bluuebunny/crossref_metadata_2025 huggingface dataset:
Langzeitüberleben von Patienten mit Kolon- und Rektumkarzinomen: Ein Vergleich von Darmkrebszentren und nicht zertifizierten Krankenhäusern
Authors: Völkel Vinzenz , Draeger Teresa , Gerken Michael , Fürst Alois , Klinkhammer-Schalke Monika
Published: April 2018

Ziel der Studie Kliniken, die auf die Behandlung von Kolon- und Rektumkarzinomen spezialisiert sind und hohen Ansprüchen an die Struktur-, Prozess- und Ergebnisqualität genügen, können sich als Darmkrebszentren zertifizieren lassen. Es soll untersucht werden, ob eine Behandlung an Darmkrebszentren verglichen mit einer Therapie an nicht zertifizierten Krankenhäusern mit einem messbaren Überlebensvorteil einhergeht.

Methoden Grundlage dieser retrospektiven Kohortenstudie sind die bevölkerungsbezogenen Daten des klinischen Krebsregisters am Tumorzentrum Regensburg, das die süddeutsche Region Oberpfalz mit ca. 1,1 Mio. Einwohnern vollständig abdeckt. 4302 Patienten, bei denen man zwischen 2004 und 2013 ein Karzinom des Dick- oder Enddarms in radikaler Intention entfernte, wurden in 4 Vergleichsgruppen eingeteilt, um Zentren mit Nicht-Zentren zu vergleichen und die Versorgungssituation vor und nach Einführung der Zertifizierung abzubilden. Zur Untersuchung des 3-Jahres-Gesamtüberlebens kommen neben dem üblichen Kaplan-Meier-Verfahren auch multivariable Cox-Regression und Modelle zur Berechnung des relativen Überlebens zum Einsatz. Eine Sensitivitätsanalyse für fehlende Daten wird ebenfalls durchgeführt.

Ergebnisse Die geschätzte 3-Jahres-Überlebensrate von Zentrumspatienten und -patientinnen beträgt 71,6% verglichen mit 63,6% an nicht zertifizierten Krankenhäusern. Auch nach Adjustierung für wichtige Einflussvariablen ist die Behandlung an zertifizierten Darmkrebszentren mit einem signifikanten Überlebensvorteil verbunden (HR=0,808, KI: 0,665–0,982). Vergleicht man im zeitlichen Längsschnitt die Fälle heutiger Darmkrebszentren vor und nach Zertifizierung ergeben sich fast identische 3-Jahres Überlebensraten und auch in der Cox-Regression sind keine signifikanten Unterschiede festzustellen (HR=0,964, KI: 0,848–1,096).

Schlussfolgerung Die Behandlung an zertifizierten Darmkrebszentren ist im Vergleich zur Therapie an anderen Krankenhäusern mit besseren Überlebensraten assoziiert. Dass es im Längsschnitt betrachtet keinen messbaren Überlebens-Unterschied zwischen Fällen einer Klinik vor und nach ihrer Zertifizierung gibt, könnte auf eine frühzeitige und erfolgreiche Implementierung der geforderten Qualitätsstandards hinweisen.
Iodine-Mediated Intramolecular C–H Amination of Benzimidazoles: A Metal-Free Route to Dihydroimidazobenzimidazoles
Authors: Punniyamurthy Tharmalingam , De Pinaki , Pradhan Sourav , Shah Tariq
Published: April 2018

Iodine-mediated cyclization of benzimidazolylethylamines in the presence of base to give dihydroimidazobenzimidazoles via a de­hydrogenative cross-coupling of C(sp2)–H and N–H bonds is reported. Metal-free conditions, preservation of the optical purity, and substrate scope are the important practical features.
Imaging to Differentiate the Various Forms of Seronegative Arthritis
Authors: Hermann Kay-Geert , Zejden Anna , Sudoł-Szopińska Iwona , Eshed Iris
Published: April 2018

Spondyloarthritis (SpA) is a group of diseases characterized by back pain, spinal inflammation, human leukocyte antigen-B27 positivity, and peripheral findings such as dactylitis, enthesitis, and uveitis. It includes ankylosing spondylitis, psoriatic arthritis, reactive arthritis, arthritis associated with inflammatory bowel disease, and undifferentiated SpA. The role of imaging in the diagnosis, management, and follow-up of patients with SpA has become dramatically more important with the introduction of new therapies such as tumor necrosis factor-α inhibitors. Although in many instances differentiating between the SpA entities is straightforward based on the clinical presentation, often such differentiation remains challenging, and categorization of an individual patient into a subset of SpA can be difficult. Imaging, mainly radiography and magnetic resonance imaging, serves as an important diagnostic tool. Diseases in the spondyloarthritis complex share common presentation but at the same time may have distinct radiographic phenotypes. We present these common and distinct imaging manifestations that may potentially help distinguish between the entities in the diagnostic work-up.
Metatarsale Exostose bei Charcot-Marie-Tooth Syndrom Typ I
Authors: Wissing Fabian R. , Ryu Seung-Min , Menke Henrik
Published: April 2018

Erstmals von Charcot und Marie 1886 in Paris beschrieben und später von Tooth in London, ist das Charcot-Marie-Tooth Syndrom (CMT) die häufigste vererbte Erkrankung
des peripheren Nervensystems und tritt mit einer Prävalenz von 1 : 2500 auf. Die klinisch und genetisch heterogene Erkrankung ist u. a. gekennzeichnet durch
Auftreten in der 1.–2. Lebensdekade, familiäre Häufung, gering bis mäßig ausgeprägte Sensibilitätsstörung und eine langsam progrediente Muskelschwäche, welche meist
in den Beinen beginnt und dann in die obere Extremität fortschreitet 1, 2, 3.
Assessing the relative contribution of economic, political and environmental factors on past conflict and the displacement of people in East Africa
Authors: Owain Erin Llwyd , Maslin Mark Andrew
Published: April 2018

According to the UN Refugee Agency in 2016 there were over 20 million displaced people in Africa. There is considerable debate whether climate change will exacerbate this situation in the future by increasing conflict and thus displacement of people. To explore this climate-conflict-refugee nexus this study analyses whether climatic changes between 1963 and 2014 impacted the risk of conflict and displacement of people in East Africa. A new composite conflict database recording major episodes of political violence (MEPV) was compared with climatic, economic and political indicators using optimisation regression modelling. This study found that climate variations as recorded by the Palmer Drought Severity Index (PDSI) and the global temperature record did not significantly impact the level of regional conflict or the number of total displaced people (TDP). The major driving forces on the level of conflict were population growth, economic growth and the relative stability of the political regimes. Numbers of TDP seemed to be linked to population and economic growth. Within TDP, ‘refugees’ were recorded as people that were forced to cross borders between countries. In contrast to TDP and conflict, variations in refugee numbers were found to be significantly related to climatic variations as well as political stability, population and economic growth. This study suggests that climate variations played little or no part in the causation of conflict and displacement of people in East Africa over the last 50 years. Instead, we suggest rapid population growth, low or falling economic growth and political instability during the post-colonial transition were the more important controls. Nonetheless, during this period this study does shows that severe droughts were a contributing driver of refugees crossing international borders. This study demonstrates that within socially and geo-politically fragile systems, climate change may potentially exacerbate the situation particularly with regards to enforced migration.
FPGA based demodulation of laser induced fluorescence in plasmas
Authors: Mattingly Sean W. , Skiff Fred
Published: April 2018

We present a field programmable gate array (FPGA)-based system that counts photons from laser-induced fluorescence (LIF) on a laboratory plasma. This is accomplished with FPGA-based up/down counters that demodulate the data, giving a background-subtracted LIF signal stream that is updated with a new point as each laser amplitude modulation cycle completes. We demonstrate using the FPGA to modulate a laser at 1 MHz and demodulate the resulting LIF data stream. This data stream is used to calculate an LIF-based measurement sampled at 1 MHz of a plasma ion fluctuation spectrum.
First-principles investigation of diffusion and defect properties of Fe and Ni in Cr2O3
Authors: Rak Zs. , Brenner D. W.
Published: April 2018

Diffusion of Fe and Ni and the energetics of Fe- and Ni-related defects in chromium oxide (α–Cr2O3) are investigated using first-principles Density Functional Theory calculations in combination with the climbing-image nudged elastic band method. The orientations of the spin magnetic moments of the migrating ions are taken into account and their effects on migration barriers are examined. Several possible diffusion pathways were explored through interstitial and vacancy mechanisms, and it was found that the principal mode of ion transport in Cr2O3 is via vacancies. Both interstitial- and vacancy-mediated diffusions are anisotropic, with diffusion being faster in the z-direction. The energetics of defect formation indicates that the Ni-related defects are less stable than the Fe-related ones. This is consistent with Ni-diffusion being faster than Fe-diffusion. The results are compared with previous theoretical and experimental data and possible implications in corrosion control are discussed.
Electromechanical model to predict the movability of liquids in an electrowetting-on-dielectric microfluidic device
Authors: Torabinia Matin , Farzbod Ali , Moon Hyejin
Published: April 2018

In electrowetting-on-dielectric (EWOD) microfluidics, a motion of a fluid is created by a voltage applied to the fluid/surface interface. Water and aqueous solutions are the most frequently used fluids in EWOD devices. In order for EWOD microfluidics to be a versatile platform for various applications, however, movability of different types of fluids other than aqueous solutions should be understood. An electromechanical model using a simple RC circuit has been used to predict the mechanical force exerted on a liquid droplet upon voltage application. In this present study, two important features missed in previous works are addressed. Energy dissipation by contact line friction is considered in the new model as the form of resistor. The phase angle is taken into account in the analysis of the AC circuit. The new electromechanical model and computation results are validated with experimental measurements of forces on two different liquids. The model is then used to explain influences of contact angle hysteresis, surface tension, conductivity, and dielectric constant of fluids to the mechanical force on a liquid droplet.
Chemical waves in the O2 + H2 reaction on a Rh(111) surface alloyed with nickel. I. Photoelectron emission microscopy
Authors: Smolinsky Tim , von Boehn Bernhard , Imbihl Ronald
Published: April 2018

Chemical waves that arise in the H2 + O2 reaction on a bimetallic Rh(111)/Ni surface have been studied in the 10−6 and 10−5 mbar range at T = 773 K with photoelectron emission microscopy (PEEM), low-energy electron diffraction (LEED), and Auger electron spectroscopy (AES). Nickel coverages of 0.3, 0.6, and 1.0 monolayers were investigated. Coadsorbed with some oxygen, Ni starts to penetrate the Rh bulk region substantially only beyond 900 K. In the 10−5 mbar range, chemical waves are characterized by three distinct gray levels in PEEM. This number reduces to only two levels in the 10−6 mbar range. In situ LEED showed the periodic appearance of a (n × 1) (n = 8, 10) pattern during chemical waves which was assigned to a 2D-Ni oxide. With in situ AES, one observes that the bright phase in PEEM correlates with a high Ni coverage and the dark phase with a low Ni coverage.
Surface charges promote nonspecific nanoparticle adhesion to stiffer membranes
Authors: Sinha Shayandev , Jing Haoyuan , Sachar Harnoor Singh , Das Siddhartha
Published: April 2018

This letter establishes the manner in which the electric double layer induced by the surface charges of the plasma membrane (PM) enhances the nonspecific adhesion (NSA) of a metal nanoparticle (NP) to stiffer PMs (i.e., PMs with larger bending moduli). The NSA is characterized by the physical attachment of the NP to the membrane and occurs when the decrease in the surface energy (or any other mechanism) associated with the attachment process provides the energy for bending the membrane. Such an attachment does not involve receptor-ligand interactions that characterize the specific membrane-NP adhesion. Here, we demonstrate that a significant decrease in the electrostatic energy caused by the NP-attachment-induced destruction of the charged-membrane-electrolyte interface is responsible for providing the additional energy needed for bending the membrane during the NP adhesion to stiffer membranes. A smaller salt concentration and a larger membrane charge density augment this effect, which can help to design drug delivery to cells with stiffer membranes due to pathological conditions, fabricate NPs with biomimetic cholesterol-rich lipid bilayer encapsulation, etc.
Time-dependent dielectric breakdown of atomic-layer-deposited Al2O3 films on GaN
Authors: Hiraiwa Atsushi , Sasaki Toshio , Okubo Satoshi , Horikawa Kiyotaka , Kawarada Hiroshi
Published: April 2018

Atomic-layer-deposited (ALD) Al2O3 films are the most promising surface passivation and gate insulation layers in non-Si semiconductor devices. Here, we carried out an extensive study on the time-dependent dielectric breakdown characteristics of ALD-Al2O3 films formed on homo-epitaxial GaN substrates using two different oxidants at two different ALD temperatures. The breakdown times were approximated by Weibull distributions with average shape parameters of 8 or larger. These values are reasonably consistent with percolation theory predictions and are sufficiently large to neglect the wear-out lifetime distribution in assessing the long-term reliability of the Al2O3 films. The 63% lifetime of the Al2O3 films increases exponentially with a decreasing field, as observed in thermally grown SiO2 films at low fields. This exponential relationship disproves the correlation between the lifetime and the leakage current. Additionally, the lifetime decreases with measurement temperature with the most remarkable reduction observed in high-temperature (450 °C) O3-grown films. This result agrees with that from a previous study, thereby ruling out high-temperature O3 ALD as a gate insulation process. When compared at 200 °C under an equivalent SiO2 field of 4 MV/cm, which is a design guideline for thermal SiO2 on Si, high-temperature H2O-grown Al2O3 films have the longest lifetimes, uniquely achieving the reliability target of 20 years. However, this target is accomplished by a relatively narrow margin and, therefore, improvements in the lifetime are expected to be made, along with efforts to decrease the density of extrinsic Al2O3 defects, if any, to promote the practical use of ALD Al2O3 films.
Tuning metal-insulator transitions in epitaxial V2O3 thin films
Authors: Thorsteinsson Einar B. , Shayestehaminzadeh Seyedmohammad , Arnalds Unnar B.
Published: April 2018

We present a study of the synthesis of epitaxial V2O3 films on c-plane Al2O3 substrates by reactive dc-magnetron sputtering. The results reveal a temperature window, at substantially lower values than previously reported, wherein epitaxial films can be obtained when deposited on [0001] oriented surfaces. The films display a metal-insulator transition with a change in the resistance of up to four orders of magnitude, strongly dependent on the O2 partial pressure during deposition. While the electronic properties of the films show sensitivity to the amount of O2 present during deposition of the films, their crystallographic structure and surface morphology of atomically flat terraced structures with up to micrometer dimensions are maintained. The transition temperature, as well as the scale of the metal-insulator transition, is correlated with the stoichiometry and local strain in the films controllable by the deposition parameters.
Letter: Entrapment and interaction of an air bubble with an oscillating cavitation bubble
Authors: Kannan Y. S. , Karri Badarinath , Sahu Kirti Chandra
Published: April 2018

The mechanism of the formation of an air bubble due to an oscillating cavitation bubble in its vicinity is reported from an experimental study using high-speed imaging. The cavitation bubble is created close to the free surface of water using a low-voltage spark circuit comprising two copper electrodes in contact with each other. Before the bubble is created, a third copper wire is positioned in contact with the free surface of water close to the two crossing electrodes. Due to the surface tension at the triple point (wire-water-air) interface, a small dip is observed in the free surface at the point where the wire is immersed. When the cavitation bubble is created, the bubble pushes at the dip while expanding and pulls at it while collapsing. The collapse phase leads to the entrapment of an air bubble at the wire immersion point. During this phase, the air bubble undergoes a “catapult” effect, i.e., it expands to a maximum size and then collapses with a microjet at the free surface. To the best of our knowledge, this mechanism has not been reported so far. A parametric study is also conducted to understand the effects of wire orientation and bubble distance from the free surface.
Communication: Photoionization of degenerate orbitals for randomly oriented molecules: The effect of time-reversal symmetry on recoil-ion momentum angular distributions
Authors: Suzuki Yoshi-Ichi
Published: April 2018

The photoelectron asymmetry parameter β, which characterizes the direction of electrons ejected from a randomly oriented molecular ensemble by linearly polarized light, is investigated for degenerate orbitals. We show that β is totally symmetric under the symmetry operation of the point group of a molecule, and it has mixed properties under time reversal. Therefore, all degenerate molecular orbitals, except for the case of degeneracy due to time reversal, have the same β (Wigner-Eckart theorem). The exceptions are e-type complex orbitals of the Cn, Sn, Cnh, T, and Th point groups, and calculations on boric acid (C3h symmetry) are performed as an example. However, including those point groups, all degenerate orbitals have the same β if those orbitals are real. We discuss the implications of this operator formalism for molecular alignment and photoelectron circular dichroism.
A quantum dynamical study of the rotation of the dihydrogen ligand in the Fe(H)2(H2)(PEtPh2)3 coordination complex
Authors: Gonzalez Megan E. , Eckert Juergen , Aquino Adelia J. A. , Poirier Bill
Published: April 2018

Progress in the hydrogen fuel field requires a clear understanding and characterization of how materials of interest interact with hydrogen. Due to the inherently quantum mechanical nature of hydrogen nuclei, any theoretical studies of these systems must be treated quantum dynamically. One class of material that has been examined in this context are dihydrogen complexes. Since their discovery by Kubas in 1984, many such complexes have been studied both experimentally and theoretically. This particular study examines the rotational dynamics of the dihydrogen ligand in the Fe(H)2(H2)(PEtPh2)3 complex, allowing for full motion in both the rotational degrees of freedom and treating the quantum dynamics (QD) explicitly. A “gas-phase” global potential energy surface is first constructed using density functional theory with the Becke, 3-parameter, Lee-Yang-Parr functional; this is followed by an exact QD calculation of the corresponding rotation/libration states. The results provide insight into the dynamical correlation of the two rotation angles as well as a comprehensive analysis of both ground- and excited-state librational tunneling splittings. The latter was computed to be 6.914 cm−1—in excellent agreement with the experimental value of 6.4 cm−1. This work represents the first full-dimensional ab initio exact QD calculation ever performed for dihydrogen ligand rotation in a coordination complex.
High-temperature conduction behavior of carbon nanotube fiber from 25 °C to 1100 °C
Authors: Zhang Xiaoshan , Yang Lingwei , Liu Haitao
Published: April 2018

The high-temperature conduction behaviors of pure CNT fibers and CNT/SiC and CNT/C composite-fibers from 25 °C to 1100 °C in a N2 atmosphere are reported. The results show a significant increase in the electrical conductivities of CNT fibers in the temperature regime, as the semi-conductive SiC and conductive C matrices were introduced. As the temperature increased, the conductivities of all fibers increase with temperature up to a critical temperature, Tc, beyond which the decrease in the conductivities was observed. The conduction behaviors of all fibers can be well explained by the three-dimensional variable range hopping mechanism at the temperature below Tc and followed a heterogeneous mechanism above Tc. Interestingly, Tc was reduced after the introductions of SiC and C matrices, and this is explained by the competing effect of the internal nanotube resistance and the contact resistance between nanotubes which decreases with the introduction of SiC and C matrices. We propose that the study of high-temperature conduction behaviors of the CNT fibers aids in improving their conductivities and applications at high temperatures, and the presented conduction mechanisms could be used for other kinds of CNT-structured fibers.
A detailed examination of laser-ion acceleration mechanisms in the relativistic transparency regime using tracers
Authors: Stark David J. , Yin Lin , Albright Brian J. , Nystrom William , Bird Robert
Published: April 2018

We present a particle-in-cell study of linearly polarized laser-ion acceleration systems, in which we use both two-dimensional (2D) and three-dimensional (3D) simulations to characterize the ion acceleration mechanisms in targets which become transparent to the laser pulse during irradiation. First, we perform a target length scan to optimize the peak ion energies in both 2D and 3D, and the predictive capabilities of 2D simulations are discussed. Tracer analysis allows us to isolate the acceleration into stages of target normal sheath acceleration (TNSA), hole boring (HB), and break-out afterburner (BOA) acceleration, which vary in effectiveness based on the simulation parameters. The thinnest targets reveal that enhanced TNSA is responsible for accelerating the most energetic ions, whereas the thickest targets have ions undergoing successive phases of HB and TNSA (in 2D) or BOA and TNSA (in 3D); HB is not observed to be a dominant acceleration mechanism in the 3D simulations. It is in the intermediate optimal regime, both when the laser breaks through the target with appreciable amplitude and when there is enough plasma to form a sustained high density flow, that BOA is most effective and is responsible for the most energetic ions. Eliminating the transverse laser spot size effects by performing a plane wave simulation, we can isolate with greater confidence the underlying physics behind the ion dynamics we observe. Specifically, supplemented by wavelet and FFT analyses, we match the post-transparency BOA acceleration with a wave-particle resonance with a high-amplitude low-frequency electrostatic wave of increasing phase velocity, consistent with that predicted by the Buneman instability.
Using high thermal stability flexible thin film thermoelectric generator at moderate temperature
Authors: Zheng Zhuang-Hao , Luo Jing-Ting , Chen Tian-Bao , Zhang Xiang-Hua , Liang Guang-Xing , Fan Ping
Published: April 2018

Flexible thin film thermoelectric devices are extensively used in the microscale industry for powering wearable electronics. In this study, comprehensive optimization was conducted in materials and connection design for fabricating a high thermal stability flexible thin film thermoelectric generator. First, the thin films in the generator, including the electrodes, were prepared by magnetron sputtering deposition. The “NiCu–Cu–NiCu” multilayer electrode structure was applied to ensure the thermal stability of the device used at moderate temperature in an air atmosphere. A design with metal layer bonding and series accordant connection was then employed. The maximum efficiency of a single PN thermocouple generator is >11%, and the output power loss of the generator is <10% after integration.
Mutations in the pancreatic secretory enzymes
CPA1
and
CPB1
are associated with pancreatic cancer
Authors: Tamura Koji , Yu Jun , Hata Tatsuo , Suenaga Masaya , Shindo Koji , Abe Toshiya , MacGregor-Das Anne , Borges Michael , Wolfgang Christopher L. , Weiss Matthew J. , He Jin , Canto Marcia Irene , Petersen Gloria M. , Gallinger Steven , Syngal Sapna , Brand Randall E. , Rustgi Anil , Olson Sara H. , Stoffel Elena , Cote Michele L. , Zogopoulos George , Potash James B. , Goes Fernando S. , McCombie Richard W. , Zandi Peter P. , Pirooznia Mehdi , Kramer Melissa , Parla Jennifer , Eshleman James R. , Roberts Nicholas J. , Hruban Ralph H. , Klein Alison Patricia , Goggins Michael
Published: April 2018

Significance

Much of the inherited susceptibility to pancreatic cancer remains unexplained. Germline variants that cause protein misfolding and impaired secretion of pancreatic enzymes such as
CPA1
(encoding carboxypeptidase A1) can cause pancreatic acinar cell endoplasmic reticulum (ER) stress. We investigated the hypothesis that pancreatic cancer could arise from germline variants in genes encoding pancreatic secretory enzymes that induce pancreatic acinar cell stress. We find ∼1% of 1,579 patients with pancreatic cancer vs. 1 of 2,012 controls have germline variants in the genes encoding
CPA1
and
CPB1
(carboxypeptidase B1) that impair secretion of its protein product and induce ER stress. These findings implicate pancreatic acinar cell stress as a mechanism of pancreatic cancer susceptibility.
Druggable negative allosteric site of P2X3 receptors
Authors: Wang Jin , Wang Yao , Cui Wen-Wen , Huang Yichen , Yang Yang , Liu Yan , Zhao Wen-Shan , Cheng Xiao-Yang , Sun Wang-Sheng , Cao Peng , Zhu Michael X. , Wang Rui , Hattori Motoyuki , Yu Ye
Published: April 2018

Significance

Allosteric regulation, produced by the binding of a ligand at an allosteric site topographically distinct from the orthosteric site, represents a direct and efficient means for modulation of biological macromolecule function. Because allosteric modulators have advantages over classic orthosteric ligands as therapeutic agents, understanding the mechanism underlying allosteric modulation may open new therapeutic avenues. Here, we focused on allosteric regulation of P2X receptors, which are implicated in diverse pathophysiological processes, such as blood clotting, pain sensation, inflammation, and rheumatoid arthritis. Combining structural determination, molecular modeling, and mutagenesis, we identified a druggable allosteric site on P2X3. Our findings will facilitate the development of novel therapeutics targeting these receptors.
Rationalizing the Irrational: Reza Attaran’s Popularity, Stardom, and the Recent Cycle of Iranian Absurd Films
Authors: Tabarraee Babak
Published: April 2018

Reza Attaran is one of the most successful stars of the Iranian popular cinema. This article explores the social circumstances, performative components, and political consequences of Attaran’s popularity and stardom, and the evolution of comedy and satire in the Iranian media after the 1979 Revolution. Analyzing the contextual elements and media texts over the last twenty-five years, the article argues that Attaran actively reflects a complex interaction between the social, political, and artistic demands of each period, best represented through his contribution to the television sketch comedies in the 1990s, and the lowbrow comedies and highbrow absurd films in the 2010s. The trajectory of Attaran’s stardom demonstrates the mechanism by which he serves the maintenance of the status quo.
HFSP: high speed homology-driven function annotation of proteins
Authors: Mahlich Yannick , Steinegger Martin , Rost Burkhard , Bromberg Yana
Published: April 2018

Motivation

The rapid drop in sequencing costs has produced many more (predicted) protein sequences than can feasibly be functionally annotated with wet-lab experiments. Thus, many computational methods have been developed for this purpose. Most of these methods employ homology-based inference, approximated via sequence alignments, to transfer functional annotations between proteins. The increase in the number of available sequences, however, has drastically increased the search space, thus significantly slowing down alignment methods.

Results

Here we describe homology-derived functional similarity of proteins (HFSP), a novel computational method that uses results of a high-speed alignment algorithm, MMseqs2, to infer functional similarity of proteins on the basis of their alignment length and sequence identity. We show that our method is accurate (85% precision) and fast (more than 40-fold speed increase over state-of-the-art). HFSP can help correct at least a 16% error in legacy curations, even for a resource of as high quality as Swiss-Prot. These findings suggest HFSP as an ideal resource for large-scale functional annotation efforts.

Supplementary information

Supplementary data are available at Bioinformatics online.
comoRbidity: an R package for the systematic analysis of disease comorbidities
Authors: Gutiérrez-Sacristán Alba , Bravo Àlex , Giannoula Alexia , Mayer Miguel A , Sanz Ferran , Furlong Laura I
Published: April 2018

Motivation

The study of comorbidities is a major priority due to their impact on life expectancy, quality of life and healthcare cost. The availability of electronic health records (EHRs) for data mining offers the opportunity to discover disease associations and comorbidity patterns from the clinical history of patients gathered during routine medical care. This opens the need for analytical tools for detection of disease comorbidities, including the investigation of their underlying genetic basis.

Results

We present comoRbidity, an R package aimed at providing a systematic and comprehensive analysis of disease comorbidities from both the clinical and molecular perspectives. comoRbidity leverages from (i) user provided clinical data from EHR databases (the clinical comorbidity analysis) and (ii) genotype-phenotype information of the diseases under study (the molecular comorbidity analysis) for a comprehensive analysis of disease comorbidities. The clinical comorbidity analysis enables identifying significant disease comorbidities from clinical data, including sex and age stratification and temporal directionality analyses, while the molecular comorbidity analysis supports the generation of hypothesis on the underlying mechanisms of the disease comorbidities by exploring shared genes among disorders. The open-source comoRbidity package is a software tool aimed at expediting the integrative analysis of disease comorbidities by incorporating several analytical and visualization functions.

Availability and implementation

https://bitbucket.org/ibi_group/comorbidity

Supplementary information

Supplementary data are available at Bioinformatics online.
CONICS integrates scRNA-seq with DNA sequencing to map gene expression to tumor sub-clones
Authors: Müller Sören , Cho Ara , Liu Siyuan J , Lim Daniel A , Diaz Aaron
Published: April 2018

Motivation

Single-cell RNA-sequencing (scRNA-seq) has enabled studies of tissue composition at unprecedented resolution. However, the application of scRNA-seq to clinical cancer samples has been limited, partly due to a lack of scRNA-seq algorithms that integrate genomic mutation data.

Results

To address this, we present

CONICS

COpy-Number analysis In single-Cell RNA-Sequencing. CONICS is a software tool for mapping gene expression from scRNA-seq to tumor clones and phylogenies, with routines enabling: the quantitation of copy-number alterations in scRNA-seq, robust separation of neoplastic cells from tumor-infiltrating stroma, inter-clone differential-expression analysis and intra-clone co-expression analysis.

Availability and implementation

CONICS is written in Python and R, and is available from https://github.com/diazlab/CONICS.

Supplementary information

Supplementary data are available at Bioinformatics online.
GlycoStore: a database of retention properties for glycan analysis
Authors: Zhao Sophie , Walsh Ian , Abrahams Jodie L , Royle Louise , Nguyen-Khuong Terry , Spencer Daniel , Fernandes Daryl L , Packer Nicolle H , Rudd Pauline M , Campbell Matthew P
Published: April 2018

GlycoStore is a curated chromatographic, electrophoretic and mass-spectrometry composition database of N-, O-, glycosphingolipid (GSL) glycans and free oligosaccharides associated with a range of glycoproteins, glycolipids and biotherapeutics. The database is built on publicly available experimental datasets from GlycoBase developed in the Oxford Glycobiology Institute and then the National Institute for Bioprocessing Research and Training (NIBRT). It has now been extended to include recently published and in-house data collections from the Bioprocessing Technology Institute (BTI) A*STAR, Macquarie University and Ludger Ltd. GlycoStore provides access to approximately 850 unique glycan structure entries supported by over 8500 retention positions determined by: (i) hydrophilic interaction chromatography (HILIC) ultra-high performance liquid chromatography (U/HPLC) and reversed phase (RP)-U/HPLC with fluorescent detection; (ii) porous graphitized carbon (PGC) chromatography in combination with ESI-MS/MS detection; and (iii) capillary electrophoresis with laser induced fluorescence detection (CE-LIF). GlycoStore enhances many features previously available in GlycoBase while addressing the limitations of the data collections and model of this popular resource. GlycoStore aims to support detailed glycan analysis by providing a resource that underpins current workflows. It will be regularly updated by expert annotation of published data and data obtained from the project partners.

Availability and implementation

http://www.glycostore.org

Supplementary information

Supplementary data are available at Bioinformatics online.
MARDy: Mycology Antifungal Resistance Database
Authors: Nash Anthony , Sewell Thomas , Farrer Rhys A , Abdolrasouli Alireza , Shelton Jennifer M G , Fisher Matthew C , Rhodes Johanna
Published: April 2018

The increase of antifungal drug resistance is a major global human health concern and threatens agriculture and food security; in order to tackle these concerns, it is important to understand the mechanisms that cause antifungal resistance. The curated Mycology Antifungal Resistance Database (MARDy) is a web-service of antifungal drug resistance mechanisms, including amino acid substitutions, tandem repeat sequences and genome ploidy. MARDy is implemented on a Linux, Apache, MySQL and PHP web development platform and includes a local installation of BLASTn of the database of curated genes.

Availability and implementation

MARDy can be accessed at http://www.mardy.net and is free to use. The complete database can be retrieved, ordered by organism, gene and drug. Missing or new mycological antifungal resistance data can be relayed to the development team through a contribute entry form. Updates and news will be publicized via a dedicated Twitter feed: @MARDYfungi.
Spatial quantification of the synaptic activity phenotype across large populations of neurons with Markov random fields
Authors: Robinson Sean , Courtney Michael J
Published: April 2018

Motivation

The collective and co-ordinated synaptic activity of large neuronal populations is relevant to neuronal development as well as a range of neurological diseases. Quantification of synaptically-mediated neuronal signalling permits further downstream analysis as well as potential application in target validation and in vitro screening assays. Our aim is to develop a phenotypic quantification for neuronal activity imaging data of large populations of neurons, in particular relating to the spatial component of the activity.

Results

We extend the use of Markov random field (MRF) models to achieve this aim. In particular, we consider Bayesian posterior densities of model parameters in Gaussian MRFs to directly model changes in calcium fluorescence intensity rather than using spike trains. The basis of our model is defining neuron ‘neighbours’ by the relative spatial positions of the neuronal somata as obtained from the image data whereas previously this has been limited to defining an artificial square grid across the field of view and spike binning. We demonstrate that our spatial phenotypic quantification is applicable for both in vitro and in vivo data consisting of thousands of neurons over hundreds of time points. We show how our approach provides insight beyond that attained by conventional spike counting and discuss how it could be used to facilitate screening assays for modifiers of disease-associated defects of communication between cells.

Availability and implementation

We supply the MATLAB code and data to obtain all of the results in the paper.

Supplementary information

Supplementary data are available at Bioinformatics online.
Decomposition Spaces and Restriction Species
Authors: Gálvez-Carrillo Imma , Kock Joachim , Tonks Andrew
Published: April 2018

We show that Schmitt’s restriction species (such as graphs, matroids, posets, etc.) naturally induce decomposition spaces (a.k.a. unital $2$-Segal spaces), and that their associated coalgebras are an instance of the general construction of incidence coalgebras of decomposition spaces. We introduce directed restriction species that subsume Schmitt’s restriction species and also induce decomposition spaces. Whereas ordinary restriction species are presheaves on the category of finite sets and injections, directed restriction species are presheaves on the category of finite posets and convex maps. We also introduce the notion of monoidal (directed) restriction species, which induce monoidal decomposition spaces and hence bialgebras, most often Hopf algebras. Examples of this notion include rooted forests, directed graphs, posets, double posets, and many related structures. A prominent instance of a resulting incidence bialgebra is the Butcher–Connes–Kreimer Hopf algebra of rooted trees. Both ordinary and directed restriction species are shown to be examples of a construction of decomposition spaces from certain cocartesian fibrations over the category of finite ordinals that are also cartesian over convex maps. The proofs rely on some beautiful simplicial combinatorics, where the notion of convexity plays a key role. The methods developed are of independent interest as techniques for constructing decomposition spaces.
Clinicopathological predictors for progression of chronic kidney disease in nephrosclerosis: a biopsy-based cohort study
Authors: Yamanouchi Masayuki , Hoshino Junichi , Ubara Yoshifumi , Takaichi Kenmei , Kinowaki Keiichi , Fujii Takeshi , Ohashi Kenichi , Mise Koki , Toyama Tadashi , Hara Akinori , Shimizu Miho , Furuichi Kengo , Wada Takashi
Published: April 2018

Background

Biopsy-based studies on nephrosclerosis are lacking and the clinicopathological predictors for progression of chronic kidney disease (CKD) are not well established.

Methods

We retrospectively assessed 401 patients with biopsy-proven nephrosclerosis in Japan. Progression of CKD was defined as new-onset end-stage renal disease, decrease of estimated glomerular filtration rate (eGFR) by  ≥50% or doubling of serum creatinine, and the sub-distribution hazard ratio (SHR) with 95% confidence interval (CI) for CKD progression was determined for various clinical and histological characteristics in competing risks analysis. The incremental value of pathological information for predicting CKD progression was assessed by calculating Harrell’s C-statistics, the Akaike information criterion (AIC), net reclassification improvement and integrated discrimination improvement.

Results

During a median follow-up period of 5.3 years, 117 patients showed progression of CKD and 10 patients died before the defined kidney event. Multivariable sub-distribution hazards model identified serum albumin (SHR 0.48; 95% CI 0.35–0.67), hemoglobin A1c (SHR 0.71; 95% CI 0.54–0.94), eGFR (SHR 0.98; 95% CI 0.97–0.99), urinary albumin/creatinine ratio (UACR) (SHR 1.18; 95% CI 1.08–1.29), percentage of segmental/global glomerulosclerosis (%GS) (SHR 1.01; 95% CI 1.00–1.02) and interstitial fibrosis and tubular atrophy (IFTA) (SHR 1.52; 95% CI 1.20–1.92) as risk factors for CKD progression. The C-statistic of a model with only clinical variables was improved by adding %GS (0.790 versus 0.796, P < 0.01) and IFTA (0.790 versus 0.811, P < 0.01). The reclassification statistic was also improved after adding the biopsy data to the clinical data. The model including IFTA was superior, with the lowest AIC.

Conclusions

The study implies that in addition to the traditional markers of eGFR and UACR, we may explore the markers of serum albumin and hemoglobin A1c, which are widely available but not routinely measured in patients with nephrosclerosis, and the biopsy data, especially the data on the severity of interstitial damage, for the better prediction of CKD progression in patients with nephrosclerosis.
Gifting Melons to the Shining Prince
Authors: Watanabe Takeshi
Published: April 2018

This chapter focuses on solving the mystery of cuisine during the Heian period (794–1185), Japan’s classical age, when court literature, poetry, and arts flourished. While literature from the era often addresses the carnal appetites of courtiers, accounts of actual foods and foodways are largely absent. The chapter puts together Heian-era references to food from various sources, including Buddhist morality tales, historical anecdotes, and poetry, to produce an account of the era’s conflicted attitudes toward food as a source of both guilt and pleasure, and as an important means of mediating human relationships. It also reveals that the foods of classical-era courtiers diverged from the contemporary “hallmarks of Japanese cuisine” such as aesthetics and seasonality, relying heavily on preserved and dried foodstuffs and served on plain, round dishes.
Miso Mama
Authors: Seaman Amanda C.
Published: April 2018

This chapter considers how pregnancy manuals and literature, from the Edo period until present day, advocate strict weight management and a restrictive dietary regime for the mother, warning that maternal and fetal well-being are dependent upon the mother's ability to control her appetite and engage in self-sacrifice. Despite the medicalization of birth practices in the Meiji era (1868–1912), folk wisdom restrictions on pregnancy foods remains unchanged; traditional Japanese foods, such as brown rice, tofu, and fish are considered the proper diet for the pregnant body, while “foreign foods” endanger maternal and fetal health. The chapter also notes the increasing association between the maternal and national body with the advent of modernity.
Afterword
Authors: Rath Eric C.
Published: April 2018

In 1946 an English-language guidebook to Japanese food began with the following warning:

Initiation of foreigners into Japanese dishes must be a gradual one proceeding from the familiar to the unfamiliar. Raw fish in slices (“sashimi”) and pickled vegetables (“konomono”), so dear and delicious to the Japanese palate, should be reserved for the initiated—these are dangerous things to offer to the beginner; dangerous because they may repel and disgust those who will come to appreciate Japanese delicacies when introduced to them from other easier approaches where they have to tackle with the line of least resistance....
Jonathan Edwards’ Scriptural Practices
Authors: Minkema Kenneth P.
Published: April 2018

Kenneth P. Minkema gives readers a view into Jonathan Edwards’ day-to-day practices of engaging with Scripture. He shows how Edwards kept various exegetical manuscripts and developed detailed systems for organizing and indexing his reflections on the Bible. These practices made it easier for him to draw from this material as he constructed theological treatises and developed and repreached sermons. Edwards also regularly conducted “canonical reviews” to systematically examine how Scripture treated different theological themes. This understanding of Edwards’ direct engagement with the Bible and application of his exegetical materials, as Minkema demonstrates, opens up many lines of inquiry into the further study of Edwards as exegete.
Jonathan Edwards’ Principles of Interpreting Scripture
Authors: Nichols Stephen R. C.
Published: April 2018

Stephen R. C. Nichols explores the principles of interpretation at play in Jonathan Edwards’ exegesis. He argues that the underlying principle of his exegesis was harmony. This principle carried several implications for interpreting Scripture: that Scripture is the best interpreter of Scripture (that is, Scripture is harmonious with itself); that the Bible exhibits doctrinal harmony; and that Scripture achieves a harmony with the regenerate reader. Despite this view of harmony and Edwards’ continuity with the Reformed and Puritan traditions of interpretation, Nichols also holds that he was willing to experiment with that tradition, particularly in relation to typology, sometimes blurring the line between typology and allegory. Nichols concludes that Edwards both functioned within the boundaries of his tradition and explored creative innovations.
Early Modern Biblical Commentary and Jonathan Edwards
Authors: Neele Adriaan C.
Published: April 2018

Adriaan C. Neele introduces the early modern context of biblical interpretation by discussing Matthew Poole’s Synopsis Criticorum aliorumque Sacrae Scripturae (1669–1674), a frequently referenced volume for many biblical interpreters, whether in England, on the European continent, or in the New World. Neele shows how this work represents early modern exegesis well and how it became an important channel for bringing medieval commentaries into the hands of post-Reformation exegetes. He also establishes the high esteem that this multivolume work gained in New England and its important role in Jonthan Edwards’ exegesis. The Synopsis gives us insight into early modern interpretation yet also serves as a contrast to New England exegesis, helping us set Edwards in his time.
Spiritual Meaning and Experimental Piety in the Exegesis of Cotton Mather and Jonathan Edwards
Authors: Stievermann Jan , Hoselton Ryan P.
Published: April 2018

Jan Stievermann and Ryan P. Hoselton consider the role of experiential piety in the exegesis of Cotton Mather and Jonathan Edwards. Both were deeply engaged in the new critical questions of their day, and both were also committed to nurturing religious piety—though they differed somewhat in how they handled these concerns. Although Mather was profoundly interested in the philological and historical issues in the Bible, he prioritized devotional and contemplative engagement with Scripture. Edwards, Stievermann and Hoselton argue, drew on the experimental language and philosophy of the Enlightenment to construct a case for the supernatural authority of the Bible against increasingly naturalistic arguments. Edwards held that one gains spiritual understanding as the Holy Spirit harmonizes the believer’s internal senses with the Word; this reconstruction affected Edwards’ approach to the emotive element in Scripture, the dynamism of typology, and the nature of the regenerate interpreter of the Bible.
Jacob Wrestling with “a Man”
Authors: Noll Mark A.
Published: April 2018

Mark A. Noll provides a detailed comparison of Jonthan Edwards’ biblical interpretation with that of other interpreters in his surrounding context by focusing on Genesis 32:22–32, the account of Jacob wrestling with “a man,” as a case study. He offers a careful comparative analysis of Edwards’ exegesis of this passage across his corpus, and then he compares him with six exegetes: Matthew Poole, Matthew Henry, Cotton Mather, August Hermann Francke, Charles Wesley, and Thomas Scott. These interpreters represent eras prior to, during, and after Edwards’ lifetime; some come from his theological tradition, whereas others do not. By tracing continuities and discontinuities in this exercise, Noll makes incisive observations about Edwards’ exegesis and proposes paths forward in the study of Edwards’ engagement with the Bible.