assessment of the flight performance of P. fengningensis. Our aerodynamic considerations indicate that this early enantiornithine was capable of intermittent flight (bounding or flap‐gliding), thus marking the earliest occurrence of such energy‐saving aerial strategy. Anat Rec, 303:716–731, 2020. © 2019 American Association for Anatomy
Design partnerships for participatory librarianship: A conceptual model for understanding librarians co designing With digital youth
Authors: Yip Jason C. , Lee Kung Jin , Lee Jin Ha
Published: December 2019

Libraries play a central role for youth and digital learning. As libraries transition to learning spaces, youth librarians can engage in aspects of democratic design that empowers youth. Participatory design (PD) is a user‐centered design method that can support librarians in the democratic development of digital learning spaces. However, while PD has been used in libraries, we have little knowledge of how youth librarians can act as codesign partners. We need a conceptual model to understand the role of youth librarians in codesign, and how their experiences are integrated into youth design partnerships. To generate this model, we examine a case study of the evolutionary process of a single librarian and the development of a library system's learning activities through PD. Using the idea of equal design partnerships, we analyzed video recordings and stakeholder interviews on how children (ages 7–11) worked together with a librarian to develop new digital learning activities. Our discussion focuses on the development of a participatory librarian design conceptual model that situates librarians as design partners with youth. The article concludes with recommendations for integrating PD methods into libraries to create digital learning spaces and suggestions for moving forward with this design perspective.
Neonatal Thyroid Stimulating Hormone and Subsequent Diagnosis of Autism Spectrum Disorders and Intellectual Disability
Authors: Ames Jennifer L. , Windham Gayle C. , Lyall Kristen , Pearl Michelle , Kharrazi Martin , Yoshida Cathleen K. , Van de Water Judy , Ashwood Paul , Croen Lisa A.
Published: December 2019

Hypothyroid conditions in early life, if left untreated, are associated with adverse neurodevelopmental outcomes, including intellectual disability (ID). However, evidence addressing the role of neonatal thyroid hormone insufficiencies in the altered neurobiology underlying autism spectrum disorders (ASD), particularly among its subphenotypes, is limited. We conducted a population‐based, case–control study among a sample of children born during 2000–2003 in Southern California. We examined neonatal thyroid‐stimulating hormone (TSH) measured during routine newborn screening among children later diagnosed with ASD (n = 518) or ID (n = 145) and general population (GP) controls (n = 399). TSH was further analyzed in relation to ASD subgroups of intellectual ability and onset type (early‐onset ASD vs. ASD with regression) ascertained by expert review of developmental services records. Odds ratios (ORs) of the differences in TSH between groups were obtained from multivariate logistic regression. We examined neonatal TSH as continuous (ln‐transformed) and as quartiles. We found no association between continuous neonatal TSH levels and ASD (adj‐OR: 1.00, 95% CI: 0.79–1.26) nor ID (adj‐OR = 1.01, 95% CI: 0.73–1.40). Among ASD subphenotypes, we observed a suggestive inverse trend between ASD with regression and TSH, though the association only reached statistical significance in the highest TSH quartile (adj‐OR: 0.50, 95% CI: 0.26–0.98). While there was little evidence that neonatal TSH is related to overall ASD risk, more work is needed to understand the influence of thyroid hormones on ASD subphenotypes. Autism Res 2020, 13: 444–455. © 2019 International Society for Autism Research,Wiley Periodicals, Inc.

Lay Summary

Low levels of thyroid hormone at birth can negatively impact brain development. We studied whether newborn levels of thyroid stimulating hormone (TSH) were associated with autism spectrum disorder (ASD) and its subtypes in a sample of children born in California. Newborn TSH was not related to the overall risk of ASD or intellectual disability. However, the relationships of thyroid hormone levels at birth and specific subtypes of ASD, particularly ASD with developmental regression, may need more research.
Fermentation of hemicellulose liquor from Brewer's spent grain using Scheffersomyces stipitis and Pachysolen tannophilus for production of 2G ethanol and xylitol
Authors: da Silva Elizabeth G. , Borges Alex S. , Maione Nicole R. , Castiglioni Gabriel L. , Suarez Carlos A. G. , Montano Inti D. C.
Published: December 2019

Beer production generates brewer's spent grain as a byproduct. This biomass contains lignin, cellulose, and hemicellulose, and can be used for the production of second‐generation (2G) ethanol and xylitol. For this to be economically viable, fermentable fractions must be used, allowing the conversion of cellulose and hemicellulose to ethanol. This study evaluated the fermentation of hemicellulose liquor from brewer's spent grain (HLBS) in aerobic and oxygen‐ limited conditions using Scheffersomyces stipitis and Pachysolen tannophilus. Results were compared with data obtained in a complex medium (YPX) and a minimal medium (MMX). In aerobic conditions, for S. stipitis in the HLBS medium, μ
max = 0.12 h−1, Y
ethanol/xylose = 0.14 and selectivity for ethanol over xylitol (S
ethanol/xylitol) 3.4 gethanol g−1
xylitol were obtained. Under oxygen‐limited conditions, Y
ethanol/xylose = 0.22 and S
ethanol/xylitol = 1.17 gethanol g−1
xylitol were obtained. For P. tannophilus, under aerobic conditions, the HLBS medium gave μ
max = 0.08 h−1, and Y
ethanol/xylose = 0.005, with selectivity for ethanol over xylitol (S
ethanol/xylitol) of 0.12 gethanol g−1
xylitol. In oxygen‐limited conditions, Y
ethanol/xylose = 0.09 and S
ethanol/xylitol = 0.20 gethanol g−1
xylitol were obtained. This is because the metabolism of these aerobic yeasts directs the carbon flow to cell growth, while with oxygen limitation it is directed to metabolite production. The HLBS medium was promising for production in the context of a biorefinery. When comparing the two yeasts, S. stipitis presented better ethanol production and P. tannophilus better xylitol production under the conditions that were studied. © 2019 Society of Chemical Industry and John Wiley & Sons, Ltd
PBX‐WNT‐P63‐IRF6pathway in nonsyndromic cleft lip and palate
Authors: Maili Lorena , Letra Ariadne , Silva Renato , Buchanan Edward P. , Mulliken John B. , Greives Matthew R. , Teichgraeber John F. , Blackwell Steven J. , Ummer Rohit , Weber Ryan , Chiquet Brett , Blanton Susan H. , Hecht Jacqueline T.
Published: December 2019

Nonsyndromic cleft lip and palate (NSCLP) is one of the most common craniofacial anomalies in humans, affecting more than 135,000 newborns worldwide. NSCLP has a multifactorial etiology with more than 50 genes postulated to play an etiologic role. The genetic pathway comprised ofPbx‐Wnt‐p63‐Irf6genes was shown to control facial morphogenesis in mice and proposed as a regulatory pathway for NSCLP. Based on these findings, we investigated whether variation inPBX1,PBX2, andTP63, and their proposed interactions were associated with NSCLP. Fourteen single nucleotide variants (SNVs) in/nearbyPBX1,PBX2, andTP63were genotyped in 780 NSCLP families of nonHispanic white (NHW) and Hispanic ethnicities. Family‐based association tests were performed for individual SNVs stratified by ethnicity and family history of NSCLP. Gene–gene interactions were also tested. A significant association was found forPBX2rs3131300 and NSCLP in combined Hispanic families (p= .003) while nominal association was found forTP63rs9332461 in multiplex Hispanic families (p= .005). Significant haplotype associations were observed forPBX2in NHW (p= .0002) and Hispanic families (p= .003), and forTP63in multiplex Hispanic families (.003). An independent case–control group was used to validate findings, and significant associations were found withPBX1rs6426870 (p= .007) andTP63rs9332461 (p= .03). Gene–gene interactions were detected betweenPBX1/PBX2/TP63withIRF6in NHW families, and betweenPBX1withWNT9Bin both NHW and Hispanic families (p < .0018). This study provides the first evidence for a role ofPBX1andPBX2, additional evidence for the role ofTP63, and support for the proposedPBX‐WNT‐TP63‐IRF6regulatory pathway in the etiology of NSCLP.
Rapid analysis of Saposhnikovia divaricate decoction metabolism in rats by UHPLC–Q‐TOFMS and multivariate statistical analysis
Authors: Li Yueyue , Zhao Liang , Lv Diya , Wang Rong , Zhu Zhenyu , Yuan Yongfang
Published: December 2019

Saposhnikovia divaricata is a commonly used traditional Chinese medicine in treating various diseases such as pyrexia, rheumatism and headache. So far, there have been few reports on the metabolism of orally administered Saposhnikovia divaricate decoction (SDD), hindering further study on its bioactive components and their pharmacological characteristics. In the present study, ultra‐performance liquid chromatography–quadrupole time‐of‐flight mass spectrometry (UHPLC–Q‐TOFMS) was used coupled with principal component analysis (PCA) and partial least squared discriminant analysis (PLS‐DA) to rapidly discover and identify the metabolites of SDD. According to the result of PLS‐DA, a total of 139 ions of interest including 87 positive ions and 52 negative ions were extracted as SDD‐related xenobiotics in urine. Finally, 12 and 65 compounds were identified as absorbed parent components and metabolites of SDD, respectively. Among them, 40 new metabolites were reported for the first time. Our results suggested that hydrolysis, hydroxylation, glucuronidation and sulfation are the major metabolic pathways of chromones, while hydroxylation, hydrogenation and sulfation are the main metabolic pathways of coumarins. This study is the first to explore the absorption and metabolism of SDD using UHPLC–Q‐TOFMS, with results providing a basis for further study of its pharmacokinetics and discovery of its bioactive components.
Effects of cysteine, asparagine, or glutamine limitations in Chinese hamster ovary cell batch and fed‐batch cultures
Authors: Ghaffari Navid , Jardon Mario A. , Krahn Natalie , Butler Michael , Kennard Malcolm , Turner Robin F. B. , Gopaluni Bhushan , Piret James M.
Published: December 2019

Amino acid availability is a key factor that can be controlled to optimize the productivity of fed‐batch cultures. To study amino acid limitation effects, a serum‐free chemically defined basal medium was formulated to exclude the amino acids that became depleted in batch culture. The effect of limiting glutamine, asparagine, and cysteine on the cell growth, metabolism, antibody productivity, and product glycosylation was investigated in three Chinese hamster ovary (CHO) cell lines (CHO‐DXB11, CHO‐K1SV, and CHO‐S). Cysteine limitation was detrimental to both cell proliferation and productivity for all three CHO cell lines. Glutamine limitation reduced growth but not cell specific productivity, whereas asparagine limitation had no significant effect on either growth or cell specific productivity. Neither glutamine nor asparagine limitation significantly affected antibody glycosylation. Replenishing the CHO‐DXB11 culture with cysteine after 1 day of cysteine limitation allowed the cells to partially recover their growth and productivity. This recovery was not observed after 2 days of cysteine limitation. Based on these findings, a fed‐batch protocol was developed using single or mixed amino acid supplementation. Although cell density and antibody concentration were lower compared to a commercial feed, the feeds based on cysteine supplementation yielded comparable cell specific productivity. Overall, this study showed that different amino acid limitations have varied effects on the performance of CHO cell cultures and that maintaining cysteine availability is a critical process parameter for the three cell lines investigated.
Identification of chemoresistance‐related mRNAs based on gemcitabine‐resistant pancreatic cancer cell lines
Authors: Zhou Jiarong , Zhang Linshi , Zheng Huilin , Ge Wenhao , Huang Yu , Yan Yingcai , Zhou Xiaohu , Zhu Wei , Kong Yang , Ding Yuan , Wang Weilin
Published: December 2019

Gemcitabine (GEM) alone and GEM‐based chemotherapy are the preferred regimens for treating advanced unresectable and metastatic pancreatic cancer (PC). However, these treatments have limited efficacy due to acquired resistance of cancer cells to chemotherapy, the mechanisms of which are not fully understood. In this study, we established two stable multidrug‐resistant cell lines, BxPC‐3‐GR and CFPAC‐1‐GR, from their corresponding parental cells through exposure to GEM following a stepwise incremental dosing strategy. The GEM IC50 values of BxPC‐3‐GR and CFPAC‐1‐GR increased 112‐fold and 210‐fold, respectively, compared to parental cell lines. In vitro and in vivo experiments confirmed that both GEM‐resistant cell subgroups declined in proliferative capacity, but were more resistant to GEM. Unlike CFPAC‐1‐GR, BxPC‐3‐GR exhibited enhanced migratory and invasive properties compared with BxPC‐3 in vitro. We also compared differentially expressed mRNA profiles between parental and GEM‐resistant cells using transcriptome sequencing. RRM1, STIM1, and TRIM21 were significantly upregulated in both GEM‐resistant cell lines and confirmed to be associated with the degree of GEM resistance by quantitative reverse‐transcription polymerase chain reaction and western blot analysis. These three genes were more highly expressed in PC tissues and potentially regarded as prognostic biomarkers through database mining. Thus, our findings provide chemo‐resistant cell models to better understand the underlying mechanisms of chemoresistance, and to explore potential biomarkers for GEM response in PC patients.
A Thermodynamic Approach for Selection of Anodizing Electrolytes in Aluminium‐Holmium System
Authors: Shahzad Khurram , Mardare Cezarina Cela , Mardare Andrei Ionut , Hassel Achim Walter
Published: December 2019

In this paper, an approach is described for the electrolyte selection to grow optimally anodic films on thermally co‐evaporated aluminium and holmium combinatorial alloys. This method based on thermodynamic and electrochemical principles proves that electrolyte selection for anodizing of alloys having different microstructures and electrochemical behaviour of individual constituents can be decided by superimposing potential‐pHdiagrams of individual constituents of the alloy. For the application of this approach, the most widely investigated valve metal, aluminium, and a non‐valve metal rare earth, holmium, have been chosen as a model case. Based on self‐constructedEh‐pHdiagrams and solubility data, suitable electrolytes andpHrange leading to the formation of barrier‐type anodic films on aluminium and holmium as well as on their alloys are proposed.
Reduced Lithium/Nickel Disorder Degree of Sodium‐Doped Lithium‐Rich Layered Oxides for Cathode Materials: Experiments and Calculations
Authors: Hu Yongyuan , Qin Zhongzheng , Pei Jian , Cong Bowen , Yang Xu , Chen Gang
Published: December 2019

Sluggish kinetics and poor electrochemical stability limit the implications of Li‐rich layered oxide cathode materials, which are regarded as one of the most promising potential cathode materials for lithium‐ion batteries. In this work, a Na‐doped Li‐rich layered oxide (abbreviated as N‐LLO) cathode material is prepared through co‐precipitation combined with calcination. During the annealing process, partial Li2CO3 is substituted by Na2CO3, which helps to optimize the primary particles and realize Na doping. The obtained N‐LLO cathode exhibits a greater specific capacity and excellent rate performance. The characterization and DFT calculations suggest that the doped Na ions could reduce the formation of Li/Ni disorder defects, change local bond length, and enlarge Li interslab spacing conducive to Li‐ion diffusion, improving the rate performance.
Modified PCA and PLS: Towards a better classification in Raman spectroscopy–based biological applications
Authors: Guo Shuxia , Rösch Petra , Popp Jürgen , Bocklitz Thomas
Published: December 2019

Raman spectra of biological samples often exhibit variations originating from changes of spectrometers, measurement conditions, and cultivation conditions. Such unwanted variations make a classification extremely challenging, especially if they are more significant compared with the differences between groups to be separated. A classifier is prone to such unwanted variations (ie, intragroup variations) and can fail to learn the patterns that can help separate different groups (ie, intergroup differences). This often leads to a poor generalization performance and a degraded transferability of the trained model. A natural solution is to separate the intragroup variations from the intergroup differences and build the classifier based on merely the latter information, for example, by a well‐designed feature extraction. This forms the idea of this contribution. Herein, we modified two commonly applied feature extraction approaches, principal component analysis (PCA) and partial least squares (PLS), in order to extract merely the features representing the intergroup differences. Both of the methods were verified with two Raman spectral datasets measured from bacterial cultures and colon tissues of mice, respectively. In comparison to ordinary PCA and PLS, the modified PCA was able to improve the prediction on the testing data that bears significant difference to the training data, while the modified PLS could help avoid overfitting and lead to a more stable classification.
Estimating prediction error for complex samples
Authors: Holbrook Andrew , Lumley Thomas , Gillen Daniel
Published: December 2019

With a growing interest in using non‐representative samples to train prediction models for numerous outcomes it is necessary to account for the sampling design that gives rise to the data in order to assess the generalized predictive utility of a proposed prediction rule. After learning a prediction rule based on a non‐uniform sample, it is of interest to estimate the rule's error rate when applied to unobserved members of the population. Efron (1986) proposed a general class of covariance penalty inflated prediction error estimators that assume the available training data are representative of the target population for which the prediction rule is to be applied. We extend Efron's estimator to the complex sample context by incorporating Horvitz–Thompson sampling weights and show that it is consistent for the true generalization error rate when applied to the underlying superpopulation. The resulting Horvitz–Thompson–Efron estimator is equivalent to dAIC, a recent extension of Akaike's information criteria to survey sampling data, but is more widely applicable. The proposed methodology is assessed with simulations and is applied to models predicting renal function obtained from the large‐scale National Health and Nutrition Examination Study survey. The Canadian Journal of Statistics 48: 204–221; 2020 © 2019 Statistical Society of Canada
Perioperative care of the geriatric patient for noncardiac surgery
Authors: Wolfe Jonathan D. , Wolfe Natasha K. , Rich Michael W.
Published: December 2019

Adults age 65 and over are the fastest growing segment of the population in the United States and around the world. As the size of this population expands, the number of older adults referred for surgical procedures will continue to increase. Due to the physiologic changes of aging and the increased frequency of comorbidities, older adults are at increased risk for adverse outcomes, and perioperative care is inherently more complex than in younger individuals. In this review, we discuss the physiologic changes of aging relevant to the surgical patient, comprehensive preoperative assessment, and postoperative management of common complications in older adults in order to promote optimal clinical outcomes both perioperatively and long‐term.
Respiratory support in acute heart failure with preserved vs reduced ejection fraction
Authors: Metkus Thomas S. , Stephens Robert Scott , Schulman Steven , Hsu Steven , Morrow David A. , Eid Shaker M.
Published: December 2019

Background

There is little evidence addressing the use and differential impact of respiratory support in acute heart failure (AHF) patients with preserved (HFPEF) vs reduced (HFREF) ejection fraction. Therefore, our objective was to determine the usage and clinical outcomes of critical care respiratory support in AHF across the two populations.

Hypothesis

Respiratory support would be associated with adverse outcome in both HFPEF and HFREF.

Methods

We identified HFPEF, HFREF, invasive mechanical ventilation (IMV), and noninvasive ventilation (NIV) using International Classification of Disease‐Ninth Edition codes in the National Inpatient Sample between January 1, 2008 and December 31, 2014. We determined rates of IMV and NIV use. We identified predictors of need for IMV and NIV and the association between ventilation strategies and in‐hospital mortality in HFPEF vs HFREF.

Results

1.3 million AHF‐HFPEF and 1.7 million AHF‐HFREF hospitalizations were included; 5.98% of AHF HFPEF hospitalizations included NIV and 0.57% included IMV. Among HFREF hospitalizations, fewer (4.1%) included NIV and more (0.93%) included IMV. In HFPEF hospitalization, NIV use was associated with 2.24‐fold increased risk for death compared to no respiratory support in an adjusted model (HR 2.24 95% CI 2.05‐2.44) and IMV use was associated with 2.85‐fold increased risk for death (HR 2.85 95% CI 2.30‐3.53). This increased risk of in‐hospital mortality was similar among HFREF patients.

Conclusions

Use of respiratory support is increasing among patients with both HFPEF and HFREF and associated with substantially increased mortality in both heart failure subtypes.
Efficacy and safety of trabectedin for patients with unresectable and relapsed soft‐tissue sarcoma in Japan: A Japanese Musculoskeletal Oncology Group study
Authors: Kobayashi Hiroshi , Iwata Shintaro , Wakamatsu Toru , Hayakawa Keiko , Yonemoto Tsukasa , Wasa Junji , Oka Hiroyuki , Ueda Takafumi , Tanaka Sakae
Published: December 2019

Background

Although initial trabectedin (1.2 mg/m2) is safe and effective for patients with translocation‐related sarcoma (TRS) in Japan, its efficacy in other types of soft‐tissue sarcomas (STSs) remains unknown. This study retrospectively investigated its efficacy and safety through postmarketing surveillance of trabectedin in patients with unresectable and relapsed STS.

Methods

One hundred forty patients received intravenous trabectedin (1.2 mg/m2 on day 1 every 21 days) over the course of 24 hours. The primary endpoint was the efficacy and safety of trabectedin.

Results

Grade 3 or higher adverse events occurred in 100 patients (71%) and included hepatotoxicity (37.8%), neutropenia (32.8%), and rhabdomyolysis (3.6%). Patients at high risk for grade 3 or higher rhabdomyolysis (36%) were classified by height (≥170.3 cm) and age (≤32 years) through a classification and regression tree model (area under the curve, 0.9). The overall median progression‐free survival (PFS) was 3.7 months; with respect to the histological type, the median PFS was 17.4 months for myxoid liposarcoma, 4.9 months for leiomyosarcoma, 5.6 months for synovial sarcoma, and 3.7 months for dedifferentiated liposarcoma. Histological type (liposarcoma/leiomyosarcoma [L‐sarcoma] and TRS) and grade 3 neutropenia (but not grade 4) were associated with significantly improved PFS after trabectedin treatment (P = .003, P = .04, and P = .001). The median growth modulation index (GMI) was 0.91; 37 patients (36.7%) experienced a GMI > 1.33, and among patients with solitary fibrous tumors and undifferentiated pleomorphic sarcoma, 60% and 42.9%, respectively, had a GMI > 1.33. The median overall survival (OS) was 16.4 months. A GMI > 1.33 was associated with significantly improved OS (P = .0006).

Conclusions

Initial trabectedin at 1.2 mg/m2 has clinically meaningful benefits for patients with L‐sarcoma and certain histological subtypes of TRS.
A comparison of colour appearance for surface colours between outdoor and indoor environments
Authors: Ou Li‐Chen , Liang Ya‐Chen
Published: December 2019

Psychophysical experiments of colour appearance, in terms of lightness, colourfulness, and hue, were conducted outdoors and indoors to investigate whether there was any difference in colour appearance between outdoor and indoor environments. A panel of 10 observers participated in the outdoor experiment, while 13 observers took part in the indoor experiment. The reference white had an average luminance of 12784 cd/m2 in the outdoor experiment and 129 cd/m2 in the indoor experiment. Test colours included 42 colour patches selected from the Practical Coordinate Color System to achieve a reasonable uniform distribution of samples in CIECAM02. Experimental results show that for both outdoor and indoor environments, there was good agreement between visual data and predicted values by CIECAM02 for the three colour appearance scales, with the coefficient of variation values all lower than 25 and the R2 values all higher than 0.73, indicating little difference in the three dimensions of colour appearance between indoor and outdoor viewing conditions. Experimental data also suggest that the observers were more sensitive to variation in lightness for grayish colours than for highly saturated colours, a phenomenon that seems to relate with the Helmholtz‐Kohlrausch effect. This phenomenon was modeled for predicting perceived lightness (J′) using the present experimental data. The new J′ model was tested using three extra sets of visual data obtained both outdoors and indoors, showing good predictive performance of the new model, with an average coefficient of variation of 14, an average R2 of 0.88, and an average STRESS index of 14.18.
CD15, CD30, and PAX5 evaluation in Hodgkin's lymphoma on fine‐needle aspiration cytology samples
Authors: Cozzolino Immacolata , Vitagliano Giulio , Caputo Alessandro , Montella Marco , Franco Renato , Ciancia Giuseppe , Selleri Carmine , Zeppa Pio
Published: December 2019

Background

The phenotypical identification of diagnostic cells is crucial for the diagnosis of Hodgkin's lymphoma (HL) on fine‐needle aspiration cytology (FNAC). The aim of this study is to evaluate the immunocytochemical (ICC) expression of CD30, CD15, and PAX5 in Hodgkin's cells (HC) and Reed‐Sternberg cells (RSC) on smears and cell‐blocks (CB) of HL and to compare the performance of each antibody on smears and CB.

Methods

In 21 FNAC cases of histologically confirmed classical HL, ICC identification of HC and RSC was performed using CD15, CD30, and PAX5 on smears and CB, respectively.

Results

CD30 was positive in 19/21 cases (90.5%; 11/11 smears and 8/10 CB), CD15 was positive in 14/21 cases (66.7%; 5/11 smears and 9/10 CB), and PAX5 was positive in 13/21 cases (61.9%; 9/11 smears and 4/10CB).

Conclusions

CD15, CD30, and PAX5 are useful to the FNAC identification of HC and RSC. CD30 is the most sensitive, followed by CD15 and PAX5, which are more effective on CB and smears, respectively.
Climatic and vegetational drivers of insect beta diversity at the continental scale
Authors: Chesters Douglas , Beckschäfer Philip , Orr Michael C. , Adamowicz Sarah J. , Chun Kwok‐Pan , Zhu Chao‐Dong
Published: December 2019

Aim

We construct a framework for mapping pattern and drivers of insect diversity at the continental scale and use it to test whether and which environmental gradients drive insect beta diversity.

Location

Global; North and Central America; Western Europe.

Time period

21st century.

Major taxa studied

Insects.

Methods

An informatics system was developed to integrate terrestrial data on insects with environmental parameters. We mined repositories of data for distribution, climatic data were retrieved (WorldClim), and vegetation parameters inferred from remote sensing analysis (MODIS Vegetation Continuous Fields). Beta diversity between sites was calculated and then modeled with two methods, Mantel test with multiple regression and generalized dissimilarity modeling.

Results

Geographic distance was the main driver of insect beta diversity. Independent of geographic distance, bioclimate variables explained more variance in dissimilarity than vegetation variables, although the particular variables found to be significant were more consistent in the latter, particularly, tree cover. Tree cover gradients drove compositional dissimilarity at denser coverages, in both continental case studies. For climate, gradients in temperature parameters were significant in driving beta diversity more so than gradients in precipitation parameters.

Main conclusions

Although environmental gradients drive insect beta diversity independently of geography, the relative contribution of different climatic and vegetational parameters is not expected to be consistent in different study systems. With further incorporation of additional temporal information and variables, this approach will enable the development of a predictive framework for conserving insect biodiversity at the global scale.
Drug discovery and treatment paradigms in nonalcoholic steatohepatitis
Authors: Noureddin Mazen , Muthiah Mark D. , Sanyal Arun J.
Published: December 2019

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in western populations, and is closely associated with features of the metabolic syndrome. The burden of disease is set to rise exponentially, and this is further compounded by the lack of good medications. In addition, these patients tend to have multiple comorbidities that may not be adequately managed. In this article, we review the biological basis of potential therapies in nonalcoholic steatohepatitis (NASH), the current drugs being tested in clinical trials, as well some practical considerations in managing patients in the clinic.
Impact of diabetes on mortality and rehospitalization in acute heart failure patients stratified by ejection fraction
Authors: Al‐Jarallah Mohammed , Rajan Rajesh , Al‐Zakwani Ibrahim , Dashti Raja , Bulbanat Bassam , Ridha Mustafa , Sulaiman Kadhim , Alsheikh‐Ali Alawi A. , Panduranga Prashanth , AlHabib Khalid F. , Al Suwaidi Jassim , Al‐Mahmeed Wael , AlFaleh Hussam , Elasfar Abdelfatah , Al‐Motarreb Ahmed , Bazargani Nooshin , Asaad Nidal , Amin Haitham
Published: December 2019

Aims

The aim of this study is to determine the impact of diabetes mellitus on all‐cause mortality and rehospitalization rates at 3 months and at 1 year in patients admitted with acute heart failure (AHF) stratified by left ventricular ejection fraction (EF).

Methods and results

We analysed consecutive patients admitted to 47 hospitals in seven Middle Eastern countries (Saudi Arabia, Oman, Yemen, Kuwait, United Arab Emirates, Qatar, and Bahrain) with AHF from February to November 2012 with AHF who were enrolled in Gulf CARE, a multinational registry of patients with heart failure (HF). AHF patients were stratified into three groups: HF patients with reduced (EF) (HFrEF) (<40%), HF with mid‐range EF (HFmrEF) (40–49%), and HF patients with preserved EF (HFpEF) (≥50%). Analyses were performed using univariate and multivariate statistical techniques. The mean age of the cohort was 59 ± 15 years (ranging from 18 to 99 years), and 63% (n = 2887) of the patients were males. A total of 2258 (49%) AHF patients had diabetes mellitus. The mean EF was 37 ± 14%. A reduced EF was observed in 2683 patients (59%), whereas 962 patients (21%) had mid‐range and 932 patients (20%) had preserved EF. Multivariable analyses demonstrated no significant differences in all‐cause mortality between diabetics and non‐diabetics in all the three types of HF; at 3 months follow‐up: HFrEF [adjusted odds ratio (aOR), 1.30; 95% confidence interval (CI): 0.94–1.80; P = 0.119], HFmrEF (aOR, 0.98; 95% CI: 0.51–1.87; P = 0.952), and HFpEF (aOR, 0.69; 95% CI: 0.38–1.26; P = 0.225); and at 12‐months follow‐up: HFrEF (aOR, 1.25; 95% CI: 0.97–1.62; P = 0.080), HFmrEF (aOR, 1.07; 95% CI: 0.68–1.68; P = 0.783), and HFpEF (aOR, 1.07; 95% CI: 0.67–1.72; P = 0.779). There were also no significant differences in rehospitalization rates between diabetics and non‐diabetics in all the three types of HF; at 3 months follow‐up: HFrEF (aOR, 0.94; 95% CI: 0.74–1.19; P = 0.581), HFmrEF (aOR, 0.82; 95% CI: 0.53–1.26; P = 0.369), and HFpEF (aOR, 1.06; 95% CI: 0.64–1.78; P = 0.812); and at 12‐months follow‐up: HFrEF (aOR, 0.93; 95% CI: 0.73–1.17; P = 0.524), HFmrEF (aOR, 0.81; 95% CI: 0.56–1.17; P = 0.257), and HFpEF (aOR, 1.29; 95% CI: 0.82–2.05; P = 0.271).

Conclusions

There were no significant differences in 3 and 12 months all‐cause mortality as well as rehospitalization rates between diabetics and non‐diabetic patients in all the three types of AHF patients stratified by left ventricular ejection fraction.
Type 2 diabetes increases the long‐term risk of heart failure and mortality in patients with atrial fibrillation
Authors: Polovina Marija , Lund Lars H. , Đikić Dijana , Petrović‐Đorđević Ivana , Krljanac Gordana , Milinković Ivan , Veljić Ivana , Piepoli Massimo F. , Rosano Giuseppe M.C. , Ristić Arsen D. , Ašanin Milika , Seferović Petar M.
Published: December 2019

Aims

Impact of type 2 diabetes mellitus (T2DM) on non‐thromboembolic outcomes in atrial fibrillation (AF) is insufficiently explored. This prospective cohort study of AF patients aimed (i) to analyse the association between T2DM and heart failure (HF) events (including new‐onset HF), and all‐cause and cardiovascular mortality, (ii) to assess the impact of baseline T2DM treatment on outcomes, and (iii) to explore characteristics of new‐onset HF phenotypes in relation to T2DM status.

Methods and results

Of 1803 AF patients (515/1288, with/without prior HF), 389 (22%) had T2DM at baseline. After 5 years of median follow‐up, T2DM patients had an 85% greater risk of HF events [adjusted hazard ratio (aHR) 1.85; 95% confidence interval (CI) 1.51–2.28; P < 0.001], including a 45% increased risk for new‐onset HF (1.45; 1.17–2.28; P = 0.015). T2DM conferred a 56% higher all‐cause (1.56, 1.22–2.01; P = 0.003) and a 48% higher cardiovascular mortality (1.48; 1.34–1.93; P = 0.007). Fine–Gray analysis, with mortality as a competing risk, confirmed greater HF risk among T2DM patients. All risks were highest among insulin‐treated patients. The prevalence of new‐onset HF phenotypes was as follows: 67% preserved ejection fraction (HFpEF), 20% mid‐range ejection fraction (HFmrEF) and 13% reduced ejection fraction (HFrEF). On time‐dependent Cox regression, adjusted for baseline characteristics and an interim acute coronary event, T2DM increased aHRs for new‐onset HFpEF (2.38; 1.30–4.58; P <0.001) and the combined HFmrEF/HFrEF (1.77; 1.11–3.62; P = 0.017).

Conclusions

Atrial fibrillation patients with T2DM have independently increased risk of new‐onset/recurrent HF events, cardiovascular and all‐cause mortality, particularly when insulin‐treated. The prevailing phenotype of new‐onset HF was HFpEF; T2DM conferred higher risk of both HFpEF and HFmrEF/HFrEF.
P‐Stereogenic Phosphonates via Dynamic Kinetic Resolution: A Route towards Enantiopure Tertiary Phosphine Oxides
Authors: Mohd Aabid , Anitha Thippani , Reddy Kallu Rajender , Wencel‐Delord Joanna , Colobert Françoise
Published: December 2019

Asymmetric synthesis of P‐stereogenic phosphonates presents a great challenge. Following this target we disclose herein a DKR strategy towards the O–P coupling reaction between an easily accessible enantiopure phenol bearing a chiral sulfinyl auxiliary and a commercially available or easily accessible racemic H‐phosphinate. Although moderate to high chiral induction is achieved, several diastereopure phosphonates can be afforded either by crystallization or flash chromatography. Thus accessed optically pure P‐stereogenic precursors may be used as appealing building blocks to rapidly assembly original privileged scaffolds as illustrated via the synthesis of a chiral ligand such as PAMPO.
Synthesis of 2‐Substituted 1,2,3‐Triazoles via an Intramolecular N–N Bond Formation
Authors: Chen Cheng‐yi , Lu Xiaowei , Holland Mareike C. , Lv Shichang , Ji Xuebao , Liu Wei , Liu Jie , Depre Dominique , Westerduin Pieter
Published: December 2019

An efficient synthesis of 2‐aryl 1,2,3‐triazoles based on an intramolecular N–N bond formation is described. Selective activation of bis‐hydrazone at the dimethylamino hydrazone group with MeI forms a mono‐hydrazonium species. Treatment of the hydrazonium species with a base smoothly leads to the formation of a wide variety of 2‐aryl‐1,2,3‐triazoles in good to excellent yields. The reaction likely follows an intramolecular SN2 displacement mechanism with the trimethylammonium moiety serving as a good leaving group for the intramolecular N–N bond formation.
Enantiodivergent Synthesis of Axially Chiral Biphenyls from σ‐Symmetric 1,1'‐Biphenyl‐2,6‐diol Derivatives by Single Lipase‐Catalyzed Acylative and Hydrolytic Desymmetrization
Authors: Kasama Kengo , Aoyama Hiroshi , Akai Shuji
Published: December 2019

The enzymatic acylative desymmetrization of σ‐symmetric 2'‐halo‐1,1'‐biphenyl‐2,6‐diols was achieved for the first time using commercially available Burkholderia cepacia lipase immobilized on diatomaceous earth to give (S)‐mono esters. The hydrolytic desymmetrization of the corresponding diacetates was also achieved using the same lipase to give (R)‐mono esters. Our results, therefore, demonstrate that a single lipase can conduct the enantiodivergent synthesis of axially chiral biphenyl compounds in high chemical and optical yields.
Chemoenzymatic Synthesis of Sertraline
Authors: Marx Lisa , Ríos‐Lombardía Nicolás , Süss Philipp , Höhne Matthias , Morís Francisco , González‐Sabín Javier , Berglund Per
Published: December 2019

A chemoenzymatic approach has been developed for the preparation of sertraline, an established anti‐depressant drug. Ketoreductases (KREDs) were employed to yield a key chiral precursor. The bioreduction of the racemic tetralone exhibited excellent enantioselectivity (>99 % ee) and diastereomeric ratio (99:1) at 29 % conversion (the maximum theoretical yield is 50 %) after 7 hours. The resulting (S,S)‐alcohol was efficiently oxidized to an enantiopure (S)‐ketone, an immediate precursor of sertraline, by using sodium hypochlorite as oxidant and 2‐azaadamantane N‐oxyl (AZADO) as organocatalyst. Alternative routes aiming at the direct biocatalytic amination using imine reductases and transaminases were unsuccessful.
Limonene, the compound in essential oil of nutmeg displayed antioxidant effect in sunflower oil during the deep‐frying of Chinese Maye
Authors: Wang Dongying , Dong Ying , Wang Qing , Wang Xuede , Fan Wenchang
Published: December 2019

The deep‐frying process for plenty of fried products using vegetable oils needs safe and effective antioxidants. In the present exploration, the nutmeg essential oil (NEO) was employed as a potential antioxidant for sunflower oil during the deep‐frying of Chinese Maye at 180°C for 30 hr. In the comparative study, the additions for NEO at 0.12 g/kg, TBHQ at 0.12 g/kg, BHA at 0.08 g/kg, and BHT at 0.08 g/kg to sunflower oil were able to obviously improve its oxidative stability during the deep‐frying process, and their antioxidant effects were in the relative order: TBHQ at 0.12 g/kg > NEO at 0.12 g/kg > BHA at 0.08 g/kg > BHT at 0.08 g/kg (p < .05). Besides, NEO at 0.12 g/kg could markedly ameliorate the sensory properties including flavor, taste, crispness, and overall acceptability of the fried products, Chinese Maye (p < .05 or p < .01). In addition, using antioxidant activity‐guided fractionation, three active compounds including limonene, terpinolene, and geranyl acetate were isolated from NEO. Among them, limonene was demonstrated to not only significantly increase the oxidative stability of sunflower oil in the deep‐frying process, but also significantly increase the sensory properties of the fried products, Chinese Maye (p < .05 or p < .01). Consequently, limonene could be employed as antioxidants in sunflower oil for the deep‐frying of Chinese Maye, and the sunflower oil flavored by NEO could be used as frying oils for its oxidative stability and unique flavor.
Enhancement of Electrochemical Properties, Impedance and Resistances of Micro‐tubular IT‐SOFCs with Novel Asymmetric Structure Based on BaZr0.1Ce0.7Y0.1Yb0.1O3−δ Proton Conducting Electrolyte
Authors: Dong Y. , Chen C. , Liu M. , Rainwater B. H. , Bai Y.
Published: December 2019

Anode‐supported micro‐tubular SOFCs based on a proton and oxide ion mixed conductor electrolyte, BaZr0.1Ce0.7Y0.1Yb0.1O3−δ (BZCYYb), have been successfully fabricated via phase‐inversion process. Typical micro‐tubular cell with the configuration of Ni‐BZCYYb|BZCYYb|La0.6Sr0.4Co0.2Fe0.8O3–δ, consists of anode support, electrolyte and cathode with thicknesses of 200, 12, and 10 μm, respectively. The cells show excellent electrochemical performance with the peak power densities of 1.040, 0.902, 0.721, and 0.590 W cm−2 at 750, 700, 650, and 600 °C, respectively, with humidified (3 vol.% H2O) hydrogen as fuel and ambient air as oxidant. The AC impedance spectroscopy result shows low concentration polarization values of 0.016–0.021 Ω cm2 at 750–600 °C. Further, significant performance enhancement is observed during long‐term stability test at 600 and 750 °C under constant voltage of 0.5 and 0.7 V over 120 h, respectively, indicating excellent stability of BZCYYb under fuel cell operating condition. The high performance is attributed to high‐quality cell, validated by the dense, crack‐free BZCYYb electrolyte film supported by the anode with micro sponge‐like pores.
Uterine devascularization associated with compressive uterine suture (UD‐CUS) in surgical treatment of postpartum hemorrhage
Authors: Alves Álvaro Luiz Lage , Senra Janaína Campos , de São José Carolina Nogueira , Ribeiro Bruna Roque , de Souza Furtado Rafaela , Silva Lucas Barbosa , Silva‐Filho Agnaldo Lopes
Published: December 2019

The use of compressive vertical uterine braces with bilateral ligature of the ascendant uterine branches is an effective strategy for controlling bleeding and preserving the uterus in patients suffering from postpartum hemorrhage.