bluuebunny/crossref_metadata_2025_split huggingface dataset:
Controlling the Risk Domain in Pediatric Asthma through Personalized Care
Authors: Szefler Stanley , Anderson William 
Published: February 2018

AbstractStrategies to control the risk domain of NHLBI EPR-3 (National Heart, Lung, and Blood Institute Expert Panel Report-3) asthma guidelines, which includes exacerbations requiring systemic corticosteroids, reduction in lung growth, and progressive loss of lung function, and treatment-related adverse effects, are evolving in children and adolescents. Increasing evidence demonstrates that children and adolescents with asthma are at risk of a reduction in lung growth, leading to lower lung function and potentially chronic obstructive pulmonary disease as adults. Readily available clinical biomarkers for atopy, including aeroallergen testing, total serum IgE, blood eosinophilia, and spirometry, are being utilized to phenotype difficult-to-treat pediatric patients, to assess risk for seasonal exacerbations, and to predict response to controller therapies. The Composite Asthma Severity Index is a novel, freely available scoring system to define asthma control, incorporating NHLBI EPR-3 risk and impairment domains. As new asthma controller therapies, such as tiotropium, are introduced for pediatric use, the safety of established controller therapies including inhaled corticosteroid and long-acting beta-agonist are being reexamined. Macrolide antibiotics may be an oral corticosteroid sparing alternative for the treatment of severe respiratory tract infection in preschool-aged children. Seasonally directed courses of omalizumab may provide an alternative approach to prevent fall asthma exacerbations in children. Combining these pharmaceuticals and biomarker-directed therapies provide potential new options and personalized approaches to gain asthma control in pediatric patients failing current management.
Pediatric Neurotoxicity of Anesthetic Agents: Are We too Worried or too Little?
Authors: Bhatt Rashmi , Khanna Puneet 
Published: February 2018

AbstractThe debate on possible neurocognitive adverse effects of anesthetic agents refuses to cease. As evidence builds up, both for and against the debate, a conclusion evades us. More human studies on the subject have now been carried out, and yet we do not have a consensus. In this review, we attempt to relook at the existing evidence, as well as examine some new information as we pursue a greater understanding of this complex matter.
Das reversible zerebrale Vasokonstriktionssyndrom
Authors: Kamm K. , Ruscheweyh R. , Straube A. 
Published: February 2018

ZusammenfassungDas reversible zerebrale Vasokonstriktionssyndrom (RCVS) ist eine häufige, wahrscheinlich unterdiagnostizierte Ursache des Donnerschlagkopfschmerzes. Typischerweise präsentiert sich das RCVS mit einem stärksten, innerhalb von weniger als 1 Minute sein Maximum erreichenden Kopfschmerz. Dieser kann innerhalb von wenigen Wochen, oft getriggert durch körperliche Anstrengung, emotionale Belastung oder Valsalva-Manöver, immer wieder auftreten. Die Erkrankung verläuft meist monosymptomatisch, selbstlimitierend und benigne, allerdings können intrazerebrale Blutungen, Ischämien oder ein PRES komplizierend auftreten. Im folgenden Artikel sollen die typische Präsentation des RCVS, Komplikationen, Verlauf, Therapie und Pathophysiologie vorgestellt werden.
Symptomatischer Clusterkopfschmerz
Authors: Holle-Lee D. , Gaul C. 
Published: February 2018

ZusammenfassungDie Erstdiagnose eines Clusterkopfschmerzes macht immer eine weitere Diagnostik zum Ausschluss einer sekundären Ursache notwendig. Eine ungewöhnliche Anamnese oder ein auffälliger neurologischer Untersuchungsbefund können auf eine symptomatische Kopfschmerzursache hinweisen, eine typische Anamnese und ein unauffälliger Untersuchungsbefund schließen jedoch einen sekundären Clusterkopfschmerz keinesfalls aus. Eine Zusatzuntersuchung mittels cMRT sollte bei Erstdiagnose immer durchgeführt werden. Hypophysäre Raumforderungen und Dissektionen der Hirnversorgenden Gefäße sind häufige Grunderkrankungen, die phänomenologisch als Clusterkopfschmerz erscheinen können. Die Therapie richtet sich nach der Ursache der Clusterkopfschmerzen.
Morbus Hirschsprung
Authors: Lacher M. 
Published: February 2018

ZusammenfassungDer Morbus Hirschsprung ist ein häufiges kinderchirurgisches Krankheitsbild.Auch wenn eine Vielzahl von genetischen Mutationen beschrieben wurde, besteht die Trias der Diagnosestellung weiterhin in der sorgfältigen Anamnese, Kolon-Kontrastmitteluntersuchung und Rektumbiopsie.Die Durchzugsoperation hat zum Ziel, den aganglionären Darm zu entfernen und die intestinale Passage durch Anastomosierung des innervierten Darms mit dem Analkanal unmittelbar oberhalb der Linea dentata zu rekonstruieren, sodass der Analkanal und die Sphinkterfunktion erhalten bleiben. Zu den häufigsten Techniken gehören die Operationen nach Swenson, Soave (de la Torre) und Duhamel. Diese können auch laparoskopisch assistiert durchgeführt werden.Obwohl der Morbus Hirschsprung durch Resektion des aganglionären Darmes primär gut zu behandeln ist, ist die Langzeitmorbidität hoch. Diese wird vor allem durch die fort-bestehende Obstipation bis hin zur Stuhlinkontinenz oder rezidivierende Episoden einer Enterokolitis bestimmt. Durch eine zielgerichtete Diagnostik und multidisziplinäre Behandlung können diese Symptome meist im Verlauf mehrerer Jahre erfolgreich behandelt werden.Der Pädiater spielt beim Erkennen und Management dieser Kinder eine wichtige Rolle.
Psychosoziale Aspekte der Stuhlinkontinenz
Authors: Klitzing K. v. , Scholz D. 
Published: February 2018

ZusammenfassungStuhlkontinenz ist nach WHO-Definition die erlernte Fähigkeit, Stuhlgang willentlich ortund zeitgerecht abzusetzen (1). Zum Erwerb dieser sozialen Kompetenz muss das Kind den Konflikt zwischen Autonomie und Konformität lösen. Der lustvolle Umgang mit den Ausscheidungen wird dem Ekelregime unterworfen. Misslingt dieser Entwicklungsschritt, ist die gesellschaftliche Teilhabe gefährdet. Das Ringen um Sauberkeitsprinzipien stellt die pädagogischen Fähigkeiten der Eltern auf die Probe. Die von Eltern bei der eigenen Reinlichkeitserziehung erlebten Emotionen werden in Familien mit stuhlinkontinenten Kindern reaktiviert. Subklinische psychische Symptome bis hin zu manifesten psychischen Störungen finden sich bei stuhlinkontinenten Kindern und deren Familienangehörigen deutlich häufiger als in der Normalbevölke-rung. Sie können sowohl Ursache und aufrechterhaltender Faktor als auch Folge der kindlichen Symptomatik und der damit verbundenen familiären Interaktionsproblematik sein. Sekundäre Stuhlinkontinenz kann durch Belastungssituationen ausgelöst werden. Invasive Diagnostik und rigide Behandlungsschemata können traumatisieren und dysfunktionales Verhalten chronifizieren.
Hautkrebsprävention und Sonnenschutzcreme: ein Update
Authors: Lademann J. , Patzelt A. , Zastrow L. , Meinke M. , Darvin M. , Knorr F. 
Published: February 2018

ZusammenfassungIn den letzten Jahren sind die Hautkrebsraten weltweit gestiegen. Die Anwendung von Sonnenschutzmitteln ist eine weit verbreitete Strategie in der Prävention gegen Hautkrebs, Sonnenbrand und Photoalterung. Es sollten kombinierte Breitbandfiltersysteme mit hoher Wirkung gegen UV-B- und UV-A-Strahlung eingesetzt werden. Weitere Studien sind notwendig, um die Entwicklung von Sonnenschutzmitteln gegen die ebenfalls schädlichen IRA-Strahlen voranzutreiben. Obwohl die regelmäßige Anwendung von Sonnenschutzmitteln ein wesentlicher Bestandteil in der Hautkrebsprävention ist, sollten insbesondere bei Kindern kombinierte Schutzmaßnahmen angewendet werden: Sonnenkarenz bei starker Sonneneinstrahlung, textiler Sonnenschutz, Aufenthalt im Schatten und die Anwendung von Sonnenschutzmitteln.
Editorial
Authors: Reimer Jens 
Published: February 2018

Sehr geehrte Leserinnen und Leser,die Suche nach Glück bewegt uns in den letzten Dekaden zunehmend. Als Faktoren, die zum Glück beitragen, sind soziale Fürsorge, Generosität, Redlichkeit, Gesundheit, Freiheit, Einkommen und gute Regierungsführung zu nennen. Im Weltglücksreport 2017 nehmen 3 skandinavische Länder, nämlich Norwegen, Dänemark und Island, die Toppositionen ein.
Orientation towards otherness in the social and literary spaces of today’s Europe
Authors: Arias Rosario , Bryla Martyna 
Published: February 2018

Abstract
This paper addresses current narratives on refugees and Muslim others within the social and literary spaces of today’s Europe. Drawing on Sara Ahmed and others, it sets out to better comprehend what lies behind European fears of the other and, in doing so, raise questions about the ways of facing those who are desperately knocking on Europe’s door.
Integrity and Its counterfeits: implications for economy, business and management
Authors: Sun William , Robinson Simon , Polowczyk Paweł Łukasz 
Published: February 2018

Abstract
While the concept of integrity has long been explored by great philosophers and thinkers, its application in modern and postmodern business and economic contexts has been underdeveloped. Little have been done to address the vagueness and paradoxicality of integrity and its shadow reality of counterfeits. The thematic collection, which this paper complements, entitled ‘Integrity and Its Counterfeits: Implications for Economy, Business and Management’, makes a contribution towards filling the gap between the abstract concept of integrity and its application into business and economy, with a particular attention on the ambiguous, equivocal and diverse meanings of the concept, the complex and dynamic practicality of integrity, and the grey and dark areas of business out of integrity. This article introduces the background of the research theme and provides exemplary debates and emerging avenues of discussion on this topic.
Integration and authority: rescuing the ‘one thought too many’ problem
Authors: Smyth Nicholas 
Published: February 2018

AbstractFour decades ago, Bernard Williams accused Kantian moral theory of providing agents with ‘one thought too many’. The general consensus among contemporary Kantians is that this objection has been decisively answered. In this paper, I reconstruct the problem, showing that Williams was not principally concerned with how agents are to think in emergency situations, but rather with how moral theories are to be integrated into recognizably human lives. I show that various Kantian responses to Williams provide inadequate materials for solving this ‘integration problem’, and that they are correspondingly ill-positioned to account for the authority of morality, as Williams suspected all along.
Enhancing protein fold determination by exploring the complementary information of chemical cross-linking and coevolutionary signals
Authors: dos Santos Ricardo N , Ferrari Allan J R , de Jesus Hugo C R , Gozzo Fábio C , Morcos Faruck , Martínez Leandro 
Published: February 2018

Abstract

Motivation
Elucidation of protein native states from amino acid sequences is a primary computational challenge. Modern computational and experimental methodologies, such as molecular coevolution and chemical cross-linking mass-spectrometry allowed protein structural characterization to previously intangible systems. Despite several independent successful examples, data from these distinct methodologies have not been systematically studied in conjunction. One challenge of structural inference using coevolution is that it is limited to sequence fragments within a conserved and unique domain for which sufficient sequence datasets are available. Therefore, coupling coevolutionary data with complimentary distance constraints from orthogonal sources can provide additional precision to structure prediction methodologies.

Results
In this work, we present a methodology to combine residue interaction data obtained from coevolutionary information and cross-linking/mass spectrometry distance constraints in order to identify functional states of proteins. Using a combination of structure-based models (SBMs) with optimized Gaussian-like potentials, secondary structure estimation and simulated annealing molecular dynamics, we provide an automated methodology to integrate constraint data from diverse sources in order to elucidate the native conformation of full protein systems with distinct complexity and structural topologies. We show that cross-linking mass spectrometry constraints improve the structure predictions obtained from SBMs and coevolution signals, and that the constraints obtained by each method have a useful degree of complementarity that promotes enhanced fold estimates.

Availability and implementation
Scripts and procedures to implement the methodology presented herein are available at https://github.com/mcubeg/DCAXL.

Supplementary information
Supplementary data are available at Bioinformatics online.
ssbio: a Python framework for structural systems biology
Authors: Mih Nathan , Brunk Elizabeth , Chen Ke , Catoiu Edward , Sastry Anand , Kavvas Erol , Monk Jonathan M , Zhang Zhen , Palsson Bernhard O 
Published: February 2018

Abstract

Summary
Working with protein structures at the genome-scale has been challenging in a variety of ways. Here, we present ssbio, a Python package that provides a framework to easily work with structural information in the context of genome-scale network reconstructions, which can contain thousands of individual proteins. The ssbio package provides an automated pipeline to construct high quality genome-scale models with protein structures (GEM-PROs), wrappers to popular third-party programs to compute associated protein properties, and methods to visualize and annotate structures directly in Jupyter notebooks, thus lowering the barrier of linking 3D structural data with established systems workflows.

Availability and implementation
ssbio is implemented in Python and available to download under the MIT license at http://github.com/SBRG/ssbio. Documentation and Jupyter notebook tutorials are available at http://ssbio.readthedocs.io/en/latest/. Interactive notebooks can be launched using Binder at https://mybinder.org/v2/gh/SBRG/ssbio/master?filepath=Binder.ipynb.

Supplementary information
Supplementary data are available at Bioinformatics online.
Draft genomes of two blister beetles Hycleus cichorii and Hycleus phaleratus
Authors: Wu Yuan-Ming , Li Jiang , Chen Xiang-Sheng 
Published: February 2018

Abstract

Background
Commonly known as blister beetles or Spanish fly, there are more than 1500 species in the Meloidae family (Hexapoda: Coleoptera: Tenebrionoidea) that produce the potent defensive blistering agent cantharidin. Cantharidin and its derivatives have been used to treat cancers such as liver, stomach, lung, and esophageal cancers. Hycleus cichorii and Hycleus phaleratus are the most commercially important blister beetles in China due to their ability to biosynthesize this potent vesicant. However, there is a lack of genome reference, which has hindered development of studies on the biosynthesis of cantharidin and a better understanding of its biology and pharmacology.

Results
We report 2 draft genomes and quantified gene sets for the blister beetles H. cichorii and H. phaleratus, 2 complex genomes with &gt;72% repeats and approximately 1% heterozygosity, using Illumina sequencing data. An integrated assembly pipeline was performed for assembly, and most of the coding regions were obtained. Benchmarking universal single-copy orthologs (BUSCO) assessment showed that our assembly obtained more than 98% of the Endopterygota universal single-copy orthologs. Comparison analysis showed that the completeness of coding genes in our assembly was comparable to other beetle genomes such as Dendroctonus ponderosae and Agrilus planipennis. Gene annotation yielded 13 813 and 13 725 protein-coding genes in H. cichorii and H. phaleratus, of which approximately 89% were functionally annotated. BUSCO assessment showed that approximately 86% and 84% of the Endopterygota universal single-copy orthologs were annotated completely in these 2 gene sets, whose completeness is comparable to that of D. ponderosae and A. planipennis.

Conclusions
Assembly of both blister beetle genomes provides a valuable resource for future biosynthesis of cantharidin and comparative genomic studies of blister beetles and other beetles.
Sofosbuvir-Based Direct-Acting Antiviral Therapies for HCV in People Receiving Opioid Substitution Therapy: An Analysis of Phase 3 Studies
Authors: Grebely Jason , Feld Jordan J , Wyles David , Sulkowski Mark , Ni Liyun , Llewellyn Joe , Mir Heshaam M , Sajed Nika , Stamm Luisa M , Hyland Robert H , McNally John , Brainard Diana M , Jacobson Ira , Zeuzem Stefan , Bourlière Marc , Foster Graham , Afdhal Nezam , Dore Gregory J 
Published: February 2018

Abstract

Background
Hepatitis C virus (HCV) direct-acting antiviral therapy is effective among people receiving opioid substitution therapy (OST), but studies are limited by small numbers of nongenotype 1 (GT1) patients. The aim of this study was to evaluate the treatment completion, adherence, SVR12, and safety of sofosbuvir-based therapies in HCV patients receiving and not receiving OST.

Methods
Ten phase 3 studies of sofosbuvir-based regimens included ION (ledipasvir/sofosbuvir ± ribavirin for 8, 12, or 24 weeks in GT1), ASTRAL (sofosbuvir/velpatasvir for 12 weeks in GT1-6), and POLARIS (sofosbuvir/velpatasvir and sofosbuvir/velpatasvir/voxilaprevir in GT1-6). Patients with clinically significant drug use (last 12 months) or noncannabinoids detected at screening were ineligible.

Results
Among 4743 patients, 4% (n = 194) were receiving OST (methadone; n = 113; buprenorphine, n = 75; other, n = 6). Compared with those not receiving OST (n = 4549), those receiving OST (n = 194) were younger (mean age, 48 vs 54), more often male (73% vs 61%), GT3 (38% vs 17%), treatment-naïve (78% vs 65%), and cirrhotic (36% vs 23%). Among those receiving and not receiving OST, there was no significant difference in treatment completion (97% vs 99%, P = .06), SVR12 (94% vs 97%, P = .06), relapse (0.5% vs 2.1%, P = .19), adverse events (78% vs 77%, P = .79), or serious adverse events (3.6% vs 2.4%, P = .24). There was no difference in SVR12 in patients with cirrhosis (99% vs 95%, P = .25) or those with G3 (95% vs 95%, P = .77) in those receiving OST. Among patients receiving OST, SVR12 was high among those receiving methadone (95%) and buprenorphine (96%).

Conclusion
Sofosbuvir-based therapies are effective and safe in patients receiving OST.
Efficacy and Outcomes of Posterior Inferior Cerebellar Artery (PICA) Bypass for Proximal PICA and Vertebral Artery-PICA Aneurysms: A Case Series
Authors: Rennert Robert C , Strickland Ben A , Ravina Kristine , Bakhsheshian Joshua , Fredrickson Vance , Tenser Matthew , Amar Arun , Mack William , Carey Joseph , Russin Jonathan J 
Published: February 2018

Abstract

BACKGROUND
Nonsaccular vertebral artery (VA) and posterior inferior cerebellar artery (PICA) aneurysms have high morbidity and mortality rates and are difficult to treat using standard microsurgical or endovascular techniques. Definitive revascularization can require clip trapping and/or vessel sacrifice, with PICA bypass. The published surgical experience with these approaches is limited. We herein review our recent surgical experience with PICA revascularization for complex PICA and VA/PICA aneurysms.

OBJECTIVE
To determine the efficacy and outcomes of PICA bypass for revascularization of nonsaccular PICA and VA/PICA aneurysms.

METHODS
Retrospective analysis of an institutional review board-approved, prospective database was performed to identify patients with PICA and VA/PICA aneurysms treated with PICA bypass at a single institution. Demographic information, aneurysm characteristics, temporary clip time, and neurological outcomes were recorded.

RESULTS
Ten cases of PICA revascularization were performed for both ruptured (n = 8) and unruptured (n = 2) nonsaccular proximal PICA or VA/PICA aneurysms. Seven cases were performed without vessel grafts; 3 cases required harvest of the descending branch of the lateral femoral circumflex artery. Mean temporary clip time was 38 min (range 27-50 min). Good outcomes (Glasgow Outcomes Scale score of 5) were achieved in 70% (n = 7) of patients at time of discharge; the remaining patients had a Glasgow Outcomes Scale of 3. Two bypass-related complications occurred in this series; a hematoma at the graft harvest site requiring evacuation, and severe bypass graft spasm requiring multiple endovascular treatments.

CONCLUSION
PICA bypass can be a safe, effective, and highly customizable tool for the revascularization of patients with nonsaccular proximal PICA and VA/PICA aneurysms.
Temporal Bone Meningo-Encephalic-Herniation: Etiological Categorization and Surgical Strategy
Authors: Grinblat Golda , Dandinarasaiah Manjunath , Prasad Sampath Chandra , Piras Gianluca , Piccirillo Enrico , Fulcheri Andrea , Sanna Mario 
Published: February 2018

Objective:To study the clinical presentation, intraoperative findings and surgical management in meningo-encephalic-herniation (MEH) based on the etiology.Study Design:A retrospective clinical study and is a follow-up on the previously published report in 2009.Setting:A quaternary referral otology and skull base centerPatients and Methods:The inclusion criteria were intraoperatively verified MEH in patients with a minimum follow-up of 12 months, which yielded 262 operated ears. The data were extracted regarding demographics, laterality, clinical presentation, past surgeries, contralateral-ear condition, intraoperative findings, complications, recurrences, revision-surgeries, audiometric-data, and follow-up.Results:The mean age at surgery was 49.7 years with the involvement of right-ear in 53.8% of patients. Lesions were categorized based on the etiology as chronic-otitis-media with/without cholesteatoma-MEH (COM/CHOL-MEH)-47.7%, iatrogenic-MEHs −20.9%; traumatic-MEHs −8% and spontaneous-MEHs −23.3%. At presentation, hearing loss (100 and 98.2%) and otorrhea (65.6 and 49.1%) were predominant in COM/CHOL-MEHs and iatrogenic-MEHs, respectively. On the other hand, meningitis (23.9 and 14.3%) and cerebrospinal fluid-leak (52.4 and 42.8%) were more pronounced in spontaneous and traumatic MEHs, respectively. Surgical approaches included 1) transmastoid, 2) middle-cranial-fossa-approach, 3) combined, and 4) middle-ear-obliteration (MEO) techniques. A total of 52.8% of COM/CHOL-MEHs and 49.1% of iatrogenic-MEHs underwent MEO. Middle-cranial-fossa approach was predominantly used in spontaneous-MEHs (52.5%) and traumatic-MEHs (38.1%). The defect was mostly single (75.2%). Smaller, multiple, bilateral lesions were more common in spontaneous-MEHs with tegmen-tympani involvement (57.4%).Conclusion:Incorporating etiology into MEHs is a key-step that can be used as a guidance in choosing the right surgery. MEO is a part of armamentarium, and should be used whenever needed, if the objective is performing a definitive surgery.
Overview of aldosterone-related genetic syndromes and recent advances
Authors: Zennaro Maria-Christina , Fernandes-Rosa Fabio L. , Boulkroun Sheerazed 
Published: February 2018

Purpose of review
Primary aldosteronism is the most common form of secondary hypertension. Early diagnosis and treatment are key to cure of hypertension and prevention of cardiovascular complications. Recent genetic discoveries have improved our understanding on the pathophysiology of aldosterone production and triggered the development of new diagnostic procedures and targeted treatments for primary aldosteronism.

Recent findings
Different inherited genetic abnormalities distinguish specific forms of familial hyperaldosteronism. Somatic mutations are found not only in aldosterone-producing adenoma (APA), leading to primary aldosteronism, but also in aldosterone producing cell clusters of normal and micronodules from image-negative adrenal glands. Genetic knowledge has allowed the discovery of surrogate biomarkers and specific pharmacological inhibitors. Ageing appears to be associated with dysregulated and relatively autonomous aldosterone production.

Summary
New biochemical markers and pharmacological approaches may allow preoperative identification of somatic mutation carriers and use of targeted treatments.