bluuebunny/crossref_metadata_2025 huggingface dataset:
Preferential Formation of Mono‐Metallofullerenes Governed by the Encapsulation Energy of the Metal Elements: A Case Study on Eu@C2n (2n=74–84) Revealing a General Rule
Authors: Bao Lipiao , Li Ying , Yu Pengyuan , Shen Wangqiang , Jin Peng , Lu Xing
Published: December 2019

Encapsulating one to three metal atoms or a metallic cluster inside fullerene cages affords endohedral metallofullerenes (EMFs) classified as mono‐, di‐, tri‐, and cluster‐EMFs, respectively. Although the coexistence of various EMF species in soot is common for rare‐earth metals, we herein report that europium tends to prefer the formation of mono‐EMFs. Mass spectroscopy reveals that mono‐EMFs (Eu@C2n) prevail in the Eu‐containing soot. Theoretical calculations demonstrate that the encapsulation energy of the endohedral metal accounts for the selective formation of mono‐EMFs and rationalize similar observations for EMFs containing other metals like Ca, Sr, Ba, or Yb. Consistently, all isolated Eu‐EMFs are mono‐EMFs, including Eu@D3h(1)‐C74, Eu@C2v(19138)‐C76, Eu@C2v(3)‐C78, Eu@C2v(3)‐C80, and Eu@D3d(19)‐C84, which are identified by crystallography. Remarkably, Eu@C2v(19138)‐C76 represents the first Eu‐containing EMF with a cage that violates the isolated‐pentagon‐rule, and Eu@C2v(3)‐C78 is the first C78‐based EMF stabilized by merely one metal atom.
Open Dialogue: Frequently Asked Questions
Authors: Ong Ben , Barbara‐May Rachel , Brown Judith M , Dawson Lisa , Gray Carl , McCloughen Andrea , Mikes‐Liu Kristof , Sidis Anna , Singh Rajiv , Thorpe Campbell R. , Buus Niels
Published: December 2019

Open Dialogue is an approach to working with people and their families experiencing psychosocial distress. Interest in Open Dialogue in Australia has been growing recently, raising questions about its adaption and implementation to local contexts. This article is an attempt to answer some of the frequently asked questions we have encountered in training and discussions about Open Dialogue. We attempt to provide responses to questions of how Open Dialogue is different to what is done already, how it fits with current approaches, how you know if you are doing it, whether it is passive or just about doing reflections, issues about including the social network, and concerns about the evidence base. This article aims to present a variety of viewpoints in relation to these questions and to hopefully further discussions on how Open Dialogue can be implemented and adapted to Australian health care and social care contexts.
A study on high‐temperature co‐gasification reactivity characteristics and kinetics analysis of Hami coal and its liquefaction residue
Authors: Guo Qinghua , Huang Yuchen , Gong Yan , Wei Juntao , Yu Guangsuo
Published: December 2019

In this study, the rapid pyrolysis chars of Hami bituminous coal and its liquefaction residue were prepared using a high‐frequency furnace. A thermogravimetric analyzer was used to investigate the gasification reactivity and determine the mixing ratio of coal and its liquefaction residue. In addition, a scanning electron microscope, a physisorption analyzer, and a laser raman spectrometer were used to characterize the physicochemical properties of samples. Furthermore, kinetics analysis using the isoconversional method was conducted. The results showed that the gasification reactivity was affected by gasification temperature, pore structure, and carbon structure. When the gasification temperature increased to 1300 °C, the gasification reactivity of the liquefaction residue char was close to that of coal char. From the gasification reactivity point of view, the liquefaction residue could be utilized as a raw material in entrained‐flow gasification. The mixing ratio of the raw coal to the liquefaction residue was preferably 2:1. The research on activation energy showed that the gasification process belonged to pore diffusion control in the range of temperatures investigated. Specifically, there was a synergistic effect between the coal char and the liquefaction residue char in co‐gasification, which was beneficial to the gasification reaction.
A yeast optogenetic toolkit (yOTK) for gene expression control in Saccharomyces cerevisiae
Authors: An‐adirekkun Jidapas (My) , Stewart Cameron J. , Geller Stephanie H. , Patel Michael T. , Melendez Justin , Oakes Benjamin L. , Noyes Marcus B. , McClean Megan N.
Published: December 2019

Optogenetic tools for controlling gene expression are ideal for tuning synthetic biological networks due to the exquisite spatiotemporal control available with light. Here we develop an optogenetic system for gene expression control integrated with an existing yeast toolkit allowing for rapid, modular assembly of light‐controlled circuits in the important chassis organism Saccharomyces cerevisiae. We reconstitute activity of a split synthetic zinc‐finger transcription factor (TF) using light‐induced dimerization mediated by the proteins CRY2 and CIB1. We optimize function of this split TF and demonstrate the utility of the toolkit workflow by assembling cassettes expressing the TF activation domain and DNA‐binding domain at different levels. Utilizing this TF and a synthetic promoter we demonstrate that light intensity and duty cycle can be used to modulate gene expression over the range currently available from natural yeast promoters. This study allows for rapid generation and prototyping of optogenetic circuits to control gene expression in S. cerevisiae.
Process intensification by frontal chromatography: Performance comparison of resin and membrane adsorber for monovalent antibody aggregate removal
Authors: Vogg Sebastian , Pfeifer Felix , Ulmer Nicole , Morbidelli Massimo
Published: December 2019

Aggregates are amongst the most important product‐related impurities to be removed during the downstream processing of antibodies due to their potential immunogenicity. Traditional operations use cation‐exchange resins in bind‐elute mode for their separation. However, frontal analysis is emerging as an alternative. In this study, a three‐step process development for a membrane adsorber and a resin material is carried out, allowing the comparison between the stationary phases. Based on a screening study, optimal loading conditions are determined, which show that weak binding is favored on the membrane and strong binding on the resin. Transfer of these findings to breakthrough experiments shows that at 99% pool purity the yield is higher for the membrane, while the resin can be loaded twice as high, exceeding yields of 85%. For the investigated antibody and based on a given regeneration protocol, the productivity of the two phases is similar, ranging around 200  g/(L·h). Due to the higher loading, the resin requires about one‐third less buffer than the membrane. Furthermore, the implementation of a wash step after loading allows to further increase yield by about 5%. In comparison to a generic bind‐elute process, productivity and buffer consumption are improved by an order of magnitude.
Understanding mAb aggregation during low pH viral inactivation and subsequent neutralization
Authors: Wälchli Ruben , Ressurreição Mariana , Vogg Sebastian , Feidl Fabian , Angelo James , Xu Xuankuo , Ghose Sanchayita , Jian Li Zheng , Le Saoût Xavier , Souquet Jonathan , Broly Hervé , Morbidelli Massimo
Published: December 2019

Monoclonal antibodies (mAbs) and related recombinant proteins continue to gain importance in the treatment of a great variety of diseases. Despite significant advances, their manufacturing can still present challenges owing to their molecular complexity and stringent regulations with respect to product purity, stability, safety, and so forth. In this context, protein aggregates are of particular concern due to their immunogenic potential. During manufacturing, mAbs routinely undergo acidic treatment to inactivate viral contamination, which can lead to their aggregation and thereby to product loss. To better understand the underlying mechanism so as to propose strategies to mitigate the issue, we systematically investigated the denaturation and aggregation of two mAbs at low pH as well as after neutralization. We observed that at low pH and low ionic strength, mAb surface hydrophobicity increased whereas molecular size remained constant. After neutralization of acidic mAb solutions, the fraction of monomeric mAb started to decrease accompanied by an increase on average mAb size. This indicates that electrostatic repulsion prevents denatured mAb molecules from aggregation under acidic pH and low ionic strength, whereas neutralization reduces this repulsion and coagulation initiates. Limiting denaturation at low pH by d‐sorbitol addition or temperature reduction effectively improved monomer recovery after neutralization. Our findings might be used to develop innovative viral inactivation procedures during mAb manufacturing that result in higher product yields.
Computational fluid dynamic analysis of bioprinted self‐supporting perfused tissue models
Authors: Sego T. J. , Prideaux Matthew , Sterner Jane , McCarthy Brian Paul , Li Ping , Bonewald Lynda F. , Ekser Burcin , Tovar Andres , Jeshua Smith Lester
Published: December 2019

Natural tissues are incorporated with vasculature, which is further integrated with a cardiovascular system responsible for driving perfusion of nutrient‐rich oxygenated blood through the vasculature to support cell metabolism within most cell‐dense tissues. Since scaffold‐free biofabricated tissues being developed into clinical implants, research models, and pharmaceutical testing platforms should similarly exhibit perfused tissue‐like structures, we generated a generalizable biofabrication method resulting in self‐supporting perfused (SSuPer) tissue constructs incorporated with perfusible microchannels and integrated with the modular FABRICA perfusion bioreactor. As proof of concept, we perfused an MLO‐A5 osteoblast‐based SSuPer tissue in the FABRICA. Although our resulting SSuPer tissue replicated vascularization and perfusion observed in situ, supported its own weight, and stained positively for mineral using Von Kossa staining, our in vitro results indicated that computational fluid dynamics (CFD) should be used to drive future construct design and flow application before further tissue biofabrication and perfusion. We built a CFD model of the SSuPer tissue integrated in the FABRICA and analyzed flow characteristics (net force, pressure distribution, shear stress, and oxygen distribution) through five SSuPer tissue microchannel patterns in two flow directions and at increasing flow rates. Important flow parameters include flow direction, fully developed flow, and tissue microchannel diameters matched and aligned with bioreactor flow channels. We observed that the SSuPer tissue platform is capable of providing direct perfusion to tissue constructs and proper culture conditions (oxygenation, with controllable shear and flow rates), indicating that our approach can be used to biofabricate tissue representing primary tissues and that we can model the system in silico.
Construction of hypervesiculation Escherichia coli strains and application for secretory protein production
Authors: Ojima Yoshihiro , Sawabe Tomomi , Konami Katsuya , Azuma Masayuki
Published: December 2019

Outer membrane vesicles (OMVs) are extracellular vesicles released from the surface of Gram‐negative bacteria, including Escherichia coli. Several gene‐deficient mutants relating to envelope stress (nlpI and degP) and phospholipid accumulation in the outer leaflet of the outer membrane (mlaA and mlaE) increase OMV production. This study examined the combinatorial deletion of these genes in E. coli and its effect on OMV production. The nlpI and mlaE double‐gene‐knockout mutant (ΔmlaEΔnlpI) showed the highest OMV production. Sodium dodecyl sulfate‐polyacrylamide gel electrophoresis‐based quantitative analysis showed that OMV production by strain ΔmlaEΔnlpI was ~30 times that by the wild‐type (WT). In addition, to evaluate the protein secretion capacity of OMVs, a green fluorescent protein (GFP) fused with outer membrane protein W (OmpW) was expressed in OMVs. Western blot analysis showed that GFP secretion through OMVs reached 3.3 mg/L in the culture medium of strain ΔmlaEΔnlpI/gfp, 500 times that for the WT. Our approach using OMVs for extracellular protein secretion in E. coli is an entirely new concept compared with existing secretion systems.
When companies improve the sustainability of the natural environment: A study of large U.S. companies
Authors: De Mendonca Taryn , Zhou Yan
Published: December 2019

In light of the call for companies to abandon current approaches to environmental management, this study adds to the environmental strategy literature and uses the evidence of competitive dynamics among companies to identify a mechanism by which companies invest in proactive environmental strategies and thereby improve the sustainability of the natural environment. An examination utilizing fixed effects regressions on a sample of large U.S.‐based companies reveal that even after controlling the number, environmental and financial performance of leading (environmental) companies, laggard (environmental) companies are more likely to invest in proactive environmental strategies when their leading peers display higher sustainability orientations. Neither the expectation of government regulation nor social movement pressure was found to be influential in this relationship. Therefore, the future dominance of companies' investments in the sustainability of the natural environment will be driven by companies themselves as long as competitive advantages are expected.
Origin of Regio‐ and Stereoselectivity in the NHC‐catalyzed Reaction of Alkyl Pyridinium with Aliphatic Enal
Authors: Wang Yang , Qu Ling‐Bo , Lan Yu , Wei Donghui
Published: December 2019

The mechanisms of N‐heterocyclic carbene (NHC)‐catalyzed dearomatization reaction of alkyl pyridinium have been intensively studied using the density functional theory (DFT) method. The chemoselectivity and stereoselectivity were both analyzed based on the established mechanisms. The computational results showed that the chemoselective C4‐addition occurred before the C2‐addition, which is mainly because the C4 atom was more reactive according to the local reactivity analysis. The stereoselectivity was also investigated, and the C−C bond formation step was identified as the stereoselectivity‐determining step. The C−H⋅⋅⋅F and O−H⋅⋅⋅N interactions are identified as the main factors that govern the stereoselectivity by NCI analysis, and the preferred product was the RS‐configuration. This theoretical investigation would provide a case for understanding and predicting the selectivity of the organocatalytic dearomatization reactions of alkyl pyridinium.
Activation of α‐Fe2O3 for Photoelectrochemical Water Splitting Strongly Enhanced by Low Temperature Annealing in Low Oxygen Containing Ambient
Authors: Makimizu Yoichi , Nguyen Nhat Truong , Tucek Jiri , Ahn Hyo‐Jin , Yoo JeongEun , Poornajar Mahshid , Hwang Imgon , Kment Stepan , Schmuki Patrik
Published: December 2019

Photoelectrochemical (PEC) water splitting is a promising method for the conversion of solar energy into chemical energy stored in the form of hydrogen. Nanostructured hematite (α‐Fe2O3) is one of the most attractive materials for a highly efficient charge carrier generation and collection due to its large specific surface area and the short minority carrier diffusion length. In the present work, the PEC water splitting performance of nanostructured α‐Fe2O3 is investigated which was prepared by anodization followed by annealing in a low oxygen ambient (0.03 % O2 in Ar). It was found that low oxygen annealing can activate a significant PEC response of α‐Fe2O3 even at a low temperature of 400 °C and provide an excellent PEC performance compared with classic air annealing. The photocurrent of the α‐Fe2O3 annealed in the low oxygen at 1.5 V vs. RHE results as 0.5 mA cm−2, being 20 times higher than that of annealing in air. The obtained results show that the α‐Fe2O3 annealed in low oxygen contains beneficial defects and promotes the transport of holes; it can be attributed to the improvement of conductivity due to the introduction of suitable oxygen vacancies in the α‐Fe2O3. Additionally, we demonstrate the photocurrent of α‐Fe2O3 annealed in low oxygen ambient can be further enhanced by Zn‐Co LDH, which is a co‐catalyst of oxygen evolution reaction. This indicates low oxygen annealing generates a promising method to obtain an excellent PEC water splitting performance from α‐Fe2O3 photoanodes.
Kinetische Parameteridentifikation und Modelldiskriminierung am Beispiel der nassen Oxidation von Thiosulfat
Authors: Holz Stephan , Stewers Lennart , Thielert Holger , Guetta Zion , Repke Jens‐Uwe
Published: December 2019

In der Kokereitechnik fallen belastete Abwässer an, die effizient behandelt werden müssen, um die Umwelt nicht zu belasten und den gesetzlichen Verordnungen gerecht zu werden. Hierzu ist ein genaues Prozessverständnis notwendig. Aufgrund der Vielzahl an möglichen Modifikationen nehmen Schwefelverbindungen eine Sonderstellung ein, weswegen die Kenntnis der verschiedenen Reaktionspfade und ‐kinetiken für die Auslegung der Apparate essenziell ist. Mittels Parameterschätzung und Modeldiskriminierung werden in diesem Beitrag Kinetiken anhand von Experimentaldaten ermittelt und Reaktionsschemata der Nassoxidation von Thiosulfat bewertet, um den Konzentrationsverlauf aller Spezies hinreichend genau beschreiben zu können.
Analysing the use of tools, initiatives, and approaches to promote sustainability in corporations
Authors: Lozano Rodrigo
Published: December 2019

Interest in sustainability from the corporate sector is evidenced by over 13,000 companies in 160 countries that have signed the United Nations Global Compact. In this context, a number of tools, initiatives, and approaches (TIAs), e.g., circular economy, corporate social responsibility, eco‐efficiency, life cycle assessment, and sustainability reporting have been developed by and for corporations to engage and promote sustainability within their systems. Each of the TIAs has advantages when addressing sustainability issues and the company system's elements, but it has disadvantages in dealing with their complexities and interactions. Relying only on one TIA results in a limited contribution to sustainability, whereas using too many TIAs wastes resources and energy. The Corporate and Industrial Voluntary Initiatives for Sustainability (CIVIS) has been proposed to better combine the TIAs. A survey was developed to investigate the use of 24 TIAs. The survey was sent to a database of 5,299 organisations (of which 3,603 were companies), from which 202 responses were obtained. The responses were analysed using ratio analysis, principal component analysis, and cluster analysis. The responses show that some TIAs are well known and provide good results when used, for example, corporate social responsibility, corporate sustainability, and Global Reporting Initiative reports. The analyses show a number of groups of the TIAs that can help to better combine them. The paper updates the CIVIS framework in order to provide clearer guidance on how to combine the TIAs. A combination of between four and six initiatives appears to be most effective way to promote sustainability. The TIAs can help to promote sustainability in corporations, but they need to be combined correctly in order to address holistically the four dimensions of sustainability, the system elements, and stakeholders, while avoiding duplication of tasks and wasting resources.
EUS‐FNA diagnosis of pancreatic serous cystadenoma with the aid of cell blocks and α‐inhibin immunochemistry: A case series
Authors: Sydney Guy I. , Ioakim Kalliopi J. , Michaelides Constantinos , Sepsa Athanasia , Sopaki‐Valalaki Anastasia , Tsiotos Gregory G. , Theocharis Stamatios , Salla Charitini , Nikas Ilias
Published: December 2019

Serous cystadenoma (SCA) is an uncommon benign pancreatic neoplasm that is most often managed conservatively with follow‐up rather than surgical excision. Therefore, to avoid the serious complications of pancreatic surgery, SCA should be diagnosed accurately at the preoperative level. Preoperative SCA diagnosis requires a multimodal diagnostic approach that includes imaging, cystic fluid biochemical analysis and/or endoscopic ultrasound fine‐needle aspiration (EUS‐FNA). In this brief report, we describe six EUS‐FNA cases from five patients that were reported as “benign, consistent with serous cystadenoma”. Samples were hypocellular, composed of loose clusters and single cuboidal, bland‐looking cells among epithelial sheets representing gastrointestinal contamination. Cell blocks were prepared and all six FNA cases revealed cuboidal cells with a positive α‐inhibin immunophenotype, consistent with a diagnosis of SCA. As EUS‐FNAs of SCA commonly result in non‐diagnostic interpretations, cell block preparations with subsequent immunochemistry can increase their diagnostic accuracy and guide patient management.
Potential effects of climate change on NRCS Wetland Restoration Easements: An ecohydrological assessment
Authors: Cassatt Molly Stetz , Wilcox Douglas A.
Published: December 2019

Water cycles are expected to change globally with predicted climate warming. Yet predicted shifts in hydrological regimes are rarely incorporated into wetland restoration planning, despite large investments in projects very susceptible to hydrological changes. We assessed potential effects of climate change on previously restored wetlands to identify siting and design issues for use in guiding adaptive management or planning future restoration projects. Five United States Department of Agriculture Natural Resources Conservation Service Wetland Reserve Easements in Genesee County, New York, were studied from 2013 through 2014. Elevations of surface water and groundwater were monitored, piezometric measurements made, and water chemistry and plant community data collected. Precipitation, surface water, and groundwater hydrologic data were used to relate each restored wetland to vulnerability of climate change. Although all five sites were functioning as planned, three sites had less vulnerability to climate change due to their connection to more stable sources of groundwater, position within the hydrological landscape, or design features that mimic the natural landscape. Suggestions for adaptive management on already implemented projects include actively managing water‐control structures, enhancing microtopography, and increasing plant diversity by planting or seeding. Potential sites for future restoration projects should be ranked based on location in the watershed, presence of hydric soils, past and potential hydrological connections, and sustainability of hydrology, especially groundwater sourcing. Design options should attempt to mimic natural landscape features, refrain from overengineering, and allow for flexible management of hydroperiods.
Conjugate Addition Routes to 2‐Alkyl‐2,3‐dihydroquinolin‐4(1H)‐ones and 2‐Alkyl‐4‐hydroxy‐1,2‐dihydroquinoline‐3‐carboxylates
Authors: Kingsbury Alex , Brough Steve , McCarthy Antonio Pedrina , Lewis William , Woodward Simon
Published: December 2019

Under CuBr·SMe2/PPh3 catalysis (5/10 mol‐%) RMgCl (R = Me, Et, nPr, CH=CH2, nBu, iBu, nC5H11, cC6H11, Bn, CH2Bn, nC11H23) readily (–78 °C) undergo 1,4‐addition to Cbz or Boc protected quinolin‐4(1H)‐ones to provide 2‐alkyl‐2,3‐dihydroquinolin‐4(1H)‐ones (14 examples, 54–99 % yield). Asymmetric versions require AlEt3 to Boc‐protected ethyl 6‐substituted 4(1H)‐quinolone‐3‐carboxylates (6‐R group = all halogens, n/i/t‐alkyls, CF3) and provide 61–91 % yield, 30–86 % ee; any halogen, Me, or CF3 provide the highest stereoselectivities (76–86 % ee). Additions of AlMe3 or Al(nC8H17)3 provide ≈ 45 and ≈ 75 % ee on addition to the parent (6‐R = H). Ligand (S)‐(BINOL)P–N(CHPh2)(cC6H11) provides the highest ee values engendering addition to the Si face of the 4(1H)‐quinolone‐3‐carboxylate. Allylation and deprotection of a representative 1,4‐addition product example confirm the facial selectivity (X‐ray crystallography).
Radical Reactions for the Synthesis of 3‐Substituted Chroman‐4‐ones
Authors: Xiong Li , Hu Hao , Wei Chuan‐Wan , Yu Bing
Published: December 2019

Radical cascade cyclizations of o‐allyloxybenzaldehydes have emerged as a powerful strategy for the synthesis of 3‐substituted chroman‐4‐ones. This minireview summarizes the incorporation of various functional groups into the C3‐position of chroman‐4‐ones by employing appropriate radical precursors through transition‐metal‐free systems, silver‐catalyzed systems, or visible‐light‐promoted systems.
Comparative study of the fire protection performance and thermal stability of intumescent fire‐retardant coatings filled with three types of clay nano‐fillers
Authors: Xu Zhisheng , Zhou Huan , Yan Long , Jia Hongyu
Published: December 2019

The fire protection and thermal stability properties of intumescent fire‐retardant coatings filled with three various clay nano‐fillers (layer double hydroxide [LDH], montmorillonite [MMT], and sepiolite) were compared by fire protection tests and thermo‐gravimetric analysis. The fire protection tests show that the incorporation of three fillers improves the fire protection properties of the intumescent fire‐retardant coatings and the addition of 1 wt% sepiolite exhibits the lowest flame spread rating of 9.9 and equilibrium backside temperature of 164.5°C at 900 seconds. TG analysis shows that the incorporation of nano‐fillers imparts a considerable enhancement of thermal stability and char formation to the intumescent coatings. Especially, the coating with 1 wt% sepiolite acquires the highest residual weight of 34.2% among the samples. Char residue analysis presents that the introduction of clay nano‐fillers plays a positive role in enhancing the compactness and anti‐oxidation ability of the char residues, and this positive effect as well as the flame‐retardant efficiency depends on the types of clay nano‐fillers. The three types of layered clay nano‐fillers exhibit synergistic flame‐retardant effectiveness in the order of sepiolite > MMT > LDH.
Longitudinal brain atrophy distribution in advanced Parkinson's disease: What makes the difference in “cognitive status” converters?
Authors: Gorges Martin , Kunz Martin S. , Müller Hans‐Peter , Liepelt‐Scarfone Inga , Storch Alexander , Dodel Richard , Hilker‐Roggendorf Rüdiger ,   LANDSCAPE Consortium, Berg Daniela , Kalbe Elke , Braak Heiko , Del Tredici Kelly , Baudrexel Simon , Huppertz Hans‐Jürgen , Kassubek Jan
Published: December 2019

We investigated the brain atrophy distribution pattern and rate of regional atrophy change in Parkinson's disease (PD) in association with the cognitive status to identify the morphological characteristics of conversion to mild cognitive impairment (MCI) and dementia (PDD). T1‐weighted longitudinal 3T MRI data (up to four follow‐up assessments) from neuropsychologically well‐characterized advanced PD patients (n = 172, 8.9 years disease duration) and healthy elderly controls (n = 85) enrolled in the LANDSCAPE study were longitudinally analyzed using a linear mixed effect model and atlas‐based volumetry and cortical thickness measures. At baseline, PD patients presented with cerebral atrophy and cortical thinning including striatum, temporoparietal regions, and primary/premotor cortex. The atrophy was already observed in “cognitively normal” PD patients (PD‐N) and was considerably more pronounced in cognitively impaired PD patients. Linear mixed effect modeling revealed almost similar rates of atrophy change in PD and controls. The group comparison at baseline between those PD‐N whose cognitive performance remained stable (n = 42) and those PD‐N patients who converted to MCI/PDD (“converter” cPD‐N, n = 26) indicated suggested cortical thinning in the anterior cingulate cortex in cPD‐N patients which was correlated with cognitive performance. Our results suggest that cortical brain atrophy has been already expanded in advanced PD patients without overt cognitive deficits while atrophy progression in late disease did not differ from “normal” aging regardless of the cognitive status. It appears that cortical atrophy begins early and progresses already in the initial disease stages emphasizing the need for therapeutic interventions already at disease onset.
Long‐term opioid use in curative‐intent radiotherapy: One‐Year outcomes in head/neck cancer patients
Authors: Schumacher Leif‐Erik D. , Sargi Zoukaa B. , Masforroll Melissa , Kwon Deukwoo , Zhao Wei , Rueda‐Lara Maria A. , Freedman Laura M. , Elsayyad Nagy , Samuels Stuart E. , Abramowitz Matthew C. , Samuels Michael A.
Published: December 2019

Background

No study has determined the incidence of long‐term opioid use, or risk factors for long‐term use, ≥1 year after radiotherapy.

Methods

Medical records of 276 head/neck cancer patients were retrospectively assessed for persistent opioid use 1‐year after curative‐intent radiotherapy. Numerous potential risk factors were assessed and the physicians' documented reasons for continued use were qualitatively categorized as suspected opioid use disorder (OUD) or as medically indicated for control of ongoing pain.

Results

Of note, 20 of 276 patients continued using opioids long‐term. High maximum opioid dose and the use of opioids and/or psychotropics/non‐opioid analgesics at the radiation oncology intake visit were associated with this outcome. Three patients continued due to suspected OUD and 17 due to medical indications.

Conclusion

Of note, 7.2% of patients developed long‐term opioid use, which was associated with high maximum opioid dose and early initiation of opioids and/or psychotropics/non‐opioid analgesics. Physicians cited medical indications as the primary reason for continued use.
Insights From Liver‐Humanized Mice on Cholesterol Lipoprotein Metabolism and LXR‐Agonist Pharmacodynamics in Humans
Authors: Minniti Mirko E. , Pedrelli Matteo , Vedin Lise‐Lotte , Delbès Anne‐Sophie , Denis Raphaël G.P. , Öörni Katariina , Sala Claudia , Pirazzini Chiara , Thiagarajan Divya , Nurmi Harri J. , Grompe Markus , Mills Kevin , Garagnani Paolo , Ellis Ewa C.S. , Strom Stephen C. , Luquet Serge H. , Wilson Elizabeth M. , Bial John , Steffensen Knut R. , Parini Paolo
Published: December 2019

Background and Aims

Genetically modified mice have been used extensively to study human disease. However, the data gained are not always translatable to humans because of major species differences. Liver‐humanized mice (LHM) are considered a promising model to study human hepatic and systemic metabolism. Therefore, we aimed to further explore their lipoprotein metabolism and to characterize key hepatic species‐related, physiological differences.

Approach and Results

Fah−/−
, Rag2−/−
, and Il2rg−/−
knockout mice on the nonobese diabetic (FRGN) background were repopulated with primary human hepatocytes from different donors. Cholesterol lipoprotein profiles of LHM showed a human‐like pattern, characterized by a high ratio of low‐density lipoprotein to high‐density lipoprotein, and dependency on the human donor. This pattern was determined by a higher level of apolipoprotein B100 in circulation, as a result of lower hepatic mRNA editing and low‐density lipoprotein receptor expression, and higher levels of circulating proprotein convertase subtilisin/kexin type 9. As a consequence, LHM lipoproteins bind to human aortic proteoglycans in a pattern similar to human lipoproteins. Unexpectedly, cholesteryl ester transfer protein was not required to determine the human‐like cholesterol lipoprotein profile. Moreover, LHM treated with GW3965 mimicked the negative lipid outcomes of the first human trial of liver X receptor stimulation (i.e., a dramatic increase of cholesterol and triglycerides in circulation). Innovatively, LHM allowed the characterization of these effects at a molecular level.

Conclusions

LHM represent an interesting translatable model of human hepatic and lipoprotein metabolism. Because several metabolic parameters displayed donor dependency, LHM may also be used in studies for personalized medicine.
Effects of line length, orientation angle, and drawing direction on the straight‐line drawing performance of elderly Taiwanese adults during iPad use
Authors: Wu Chia‐Chen , Huang Kuo‐Chen
Published: December 2019

The present study investigated the effects of drawing direction (top‐down or bottom‐up) and orientation angle (0°, 60°, or 300°) on the stability of straight‐line drawing with varied line length (5.7, 11.4, or 17.1 cm) of elderly Taiwanese adults. These three independent variables were within‐subject factors. In total, 38 elderly adults participated. The straight‐line drawing task was performed on an iPad using an electronic pen. Straight‐line drawing performance was analyzed using three‐way repeated analysis of variance measures. The results indicated that the error rate was significantly higher in the top‐down condition than in the bottom‐up condition and was higher for the 5.7‐cm line length than for the 11.4 or 17.1 cm lengths. In addition, the average drawing speed in the top‐down condition was significantly greater than that in the bottom‐up condition and was significantly greater at 17.1 and 11.4 cm than at 5.7 cm. The orientation angle also significantly affected the average drawing speed, which demonstrated that the 60° condition yielded a significantly greater speed than the 0° or 300° conditions. Our findings have implications for product design and computer–human interface design for seniors. Further studies are needed to determine whether these findings can be generalized to more complex motor movements and cognitive abilities.
Voluntary private health insurance demand determinants and risk preferences: Evidence from SHARE
Authors: Tavares Aida Isabel
Published: December 2019

The demand for voluntary private health insurance (VPHI) in universal coverage health systems in Europe raises some questions. The aim of this paper is to determine the factors that explain the decision to purchase VPHI, to analyse the role of individual risk attitudes and self‐assessed health (SAH) in purchasing VPHI, to explore the factors that explain individual risk preferences, and to test how SAH relates to those preferences. To achieve this aim, two recursive simultaneous probits are estimated using data collected by SHARE, wave 6. The main results indicate that people who are more satisfied with the health system coverage are more likely to buy VPHI; SAH is negative correlated with VPHI, but being a risk taker contributes to that decision; however, being a risk taker is positively influenced by good health status. This paper contributes to the discussion on the role of SAH and risk preferences in the decision to buy VPHI. It brings new insights for the health insurance companies and for health policy makers.

Highlights

People who are more satisfied with the health system coverage are more likely to buy voluntary private health insurance.

The longer the planning horizon assumed by individuals, the greater the likelihood they are risk takers.

People reporting being risk takers are more likely to have taken out voluntary private health insurance.

Self‐assessed health influences the decision to buy voluntary private health insurance in two ways: a direct one, where better health lowers the odds of having insurance, and an indirect one through risk taking, which increases the odds of having insurance.

Contributions of this work are mainly for health policy makers and insurance companies.
Circulating ensembles of tumor‐associated cells: A redoubtable new systemic hallmark of cancer
Authors: Akolkar Dadasaheb , Patil Darshana , Crook Timothy , Limaye Sewanti , Page Raymond , Datta Vineet , Patil Revati , Sims Cynthe , Ranade Anantbhushan , Fulmali Pradeep , Fulmali Pooja , Srivastava Navin , Devhare Pradip , Apurwa Sachin , Patel Shoeb , Patil Sanket , Adhav Archana , Pawar Sushant , Ainwale Akshay , Chougule Rohit , Apastamb Madhavi , Srinivasan Ajay , Datar Rajan
Published: December 2019

Circulating ensembles of tumor‐associated cells (C‐ETACs) which comprise tumor emboli, immune cells and fibroblasts pose well‐recognized risks of thrombosis and aggressive metastasis. However, the detection, prevalence and characterization of C‐ETACs have been impaired due to methodological difficulties. Our findings show extensive pan‐cancer prevalence of C‐ETACs on a hitherto unreported scale in cancer patients and virtual undetectability in asymptomatic individuals. Peripheral blood mononuclear cells (PBMCs) were isolated from blood samples of 16,134 subjects including 5,509 patients with epithelial malignancies in various organs and 10,625 asymptomatic individuals with age related higher cancer risk. PBMCs were treated with stabilizing reagents to protect and harvest apoptosis‐resistant C‐ETACs, which are defined as cell clusters comprising at least three EpCAM+ and CK+ cells irrespective of leucocyte common antigen (CD45) status. All asymptomatic individuals underwent screening investigations for malignancy including PAP smear, mammography, low‐dose computed tomography, evaluation of cancer antigen 125, cancer antigen 19‐9, alpha fetoprotein, carcinoembryonic antigen, prostate specific antigen (PSA) levels and clinical examination to identify healthy individuals with no indication of cancer. C‐ETACs were detected in 4,944 (89.8%, 95% CI: 89.0–90.7%) out of 5,509 cases of cancer. C‐ETACs were detected in 255 (3%, 95% CI: 2.7–3.4%) of the 8,493 individuals with no abnormal findings in screening. C‐ETACs were detected in 137 (6.4%, 95% CI: 5.4–7.4%) of the 2,132 asymptomatic individuals with abnormal results in one or more screening tests. Our study shows that heterotypic C‐ETACs are ubiquitous in epithelial cancers irrespective of radiological, metastatic or therapy status. C‐ETACs thus qualify to be a systemic hallmark of cancer.
Tissue‐engineered islet‐like cell clusters generated from adipose tissue‐derived stem cells on three‐dimensional electrospun scaffolds can reverse diabetes in an experimental rat model and the role of porosity of scaffolds on cluster differentiation
Authors: Anitha Rakhi , Vaikkath Dhanesh , Shenoy Sachin J. , Nair Prabha D.
Published: December 2019

In the current study, three‐dimensional (3D) nanofibrous scaffolds with pore sizes in the range of 24–250 μm and 24–190 μm were fabricated via a two‐step electrospinning method to overcome the limitation of obtaining three‐dimensionality with large pore sizes for islet culture using conventional electrospinning. The scaffolds supported the growth and differentiation of adipose‐derived mesenchymal stem cells to islet‐like clusters (ILCs). The pore size of the scaffolds was found to influence the cluster size, viability and insulin release of the differentiated islets. Hence, islet clusters of the desired size could be developed for transplantation to overcome the loss of bigger islets due to hypoxia which adversely impacts the outcome of transplantation. The tissue‐engineered constructs with ILC diameter of 50 μm reduced glycemic value within 3–4 weeks after implantation in the omental pouch of diabetic rats. Detection of insulin in the serum of implanted rats demonstrates that the tissue‐engineered construct is efficient to control hyperglycemia. Our findings prove that the 3D architecture and pore size of scaffolds regulates the morphology and size of islets during differentiation which is critical in the survival and function of ILCs in vitro and in vivo.
Peripheral blood mononuclear cell microRNAs in coronary artery disease
Authors: Sanlialp Musa , Dodurga Yavuz , Uludag Burcu , Alihanoglu Yusuf I. , Enli Yasar , Secme Mucahit , Bostanci Hayrani Eren , Cetin Sanlialp Sara , Tok Ozge Ozden , Kaftan Asuman , Kilic Ismail Dogu
Published: December 2019

The accuracy of risk prediction for coronary artery disease can be improved with the use of novel molecular or genetic biomarkers. In this study, we investigated the difference of five selected microRNAs (miR or miRNA) in patients with coronary artery disease (CAD) and controls, assessed by coronary angiography. The study population consisted of 85 subjects, aged between 18 and 75 years and underwent invasive coronary angiography. Subjects with more than 30% stenosis in at least one coronary artery, patients with a history of prior percutaneous coronary intervention or coronary by‐pass surgery were allocated to the patient group; whereas the subjects without at least 30% stenosis consisted the control group. Groups were similar in age, presence of hypertension, and smoking status. However, the proportion of males and subjects taking angiotensin‐converting enzyme inhibitors or angiotensin receptor blockers, beta blockers, nitrates, and statins were higher in the patient group. miR‐221 and miR‐155 were downregulated (P = .02 and .001, respectively), while miR‐21 levels were significantly increased (P = .003) in the patient group compared to controls. Changes in miR‐145 and miR‐126 did not reach statistical significance (P > .05). miRNA‐ 21, miR‐155, and miR‐221 were differentially expressed between the patients and controls. miRNAs are promising biomarkers for CAD diagnosis, however, this requires further research with larger groups.
Synthesis of size‐tunable zinc blende ZnS nanocrystals
Authors: Lee An‐Ting , Huang Michael H.
Published: December 2019

Quasi‐polyhedral ZnS nanocrystals with monodisperse tunable sizes of 40, 52, 62, 73, 82, 94, 103, and 110 nm have been synthesized in aqueous solution by regulating the amounts of thioacetamide, zinc acetate, and acetic acid added. The mixture was heated to 120°C in an oven for 10–20 min to produce the nanocrystals. Structural characterization reveals the formation of cubic zinc blende ZnS with some polycrystallinity, which possibly influences their optical properties, that is, the measured band gaps do not give a continuous narrowing trend with increasing particle size. However, when particle sizes are expressed in terms of volumes, the absorption band positions show steady red shifts with increasing crystal dimensions and very small wavelength changes for nanocrystals beyond 90 nm. Thus, these ZnS nanocrystals still possess some size‐dependent optical properties despite their polycrystalline nature.
Clinical profile of patients presenting with dysphagia ‐ an experience from a tertiary care center in North India
Authors: Mitra Tuhin , Dixit Vinod K , Shukla Sunit K , Yadav Dawesh P , Thakur Piyush , Thakur Ravi K
Published: December 2019

Background and Aim

Dysphagia can lead to substantial morbidity and mortality, especially in the elderly. It has both benign and malignant causes. Despite having a varied etiology, there have been few studies in India. Therefore, a study was undertaken to evaluate the clinical profile and various etiologies of dysphagia.

Methods

A prospective study was conducted on 220 patients with a complaint of dysphagia. Detailed history and examination, endoscopy and biopsies, and barium swallow were performed. Computed tomography and magnetic resonance imaging were performed wherever required. Patients who had an oropharyngeal or neurological cause of dysphagia were excluded.

Results

The mean age of patients was 57.2 years, with the male: female ratio being 1.7:1. Of the patients, 35% (78 patients) had malignant etiology, with a mean age of 65.2 years, and 65% (142 patients) had a benign etiology, with a mean age of 51 years. Among the patients with malignancy, 56 had squamous cell carcinoma of esophagus (71.7%), 20 had adenocarcinoma of esophagus (25.7%), and 2 had gastric cardia adenocarcinoma (2.6%). Malignancy was most commonly located in distal esophagus (48 patients), and among the cases, 18 had involvement of the gastroesophageal junction. The most common benign cause was esophagitis secondary to reflux in 25.5% (56 patients), followed by esophageal ulcer in 5.9%, achalasia in 5%, corrosive stricture in 4.5%, and peptic stricture in 3.6%.

Conclusion

Dysphagia has diverse etiology, and a majority can be diagnosed by endoscopy and barium swallow. Malignancy is an important cause of dysphagia in elderly. Esophageal squamous cell carcinoma remains the most common malignancy, but the incidence of gastroesophageal junctional adenocarcinoma is increasing.
Copper‐catalyzed domino reaction between terminal alkynes, isocyanates, and oxiranes: An atom‐economic route to morpholine derivatives
Authors: Beigi‐Somar Vahid , Homami Seyed Saied , Ghazanfarpour‐Darjani Majid , Monzavi Amirhossein
Published: December 2019

In situ generated copper acetylides react with isocyanates and oxiranes to form a decent range of morpholine derivatives. The reactions proceeded with acceptable yields and excellent regioselectivity. The presence of oxygen and moisture completely inhibited the reaction. The scope of the reaction is wide and the reactions involve consecutive C–C, C–N, and C–O bond formations.
Longitudinal Reproducibility of MR Perfusion Using 3D Pseudocontinuous Arterial Spin Labeling With Hadamard‐Encoded Multiple Postlabeling Delays
Authors: Cohen Alexander D. , Agarwal Mohit , Jagra Amritpal S. , Nencka Andrew S. , Meier Timothy B. , Lebel R. Marc , McCrea Michael A. , Wang Yang
Published: December 2019

Background

Arterial spin labeling (ASL) can be confounded by varying arterial transit times (ATT) across the brain and with disease. Hadamard encoding schemes can be applied to 3D pseudocontinuous ASL (pCASL) to acquire ASL data with multiple postlabeling delays (PLDs) to estimate ATT and then correct cerebral blood flow (CBF).

Purpose

To assess the longitudinal reproducibility of 3D pCASL with Hadamard‐encoded multiple PLDs.

Study Type

Prospective, longitudinal.

Population

Fifty‐two healthy, right‐handed male subjects who underwent imaging at four timepoints over 45 days.

Field Strength/Sequence

A Hadamard‐encoded 3D pCASL sequence was acquired at 3.0T with seven PLDs from 1.0–3.7 sec.

Assessment

ATT and corrected CBF (cCBF) were computed. Conventional uncorrected CBF (unCBF) was also estimated. Within‐ and between‐subject coefficient of variation (wCV and bCV, respectively) and intraclass correlation coefficient (ICC) were evaluated across four time intervals: 7, 14, 30, and 45 days, in gray matter and 17 independent regions of interest (ROIs). A power analysis was also conducted.

Statistical Tests

A repeated‐measures analysis of variance (ANOVA) was used to compare ATT, cCBF, and unCBF across the four scan sessions. A paired two‐sample t‐test was used to compare cCBF and unCBF. Pearson's correlation was used to examine the relationship between the cCBF and unCBF difference and ATT. Power calculations were completed using both the cCBF and unCBF variances.

Results

ATT showed the lowest wCV and bCV (3.3–4.4% and 6.0–6.3%, respectively) compared to both cCBF (10.5–11.7% and 20.6–22.2%, respectively) and unCBF (12.0–13.6% and 22.7–23.7%, respectively). wCV and bCV were lower for cCBF vs. unCBF. A significant difference between cCBF and unCBF was found in most regions (P = 5.5 × 10‐5–3.8 × 10‐4 in gray matter) that was highly correlated with ATT (R2 = 0.79–0.86). A power analysis yielded acceptable power at feasible sample sizes using cCBF.

Data Conclusion

ATT and ATT‐corrected CBF were longitudinally stable, indicating that ATT and CBF changes can be reliably evaluated with Hadamard‐encoded 3D pCASL with multiple PLDs.

Level of Evidence: 1

Technical Efficacy Stage: 2

J. Magn. Reson. Imaging 2020;51:1846–1853.