bluuebunny/crossref_metadata_2025 huggingface dataset:
Developing the Digital Kyoto Collection in Education and Research
Authors: Hill Mark Anthony
Published: April 2018

The Kyoto embryo collection was begun in 1961 by Dr. Hideo Nishimura. The collection has been continuously developed and currently contains over 44,000 human normal and abnormal specimens. Beginning online in 1997, the internet provided an opportunity to make embryos from the collection widely available for research and educational purposes (http://tiny.cc/Embryo). These embryonic development resources have been continuously published and available from that time until today. Published in Japanese as an Atlas of Embryonic Development. Published online as the Kyoto Human Embryo Visualization Project (http://atlas.cac.med.kyoto-u.ac.jp) and also as the Human Embryo Atlas (http://tiny.cc/Human_Embryo_Atlas). Published now electronically as a digital eBook (http://tiny.cc/Kyoto_Collection_eBook). This new digital format allows incorporation of whole embryo and histology manipulable images, labels, and a linked glossary. New imaging modalities of magnetic resonance imaging (MRI) and episcopic fluorescence image capture (EFIC) can also be easily displayed as animations. For research, the collection specimens and histological sections have been extensively studied and published in several hundred papers, discussed here and elsewhere in this special edition. I will also describe how the Kyoto collection will now form a major partner of a new international embryology research group, the Digital Embryology Consortium (https://human-embryology.org). The digital Kyoto collection will be made available for remote researcher access, analysis, and comparison with other collections allowing new research and educational applications. This work was presented at the 40th Anniversary Commemoration Symposium of the Congenital Anomaly Research Center, Graduate School of Medicine, Kyoto University, Japan, November, 2015. Anat Rec, 301:998–1003, 2018. © 2018 Wiley Periodicals, Inc.
The Beginning of Kyoto Collection: Focus on Memories
Authors: Yasuda Mineo
Published: April 2018

The early history of Kyoto Collection of Human Embryos and Fetuses was briefly described including reasons for planning the collection, ethical considerations, procedures for the collection, procedures for obtained specimens, research grants, participating members, and Professor Nishimura's Motto Anat Rec, 301:951–954, 2018. © 2018 Wiley Periodicals, Inc.
Convergent Synthesis of a Bisecting N‐Acetylglucosamine (GlcNAc)‐Containing N‐Glycan
Authors: Manabe Yoshiyuki , Shomura Hiroki , Minamoto Naoya , Nagasaki Masahiro , Takakura Yohei , Tanaka Katsunori , Silipo Alba , Molinaro Antonio , Fukase Koichi
Published: April 2018

The chemical synthesis of a bisecting N‐acetylglucosamine (GlcNAc)‐containing N‐glycan was achieved by a convergent synthetic route through [4+2] and [6+2] glycosylations. This synthetic route reduced the number of reaction steps, although the key glycosylations were challenging in terms of yields and selectivities owing to steric hindrance at the glycosylation site and a lack of neighboring group participation. The yields of these glycosylations were enhanced by stabilizing the oxocarbenium ion intermediate through ether coordination. Glycosyl donor protecting groups were explored in an effort to realize perfect α selectivity by manipulating remote participation. The simultaneous glycosylations of a tetrasaccharide with two disaccharides was investigated to efficiently construct a bisecting GlcNAc‐containing N‐glycan.
Big brother or harbinger of best practice: Can lecture capture actually improve teaching?
Authors: Joseph‐Richard Paul , Jessop Tansy , Okafor Godwin , Almpanis Timos , Price Daran
Published: April 2018

Lecture capture is used increasingly in the UK, and has become a normal feature of higher education. Most studies on the impact of lecture capture have focused on benefits to student learning, the flipped classroom or student non‐attendance at lectures following its introduction. It is less clear how the use of lecture capture has impacted on lecturers’ own academic practice. In this study, we use a mixed‐methods approach to explore the impact of this intrusive yet invisible technology on the quality of teaching. We have mapped our findings to the UK Professional Standards Framework (UKPSF). In doing so, our data paints a mixed picture of lecture capture's Janus‐faced reality. On the one hand, it enhances lecturer self‐awareness, planning and conscious ‘performance’; on the other hand, it crushes spontaneity, impairs interaction and breeds wariness through constant surveillance. While the Teaching Excellence Framework rewards institutions for providing state‐of‐the‐art technology and lecture recording systems, our findings pose awkward questions as to whether lecture capture is making teaching more bland and instrumental, albeit neatly aligned to dimensions of the UKPSF. We provide contradictory evidence about lecture capture technology, embraced by students, yet tentatively adopted by most academics. The implications of our study are not straightforward, except to proceed with caution, valuing the benefits but ensuring that learning is not dehumanised through blind acceptance at the moment we press the record button.
Synthesis and luminescence properties of novel 8‐hydroxyquinoline derivatives and their Eu(III) complexes
Authors: Wu Yongqiang , Guo Tiantong , Shu Dehua , Zhang Wu , Luan Fangfei , Shi Ling , Guo Dongcai
Published: April 2018

Six novel 8‐hydroxyquinoline derivatives were synthesized using 2‐methyl‐8‐hydroxyquinoline and para‐substituted phenol as the main starting materials, and were characterized by 1H nuclear magnetic resonance (NMR), mass spectrometry (MS), ultraviolet (UV) light analysis and infra‐red (IR) light analysis. Their complexes with Eu(III) were also prepared and characterized by elemental analysis, molar conductivity, UV light analysis, IR light analysis, and thermogravimetric–differential thermal analysis (TG–DTA). The results showed that the ligand coordinated well with Eu(III) ions and had excellent thermal stability. The structure of the target complex was EuY1–6(NO3)3.2H2O. The luminescence properties of the target complexes were investigated, the results indicated that all target complexes had favorable luminescence properties and that the introduction of an electron‐donating group could enhance the luminescence intensity of the corresponding complexes, but the addition of an electron‐withdrawing group had the opposite effect. Among all the target complexes, the methoxy‐substituted complex (–OCH3) had the highest fluorescence intensity and the nitro‐substituted complex (–NO2) had the weakest fluorescence intensity. The results showed that 8‐hydroxyquinoline derivatives had good energy transfer efficiency for the Eu(III) ion. All the target complexes had a relatively high fluorescence quantum yield. The fluorescence quantum yield of the complex EuY3(NO3)3.2H2O was highest among all target complexes and was up to 0.628. Because of excellent luminescence properties and thermal stabilities of the Eu(III) complexes, they could be used as promising candidate luminescent materials.
Contributions of depth filter components to protein adsorption in bioprocessing
Authors: Khanal Ohnmar , Singh Nripen , Traylor Steven J. , Xu Xuankuo , Ghose Sanchayita , Li Zheng J. , Lenhoff Abraham M.
Published: April 2018

Depth filtration is widely used in downstream bioprocessing to remove particulate contaminants via depth straining and is therefore applied to harvest clarification and other processing steps. However, depth filtration also removes proteins via adsorption, which can contribute variously to impurity clearance and to reduction in product yield. The adsorption may occur on the different components of the depth filter, that is, filter aid, binder, and cellulose filter. We measured adsorption of several model proteins and therapeutic proteins onto filter aids, cellulose, and commercial depth filters at pH 5–8 and ionic strengths <50 mM and correlated the adsorption data to bulk measured properties such as surface area, morphology, surface charge density, and composition. We also explored the role of each depth filter component in the adsorption of proteins with different net charges, using confocal microscopy. Our findings show that a complete depth filter's maximum adsorptive capacity for proteins can be estimated by its protein monolayer coverage values, which are of order mg/m2, depending on the protein size. Furthermore, the extent of adsorption of different proteins appears to depend on the nature of the resin binder and its extent of coating over the depth filter surface, particularly in masking the cation‐exchanger‐like capacity of the siliceous filter aids. In addition to guiding improved depth filter selection, the findings can be leveraged in inspiring a more intentional selection of components and design of depth filter construction for particular impurity removal targets.
Three‐dimensional collagenous niche and azacytidine selectively promote time‐dependent cardiomyogenesis from human bone marrow‐derived MSC spheroids
Authors: Joshi Jyotsna , Mahajan Gautam , Kothapalli Chandrasekhar R.
Published: April 2018

Endogenous adult cardiac regenerative machinery is not capable of replacing the lost cells following myocardial infarction, often leading to permanent alterations in structure‐function‐mechanical properties. Regenerative therapies based on delivering autologous stem cells within an appropriate 3D milieu could meet such demand, by enabling homing and directed differentiation of the transplanted cells into lost specialized cell populations. Since type I collagen is the predominant cardiac tissue matrix protein, we here optimized the 3D niche which could promote time‐dependent evolution of cardiomyogenesis from human bone marrow‐derived mesenchymal stem cells (BM‐MSC). 3D collagen gel physical and mechanical characteristics were assessed using SEM and AFM, respectively, while the standalone and combined effects of collagen concentration, culture duration, and 5‐azacytidine (aza) dose on the phenotype and genotype of MSC spheroids were quantified using immunofluorescence labeling and RT‐PCR analysis. Increasing collagen concentration led to a significant increase in Young's modulus (p < 0.01) but simultaneous decrease in the mean pore size, resulting in stiffer gels. Spheroid formation significantly modulated MSC differentiation and genotype, mostly due to better cell–cell interactions. Among the aza dosages tested, 10 μM appears to be optimal, while 3 mg/ml gels resulted in significantly lower cell viability compared to 1 or 2 mg/ml gels. Stiffer gels (2 and 3 mg/ml) and exposure to 10 μM aza upregulated early and late cardiac marker expressions in a time‐dependent fashion. On the other hand, cell–cell signaling within the MSC spheroids seem to have a strong role in influencing mature cardiac markers expression, since neither aza nor gel stiffness seem to significantly improve their expression. Western blot analysis suggested that canonical Wnt/β‐catenin signaling pathway might be primarily mediating the observed benefits of aza on cardiac differentiation of MSC spheroids. In conclusion, 2 mg/ml collagen and 10 μM aza appears to offer optimal 3D microenvironment in terms of cell viability and time‐dependent evolution of cardiomyogenesis from human BM‐MSCs, with significant applications in cardiac tissue engineering and stem cell transplantation for regenerating lost cardiac tissue.
Stable miRNA overexpression in human CAP cells: Engineering alternative production systems for advanced manufacturing of biologics using miR‐136 and miR‐3074
Authors: Weis Benjamin L. , Guth Nadine , Fischer Simon , Wissing Silke , Fradin Simon , Holzmann Karl‐Heinz , Handrick René , Otte Kerstin
Published: April 2018

Chinese hamster ovary (CHO) cells still represent the major production host for therapeutic proteins. However, multiple limitations have been acknowledged leading to the search for alternative expression systems. CEVEC's amniocyte production (CAP) cells are human production cells demonstrated to enable efficient overexpression of recombinant proteins with human glycosylation pattern. However, CAP cells have not yet undergone any engineering approaches to optimize process parameters for a cheaper and more sustainable production of biopharmaceuticals. Thus, we assessed the possibility to enhance CAP cell production capacity via cell engineering using miRNA technology. Based on a previous high‐content miRNA screen in CHO‐SEAP cells, selected pro‐productive miRNAs including, miR‐99b‐3p, 30a‐5p, 329‐3p, 483‐3p, 370‐3p, 219‐1‐3p, 3074‐5p, 136‐3p, 30e‐5p, 1a‐3p, and 484‐5p, were shown to act pro‐productive and product independent upon transient transfection in CAP and CHO antibody expressing cell lines. Stable expression of miRNAs established seven CAP cell pools with an overexpression of the pro‐productive miRNA strand. Subsequent small‐scale screening as well as upscaling batch experiments identified miR‐136 and miR‐3074 to significantly increase final mAb concentration in CAP‐mAb cells. Transcriptomic changes analyzed by microarrays identified several lncRNAs as well as growth and apoptosis‐related miRNAs to be differentially regulated in CAP‐mAb‐miR‐136 and ‐miR‐3074. This study presents the first engineering approach to optimize the alternative human expression system of CAP‐cells.
Nationwide trends in the incidence and outcome of patients with gastrointestinal stromal tumour in the imatinib era
Authors: van der Graaf W T A , Tielen R , Bonenkamp J J , Lemmens V , Verhoeven R H A , de Wilt J H W
Published: April 2018

Background

The incidence, treatment and outcome of patients with newly diagnosed gastrointestinal stromal tumour (GIST) were studied in an era known for advances in diagnosis and treatment.

Methods

Nationwide population-based data were retrieved from the Netherlands Cancer Registry. All patients with GIST diagnosed between 2001 and 2012 were included. Primary treatment, defined as any treatment within the first 6–9 months after diagnosis, was studied. Age-standardized incidence was calculated according to the European standard population. Changes in incidence were evaluated by calculating the estimated annual percentage change (EAPC). Relative survival was used for survival calculations with follow-up available to January 2017.

Results

A total of 1749 patients (54·0 per cent male and median age 66 years) were diagnosed with a GIST. The incidence of non-metastatic GIST increased from 3·1 per million person-years in 2001 to 7·0 per million person-years in 2012; the EAPC was 7·1 (95 per cent c.i. 4·1 to 10·2) per cent (P < 0·001). The incidence of primary metastatic GIST was 1·3 per million person-years, in both 2001 and 2012. The 5-year relative survival rate increased from 71·0 per cent in 2001–2004 to 81·4 per cent in 2009–2012. Women had a better outcome than men. Overall, patients with primary metastatic GIST had a 5-year relative survival rate of 48·2 (95 per cent c.i. 42·0 to 54·2) per cent compared with 88·8 (86·0 to 91·4) per cent in those with non-metastatic GIST.

Conclusion

This population-based nationwide study found an incidence of GIST in the Netherlands of approximately 8 per million person-years. One in five patients presented with metastatic disease, but relative survival improved significantly over time for all patients with GIST in the imatinib era.
Prognostic significance of gross extrathyroidal extension invading only strap muscles in differentiated thyroid carcinoma
Authors: Park S Y , Kim H I , Kim J-H , Kim J S , Oh Y L , Kim S W , Chung J H , Jang H W , Kim T H
Published: April 2018

Background

In the eighth edition of the AJCC staging system for differentiated thyroid carcinoma (DTC), minimal extrathyroidal extension (ETE) is no longer a determinant of T3 category. Instead, gross ETE invading only strap muscles has been designated as a new T3b category. The long-term prognosis of patients with DTC and gross ETE invading only strap muscles was investigated.

Methods

This was a retrospective analysis of patients who underwent thyroidectomy between 1996 and 2005. Differences in cancer-specific and recurrence-free survival according to extent of ETE were assessed.

Results

A total of 3174 patients with DTC were included. No significant differences were observed in 10-year cancer-specific survival among patients with no ETE (98·6 per cent), microscopic ETE (98·3 per cent) and gross ETE invading only strap muscles (98·9 per cent) (P = 0·375). The 10-year recurrence-free survival rate for patients with gross ETE invading only strap muscles (89·2 per cent) was shorter than that for patients with no ETE (93·7 per cent; P = 0·016), but similar to that of patients with microscopic ETE (90·3 per cent). In univariable analysis, patients with gross ETE invading only strap muscles had a significantly higher risk of recurrence than those with no ETE (hazard ratio (HR) 1·67, 95 per cent c.i. 1·10 to 2·55; P = 0·017). In multivariable analysis, gross ETE invading only strap muscles was not an independent predictor of recurrence (HR 1·09, 0·71 to 1·69; P = 0·685).

Conclusion

Although gross ETE invading only strap muscles may provide prognostic information about long-term recurrence, it does not affect mortality. The actual impact of gross ETE invading only strap muscles will be important in revising the staging system in the future.
Firm sustainable development and stakeholder engagement: The role of government support
Authors: Quan Yi , Wu Huiying , Li Sihai , Ying Sammy Xiaoyan
Published: April 2018

This study examines the sustainable development of Chinese firms in the context of the government implementing environmental policies that support green initiatives, from a resource‐based perspective. Using a sample of Chinese listed firms in the most polluting industries during the period 2001–2015, we find a positive relationship between environmental performance and economic performance. We also find that government‐controlled resources, including bank loans and tax benefits, are the mechanisms through which the effects of environmental investments are transformed into economic gains. Further analyses show that the positive association between environmental and economic performance holds for state‐owned firms only. These results indicate that although “being green” is associated with improvements in firm performance, such a strategy benefits only those firms that receive preferential treatment from the government. This study reveals that the Chinese Government, as the most influential stakeholder, plays an important role in determining the impact of environmental performance on economic performance.
Online sexual activity involving webcams—An overview of existing literature and implications for sexual boundary violations of children and adolescents
Authors: Koops Thula , Dekker Arne , Briken Peer
Published: April 2018

Despite the relevance of the Internet and its increasing use for sexual purposes, research into online sexual activity (OSA) involving webcams is limited. Aside from positive experiences, OSA may implicate violations of sexual boundaries, reaching from minor issues to serious forms of sexual abuse. To provide a basis for a classification of sexual boundary violations online and a conceptualization of preventive measures, a systematic review of the literature on OSA involving webcams was conducted, resulting in publications from four thematic categories: webcam use in common OSA, psychopathological phenomena, sex work, and crime and indecency (commercial sexual exploitation, trafficking, and sexual boundary violations). The discussion addresses the implications of different types of sexual boundary violation of children and adolescents on the Internet. The study's Internet findings could promote prevention and law enforcement strategies tailored to these types of offense as well as different target groups.
“OslerWarned”: WasWilliamOsler aGraveRobber While atMcGill or Was He a Victim (or Perpetrator) of One Final Practical Joke?
Authors: Wright James R.
Published: April 2018

Bodysnatching was an illegal way to procure cadavers for anatomical dissection before the existence of effective anatomy legislation. As knowledge of anatomy was fundamental to medical practice, many famous nineteenth century physicians turned a blind eye to this activity or even participated. Sir William Osler, perhaps the most revered physician of all time, received his medical degree from McGill University in 1872 and then served as pathologist at Montreal General Hospital from 1874 to 1884, where he began a career which culminated in him becoming both the first Professor of Medicine at Johns Hopkins and then Regius Professor at Oxford. Quebec had been slow to enact effective anatomy legislation, and most of the cadavers in the McGill anatomy laboratory were resurrected; Osler's close friend and Anatomy Demonstrator Francis Shepherd was convicted of this offence on several occasions. In 1940, a letter was discovered in the archives at the McGill's William Osler Library, purportedly written in 1880, accusing Osler of being a grave robber while in Montreal. My paper dissects the letter to assess its credibility in the historical context of Osler's early life and the fact that Osler was a lifelong notorious practical joker with his own pseudonym, Dr. Egerton Yorrick Davis, who helped with his pranks. The provenance of the letter is analyzed and the paper explores, using historical context and forensic handwriting analysis, whether this letter is a revenge‐motivated practical joke played on him by one of his famous colleagues or represents Osler's last practical joke for posterity. Clin. Anat. 31:632–640, 2018. © 2018 Wiley Periodicals, Inc.
MiR‐21 improves invasion and migration of drug‐resistant lung adenocarcinoma cancer cell and transformation of EMT through targeting HBP1
Authors: Su Chongyu , Cheng Xu , Li Yunsong , Han Yi , Song Xiaoyun , Yu Daping , Cao Xiaoqing , Liu Zhidong
Published: April 2018

This study was aimed at the investigation of the effects of miR‐21 on drug resistance, invasion, migration, and epithelial–mesenchymal transition (EMT) of lung adenocarcinoma cells and the related molecular mechanisms. Cell viability of A549 cell line was measured by MTT assay. Wound healing assay and transwell assay were, respectively, employed to examine cell migration and invasion abilities. The cells were transfected with miR‐21 mimic or inhibitor using Lipofectamine 3000. The target relationship between miR‐21 and HBP1 was confirmed by luciferase reporter gene assay. Western blot and qRT‐PCR were used to examine the expression of HBP1 and EMT‐related molecules. Compared with A549 cells, drug resistance of A549/PTX cells and A549/DDP cells were obviously stronger. A549/PTX cells and A549/DDP cells had stronger ability of migration and invasion compared with parental A549 cells. Meanwhile, EMT of A549/PTX and A549/DDP was significantly higher than that of A549 cells. MiR‐21 promoted migration, invasion, and EMT of human lung adenocarcinoma cancer cells. Our experiment also verified the target relationship between miR‐21 and HBP1. MiR‐21 may affect migration and invasion ability of drug‐resistant lung adenocarcinoma cells by targeting HBP1, therefore modulating EMT.
Association between operative technique and intrusive thoughts on health‐related Quality of Life 3 years after APE/ELAPE for rectal cancer: results from a national Swedish cohort with comparison with normative Swedish data
Authors: Prytz Mattias , Ledebo Anna , Angenete Eva , Bock David , Haglind Eva
Published: April 2018

The aim of this prospective registry‐based population study was to investigate the association between QoL 3 years after surgery for rectal cancer and intrusive thoughts and to assess the association with the type of surgery (i.e., APE or ELAPE) in a population‐based national cohort. ELAPE has been proposed as a superior surgical technique for distal rectal cancer, but long‐term effects on QoL are not known. There are also no studies on the association of negative intrusive thoughts on patients′ self‐reported Quality of Life following surgery for distal rectal cancer. Negative intrusive thoughts are regarded as a marker of incomplete cognitive processing of the psychological trauma caused by, for example, a cancer diagnosis. Intrusive thoughts have been recognized as an important factor associated Quality of Life outcome following surgery for other malignancies. All Swedish patients operated with any kind of abdominoperineal resection in the years 2007–2009 were identified through the Swedish ColoRectal Cancer Registry (SCRCR)—the APER population. All patients alive 3 years after surgery and willing to participate were included. Data were collected from three different sources: the registry, the original operative notes, and a study‐specific questionnaire regarding health‐related QoL answered by the patients. Questions on QoL from a normative reference population were also collected for comparison. Fifty‐six percent of the APER population reported a low overall Quality of Life. There was no significant difference between the sexes. Among men, there was a difference in overall QoL, with a higher level in the normative population (48%) compared with the male APER population (39%). Overall QoL was compared to a normative Swedish population. Almost half of the patients experienced negative intrusive thoughts, which was associated with a lower overall Quality of Life. The frequency and severity of negative intrusive thoughts were significantly associated with a low overall QoL. There was no difference in overall QoL after standard, compared with extralevator abdominoperineal excision. A large proportion of survivors after abdominoperineal excision for rectal cancer has a Quality of Life compared with a normative population, but many suffer from negative intrusive thoughts, a symptom of stress, which significantly decrease overall Quality of Life.
BCR‐ABL enhances the prolyl isomerase activity of Pin 1 by interacting with DAPK1 in ph+ALL
Authors: Cao Wen‐bin , Yao Jian‐feng , Feng Si‐zhou , He Yi , Jiang Er‐lie , Zhang Rong‐li , Yang Dong‐lin , Gong Ming , Zheng Xiao‐hui , Chen Shu‐lian , Sun Jia‐li , Zhou Lu‐kun , Han Ming‐zhe
Published: April 2018

Philadelphia chromosome (Ph)/BCR‐ABL‐positive (ph+) ALL is the most common genetic abnormality associated with ALL and has been shown to confer the worst prognosis to both children and adults. Increasing evidence has revealed that the dysregulation of prolyl isomerase Pin 1 contributes to multicancer development and progression, including ALL, although the underlying molecular mechanisms remain unclear. Here, we report that the expression of Pin 1 was enhanced in ph+ ALL patient samples and was associated positively with the expression of BCR‐ABL. Genetically or pharmacologically inhibiting Pin 1 expression or activity produces potent therapeutic efficacy against ph+ ALL. We further demonstrated that BCR‐ABL enhances the prolyl isomerase activity of Pin 1 by decreasing the phosphorylated level of Pin 1 at Ser 71 and interacting with DAPK1. The inhibition of BCR‐ABL activity by imatinib in human ph+ ALL cells reduces the prolyl isomerase activity of Pin 1, further suggesting a key role of the newly identified BCR‐ABL‐Pin 1 axis in ph+ ALL progression. Thus, the combined suppression of Pin 1 and BCR‐ABL proteins may be exploited as an additional target therapy for ph+ ALL.
Risk factors for length of stay and charge per day differ between older and younger hospitalized patients withAML
Authors: Kumar Anita J. , Henzer Tobi , Rodday Angie Mae , Parsons Susan K.
Published: April 2018

Acute myeloid leukemia (AML) is associated with frequent hospitalizations. We evaluated factors associated with length of stay (LOS) and charge per day (CPD) for admissions in older (≥60 years) and younger patients (<60 years). We identified patients withICD‐9‐CMcodes forAMLor myeloid sarcoma in the 2012HCUP‐NIS. In separate models based on age, we examined patient (sex, race, income, insurance payer, chronic conditions, chemotherapy administration, death) and hospital (type, geography) characteristics. Multivariable negative binomial regression estimated factor effects onLOSandCPDusing rate ratios, withHCUP‐NISweights. In 43,820 discharges,LOSwas longer in patients <60 than ≥60 (6.8 vs. 5.4 days). For patients <60, longerLOSwas seen with more chronic conditions (RR = 1.10), Black race (RR = 1.16), chemotherapy (RR = 2.27), and geography; shorterLOSwas associated with older age (RR = 0.93), Medicare (RR = 0.83), and hospital type. For patients ≥60, longerLOSassociated with chronic conditions (RR = 1.07) and Asian race (RR = 1.33). ShorterLOSassociated with older age (RR = 0.86), higher income (RR = 0.93), and hospital type. For patients <60, higherCPDassociated with chronic conditions (RR = 1.05), death (RR = 1.93), and geography; lowerCPDassociated with increasing age (RR = 0.96), Medicaid (RR = 0.93), and rural hospitals (RR = 0.65). For patients ≥60, higherCPDassociated with Medicare (RR = 1.05), more chronic conditions (RR = 1.02), younger age (RR = 1.1), west geography (RR = 1.37), death (RR = 1.45), and Hispanic race (RR = 1.15). We identify predictors for increased healthcare utilization in hospitalized patients withAML, which differ within age groups. Future efforts are needed to link utilization outcomes with clinical treatments and response.
The influence of retailer size on consumer responses to social responsibility initiatives
Authors: Green Todd , Allen Alexis M. , Peloza John
Published: April 2018

The current research demonstrates that retailer size moderates the positive effect of corporate social responsibility (CSR) initiatives on consumer outcomes such as increased purchase intentions and perceptions of CSR. Retailer size is introduced as a factor that leads consumers to respond more positively to small retailers' CSR activities, relative to CSR from large retailers. We also provide support for the ability of consistency/commitment to CSR to serve as a means by which larger retailers can counter their size liability. We replicate and generalize these results across multiple CSR forms. Implications for retail management and future research are discussed.
Status of Demand‐Driven Biogas Concepts to Cover Residual Load Rises
Authors: Peters Lena , Uhlenhut Frank , Biernacki Piotr , Steinigeweg Sven
Published: April 2018

Fluctuations in wind and solar energy due to climatic conditions as well as the rising demand of renewable energy puts an increasingly stronger focus on alternative systems like the demand‐driven biogas production. Hence, currently examined concepts for flexibilization of biogas plants are described. The biogas storage as well as the demand‐driven biogas production by feeding management, variable conversion in electricity, disintegration processes, or packed‐bed fermentation belong to these concepts. Also, the combination with power‐to‐gas or power‐to‐heat systems seems promising and is discussed.
Thioether Macrocyclic Peptides Selected against TET1 Compact Catalytic Domain Inhibit TET1 Catalytic Activity
Authors: Nishio Kosuke , Belle Roman , Katoh Takayuki , Kawamura Akane , Sengoku Toru , Hanada Kazuharu , Ohsawa Noboru , Shirouzu Mikako , Yokoyama Shigeyuki , Suga Hiroaki
Published: April 2018

The ten–eleven translocation (TET) protein family, consisting of three isoforms (TET1/2/3), have been found in mammalian cells and have a crucial role in 5‐methylcytosine demethylation in genomic DNA through the catalysis of oxidation reactions assisted by 2‐oxoglutarate (2OG). DNA methylation/demethylation contributes to the regulation of gene expression at the transcriptional level, and recent studies have revealed that TET1 is highly elevated in malignant cells of various diseases and related to malignant alteration. TET1 inhibitors based on a scaffold of thioether macrocyclic peptides, which have been discovered by the random nonstandard peptide integrated discovery (RaPID) system, are reported. The affinity‐based selection was performed against the TET1 compact catalytic domain (TET1CCD) to yield thioether macrocyclic peptides. These peptides exhibited inhibitory activity of the TET1 catalytic domain (TET1CD), with an IC50 value as low as 1.1 μm. One of the peptides, TiP1, was also able to inhibit TET1CD over TET2CD with tenfold selectivity, although it was likely to target the 2OG binding site; this provides a good starting point to develop more selective inhibitors.
A Tryptophan Prenyltransferase with Broad Substrate Tolerance from Bacillus subtilis subsp. natto
Authors: Sugita Tomotoshi , Okada Masahiro , Nakashima Yu , Tian Tian , Abe Ikuro
Published: April 2018

Bacillus subtilis subsp. natto secretes the ComXnatto pheromone as a quorum‐sensing pheromone to produce poly‐γ‐glutamate for biofilm formation. The amino‐acid sequence of the pheromone is Lys‐Trp‐Pro‐Pro‐Ile‐Glu, and the tryptophan residue is post‐translationally modified with a farnesyl group to form a tricyclic scaffold. Unlike other Bacillus ComX pheromones, the tryptophan residue is distant from the C‐terminal end of the precursor peptide ComXnatto. Here, we report the functional analysis of ComQnatto, which catalyzes a unique farnesyl‐transfer reaction. ComQnatto recognizes not only full‐length ComXnatto but also N‐ and/or C‐terminal truncated ComXnatto analogues and even a single tryptophan for modification with a farnesyl group in vitro. These results, together with the calculated kinetic parameters, suggest that ComQnatto does not require a leader sequence for substrate recognition and is a promising enzyme with broad substrate tolerance for the synthesis of various prenylated tryptophan derivatives.
Listeria monocytogenes meningitis
Authors: Matsuo Takahiro , Mori Nobuyoshi , Sakurai Aki , Furukawa Keiichi
Published: April 2018

Key Clinical Message

Tumbling motility is one of the useful characteristics of Listeria monocytogenes. This can be helpful to identify the causative pathogen along with Gram staining before the confirmatory microbiological examination.
Single Metal Atoms Anchored in Two‐Dimensional Materials: Bifunctional Catalysts for Fuel Cell Applications
Authors: Back Seoin , Kulkarni Ambarish R. , Siahrostami Samira
Published: April 2018

Single metal atoms doped in two‐dimensional materials have attracted particular attention for various catalytic reactions, due to their unique properties beyond metal catalysts. Herein we present density functional theory (DFT) calculations to study a wide range of such systems for oxygen reduction reaction (ORR) and hydrogen oxidation reaction (HOR) for application in cathode and anode of fuel cell, respectively. We find that the scaling relation of adsorption free energies of relevant ORR intermediates changes in the direction of improved activity. By considering more than 50 combinations, various ORR and HOR candidates are identified with improved catalytic activities compared to the state‐of‐the‐art Pt (111). Particularly, Rh embedded in N‐doped graphene is predicted to be markedly active for bifunctional fuel cell catalysis. This work highlights the potential of these systems as new classes of electrocatalysts to maximize the ORR catalytic activity and alleviate the use of precious metals
Redox‐Responsive Covalent Organic Nanosheets from Viologens and Calix[4]arene for Iodine and Toxic Dye Capture
Authors: Skorjanc Tina , Shetty Dinesh , Sharma Sudhir Kumar , Raya Jesus , Traboulsi Hassan , Han Dong Suk , Lalla Jayesh , Newlon Ryan , Jagannathan Ramesh , Kirmizialtin Serdal , Olsen John‐Carl , Trabolsi Ali
Published: April 2018

Owing to their chemical and thermal stabilities, high uptake capacities, and easy recyclability, covalent organic polymers (COPs) have shown promise as pollutant sponges. Herein, we describe the use of diazo coupling to synthesize two cationic COPs, COP1++ and COP2++, that incorporate a viologen‐based molecular switch and an organic macrocycle, calix[4]arene. The COPs form nanosheets that have height profiles of 6.00 nm and 8.00 nm, respectively, based on AFM measurements. The sheets remain morphologically intact upon one‐ or two‐electron reductions of their viologen subunits. MD simulations of the COPs containing dicationic viologens indicate that the calix[4]arenes adopt a partial cone conformation and that, in height, the individual 2D polymer layers are 5.48 Å in COP1++ and 5.65 Å in COP2++, which, together with the AFM measurements, suggests that the nanosheets are composed of 11 and 14 layers, respectively. Whether their viologens are in dicationic, radical cationic, or neutral form, the COPs exhibit high affinity for iodine, reaching up to 200 % mass increase when exposed to iodine vapor at 70 °C, which makes the materials among the best‐performing nanosheets for iodine capture reported in the literature. In addition, the COPs effectively remove Congo red from solution in the pH range of 2–10, reaching nearly 100 % removal within 15 minutes at acidic pH.
Detecting Proton Transfer in CO2 Species Chemisorbed on Amine‐Modified Mesoporous Silicas by Using 13C NMR Chemical Shift Anisotropy and Smart Control of Amine Surface Density
Authors: Čendak Tomaž , Sequeira Lisa , Sardo Mariana , Valente Anabela , Pinto Moisés L. , Mafra Luís
Published: April 2018

The wealth of site‐selective structural information on CO2 speciation, obtained by spectroscopic techniques, is often hampered by the lack of easy‐to‐control synthetic routes. Herein, an alternative experimental protocol that relies on the high sensitivity of 13C chemical shift anisotropy (CSA) tensors to proton transfer, is presented to unambiguously distinguish between ionic/charged and neutral CO2 species, formed upon adsorption of 13CO2 in amine‐modified porous materials. Control of the surface amine spacing was achieved through the use of amine protecting groups during functionalisation prior to CO2 adsorption. This approach enabled the formation of either “isolated” or “paired” carbamate/carbamic acid species, providing a first experimental NMR proof towards the identification of both aggregation states. Computer modelling of surface CO2‐amine adducts assisted the solid‐state NMR assignments and validated various hydrogen‐bond arrangements occurring upon formation of isolated/aggregated carbamic acid and alkylammonium carbamate ion species. This work extends the understanding of chemisorbed CO2 structures formed at pore surfaces and reveals structural insight about the protonation source responsible for the proton‐transfer mechanism in such aggregates.
Synthesis of 3H‐Benzo[e]indoline and Its Application to Small‐Molecule Organic Solar Cells
Authors: Chen Yao , Wu Jianglin , Yang Lin , Hu Bin , Yang Daobin , Lu Zhiyun , Huang Yan
Published: April 2018

A squaraine‐based small molecule (USQ‐BI) bearing 3H‐benzo[e]indoline was synthesized as an electron donor, and the corresponding organic solar cells show power conversion efficiency of 5.35 % with an excellent short circuit current of over 15 mA cm−2. The hole mobility of USQ‐BI was about 5 times (9.57×10−5 vs. 2.00×10−5 cm2 V−1 s−1) higher than that of indoline‐based squaraine.
Luminescent‐Substituted Fluoranthenes—Synthesis, Structure, Electrochemistry, and Optical Properties
Authors: Slodek Aneta , Maroń Anna , Pająk Michał , Matussek Marek , Grudzka‐Flak Iwona , Małecki Jan G. , Świtlicka Anna , Krompiec Stanisław , Danikiewicz Witold , Grela Małgorzata , Gryca Izabela , Penkala Mateusz
Published: April 2018

Six novel fluoranthene derivatives, namely, three terminally substituted and three bis(fluoranthene) units with fluorene, bithiophene, and carbazole spacers, were obtained through [2+2+2] cycloaddition and characterized completely. Based on the conducted studies, the obtained derivatives can be classified as donor–acceptor (D‐A) and acceptor‐donor‐acceptor (A‐D‐A) systems, in which the fluoranthene unit acts as an electron‐withdrawing unit. The optical results revealed that novel fluoranthene derivatives absorb light in the range λ=236–417 nm, which originates from a π→π* transition within the conjugated system. The compounds exhibit fluorescence that range from deep blue to green, which mainly arises from intramolecular charge transfer (ICT) states. High Stoke shifts and high quantum yields in solution (ϕ=0.22–0.57) and in the solid state (ϕ=0.18–0.44) have been observed for fluoranthene derivatives. All the derivatives display multistep oxidation processes at low potentials. The electronic structure of the presented compounds is additionally supported by time‐dependent DFT computations.
A General Pathway for the Synthesis of Gallastibenes containing Ga=Sb Double Bonds
Authors: Krüger Julia , Ganesamoorthy Chelladurai , John Lukas , Wölper Christoph , Schulz Stephan
Published: April 2018

Reactions of three equivalents of LGa {L=HC[C(Me)N(2,6‐iPr2C6H3)]2} with SbX3 (X=F, Cl, Br, I) proceed with insertion into the Sb−X bond, elimination of LGaX2, and formation of LGaSbGa(X)L (X=F 1, Cl 2, Br 3, I 4) containing a Ga=Sb double bond. In contrast, the 2:1 molar ratio reaction of LGa and SbCl3 initially gives the twofold insertion product [L(Cl)Ga]2SbCl 7, which could not be isolated due to its strong tendency toward elimination of LGaCl2 and formation of distibene [L(Cl)GaSb]2 5 at 25 °C or cyclotristibine [L(Cl)GaSb]3 6 at 8 °C. The formation of 1–6 can be rationalized by formation of the Ga‐substituted stibinidene L(X)GaSb as reaction intermediate.
Photochemical and Electrochemical Carbon Dioxide Utilization with Organic Compounds
Authors: Cao Yu , He Xing , Wang Ning , Li Hong‐Ru , He Liang‐Nian
Published: April 2018

In the last few years, photochemical and electrochemical CO2 transformations have attracted increasing attention in response to topical interest in renewable energy and green chemistry. The present minireview offers an overview about the current approaches for the photochemical and electrochemical carbon dioxide fixation with organic compounds. Valuable products, including carboxylic acids and heterocyclic compounds, are accessible through carboxylation and carboxylative cyclization, respectively. In photochemical and electrochemical processes, photo‐ or electro‐induced radical ions or other high‐energy organic compounds are considered as key intermediates to react with CO2. Besides, activation of CO2 to produce radical anion has also been reported.
Back Cover: Lactonization of C(sp2)—H Bonds in Enamides with CO2 (Chin. J. Chem. 5/2018)
Authors: Zhang Zhen , Zhu Chun‐Jun , Miao Meng , Han Jie‐Lian , Ju Tao , Song Lei , Ye Jian‐Heng , Li Jing , Yu Da‐Gang
Published: April 2018

The back cover picture shows a novel synthesis of 1,3‐oxazin‐6‐ones from enamides with CO2 through C—H carboxylation and one‐pot cyclization. The concept of “CO2 = CO + O”, using CO2 to replace toxic CO and stoichiometric oxidant, guilds the development of this chemistry as well as green and safe synthetic methods in the future. More details are discussed in the article by Yu et al. on page 430–436.

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Time trends in antithrombotic management of patients with atrial fibrillation treated with coronary stents: Results from TALENT‐AF (The internAtionaL stENT – Atrial Fibrillation study) multicenter registry
Authors: Potter Brian J. , Andò Giuseppe , Cimmino Giovanni , Ladeiras‐Lopes Ricardo , Frikah Zied , Chen Xin Yue , Virga Vittorio , Goncalves‐Almeida Joao , Camm A. John , Fox Keith A.A.
Published: April 2018

Background

Antithrombotic management of patients with atrial fibrillation (AF) requiring percutaneous coronary intervention (PCI) is highly variable; limited evidence‐based guidelines exist to influence practice.

Hypothesis

Patient characteristics and availability of novel drugs may have contributed to practice variability.

Methods

We undertook an international multicenter retrospective registry of AF patients treated with PCI. The primary measures of interest were antiplatelet and OAC prescriptions at discharge. We compared temporal trends between Prior (2010–2012) and Recent (2013–2015) cohorts and investigated variables associated with OAC prescription.

Results

We identified 488 cases (140 Prior, 348 Recent). Median CHADS2 and HAS‐BLED scores were 2 (IQR, 1–3) and 2 (IQR, 2–3). Clinical characteristics were similar between cohorts, with high (85%) prevalence of ACS. More patients in the Recent cohort, compared with Prior, received OAC (56.9% vs 44.3%; P = 0.01) and NOAC (27.3% vs 3.6%; P < 0.01) at baseline. Triple therapy at discharge was not different between the cohorts. Clinical presentation with ACS and consequent use of potent P2Y12 inhibitors were associated with reduced odds of OAC prescription at discharge (OR: 0.57, P = 0.045 and OR: 0.38, P = 0.023, respectively).

Conclusions

Despite little change over time in clinical characteristics of AF patients undergoing PCI, significantly more patients received OAC at presentation. However, triple therapy was not more frequent in the Recent cohort, and ACS presentation was associated with lack of OAC at discharge. We underscore the need for trial evidence and use of updated guidelines to assist clinicians in balancing ischemic and bleeding risks.
Complexity of scar and ventricular arrhythmias in dilated cardiomyopathy of any etiology: Long‐term data from the SCARFEAR (Cardiovascular Magnetic Resonance Predictors of Appropriate Implantable Cardioverter‐Defibrillator Therapy Delivery) Registry
Authors: Pedretti Stefano , Vargiu Sara , Baroni Matteo , Dellegrottaglie Santo , Lanzarin Barbara , Roghi Alberto , Milazzo Angela , Quattrocchi Giuseppina , Lunati Maurizio , Pedrotti Patrizia
Published: April 2018

Background

Late gadolinium enhancement (LGE) assessed with cardiovascular magnetic resonance (CMR) correlates with ventricular arrhythmias and survival in patients with structural heart disease. Whether some LGE characteristics may specifically improve prediction of arrhythmic outcomes is unknown.

Hypothesis

We sought to evaluate scar characteristics assessed with CMR to predict implantable cardioverter‐defibrillator (ICD) interventions in dilated cardiomyopathy of different etiology.

Methods

96 consecutive patients evaluated with CMR received an ICD. Biventricular volumes, ejection fraction, and myocardial LGE were evaluated. LGE was defined as “complex” (Cx‐LGE) in presence of ≥1 of the following: ischemic pattern, involving ≥2 different coronary territories; epicardial pattern; global endocardial pattern; and presence of ≥2 different patterns. The primary endpoint was occurrence of any appropriate ICD intervention. A composite secondary endpoint of cardiovascular death, cardiac transplantation, or ventricular assist device implantation was also considered.

Results

During a median follow‐up of 75 months, 30 and 25 patients reached the primary and secondary endpoints, respectively. Cx‐LGE was correlated with a worse primary endpoint survival (log‐rank P < 0.001). Cx‐LGE and right ventricular end‐diastolic volume were independently associated with the primary endpoint (HR: 3.22, 95% CI: 1.56–6.65, P = 0.002; and HR: 1.06, 95% CI: 1.00–1.12, P = 0.045, respectively), but not with the secondary endpoint.

Conclusions

Cx‐LGE identified at CMR imaging seems promising as an independent and specific prognostic factor of ventricular arrhythmias requiring ICD therapy in dilated cardiomyopathy of different etiologies.