bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of variant microscopic interpretation of the uCyt+ immunocytological urine test for the detection of bladder cancer
Authors: Deininger Susanne , Todenhöfer Tilman , Hennenlotter Jörg , Gerber Valentina , Schwarz Jennifer , Bedke Jens , Schwentner Christian , Stenzl Arnulf , Rausch Steffen
Published: November 2017

Background

Urinary marker tests for bladder cancer (BC) detection and surveillance represent a desirable approach to diagnosis and follow‐up. The SCIMEDX uCyt+ assay detects antigens expressed by BC cells (mucin glycoprotein and carcinoembryonic antigen) using green and red fluorescence and is interpreted according to specific manufacturer's recommendations. In the present study, we evaluated divergent approaches of numeric and morphological analysis of uCyt+ to generate a rationale for alternative test interpretation strategies.

Methods

A total of 444 patients with hematuria and without history of BC underwent uCyt+ analysis, cystoscopy and histological examination of tissue biopsies. Beside positive cells according to the manufacturer's definition (definitely positive cells, DPC), (i) cells showing borderline character (borderline cells, BLC), and (ii) cells with staining present below defined border (subliminal cells, SLC) were included into the analytical algorithm. Different cut‐off levels for cell counts (>0, ≥3, ≥5) were evaluated separately with regard to their diagnostic accuracy. Moreover, the influence of clinical factors on test results were evaluated.

Results

Adding BLC at a cut‐off of ≥3 cells resulted in Area Under the Curve (AUC) of 0.70 for green and 0.77 for red fluorescence, respectively. Adding SLC led to reduced AUC (0.62 and 0.73, respectively). Male gender was significantly associated with false positive results in the “best AUC” groups (P = .0101). No further correlations to clinical influencing factors were observed.

Conclusions

Adding microscopic BLC as test‐positive and adjusting cut‐off level for the interpretation of uCyt+ may improve assay performance independent of clinical factors.
Carcinoma showing thymus like elements: Report of a case with EGFR T790M mutation
Authors: Rajeshwari Madhu , Singh Varsha , Nambirajan Aruna , Mridha Asit Ranjan , Jain Deepali
Published: November 2017

Carcinoma showing thymus‐like differentiation of the thyroid (CASTLE) is a rare tumor involving the thyroid and perithyroidal soft tissues. It shares morphological, immunohistochemical and molecular similarities with thymic carcinomas. Due to its relatively better prognosis, it needs differentiation from other primary and metastatic tumors of this region. A 40‐year‐old lady presented with a gradually progressive anterior neck swelling for one year. Imaging showed bulky right and left lobes of thyroid along with a solid soft tissue mass in the pretracheal region. Fine needle aspiration smears showed features of poorly differentiated carcinoma. Total thyroidectomy with excision of the mass revealed histopathological features characteristic of CASTLE, with evidence of thyroiditis in adjoining thyroid. Epidermal growth factor receptor (EGFR) assay revealed presence of EGFR T790M somatic mutation in exon 20. The same was not detectable on direct sequencing. We present a rare case of CASTLE, occurring in association with Hashimoto thyroiditis, with emphasis on cytological features and report for the first time the presence of a low level somatic mutation in EGFR (EGFR T790M mutation).
Generation and characterization of an estrogen receptor alpha‐iCre knock‐in mouse
Authors: Park Chan Jin , Chen Guanglin , Koo Yongbum , Lin Po‐Ching P. , Cacioppo Joseph A. , Prohaska Hailey , Ko CheMyong J.
Published: November 2017

Two estrogen receptors, ESR1 and ESR2, are responsible for the classical actions of estrogens in mammalian species. They display different spatiotemporal expression patterns and nonoverlapping functions in various tissues and physiological conditions. In this study, a novel knock‐in mouse line that expresses codon‐improved Cre recombinase (iCre) under regulation of the natural Esr1 promoter (Esr1–iCre) was developed. Functional characterization of iCre expression by crossing them with reporter lines (ROSA26‐lacZ or Ai9‐RFP) showed that iCre is faithfully expressed in Esr1‐lineage cells. This novel transgenic mouse line will be a useful animal model for lineage‐tracing Esr1‐expressing cells, selective gene ablation in the Esr1‐lineage cells and for generating global Esr1 knockout mice.
Scavenging along an ecological interface: utilization of amphibian and reptile carcasses around isolated wetlands
Authors: Abernethy Erin F. , Turner Kelsey L. , Beasley James C. , Rhodes Olin E.
Published: November 2017

Scavenging is an influential ecosystem process, providing many weak, but stabilizing food web links. Amphibians and reptiles (i.e., herpetofauna) utilize land/water interfaces and can have large biomasses concentrated here, making them important vectors of nutrients between aquatic and terrestrial systems and a valuable resource to scavengers. There are limited data on the fate of herpetofauna carrion, and thus, it is unknown how such carcasses are incorporated into food webs or how habitat and carcass characteristics influence which scavengers acquire these resources. We used camera traps to determine the proportion of experimental amphibian and reptile carcasses (lizards, salamanders, frogs, and toads) scavenged by vertebrates and invertebrates in two different habitats (wetland and upland) during the spring in the southeastern USA. Vertebrates removed 19.8% of all herpetofauna carcasses in both habitats, with the remaining carcasses removed by invertebrates (80.2%). We used log‐linear models to evaluate the impact of habitat and carcass type on scavenging. We determined that habitat, but not carcass type, was influential in determining whether a vertebrate or invertebrate scavenged a carcass, with vertebrates able to scavenge more carcasses in wetland than in upland areas. In less than two days, 86.2% of all carcasses in both habitat types were completely scavenged, and carcasses in wetlands were removed more quickly, suggesting intense competition between vertebrates and invertebrates. Additionally, we observed low vertebrate scavenger richness, which we attribute to high invertebrate activity in the spring and the small size of the herpetofauna carcasses (<100 g). We identified the scavenging pathways along which herpetofauna are incorporated into the food web and the factors that influence those pathways, suggesting the large extent and spatial scale of this resource's influence on food web connections and consequently food web and ecosystem stability.
Maintenance of memory CD8 T cells: Divided over division
Authors: Nolte Martijn A. , Goedhart Marieke , Geginat Jens
Published: November 2017

Once generated during an infection, memory CD8+ T cells can provide long‐lasting protection against reinfection with an intracellular pathogen, but the longevity of this defense depends on the ability of these pathogen‐specific memory cells to be maintained. It is generally believed that the bone marrow plays an important role in this respect, where memory CD8 T cells receive reinvigorating signals from cytokines that induce homeostatic proliferation. However, in the current issue of the European Journal of Immunology, Siracusa et al. (Eur. J. Immunol. 2017. 47: 1900–1905) argue against this dogma, as they provide evidence that CD8 memory T cells in murine bone marrow are not proliferating, but largely quiescent, which protects them from elimination by the cytostatic drug Cyclophosphamide. Interestingly, this is in sharp contrast to the proliferating cell counterparts in the spleen, which are eliminated by this treatment. Here, we will discuss the impact of these results, how they relate to opposing findings by others in the field, and what the relevance of these findings is for humans and clinical applications.
Alkylpyridinium Tetrahalidometallate Ionic Liquids and Ionic Liquid Crystals: Insights into the Origin of Their Phase Behavior
Authors: Abouserie Ahed , Zehbe Kerstin , Metzner Philipp , Kelling Alexandra , Günter Christina , Schilde Uwe , Strauch Peter , Körzdörfer Thomas , Taubert Andreas
Published: November 2017

Six N‐alkylpyridinium salts [CnPy]2[MCl4] (n = 4 or 12 and M = Co, Cu, Zn) were synthesized, and their structure and thermal properties were studied. The [C4Py]2[MCl4] compounds are monoclinic and crystallize in the space group P21/n. The crystals of the longer chain analogues [C12Py]2[MCl4] are triclinic and crystallize in the space group P1. Above the melting temperature, all compounds are ionic liquids (ILs). The derivatives with the longer C12 chain exhibit liquid crystallinity and the shorter chain compounds only show a melting transition. Consistent with single‐crystal analysis, electron paramagnetic resonance spectroscopy suggests that the [CuCl4]2– ions in the Cu‐based ILs have a distorted tetrahedral geometry.
Validation of a Simple Extraction Method for Oil Bodies Isolated from Peanuts
Authors: Zaaboul Farah , Matabaro Emmanuel , Raza Husnain , Xin Boxin D. , Duhoranimana Emmanuel , Cao Chen , Liu Yuanfa
Published: November 2017

Peanut preserves lipids in the form of oil bodies (OBs) which have great potential to be used in the food industries. In this study, a simple aqueous extraction method is used to extract peanut OBs and its effect on the properties and the stability of the resulted emulsions is evaluated. The above‐mentioned method involves, successive mechanical steps in order to release OBs from their cell networks, followed by purification using different recovery pHs and washing. Results shows that crude OBs had a high amount of extrinsic proteins and low physical stability. Washing OBs twice with the increase in recovery pH decreased the extrinsic proteins, the lipid oxidation, and improved the storage stability. The physical and the oxidative stability of all OBs emulsions was significantly enhanced by heating. These results suggest that peanut OBs extracted using this aqueous extraction method, can be used to prepare natural emulsions with improved long‐term stability.

Practical Applications: Peanut oil is widely used in food industries in the form of emulsified oil. OBs can be represented as a better alternative solution of stable emulsified oil with a high content of antioxidant and phytosterols. Our results shows that peanut OBs can be isolated and purified by a simple aqueous extraction method. Therefore, the OBs emulsion resultant from this extraction under specific conditions (pH recovery 8.0 and washing twice with the same pH) is physically and chemically stable. Heat treatment such as pasteurization and sterilization which are essential processing steps in food industries can enhance the OBs emulsion properties by giving the emulsion better physical stability, lipid oxidation, and shelf life.

Crude OBs: i) Have high content of extrinsic proteins; and ii) are not physically stable non matter the pH recovery used for the isolation. Washed OBs: i) The pI increased with washing and the increase of pH recovery; ii) pH recovery 8.0 gave the most physically stable OBs; and iii) pH recovery 11.0 gave the most stable OBs to lipid deterioration. Heated OBs: i) Heat did not enhance the stability of OBs recovered by pH 6.8; ii) heat increased reversibly the OBs particle size; and iii) heat can improve the OBs shelf life.
Anti‐Apoptotic Effect of N‐Palmitoyl Serotonin on Glutamate‐Mediated Apoptosis Through Secretion of BDNF and Activation of TrkB/CREB Pathway in HT‐22 Cells
Authors: Yoo Jae‐Myung , Lee Bo Dam , Lee Su Jin , Ma Jin Yeul , Kim Mee Ree
Published: November 2017

Recently, N‐acyl serotonins have been reported to exert neuroprotective actions against oxidative stress by inducing antioxidant enzymes. However, the mechanisms for the neuroprotective action of N‐acyl serotonins are still not clarified. In this study, we focuse on the suppressive effect of N‐palmitoyl serotonin on glutamate‐induced apoptosis in HT‐22 cells, and then examine the molecular mechanism for anti‐apoptotic action of N‐palmitoyl serotonin. For this purpose, flow cytometry, immunoblotting analysis and antibody‐mediated neutralization is formed. When HT‐22 cells are preincubated with N‐palmitoyl serotonin prior to glutamate treatment, N‐palmitoyl serotonin dose‐dependently reduces apoptotic bodies, and recoveres mitochondrial potential in glutamate‐treated HT‐22 cells. Further, N‐palmitoyl serotonin concentration‐dependently increases the expression of B‐cell lymphoma 2 (Bcl‐2), an anti‐apoptotic factor, whereas it reduces the expression of Bcl‐2‐associated X protein, apoptosis‐inducing factor, Ca2+‐dependent non‐lysosomal cysteine protease, cytochrome c, and cleaves caspase‐3. Meanwhile, N‐palmitoyl serotonin enhanced phosphorylation of tropomyosin‐related kinase receptors (TrkB) and cAMP response element‐binding protein (CREB) as well as expression of brain‐derived neurotrophic factor (BDNF). Separately, the inclusion of anti‐BDNF antibody neutralizes the neuroprotective action of N‐palmitoyl serotonin against glutamate‐induced cell death. In addition, K252a, a TrkB inhibitor, also reverses neuroprotective effect of N‐palmitoyl serotonin, suggesting that the action of N‐palmitoyl serotonin may be expressed through the formation of BDNF. Based on these results, it is proposed that N‐palmitoyl serotonin promotes formation and secretion of BDNF, and then protects neuronal cells against oxidative stress‐induced apoptosis through activation of TrkB/CREB pathway.

Practical Applications: The results may provide further information for the application of N‐acyl serotonins as a therapeutic or preventive agent for neurodegenerative diseases.

N‐Palmitoyl 2 serotonin (Pal‐5HT) not only induces brain‐derived neurotrophic factor (BDNF) expression but also protects neuronal cells against oxidative stress.
Densely Functionalized 2‐Methylideneazetidines from Nitrodienic Building Blocks
Authors: Tavani Cinzia , Bianchi Lara , Giorgi Gianluca , Maccagno Massimo , Petrillo Giovanni
Published: November 2017

Novel, densely functionalized 2‐methylideneazetidines can be obtained in high yields under mild conditions from the reactions of nitropentadienoates with primary amines, most likely through an aza‐Michael addition followed by a 4‐exo‐trig cyclization. The initial, selective trans arrangement of the C3 and C4 ring hydrogens undergoes stereomutation due to the presence of an easily enolizable site at C3, eventually leading to mixtures in which the cis isomer generally prevails.
Lactofen – Electrochemical Sensing and Interaction with dsDNA
Authors: Guziejewski Dariusz , Morawska Kamila , Popławski Tomasz , Metelka Radovan , Ciesielski Witold , Smarzewska Sylwia
Published: November 2017

The electrochemical reduction of lactofen (LCT) at the glassy carbon (GCE) and silver amalgam film electrode (AMFE) is investigatedin detail by the means of square wave voltammetry (SWV), square wave stripping voltammetry (SWSV) and cyclic voltammetry. The influence of various factors such as supporting electrolyte composition and SW parameters were studied. The AMFE electrode showed an excellent electrochemical activity toward the electro‐reduction of LCT, leading to a significant improvement in sensitivity as compared to the glassy carbon electrode.The SWSV detection limits for GCE and AMFE were 285.0 nM and 2.0 nM, respectively. The applicability of the developed voltammetric method for analysis of tap water and river water is illustrated with spiked samples analysis. Moreover, as lactofen is highly toxic to fish and other aquatic organisms, its interaction with dsDNA isolated from salmon sperm was tested. The intercalative mode of LCT binding to dsDNA was estimated. The heterogeneous rate constants were calculated for the free LCT and the LCT‐dsDNA complex. Moreover, LCT‐dsDNA complex binding ratio and equilibrium constant were determined. The decrease in the SWV peak current of LCT in the presence of dsDNA was used for the determination of dsDNA.
Joule heating induced stream broadening in free‐flow zone electrophoresis
Authors: Dutta Debashis
Published: November 2017

The use of an electric field in free‐flow zone electrophoresis (FFZE) automatically leads to Joule heating yielding a higher temperature at the center of the separation chamber relative to that around the channel walls. For small amounts of heat generated, this thermal effect introduces a variation in the equilibrium position of the analyte molecules due to the dependence of liquid viscosity and analyte diffusivity on temperature leading to a modification in the position of the analyte stream as well as the zone width. In this article, an analytic theory is presented to quantitate such effects of Joule heating on FFZE assays in the limit of small temperature differentials across the channel gap yielding a closed form expression for the stream position and zone variance under equilibrium conditions. A method‐of‐moments approach is employed to develop this analytic theory, which is further validated with numerical solutions of the governing equations. Interestingly, the noted analyses predict that Joule heating can drift the location of the analyte stream either way of its equilibrium position realized in the absence of any temperature rise in the system, and also tends to reduce zone dispersion. The extent of these modifications, however, is governed by the electric field induced temperature rise and three Péclet numbers evaluated based on the axial pressure‐driven flow, transverse electroosmotic and electrophoretic solute velocities in the separation chamber. Monte Carlo simulations of the FFZE system further establish a time and a length scale over which the results from the analytic theory are valid.
Influence of ionic constituents and electrical conductivity on the propagation of charged nanoscale objects in passivated gel electrophoresis
Authors: Bikos Dimitri A. , Mason Thomas G.
Published: November 2017

When determining the electric field E acting on charged objects in gel electrophoresis, the electrical conductivity of the buffer solution is often overlooked; E is typically calculated by dividing the applied voltage by a separation distance between electrodes. However, as a consequence of electrolytic reactions, which occur at the electrodes, gradients in the ionic content of the buffer solution and its conductivity can potentially develop over time, thereby impacting E and affecting propagation velocities of charged objects, v, directly. Here, we explore how the types and concentrations of ionic constituents of the buffer solution, which largely control its conductivity, when used in passivated gel electrophoresis (P‐gelEP), can influence E, thereby altering v of charged nanospheres propagating through large‐pore gels. We measure the conductivity of the buffer solution in the center of the gel region near propagating bands of nanospheres, and we show that predictions of E based on conductivity closely correlate with v. We also explore P‐gelEP involving two different types of passivation agents: nonionic polyethylene glycol (PEG) and anionic sodium dodecyl sulfate (SDS). Our observations indicate that using a conductivity model to determine E from the local current density and the conductivity where spheres are propagating can lead to a better estimate than the standard approach of a voltage divided by a separation. Moreover, this conductivity model also provides a starting point for interpreting the complex behavior created by amphiphilic ionic passivation agents, such as SDS, on propagating nanospheres used in some P‐gelEP experiments.
Influence of cavitation and high shear stress on HSA aggregation behavior
Authors: Duerkop Mark , Berger Eva , Dürauer Astrid , Jungbauer Alois
Published: November 2017

Neither the influence of high shear rates nor the impact of cavitation on protein aggregation is fully understood. The effect of cavitation bubble collapse‐derived hydroxyl radicals on the aggregation behavior of human serum albumin (HSA) was investigated. Radicals were generated by pumping through a micro‐orifice, ultra‐sonication, or chemically by Fenton's reaction. The amount of radicals produced by the two mechanical methods (0.12 and 11.25 nmol/(L min)) was not enough to change the protein integrity. In contrast, Fenton's reaction resulted in 382 nmol/(L min) of radicals, inducing protein aggregation. However, the micro‐orifice promoted the formation of soluble dimeric HSA aggregates. A validated computational fluid dynamic model of the orifice revealed a maximum and average shear rate on the order of 108 s−1 and 1.2 × 106 s−1, respectively. Although these values are among the highest ever reported in the literature, dimer formation did not occur when we used the same flow rate but suppressed cavitation. Therefore, aggregation is most likely caused by the increased surface area due to cavitation‐mediated bubble growth, not by hydroxyl radical release or shear stress as often reported.
Protein adsorption onto monoliths: A surface energetics study
Authors: Aasim Muhammad , Hidayatullah Khan Muhammad , Bibi Noor Shad , Zaman Khan Nadir
Published: November 2017

This part of work was done to explore the basic understanding of the adsorption chromatography by determining the interaction of selected model proteins (n = 5) to monolithic chromatographic materials, with varying densities of butyl and phenyl ligands. Surface energetics approach was applied to study the interaction behavior. The physicochemical properties of the proteins and monolithic chromatographic materials were explored by contact angle and zeta potential values. These values were used to study protein to monolith interaction under various operating conditions. Surface energetics approach allowed the calculation of interaction energy as a function of distance, i.e. energy minimum values. Calculations were performed at various conditions to analyze the effect of major operating parameters on the interaction strength. The interaction strength exposed the hydrophobic nature of the monoliths which increases with increasing ligand density. Further, interaction energy of proteins were higher with monolith with butyl ligand compared to monolith with phenyl ligand. For instance, lactoferrin interaction to monoliths with butyl represents more interaction, i.e. 24.38 kT as compared to monoliths with phenyl i.e. 23.28 kT, keeping lambda as 0.2 nm and salt concentration as 100 mM of ammonium sulphate. Hence, more energy and time will be consumed for elution of proteins immobilized to monoliths with butyl. Similarly, the effect of solid surface for proteins immobilization, effect of ligand density and effect of lambda showed some interesting insights on the interaction behavior. The knowledge generated from the present work will help in the basic understanding as well as development of an efficient, low cost downstream processing design and may mimic the real chromatographic experiments.
Glycosylphosphatidylinositol (GPI) anchored protein deficiency serves as a reliable reporter of Pig‐a gene Mutation: Support from an in vitro assay based on L5178Y/Tk+/− cells and the CD90.2 antigen
Authors: Bemis Jeffrey C. , Avlasevich Svetlana L. , Labash Carson , McKinzie Page , Revollo Javier , Dobrovolsky Vasily N. , Dertinger Stephen D.
Published: November 2017

Lack of cell surface glycosylphosphatidylinositol (GPI)‐anchored protein(s) has been used as a reporter of Pig‐a gene mutation in several model systems. As an extension of this work, our laboratory initiated development of an in vitro mutation assay based on the flow cytometric assessment of CD90.2 expression on the cell surface of the mouse lymphoma cell line L5178Y/Tk+/−. Cells were exposed to mutagenic and nonmutagenic compounds for 24 hr followed by washout and incubation for an additional 7 days. Following this mutant manifestation time, cells were labeled with fluorescent antibodies against CD90.2 and CD45 antigens. These reagents indicated the presence of GPI‐anchored proteins and general cell surface membrane receptor integrity, respectively. Instrument set‐up was aided by parallel processing of a GPI anchor‐deficient subclone. Results show that the mutagens reproducibly caused increased frequencies of mutant phenotype cells, while the nonmutagens did not. Further modifications to the method, including application of a viability dye and an isotype control for instrument set‐up, were investigated. As a means to verify that the GPI‐anchored protein‐negative phenotype reflects bona fide Pig‐a gene mutation, sequencing was performed on 38 CD90.2‐negative L5178Y/Tk+/− clones derived from cultures treated with ethyl methanesulfonate. All clones were found to have mutation(s) within the Pig‐a gene. The continued investigation of L5178Y/Tk+/− cells, CD90.2 labeling, and flow cytometric analysis as the basis of an in vitro mutation assay is clearly supported by this work. These data also provide evidence of the reliability of using GPI anchor‐deficiency as a valid reporter of Pig‐a gene mutation. Environ. Mol. Mutagen. 59:18–29, 2018. © 2017 Wiley Periodicals, Inc.
Sanierungstunnel Belchen – Inertstoffdeponie Fasiswald
Authors: Weissenberger Lorenz , Schwalt Markus , Böheim Sebastian
Published: November 2017

Derzeit werden die beiden Röhren des Belchentunnels des Autobahndreiecks Bern–Zürich–Basel um eine dritte Röhre erweitert. Dabei fällt Gipskeuper als problematisches Ausbruchmaterial an. Die wenig oberhalb des Tunnels gelegene, stillgelegte Tongrube Fasiswald wird als Inertstoffdeponie verwendet, um den Gipskeuper zu deponieren. Dabei stehen die maximale Nutzung des Deponievolumens und die Langzeitstabilität der Deponie im Vordergrund. Als dichtendes Material liegt Opalinuston (OPA) vor, der ursprünglich Gegenstand des Abbaus und daher Gegenstand der Entstehung der Abbaugrube war. Dieser OPA bestimmt aufgrund seiner Verwitterungsanfälligkeit und der ungünstigen geotechnischen Parameter langfristig die Stabilität der Deponie. Um die Stabilität nachzuweisen, wurden Berechnungen angestellt. Die Verbesserung der Stabilität erfolgte durch eine Optimierung der Deponierform. Als günstig erwies sich eine in Längsrichtung flach ansteigende Deponieoberfläche mit erhöhtem Deponiefuß. Mit dieser Form ist langfristig auch bei fortgeschrittener Verwitterung des OPA die Stabilität der Deponie gewährleistet.
Magmatic events recorded in granitic gneisses from the Hatu area, eastern East Kunlun Orogen: Response to the assembly of Rodinia
Authors: Chen Youxin , Pei Xianzhi , Li Zuochen , Li Ruibao , Liu Chengjun , Wang Meng
Published: November 2017

A suite of granitic gneisses has been identified in the Hatu area, eastern segment of the East Kunlun Orogen. Zircon U–Pb dating of granitic gneisses indicates magmatic crystallization at 895.4 ± 9.3 Ma. However, some zircons yield a metamorphic age of 433.8 ± 6.2 Ma. When taken together, these data reveal that the Early Neoproterozoic granites experienced Early Paleozoic metamorphism. The granitic gneisses are characterized by high contents of SiO2, Al2O3, and K2O + Na2O and low concentrations of TiO2, MnO, and CaO. The petrochemical character (average A/CNK = 1.09 and average A/NK = 1.42) and the mineral assemblages suggest that the granites are of S type and peraluminous. The chondrite‐normalized rare earth element patterns of the samples show enrichment of light rare earth elements ((La/Yb)N = 13.84) and moderate negative Eu anomalies (δEu = 0.60). The primitive‐mantle‐normalized trace element diagrams show an enrichment of Rb and Th and a depletion of Ta, Nb, Sr, P, and Ti. The granitic gneisses have features of crust‐derived and typical continent–continent syn‐collisional granites. All the above characteristics suggest that the Paleoproterozoic Baishahe Formation probably served as the source rocks and that the granitic gneisses were generated by partial melting of the metasedimentary material related to crustal thickening. They also reveal a collision between the micro‐block in the Early Neoproterozoic in response to the assembly of the supercontinent Rodinia in East Kunlun.
Petrogenesis of the Jurassic adakitic rocks in Gan‐Hang Belt South China: Response to the Palaeo‐Pacific Plate oblique subduction
Authors: Zhao Xilin , Mao Jianren , Liu Kai , Li Zilong , Ye Haimin , Zhou Jing , Hu Yizhou
Published: November 2017

To explain the roughly contemporary magmatic activities between Cathaysia Block and both sides of the Jiangnan Orogenic Belt, we discussed the magmatic‐ore related and closely compressive tectonism in the Gan‐Hang Belt. Also, we compared the Yongping Pluton and Yinshan volcanic‐plutonic rocks in northeastern Jiangxi, and Huangshitan and other plutons in the northern Zhejiang, which were produced in the setting of compressive tectonism. We compared bimodel dikes and Sanqingshan A‐type granite in the northeastern Jiangxi, and Huanshitan and other A‐type granites in the northern Zhejiang, which formed in the setting of extension. We proposed that approximately in Middle Jurassic time (175 ± 5 Ma), South China entered into the tectonic system, roughly from south to north oblique subduction of the Paleo‐Pacific Plate. The intermission period of the magmatic activities in Japan and South Korea (~170–120 Ma) was actually the period of the large‐scale magmatic‐ore forming activities in South China. Thus, this oblique subduction resulted in the dynamic imbalance and mutual movement from the deep part to the shallow part of the crust among surrounding blocks of South China and the multiple blocks of South China including those orogens between the North and South China blocks, between the Yangtze Craton and Cathayasian Block, and between the South China Block and Indosinian Block, as well as microcontinental blocks within Cathaysia Block. At present, we cannot rule out the influence of compressional–extensional tectonism for the Gan‐Hang Belt controlled by the Paleo‐Asia tectonic system.
Origin and Palaeozoic reworking of the Central Tianshan Block, southern CAOB: Constraints from provenance analysis of metasedimentary rocks in northern Xinjiang Province and adjacent region
Authors: Zhou Hai , Chen Liang , Sun Yong , He Yanhong
Published: November 2017

There are several Precambrian microcontinents in the Central Asian Orogenic Belt (CAOB). Across these microcontinents, there are many metasedimentary rocks which were not all deposited in the Precambrian. We report on a field‐based petrological and zircon geochronological study of metasedimentary rocks from the Tianshan and Beishan orogens, southern CAOB, in order to reveal the Precambrian affinity and Palaeozoic reworking. Most metasedimentary rocks in the Central Tianshan Block (CTB) and Dunhuang arc accretionary system reveal Palaeozoic records of arc accretion, collision, and postcollisional processes. The zircon age patterns of these metasedimentary rocks in the CTB show strong affinity to the Tarim Craton, whereas those of the Dunhuang arc accretionary system suggest a Mongolian affinity. The CTB constituted an independent microcontinent during the Palaeozoic accretionary process and was transformed into a Japan‐type arc until it became amalgamated with the Tarim Block in the late Permian. In contrast, the Dunhuang Block shows a probable Mongolian affinity and was a stable unit during the late Mesoproterozoic to Neoproterozoic until the beginning of CAOB orogenesis.
Petrogenesis and tectonic setting of Carboniferous hornblende gabbros of the northern Great Xing'an Range, NE China: Constraints from geochronology, geochemistry, mineral chemistry, and zircon Hf isotopes
Authors: Yang Dong‐Guang , Sun De‐You , Gou Jun , Hou Xue‐Gang
Published: November 2017

This study presents new information on the petrogenesis and tectonic setting of a hornblende gabbro in the northern Great Xing'an Range of northeastern China using new whole‐rock geochemical, mineral geochemical, and in situ zircon U–Pb and Hf isotopic data obtained for samples taken from near the town of Tayuan. Zircon U–Pb dating indicates that the hornblende gabbro was emplaced during the late Carboniferous (~311 Ma). The hornblende gabbros are alkaline with high K2O + Na2O (4.25–6.42 wt.%), low SiO2 (41.69–50.22 wt.%), and variable MgO (4.49–7.16 wt.%) and TiO2 (1.23–2.77 wt.%) contents. The pressure and temperature conditions of gabbro crystallization were determined using amphibole–plagioclase and amphibole thermobarometry, which indicate that the Tayuan hornblende gabbro formed at pressures of 4.1–6.9 kbar and temperatures of 686–762 °C, respectively. The hornblende gabbros are enriched in light rare earth elements and large ion lithophile elements, are depleted in the heavy rare earth elements and high field strength elements, and have positive zircon εHf(t) values (+3.9 to +9.9), all of which are indicative of formation from magmas generated by the partial melting of a depleted region of the lithospheric mantle that was previously metasomatized by subducted slab‐derived fluids and/or melts just before the generation of the hornblende gabbro magmas. The field observational, geochronological, geochemical, mineral geochemical, and zircon Hf isotopic data presented here are indicative of a complex petrogenetic history that involved crystal fractionation and magma mixing. These hornblende gabbros were emplaced in an extensional setting associated with the collision of the Xing'an and Songnen massifs.
Promoting normal birth and reducing caesarean section rates: An evaluation of the Rapid Improvement Programme
Authors: Cookson Graham , Laliotis Ioannis
Published: November 2017

This paper evaluates the impact of the 2008 Rapid Improvement Programme that aimed at promoting normal birth and reducing caesarean section rates in the English National Health Service. Using Hospital Episode Statistics maternity records for the period 2001–2013, a panel data analysis was performed to determine whether the implementation of the programme reduced caesarean sections rates in participating hospitals. The results obtained using either the unadjusted sample of hospitals or a trimmed sample determined by a propensity score matching approach indicate that the impact of the programme was small. More specifically there were 2.3 to 3.4 fewer caesarean deliveries in participating hospitals, on average, during the postprogramme period offering a limited scope for cost reduction. This result mainly comes from the reduction in the number of emergency caesareans as no significant effect was uncovered for planned caesarean deliveries.
Increased hippocampus to ventromedial prefrontal connectivity during the construction of episodic future events
Authors: Campbell Karen L. , Madore Kevin P. , Benoit Roland G. , Thakral Preston P. , Schacter Daniel L.
Published: November 2017

Both the hippocampus and ventromedial prefrontal cortex (vmPFC) appear to be critical for episodic future simulation. Damage to either structure affects one's ability to remember the past and imagine the future, and both structures are commonly activated as part of a wider core network during future simulation. However, the precise role played by each of these structures and, indeed, the direction of information flow between them during episodic simulation, is still not well understood. In this study, we scanned participants using functional magnetic resonance imaging while they imagined future events in response to object cues. We then used dynamic causal modeling to examine effective connectivity between the left anterior hippocampus and vmPFC during the initial mental construction of the events. Our results show that while there is strong bidirectional intrinsic connectivity between these regions (i.e., irrespective of task conditions), only the hippocampus to vmPFC connection increases during the construction of episodic future events, suggesting that the hippocampus initiates event simulation in response to retrieval cues, driving activation in the vmPFC where episodic details may be further integrated.
A comprehensive analysis of polymorphic variants in steroid hormone and insulin‐like growth factor‐1 metabolism and risk of in situ breast cancer: Results from the Breast and Prostate Cancer Cohort Consortium
Authors: Barrdahl Myrto , Canzian Federico , Gaudet Mia M. , Gapstur Susan M. , Trichopoulou Antonia , Tsilidis Kostas , van Gils Carla H. , Borgquist Signe , Weiderpass Elisabete , Khaw Kay‐Tee , Giles Graham G. , Milne Roger L. , Le Marchand Loic , Haiman Christopher , Lindström Sara , Kraft Peter , Hunter David J. , Ziegler Regina , Chanock Stephen J. , Yang Xiaohong R. , Buring Julie E. , Lee I‐Min , Kaaks Rudolf , Campa Daniele
Published: November 2017

We assessed the association between 1,414 single nucleotide polymorphisms (SNPs) in genes involved in synthesis and metabolism of steroid hormones and insulin‐like growth factor 1, and risk of breast cancer in situ (BCIS), with the aim of determining whether any of these were disease specific. This was carried out using 1,062 BCIS cases and 10,126 controls as well as 6,113 invasive breast cancer cases from the Breast and Prostate Cancer Cohort Consortium (BPC3). Three SNPs showed at least one nominally significant association in homozygous minor versus homozygous major models. ACVR2A‐rs2382112 (ORhom = 3.05, 95%CI = 1.72–5.44, Phom = 1.47 × 10−4), MAST2‐rs12124649 (ORhom = 1.73, 95% CI =1.18–2.54, Phom = 5.24 × 10−3), and INSR‐rs10500204 (ORhom = 1.96, 95% CI = 1.44–2.67, Phom=1.68 × 10−5) were associated with increased risk of BCIS; however, only the latter association was significant after correcting for multiple testing. Furthermore, INSR‐rs10500204 was more strongly associated with the risk of BCIS than invasive disease in case‐only analyses using the homozygous minor versus homozygous major model (ORhom = 1.78, 95% CI = 1.30–2.44, Phom = 3.23 × 10−4). The SNP INSR‐rs10500204 is located in an intron of the INSR gene and is likely to affect binding of the promyelocytic leukemia (PML) protein. The PML gene is known as a tumor suppressor and growth regulator in cancer. However, it is not clear on what pathway the A‐allele of rs10500204 could operate to influence the binding of the protein. Hence, functional studies are warranted to investigate this further.
Circulating concentrations of vitamin D in relation to pancreatic cancer risk in European populations
Authors: van Duijnhoven Fränzel J.B. , Jenab Mazda , Hveem Kristian , Siersema Peter D. , Fedirko Veronika , Duell Eric J. , Kampman Ellen , Halfweeg Anouk , van Kranen Henk J. , van den Ouweland Jody M.W. , Weiderpass Elisabete , Murphy Neil , Langhammer Arnulf , Ness‐Jensen Eivind , Olsen Anja , Tjønneland Anne , Overvad Kim , Cadeau Claire , Kvaskoff Marina , Boutron‐Ruault Marie‐Christine , Katzke Verena A. , Kühn Tilman , Boeing Heiner , Trichopoulou Antonia , Kotanidou Anastasia , Kritikou Maria , Palli Domenico , Agnoli Claudia , Tumino Rosario , Panico Salvatore , Matullo Giuseppe , Peeters Petra , Brustad Magritt , Olsen Karina Standahl , Lasheras Cristina , Obón‐Santacana Mireia , Sánchez María‐José , Dorronsoro Miren , Chirlaque Maria‐Dolores , Barricarte Aurelio , Manjer Jonas , Almquist Martin , Renström Frida , Ye Weimin , Wareham Nick , Khaw Kay‐Tee , Bradbury Kathryn E. , Freisling Heinz , Aune Dagfinn , Norat Teresa , Riboli Elio , Bueno‐de‐Mesquita H. B(as)
Published: November 2017

Evidence from in vivo, in vitro and ecological studies are suggestive of a protective effect of vitamin D against pancreatic cancer (PC). However, this has not been confirmed by analytical epidemiological studies. We aimed to examine the association between pre‐diagnostic circulating vitamin D concentrations and PC incidence in European populations. We conducted a pooled nested case‐control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Nord‐Trøndelag Health Study's second survey (HUNT2) cohorts. In total, 738 primary incident PC cases (EPIC n = 626; HUNT2 n = 112; median follow‐up = 6.9 years) were matched to 738 controls. Vitamin D [25(OH)D2 and 25(OH)D3 combined] concentrations were determined using isotope‐dilution liquid chromatography‐tandem mass spectrometry. Conditional logistic regression models with adjustments for body mass index and smoking habits were used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (95%CI). Compared with a reference category of >50 to 75 nmol/L vitamin D, the IRRs (95% CIs) were 0.71 (0.42–1.20); 0.94 (0.72–1.22); 1.12 (0.82–1.53) and 1.26 (0.79–2.01) for clinically pre‐defined categories of ≤25; >25 to 50; >75 to 100; and >100 nmol/L vitamin D, respectively (p for trend = 0.09). Corresponding analyses by quintiles of season‐standardized vitamin D concentrations also did not reveal associations with PC risk (p for trend = 0.23). Although these findings among participants from the largest combination of European cohort studies to date show increasing effect estimates of PC risk with increasing pre‐diagnostic concentrations of vitamin D, they are not statistically significant.
Hyperconjugative effects in π‐hydrogen bonding: Theory and experiment
Authors: Galabov Boris , Nikolova Valia , Cheshmedzhieva Diana , Hadjieva Boriana , Schaefer Henry F.
Published: November 2017

Density functional theory computations with the B3LYP/6‐311++G(2df,2p) method and IR spectroscopy are employed in investigating the properties of twenty π‐hydrogen bonded complexes between substituted phenols and hexamethylbenzene. All complexes possess T‐shaped structures. The methyl hyperconjugative effects on interactions energies and OH stretching frequencies are estimated via comparisons with previously reported theoretical and experimental results for analogous phenol complexes with benzene. The theoretical computations provide excellent quantitative predictions of the OH stretching frequency shifts (ΔνOH) resulting from the hydrogen bonding. The ΔνOH shifts in the hexamethylbenzene complexes are approximately twice as large as the corresponding shifts for the benzene complexes. Hirshfeld charges, electrostatic potential at nuclei values, and molecular electrostatic potential maps are employed in gaining insights into the mechanisms of methyl hyperconjugative effects on complex formation. © 2017 Wiley Periodicals, Inc.
Emotion regulation difficulties in obsessive‐compulsive disorder
Authors: Yap Keong , Mogan Christopher , Moriarty Anna , Dowling Nathan , Blair‐West Scott , Gelgec Celin , Moulding Richard
Published: November 2017

Objective

Emotion regulation difficulties are implicated in psychological disorders but their role in obsessive‐compulsive disorder (OCD) is unclear. Two studies examining these difficulties in OCD are presented.

Method

A community sample (Study 1; n = 306) and a clinical OCD sample (Study 2; n = 59) completed the Difficulties in Emotion Regulation Scale (DERS) and measures of depression, anxiety, and OCD. In Study 2, the OCD sample was compared to a matched control group (n = 59, selected from Study 1).

Results

In Study 1, OCD was positively correlated with DERS total and subscale scores, and the DERS significantly predicted OCD severity even after accounting for age, gender, depression, and anxiety. In Study 2, emotion regulation difficulties were significantly higher in the clinical sample compared to the matched control group, even after accounting for depression and anxiety.

Conclusion

Results showed that emotion regulation difficulties in OCD cannot simply be attributed to mood difficulties. Theoretical and treatment implications are discussed.
Methylation‐independent CHFR expression is a potential biomarker affecting prognosis in acute myeloid leukemia
Authors: Zhou Jing‐Dong , Zhang Ting‐Juan , Li Xi‐Xi , Ma Ji‐Chun , Guo Hong , Wen Xiang‐Mei , Yao Dong‐Ming , Zhang Wei , Lin Jiang , Qian Jun
Published: November 2017

CHFR acts as a tumor suppressor gene, which is frequently inactivated caused by its promoter hypermethylation in various solid tumors. Although a recent study showed that CHFR hypermethylation was a frequent event in acute myeloid leukemia (AML) and correlated with adverse clinical outcome, herein, we found that CHFR methylation was a rare event in patients with myeloid malignancies (including AML, chronic myeloid leukemia, and myelodysplastic syndromes), but its expression may serve as an independent prognostic biomarker in AML. CHFR expression was assessed by real‐time quantitative PCR, whereas CHFR methylation was detected by methylation‐specific PCR and bisulfite sequencing PCR. In AML patients, lower CHFR expression was associated with lower complete remission (CR) rate, and CHFR expression was significantly increased in CR after chemotherapy. Moreover, patients with lower CHFR expression showed shorter overall survival and leukemia‐free survival, and multivariate analysis confirmed that lower CHFR expression was an independent risk factor in AML. Importantly, the prognostic value of CHFR expression was validated using the published Gene Expression Omnibus datasets. Notably, CHFR promoter was nearly unmethylated in patients with myeloid malignancies. Our findings revealed that lower CHFR expression was independently associated with unfavorable prognosis in AML. Moreover, aberrant CHFR promoter methylation was a rare event in myeloid malignances.
Four differentially methylated gene pairs to predict the prognosis for early stage hepatocellular carcinoma patients
Authors: Liu Shaoguang , Miao Changfeng , Liu Juan , Wang Chang‐Cheng , Lu Xiao‐Jie
Published: November 2017

Hepatocellular carcinoma (HCC) was the second most common malignant tumor with a poor prognostic condition. We aimed to identify novel methylation signatures to predict HCC patients at their early stages. Differentially expressed methylated genes between HCC patients and normal liver tissues retrieved from TCGA were screened out by SAM. Genes highly related to patients’ survival were figured out by COX. The signatures that could identify relapse HCC patients were identified by the forwarding search algorithm. Besides, functional enrichment analysis was performed on the methylation genes in the signature. A total of 5,392 CPG sites that differentially methylated expressed were found out and 4,294 differentially expressed genes were obtained. A total of 197 genes among were associated with RFS of HCC patients at both stage I and stage II. Signature composed of 21 pairs was obtained to predict the prognostic situation by C‐index forward search method. The function of these genes was figured out by functional enrichment analysis. To summary, the signature composed of 21 gene pairs that can predict the prognostic situation of HCC patients at both stage I and stage II, provided a reference standard for the adjuvant therapy of HCC patients after surgery.