bluuebunny/crossref_metadata_2025_split huggingface dataset:
A systems-level integrative framework for genome-wide DNA methylation and gene expression data identifies differential gene expression modules under epigenetic control
Authors: Jiao Yinming , Widschwendter Martin , Teschendorff Andrew E. 
Published: May 2014

Motivation: There is a growing number of studies generating matched Illumina Infinium HumanMethylation450 and gene expression data, yet there is a corresponding shortage of statistical tools aimed at their integrative analysis. Such integrative tools are important for the discovery of epigenetically regulated gene modules or molecular pathways, which play key roles in cellular differentiation and disease.
Results: Here, we present a novel functional supervised algorithm, called Functional Epigenetic Modules (FEM), for the integrative analysis of Infinium 450k DNA methylation and matched or unmatched gene expression data. The algorithm identifies gene modules of coordinated differential methylation and differential expression in the context of a human interactome. We validate the FEM algorithm on simulated and real data, demonstrating how it successfully retrieves an epigenetically deregulated gene, previously known to drive endometrial cancer development. Importantly, in the same cancer, FEM identified a novel epigenetically deregulated hotspot, directly upstream of the well-known progesterone receptor tumour suppressor pathway. In the context of cellular differentiation, FEM successfully identifies known endothelial cell subtype-specific gene expression markers, as well as a novel gene module whose overexpression in blood endothelial cells is mediated by DNA hypomethylation. The systems-level integrative framework presented here could be used to identify novel key genes or signalling pathways, which drive cellular differentiation or disease through an underlying epigenetic mechanism.
Availability and implementation: FEM is freely available as an R-package from http://sourceforge.net/projects/funepimod.
Contact: andrew@picb.ac.cn
Supplementary information: Supplementary Data are available at Bioinformatics online.
Introduction: Marine Harvesting in the Arctic
Authors: Haug Tore , Aschan Michaela , Hoel Alf Håkon , Johansen Torild , Sundet Jan H. 
Published: May 2014

Abstract
In a warmer Arctic, living conditions will change at all trophic levels of the marine ecosystem. Increased air and water temperatures will likely substantially reduce ice coverage. Trophic interactions might change and increased competition between resident Arctic species and invasive species seems likely. A theme session on “Marine harvesting in the Arctic” was held at the international Arctic Frontiers Conference in Tromsø, Norway, in January 2013. The theme session partitioned the topic into two sub-sessions: (i) introduced species, immigration and fate of resident species and (ii) prospective harvesting of marine biological resources in the Arctic. The four articles that follow this introduction are based on presentations made at the Arctic Frontiers theme session. These articles cover topics such as: how ice breeding seals (Pagophilus groenlandicus) can cope with ice retention in the Northwest Atlantic, how planktonic stages of the resident polar cod (Boreogadus saida) and the pole-ward expanding Pacific sand lance (Ammodytes hexapterus) may compete for food in the warming Beaufort Sea, and how the introduced red king crab (Paralithodes camtschaticus) disperse in the Barents Sea. The fourth article shows how differences in the life-history strategies of keystone zooplankton species will likely affect future productivity of commercial fisheries in polar regions.
Regulation of the gut microbiota by the mucosal immune system in mice
Authors: Hasegawa Mizuho , Inohara Naohiro 
Published: May 2014

Abstract
The benefits of commensal bacteria to the health of the host have been well documented, such as providing stimulation to potentiate host immune responses, generation of useful metabolites, and direct competition with pathogens. However, the ability of the host immune system to control the microbiota remains less well understood. Recent microbiota analyses in mouse models have revealed detailed structures and diversities of microbiota at different sites of the digestive tract in mouse populations. The contradictory findings of previous studies on the role of host immune responses in overall microbiota composition are likely attributable to the high β-diversity in mouse populations as well as technical limitations of the methods to analyze microbiota. The host employs multiple systems to strictly regulate their interactions with the microbiota. A spatial segregation between the host and microbiota is achieved with the mucosal epithelium, which is further fortified with a mucus layer on the luminal side and Paneth cells that produce antimicrobial peptides. When commensal bacteria or pathogens breach the epithelial barrier and translocate to peripheral tissues, the host immune system is activated to eliminate them. Defective segregation and tissue elimination of commensals result in exaggerated inflammatory responses and possibly death of the host. In this review, we discuss the current understanding of mouse microbiota, its common features with human microbiota, the technologies utilized to analyze microbiota, and finally the challenges faced to delineate the role of host immune responses in the composition of the luminal microbiota.
Starbursts triggered by intergalactic tides andinterstellar compressive turbulence
Authors: Renaud Florent , Bournaud Frédéric , Kraljic Katarina , Duc Pierre-Alain 
Published: May 2014

AbstractUsing parsec-resolution simulations of a typical galaxy merger, we study the triggering of starbursts by connecting the (inter-)galactic dynamics to the structure of the interstellar medium. The gravitational encounter between two galaxies enhances tidal compression over large volumes, which increases and modifies the turbulence, in particular its compressive mode with respect to the solenoidal one. This generates an excess of dense gas leading to intense star formation activity. Along the interaction, the compressive turbulence modifies the efficiency of gas-to-star conversion which, in the Schmidt–Kennicutt diagram, drives the galaxies from the sequence of discs to that of starbursts.
Dissecting the Spitzer colour–magnitude diagrams of extreme Large Magellanic Cloud asymptotic giant branch stars
Authors: Dell'Agli F. , Ventura P. , García Hernández D. A. , Schneider R. , Di Criscienzo M. , Brocato E. , D'Antona F. , Rossi C. 
Published: May 2014

Abstract
We trace the full evolution of low- and intermediate-mass stars (1 ≤ M ≤ 8 M⊙) during the asymptotic giant branch (AGB) phase in the Spitzer two-colour and colour–magnitude diagrams. We follow the formation and growth of dust particles in the circumstellar envelope with an isotropically expanding wind, in which gas molecules impinge upon pre-existing seed nuclei, favour their growth. These models are the first able to identify the main regions in the Spitzer data occupied by AGB stars in the Large Magellanic Cloud (LMC). The main diagonal sequence traced by LMC extreme stars in the [3.6] − [4.5] versus [5.8] − [8.0] and [3.6] − [8.0] versus [8.0] planes is nicely fit by carbon stars models; it results to be an evolutionary sequence with the reddest objects being at the final stages of their AGB evolution. The most extreme stars, with [3.6] − [4.5] &gt; 1.5 and [3.6] − [8.0] &gt; 3, are 2.5–3 M⊙ stars surrounded by solid carbon grains. In higher mass (&gt;3 M⊙) models dust formation is driven by the extent of hot bottom burning (HBB) – most of the dust formed is in the form of silicates and the maximum obscuration phase by dust particles occurs when the HBB experienced is strongest, before the mass of the envelope is considerably reduced.
The incidence of cerebrovascular accidents and second brain tumors in patients with pituitary adenoma: a population-based study
Authors: Brown Paul D. , Blanchard Miran , Jethwa Krishan , Flemming Kelly D. , Brown Cerise A. , Kline Robert W. , Jacobson Debra J. , St. Sauver Jennifer , Pollock Bruce E. , Garces Yolanda I. , Stafford Scott L. , Link Michael J. , Erickson Dana , Foote Robert L. , Laack Nadia N.I. 
Published: May 2014

AbstractBackgroundTo assess the risk of cerebrovascular accidents (CVAs) and second brain tumors (SBTs) in patients with pituitary adenoma after surgery or radiotherapy.MethodsA cohort of 143 people from Olmsted County, who were diagnosed with pituitary adenoma between 1933 and 2000, was studied. Only patients from Olmsted County were included because of the unique nature of medical care in Olmsted County, which allows the ascertainment of virtually all cases of pituitary adenoma for this community's residents and comparisons to the general population in the county. Surgical resection was performed in 76 patients, 29 patients underwent radiotherapy (with 21 undergoing both surgery and radiotherapy), 5 patients were reirradiated, and 59 patients were managed conservatively and observed.ResultsMedian follow-up was 15.5 years. There was no difference in CVA-free survival between treatment groups. On univariate analysis age > 60 years (hazard ratio [HR], 11.93; 95% CI, 6.26–23.03; P < .001); male sex (HR, 3.67; 95% CI, 2.03–6.84; P < .001), and reirradiation (HR, 3.41; 95% CI, 1.05–9.68; P = .04) were associated with worse CVA-free survival. In multivariate analysis, only age > 60 years was associated with worse CVA-free survival. Compared with the general population, there was a 4-fold increase in the rate of CVAs in pituitary adenoma patients (HR, 4.2; 95% CI, 2.8–6.1). Two patients developed SBT (an irradiated patient and a surgically managed patient).ConclusionCVA is a significant risk for patients with pituitary tumors, but treatment does not seem to impact the risk. Even with long-term follow-up, SBTs are a rare event regardless of treatment modality.
Cancer around the brain
Authors: Grisold Wolfgang , Grisold Anna 
Published: May 2014

AbstractBackgroundNeuro-oncologists are familiar with primary brain tumors, intracerebral metastases meningeal carcinomatosis and extracerebral intracranial tumors as meningeoma. For these conditions, and also some other rare tumor entities several treatment options exist. Cancer can also involve structures around the brain as the dura, the base of the skull, the cavities of the skull and tissue around the bony skull, the skin, the tissue of the neck. and either compress, invade or spread in the central or peripheral nervous system.MethodsA systematic literature research was conducted determining symptoms and signs, tumor sites of nerve invasion, tumor types, diagnostic techniques, mechanisms of nerve invasion, and important differential diagnosis. Additional cases from own experience were added for illustration.ResultsThe mechanisms of tumor invasion of cranial nerves is heterogenous and not only involves several types of invasion, but also spread along the cranial nerves in antero- and retrograde fashion and even spread into different nerve territories via anastomosis. In addition the concept of angiosomas may have an influence on the spread of metastases.ConclusionIn addition to the well described tumor spread in meningeal carcinomatosis and base of the skull metastases, dural spread, lesions of the bony skull, the cavities of the skull and skin of the face and tissue of the neck region need to be considered, and have an impact on therapeutic decisions.
Cleopatra
Authors: Roller Duane W. 
Published: May 2014

Cleopatra (Kleopatra) VII is arguably the most famous woman from classical antiquity, and one of the most familiar personalities in human history. She is best known through the extensive art and literature that was generated after her death. The information from Greek and Roman sources about Cleopatra herself is surprisingly sparse and generally misinterpreted. She is familiar today largely through her representation by Shakespeare and in modern film, as a seductress who ruined the men in her life and destroyed her kingdom, an erroneous depiction that is in large part the result of extremely eloquent opponents and male-dominated historiography. More accurately, she was a capable administrator and military commander, a linguist who knew a dozen languages, and a published scholarly author. Yet she was also the last ruler of her kingdom, and her defeat by the Romans led to the destruction of her reputation. She ruled for twenty-one years, from 51 to 30 bce, and skillfully attempted to salvage her dying kingdom in the face of growing Roman power and involvement in the affairs of the eastern Mediterranean. Best remembered for her liaisons with Julius Caesar, and Marcus Antonius (Mark Antony), she in fact carefully chose her partners in order to produce heirs who could carry on the kingdom. But her own plans became caught up in the ongoing civil war at Rome, beginning with the assassination of Caesar in 44 bce. Her original relations with Antonius were a matter of stabilizing her kingdom and creating a mutually beneficial relationship between Egypt and Rome, but the personal involvement between the two eventually hampered these plans, and allowed Octavian (the future emperor Augustus), in power in Rome, to marginalize Antonius (who was his brother-in-law) and to claim that he was being destroyed by an eastern seductress. Matters quickly moved out of control in the 30s bce, and eventually a Roman invasion of Greece was mounted. Cleopatra attempted to disassociate herself from Antonius in order to salvage her kingdom, but would not give it over to Octavian, and was driven to suicide in August of 30 bce at the age of thirty-nine. Her son Kaisarion ruled for a few weeks, but soon the Romans took over the kingdom. Although the Roman literary machine turned her into a dangerous monster who almost destroyed Rome, within Egypt she was honored for centuries.
Interaction of clopidogrel and statins in secondary prevention after cerebral ischaemia – a randomized, double‐blind, double‐dummy crossover study
Authors: Siepmann Timo , Heinke Denise , Kepplinger Jessica , Barlinn Kristian , Gehrisch Siegmund , Grählert Xina , Schwanebeck Uta , Reichmann Heinz , Puetz Volker , Bodechtel Ulf , Gahn Georg 
Published: May 2014

AimsVariability in responsiveness to clopidogrel is a clinical problem in secondary prevention after cerebral ischaemia which has been suggested to be linked to competitive metabolization of clopidogrel and cytochrome P450 (CYP) 3A4‐oxidated statins such as simvastatin. We assessed the hypothesis that simvastatin, in contrast to CYP 2C9‐metabolized fluvastatin, reduces clopidogrel‐mediated platelet inhibition.MethodsWe performed a randomized, double‐blind, double‐dummy, two period crossover study in 13 patients with cerebral ischaemia (8F, 5 M), aged 64.1 ± 8.0 years (mean ± SD). After a 14 day period in which all patients received 75 mg clopidogrel day−1, patients additionally received either 20 mg simvastatin day−1 or 80 mg fluvastatin day−1 for 14 days. Regimens were crossed over after a 14 day wash‐out period and switched regimens were continued for another 14 days. Platelet aggregation, clopidogrel active metabolite (CAM) plasma concentrations and routine laboratory parameters including prothrombin time (PT) Quick percent value were assessed at baseline and following each treatment phase.ResultsClopidogrel reduced platelet aggregation in all patients as expected. Platelet aggregation and CAM plasma concentrations were unaltered when simvastatin or fluvastatin was added to clopidogrel. Simvastatin decreased PT Quick percent value (decrease from 109 ± 10.5% to 103 ± 11%, P < 0.05) when combined with clopidogrel but there was no such change following treatment with fluvastatin and clopidogrel.ConclusionsOur data indicate that treatment with CYP 3A4‐metabolized simvastatin does not jeopardize clopidogrel‐mediated inhibition of platelet aggregation. After co‐administration of simvastatin and clopidogrel we observed a decrease in the PT Quick percent value which could be due to simvastatin‐induced reduction of activity of prothrombin fragment 1 + 2.
Real‐time transrectal ultrasonography‐guided hands‐free technique for focal cryoablation of the prostate
Authors: de Castro Abreu Andre Luis , Bahn Duke , Chopra Sameer , Leslie Scott , Matsugasumi Toru , Gill Inderbir S. , Ukimura Osamu 
Published: May 2014

ObjectivesTo describe, step‐by‐step, our hands‐free technique for focal cryoablation of prostate cancer.Materials and MethodsAfter detailed discussion of its limitations and benefits, consent was obtained to perform focal cryoablation in patients with biopsy‐proven unilateral low‐ to intermediate‐risk prostate cancer. The procedure was performed transperineally, using a hands‐free technique (without an external grid template) under real‐time bi‐plane transrectal ultrasonography (TRUS) guidance, using an argon/helium‐gas‐based third generation cryoablation system. Follow‐up consisted of validated questionnaires, physical examination, PSA measures, multiparametric TRUS and/or magnetic resonance imaging (MRI) and mandatory biopsy.ResultsThe important steps for achieving safety, satisfactory oncological and functional outcomes included: patient selection, including TRUS/MRI fusion target biopsy; thermocouple and cryoprobe placement with a hands‐free technique, allowing delivery in unrestricted angulations according to the prostatic contour, the course of the neurovascular bundle and the rectal wall angle; and hands‐free bi‐plane TRUS probe manipulation to facilitate real‐time monitoring of anatomical landmarks at the ideal angle of the image plane. To achieve a lethal temperature in the known cancer area, while preserving the urinary sphincter, neurovascular bundle, urethra and rectal wall, continuous intraoperative control of the thermocouple temperatures was necessary, as were real‐time TRUS monitoring of ice‐ball size, control of the energy delivered and the use of a warming urethral catheter.ConclusionWe have described step‐by‐step the focal cryoablation of prostate cancer using a hands‐free technique. This technique facilitates the effective delivery of cryoprobes and the intra‐operative real‐time quick manipulation of the TRUS probe.
The Contributions of Explanation and Exploration to Children's Scientific Reasoning
Authors: Legare Cristine H. 
Published: May 2014

AbstractBoth explanation and exploration can foster causal learning, yet the mechanisms underlying these effects are largely unknown, especially in early childhood. In this article, I provide an overview of research on the relation among explanation, exploration, and the development of scientific reasoning. I propose that explaining and exploring operate in tandem as hypothesis‐generating and hypothesis‐testing mechanisms. I review evidence that supports this claim by demonstrating that inconsistency with prior knowledge selectively motivates children to construct explanations, guides discovery‐oriented behavior, and drives the early‐developing capacity to reason scientifically. I conclude with a discussion of the educational applications of research on the development of children's scientific reasoning in informal learning settings.
Der allergologische Notfall – Management der Anaphylaxie
Authors: Werner‐Busse Alexandra , Zuberbier Torsten , Worm Margitta 
Published: May 2014

ZusammenfassungWenn eine Anaphylaxie auftritt, liegt ein allergologischer Notfall vor. Diese ist definiert durch das plötzliche Auftreten allergischer Symptome an zwei oder mehr Organsystemen. Aufgrund der Akuität der Symptome und der potenziellen Lebensbedrohung für den Patienten ergeben sich besondere Anforderungen an die medizinische Betreuung. Die Inzidenz der Anaphylaxie hat in den letzten Jahren zugenommen. Die häufigsten Auslöser der mastzellvermittelten und zumeist histaminabhängigen Anaphylaxie sind Nahrungsmittel, Insektengifte und Medikamente. Der Schweregrad einer Anaphylaxie wird nach Ring und Messmer in vier klinische Stadien eingeteilt, wobei im Stadium I ausschließlich kutane Symptome auftreten, während im Stadium IV eine Schocksituation mit Herzkreislauf‐ und/oder Atemstillstand einsetzt.Die adäquate Therapie der Anaphylaxie muss stadienorientiert erfolgen. Als medikamentöse Erstmaßnahme wird die intramuskuläre Applikation von Adrenalin in die Oberschenkelauflenseite für alle Reaktionen, die nicht nur Haut bzw. Schleimhaut, sondern auch das respiratorische und/oder das Herz‐Kreislauf‐System betreffen, empfohlen. Die weitere medikamentöse Therapie beinhaltet die idealerweise intravenöse Gabe von Antihistaminika und gewichtsadaptiert Kortikosteroiden, zur Selbstbehandlung im Notfall sollten die Präparate als Tabletten vorliegen.
Optimierungspotentiale der Qualitätssicherung in der Zusammenarbeit zwischen Unfallversicherungsträgern und berufsdermatologisch tätigen Ärzten
Authors: Elsner Peter , Aberer Werner , Bauer Andrea , Diepgen Thomas Ludwig , Drexler Hans , Fartasch Manigè , John Swen Malte , Schuhmacher‐Stock Uta , Wehrmann Wolfgang , Weisshaar Elke 
Published: May 2014

ZusammenfassungHintergrundQualitätssicherung ist Aufgabe der Ärzteschaft, aber auch der gesetzlichen Unfallversicherung (GUV). Daten zur Qualität der Interaktion zwischen berufsdermatologisch tätigen Ärzten und Unfallversicherungsträgern stehen nur begrenzt zur Verfügung.Material und MethodikBei 854 Mitgliedern der Arbeitsgemeinschaft für Berufs‐ und Umweltdermatologie in Deutschland wurde im Oktober 2013 eine Online‐Umfrage durchgeführt. Erfasst wurden demographische Daten, die Beurteilung der Zusammenarbeit mit den Trägern der GUV, eine betriebswirtschaftliche Beurteilung der Vergütung berufsdermatologischer Leistungen sowie prioritär zu optimierende Fragestellung(en) in der Zusammenarbeit.ErgebnisseDie Beteiligung an der Umfrage lag bei 182 Teilnehmern (21,3 % der Befragten). Die Zusammenarbeit mit den Unfallversicherungsträgern beurteilten 10,8 % als „sehr gut“, 56,7 % als „gut“, 24,2 % als „befriedigend“, 7,0 % als „ausreichend“ und nur 1,3 % als „mangelhaft“. 93,4 % äußerten sich zu Problemen bzw. Verbesserungspotenzial in der Zusammenarbeit Ihrer Praxis/Klinik mit der GUV. An vorderer Stelle stehen Abrechnungsfragen (44,7 %), gefolgt von Eingriffen in die Behandlungsfreiheit (36,5 %) und dem Behandlungsauftrag im Hautarztverfahren (29,4 %).SchlussfolgerungenOptimierungspotenziale für die Zusammenarbeit zwischen berufsdermatologisch tätigen Ärzten und GUV bestehen in der Vergütung der dermatologischen Leistungen bezüglich der „sprechenden Medizin“, in der Ermöglichung leitliniengerechter Diagnostik und Therapie und in zeitnaher Erteilung von Behandlungsaufträgen im Hautarztverfahren zur Nutzung des therapeutischen Fensters in der Prävention von Berufsdermatosen.