bluuebunny/crossref_metadata_2025_split huggingface dataset:
Der Stellenwert der klassischen Verbundosteosynthese langer Röhrenknochen und des Beckens
Authors: Pape Alexander , Hofbauer Christine , Kleber Christian , Pyrc Jaroslaw , Fritzsche Hagen , Schaser Klaus-Dieter 
Published: June 2017

ZusammenfassungAufgrund optimierter systemischer onkologischer Therapien und deutlich weiterentwickelter chirurgischer Verfahren zur Resektion und Defektrekonstruktion ist eine gesteigerte Lebenserwartung von Patienten mit muskuloskeletalen Tumoren zu verzeichnen. Insbesondere steigt die Inzidenz von skeletalen Metastasen primärer Tumoren mit osteotropem Metastasierungsmuster (Schilddrüsen-, Mamma-, Nierenzell-, Prostata- und Bronchialkarzinom) erheblich an. Trotz weiterentwickelter Implantatsysteme (winkelstabile Plattenfixateure, fortgeschrittene Marknagelgenerationen) bleibt die Defektrekonstruktion im osteoporotisch, tumorös oder bestrahlungsinduziert geschwächten Knochen eine Herausforderung. Die Kombination von extra-/intramedullären Osteosyntheseverfahren mit Knochenzement bietet dabei vor allem bei großen Defekten/segmentalem Knochenverlust/pathologischen Frakturen eine valide Option zur Erlangung einer belastungsstabilen Osteosynthese und konsekutiver Schmerzreduktion. Im Hinblick auf die reduzierte Lebenserwartung von Patienten mit Skelettmetastasen erlaubt die klassische Verbundosteosynthese einen hohen Grad an Primärstabilität und somit eine unmittelbare Mobilisierung des Patienten. Die Kombination von Zement und unterschiedlichen Implantatsystemen kann dabei an nahezu allen Skelettabschnitten relativ komplikationsarm angewendet werden.
Psychosoziale Interventionen für sexuelle Funktionsstörungen bei Männern
Authors: Schmidt Hannah Maren , Höhn Cindy , Widmeier Eugen , Berner Michael Martin 
Published: June 2017

ÜbersichtDiese systematische Übersichtsarbeit untersucht die Wirksamkeit psychosozialer Interventionen bei Männern mit formal diagnostizierten
sexuellen Funktionsstörungen (SFS). Eingeschlossen sind randomisierte kontrollierte Studien (RCT) und kontrollierte klinische Studien (CCT)
zwischen 1985 und 2014, welche mindestens eine psychosoziale Intervention und eine aktive Vergleichsgruppe (z. B. andere psychosoziale
Intervention, medikamentöse oder somatische Behandlung) oder eine Kontrollgruppe (z. B. Warteliste, Placebo) einschließen.
Studiencharakteristika und Ergebnisse sind durch zwei unabhängige Rater_innen nach einem standardisierten Manual extrahiert worden.
Beurteilt wird zudem das Risiko einer systematischen Verzerrung (Risk of Bias). Es sind 25 Studien eingeschlossen. Die meisten
Studien untersuchen Männer mit Erektionsstörung. Mehr als die Hälfte der Studien verwendet ein sexualtherapeutisches Konzept nach Masters
und Johnson oder ein kognitiv-verhaltenstherapeutisches Behandlungskonzept. Insgesamt verbessern psychosoziale Interventionen die sexuelle
Funktionsfähigkeit und Zufriedenheit. Teilweise ergibt sich jedoch auch in der Wartekontroll- oder der Placebo-Gruppe eine Verbesserung der
sexuellen Symptomatik. Bei Erektionsstörungen zeigen sich unterschiedliche Ergebnisse im Hinblick auf die Frage, ob psychosoziale
Interventionen einer pharmakologischen Behandlung überlegen sind. Der vorzeitige Orgasmus wird vermehrt in neueren Studien untersucht;
vermindertes sexuelles Verlangen und verzögerter Orgasmus werden jedoch kaum und nur zusammen mit anderen Störungsbildern betrachtet. Eine
Einschränkung stellt die oft ungenaue Berichterstattung der Primärstudien dar. Die verglichenen Interventionen zeigen meist eine
vergleichbare Wirksamkeit, was auf gemeinsame zugrunde liegende Wirkfaktoren hindeuten kann.
Arterielle Hyper- und Hypotonie assoziiert mit Psychopharmaka: eine Risikobewertung basierend auf den Fachinformationen
Authors: Freudenmann Roland , Freudenmann Ninja , Zurowski Bartosz , Schönfeldt-Lecuona Carlos , Maier Ludwig , Schmieder Roland , Lange-Asschenfeldt Christian , Gahr Maximilian 
Published: June 2017

Zusammenfassung
Einleitung Psychopharmaka sind gut bekannte Auslöser klinisch bedeutsamer Blutdruckänderungen. Unser Ziel war es, Rangreihen für das Risiko einer Psychopharmaka-assoziierten arteriellen Hyper- bzw. Hypotonie zu erstellen.
Methoden Es wurden für 105 in Deutschland in der Erwachsenenpsychiatrie zugelassene Psychopharmaka sämtliche in der Roten oder Gelben Liste online verfügbaren 784 Fachinformationen (FI) ausgewertet und die dort standardisiert genannten Risiken einer Blutdrucksteigerung oder -senkung extrahiert.
Ergebnisse Für blutdrucksteigernde Effekte hatte Atomoxetin laut FI das höchste Risiko („sehr häufig“, > 10 %) und 15 weitere Psychopharmaka waren in der Kategorie „häufig“ (> 1 %): Duloxetin, Milnacipran, Venlafaxin, Bupropion, Citalopram, Tranylcypromin (v. a. bei Diätfehlern), Reboxetin, Methylphenidat, Clozapin, Paliperidon, Risperidon, Buprenorphin+Naloxon, Memantin, Galantamin und Rivastigmin. Umgekehrt waren mit Amitriptylin, Tranylcypromin, Chlorprothixen, Flupentixol, Levomepromazin, Olanzapin und Trimipramin 7 Stoffe „sehr häufig“ als mit blutdrucksenkenden Effekten assoziiert beschrieben, weitere 25 „häufig“. Für viele andere Psychopharmaka war kein Hypertonie- bzw. Hypotonie-Risiko dokumentiert. Nebenbefundlich fanden sich in den FIs verschiedener Hersteller zu einer Substanz teils erhebliche Unterschiede (z. B. bei Citalopram), sodass für viele Stoffe keine eindeutige Risikozuordnung bestand.
Diskussion Gemäß den FIs weisen viele Psychopharmaka ein Hypertonie- und stärker noch ein Hypotonie-Risiko auf. Nur vereinzelt zeigten sich Gruppeneffekte, z. B. Blutdruckerhöhung durch noradrenerge Antidepressiva. Gängige Tabellen zu medikamentösen Ursachen der arteriellen Hypertonie sind im Bereich Psychopharmaka revisionswürdig. Unsere Rangreihen dienen der Auswahl geeigneter Psychopharmaka bei Patienten mit bekanntem Hypertonus bzw. Synkopenneigung und bei Blutdruckentgleisungen unter Psychopharmaka. Für eine definitive Risikobewertung sind allerdings kontrollierte Studien nötig.
Labor market institutions, the insider/outsider divide and social inequalities in employment in affluent countries
Authors: Biegert Thomas 
Published: June 2017

Abstract
This article investigates the role of labor market institutions for social inequalities in employment. To distinguish institutional impacts for men and women, age groups and educational levels the analysis draws on data from 21 countries using the European Union Labor Force Survey and the Current Population Survey 1992–2012. The analysis demonstrates that there is significant heterogeneity in the relationship between institutions and employment across social groups. In line with the literature on dualization, institutions that arguably protect labor market insiders, i.e. employment protection, unionization and unemployment benefits, are frequently associated with greater inequality between typically disadvantaged groups and their insider peers. By contrast, institutions that discriminate less between insiders and outsiders, i.e. active labor market policies, minimum income benefits and centralized wage bargaining at times boost social equality on the labor market. The insider/outsider argument provides a valuable heuristic for assessing heterogeneity in institutional impacts, yet in several instances the results deviate from the expectations.
ITPA Activity in Adults and Children Treated With or Without Azathioprine: Relationship Between TPMT Activity, Thiopurine Metabolites, and Co-medications
Authors: Citterio-Quentin Antony , Moulsma Mustapha , Gustin Marie-Paule , Boulieu Roselyne 
Published: June 2017

Background:
The implication of inosine triphosphate pyrophosphatase (ITPA) on thiopurine drug response variability has been investigated but little data are available on its role on thiopurine metabolites. The ability of ITPA to modify the thiopurine metabolite levels is currently used to optimize azathioprine (AZA) therapy in relation to thiopurine S-methyltransferase (TPMT) activity, the aim of this study is to investigate ITPA phenotype in a large population and to evaluate the relation between ITPA and TPMT activities and thiopurine metabolites.

Methods:
ITPA activity was determined in 183 adults and 138 children with or without AZA therapy. 6-thioguanine nucleotides (6-TGN), 6-methylmercaptopurine nucleotides (6-MeMPN) levels, and ITPA as well as TPMT activities were measured in red blood cells. Using the Gaussian mixture model, distribution of ITPA activity was evaluated. Intraindividual variability and influence of age, sex, AZA treatment and associated co-medications on ITPA activity were also assessed.

Results:
This retrospective study shows a quadrimodal distribution in ITPA activity. No influence of age, sex, AZA therapy, and co-medications was found. In adults, ITPA activity was not significantly associated with 6-TGN or 6-MeMPN concentrations, whereas a weak negative correlation was observed with 6-MeMPN levels in pediatric populations (rs = −0.261; P = 0.024). A weak positive correlation was observed between ITPA and TPMT activities in children (rs = 0.289; P = 0.001).

Conclusions:
ITPA activity was poorly influenced by nongenetic parameters and has no influence on 6-TGN and 6-MeMPN concentrations in adults and only a weak correlation with 6-MeMPN and TPMT activity in children. These results demonstrate that ITPA is not a rate-limiting enzyme in the formation of 6-TGN but suggest that a decrease in ITPA activity in children may be a risk factor for accumulation of 6-MeMPN in cells.
Bone Morphogenetic Protein-7 Enhances Degradation of Osteoinductive Bioceramic Implants in an Ectopic Model
Authors: Roldán J. Camilo , Klünter Tim , Schulz Peter , Deisinger Ulrike , Diez Claudius , Waiss Waltraud , Kirschneck Christian , Reichert Torsten E. , Detsch Rainer 
Published: June 2017

Background:
The aim of the present study was to evaluate the degradation pattern of highly porous bioceramics as well as the bone formation in presence of bone morphogenetic protein 7 (BMP-7) in an ectopic site.

Methods:
Novel calcium phosphate ceramic cylinders sintered at 1,300°C with a total porosity of 92–94 vol%, 45 pores per inch, and sized 15 mm (Ø) × 5 mm were grafted on the musculus latissimus dorsi bilaterally in 10 Göttingen minipigs: group I (n = 5): hydroxyapatite (HA) versus biphasic calcium phosphate (BCP), a mixture of HA and tricalcium phosphate (TCP) in a ratio of 60/40 wt%; group II (n = 5): TCP versus BCP. A test side was supplied in situ with 250 μg BMP-7. Fluorochrome bone labeling and computed tomography were performed in vivo. Specimens were evaluated 14 weeks after surgery by environmental scanning electron microscopy, fluorescence microscopy, tartrate-resistant acid phosphatase, and pentachrome staining.

Results:
Bone formation was enhanced in the presence of BMP-7 in all ceramics (P = 0.001). Small spots of newly formed bone were observed in all implants in the absence of BMP-7. Degradation of HA and BCP was enhanced in the presence of BMP-7 (P = 0.001). In those ceramics, osteoclasts were observed. TCP ceramics were almost completely degraded independently of the effect of BMP-7 after 14 weeks (P = 0.76), osteoclasts were not observed.

Conclusions:
BMP-7 enhanced bone formation and degradation of HA and BCP ceramics via osteoclast resorption. TCP degraded via dissolution. All ceramics were osteoinductive. Novel degradable HA and BCP ceramics in the presence of BMP-7 are promising bone substitutes in the growing individual.
Annular Pink Plaque on the Hand
Authors: So Jessica Kim , Jacob Sharon E. 
Published: June 2017

ABSTRACT
Teledermatology is a term to describe the provision of dermatologic medical services through telecommunication technology. In this modality, there is transfer of patient medical information electronically (including history and visual data) obtained in one location to a provider who is in another location. The construct of this column is such that cases are presented in a standardized teledermatology reader format. This is a case of an annular pink plaque on the hand.
Community Priorities for Hospital-Based Prevention Initiatives: Results From a Deliberating Public
Authors: Gold Marthe R. , Realmuto Lindsey , Scherer Maya , Kamler Alexandra , Weiss Linda 
Published: June 2017

Context:
Internal revenue service provisions require not-for-profit hospitals to provide “community benefit.” In addition, the Affordable Care Act requires these hospitals to conduct community health needs assessments that involve appropriate stakeholders. These requirements signal government interest in creating opportunities for developing programs that are well tailored and responsive to the needs of the communities served. Gaining meaningful input from residents is a critical aspect of these processes.

Objective:
To implement public deliberations that explore local resident priorities for use of a hospital's community benefit resources to prevent chronic disease.

Methods:
Public deliberation is a method of community engagement that can provide guidance to decision makers on value-laden issues when technical solutions alone are inadequate to provide direction or set priorities. Three deliberations featuring presentations by experts and discussions among participants were convened with a cross section of residents in Brooklyn, New York. Participants were asked whether new hospital initiatives should prioritize: clinical prevention, community-based interventions, or action on broader policies affecting population health. Pre- and postsurveys, as well as qualitative methods, were used to assess knowledge and attitudes.

Results:
Postdeliberation, participants had significant changes in knowledge, particularly on the impact of education on health. Participants prioritized community-based and policy interventions over expanding clinical prevention capacity.

Conclusions:
Public deliberation offers a method to probe informed constituent views of how a hospital can best promote its community's health. Informed local residents felt that hospitals should frame health-promoting activities more broadly than is current practice. Not-for-profit hospitals gain significant tax advantages. Increased insurance rates suggest that some hospitals will experience savings in uncompensated care that can be used to promote health more broadly. Vetting priorities for the use of new resources with informed community members can be accomplished through public deliberation. These results suggest community support for nonclinical approaches to disease prevention.
Proteins with prion-like domains can form viscoelastic condensates that enable membrane remodeling and endocytosis
Authors: Bergeron-Sandoval Louis-Philippe , Kumar Sandeep , Heris Hossein Khadivi , Chang Catherine , Cornell Caitlin E. , Keller Sarah L. , François Paul , Hendricks Adam G. , Ehrlicher Allen J. , Pappu Rohit V. , Michnick Stephen W. 
Published: June 2017

SummaryMembrane invagination and vesicle formation are key steps in endocytosis and cellular trafficking. Here, we show that endocytic coat proteins with prion-like domains (PLDs) form hemispherical puncta in the budding yeast,S. cerevisiae. These puncta have the hallmarks of biomolecular condensates and enable membrane remodeling to drive actin-independent endocytosis. The puncta, which we refer to as endocytic condensates, form and dissolve reversibly in response to changes in temperature and solution conditions. The condensates are organized around dynamic protein-protein interaction networks, which involve interactions among PLDs with high glutamine contents. The endocytic coat protein Sla1 is at the hub of the protein-protein interaction network. Using active rheology, we indirectly characterized the material properties of endocytic condensates. These experiments show that endocytic condensates are viscoelastic materials and allow us to estimate the interfacial tension between endocytic condensates and their surroundings. We then adapt the physics of contact mechanics, specifically the contact theory of Hertz, to develop a quantitative framework for describing how interfacial tensions among condensates, the membrane, and the cytosol can deform the plasma membrane to enable actin independent endocytosis.
Type III CRISPR-Cas systems generate cyclic oligoadenylate second messengers to activate Csm6 RNases
Authors: Niewoehner Ole , Garcia-Doval Carmela , Rostøl Jakob T. , Berk Christian , Schwede Frank , Bigler Laurent , Hall Jonathan , Marraffini Luciano A. , Jinek Martin 
Published: June 2017

ABSTRACTIn many prokaryotes, type III CRISPR–Cas systems detect and degrade invasive genetic elements by an RNA-guided, RNA-targeting multisubunit interference complex that possesses dual RNase and DNase activities. The CRISPR-associated protein Csm6 additionally contributes to interference by functioning as a standalone ribonuclease that degrades invader RNA transcripts, but the mechanism linking invader sensing to Csm6 activity is not understood. Here we show that Csm6 proteins are activated through a second messenger generated by the type III interference complex. Upon target RNA binding by the type III interference complex, the Cas10 subunit converts ATP into a cyclic oligoadenylate product, which allosterically activates Csm6 by binding to its CARF domain. CARF domain mutations that abolish allosteric activation inhibit Csm6 activityin vivo, and mutations in the Cas10 Palm domain phenocopy loss of Csm6. Together, these results point to a hitherto unprecedented mechanism for regulation of CRISPR interference that bears striking conceptual similarity to oligoadenylate signalling in mammalian innate immunity.
Combining next-generation sequencing and mtDNA data to uncover cryptic lineages of Mexican highland frogs
Authors: Zarza Eugenia , Connors Elizabeth M. , Maley James M. , Tsai Whitney L.E. , Heimes Peter , Kaplan Moises , McCormack John E. 
Published: June 2017

AbstractRecently, molecular studies have uncovered significant cryptic diversity in the Mexican Highlands, leading to the description of many new endemic species. DNA approaches to this kind of species discovery have included both mitochondrial DNA (mtDNA) sequencing and multilocus genomic methods. While these marker types have often been pitted against one another, there are benefits to deploying them together, as linked mtDNA data can provide the bridge between uncovering lineages through rigorous multilocus genomic analysis and identifying lineages through comparison to existing mtDNA databases. Here, we apply one class of multilocus genomic marker, ultraconserved elements (UCEs), and linked mtDNA data to a species complex of frogs (Sarcohyla bistincta) found in the Mexican Highlands. We generated data from 1,891 UCEs, which contained 1,742 informative SNPs forS. bistinctaand closely related species and captured mitochondrial genomes for most samples. Genetic analyses based on both whole loci and SNPs agree there are numerous distinct and divergent lineages withinS. bistincta. The SNP-based species tree provides the most conservative estimate of 8 well-supported lineages in three major clades. Having linked mtDNA data allowed us to tap into the large number of mtDNA sequences available on GenBank and identify one of these lineages as an already-described species,S. pentheter. One identified clade (containing 2 of the 8 lineages) was 10% divergent in mtDNA and paraphyletic with otherS. bistincta, making this clade a clear candidate for species status. Phylogenies from UCEs and mtDNA mostly agreed in their topologies, but differed in that mtDNA suggested a more complex evolutionary history perhaps influenced by gene flow between some neighboring lineages. Our study demonstrates that the Mexican Highlands still hold substantial undescribed diversity. Combining multilocus genomic data with linked mtDNA data is a useful approach for identifying potential new species and associating them with already described taxa, which is especially important in groups with undescribed subadult phenotypes, where geographic ranges are unclear, or where phenotypes are conserved.
A quantitative systems pharmacology analysis of KRAS G12C covalent inhibitors
Authors: Stites Edward C. , Shaw Andrey S. 
Published: June 2017

AbstractThe KRAS oncogene is the most common, activating, oncogenic mutation in human cancer. KRAS has proven difficult to target effectively. Two different strategies have recently been described for covalently targeting the most common activating KRAS mutant in lung cancer, KRAS G12C. Previously, we have developed a computational model of the processes that regulate Ras activation and this model has proven useful for understanding the complex behaviors of Ras signaling. Here, we use this model to perform a computational systems pharmacology analysis of KRAS G12C targeted covalent inhibitors. After updating our model to include Ras protein turnover, we verified the validity of our model for problems in this domain by comparing model behaviors with experimental behaviors. The model naturally reproduces previous experimental data, including several experimental observations that were interpreted as being contrary to conventional wisdom. Overall, this suggests that our model describes the Ras system well, including those areas where conventional wisdom struggles. We then used the model to investigate possible strategies to improve the ability of KRAS G12C inhibitors to inhibit Ras pathway signaling. We identify one, as of yet unexplored mechanism, that, if optimized, could improve the effectiveness of one class of KRAS inhibitor. We also simulated resistance to targeted therapies and found that resistance promoting mutations may reverse which class of KRAS G12C inhibitor inhibits the system better, suggesting that there may be value to pursuing both types of KRAS G12C inhibitors. Overall, this work demonstrates that systems biology approaches can provide insights that inform the drug development process.
Diffusion MRI of white matter microstructure development in childhood and adolescence: Methods, challenges and progress
Authors: Tamnes Christian K. , Roalf David R. , Goddings Anne-Lise , Lebel Catherine 
Published: June 2017

AbstractDiffusion magnetic resonance imaging (dMRI) continues to grow in popularity as a useful neuroimaging method to study brain development, and longitudinal studies that track the same individuals over time are emerging. Over the last decade, seminal work using dMRI has provided new insights into the development of brain white matter (WM) microstructure, connections and networks throughout childhood and adolescence. This review provides an introduction to dMRI, both diffusion tensor imaging (DTI) and other dMRI models, as well as common acquisition and analysis approaches. We highlight the difficulties associated with ascribing these imaging measurements and their changes over time to specific underlying cellular and molecular events. We also discuss selected methodological challenges that are of particular relevance for studies of development, including critical choices related to image acquisition, image analysis, quality control assessment, and the within-subject and longitudinal reliability of dMRI measurements. Next, we review the exciting progress in the characterization and understanding of brain development that has resulted from dMRI studies in childhood and adolescence, including brief overviews and discussions of studies focusing on sex and individual differences. Finally, we outline future directions that will be beneficial to the field.