bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Gpr1-regulated Sur7 family protein Sfp2 is required for hyphal growth and cell wall stability in the mycoparasite Trichoderma atroviride
Authors: Atanasova Lea , Gruber Sabine , Lichius Alexander , Radebner Theresa , Abendstein Leoni , Münsterkötter Martin , Stralis-Pavese Nancy , Łabaj Paweł P. , Kreil David P. , Zeilinger Susanne 
Published: August 2018

AbstractMycoparasites, e.g. fungi feeding on other fungi, are prominent within the genus Trichoderma and represent a promising alternative to chemical fungicides for plant disease control. We previously showed that the seven-transmembrane receptor Gpr1 regulates mycelial growth and asexual development and governs mycoparasitism-related processes in Trichoderma atroviride. We now describe the identification of genes being targeted by Gpr1 under mycoparasitic conditions. The identified gene set includes a candidate, sfp2, encoding a protein of the fungal-specific Sur7 superfamily, whose upregulation in T. atroviride upon interaction with a fungal prey is dependent on Gpr1. Sur7 family proteins are typical residents of membrane microdomains such as the membrane compartment of Can1 (MCC)/eisosome in yeast. We found that GFP-labeled Gpr1 and Sfp2 proteins show partly overlapping localization patterns in T. atroviride hyphae, which may point to shared functions and potential interaction during signal perception and endocytosis. Deletion of sfp2 caused heavily altered colony morphology, defects in polarized growth, cell wall integrity and endocytosis, and significantly reduced mycoparasitic activity, whereas sfp2 overexpression enhanced full overgrowth and killing of the prey. Transcriptional activation of a chitinase specific for hyphal growth and network formation and strong downregulation of chitin synthase-encoding genes were observed in Δsfp2. Taken together, these findings imply crucial functions of Sfp2 in hyphal morphogenesis of T. atroviride and its interaction with prey fungi.
Drug-based perturbation screen uncovers synergistic drug combinations in Burkitt lymphoma
Authors: Tomska K. , Kurilov R. , Lee K. S. , Hüllein J. , Lukas M. , Sellner L. , Walther T. , Wagner L. , Oleś M. , Brors B. , Huber W. , Zenz T. 
Published: August 2018

AbstractBurkitt lymphoma (BL) is a highly aggressive B-cell lymphoma associated with MYC translocation. Here, we describe drug response profiling of 42 blood cancer cell lines including 17 BL to 32 drugs targeting key cancer pathways and provide a systematic study of drug combinations in BL cell lines. Based on drug response, we identified cell line specific sensitivities, i.e. to venetoclax driven by BCL2 overexpression and partitioned subsets of BL driven by response to kinase inhibitors. In the combination screen, including BET, BTK and PI3K inhibitors, we identified synergistic combinations of PI3K and BTK inhibition with drugs targeting Akt, mTOR, BET and doxorubicin. A detailed comparison of PI3K and BTKi combinations identified subtle differences, in line with convergent pathway activity. Most synergistic combinations were identified for the BET inhibitor OTX015, which showed synergistic effects for 41% of combinations including inhibitors of PI3K/AKT/mTOR signalling. The strongest synergy was observed for the combination of the CDK 2/7/9 inhibitor SNS032 and OTX015. Our data provide a landscape of drug combination effects in BL and suggest that targeting CDK and BET could provide a novel vulnerability of BL.
Analysis of sequencing strategies and tools for taxonomic annotation: Defining standards for progressive metagenomics
Authors: Escobar-Zepeda Alejandra , Godoy-Lozano Elizabeth Ernestina , Raggi Luciana , Segovia Lorenzo , Merino Enrique , Gutiérrez-Rios Rosa María , Juarez Katy , Licea-Navarro Alexei F. , Pardo-Lopez Liliana , Sanchez-Flores Alejandro 
Published: August 2018

AbstractMetagenomics research has recently thrived due to DNA sequencing technologies improvement, driving the emergence of new analysis tools and the growth of taxonomic databases. However, there is no all-purpose strategy that can guarantee the best result for a given project and there are several combinations of software, parameters and databases that can be tested. Therefore, we performed an impartial comparison, using statistical measures of classification for eight bioinformatic tools and four taxonomic databases, defining a benchmark framework to evaluate each tool in a standardized context. Using in silico simulated data for 16S rRNA amplicons and whole metagenome shotgun data, we compared the results from different software and database combinations to detect biases related to algorithms or database annotation. Using our benchmark framework, researchers can define cut-off values to evaluate the expected error rate and coverage for their results, regardless the score used by each software. A quick guide to select the best tool, all datasets and scripts to reproduce our results and benchmark any new method are available at https://github.com/Ales-ibt/Metagenomic-benchmark. Finally, we stress out the importance of gold standards, database curation and manual inspection of taxonomic profiling results, for a better and more accurate microbial diversity description.
A factor VII-based method for the prediction of anticoagulant response to warfarin
Authors: Ooi Qing-Xi , Wright Daniel F. B. , Isbister Geoffrey K. , Duffull Stephen B. 
Published: August 2018

AbstractWarfarin dosing methods based on existing models for warfarin and the international normalised ratio (INR) give biased maintenance dose predictions at the upper and lower quantiles of dose requirements. The aim of this work is to propose a conceptually different approach to predict INR after warfarin dosing. Factor VII concentration was proposed as the principal driving force for the INR. The time to steady-state INR (tSS,INR) was determined based on the INR response to changes in factor VII concentrations following warfarin initiation, and from this the steady-state INR (INRSS) was derived. The proposed method requires timed, paired blood samples of INR and factor VII. At different simulated warfarin dose rates, the prediction error associated with the proposed method was shown to be within clinically acceptable limits for both the tSS,INR (±2 days) and INRSS (±0.2). The use of the method was demonstrated in two patients who were initiated with 5 mg of warfarin daily. The difference in predicted versus actual steady-state INR were 0.0 and −0.4. The proposed method represents a unique approach to predict the INR. It considers factor VII as the main driver for INR and provides valuable information about the time to steady state INR.
Turn-off colorimetric sensor for sequence-specific recognition of single-stranded DNA based upon Y-shaped DNA structure
Authors: Zhang Hong , Li Xintong , He Fan , Zhao Mingqin , Ling Liansheng 
Published: August 2018

AbstractA novel turn-off colorimetric sensor for sequence-specific recognition of single-stranded DNA (ssDNA) was established by combining Y-shaped DNA duplex and G-quadruplex-hemin DNAzyme. A G-rich single-stranded DNA (Oligo-1) displays peroxidase mimicking catalytic activity due to the specific binding with hemin in the presence of K+, which was able to catalyze the oxidation of colorless 2,2′-azinobis(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS2−) by H2O2 to generate green ABTS•− radical for colorimetric assay. Oligonucleotide 2 (Oligo-2) was partly complementary with Oligo-1 and the target DNA. Upon addition of target DNA, Oligo-1, Oligo-2 and target DNA can hybridize with each other to form Y-shaped DNA duplex. The DNAzyme sequence of Oligo-1 was partly caged into Y-shaped DNA duplex, resulting in the inactivation of the DNAzyme and a sharp decrease of the absorbance of the oxidation product of ABTS2−. Under the optimum condition, the absorbance decreased linearly with the concentration of target DNA over the range of 1.0–250 nM and the detection limit was 0.95 nM (3σ/slope) Moreover, satisfied result was obtained for the discrimination of single-base or two-base mismatched DNA.
Comparative toxicity of synchrotron and conventional radiation therapy based on total and partial body irradiation in a murine model
Authors: Smyth Lloyd M. L. , Donoghue Jacqueline F. , Ventura Jessica A. , Livingstone Jayde , Bailey Tracy , Day Liam R. J. , Crosbie Jeffrey C. , Rogers Peter A. W. 
Published: August 2018

AbstractSynchrotron radiation can facilitate novel radiation therapy modalities such as microbeam radiation therapy (MRT) and high dose-rate synchrotron broad-beam radiation therapy (SBBR). Both of these modalities have unique physical properties that could be exploited for an improved therapeutic effect. While pre-clinical studies report promising normal tissue sparing phenomena, systematic toxicity data are still required. Our objective was to characterise the toxicity of SBBR and MRT and to calculate equivalent doses of conventional radiation therapy (CRT). A dose-escalation study was performed on C57BLJ/6 mice using total body and partial body irradiations. Dose-response curves and TD50 values were subsequently calculated using PROBIT analysis. For SBBR at dose-rates of 37 to 41 Gy/s, we found no evidence of a normal tissue sparing effect relative to CRT. Our findings also show that the MRT valley dose, rather than the peak dose, best correlates with CRT doses for acute toxicity. Importantly, longer-term weight tracking of irradiated animals revealed more pronounced growth impairment following MRT compared to both SBBR and CRT. Overall, this study provides the first in vivo dose-equivalence data between MRT, SBBR and CRT and presents systematic toxicity data for a range of organs that can be used as a reference point for future pre-clinical work.
Determining Relative Dynamic Stability of Cell States Using Boolean Network Model
Authors: Joo Jae Il , Zhou Joseph X. , Huang Sui , Cho Kwang-Hyun 
Published: August 2018

AbstractCell state transition is at the core of biological processes in metazoan, which includes cell differentiation, epithelial-to-mesenchymal transition (EMT) and cell reprogramming. In these cases, it is important to understand the molecular mechanism of cellular stability and how the transitions happen between different cell states, which is controlled by a gene regulatory network (GRN) hard-wired in the genome. Here we use Boolean modeling of GRN to study the cell state transition of EMT and systematically compare four available methods to calculate the cellular stability of three cell states in EMT in both normal and genetically mutated cases. The results produced from four methods generally agree but do not totally agree with each other. We show that distribution of one-degree neighborhood of cell states, which are the nearest states by Hamming distance, causes the difference among the methods. From that, we propose a new method based on one-degree neighborhood, which is the simplest one and agrees with other methods to estimate the cellular stability in all scenarios of our EMT model. This new method will help the researchers in the field of cell differentiation and cell reprogramming to calculate cellular stability using Boolean model, and then rationally design their experimental protocols to manipulate the cell state transition.
Dislocation driven nanosample plasticity: new insights from quantitative in-situ TEM tensile testing
Authors: Samaee Vahid , Gatti Riccardo , Devincre Benoit , Pardoen Thomas , Schryvers Dominique , Idrissi Hosni 
Published: August 2018

AbstractIntrinsic dislocation mechanisms in the vicinity of free surfaces of an almost FIB damage-free single crystal Ni sample have been quantitatively investigated owing to a novel sample preparation method combining twin-jet electro-polishing, in-situ TEM heating and FIB. The results reveal that the small-scale plasticity is mainly controlled by the conversion of few tangled dislocations, still present after heating, into stable single arm sources (SASs) as well as by the successive operation of these sources. Strain hardening resulting from the operation of an individual SAS is reported and attributed to the decrease of the length of the source. Moreover, the impact of the shortening of the dislocation source on the intermittent plastic flow, characteristic of SASs, is discussed. These findings provide essential information for the understanding of the regime of ‘dislocation source’ controlled plasticity and the related mechanical size effect.
Novel clinical device tracking and tissue event characterization using proximally placed audio signal acquisition and processing
Authors: Illanes Alfredo , Boese Axel , Maldonado Iván , Pashazadeh Ali , Schaufler Anna , Navab Nassir , Friebe Michael 
Published: August 2018

AbstractWe propose a new and complementary approach to image guidance for monitoring medical interventional devices (MID) with human tissue interaction and surgery augmentation by acquiring acoustic emission data from the proximal end of the MID outside the patient to extract dynamical characteristics of the interaction between the distal tip and the tissue touched or penetrated by the MID. We conducted phantom based experiments (n = 955) to show dynamic tool/tissue interaction during tissue needle passage (a) and vessel perforation caused by guide wire artery perforation (b). We use time-varying auto-regressive (TV-AR) modelling to characterize the dynamic changes and time-varying maximal energy pole (TV-MEP) to compute subsequent analysis of MID/tissue interaction characterization patterns. Qualitative and quantitative analysis showed that the TV-AR spectrum and the TV-MEP indicated the time instants of the needle path through different phantom objects (a) and clearly showed a perforation versus other generated artefacts (b). We demonstrated that audio signals acquired from the proximal part of an MID could provide valuable additional information to surgeons during minimally invasive procedures.
A database of metazoan cytochrome c oxidase subunit I gene sequences derived from GenBank with CO-ARBitrator
Authors: Heller Philip , Casaletto James , Ruiz Gregory , Geller Jonathan 
Published: August 2018

AbstractThe Cytochrome C Oxidase subunit I gene (“COI”) is the de facto standard for animal DNA barcoding. Organism identification based on COI requires an accurate and extensive annotated database of COI sequences. Such a database can also be of value in reconstructing evolutionary history and in diversity studies. Two COI databases are currently available: BOLD and Midori. BOLD’s submissions conform to stringent sequence and metadata requirements; BOLD is specific to COI but makes no attempt to be comprehensive. Midori, derived from GenBank, has more sequences but less stringent standards than BOLD, resulting in higher error rates. To address the need for a comprehensive and accurate COI database, we adapted the ARBitrator algorithm, which classifies based only on sequence properties and has successfully auto-curated bacterial genes mined from GenBank. The adapted algorithm, which we call CO-ARBitrator, built a database of over a million metazoan COI sequences. Sensitivity and specificity are significantly higher than Midori. Specificity is comparable to what BOLD achieves with data quality prerequisites. Results and software are publicly available.
Bulk linearisation of the MOS resistor
Authors: Arnaud A. , Miguez M. 
Published: August 2018

A bulk‐linearised composite MOSFET is presented, with an extended linear range and an equivalent saturation voltage of up to several hundred mV even in weak inversion. Some preliminary measurements are presented as well as a 300 MΩ equivalent resistor, with almost a 1 V quasi‐linear range. A low frequency, 28 dB gain, biomedical bandpass filter/amplifier is also shown, taking advantage of the linearised MOSFETs to consume only 16 nA of supply current.
Two-dimensional simulations of mixing in classical novae: The effect of white dwarf composition and mass
Authors: Casanova Jordi , José Jordi , Shore Steven N. 
Published: August 2018

Context. Classical novae are explosive phenomena that take place in stellar binary systems. They are powered by mass transfer from a low-mass main sequence star onto either a CO or ONe white dwarf. The material accumulates for 104–105yr until ignition under degenerate conditions, resulting in a thermonuclear runaway. The nuclear energy released produces peak temperatures of ∼0.1–0.4 GK. During these events, 10−7−10−3M⊙enriched in intermediate-mass elements, with respect to solar abundances, are ejected into the interstellar medium. However, the origin of the large metallicity enhancements and the inhomogeneous distribution of chemical species observed in high-resolution spectra of ejected nova shells is not fully understood.Aims. Recent multidimensional simulations have demonstrated that Kelvin-Helmholtz instabilities that operate at the core-envelope interface can naturally produce self-enrichment of the accreted envelope with material from the underlying white dwarf at levels that agree with observations. However, such multidimensional simulations have been performed for a small number of cases and much of the parameter space remains unexplored.Methods. We investigated the dredge-up, driven by Kelvin-Helmholtz instabilities, for white dwarf masses in the range 0.8–1.25M⊙and different core compositions, that is, CO-rich and ONe-rich substrates. We present a set of five numerical simulations performed in two dimensions aimed at analyzing the possible impact of the white dwarf mass, and composition, on the metallicity enhancement and explosion characteristics.Results. At the time we stop the simulations, we observe greater mixing (∼30% higher when measured in the same conditions) and more energetic outbursts for ONe-rich substrates than for CO-rich substrates and more massive white dwarfs.
Befragung von Ärzten zum Umgang mit dem Thema „Tabakkonsum bei Patienten mit Lungenkrebs“
Authors: Bleckwenn Markus , Kaluç Asya , Zipfel Mathias , Schnakenberg Rieke , Brossart Peter , Weckbecker Klaus 
Published: August 2018

Zusammenfassung
Einleitung Etwa 40 % der Patienten sind bei der Diagnosestellung Lungenkrebs aktive Raucher. Die Hälfte dieser Patienten setzt den Nikotinkonsum trotz bestehender Krebserkrankung fort. Die Gesamtsterblichkeit liegt bei diesen Patienten um den Faktor 3 höher. Zudem steigt die Lebensqualität und Symptome wie Husten und Luftnot werden reduziert.
Fragestellung Wie gehen die behandelnden Ärzte mit dem Tabakkonsum ihrer Patienten mit Lungenkrebs um?
Methoden Es wurden insgesamt 14 Ärzte des Universitätsklinikums Bonn aus den Abteilungen Pneumologie, Onkologie und Thoraxchirurgie befragt, die in die Behandlung des Lungenkrebses eingebunden sind. Die Interviews wurden transkribiert und nach der qualitativen Inhaltsanalyse nach Mayring mit MAXQDA®12 ausgewertet.
Ergebnisse Die Ärzte gingen sehr individuell mit dem Nikotinkonsum ihrer Patienten um. Dabei orientierten sich die Ärzte vorwiegend an der möglichen Lebenserwartung der Patienten. Bei einem kurativen Behandlungsansatz setzten die Ärzte einen Rauchstopp bei ihren Patienten für eine erfolgreiche Behandlung voraus. Im Rahmen einer palliativen Behandlung wollten viele Ärzte ihren Patienten die Belastung einer Raucherentwöhnung nicht mehr zumuten. Kam der Wunsch nach einer Entwöhnungstherapie beim Patienten auf, wurde in der Regel auf Kollegen verwiesen, die in Raucherentwöhnung geschult waren. Hindernisse für die selbstständige Durchführung einer Raucherentwöhnung waren insbesondere fehlende Kenntnisse und kurze Behandlungszeiten bzw. eine hohe Anzahl an Patienten, vor allem während der Sprechstunde.
Diskussion Die Ärzte waren durchaus vom Nutzen eines Rauchstopps bei der Behandlung des Lungenkarzinoms überzeugt. Patienten mit Lungenkrebs würden davon profitieren, wenn die Raucherentwöhnung noch mehr in die Gesamttherapie integriert wäre. Dazu könnte man auf bereits etablierte Entwöhnungsprogramme und Konzepte für Kliniken zurückgreifen.
Systemische Chemotherapie beim Urothelkarzinom in Deutschland – Eine Umfrage der Arbeitsgemeinschaften Urologische Onkologie und Internistische Onkologie der Deutschen Krebsgesellschaft e.V.
Authors: Hupe Marie , Merseburger Axel , de Wit Maike , Rexer Heidrun , Gschwend Jürgen , Krege Susanne 
Published: August 2018

Zusammenfassung
Hintergrund Im Jahr 2016 wurde die erste deutsche S3-Leitlinie zum Harnblasenkarzinom veröffentlicht. Im Rahmen dieser Studie soll die nationale Versorgungssituation des Urothelkarzinoms in Deutschland mit Fokus auf die medikamentöse Therapie aufgearbeitet, anhand aktueller Leitlinienempfehlungen bewertet sowie mit internationaler Literatur zu ähnlicher Fragestellung verglichen werden.
Material und Methoden Es wurde ein Fragebogen entwickelt und an über 4000 Urologen und Onkologen in Deutschland versandt. Der Fragebogen beinhaltete Fragen zum jährlichen Patientenaufkommen sowie zur Anwendung der operativen und hauptsächlich medikamentösen Therapieoptionen in den verschiedenen Stadien des Urothelkarzinoms. Es konnten 278 Fragebögen ausgewertet werden.
Ergebnisse Dieses ist die größte deutschlandweite Querschnittsstudie zur systemischen Therapie des Urothelkarzinoms. Im Bereich der palliativen Systemtherapie werden die Leitlinienempfehlungen ausgeschöpft. Bei den Indikationen für eine intravesikale Instillationstherapie sowie (neo)adjuvante Chemotherapie besteht Optimierungspotenzial hinsichtlich der Leitlinienadhärenz, v. a. im Hinblick auf die Anzahl verabreichter Chemotherapiezyklen.
Schlussfolgerung Insgesamt sollte die Leitlinienadhärenz verbessert werden. Neben neuen Diagnose- oder Therapieoptionen könnte auch eine striktere Leitlinienadhärenz die krebsspezifische Mortalität perspektivisch verringern.
Implementation of a Quality Control System for Laparoscopic Pyloromyotomy in Hypertrophic Pyloric Stenosis: Hurdles and Pitfalls
Authors: Ploeg Mirjam , Keyzer-Dekker Claudia M. G. , Sloots Cornelius E. J. , van de Ven Cornelis P. , Meeussen Conny , Wijnen Rene M. H. , Vlot John 
Published: August 2018

Background In 2011, we implemented a new video-based system for quality control of laparoscopic pyloromyotomy. More than 3 years later, we evaluated how the implementation had gone and assessed its usability in predicting postoperative outcomes.
Materials and Methods Four key point images or short video-segments were to be recorded perioperatively: prepyloromyotomy, parallel-mobility testing, perforation testing, and postpyloromyotomy. Data of all 134 patients undergoing laparoscopic pyloromyotomy from September 2011 to December 2014 were analyzed retrospectively. Five pediatric surgeons independently assessed the anonymized operative images for predicting reoperation and time to full-enteral feeding.
Results The percentage of operations during which images were recorded increased from 45% in 2012 to 75% in 2014. Over the study period, one or more images were recorded in 89 of the 134 (66%) patients. In only 17 of 89 patients (19%), all four images were documented. The key point images or videos were made for prepyloromyotomy in 49%, parallel-mobility testing in 85%, perforation testing in 42%, and postpyloromyotomy in 94% of 89 patients. Five patients (3.7%) were reoperated for incomplete pyloromyotomy (N = 4) or mucosal perforation (N = 1). Images were recorded during the first operation in four of the five reoperated patients. The need of reoperation was correctly predicted for two of the four patients. Full-enteral feeding within 24 hours was correctly predicted for 67% of the patients (range: 47–88%).
Conclusion The increase in recorded images over the years is promising. The implementation of the quality control system did not contribute to a significant decrease in the complication rate, which was already very low. Still, reoperation or a protracted postoperative course could only be predicted with moderate accuracy from the operative images, therefore, for now the use of perioperative images in a medicolegal setting should be advised against. Improved compliance with image recording and better instructions for evaluating the images might improve the usefulness of perioperative images in, e.g., telementoring, education, and medicolegal practice.