bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nicotine and sleep deprivation: impact on pain sensitivity and immune modulation in rats
Authors: Hirotsu Camila , Pedroni Matheus Negrao , Berro Laís Fernanda , Tufik Sergio , Andersen Monica Levy 
Published: September 2018

AbstractRepeated nicotine administration has been associated with increased paradoxical sleep in rats and antinociceptive properties, whereas paradoxical sleep deprivation (PSD) elicits pronociceptive and inflammatory responses. Thus, we aimed to evaluate the effect of repeated nicotine administration and its withdrawal combined with PSD on pain sensitivity and inflammatory markers. Sixty adult male Wistar rats were subjected to repeated injections of saline (SAL) or nicotine (NIC) for 12 days or 7 days of nicotine followed by acute mecamylamine administration on day 8 to precipitate nicotine abstinence (ABST). On day 9, the animals were submitted to PSD for 72 h or remained in control condition (CTRL); on day 12, thermal pain threshold was assessed by the hot plate test. PSD significantly decreased the latency to paw withdrawal in all groups compared to their respective controls. ABST-PSD animals presented higher levels of interleukin (IL)-6 compared to all groups, except ABST-CTRL. After adjustment for weight loss, IL-6, IL-4 and tumor necrosis factor alpha, ABST-PSD was associated with the lowest pain threshold. Nicotine and IL-4 levels were predictors of higher pain threshold. Hyperalgesia induced by PSD prevailed over the antinociceptive action of nicotine, while the association between PSD and ABST synergistically increased IL-6 concentrations and decreased pain threshold.
Engineered hexavalent Fc proteins with enhanced Fc-gamma receptor avidity provide insights into immune-complex interactions
Authors: Rowley Tania F. , Peters Shirley J. , Aylott Mike , Griffin Robert , Davies Nicola L. , Healy Louise J. , Cutler Rona M. , Eddleston Alison , Pither Thomas L. , Sopp Joshua M. , Zaccheo Oliver , Fossati Gianluca , Cain Katharine , Ventom Andrew M. , Hailu Hanna , Ward Eleanor J. , Sherington John , Brennan Frank R. , Fallah-Arani Farnaz , Humphreys David P. 
Published: September 2018

AbstractAutoantibody-mediated diseases are currently treated with intravenous immunoglobulin, which is thought to act in part via blockade of Fc gamma receptors, thereby inhibiting autoantibody effector functions and subsequent pathology. We aimed to develop recombinant molecules with enhanced Fc receptor avidity and thus increased potency over intravenous immunoglobulin. Here we describe the molecular engineering of human Fc hexamers and explore their therapeutic and safety profiles. We show Fc hexamers were more potent than IVIG in phagocytosis blockade and disease models. However, in human whole-blood safety assays incubation with IgG1 isotype Fc hexamers resulted in cytokine release, platelet and complement activation, whereas the IgG4 version did not. We used a statistically designed mutagenesis approach to identify the key Fc residues involved in these processes. Cytokine release was found to be dependent on neutrophil FcγRIIIb interactions with L234 and A327 in the Fc. Therefore, Fc hexamers provide unique insights into Fc receptor biology.
Global millimeter VLBI array survey of ultracompact extragalactic radio sources at 86 GHz
Authors: Nair Dhanya G. , Lobanov Andrei P. , Krichbaum Thomas P. , Ros Eduardo , Zensus Johann Anton , Kovalev Yuri Y. , Lee Sang-Sung , Mertens Florent , Hagiwara Yoshiaki , Bremer Michael , Lindqvist Michael , de Vicente Pablo 
Published: September 2018

Context. Very long baseline interferometry (VLBI) observations at 86 GHz (wavelength, λ = 3 mm) reach a resolution of about 50 μas, probing the collimation and acceleration regions of relativistic outflows in active galactic nuclei (AGN). The physical conditions in these regions can be studied by performing 86 GHz VLBI surveys of representative samples of compact extragalactic radio sources.
Aims. To extend the statistical studies of compact extragalactic jets, a large global 86 GHz VLBI survey of 162 compact radio sources was conducted in 2010–2011 using the Global Millimeter VLBI Array (GMVA).
Methods. The survey observations were made in a snapshot mode, with up to five scans per target spread over a range of hour angles in order to optimize the visibility coverage. The survey data attained a typical baseline sensitivity of 0.1 Jy and a typical image sensitivity of 5 mJy beam−1, providing successful detections and images for all of the survey targets. For 138 objects, the survey provides the first ever VLBI images made at 86 GHz. Gaussian model fitting of the visibility data was applied to represent the structure of the observed sources and to estimate the flux densities and sizes of distinct emitting regions (components) in their jets. These estimates were used for calculating the brightness temperature (Tb) at the jet base (core) and in one or more moving regions (jet components) downstream from the core. These model-fit-based estimates of Tb were compared to the estimates of brightness temperature limits made directly from the visibility data, demonstrating a good agreement between the two methods.
Results. The apparent brightness temperature estimates for the jet cores in our sample range from 2.5 × 109 K to 1.3 × 1012 K, with the mean value of 1.8 × 1011 K. The apparent brightness temperature estimates for the inner jet components in our sample range from 7.0 × 107 K to 4.0 × 1011 K. A simple population model with a single intrinsic value of brightness temperature, T0, is applied to reproduce the observed distribution. It yields T0 = (3.77−0.14+0.10) × 1011 K for the jet cores, implying that the inverse Compton losses dominate the emission. In the nearest jet components, T0 = (1.42−0.19+0.16) × 1011 K is found, which is slightly higher than the equipartition limit of ∼5 × 1010 K expected for these jet regions. For objects with sufficient structural detail detected, the adiabatic energy losses are shown to dominate the observed changes of brightness temperature along the jet.
Was wissen wir über die reale Dauer der ärztlichen Weiterbildung in Deutschland?
Authors: van den Bussche Hendrik , Nehls Sarah , Boczor Sigrid , Siegert Stephanie , Kocalevent Rüya-Daniela , Scherer Martin 
Published: September 2018

Zusammenfassung
Zielsetzung In diesem Aufsatz wird untersucht, wie lange die ärztliche Weiterbildung tatsächlich dauert, welche Gründe bei einer Überschreitung der vorgeschriebenen Mindestzeiten eine Rolle spielen und wie hoch die Unterbrecherquote bzw. die Abbruchquote ist.
Methodik Multizentrische jährliche postalische Befragung des PJ-Jahrganges 2008/09 von 7 deutschen medizinischen Fakultäten. Für die Analysen wurden deskriptive Statistiken verwendet.
Ergebnisse Mehr als die Hälfte der Ärzte und Ärztinnen in Weiterbildung (58 %) gab im 5. Jahr der Weiterbildung an, für den Abschluss (deutlich) länger als die als Mindestdauer vorgeschriebene Zeit zu brauchen. Bei Ärztinnen (65 %) war dieser Anteil höher als bei Ärzten (43 %), bei Ärztinnen mit Kind erreichte er mit ca. 91 % den höchsten Wert. Ärztinnen, die eine vermutliche Verlängerung voraussahen, schätzten diesen Zeitraum im Mittel auf 19,6 Monate (SD = 14,7), Ärzte auf 11,5 Monate (SD = 8,6).Bei Ärztinnen spielte der Faktor Kind/Eltern die wichtigste Rolle. Die Hälfte aller Angaben der Ärzte (und 31 % der Ärztinnen) beziehen sich auf organisatorische und curriculare Probleme der Weiterbildung.
Schlussfolgerung Es ist einerseits erforderlich, Maßnahmen zu ergreifen, um die Erschwernisse der Weiterführung der Weiterbildung im Zusammenhang mit Elternwerden zu minimieren bzw. eine Wiederaufnahme der Berufstätigkeit zu erleichtern. Hierzu sollten curriculare und organisatorische Maßnahmen, beispielsweise verbindlichere Rotationspläne bzw. bessere Möglichkeiten der Weiterbildung in Teilzeit, implementiert werden.
Einnahme vor oder nach dem Essen? Das ist nicht
alles…
Authors: Smollich Martin 
Published: September 2018

ZusammenfassungWechselwirkungen zwischen Arzneimitteln und Lebensmitteln können sich für die
Betroffenen gravierend auswirken: So können die Folgen einer nicht erkannten
Wechselwirkung zwischen einem Arzneimittel und der zeitnah verzehrten Nahrung
von Wirkungsabschwächung und völligem Wirkungsverlust bis hin zu
lebensgefährlichen Überdosierungen reichen 1.
Obwohl die Risiken dieser Wechselwirkungen mitunter erheblich sind, ist der
kausale Zusammenhang den meisten Patienten, aber auch vielen Ärzten weitgehend
unbekannt.
Sarcopenia – Endocrinological and Neurological Aspects
Authors: Stangl Michaela , Böcker Wolfgang , Chubanov Vladimir , Ferrari Uta , Fischereder Michael , Gudermann Thomas , Hesse Eric , Meinke Peter , Reincke Martin , Reisch Nicole , Saller Maximilian , Seissler Jochen , Schmidmaier Ralf , Schoser Benedikt , Then Cornelia , Thorand Barbara , Drey Michael 
Published: September 2018

AbstractSarcopenia in geriatric patients is often associated with or even caused by changes of the endocrine and nervous system. The multifactorial pathogenesis of sarcopenia and additional multimorbidity in geriatric patients makes it difficult to study distinct pathogenic pathways leading to sarcopenia. Patients suffering from diabetes, Cushing’s syndrome, chronic kidney disease, Klinefelter’s syndrome or motor neuron diseases, such as amyotrophic lateral sclerosis for example are known to have impaired muscle property and reduced physical performance. These patients are typically younger and suffer from conditions caused by a known molecular disease mechanism and a peculiar sarcopenic phenotype. Therefore, these sequelae can serve as prototypic disease models to study isolated endocrinological and neurodegenerative causes for sarcopenia. This review focuses on diseases whose etiopathogenesis of muscle impairment is known. The idea is to use these diseases as proof of principles to develop a classification algorithm of sarcopenia in the elderly to make a more mechanism-oriented therapy be possible.
Kardiovaskuläre Ereignisse nach Nierentransplantation
Authors: van der Giet Markus 
Published: September 2018

ZusammenfassungNach einer Nierentransplantation ist das Risiko für das Auftreten kardiovaskulärer Ereignisse leider immer noch hoch. Traditionelle Risikofaktoren spielen
hierbei neben dem Immunsystem – einschließlich der T- und B-Zellen – eine nichtzu unterschätzende Rolle. Mittlerweile gibt es viele Hinweise, darauf, dass das
Immunsystem in der Pathogenese von Hochdruck, Atherosklerose und koronarer Herzerkrankung wichtige Weichen stellt. Gerade die Expansion proinflammatorisch
wirksamer, zytotoxischer CD4+CD28null-positiver T-Zellen ist stark mit dem Auftreten von kardiovaskulären Ereignissen nach einer
Nierentransplantation assoziiert. Die humorale Antwort nach der Organtransplantation hat ebenfalls Einfluss auf die vaskuläre Inflammation mit Endothelschaden.
In der vorliegenden Arbeit werden die immunologischen Mechanismen zusammengefasst und auch die bekannten Effekte der häufig verwandten immunsuppressiven
Medikamente mit ihrem bereits bekannten Einfluss auf das kardiovaskuläre System dargestellt.
Augmentation of Pharmacotherapy by Sleep Deprivation with Sleep Phase Advance in Treatment-Resistant Depression
Authors: Kurczewska Ewa , Ferensztajn-Rochowiak Ewa , Jasińska-Mikołajczyk Anna , Chłopocka-Woźniak Maria , Rybakowski Janusz K. 
Published: September 2018

Abstract
Introduction The aim was to assess the efficacy of total sleep deprivation (TSD) with sleep phase advance (SPA) in treatment-resistant depression (TRD) and associated biochemical factors.
Methods We studied nine males and 12 females, aged 49±14 years, with treatment-resistant unipolar or bipolar depression, receiving antidepressant and mood-stabilizing drugs. The four-day schedule included single TSD and three consecutive nights with SPA. Biochemical markers were measured on the day before and on 1st, 7th and 14th day after the TSD.
Results Ten subjects met criteria for response, defined as a reduction of ≥50% in the Hamilton Depression Rating Scale, on the 14th day. Concentrations of cortisol at baseline were lower in responders, and they decreased during therapy in both groups. In responders, there was an increase of interleukin-10 (IL-10) and IL-1β on the 14th day.
Discussion Our preliminary study demonstrated the efficacy of pharmacotherapy augmentation by TSD and SPA in half of the patients with TRD. The main biochemical factors related to clinical response included status of cortisol and increase in IL-10 and IL-1β levels.
2,6-Dimethoxy-1,4-benzoquinone Inhibits 3T3-L1 Adipocyte Differentiation via Regulation of AMPK and mTORC1
Authors: Son Hyo , Jang Young , Jung Chang , Ahn Jiyun , Ha Tae 
Published: September 2018

Abstract2,6-Dimethoxy-1,4-benzoquinone is a natural phytochemical present in fermented wheat germ. It has been reported to exhibit anti-inflammatory, antitumor, and antibacterial activities. However, the anti-adipogenic effects of 2,6-dimethoxy-1,4-benzoquinone and the mechanisms responsible have not previously been elucidated. Such findings may have ramifications for the treatment of obesity. 2,6-Dimethoxy-1,4-benzoquinone (5 and 7.5 µM) significantly reduced the expression of various adipogenic transcription factors, including peroxisome proliferator-activated receptor-γ and CCAAT/enhancer binding protein α as well as adipocyte protein 2 and fatty acid synthase. 2,6-Dimethoxy-1,4-benzoquinone upregulated AMP-dependent protein kinase phosphorylation and inhibited the mature form of sterol regulatory element-binding protein 1c. Notably, 2,6-dimethoxy-1,4-benzoquinone attenuated mammalian target of rapamycin complex 1 activity in 3T3-L1 and mouse embryonic fibroblast cells. These findings highlight a potential role for 2,6-dimethoxy-1,4-benzoquinone in the suppression of adipogenesis. Further studies to determine the anti-obesity effects of 2,6-dimethoxy-1,4-benzoquinone in animal models appear warranted.
The Effect of Medial Tibial Slope on Anterior Tibial Translation and Short-Term ACL Reconstruction Outcome
Authors: Sauer Steffen , Clatworthy Mark 
Published: September 2018

Background Increased tibial slope has been shown to be associated with higher anterior cruciate ligament (ACL) reconstruction failure rate. Little is known about the correlation of tibial slope and anterior tibial translation in ACL deficient and reconstructed knees as well as the correlation of tibial slope and ACL reconstruction outcome.
Purpose/Hypothesis The purpose of this study was to investigate the correlation of tibial slope with anterior tibial translation and ACL reconstruction outcome. It is hypothesized that increased medial tibial slope is associated with increased anterior tibial translation in the ACL deficient knee. Medial tibial slope is neither expected to affect anterior tibial translation in the ACL reconstructed knee nor short-term ACL reconstruction outcome.
Materials and Methods A cohort of 104 patients with unilateral isolated ACL deficiency undergoing hamstring ACL reconstruction by a single surgeon between 2002 and 2004 was followed up prospectively. Preoperative data were collected including patient demographics, time to surgery, subjective and objective International Knee Documentation Committee (IKDC) outcome scores, as well as manual maximum anterior tibial translation measured with the KT-1000 measuring instrument. Medial tibial slope was assessed on long lateral X-rays using the method described by Dejour and Bonnin (1994). Intraoperative data were collected including meniscal integrity; postoperative data were collected at 1-year follow-up including manual maximum anterior tibial translation (KT-1000 measured), and subjective and objective IKDC scores.
Results A significant positive correlation was seen between medial tibial slope in ACL deficient knees and KT-1000–measured anterior tibial translation (r = 0.24; p = 0.003). The positive relationship increased when meniscal integrity was factored in (r = 0.33; p < 0.001). No significant correlation was seen between medial or lateral meniscal integrity and KT-1000–measured anterior tibial translation (r = −18; p = 0.06). No significant correlation was seen between KT-1000–measured anterior tibial translation and time to surgery. One year postoperatively, 82 patients were assessed, while 26 patients were lost to follow-up; no significant correlation was found between increased medial tibial slope and poor ACL reconstruction outcome measured by post-ACL reconstruction anterior tibial translation (KT-1000) or subjective and objective IKDC scores.
Conclusion Increased medial tibial slope is associated with increased (KT-1000 measured) anterior tibial translation in ACL deficient knees. No significant correlation is found between increased medial tibial slope and poor short-term ACL reconstruction outcome.
Functional Genomics for the Identification of Modulators of Platelet-Dependent Thrombus Formation
Authors: Vermeersch Elien , Nuyttens Benedicte , Tersteeg Claudia , Broos Katleen , De Meyer Simon , Vanhoorelbeke Karen , Deckmyn Hans 
Published: September 2018

AbstractDespite the absence of the genome in platelets, transcription profiling provides important insights into platelet function and can help clarify abnormalities in platelet disorders. The Bloodomics Consortium performed whole-genome expression analysis comparing in vitro–differentiated megakaryocytes (MKs) with in vitro–differentiated erythroblasts and different blood cell types. This allowed the identification of genes with upregulated expression in MKs compared with all other cell lineages, among the receptors BAMBI, LRRC32, ESAM, and DCBLD2. In a later correlative analysis of genome-wide platelet RNA expression with interindividual human platelet reactivity, LLRFIP and COMMD7 were additionally identified. A functional genomics approach using morpholino-based silencing in zebrafish identified various roles for all of these selected genes in thrombus formation. In this review, we summarize the role of the six identified genes in zebrafish and discuss how they correlate with subsequently performed mouse experiments.
Aktuelles zur Therapie von Melanom und Merkelzellkarzinom
Authors: Schmale Ine 
Published: September 2018

Zusammenfassung
Immunonkologische Checkpoint-Inhibitoren und BRAF/MEK-Inhibitoren sind beim malignen Melanom in der metastasierten Situation etabliert und rücken nun in das adjuvante Setting vor. In der Sitzung zu Hauttumoren wurde auf der Jahresversammlung der American Society of Clinical Oncology (ASCO) die Immuntherapie auch als wirk-same Option beim aggressiven Merkelzellkarzinom in allen Therapielinien bestätigt.
Wenig neue Marker für die Therapiestrategie
Authors: Braitmaier Helmine 
Published: September 2018

Zusammenfassung
Die Sequenziertechnologie der nächsten Generation hat viele neue genetische Verän-derungen in Tumoren aufgedeckt. Doch welche genetischen Marker können Ärzten helfen, für jede Patientin die passende Therapie zu finden? Und spielt die Krebsart überhaupt noch eine Rolle? Bisherige Studienergebnisse sind ernüchternd.
Verbesserte Therapiekonzepte beim Magenkarzinom
Authors: Schmale Ine 
Published: September 2018

Zusammenfassung
Beim Magenkarzinom sind die Therapiemöglichkeit limitiert, vor allem im fortgeschrittenen Stadium. Priv.-Doz. Dr. Sylvie Lorenzen, Klinikum rechts der Isar, München, sprach auf dem Deutschen Krebskongress über Verbesserungen der Prognose von Magenkarzinompatienten durch zielgerichtete Therapien.
Die akute lymphatische Leukämie – Diagnostik, Subgruppen und Therapien
Authors: Wermann Wiba , Gökbuget Nicola 
Published: September 2018

AbstractThe acute lymphoblastic leukemia (ALL) is a heterogenous rare malignant disease of lymphoblastic precursor cells. The peak of incidence lies in childhood (5.3/100 000), but the incidence rises again from the age of 50 onwards, showing a second peak at patients > 80 years old (2.3/100 000). The ALL is an acute life-threatening disease which untreated leads to death within a short time. The therapeutic objective is cure. By the characterization of subgroups, their targeted therapy and therapy optimization cure rates could be improved (from less than 10 % in the eighties) to more than 50 – 70 % (depending on the subgroup). To this achievement the approach has contributed with risk adapted therapy protocols, with improved supportive therapy and in particular with taking the minimal residual disease (the most important prognostic factor) as a basis for the therapy decision. Recently, with the new immunotherapies there exist further promising options of targeted therapies.
Describing strong correlation with fractional-spin correction in density functional theory
Authors: Su Neil Qiang , Li Chen , Yang Weitao 
Published: September 2018

Significance
The static correlation error inherent in commonly used density functional approximations (DFAs) has seriously hindered the application of density functional theory (DFT) to strongly correlated systems. Here, an effective fractional-spin correction against the important issue of static/strong correlation in DFT is developed. With this, the flat-plane behavior of various DFAs is largely restored, and the potential energy curves of dissociation of ionic species, single bonds, and multiple bonds are properly described, which demonstrates great improvement in the treatment of strong correlation. This work should have a significant impact on the development and application of DFT.
Nucleosomes inhibit target cleavage by CRISPR-Cas9 in vivo
Authors: Yarrington Robert M. , Verma Surbhi , Schwartz Shaina , Trautman Jonathan K. , Carroll Dana 
Published: September 2018

Significance
The efficiency of genome editing with CRISPR-Cas9 can vary widely at different targets and in different cells. Some of this variability may be due to the inherent quality of different guide RNAs, but it may also depend on the cellular context of the genomic target DNA. In this report, we demonstrate that targets bound by nucleosomes are cut much less efficiently than targets from which nucleosomes are absent or have been depleted. This information can inform target selection, particularly in cases where cells are quiescent or nucleosome mobility is limited.
Goal realization
Authors: Georgakopoulos Thanasis , Härtl Holden , Sioupi Athina 
Published: September 2018

AbstractDrawing upon recent insights into the role of Goal preference as reflector of cross-linguistic differences, this paper investigates the factors affecting the realization of Goals in motion event descriptions. In particular, it examines the interplay between the lexicalization pattern of a language, on the one hand, and grammatical viewpoint aspect, on the other – factors which have commonly been treated in isolation. In so doing, three typologically distinct languages were examined: English, German and Greek. The empirical basis of this paper includes: (a) a corpus study, in which we examined the distribution of Goals in a small set of verbs, and (b) an experimental verbalization study, from which we elicited descriptions of different motion event types. While the former does not give a clear picture concerning the cross-linguistic differences in Goal prominence, the latter indicates that lexicalization pattern assumes a more prominent role than grammatical viewpoint aspect in affecting Goal realization.