bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extended RAS Analysis of the Phase III EPIC Trial: Irinotecan + Cetuximab Versus Irinotecan as Second-Line Treatment for Patients with Metastatic Colorectal Cancer
Authors: Sobrero Alberto , Lenz Heinz-Josef , Eng Cathy , Scheithauer Werner , Middleton Gary , Chen Wenfeng , Esser Regina , Nippgen Johannes , Burris Howard 
Published: November 2020

Abstract

Background
The multicenter, open-label, randomized, phase III EPIC study (EMR 062202-025) investigated cetuximab plus irinotecan versus irinotecan in patients with epidermal growth factor receptor–detectable metastatic colorectal cancer (mCRC) that progressed on first-line fluoropyrimidine- and oxaliplatin-based chemotherapy; we report the outcomes of patients with RAS-wild-type (wt) disease.

Materials and Methods
Available DNA samples from RAS-unselected patients (n = 1,164 of 1,298 [89.7%]) were reanalyzed for RAS mutations using beads, emulsion, amplification, and magnetics. Baseline characteristics, efficacy, safety, and poststudy therapy were assessed. RAS-wt status was defined as a mutated RAS allele frequency of ≤5%, with all relevant alleles being analyzable.

Results
Baseline characteristics were comparable between the groups (n = 452 patients with RAS-wt mCRC; cetuximab plus irinotecan n = 231, irinotecan n = 221) and between the RAS-wt and RAS-unselected populations. In the cetuximab plus irinotecan versus irinotecan arms, median overall survival was 12.3 versus 12.0 months, median progression-free survival (PFS) was 5.4 versus 2.6 months, and objective response rate (ORR) was 29.4% versus 5.0%, respectively. Quality of life (QoL) was improved in the cetuximab plus irinotecan arm. Serious adverse events occurred in 45.4% (cetuximab plus irinotecan) and 42.4% (irinotecan) of patients. In total, 47.1% of patients in the irinotecan arm received subsequent cetuximab therapy.

Conclusion
PFS, ORR, and QoL were improved with cetuximab plus irinotecan as a second-line treatment in patients with RAS-wt mCRC, confirming that cetuximab-based therapy is suitable in this population. Almost half of patients in the irinotecan arm received poststudy cetuximab, masking a potential overall survival benefit of cetuximab addition.

Implications for Practice
Cetuximab is approved for the treatment of RAS–wild-type metastatic colorectal cancer (mCRC). In this retrospective analysis of the phase III EPIC study (cetuximab plus irinotecan vs. irinotecan alone as second-line treatment in patients with RAS-unselected mCRC), the subgroup of patients with RAS–wild-type mCRC who received cetuximab plus irinotecan had improved progression-free survival, objective response rate, and quality of life compared with the RAS-unselected population. These findings suggest that cetuximab-based therapy is a suitable second-line treatment for patients with RAS–wild-type mCRC.
A developmental basis for the anatomical diversity of dermis in homeostasis and wound repair
Authors: Usansky Ivy , Jaworska Patrycja , Asti Ludovica , Kenny Fiona N , Hobbs Carl , Sofra Vasiliki , Song Hanfei , Logan Malcolm , Graham Anthony , Shaw Tanya J 
Published: November 2020

AbstractThe dermis has disparate embryonic origins; abdominal dermis develops from lateral plate mesoderm, dorsal dermis from paraxial mesoderm and facial dermis from neural crest. However, the cell and molecular differences and their functional implications have not been described. We hypothesise that the embryonic origin of the dermis underpins regional characteristics of skin, including its response to wounding. We have compared abdomen, back and cheek, three anatomical sites representing the distinct embryonic tissues from which the dermis can arise, during homeostasis and wound repair using RNA sequencing, histology and fibroblast cultures. Our transcriptional analyses demonstrate differences between body sites that reflect their diverse origins. Moreover, we report histological and transcriptional variations during a wound response, including site differences in ECM composition, cell migration and proliferation, and re‐enactment of distinct developmental programmes. These findings reveal profound regional variation in the mechanisms of tissue repair. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
Assessment of a computerized quantitative quality control tool for whole slide images of kidney biopsies
Authors: Chen Yijiang , Zee Jarcy , Smith Abigail , Jayapandian Catherine , Hodgin Jeffrey , Howell David , Palmer Matthew , Thomas David , Cassol Clarissa , Farris Alton B , Perkinson Kathryn , Madabhushi Anant , Barisoni Laura , Janowczyk Andrew 
Published: November 2020

AbstractInconsistencies in the preparation of histology slides and whole‐slide images (WSIs) may lead to challenges with subsequent image analysis and machine learning approaches for interrogating the WSI. These variabilities are especially pronounced in multicenter cohorts, where batch effects (i.e. systematic technical artifacts unrelated to biological variability) may introduce biases to machine learning algorithms. To date, manual quality control (QC) has been the de facto standard for dataset curation, but remains highly subjective and is too laborious in light of the increasing scale of tissue slide digitization efforts. This study aimed to evaluate a computer‐aided QC pipeline for facilitating a reproducible QC process of WSI datasets. An open source tool, HistoQC, was employed to identify image artifacts and compute quantitative metrics describing visual attributes of WSIs to the Nephrotic Syndrome Study Network (NEPTUNE) digital pathology repository. A comparison in inter‐reader concordance between HistoQC aided and unaided curation was performed to quantify improvements in curation reproducibility. HistoQC metrics were additionally employed to quantify the presence of batch effects within NEPTUNE WSIs. Of the 1814 WSIs (458 H&E, 470 PAS, 438 silver, 448 trichrome) from n = 512 cases considered in this study, approximately 9% (163) were identified as unsuitable for subsequent computational analysis. The concordance in the identification of these WSIs among computational pathologists rose from moderate (Gwet's AC1 range 0.43 to 0.59 across stains) to excellent (Gwet's AC1 range 0.79 to 0.93 across stains) agreement when aided by HistoQC. Furthermore, statistically significant batch effects (p < 0.001) in the NEPTUNE WSI dataset were discovered. Taken together, our findings strongly suggest that quantitative QC is a necessary step in the curation of digital pathology cohorts. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Silicone composites cured under a high electric field: an electromechanical experimental study
Authors: Kumar Ajeet , Patra Karali , Hossain Mokarram 
Published: November 2020

AbstractRecently, dielectric elastomers (DEs) become enviable materials for the applications of electromechanical transducers. However, requirements of enhanced properties like high dielectric constants, low elastic moduli, high stretchability, and minimum viscous and dielectric losses are major challenges for actuator and generator applications. To enhance dielectric properties, particle‐filled DE can be prepared in the presence of an electric field during the curing process, which leads to aligned particles in a regular fashion. In this work, we develop a holistic experimental characterization approach to assess how particle alignments enhance mechanical, electrical and electro‐mechanical properties over the randomly particle filled composites. For that, a commercially available silicone polymer (Ecoflex) is used and filled with high dielectric constant barium titanate fillers. In order to substantiate electromechanical performance enhancements, mechanical, electrical, electro‐mechanical, and morphology experiments are conducted on both types of silicone composites. Dielectric composites prepared under an electric field during curing process outperform in almost all aspects of electromechanical tests. This comprehensive study provides a framework that will guide future dielectric composite preparations and electrical, mechanical, and electromechanical experiments especially for the oriented dipole fillers prepared under an electric field.
Effect of polyetherimide sizing on surface properties of carbon fiber and interfacial strength of carbon fiber/polyetheretherketone composites
Authors: Liu Hansong , Zhao Yan , Li Na , Li Shuang , Li Xuekuan , Liu Zhiwei , Cheng Sheng , Wang Kai , Du Shanyi 
Published: November 2020

AbstractThe sizing process is almost invariably performed after the manufacture of carbon fiber (CF) and the sizing agent takes the effect of protecting CF surface. However, the traditional sizing agent is not suitable for processing continuous CF reinforced thermoplastic composites (CFRTPs) with high processing temperature. In this work, polyetherimide (PEI) is chosen as the sizing agent for CF reinforced polyetheretherketone (CF/PEEK) composites, and the sizing content as well as the type of sizing agent (including solvent‐based and emulsion type) were systematically researched. After a series of characterization of CF surface properties and interfacial strength of CF/PEEK, the improvement of interfacial shear strength (IFSS) and mechanical performances of sized CF/PEEK proves the enhancement of interfacial adhesion after sizing. CF/PEEK composites which contain CF handled by emulsion type sizing agent have good mechanical properties, indicating that it has the potential to replace solvent‐based sizing agent. Besides, the miscible feature of PEEK with PEI, the raise of CF surface roughness and surface energy might cause the reinforcement of interfacial mechanical properties. This research may create a potential way for CF production field, aiming at improving the interfacial performance of CFRTPs.
Sirt3 regulates adipogenesis and adipokine secretion via its enzymatic activity
Authors: Ma Oanh , Le Truc , Talbott George , HoangThao Nguyen Tram , Ha Dorothy , Ho Linh 
Published: November 2020

AbstractThe purpose of this research was to identify if Sirt3 plays a role in marrow adipogenesis and adipokines secretion, especially adiponectin using bone marrow‐derived stroma (ST2) cell model. Sirt3 overexpression leads to a significant increase in adipogenesis compared to controls. The induction of adipogenesis by Sirt3 is associated with increased gene expression of adipocyte markers as well as adiponectin/adipokines. In sharp contrast, the inhibition of Sirt3 exhibited significantly decreased adipogenesis, adipocyte markers, and adiponectin/adipokines compared to the controls. Interestingly, perilipin 1 (Plin 1) expression was decreased in Sirt3 induction but increased in Sirt3 inhibition. One hundred and fifteen mitochondrial acetylated peptides from 67 mitochondrial proteins had lower levels of acetylation in adipocytes induced by Sirt3 overexpression (Sirt3OE) compared to the control. Of the 67 proteins less enriched in acetylation, 22 acetylated proteins were decreased by more than twofold. These proteins are considered potential Sirt3 substrates in adipogenesis. In conclusion, Sirt3 has a novel, important role in modulating adipogenesis and adiponectin/adipokine expression. The connection axis among Sirt3‐adipogenesis‐adipokines was linked to its substrates by mass spectrometry analysis. These findings contribute to the efforts of revealing Sirt3 functions and Sirt3 usage as a potential target for treatment of metabolic homeostasis and diseases including type 2 diabetes.
Reduction of Nitroarenes via Catalytic Transfer Hydrogenation Using Formic Acid as Hydrogen Source: A Comprehensive Review
Authors: Romero Angel H. 
Published: November 2020

AbstractThe reduction of nitroarenes to the corresponding aromatic amines is one of the most popular reactions in organic synthesis with significant application in pharmaceutical and manufacture industry. In the last decades, many efforts have been devoted to the design highly effective, chemoselective, low‐cost and eco‐friendly protocols. In this sense, the reduction of nitroarenes via transfer hydrogenation using formic acid as hydrogen source has gained great relevance with tremendous advance over the last year as an attractive and competitive strategy to classical protocols. The efforts have mainly been focused on the discovery of efficient catalyst based on advanced mesoporous support material loaded with transition metals or metallic nanoparticles, the optimization conditions for non‐supported catalyst as well as convenient energy source to achieve an efficient and selective catalytic transfer hydrogenation (CTH) at room temperature. In the present review, several examples of reduction of nitroarenes using formic acid are shown as well as a comprehensive discussion about the role of catalyst, energy source and mechanism of reaction in the transfer hydrogenation process.
PROTAC: A Novel Technology for Drug Development**
Authors: Li Jie , Liu Jieqing 
Published: November 2020

AbstractProteolysis targeting chimeras(PROTACs)as a novel protein degradation technology is opening up a burgeoning field which will bring surprises to drug design and development. PROTACs have attracted a great deal of attention in drug discovery due to their unique mechanism. In recent years, studies on PROTAC have made increasing and vital progresses. In this review, we briefly describe the mechanism and development of PROTAC technology. Then, emphasis is placed on the application of PROTAC technology in several diseases including cancer, neuro‐degenerative diseases, autoimmune diseases and viral infections. In addition, a series of bio‐techniques relate to PROTACs established in recent years will also be discussed. Finally, we discuss the opportunities and challenges associated with PROTAC technology and analyze some potential future challenges.
Green Synthesis of AgNPs() Ultilizing Delonix Regia Extract as Anticancer and Antimicrobial Agents**
Authors: Abu‐Dief Ahmed M. , Abdel‐Rahman Laila H. , Abd‐El Sayed M. A. , Zikry Mallak Megalea , Nafady Ayman 
Published: November 2020

AbstractSilver is an effective antimicrobial agent with low toxicity, which is important especially in the treatment of burn wounds where transient bacteremia is prevalent. In this research, the green method was employed to synthesis silver nanoparticles (AgNPs). The synthesized AgNPs were characterized using IR, XRD, DLS and UV/Visible Spectrophotometery. XRD pattern of AgNPs has a face‐centered cubic (FCC) form and crystalline lattice with a crystallite size of 12 nm. FT‐IR spectra indicate the functional groups of phytochemical compounds at Delonix regia extract DRE and AgNPs. DLS showed the distribution of average particle size of AgNPs that have 11 nm mean size of the particle. The prepared AgNPs were screened for their cytotoxic effect against colon carcinoma cells (HCT‐ 116 cell line), hepatic cellular carcinoma cells (HepG‐2) and breast carcinoma cells (MCF‐7). The cytotoxic effect of AgNPs is close to the cytotoxic effect of Doxorubicin standard drug. The toxicity of the AgNPs was tested on bacterial species such as Gm (+) positive bacteria (Bacillus subtilis) and Gm (‐) negative bacteria (Serrati amarcescence and Escherichia coli) and fungal species such as Candida albicans, Getrichm candidum and Aspergillus flavus. The antimicrobial activity of AgNPs was greater towards Gm (+) positive bacteria compared to Gm (‐) negative bacteria. These biological activities of the synthesized AgNPs could be promised to use it as a drug.
Structural and theoretical study of (4E,5Z)‐4,5‐dibenzylidene‐1,2,3,6,7,8‐hexahydroacridine
Authors: Tkachev Valeriy V. , Utenyshev Andrey N. , Kovalchukova Olga V. 
Published: November 2020

AbstractThe crystal and molecular structure of (4E,5Z)‐4,5‐dibenzylidene‐1,2,3,6,7,8‐hexahydroacridine as a biologically active substance with potential antioxidant, anti‐inflammatory and anti‐microbial activity is reported. The title compound is found to be non‐planar. The rings are twisted around the central fragment of the molecule by 54.0 and 32.5°. The dihedral angle between the two phenyl rings is 23°. In crystal, the molecules are packed in head‐to‐head stacks along the b‐axis with no intermolecular H‐bonds. DFT B3LYP theoretical modeling with the LANL2DZ basis is performed and a topological analysis of the electron density distribution is carried out in the framework of the Bader QTAIM theory for both isolated molecules and dimeric associates forming stacks in the crystal. It is found that some intermolecular and intramolecular non‐valent interactions are to some extent related to the formation of weak covalent interactions in the intermolecular and intramolecular space.
Microwave‐Assisted TBHP‐Mediated Synthesis of 2‐Amino‐1,3,4‐oxadiazoles in Water
Authors: Kumar Sigalapalli Dilep , Kadagathur Manasa , Sujat Shaikh Arbaz , Jadhav Govinda S. , Bakchi Bulti , Nagendra Babu Bathini , Tangellamudi Neelima D. 
Published: November 2020

AbstractA one‐pot synthesis of 2‐amino‐1,3,4‐oxadiazoles has been achieved from the corresponding isothiocyanates and hydrazides in the presence of tert‐butyl hydroperoxide (TBHP) and water under microwave irradiation. The thiosemicarbazides intermediate could be derived in situ which underwent an intramolecular cyclodesulfurization under microwave irradiation. Apart from being simpler and green, this method offers significant advantages, such as short reaction times, economy and no requirement for a catalyst, with easy workup procedures to afford a variety of 2‐amino‐1,3,4‐oxadiazoles in significantly high yields (85–98 %). Spectroscopic techniques were employed to elucidate the chemical structures of the final compounds and ESI‐MS technique was employed to establish the formation of thiosemicarbazide intermediate and requirement of oxygen source for the completion of reaction and the most plausible reaction mechanism.
Tantalum Oxide Nanoparticles Prepared from Imidazolium Ionic Liquids as Active Hybrid Materials for Enhanced Photocatalytic Degradation of Dyes
Authors: Kray Luciana J. , Souza Virgínia S. , Galdino Nathália M. , Scholten Jackson D. 
Published: November 2020

AbstractTantalum oxide nanoparticles prepared from the hydrolysis of 1‐alkyl‐3‐methylimidazolium hexachlorotantalate ionic liquids showed an unprecedented efficiency for the photocatalytic degradation of methylene blue and methyl orange dyes in aqueous solutions. Indeed, the photodegradation of these aqueous dyes (up to 94 %) promoted by the Ta2O5 nanoparticles occurred in shorter reaction times when compared to commercially available Ta2O5 under the same reaction conditions. Moreover, the presence of residual ionic liquid and the pH of the medium seem to play significant roles in the photodegradation process. In particular, a significant synergistic effect occurred when the remaining ionic liquid and HCl are present at the surface of the hybrid nanoparticles. This effect provided favorable hydrophilic regions and pH conditions for the photodegradation of the dyes.
Thermoelectric, Electronic, and Optical Response of Nanostructured Al‐doped ZnO @ 2D‐TiC Composite
Authors: Manyedi Sechaba , Anku William W. , Kiarii Ephraim M. , Govender Penny P. 
Published: November 2020

AbstractZnO is one of the sought‐out materials for thermoelectricity. This study investigates the effect of aluminum doping, and titanium carbide (TiC) modification on the thermoelectric properties of ZnO through the synthesis of undoped ZnO, Al‐doped ZnO (Al‐ZnO), and TiC modified Al‐doped ZnO (TiC@Al‐ZnO) nanocomposite by the hydrothermal method and mechanical alloying. XRD, TEM, and SEM were used for structural and morphological studies. The electrical and thermal conductivity measurements on the nanocomposite were obtain using Van der pauw 4 probe collinear method. A decrease in thermal conductivity of ZnO from 7.62 to 5.75 W/cm K is observed after been modified with Al and TiC. TiC@Al‐ZnO nanocomposite exhibits the lowest thermal conductivity and highest power factor than Al‐doped ZnO. Furthermore, the impact of TiC and Al revealed an enormous effect on the Seebeck coefficient of ZnO reaching 105 μV K−1 AT 960 K, and a figure of merit value of 0.28 at 960 K. The increase in negative Seebeck coefficients suggests that the amount of active charge carrier, with significant energy, was temperature and structure depend. The experimental data obtained in this work showed the effect of both Al concentration and TiC nanosheet reinforcement on the thermoelectric properties of ZnO.
Properties of a Newly Identified Acetyl Esterase and Its Degradation of Diisobutyl Phthalate
Authors: Guan Ziran , Dai Shuang , Yao Qian , Zong Wei , Deng Zujun , Liu Shan , Yun Jeonyun , Xiao Xiong , Liu Liyang , Li He 
Published: November 2020

AbstractPhthalic acid esters (PAEs) are attracting growing attention because of environmental pollution and their harms to mammals, and diisobutyl phthalate (DiBP) in PAEs is still little studied. Biodegradation is a fast, efficient and inexpensive treatment preferentially used to deal with the pollution of PAEs. In this study, the recombinant esterase Est824 was obtained by heterologous expression and purification. The optimal reaction temperature and pH of the enzyme are 40 °C and 8.0 respectively. The enzyme reserves activity above 70 % in metal ion solutions at varying concentrations and thus shows high metal ion resistance. In high‐concentration salt solutions, the enzyme activity remains above 50 %, indicating that the enzyme has strong salt tolerance. The response surface method was used to optimize the fermentation conditions. With the Box‐Behnken design, the esterase yield was 1003.54 U/L. The DiBP degradation effect of the enzyme was detected by HPLC, and the degradation rate was 100 %. Therefore, the enzyme has good industrial application prospects and may be a potential candidate for the degradation of PAEs.
Activated Carbon from Renewable Sugarcane Straw: Support for Ru catalyst in glycerol hydrogenolysis to 1,2 Propanodiol, Ethyleneglycol and Propanols
Authors: Silveira Felipe J. L. , Moreira Carla R. , Grecy Izabela D. B. , Gaspar Alexandre B. 
Published: November 2020

AbstractSugarcane straw is an important agricultural residue in the ethanol industry. In this work, an activated carbon with high surface area was prepared by activating this straw with H3PO4 (CP) and used as support for Ru catalysts. A commercial activated carbon (CA) was used for comparison. Ru/activated carbons were prepared using RuCl3 (RuCAC) and Ru(NO)(NO3)3 (RuCAN, RuCPN) and characterized by textural analysis, XRF, Boehm titration, pyridine FTIR, TPD−He, TPR, H2‐chemisorption, SEM and TEM. The catalysts were tested in the glycerol hydrogenolysis under different conditions of T, P and glycerol concentration. In the standard condition, 200 °C, 50 bar and 10 vol % glycerol (GLY), the activity was strongly influenced by the availability of Ru sites on the catalysts surface and acidity following the order RuCPN>RuCAC>RuCAN. Ethylene glycol (EG) formation in RuCAC and RuCPN catalysts was related to metallic sites instead of acidic sites. The formation of 1,2‐propanediol (1,2PD) instead of 1,3‐propanediol was ascribed to predominance of Lewis sites. Reactions with GLY, 1,2PD and EG allowed to propose a reaction scheme comprising the formation of intermediates.