bluuebunny/crossref_metadata_2025 huggingface dataset:
Cavitron Ultrasonic Surgical Aspirator-Assisted Pancreatic Resection in Hyperinsulinism
Authors: Bond Logan , Murrell Zaria , Wright Tiffany , Bond Sheldon
Published: May 2017

Introduction Diffuse congenital hyperinsulinemia continues to be poorly responsive to medical management. Surgical resection for this entity can be variable in extent and efficacy.

Materials and Methods This report describes a unique method of pancreatic resection for diffuse familial congenital hyperinsulinemia. The procedure maximizes pancreatic parenchymal removal while preserving blood supply to the vital structures adjacent to the head of the pancreas. Two cases of familial congenital hyperinsulinism are presented as well as a review of the current surgical literature.

Results The Cavitron ultrasonic surgical aspirator has been used successfully to assist in maximum resection of pancreatic tissue while preserving blood supply to the duodenum and common bile duct.

Conclusion This report describes a useful technique of maximizing pancreatic resection for patients with diffuse congenital hyperinsulinemia which preserves adjacent vital structures.
Präoperative Vorbereitung: Optimierung pulmonaler Erkrankungen
Authors: Mutlak Haitham , Grünewaldt Achim
Published: May 2017

Lungenerkrankungen wie COPD oder Asthma sind bedeutende Risikofaktoren perioperativer pulmonaler Komplikationen. Die Optimierung dieser Erkrankungen ist deshalb wichtiger Bestandteil des präoperativen Managements. Das Wissen um die Pathophysiologie und medikamentöse Therapie ist dabei essenziell.
Krisen bewältigen
Authors: Scheurich Hubert
Published: May 2017

Interventionskoffer, die Achte Mit dem Resilienztraining können
psychiatrisch Pflegende Patienten in einer schweren psychischen Krise oder mit
einer chronischen psychischen Erkrankung unterstützen. Die Übungen eignen sich
für Einzel- und Gruppeninterventionen.
Sicherheit nach außen, Freizügigkeit nach
innen
Authors: Müller Christoph
Published: May 2017

Erlebte Geschichte Das forensische Dorf in der LVR-Klinik in Düren feierte
im letzten Herbst sein 30-jähriges Bestehen. Unser Autor hat die Gelegenheit
genutzt, um mit Zeitzeugen zu sprechen.
Gemeinsam lernen
Authors: Heß Ulrike
Published: May 2017

Interprofessionelle Ausbildungsstation Inwieweit fördert der betriebliche
Lernort „Ausbildungsstation“ die Entwicklung der interprofessionellen Kompetenz
in den Gesundheitsberufen? Dieser Frage ging unsere Autorin im Rahmen ihrer
Bachelorarbeit nach. Sie zeigt Chancen und Barrieren für die Umsetzung des
interprofessionellen Lernens und Lehrens für die Praxis auf und stellt
unterschiedliche Perspektiven zur Implementierung einer interprofessionellen
Ausbildungsstation vor.
Phytochemical Profiling and In Vitro Anticancer Activity of Purified Flavonoids of Andrographis glandulosa
Authors: Cherukupalli Neeraja , Bhumireddy Sudarshana , Akella Subrahmanya , Sataniya Aaysha , Sripadi Prabhakar , Khareedu Venkateswara , Vudem Dashavantha
Published: May 2017

The genus Andrographis includes diverse species of medicinal importance. The present study for the first time unravels the chemical profiling and medicinal importance of an unexplored species, Andrographis glandulosa. LC-MS analysis of A. glandulosa methanolic extract disclosed it as a rich source of flavonoids, with 8 minor peaks and 2 major peaks (m/z 285.0749 and 283.0595). NMR and ESI-MS/MS analyses confirmed the major peaks as (R) 2',5-dihydroxy-7-methoxyflavanone and 2',5-dihydroxy-7-methoxyflavone. Purified compounds exhibited antiproliferative activity on 3 cancer cell lines (HeLa, MIA PaCa and U-87) with IC50 39.81–46.21 µM for flavanone, and 20.84–25.16 µM for flavone. IC50 values of flavone are on a par with that of the positive control quercetin (21.78–26.82 µM). HeLa cells treated with 117 µM flavanone showed a loss of MMP (~55% of cells) resulting in apoptosis (~51% of cells). Treatment with 80 µM flavone caused a loss of MMP (~88% of cells) and induced apoptosis in ~70% of cells proving its efficacy over flavanone. Purified flavonoids exhibited cytotoxicity by disrupting mitochondrial membrane, caspase 3 activation and apoptosis. Purified flavonoids appear as promising natural products for developing cancer therapeutics.
Fatigue bei Multipler Sklerose: Neuronale Korrelate und
Möglichkeiten nicht-invasiver Hirnstimulation mit tDCS
Authors: Ayache Samar S. , Chalah Moussa A. , Kümpfel Tania , Padberg Frank , Lefaucheur Jean-Pascal , Palm Ulrich
Published: May 2017

Multiple Sklerose (MS) ist eine chronisch-progressive inflammatorische Erkrankung
des zentralen Nervensystems und die häufigste Ursache nicht-traumatischer
Funktionseinschränkung bei jungen Erwachsenen. Fatigue ist ein häufiges Symptom,
das von einer Mehrzahl der MS-Patienten während des Krankheitsverlaufs berichtet
wird und ihre Lebensqualität erheblich einschränkt. Trotz ihrer häufigen
Prävalenz und ihrer Bedeutung sind die zugrundeliegenden pathophysiologischen
Mechanismen nicht gut untersucht. Fatigue wird üblicherweise in ein primäre
Fatigue mit aus der Krankheit selbst resultierenden pathologischen Veränderungen
und in eine sekundäre Fatigue als Folge von Krankheitssymptomen, komorbiden
Schlafstörungen, affektiven Störungen und Nebenwirkungen von Medikamenten
eingeteilt. Erkenntnisse aus radiologischen, neurophysiologischen und
endokrinologischen Untersuchungen führten zu Überlegungen, dass es eine
Verbindung zwischen den Symptomen der Fatigue und strukturellen bzw.
funktionellen Veränderungen in verschiedenen neuronalen Netzwerkstrukturen gibt.
Über die letzten Jahre konnte gezeigt werden, dass verschiedene nichtinvasive
Hirnstimulationsverfahren neuronale Netzwerkstrukturen modulieren können,
insbesondere für die transkranielle Gleichstromstimulation (tDCS) konnten in den
letzten Jahren übereinstimmende Ergebnisse nachgewiesen werden, wenngleich die
Datenlage aufgrund des Pilotcharakters der Studien noch dünn ist. In dieser
Übersichtsarbeit werden die neuronalen Korrelate der MS und die Rationale für
den Einsatz der tDCS in der Behandlung der Fatigue dargestellt.
Morinda citrifolia Leaf Extract Suppressed Metastasised Cancer Progression via EGFR and MAPK Pathways
Authors: Lim Swee-Ling , Mustapha Noordin , Goh Yong-Meng , Rahman Heshu , Mohamed Suhaila
Published: May 2017

Morinda citrifolia leaf has anti-inflammatory and immune enhancing effects against lung cancer. The effects of the extract on metastasised lung and liver cancer tissues were compared to Erlotinib (an anticancer drug) for cancer aggression, proliferation, and angiogenesis. Forty Balb/c mice were induced to develop metastatic lung and liver tumours via xenograft subcutaneous injection of non-small cell lung cancer A549 cells (2×107 cells/mouse) into their backs. The extract (150 and 300 mg/kg body weight) and Erlotinib (50 mg/kg body weight) were fed to the mice for 21 days, and the microstructure and mRNA expressions of the tumour tissues were analysed. The extract dose-dependently downregulated RAC-alpha serine/threonine-protein kinase, B cell leukaemia/lymphoma 2, mitogen-activated protein kinase kinase kinase 14, mitogen-activated protein kinase 1, and vascular endothelial growth factor alpha in these tissues. The scopoletin (coumarin) and epicatechin (flavonoid) standardised extract also mitigated the cancerous tissues microstructure changes, and suppressed the tissue remodeling enzyme (matrix metallopeptidase 9) and angiogenesis biomarkers (epidermal growth factor receptor and integrin). The 300 mg extract/kg body weight was more effective than the 50 mg Erlotinib/kg body weight in suppressing the lung and liver tumoor metastasis. The extract inhibited the cancer aggression by interfering with epidermal growth factor receptor and mitogen-activated protein kinase carcinogenesis pathways, and suppressing proliferation, tissue remodelling, and angiogenesis without any observable side effects at the given dose.
Effect of Dichloromethane-Methanol Extract and Tomentin Obtained from Sphaeralcea angustifolia Cell Suspensions in a Model of Kaolin/Carrageenan-Induced Arthritis
Authors: del Pilar Nicasio-Torres María , Serrano-Román Jade , Pérez-Hernández Juanita , Jiménez-Ferrer Enrique , Herrera-Ruiz Maribel
Published: May 2017

Cell suspension cultures from Sphaeralcea angustifolia produce compounds with anti-inflammatory activity, including scopoletin, tomentin, and sphaeralcic acid. Antiarthritic activity of scopoletin isolated from S. angustifolia and Erycibe obtusifolia wild plants was demonstrated in a complete Freud’s adjuvant-induced arthritis model. In this project, the dichloromethane-methanol extract and tomentin isolated from S. angustifolia cell suspension were evaluated in mice using a kaolin/carrageenan-induced arthritis model. After 9 days of treatment, the anti-inflammatory effect of S. angustifolia dichloromethane-methanol extract was 72% at a dose of 100 mg/kg, a recovery of 55% was observed with methotrexate (5.0 mg/kg), and the anti-inflammatory effect for tomentin was dose-dependent with a median effective dose of 10.32 mg/kg. The concentration of pro-inflammatory cytokines interleukin-1β and tumor necrosis factor alpha in the left joint of groups treated with S. angustifolia dichloromethane-methanol extract and tomentin at different doses was significantly lower than that detected in the group damaged with kaolin/carrageenan, and the concentration of interleukin-10 and interleukin-4 (anti-inflammatory cytokines) was significantly higher. The drop in mean body weight of mice treated with methotrexate (−4.34±0.47 g) was higher in comparison with the kaolin/carrageenan group (−2.40±0.29 g). On the other hand, the mean body weight of mice treated with S. angustifolia dichloromethane-methanol extract (−1.19±0.17 g) was similar, and mice treated with tomentin (0.19±0.11 g) was lower. The dichloromethane-methanol extract and tomentin isolated from S. angustifolia diminished joint edema induced by kaolin/carrageenan, possibly by acting as an immunomodulatory of the inflammatory response.
Aktuelle Änderungen der S3-Leitlinie Maligne Ovarialtumore (Version 2.0 - Oktober 2016)
Authors: Sehouli Jalid , Mahner Sven , Harter Philip , Hilpert Felix , du Bois Andreas , Reuss Alexander , Wagner Uwe
Published: May 2017

Basierend auf den aktuellen Publikationen zur Tumorgenese, Diagnostik, Therapie und Nachsorge wurde die aktuelle, interdisziplinär und interprofessionell erstellte S3-Leitlinie aktualisiert. Im vorliegenden Artikel werden praxisrelevante Änderungen diskutiert.

Besonders wird auf Aspekte des Screenings, Patienteninformation, Prävention, Pathologie, prognostische Faktoren, Pathologie, Operation, Rezidivtherapie sowie Nachsorge und Langzeitüberleben eingegangen.
Interventionelle Therapie des Schlaganfalls
Authors: Erbguth Frank
Published: May 2017

Die mechanische Thrombektomie (MT) von Verschlüssen großer Hirngefäße in Kombination mit der systemischen intravenösen Thrombolyse (IVT) hat sich in den letzten Jahren zu einem hocheffektiven evidenzbasierten Verfahren der Akuttherapie des Hirninfarkts entwickelt. Die Chance auf ein behinderungsfreies Überleben der in der Regel schwer betroffenen Patienten wird um ca. 75% erhöht. Allerdings stellt die MT nur für maximal 1-5 % der Patienten mit ischämischem Schlaganfall eine Therapieoption dar. Die Akuttherapie der ischämischen Schlaganfälle fußt daher weiter hauptsächlich auf den etablierten Maßnahmen wie Stroke-Unit-Behandlung, frühe Sekundärprophylaxe und IVT. Die flächendeckende Versorgung der Kandidaten für eine MT stellt eine logistische Herausforderung dar, zu denen auch die Optimierung der interdisziplinären Zusammenarbeit gehört. Die MT hat auch Implikationen für die Akuttherapie oral antikoagulierter Schlaganfallpatienten. Eine moderne Schlaganfallbehandlung erfordert die interdisziplinäre Kooperation von Neurologie, Neuroradiologie, Neurochirurgie, Kardiologie, Gefäßchirurgie und Anästhesie.
Diagnostik und Therapie des Vulvakarzinoms
Authors: Mehlhorn Grit , Schulmeyer Carla , Koch Martin , Renner Simone , Gaß Paul , Beckmann Matthias
Published: May 2017

Mit einer Inzidenz von 5,8/100 000 Frauen/Jahr ist das Vulvakarzinom das vierthäufigste Genitalkarzinom der Frau. Meist werden Vulvakarzinome in einem frühen Stadium diagnostiziert. Häufigstes Symptom ist der therapieresistente Pruritus, perineale Schmerzen und/oder beim Sitzen, Dysurie und Brennen. Bei der klinischen Inspektion sollte das komplette äußere Genitale mit Vagina, Perineum, Anus sowie die Zervix inspiziert werden. Liegt eine VIN1, LSIL (vulväre intraepitheliale Neoplasie Grad 1, low-grade squamous intraepithelial lesion) ohne Symptome vor, sind regelmäßige Kontrollen ausreichend. Bei symptomatischer LSIL, HPV-assoziierter VIN2 oder VIN3 (vulväre intraepitheliale Neoplasie Grad 2 oder 3, high-grade squamous intraepithelial lesion) kann eine Laserevaporisation erfolgen. Eine komplette Vulvektomie sollte nur bei multizentrischen Tumoren erfolgen. Eine systematische Lymphonodektomie ist ab Stadium T1b mit Infiltrationstiefe > 1 mm empfohlen. Eine adjuvante Radiotherapie der Primärtumorregion sollte bei non-in-sano-Situation durchgeführt werden, falls eine Nachresektion aus funktionellen Gründen oder Patientenwunsch nicht möglich ist. Eine lebenslange Nachsorge ist notwendig, denn jede dritte Patientin mit Vulvakarzinom erleidet ein Rezidiv. Als Therapie des Lokalrezidivs ohne Beteiligung von Anus, Urethra oder Lymphknoten sollte eine operative Resektion mit R0-Situation angestrebt werden.
Zertifizierte Gynäkologische Krebszentren
Authors: Mensah Jumana , Wesselmann Simone , Beckmann Matthias
Published: May 2017

Mit dem Zertifizierungssystem für Gynäkologische Krebszentren wird das gesamte Versorgungsspektrum der gynäkologischen Krebserkrankungen abgebildet. In bislang 133 spezialisierten Zentren im In- und Ausland wird qualitätsgesicherte, leitliniengerechte Versorgung für Patientinnen mit unterschiedlichen gynäkologischen Malignomen gewährleistet. Mit den 2017 neu eingeführten, leitlinienbasierten Kennzahlen für Patientinnen mit Vulvakarzinom wird erstmals die Qualität der Behandlung auch für diese Patientinnengruppe spezifisch erfasst. Diese entitätsumfassenden Kennzahlen bilden mit den übergreifenden Anforderungen an die Diagnostik und Therapie aller gynäkologischer Tumore und den bereits bestehenden Qualitätsindikatoren für Ovarial- und Zervixkarzinome die Voraussetzung für eine umfassende Qualitätssicherung und -verbesserung.
Überall ist Sex
Authors: Hardinghaus Christian
Published: May 2017

Mit dem österreichischen Neurologen Sigmund Freud präsentieren wir in dieser Ausgabe einen Arzt, mit dem wohl die Allermeisten etwas anfangen können. Einen Freudschen Versprecher hat sich wohl auch jeder schon geleistet und sich eventuell sogar dafür geschämt. Während angehende Psychologen heute noch Freuds Theorien über das Unterbewusstsein lernen, fasziniert die Freudsche Traumdeutung weiterhin in Horoskopen, im Tarotspiel oder in der Astrologie. Über 15 Biografien über den Begründer der Psychoanalyse erschienen und mehr als 30 Sachbücher. Fünf Spielfilme über sein Leben wurden gedreht und zuletzt sogar eine Hörspielserie. Unzählige Autoren und Regisseure haben Freuds Symbolik benutzt, um fantastische Stoffe zu kreieren. Vielleicht interessieren uns die teilweise abstrusen Theorien so sehr, weil sich bei Freud mehr oder weniger alles um Sexualität zu drehen scheint. Tatsächlich begann seine Karriere mit dieser Thematik. Sein Spezialgebiet: Das Sexleben von Aalen.
Day in, day out: pop goes the city
Authors: Redhead Stephen
Published: May 2017

Today we are inhabiting an era of accelerated digitized global capitalism, what Slavoj Zizek calls the “new dark ages” and Alain Badiou refers to as the “dialectics of black”. The need is for updated new theorization of this formation and better empirical accounts. This essay looks at the recent development of digital leisure cultures around popular music in Manchester (UK) especially since the global financial crisis, which still permeates our globe in unforseen ways. This understanding of the contours of a rapidly accelerated digitized capitalism utilizes various resources. Building on this idea this article argues that what we see as “claustropolitanism” (the feeling that we want to escape the planet because we are now so foreclosed) is fast becoming a post-crash cultural condition spreading globally. For Paul Virilio, who is claustrophobic, Joy Division’s mantra “feel it closing in” from “Digital” is personal, but the mediatised global pop culture is also experiencing the same feeling. This paper draws on the author’s long-term empirical research into the city of Manchester and its popular cultural history to tease out some theoretical implications for the study of digital society and capitalism in general.
Families of quasi-exactly solvable extensions of the quantum oscillator in curved spaces
Authors: Quesne C.
Published: May 2017

We introduce two new families of quasi-exactly solvable (QES) extensions of the oscillator in a d-dimensional constant-curvature space. For the first three members of each family, we obtain closed-form expressions of the energies and wavefunctions for some allowed values of the potential parameters using the Bethe ansatz method. We prove that the first member of each family has a hidden sl(2, ℝ) symmetry and is connected with a QES equation of the first or second type, respectively. One-dimensional results are also derived from the d-dimensional ones with d≥2, thereby getting QES extensions of the Mathews-Lakshmanan nonlinear oscillator.
Compact, high-repetition-rate source for broadband sum-frequency generation spectroscopy
Authors: Heiner Zsuzsanna , Petrov Valentin , Mero Mark
Published: May 2017

We present a high-efficiency optical parametric source for broadband vibrational sum-frequency generation (BB-VSFG) for the chemically important mid-infrared spectral range at 2800–3600 cm−1 to study hydrogen bonding interactions affecting the structural organization of biomolecules at water interfaces. The source consists of a supercontinuum-seeded, dual-beam optical parametric amplifier with two broadband infrared output beams and a chirped sum-frequency mixing stage providing narrowband visible pulses with adjustable bandwidth. Utilizing a pulse energy of only 60 μJ from a turn-key, 1.03-μm pump laser operating at a repetition rate of 100 kHz, the source delivers 6-cycle infrared pulses at 1.5 and 3.2 μm with pulse energies of 4.6 and 1.8 μJ, respectively, and narrowband pulses at 0.515 μm with a pulse energy of 5.0 μJ. The 3.2-μm pulses are passively carrier envelope phase stabilized with fluctuations at the 180-mrad level over a 10-s time period. The 1.5-μm beamline can be exploited to deliver pump pulses for time-resolved studies after suitable frequency up-conversion. The high efficiency, stability, and two orders of magnitude higher repetition rate of the source compared to typically employed systems offer great potential for providing a boost in sensitivity in BB-VSFG experiments at a reduced cost.
Structure of irreducibly covariant quantum channels for finite groups
Authors: Mozrzymas Marek , Studziński Michał , Datta Nilanjana
Published: May 2017

We obtain an explicit characterization of linear maps, in particular, quantum channels, which are covariant with respect to an irreducible representation (U) of a finite group (G), whenever U⊗Uc is simply reducible (with Uc being the contragradient representation). Using the theory of group representations, we obtain the spectral decomposition of any such linear map. The eigenvalues and orthogonal projections arising in this decomposition are expressed entirely in terms of representation characteristics of the group G. This in turn yields necessary and sufficient conditions on the eigenvalues of any such linear map for it to be a quantum channel. We also obtain a wide class of quantum channels which are irreducibly covariant by construction. For two-dimensional irrreducible representations of the symmetric group S(3), and the quaternion group Q, we also characterize quantum channels which are both irreducibly covariant and entanglement breaking.
Changes in perceptual sensitivity related to spatial cues depends on subcortical activity
Authors: Lovejoy Lee P. , Krauzlis Richard J.
Published: May 2017

Significance

Our paper addresses an important question about the brain circuits for visual spatial attention: what are the mechanisms that make it possible to focus on some visual objects and ignore others? Recent work suggests that cortical and subcortical areas might make distinct contributions to attention: some cortical areas may be responsible for changes in perceptual sensitivity whereas other cortical and subcortical areas may control how subjects select between visual objects. Contrary to this suggestion, our results demonstrate that activity from a subcortical structure in the primate, the superior colliculus, is also necessary to produce changes in perceptual sensitivity in an attention-cueing paradigm. Thus, attention-related changes in perceptual sensitivity are not accomplished by cortical areas alone but also depend on subcortical signals.
Reassessment of 20th century global mean sea level rise
Authors: Dangendorf Sönke , Marcos Marta , Wöppelmann Guy , Conrad Clinton P. , Frederikse Thomas , Riva Riccardo
Published: May 2017

Significance

Estimates of global mean sea level (GMSL) before the advent of satellite altimetry vary widely, mainly because of the uneven coverage and limited temporal sampling of tide gauge records, which track local sea level rather than the global mean. Here we introduce an approach that combines recent advances in solid Earth and geoid corrections for individual tide gauges with improved knowledge about their geographical representation of ocean internal variability. Our assessment yields smaller trends before 1990 than previously reported, leading to a larger overall acceleration; identifies three major explanations for differences with previous estimates; and reconciles observational GMSL estimates with the sum of individually modeled contributions from the Coupled Model Intercomparison Project 5 database for the entire 20th century.
Diet Niche Width and Individual Specialization of Brook Trout in Adirondack Lakes
Authors: Jirka Kurt J. , Kraft Clifford E.
Published: May 2017

We evaluated diet niche width, individual diet specialization, and diet composition in six lake populations of Brook Trout Salvelinus fontinalis, a generalist predator known to exhibit benthic and pelagic trophic specialization. Population diet niche width was broad and similar across all lakes, contrasting with that of individual fish, which exhibited specialized diets in comparison with their population and other individuals. Overall, the degree of individual diet specialization was high compared with that of other fishes. The degree of individual diet specialization did not differ among study populations, although it was generally reduced in spring. Individual diet specialization was consistent across fish sizes despite observed shifts in diet composition with increasing fish length. Population diet composition varied among lakes but was consistent within lakes in all years during the 3‐year study period with regard to season and fish size. The consistency and stability in measures of population diet niche width, degree of individual diet specialization, and population diet composition for Brook Trout indicate that these metrics provide useful tools for characterizing fish foraging and measuring how it changes in response to biotic and abiotic perturbations.

Received August 11, 2016; accepted January 20, 2017 Published online May 22, 2017
CRISPRcloud: a secure cloud-based pipeline for CRISPR pooled screen deconvolution
Authors: Jeong Hyun-Hwan , Kim Seon Young , Rousseaux Maxime W C , Zoghbi Huda Y , Liu Zhandong
Published: May 2017

We present a user-friendly, cloud-based, data analysis pipeline for the deconvolution of pooled screening data. This tool, CRISPRcloud, serves a dual purpose of extracting, clustering and analyzing raw next generation sequencing files derived from pooled screening experiments while at the same time presenting them in a user-friendly way on a secure web-based platform. Moreover, CRISPRcloud serves as a useful web-based analysis pipeline for reanalysis of pooled CRISPR screening datasets. Taken together, the framework described in this study is expected to accelerate development of web-based bioinformatics tool for handling all studies which include next generation sequencing data.

Availability and implementation

http://crispr.nrihub.org

Supplementary information

Supplementary data are available at Bioinformatics online.
DNA sequence+shape kernel enables alignment-free modeling of transcription factor binding
Authors: Ma Wenxiu , Yang Lin , Rohs Remo , Noble William Stafford
Published: May 2017

Motivation

Transcription factors (TFs) bind to specific DNA sequence motifs. Several lines of evidence suggest that TF-DNA binding is mediated in part by properties of the local DNA shape: the width of the minor groove, the relative orientations of adjacent base pairs, etc. Several methods have been developed to jointly account for DNA sequence and shape properties in predicting TF binding affinity. However, a limitation of these methods is that they typically require a training set of aligned TF binding sites.

Results

We describe a sequence + shape kernel that leverages DNA sequence and shape information to better understand protein-DNA binding preference and affinity. This kernel extends an existing class of k-mer based sequence kernels, based on the recently described di-mismatch kernel. Using three in vitro benchmark datasets, derived from universal protein binding microarrays (uPBMs), genomic context PBMs (gcPBMs) and SELEX-seq data, we demonstrate that incorporating DNA shape information improves our ability to predict protein-DNA binding affinity. In particular, we observe that (i) the k-spectrum + shape model performs better than the classical k-spectrum kernel, particularly for small k values; (ii) the di-mismatch kernel performs better than the k-mer kernel, for larger k; and (iii) the di-mismatch + shape kernel performs better than the di-mismatch kernel for intermediate k values.

Availability and implementation

The software is available at https://bitbucket.org/wenxiu/sequence-shape.git.

Supplementary information

Supplementary data are available at Bioinformatics online.
ASAP: a web-based platform for the analysis and interactive visualization of single-cell RNA-seq data
Authors: Gardeux Vincent , David Fabrice P A , Shajkofci Adrian , Schwalie Petra C , Deplancke Bart
Published: May 2017

Motivation

Single-cell RNA-sequencing (scRNA-seq) allows whole transcriptome profiling of thousands of individual cells, enabling the molecular exploration of tissues at the cellular level. Such analytical capacity is of great interest to many research groups in the world, yet these groups often lack the expertise to handle complex scRNA-seq datasets.

Results

We developed a fully integrated, web-based platform aimed at the complete analysis of scRNA-seq data post genome alignment: from the parsing, filtering and normalization of the input count data files, to the visual representation of the data, identification of cell clusters, differentially expressed genes (including cluster-specific marker genes), and functional gene set enrichment. This Automated Single-cell Analysis Pipeline (ASAP) combines a wide range of commonly used algorithms with sophisticated visualization tools. Compared with existing scRNA-seq analysis platforms, researchers (including those lacking computational expertise) are able to interact with the data in a straightforward fashion and in real time. Furthermore, given the overlap between scRNA-seq and bulk RNA-seq analysis workflows, ASAP should conceptually be broadly applicable to any RNA-seq dataset. As a validation, we demonstrate how we can use ASAP to simply reproduce the results from a single-cell study of 91 mouse cells involving five distinct cell types.

Availability and implementation

The tool is freely available at asap.epfl.ch and R/Python scripts are available at github.com/DeplanckeLab/ASAP.

Supplementary information

Supplementary data are available at Bioinformatics online.
M2Align: parallel multiple sequence alignment with a multi-objective metaheuristic
Authors: Zambrano-Vega Cristian , Nebro Antonio J , García-Nieto José , Aldana-Montes José F
Published: May 2017

Motivation

Multiple sequence alignment (MSA) is an NP-complete optimization problem found in computational biology, where the time complexity of finding an optimal alignment raises exponentially along with the number of sequences and their lengths. Additionally, to assess the quality of a MSA, a number of objectives can be taken into account, such as maximizing the sum-of-pairs, maximizing the totally conserved columns, minimizing the number of gaps, or maximizing structural information based scores such as STRIKE. An approach to deal with MSA problems is to use multi-objective metaheuristics, which are non-exact stochastic optimization methods that can produce high quality solutions to complex problems having two or more objectives to be optimized at the same time. Our motivation is to provide a multi-objective metaheuristic for MSA that can run in parallel taking advantage of multi-core-based computers.

Results

The software tool we propose, called M2Align (Multi-objective Multiple Sequence Alignment), is a parallel and more efficient version of the three-objective optimizer for sequence alignments MO-SAStrE, able of reducing the algorithm computing time by exploiting the computing capabilities of common multi-core CPU clusters. Our performance evaluation over datasets of the benchmark BAliBASE (v3.0) shows that significant time reductions can be achieved by using up to 20 cores. Even in sequential executions, M2Align is faster than MO-SAStrE, thanks to the encoding method used for the alignments.

Availability and implementation

M2Align is an open source project hosted in GitHub, where the source code and sample datasets can be freely obtained: https://github.com/KhaosResearch/M2Align.

Supplementary information

Supplementary data are available at Bioinformatics online.
A fast and exhaustive method for heterogeneity and epistasis analysis based on multi-objective optimization
Authors: Li Xiong
Published: May 2017

Motivation

The existing epistasis analysis approaches have been criticized mainly for their: (i) ignoring heterogeneity during epistasis analysis; (ii) high computational costs; and (iii) volatility of performances and results. Therefore, they will not perform well in general, leading to lack of reproducibility and low power in complex disease association studies. In this work, a fast scheme is proposed to accelerate exhaustive searching based on multi-objective optimization named ESMO for concurrently analyzing heterogeneity and epistasis phenomena. In ESMO, mutual entropy and Bayesian network approaches are combined for evaluating epistatic SNP combinations. In order to be compatible with heterogeneity of complex diseases, we designed an adaptive framework based on non-dominant sort and top k selection algorithm with improved time complexity O(k*M*N). Moreover, ESMO is accelerated by strategies such as trading space for time, calculation sharing and parallel computing. Finally, ESMO is nonparametric and model-free.

Results

We compared ESMO with other recent or classic methods using different evaluating measures. The experimental results show that our method not only can quickly handle epistasis, but also can effectively detect heterogeneity of complex population structures.

Availability and implementation

https://github.com/XiongLi2016/ESMO/tree/master/ESMO-common-master.
Systemic Inflammatory and Th17 Immune Activation among Patients Treated for Lumbar Radiculopathy Exceeds that of Patients Treated for Persistent Postoperative Neuropathic Pain
Authors: Shamji Mohammed F. , Guha Daipayan , Paul Darcia , Shcharinsky Alina
Published: May 2017

BACKGROUND:The pathophysiology of lumbar radiculopathy includes both mechanical compression and biochemical irritation of apposed neural elements. Inflammatory and immune cytokines have been implicated, induced by systemic exposure of immune-privileged intervertebral disc tissue. Surgical intervention provides improved symptoms and quality of life, but persistent postoperative neuropathic pain (PPNP) afflicts a significant fraction of patients.

OBJECTIVE:To compare the inflammatory and immune phenotypes among patients undergoing structural surgery for lumbar radiculopathy and spinal cord stimulation for neuropathic pain.

METHODS:Consecutive patients undergoing surgical intervention for lumbar radiculopathy or neuropathic pain were studied. Demographic data included age, gender, and VAS and neuropathic pain scores. Serum was evaluated for cytokine levels (IL-6, Il-17, TNF-α) and cellular content [white blood cell (WBC)/differential, lymphocyte subtypes]. The primary analysis differentiated molecular and cellular profiles between radiculopathy and neuropathic pain patients. Subgroup analysis within the surgical radiculopathy population compared those patients achieving relief of symptoms and those with PPNP.

RESULTS:Heightened IL-6, Il-17, and TNF-α levels were observed for the lumbar radiculopathy group compared with the neuropathic pain group. This was complemented by higher WBC count and a greater fraction of Th17 lymphocytes among radiculopathy patients. In the lumbar discectomy subgroup, pain relief was seen among patients with preoperatively elevated IL-17 levels. Those patients with PPNP refractory to surgical discectomy exhibited normal cytokine levels.

CONCLUSION:Differences in Th17 immune activation are seen among radiculopathy and neuropathic pain patients. These cellular and molecular profiles may be translated into biomarkers to improve patient selection for structural spine surgery.
Complementation of CTB7 in the Maize Pathogen Cercospora zeina Overcomes the Lack of In Vitro Cercosporin Production
Authors: Swart Velushka , Crampton Bridget G. , Ridenour John B. , Bluhm Burt H. , Olivier Nicholas A. , Meyer J. J. Marion , Berger Dave K.
Published: May 2017

Gray leaf spot (GLS), caused by the sibling species Cercospora zeina or Cercospora zeae-maydis, is cited as one of the most important diseases threatening global maize production. C. zeina fails to produce cercosporin in vitro and, in most cases, causes large coalescing lesions during maize infection, a symptom generally absent from cercosporin-deficient mutants in other Cercospora spp. Here, we describe the C. zeina cercosporin toxin biosynthetic (CTB) gene cluster. The oxidoreductase gene CTB7 contained several insertions and deletions as compared with the C. zeae-maydis ortholog. We set out to determine whether complementing the defective CTB7 gene with the full-length gene from C. zeae-maydis could confer in vitro cercosporin production. C. zeina transformants containing C. zeae-maydis CTB7 were generated by Agrobacterium tumefaciens–mediated transformation and were evaluated for in vitro cercosporin production. When grown on nitrogen-limited medium in the light—conditions conducive to cercosporin production in other Cercospora spp.—one transformant accumulated a red pigment that was confirmed to be cercosporin by the KOH assay, thin-layer chromatography, and ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry. Our results indicated that C. zeina has a defective CTB7, but all other necessary machinery required for synthesizing cercosporin-like molecules and, thus, C. zeina may produce a structural variant of cercosporin during maize infection.
Interaction of Onion Cultivar and Growth Stages on Incidence of Pantoea ananatis Bulb Infection
Authors: Stumpf Spencer , Gitaitis Ron , Coolong Timothy , Riner Cliff , Dutta Bhabesh
Published: May 2017

Center rot, caused by Pantoea ananatis, has been one of the most important bacterial diseases of onion leading to considerable economic losses. Symptoms can be expressed in the onion foliage and bulb, with the pathogen moving from the infected leaves to bulb scales. However, little is known regarding which growth stage the plant is most susceptible to bulb infection and if there are differences in susceptibility to bulb infection among sweet onion cultivars. In this study, five cultivars of sweet onion (Pirate, Sweet Harvest, 1518, Granex YPRR, and 1407) were inoculated by clipping the tips of onion foliage and depositing 1 ml of 1 × 108 CFU/ml of P. ananatis suspension into the central leaf cavity. The inoculations were done at three growth stages (first leaf senescence, bulb initiation, and bulb swelling). Center rot incidence was assessed for precured and cured onion bulbs. In addition, total bulb incidence of center rot for each cultivar inoculated at three growth stages were also calculated. Total bulb center rot incidence was significantly higher for Granex YPRR (84%) compared with other cultivars. Also, cultivars 1518 (49%) and 1407 (33%) had significantly lower incidence of bulb infection compared with other tested cultivars. Onions were significantly more susceptible to bulb infection when inoculated during first leaf senescence (62%) as compared with bulb initiation (37%) and bulb swelling (31%) stages in precured bulbs (P = 0.041). Significantly higher incidence of center rot was observed for bulbs whose foliage were inoculated during first leaf senescence stage (64%) compared with bulb initiation (55%) and bulb swelling (52%) stages (P = 0.048). Interactions between onion cultivar and inoculation stage on center rot bulb incidence were not significant (P ≥ 0.218), when evaluated at different assessment periods. However, different cultivars displayed significant variability in susceptibility to bulb infection. The outcomes of this study may have implications in devising management strategies aimed at protecting most susceptible onion growth stages against P. ananatis.
Aggressiveness of Colletotrichum sublineola Strains from Sorghum bicolor and S. halepense to Sweet Sorghum Variety Sugar Drip, and Their Impact on Yield
Authors: Xavier K. V. , Pfeiffer T. , Parreira D. F. , Chopra S. , Vaillancourt L.
Published: May 2017

Sweet sorghum (Sorghum bicolor) has been grown in the southeastern United States for more than 150 years on a relatively limited scale, primarily for forage and for the production of table syrup. However, interest in the crop has increased recently due to its potential as a feedstock for biofuels. Colletotrichum sublineola is the causal agent of anthracnose on cultivated sorghum and on the wild sorghum relative Johnsongrass (S. halepense). Anthracnose is an important disease of grain sorghum worldwide, but little is known about its impact on sweet sorghum in the U.S. The aggressiveness of four C. sublineola isolates collected from sweet and grain sorghum and from Johnsongrass at various locations across Kentucky was measured as disease incidence and severity on the susceptible heirloom sweet sorghum inbred Sugar Drip in inoculated field trials. The isolate from sweet sorghum was the most aggressive, while the two Johnsongrass isolates caused only minimal disease symptoms. Disease incidences of up to 99%, and severities of up to 16.7% of leaf area affected, had no negative effect on the yield of biomass, grain, juice, or Brix. Removal of sorghum seed heads increased Brix in the stalks and leaves, but did not affect susceptibility to anthracnose. The same group of fungal isolates was evaluated for aggressiveness in greenhouse assays on juvenile plants, and in the laboratory on seedlings and detached leaf sheaths. These protocols will be useful for prescreening sorghum germplasm for new sources of resistance or for characterizing the aggressiveness of new fungal isolates.
Modeling Virus Coinfection to Inform Management of Maize Lethal Necrosis in Kenya
Authors: Hilker Frank M. , Allen Linda J. S. , Bokil Vrushali A. , Briggs Cheryl J. , Feng Zhilan , Garrett Karen A. , Gross Louis J. , Hamelin Frédéric M. , Jeger Michael J. , Manore Carrie A. , Power Alison G. , Redinbaugh Margaret G. , Rúa Megan A. , Cunniffe Nik J.
Published: May 2017

Maize lethal necrosis (MLN) has emerged as a serious threat to food security in sub-Saharan Africa. MLN is caused by coinfection with two viruses, Maize chlorotic mottle virus and a potyvirus, often Sugarcane mosaic virus. To better understand the dynamics of MLN and to provide insight into disease management, we modeled the spread of the viruses causing MLN within and between growing seasons. The model allows for transmission via vectors, soil, and seed, as well as exogenous sources of infection. Following model parameterization, we predict how management affects disease prevalence and crop performance over multiple seasons. Resource-rich farmers with large holdings can achieve good control by combining clean seed and insect control. However, crop rotation is often required to effect full control. Resource-poor farmers with smaller holdings must rely on rotation and roguing, and achieve more limited control. For both types of farmer, unless management is synchronized over large areas, exogenous sources of infection can thwart control. As well as providing practical guidance, our modeling framework is potentially informative for other cropping systems in which coinfection has devastating effects. Our work also emphasizes how mathematical modeling can inform management of an emerging disease even when epidemiological information remains scanty.

[Formula: see text] Copyright © 2017 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Hypersensitivity reactions to gadolinium-based contrast agents
Authors: Fok Jie Shen , Smith William B.
Published: May 2017

Purpose of review

Gadolinium-based contrast agents (GBCAs) have been utilized since the late 1980s to enhance the diagnostic value of MRI studies. They are known to have excellent safety profile and serious adverse reactions are uncommon despite widespread global use. However, immediate hypersensitivity reactions are well described in the literature, with urticaria the most common manifestation. Anaphylaxis can occur, though fatality is extremely rare. This review explores the incidence of GBCA-related hypersensitivity reactions and highlights potential risk factors.

Recent findings

Emerging evidence suggests that immediate hypersensitivity reactions to GBCAs can be IgE-mediated. Skin testing may be informative in confirmation of causality and revealing cross-reactivity patterns.

GBCA hypersensitivity is infrequent but can be serious. Familiarity with management of acute hypersensitivity reactions may be lifesaving. Appropriate use of diagnostic testing can be used to guide future management of patients who have suffered from such reactions.
Precision medicine in pediatric rheumatology
Authors: Yeo Joo Guan , Ng Chin Teck , Albani Salvatore
Published: May 2017

Purpose of review

Precision medicine is the tailoring of medical care to subcategories of disease. In pediatric rheumatology, these subcategories must first be defined by their specific molecular immunological profiles, and then the effects of growth and puberty, developmental immunological changes, and differences in treatment options and adherence considered when designing therapeutic strategies. In the present review, we summarize the unmet needs in pediatric rheumatology before such precision medical care can be effectively delivered to affected patients.

Recent findings

The current clinical classification of pediatric rheumatic diseases does not provide all the information necessary for prognostication and accurate therapeutic selection. Many studies have highlighted the molecular differences between disease subcategories and the dissimilarities in the molecular manifestations of the same disease between patients. Harnessing such discoveries by collaborating with various research networks and laboratories is required to interrogate the multifactorial nature of rheumatic diseases in a holistic manner.

Integration of big data sets generated from well defined pediatric cohorts with rheumatic diseases using different high-dimensional technological platforms will help to elucidate the underlying disease mechanisms. Distilling these data will be necessary for accurate disease stratification and will have a positive impact on prognosis and treatment choice.
Surgical Management of Thoracolumbar Kyphosis in Patients With Mucopolysaccharidosis
Authors: Williams Nicole , Cundy Peter J. , Eastwod Deborah M.
Published: May 2017

Study Design.

Systematic review.

Objective.

To determine the indications and outcomes for surgical treatment of thoracolumbar kyphosis in patients with mucopolysaccharidoses (MPS) to define future studies.

Summary of Background Data.

Improvements in the medical treatment of MPS have increased lifespan and improved quality of life for many patients, but with no effect on thoracolumbar kyphosis. A greater number of these challenging patients may now be considered spinal surgical candidates.

Methods.

In accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, a PubMed database search was conducted using relevant keywords to identify articles describing MPS patients with thoracolumbar kyphosis treated surgically. Information was collected regarding demographics, indications for surgery, surgical details and outcomes.

Results.

Sixteen articles describing 58 patients were included for review. The median age at surgery was 7 years (range 2.4–65 years) and median follow up was 3.7 years (range 7 weeks–10.3 years). The most commonly reported surgical indication was progression of deformity in 39/58 patients (67%). Preoperative neurological compromise was reported in 7/58 (12%) patients and resolved completely postoperatively in all pediatric patients. Three pediatric patients had died before final follow up. Postoperative paraplegia was reported in 2/51 patients who were neurologically intact preoperatively. Additional significant perioperative medical complications were reported in nine patients.

Conclusion.

Thoracolumbar spinal surgery is most commonly performed in MPS I. Preoperative neurological compromise associated with thoracolumbar kyphosis was reported only in MPS IV and VI, where it was associated with factors other than the degree of kyphosis. Perioperative complications are common, may be catastrophic and relate to the complexity of the MPS condition. The indications for thoracolumbar kyphosis surgery in other conditions of short stature cannot be extrapolated to MPS patients.

Level of Evidence: 4