bluuebunny/crossref_metadata_2025 huggingface dataset:
Stress-induced nuclear accumulation is dispensable for Hog1-dependent gene expression and virulence in a fungal pathogen
Authors: Day Alison M. , Herrero-de-Dios Carmen M. , MacCallum Donna M. , Brown Alistair J. P. , Quinn Janet
Published: October 2017

Stress-activated protein kinase (SAPK) pathways are evolutionarily conserved eukaryotic signalling modules that are essential for the virulence of human pathogenic fungi. The Hog1 SAPK in Candida albicans is robustly phosphorylated in response to a number of host-imposed stresses, and is essential for virulence. The current dogma is that stress-induced phosphorylation activates the SAPK, and promotes its nuclear accumulation that is necessary for the expression of SAPK-dependent stress-protective genes. Here we challenge this dogma. C. albicans strains were constructed in which Hog1 was either tethered to the plasma membrane or constitutively nuclear. Strikingly, tethering Hog1 to the plasma membrane did not abrogate stress resistance or stress-induced gene expression. Furthermore, preventing the nuclear accumulation of Hog1 had no impact on C. albicans virulence in two distinct models of systemic infection. However, tethering Hog1 to the plasma membrane did impact on signal fidelity, and on the magnitude and kinetics of the stress-induced phosphorylation of this SAPK. Taken together, these findings challenge the dogma that nuclear accumulation of SAPKs is a pre-requisite for SAPK-dependent gene expression, and reveal that stress-induced nuclear accumulation of Hog1 is dispensable for the virulence of a major human fungal pathogen.
Identify a Blood-Brain Barrier Penetrating Drug-TNB using Zebrafish Orthotopic Glioblastoma Xenograft Model
Authors: Zeng Anqi , Ye Tinghong , Cao Dan , Huang Xi , Yang Yu , Chen Xiuli , Xie Yongmei , Yao Shaohua , Zhao Chengjian
Published: October 2017

The blood–brain barrier (BBB) is necessary for maintaining brain homeostasis, but it also represents a major challenge for drug delivery to the brain tumors. A suitable in vivo Glioblastoma Multiforme (GBM) model is needed for efficient testing of BBB crossable pharmaceuticals. In this study, we firstly confirmed the BBB functionality in 3dpf zebrafish embryos by Lucifer Yellow, Evans Blue and DAPI microinjection. We then transplanted human GBM tumor cells into the zebrafish brain, in which implanted GBM cells (U87 and U251) were highly mitotic and invasive, mimicking their malignancy features in rodents’ brain. Interestingly, we found that, although extensive endothelial proliferation and vessel dilation were observed in GBM xenografts, the BBB was still not disturbed. Next, using the zebrafish orthotopic GBM xenograft model as an in vivo visual readout, we successfully identified a promising small compound named TNB, which could efficiently cross the zebrafish BBB and inhibit the progression of orthotopic GBM xenografts. These results indicate that TNB is a promising BBB crossable GBM drug worth to be further characterized in human BBB setting, also suggest the zebrafish orthotopic GBM model as an efficient visual readout for the BBB penetrating anti-GBM drugs.
Genome-wide analysis reveals differential selection involved with copy number variation in diverse Chinese Cattle
Authors: Yang Liu , Xu Lingyang , Zhu Bo , Niu Hong , Zhang Wengang , Miao Jian , Shi Xinping , Zhang Ming , Chen Yan , Zhang Lupei , Gao Xue , Gao Huijiang , Li Li , Liu George E. , Li Junya
Published: October 2017

Copy number variations (CNVs) are defined as deletions, insertions, and duplications between two individuals of a species. To investigate the diversity and population-genetic properties of CNVs and their diverse selection patterns, we performed a genome-wide CNV analysis using high density SNP array in Chinese native cattle. In this study, we detected a total of 13,225 CNV events and 3,356 CNV regions (CNVRs), overlapping with 1,522 annotated genes. Among them, approximately 71.43 Mb of novel CNVRs were detected in the Chinese cattle population for the first time, representing the unique genomic resources in cattle. A new V
i
statistic was proposed to estimate the region-specific divergence in CNVR for each group based on unbiased estimates of pairwise V
ST
. We obtained 12 and 62 candidate CNVRs at the top 1% and top 5% of genome-wide V
i
value thresholds for each of four groups (North, Northwest, Southwest and South). Moreover, we identified many lineage-differentiated CNV genes across four groups, which were associated with several important molecular functions and biological processes, including metabolic process, response to stimulus, immune system, and others. Our findings provide some insights into understanding lineage-differentiated CNVs under divergent selection in the Chinese native cattle.
A comparison of transcriptomic patterns measured in the skin of Chinese fine and coarse wool sheep breeds
Authors: Zhang Lichun , Sun Fuliang , Jin Haiguo , Dalrymple Brian P. , Cao Yang , Wei Tian , Vuocolo Tony , Zhang Mingxin , Piao Qinlin , Ingham Aaron B.
Published: October 2017

We characterised wool traits, and skin gene expression profiles of fine wool Super Merino (SM) and coarse wool Small Tail Han (STH) sheep. SM sheep had a significantly higher total density of wool follicles, heavier fleeces, finer fibre diameter, and increased crimp frequency, staple length and wool grease (lanolin) production. We found 435 genes were expressed at significantly different levels in the skin of the two breeds (127 genes more highly in SM and 308 genes more highly in STH sheep). Classification of the genes more highly expressed in SM sheep revealed numerous lipid metabolic genes as well as genes encoding keratins, keratin-associated proteins, and wool follicle stem cell markers. In contrast, mammalian epidermal development complex genes and other genes associated with skin cornification and muscle function were more highly expressed in STH sheep. Genes identified in this study may be further evaluated for inclusion in breeding programs, or as targets for therapeutic or genetic interventions, aimed at altering wool quality or yield. Expression of the lipid metabolic genes in the skin of sheep may be used as a novel trait with the potential to alter the content or properties of lanolin or the fleece.
Alterations in the host transcriptome in vitro following Rift Valley fever virus infection
Authors: Pinkham Chelsea , Dahal Bibha , de la Fuente Cynthia L. , Bracci Nicole , Beitzel Brett , Lindquist Michael , Garrison Aura , Schmaljohn Connie , Palacios Gustavo , Narayanan Aarthi , Campbell Catherine E. , Kehn-Hall Kylene
Published: October 2017

Rift Valley fever virus (RVFV) causes major outbreaks among livestock, characterized by “abortion storms” in which spontaneous abortion occurs in almost 100% of pregnant ruminants. Humans can also become infected with mild symptoms that can progress to more severe symptoms, such as hepatitis, encephalitis, and hemorrhagic fever. The goal of this study was to use RNA-sequencing (RNA-seq) to analyze the host transcriptome in response to RVFV infection. G2/M DNA damage checkpoint, ATM signaling, mitochondrial dysfunction, regulation of the antiviral response, and integrin-linked kinase (ILK) signaling were among the top altered canonical pathways with both the attenuated MP12 strain and the fully virulent ZH548 strain. Although several mRNA transcripts were highly upregulated, an increase at the protein level was not observed for the selected genes, which was at least partially due to the NSs dependent block in mRNA export. Inhibition of ILK signaling, which is involved in cell motility and cytoskeletal reorganization, resulted in reduced RVFV replication, indicating that this pathway is important for viral replication. Overall, this is the first global transcriptomic analysis of the human host response following RVFV infection, which could give insight into novel host responses that have not yet been explored.
Klotho Inhibits Interleukin-8 Secretion from Cystic Fibrosis Airway Epithelia
Authors: Krick Stefanie , Baumlin Nathalie , Aller Sheyla Paredes , Aguiar Carolina , Grabner Alexander , Sailland Juliette , Mendes Eliana , Schmid Andreas , Qi Lixin , David Nicolae V. , Geraghty Patrick , King Gwendalyn , Birket Susan E. , Rowe Steven M. , Faul Christian , Salathe Matthias
Published: October 2017

Chronic inflammation is a hallmark of cystic fibrosis (CF) and associated with increased production of transforming growth factor (TGF) β and interleukin (IL)-8. α-klotho (KL), a transmembrane or soluble protein, functions as a co-receptor for Fibroblast Growth Factor (FGF) 23, a known pro-inflammatory, prognostic marker in chronic kidney disease. KL is downregulated in airways from COPD patients. We hypothesized that both KL and FGF23 signaling modulate TGF β-induced IL-8 secretion in CF bronchial epithelia. Thus, FGF23 and soluble KL levels were measured in plasma from 48 CF patients and in primary CF bronchial epithelial cells (CF-HBEC). CF patients showed increased FGF23 plasma levels, but KL levels were not different. In CF-HBEC, TGF-β increased KL secretion and upregulated FGF receptor (FGFR) 1. Despite increases in KL, TGF-β also increased IL-8 secretion via activation of FGFR1 and Smad 3 signaling. However, KL excess via overexpression or supplementation decreased IL-8 secretion by inhibiting Smad 3 phosphorylation. Here, we identify a novel signaling pathway contributing to IL-8 secretion in the CF bronchial epithelium with KL functioning as an endocrine and local anti-inflammatory mediator that antagonizes pro-inflammatory actions of FGF23 and TGF-β.
Author correction: Wafer-scale two-dimensional ferromagnetic Fe3GeTe2 thin films grown by molecular beam epitaxy
Authors: Liu Shanshan , Yuan Xiang , Zou Yichao , Sheng Yu , Huang Ce , Zhang Enze , Ling Jiwei , Liu Yanwen , Wang Weiyi , Zhang Cheng , Zou Jin , Wang Kaiyou , Xiu Faxian
Published: October 2017

A correction to this article has been published and is linked from the HTML version of this article.
Correction: Corrigendum: Diffraction data of core-shell nanoparticles from an X-ray free electron laser
Authors: Li Xuanxuan , Chiu Chun-Ya , Wang Hsiang-Ju , Kassemeyer Stephan , Botha Sabine , Shoeman Robert L , Lawrence Robert M , Kupitz Christopher , Kirian Richard , James Daniel , Wang Dingjie , Nelson Garrett , Messerschmidt Marc , Boutet Sébastien , Williams Garth J , Hartmann Elisabeth , Jafarpour Aliakbar , Foucar Lutz M , Barty Anton , Chapman Henry , Liang Mengning , Menzel Andreas , Wang Fenglin , Basu Shibom , Fromme Raimund , Doak R.Bruce , Fromme Petra , Weierstall Uwe , Huang Michael H , Spence John C.H , Schlichting Ilme , Hogue Brenda G , Liu Haiguang
Published: October 2017

Scientific Data 4:170048 doi: 10.1038/sdata201748 (2017); Published 11 April 2017; Updated 24 October 2017. The Data Descriptor incorrectly states the number of normal incidences used to generate the plot in Fig. 4b as 209. This plot was generated from 32 normal incidence cases.
A global moderate resolution dataset of gross primary production of vegetation for 2000–2016
Authors: Zhang Yao , Xiao Xiangming , Wu Xiaocui , Zhou Sha , Zhang Geli , Qin Yuanwei , Dong Jinwei
Published: October 2017

Accurate estimation of the gross primary production (GPP) of terrestrial vegetation is vital for understanding the global carbon cycle and predicting future climate change. Multiple GPP products are currently available based on different methods, but their performances vary substantially when validated against GPP estimates from eddy covariance data. This paper provides a new GPP dataset at moderate spatial (500 m) and temporal (8-day) resolutions over the entire globe for 2000–2016. This GPP dataset is based on an improved light use efficiency theory and is driven by satellite data from MODIS and climate data from NCEP Reanalysis II. It also employs a state-of-the-art vegetation index (VI) gap-filling and smoothing algorithm and a separate treatment for C3/C4 photosynthesis pathways. All these improvements aim to solve several critical problems existing in current GPP products. With a satisfactory performance when validated against in situ GPP estimates, this dataset offers an alternative GPP estimate for regional to global carbon cycle studies.
Genome-wide association studies of smooth pursuit and antisaccade eye movements in psychotic disorders: findings from the B-SNIP study
Authors: Lencer R , Mills L J , Alliey-Rodriguez N , Shafee R , Lee A M , Reilly J L , Sprenger A , McDowell J E , McCarroll S A , Keshavan M S , Pearlson G D , Tamminga C A , Clementz B A , Gershon E S , Sweeney J A , Bishop J R
Published: October 2017

Eye movement deviations, particularly deficits of initial sensorimotor processing and sustained pursuit maintenance, and antisaccade inhibition errors, are established intermediate phenotypes for psychotic disorders. We here studied eye movement measures of 849 participants from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) study (schizophreniaN=230, schizoaffective disorderN=155, psychotic bipolar disorderN=206 and healthy controlsN=258) as quantitative phenotypes in relation to genetic data, while controlling for genetically derived ancestry measures, age and sex. A mixed-modeling genome-wide association studies approach was used including ~4.4 million genotypes (PsychChip and 1000 Genomes imputation). Across participants, sensorimotor processing at pursuit initiation was significantly associated with a single nucleotide polymorphism inIPO8(12p11.21,P=8 × 10−11), whereas suggestive associations with sustained pursuit maintenance were identified with SNPs inSH3GL2(9p22.2,P=3 × 10−8). In participants of predominantly African ancestry, sensorimotor processing was also significantly associated with SNPs inPCDH12(5q31.3,P=1.6 × 10−10), and suggestive associations were observed withNRSN1(6p22.3,P=5.4 × 10−8) andLMO7(13q22.2,P=7.3x10−8), whereas antisaccade error rate was significantly associated with a non-coding region at chromosome 7 (P=6.5 × 10−9). Exploratory pathway analyses revealed associations with nervous system development and function for 40 top genes with sensorimotor processing and pursuit maintenance (P=4.9 × 10−2–9.8 × 10−4). Our findings suggest novel patterns of genetic variation relevant for brain systems subserving eye movement control known to be impaired in psychotic disorders. They include genes involved in nuclear trafficking and gene silencing (IPO8), fast axonal guidance and synaptic specificity (PCDH12), transduction of nerve signals (NRSN1), retinal degeneration (LMO7), synaptic glutamate release (SH3GL2), and broader nervous system development and function.
Mechanochemistry: Inspiration from Biology
Authors: Chidanguro Tamuka , Weng Wengui , Simon Yoan C.
Published: October 2017

Mechanochemistry refers to the study of the evolution of the formation and disruption of chemical bonds upon application of an external force. In this chapter, the roles of mechanical forces in different biological systems are highlighted along with mechanisms and mechanotransduction pathways showing how complex biological systems can provide inspiration for materials design. Examples of how mechano-based systems have been mimicked by other scientists are also discussed including self-healing systems.
Development of defocusing micro-SORS mapping: a study of a 19th century porcelain card
Authors: Rousaki Anastasia , Botteon Alessandra , Colombo Chiara , Conti Claudia , Matousek Pavel , Moens Luc , Vandenabeele Peter
Published: October 2017

Defocusing micro-SORS mapping allows studying the pigment distribution and stratigraphy in painted artwork.
Luminescent complexes made from chelating isocyanide ligands and earth-abundant metals
Authors: Büldt Laura A. , Wenger Oliver S.
Published: October 2017

Cr(0), Mo(0), and Ni(0) complexes with diisocyanide ligands have recently been discovered as isoelectronic analogues of well-known Fe(ii), Ru(ii), and Cu(i) complexes.
Cigarette butt-derived carbons have ultra-high surface area and unprecedented hydrogen storage capacity
Authors: Blankenship L. Scott , Mokaya Robert
Published: October 2017

Cigarette butt derived carbons are highly porous (4310 m2 g−1 and 2.09 cm3 g−1) with record levels of hydrogen storage.
Modulating the catalytic activity of enzyme-like nanoparticles through their surface functionalization
Authors: Cao-Milán Roberto , He Luke D. , Shorkey Spencer , Tonga Gulen Y. , Wang Li-Sheng , Zhang Xianzhi , Uddin Imad , Das Riddha , Sulak Mine , Rotello Vincent M.
Published: October 2017

Surface functional groups of nanozyme ligands dictate their kinetic behavior.
Rational design of conjugated side chains for high-performance all-polymer solar cells
Authors: Huang Wei , Li Meilin , Lin Fengyuan , Wu Yang , Ke Zhifan , Zhang Xing , Ma Rui , Yang Tingbin , Ma Wei , Liang Yongye
Published: October 2017

High-performance all-polymer solar cells were developed by employing an asymmetric benzo[1,2-b:4,5-b′]dithiophene unit with one thiophene and one 4-methoxythiophene conjugated side chain in the donor polymer, which enabled fine-tuning of energy levels and phase separation.
XtalFluor-E® mediated proto-functionalization of N-vinyl amides: access to N-acetyl N,O-acetals
Authors: Yi Y. , Gholami H. , Morrow M. G. , Borhan B.
Published: October 2017

XtalFluor-E® catalyzes the efficient proto-functionalization of N-vinyl amides to yield N-acetyl N,O-acetals.
Synthesis, characterization and synergistic photocatalytic properties of yeast-assisted composite La0.7Sr0.3MnO3/TiO2
Authors: Yue Pan , Wei Zhi-Xian , Wu Xu-Hong , Zhang He-Dan , Ye Fan
Published: October 2017

A magnetic yeast-assisted composite Y-La0.7Sr0.3MnO3/TiO2with p–n heterojunction was prepared. And it shows an obvious synergistic photocatalytic effect on methyl orange (MO) wastewater under solar irradiation.
Sequence dependency of the thermodynamic properties of long DNA double-strands
Authors: Khodadadi Jabbar , Mirabbaszadeh Kavoos , Yarmohammadi Mohsen
Published: October 2017

Temperature and sequence dependency of the Pauli paramagnetic susceptibility (PMS) and electronic heat capacity (EHC) of selected configurations are investigated for π-electrons within a ladder model of long DNA double-strands acting as semiconducting nanowires.
Iodobenzene-catalyzed synthesis of aryl sulfonate esters from aminoquinolines via remote radical C–O cross-coupling
Authors: Shen Chao , Yang Ming , Xu Jun , Chen Chao , Zheng Kai , Shen Jiabing , Zhang Pengfei
Published: October 2017

A simple and efficient approach is established for the iodobenzene-catalyzed synthesis of aryl sulfonate esters from aminoquinolines via remote radical C–O cross-coupling in the absence of any transition metal catalysts.
Synthesis of Cu–Mg/ZnO catalysts and catalysis in dimethyl oxalate hydrogenation to ethylene glycol: enhanced catalytic behavior in the presence of a Mg2+ dopant
Authors: Kong Xiangpeng , Chen Zheng , Wu Yuehuan , Wang Ruihong , Chen Jiangang , Ding Lifeng
Published: October 2017

Mg2+ doped nanoscale Cu–Mg/ZnO catalysts prepared by the co-precipitation method have been systematically characterized focusing on the amount of Mg2+ ions incorporated.
Molecular dynamics simulation of thermotropic bolaamphiphiles with a swallow-tail lateral chain: formation of cubic network phases
Authors: Sun Yangyang , Padmanabhan Poornima , Misra Mayank , Escobedo Fernando A.
Published: October 2017

Simulations reveal how swallow tail-shaped lateral chains in bolaamphiphiles lead to the formation of ordered bi- and co-continuous networks.
A stable two-electron-donating phenothiazine for application in nonaqueous redox flow batteries
Authors: Kowalski Jeffrey A. , Casselman Matthew D. , Kaur Aman Preet , Milshtein Jarrod D. , Elliott Corrine F. , Modekrutti Subrahmanyam , Attanayake N. Harsha , Zhang Naijao , Parkin Sean R. , Risko Chad , Brushett Fikile R. , Odom Susan A.
Published: October 2017

Simple modification of N-ethylphenothiazine (left) with electron-donating substituents (right) increases the molecular charge-storage capacity of this donor.
A yolk/shell strategy for designing hybrid phase change materials for heat management in catalytic reactions
Authors: Li Kongzhai , Cheng Xianming , Li Ningning , Zhu Xing , Wei Yonggang , Zhai Kang , Wang Hua
Published: October 2017

We propose to fabricate a thermal storage functional catalystviaa yolk/shell strategy for thermal management in complex chemical processes.
Effects of water on the forward and backward conversions of lead(ii) iodide to methylammonium lead perovskite
Authors: Shoyama Kazutaka , Sato Wataru , Guo Yunlong , Nakamura Eiichi
Published: October 2017

This work has chemically addressed the enigmatic effects of water on solar cell devices based on an organic–inorganic hybrid perovskite, i.e., water can exert either beneficial or detrimental effects on device fabrication and device stability.
Photocorrosion-resistant Sb2Se3photocathodes with earth abundant MoSxhydrogen evolution catalyst
Authors: Prabhakar Rajiv Ramanujam , Septina Wilman , Siol Sebastian , Moehl Thomas , Wick-Joliat René , Tilley S. David
Published: October 2017

A highly efficient Sb2Se3photocathode is resistant to photocorrosion in strongly acidic media without protective overlayers.
ALMA discovery of a rotating SO/SO2 flow in HH212
Authors: Tabone B. , Cabrit S. , Bianchi E. , Ferreira J. , Pineau des Forêts G. , Codella C. , Gusdorf A. , Gueth F. , Podio L. , Chapillon E.
Published: October 2017

We wish to constrain the possible contribution of a magnetohydrodynamic disk wind (DW) to the HH212 molecular jet. We mapped the flow base with ALMA Cycle 4 at 0.̋13 ~ 60 au resolution and compared these observations with synthetic DW predictions. We identified, in SO/SO2, a rotating flow that is wider and slower than the axial SiO jet. The broad outflow cavity seen in C34S is not carved by a fast wide-angle wind but by this slower agent. Rotation signatures may be fitted by a DW of a moderate lever arm launched out to ~40 au with SiO tracing dust-free streamlines from 0.05−0.3 au. Such a DW could limit the core-to-star efficiency to ≤50%.
L’imagerie multiphoton des peaux naturelles et synthétiques. Un nouvel outil pour l’évaluation des produits cosmétiques
Authors: Schanne-Klein Marie-Claire
Published: October 2017

Depuis l’article fondateur de W. Webb en 1990, la microscopie multiphoton s’est imposée comme l’outil de référence pour l’imagerie tridimensionnelle des tissus biologiques. Elle est particulièrement utile en cosmétique pour visualiser le réseau de fibres de collagène présent dans le derme, et commence à s’imposer comme un outil de référence pour tester des actifs ex vivo sur des peaux naturelles ou reconstruites.
Clinical Information Systems as the Backbone of a Complex Information Logistics Process: Findings from the Clinical Information Systems Perspective for 2016
Authors: Hackl W. O. , Ganslandt T.
Published: October 2017

Objective: To summarize recent research and to propose a selection of best papers published in 2016 in the field of Clinical Information Systems (CIS).

Method: The query used to retrieve the articles for the CIS section of the 2016 edition of the IMIA Yearbook of Medical Informatics was reused. It again aimed at identifying relevant publications in the field of CIS from PubMed and Web of Science and comprised search terms from the Medical Subject Headings (MeSH) catalog as well as additional free text search terms. The retrieved articles were categorized in a multi-pass review carried out by the two section editors. The final selection of candidate papers was then peer-reviewed by Yearbook editors and external reviewers. Based on the review results, the best papers were then chosen at the selection meeting with the IMIA Yearbook editorial board. Text mining, term co-occurrence mapping, and topic modelling techniques were used to get an overview on the content of the retrieved articles.

Results: The query was carried out in mid-January 2017, yielding a consolidated result set of 2,190 articles published in 921 different journals. Out of them, 14 papers were nominated as candidate best papers and three of them were finally selected as the best papers of the CIS field. The content analysis of the articles revealed the broad spectrum of topics covered by CIS research.

Conclusions: The CIS field is multi-dimensional and complex. It is hard to draw a well-defined outline between CIS and other domains or other sections of the IMIA Yearbook. The trends observed in the previous years are progressing. Clinical information systems are more than just sociotechnical systems for data collection, processing, exchange, presentation, and archiving. They are the backbone of a complex, trans-institutional information logistics process.
Kosten der spezialisierten Palliativversorgung – eine Analyse aus Perspektive der Kostenträger
Authors: Enderlein Anne , Jülich Andreas , Schindler Caroline , Fleßa Steffen
Published: October 2017

Die Palliativmedizin wird aufgrund des demografischen Wandels und des medizinisch-technischen Fortschritts an Bedeutung zunehmen. Es ist daher zu erwarten, dass auch die Kosten für die Palliativmedizin steigen werden, jedoch liegen bislang keine wissenschaftlichen Erkenntnisse über die Höhe der Ausgaben für Palliativversorgung für unterschiedliche Leistungsträger vor. Dies ist problematisch, da insbesondere die Kenntnis der Kosten der Kostenträger (Krankenkassen) die Grundlage für die optimale Ressourcenallokation und damit die Verbesserung der Versorgung darstellt. Die vorliegende Arbeit möchte hierzu einen Beitrag aus Perspektive der Kostenträger leisten. Mittels einer Sekundärdatenanalyse erfolgte die Ermittlung der Kosten aus der Sicht der GKV der spezialisierten Palliativversorgung in Greifswald sowohl im ambulanten als auch im stationären Bereich. Die gesamten Kosten beliefen sich auf 3 409 468,78 Euro bei 12 560 Patientenbetreuungstagen. Die täglichen Kosten von Patienten, die nur auf der Palliativstation behandelt wurden, betrugen 457,94 Euro, im Hospiz 155,11 Euro sowie in der spezialisierten ambulanten Palliativversorgung 74,51 Euro. Kosten für Patienten, die während eines stationären Aufenthaltes sowohl auf anderen Stationen des Klinikums und auf der Palliativstation behandelt wurden, betrugen 888,06 Euro. Ein Vergleich der Kosten untereinander ist nicht unproblematisch, da die Versorgungsschwerpunkte der Einrichtungen unterschiedlich ausgerichtet sind, sie stellen jedoch die Grundlage für eine Budgetanalyse dar.
Graph Theoretical Analysis, In Silico Modeling, Synthesis, Anti-Microbial and Anti-TB Evaluation of Novel Quinoxaline Derivatives
Authors: Saravanan Govindaraj , Selvam Theivendren , Alagarsamy Veerachamy , Kunjiappan Selvaraj , Joshi Shrinivas , Indhumathy Murugan , Kumar Pandurangan
Published: October 2017

Background We designed to synthesize a number of 2-(2-(substituted benzylidene) hydrazinyl)-N-(4-((3-(phenyl imino)-3,4-dihydro quinoxalin-2(1 H)-ylidene)amino) phenyl) acetamide S1-S13 with the hope to obtain more active and less toxic anti-microbial and anti-TB agents.

Methods A series of novel quinoxaline Schiff bases S1-S13 were synthesized from o-phenylenediamine and oxalic acid by a multistep synthesis. In present work, we are introducing graph theoretical analysis to identify drug target. In the connection of graph theoretical analysis, we utilised KEGG database and Cytoscape software. All the title compounds were evaluated for their in-vitro anti-microbial activity by using agar well diffusion method at three different concentration levels (50, 100 and 150 µg/ml). The MIC of the compounds was also determined by agar streak dilution method.

Results The identified study report through graph theoretical analysis were highlights that the key virulence factor for pathogenic mycobacteria is a eukaryotic-like serine/threonine protein kinase, termed PknG. All compounds were found to display significant activity against entire tested bacteria and fungi. In addition the synthesized scaffolds were screened for their in vitro antituberculosis (anti-TB) activity against Mycobacterium tuberculosis (Mtb) strain H37Ra using standard drug Rifampicin.

Conclusion A number of analogs found markedly potent anti-microbial and anti-TB activity. The relationship between the functional group variation and the biological activity of the evaluated compounds were well discussed. The observed study report was showing that the compound S6 (4-nitro substitution) exhibited most potent effective anti-microbial and anti-TB activity out of various tested compounds.
Zelluläre Mechanismen der systolischen Herzinsuffizienz
Authors: Maack Christoph
Published: October 2017

Bei systolischer Herzinsuffizienz verursacht die kontraktile Dysfunktion des linken Ventrikels eine neuroendokrine Aktivierung, die zu
maladaptiven Umbauprozessen des Herzens führt. Die Antagonisierung dieser neuroendokrinen Aktivierung ist daher das derzeit wichtigste
Therapiekonzept bei systolischer Herzinsuffizienz. Auf zellulärer Ebene sind neben der Expression prohypertropher Gene insbesondere
Störungen des kardiomyozytären Ca2+- und Na+-Haushalts, ein Energiedefizit und oxidativer Stress wichtige
pathologische Veränderungen. Mitochondrien spielen hierbei eine zentrale Rolle, da sie die wichtigste Quelle für ATP, aber auch reaktive
Sauerstoffspezies sind und ihre Funktion entscheidend durch Ca2+ und Na+ reguliert wird. Neuere pharmakologische
Ansätze zielen daher auf eine Verbesserung der mitochondrialen und metabolischen Dysfunktion, um hierüber den Progress der Herzinsuffizienz
abzumildern.
Eisenmangel bei chronischer Herzinsuffizienz
Authors: von Haehling Stephan , Ottenjann Henrike , Anker Stefan D.
Published: October 2017

Eisenmangel bei chronischer Herzinsuffizienz ist ein bedeutsamer Risikoparameter, der die körperliche Leistungsfähigkeit und die
Lebensqualität der Patienten negativ beeinflusst. Zahlreiche Studien bzw. Metaanalysen legen nahe, dass eine parenterale Eisensubstitution –
im Gegensatz zur oralen Therapie – einen positiven Effekt auf Morbidität, Mortalität, Hospitalisierungsraten und Lebensqualität hat. Zudem
scheint die parenterale Eisengabe auch einen ökonomischen Benefit zu haben. Einige neu aufgelegte Studien werden zusätzliche Erkenntnisse
zutage bringen und die Empfehlungen für eine intravenöse Eisengabe bei diesem speziellen Patientengut untermauern.
Depression und Angststörungen bei Herzinsuffizienz
Authors: Wedegärtner Sonja Maria , Ukena Julia , Kindermann Ingrid
Published: October 2017

In Deutschland ist die chronische Herzinsuffizienz der häufigste krankheitsbedingte Grund für eine stationäre Aufnahme. Depressionen und
Angststörungen sind häufige Begleiterkrankungen und nachteilig für den Verlauf der Herzschwäche. Sie sind mit einer schlechteren
Medikamentenadhärenz, häufigeren Hospitalisierung und erhöhten Sterblichkeit assoziiert. Das Erkennen einer psychischen Komorbidität ist
daher von zentraler Bedeutung in der Behandlung herzinsuffizienter Patienten und sollte in die klinische Praxis integriert werden.
Chirurgische Therapie der Herzinsuffizienz
Authors: Färber Gloria , Sandhaus Tim , Noutsias Michel , Schulze Christian , Doenst Torsten
Published: October 2017

Patienten mit Herzinsuffizienz stellen eine besondere Herausforderung für den Herzchirurgen dar und erfordern u. a. aufgrund der großen
Erfolge der medikamentösen Therapie einen interdisziplinären und individualisierten Therapieansatz. Grundsätzlich ergibt sich die Indikation
für ein operatives Vorgehen aus symptomatischer und/oder prognostischer Sicht. Für die Therapie der Herzinsuffizienz ergeben sich folgende
chirurgische Behandlungsoptionen. Eine Bypassoperation kann das Leben verlängern und die Symptome lindern. Ein Aortenklappenersatz kann bei
hochgradigem Vitium das Leben verlängern und die Symptome lindern. Eine Mitralklappenoperation kann bei funktioneller
Mitralklappeninsuffizienz die Symptome lindern. Eine Herztransplantation oder ventrikuläre Herz­unterstützungssysteme können die Symptome
lindern und das Leben verlängern. Im Folgenden wird in kondensierter Form der aktuellen Stand der chirurgischen Therapiemöglichkeiten
beschrieben.
Standard- oder Therapieverändernde Entwicklungen in der Hämatologie
Authors: Haas Rainer
Published: October 2017

In den letzten beiden Jahrzehnten ist es zu einem regelrechten Paradigmenwechsel in der Behandlung von Patienten mit hämatologischen
Erkrankungen gekommen. Grund dafür ist das immer besser werdende Verständnis der molekularen Pathogenese einzelner Krankheitsentitäten,
welches ein Umdenken und Änderungen in Diagnostik oder Therapie nach sich zieht. Beispielhaft soll dies an einigen malignen und nicht
malignen hämatologischen Erkrankungen gezeigt werden.
Simulative research on reverse current in magnetically insulated coaxial diode
Authors: Zhu Danni , Zhang Jun , Zhong Huihuang , Liu Lie , Ge Xingjun
Published: October 2017

The reverse current tends to occur in the transition region of the guiding magnetic field in a magnetically insulated coaxial diode (MICD). Influence of the guiding magnetic field on characteristics of the MICD especially on the reverse current is studied by the particle-in-cell (PIC) simulation in this paper. The reverse current is confirmed to be irrelevant with the guiding magnetic field strength. However, the reverse current is clarified quantitatively to depend on the electric and magnetic field distribution in the upstream of the cathode tip. As the MICD has been widely employed in microwave tubes, a simple approach to suppress the reverse current on the premise of little change of the original diode is valuable and thus proposed. The optimum matching point between the cathode and the magnetic field is selected in consideration of the entrance depth tolerance, the diode impedance discrepancy and the reverse current coefficient.
Localization of low-abundant cancer cells in a sharply expanded microfluidic step-channel using dielectrophoresis
Authors: Kim Soo Hyeon , Ito Hiroshi , Kozuka Masahiro , Hirai Mitsuharu , Fujii Teruo
Published: October 2017

An efficient method for cell trapping onto a designated location and reduction of the sample volume is required to reduce the risk of sample losses during the discrimination and molecular characterization of low-abundant cells suspended in a large volume of the sample. In this study, we propose a novel microfluidic device that allows for highly efficient trapping of the cancer cells onto a designated location and correction of the trapped cells with a significantly reduced sample volume. The microfluidic device, which utilizes dielectrophoresis cell trapping, consists of an attraction-zone to control the vertical position of the cells and a trap-zone to capture the target cells by drastically decreasing the flow velocity around the cells with a sharply increased channel height. The device showed that 92 ± 9% of the introduced cancer cells were trapped on a designated location (500-μm behind the step) with a high inlet flow rate of 100 μl min−1. The trapped cells were corrected with a one-hundredth volume by introducing reagents for the downstream analysis to the outlet of the device. The feasibility of the system with regard to the localization and recovery of target cells was successfully demonstrated by trapping a mixture of cancer cells and white blood cells and detecting single nucleotide variants from the collected samples. We believe that our system is suitable for the sample preparation of low-abundant cells suspended in a large sample volume, owing to its ability to perform the localization and recovery of trapped cells with minimal target cell loss.
Fabrication of polygonal nanoholes by localized mask-free wet anisotropic etching
Authors: Chen Qi , Wang Yifan , Zhang Hualv , Deng Tao , Liu Zewen
Published: October 2017

Nanoholes integrated into microfluidic systems have been widely researched, due to their practical applications in biosensing fields. This paper is devoted to report a strategy for fabricating polygonal nanoholes by localized mask-free anisotropic etching. Underetching occurs at the pore mouth, causing shape modification of the original square nanohole prepared by wet etching. The influence of the etching under different etching temperatures, KOH concentrations, as well as KOH with isopropanol (IPA) addition, on the shape formation of nanoholes are carefully analyzed and verified by experiments. Under low etching temperature or low KOH concentration, the shape of nanohole turns to be dodecagonal. Under high etching temperature and high KOH concentration, the increase of etching rate of (331) planes promotes transition of the nanohole to an octagonal shaped. By adding IPA into KOH solution, the pore shape is limited to be dodecagonal, and it is irrelative to the etching temperature and KOH concentration.
Development of a Job Exposure Matrix for Noise in the Swedish Soft Tissue Paper Industry
Authors: Neitzel Richard Lee , Andersson Marianne , Eriksson Helena , Torén Kjell , Andersson Eva
Published: October 2017

Objectives

Noise exposure is a common occupational hazard, but has not been sufficiently characterized in paper mills. We developed a job-exposure matrix (JEM) for noise exposure for use in estimating exposures among Swedish soft tissue paper mill workers.

Methods

We used a combination of area and personal dosimetry noise exposure measurements made at four soft tissue paper mills by industry and research staff between 1977 and 2013 to estimate noise exposures by department, location, and job title. We then utilized these estimates, in conjunction with information on process and facility changes and use of hearing protection collected via focus groups, to create a seven-category, semi-quantitative JEM for all departments, locations, and job titles spanning the years 1940–2010.

Results

The results of the 1157 area and personal dosimetry noise measurements indicated that noise levels have generally declined in Swedish paper mills over time, though these changes have been neither uniform nor monotonic within or across the four mills. Focus group results indicated that use of hearing protection has generally increased over time. The noise JEM totals 1917 cells, with each cell representing a unique combination of operation, job title, and single year. We estimated that ~50% of workers at the four mills assessed were exposed at or above the Swedish 8-h average noise exposure limit of an 85 dBA at the conclusion of the study period in 2010.

Conclusions

Our results highlight the continuing need for hearing loss prevention and noise control efforts at these and similar mills, and the completed JEM now represents a tool for use in epidemiological studies of noise-related health outcomes.
Drug–drug interaction extraction via hierarchical RNNs on sequence and shortest dependency paths
Authors: Zhang Yijia , Zheng Wei , Lin Hongfei , Wang Jian , Yang Zhihao , Dumontier Michel
Published: October 2017

Motivation

Adverse events resulting from drug-drug interactions (DDI) pose a serious health issue. The ability to automatically extract DDIs described in the biomedical literature could further efforts for ongoing pharmacovigilance. Most of neural networks-based methods typically focus on sentence sequence to identify these DDIs, however the shortest dependency path (SDP) between the two entities contains valuable syntactic and semantic information. Effectively exploiting such information may improve DDI extraction.

Results

In this article, we present a hierarchical recurrent neural networks (RNNs)-based method to integrate the SDP and sentence sequence for DDI extraction task. Firstly, the sentence sequence is divided into three subsequences. Then, the bottom RNNs model is employed to learn the feature representation of the subsequences and SDP, and the top RNNs model is employed to learn the feature representation of both sentence sequence and SDP. Furthermore, we introduce the embedding attention mechanism to identify and enhance keywords for the DDI extraction task. We evaluate our approach using the DDI extraction 2013 corpus. Our method is competitive or superior in performance as compared with other state-of-the-art methods. Experimental results show that the sentence sequence and SDP are complementary to each other. Integrating the sentence sequence with SDP can effectively improve the DDI extraction performance.

Availability and implementation

The experimental data is available at https://github.com/zhangyijia1979/hierarchical-RNNs-model-for-DDI-extraction.

Supplementary information

Supplementary data are available at Bioinformatics online.
Clinical Predictors of Early Mortality in Colorectal Cancer Patients Undergoing Chemotherapy: Results From a Global Prospective Cohort Study
Authors: Sohal Davendra P S , Kuderer Nicole M , Shepherd Frances A , Pabinger Ingrid , Agnelli Giancarlo , Liebman Howard A , Meyer Guy , Kalady Matthew F , McCrae Keith , Lyman Gary H , Khorana Alok A
Published: October 2017

Background

Early mortality is a major problem in colorectal cancer (CRC). We have shown that Khorana Score is predictive of early mortality in other cancers. Here, we evaluated the value of this score and other prognostic variables in predicting early mortality in CRC.

Methods

CANTARISK was a prospective, noninterventional, global cohort study in patients with CRC initiating a new chemotherapy regimen. Data were collected at zero, two, four, and six months. Early mortality was defined as death within six months of enrollment. All data were compiled centrally and analyzed after the study closed. Statistically significant univariate associations were tested in multivariable models; adjusted odds ratios (ORs) are presented. Statistical tests were two-sided.

Results

From 2011 to 2012, 1789 CRC patients were enrolled. The median age was 62 years; 71% were Caucasian. One-third (35%) had a rectal primary, and 65% had metastatic disease. There were 184 (10.3%) patients who died during their first six months in the study. For low, intermediate, and high Khorana Score, there were 8.1%, 11.2% and 32.5% deaths, respectively. In multivariable analyses, Khorana Score was an independent predictor of early death (OR for high/intermediate vs low score = 1.70, P = .0027), in addition to age (OR for each incremental year = 1.03, P = .0014), presence of metastatic disease (OR = 3.28, P < .0001), and Easter Cooperative Oncology Group Performance Status Score of 2 or higher (OR = 3.85, P < .0001).

Conclusions

This study demonstrates that Khorana Score is predictive of early mortality in CRC patients. Intermediate- or high-risk patients, as defined by this score, may benefit from additional interventions aimed at reducing early mortality.
Efficacy and dissemination of psychological treatments
Authors: Barlow David H. , Hofmann Stefan G.
Published: October 2017

Chapter 5 discusses efficacy and dissemination of psychological treatments, including the comparative effectiveness of psychological, pharmacological, and combined treatments, the problems of accessibility and dissemination of effective psychosocial treatments, and the emerging role of clinical practice guidelines.
Sexual problems
Authors: Bancroft John
Published: October 2017

Chapter 10 discusses sexual problems, the sex therapy approach (including topics such as improving communication and understanding, conflict resolution, cognitive restructuring of sexual meanings, and direct modification of sexual responses), experimental evidence in the male, the role of central inhibition, and experimental evidence in women.
Cardiovascular disease
Authors: Johnston Derek W.
Published: October 2017

Chapter 14 explores the role of behavioural medicine in the treatment of cardiovascular disease. It discusses stress management in the treatment of primary hypertension, coronary heart disease, and angina pectoris, along with rehabilitation, and future developments for research and treatment.
Problem-solving treatment in primary care
Authors: Gath Dennis , Mynors-Wallis Laurence
Published: October 2017

Chapter 17 discusses problem-solving treatment in primary care and outlines a series of studies into the treatment of emotional disorders in primary care, including the effects of not prescribing anxiolytic medication for emotional disorders, the feasibility and efficacy of problem-solving for emotional disorders and poor prognosis treatment, problem-solving treatment for major depression in general practice, further evaluation of problem-solving treatment for major depression in primary care.
Evolutionary Concepts Important to Psychiatry
Authors: McGuire Michael , Troisi Alfonso
Published: October 2017

This chapter explores evolutionary concepts important to psychiatry. It discusses concepts including natural selection, adaptation, function, ultimate causation, individual fitness, self-interest, kin selection, reciprocal altruism, and traits and trait variation.
Phobias
Authors: McGuire Michael , Troisi Alfonso
Published: October 2017

This chapter outlines phobias from an evolutionary perspective. It reviews some of the ways in which the interpretation of phobias in an evolutionary context differs from the interpretations developed by prevailing models (e.g., an overlearned response, dysfunctionality of CNS receptors).
Other Conditions
Authors: McGuire Michael , Troisi Alfonso
Published: October 2017

Conditions other than those already discussed can also be illuminated by an evolutionary perspective. In this chapter, the perspective serves as the basis for assessing dissociative amnesia, adjustment disorder, two somatoform disorders (somatization disorder and conversion disorder), alcohol dependence, suicide, spousal abuse, and child abuse.
Intervention Strategies
Authors: McGuire Michael , Troisi Alfonso
Published: October 2017

This chapter explores intervention strategies and reviews their efficacy. It discusses prevailing-model interventions (psychoanalytic, psychotherapeutic, behavioral, and sociocultural), biomedical interventions, and uses an evolutionary context to present intervention principles, and case histories.
Coping
Authors: Snyder C. R. , Dinoff Beth L.
Published: October 2017

This chapter traces the history of the coping process and will arrive at a definition that encompasses modern thinking and research, considering psychodynamic roots and defense mechanisms, appraisal/transactional processes, Type A behavior patterns, and the emergence of the individual differences view.
Coping and Ego Depletion
Authors: Baumeister Roy F. , Faber Jon E. , Wallace Harry M.
Published: October 2017

This chapter discusses coping and ego depletion, and combines a new approach to the self with a traditional, standard idea about coping in order to understand the coping process. The central idea is that many operations of the self involve the consumption of a limited resource. This resource is used in volition (e.g., choice, responsible decision-making, and active responses) and self-control. Stress makes severe demands on this resource, because people must engage in active responding and must regulate themselves so as to adapt to difficult circumstances.
Focusing on Emotion
Authors: Stanton Annette L. , Franz Robert
Published: October 2017

The focus of this chapter is the adaptive roles of emotion in coping processes. It presents a review of literature that point to the potential utility of processing and expressing emotions, and theories that bear on potentially adaptive functions of coping through emotional approach (such as active processing and expression of emotion). It also addresses theoretical, empirical, and applied directions for work on this construct.
Learned Optimism in Children
Authors: Shatté Andrew J. , Reivich Karen , Gillham Jane E. , Seligman Martin E. P.
Published: October 2017

In this chapter examines learned optimism in children and examines a depression prevention program for children. It focuses on two related cognitive-behavioral risk factors for depression in children; learned helplessness and pessimistic explanatory style. It briefly profiles childhood depression and outlines the nature of learned helplessness and pessimism in children, before offering two conceptualizations of learned optimism.
Hoping
Authors: Snyder C. R. , Cheavens Jen , Michael Scott T.
Published: October 2017

Chapter 10 explores hope and hoping. It discusses the definition of a new model of hope, along with instruments to measure it in adults and children, describes the adaptive sequelae of elevated levels of hope for a variety of coping arenas, along with the literature on increasing hope. It also explores how hope can be applied to special populations.