bluuebunny/crossref_metadata_2025_split huggingface dataset:
Magma production along the Lord Howe Seamount Chain, northern Zealandia
Authors: Seton Maria , Williams Simon , Mortimer Nick , Meffre Sebastien , Micklethwaite Steven , Zahirovic Sabin 
Published: January 2019

AbstractOne of the world’s most notable intraplate volcanic regions lies on the eastern Australian plate and includes two age-progressive trails offshore (Tasmantid and Lord Howe seamount chains) and the world’s longest continental hotspot trail (Cosgrove Track). While most studies agree that these chains formed by the rapid northward motion of the Australian plate over a slowly moving mantle source, the volcanic output along these trails, their plate–mantle interactions and the source of the magmatism remain unconstrained. A geophysical mapping and dredging campaign on the RV Southern Surveyor (ss2012_v06) confirmed the prolongation of the Lord Howe Seamount Chain to the South Rennell Trough, ∼200 km further north than previously sampled. Radiometric dating of these new samples at 27–28 Ma, together with previously published results from the southern part of the chain, indicate straightforward northward motion of the Australian plate over a quasi-stationary hotspot as predicted by Indo-Atlantic and Pacific hotspot models. A peak in Lord Howe Seamount Chain magmatism in late Oligocene time, also seen in the Tasmantid and Cosgrove trails, matches a 27–23 Ma slowdown of Australian plate motion. The average magma flux of the Lord Howe hotspot is estimated at 0.4 m3 s−1, similar to rates of crustal production at the South Rennell Trough prior to cessation of spreading in middle Oligocene time, supporting a potential genetic relationship to this spreading system. In addition, plate tectonic modelling suggests that the seamounts and plateaus in the Coral Sea may host the earliest evidence of plume activity in the area.
Trends and Solar Irradiance Effects in the Mesosphere
Authors: Qian Liying , Jacobi Christoph , McInerney Joseph 
Published: January 2019

AbstractWe investigate trends and solar irradiance effects in the mesosphere using the Whole Atmosphere Community Climate Model with eXtended thermosphere and ionosphere (WACCM‐X) and radar measurements of winds at Collm (51°N, 13°E), for the period of 1980–2014. We found that in the mesosphere, dynamics significantly impact temperature and wind trends, as well as how solar irradiance affects the temperature and winds. The global average temperature trends are negative, with a maximum of ~−1 K per decade in the middle to lower mesosphere. Solar irradiance effects on the global average temperature are positive and decrease monotonically with decreasing altitude, changing from ~3 K/100 solar flux units (sfu) near the mesopause to ~1 K per 100 sfu in the lower mesosphere. In the summer upper mesosphere, temperature trends can become near 0 or positive, likely due to dynamical effects. Both wind trends and solar effects on the winds show dynamical patterns with negative and positive values, indicating that they are predominantly controlled by dynamics. The wind trends and solar effects on the winds are on the orders of ~±5 m/s per decade and ~±5 m/s per 100 sfu, respectively, and they are not as statistically significant as their temperature counterparts. At Collm (51°N, 13°E), the observed zonal winds at 90 km have a larger trend of 1.98 m/s per decade compared to the simulated zonal winds and it is statistically significant, but both the simulated and observed meridional winds do not have statistically significant trends.
Aseismic Deep Slab and Mantle Flow Beneath Alaska: Insight From Anisotropic Tomography
Authors: Gou Tao , Zhao Dapeng , Huang Zhouchuan , Wang Liangshu 
Published: January 2019

AbstractWe present high‐resolution 3‐D images of P wave velocity (Vp), azimuthal anisotropy (AAN), and radial anisotropy (RAN) down to 900‐km depth beneath Alaska obtained by inverting a large number of high‐quality arrival time data from local earthquakes and teleseismic events simultaneously. Our results show that the high‐Vp Pacific slab has subducted down to 450‐ to 500‐km depths. A prominent slab gap is revealed at depths of 65–120 km near the Wrangell volcanic field, which is likely a slab tear acting as a channel that provides ascending mantle materials to generate magmas feeding the surface volcanoes. In the back‐arc mantle wedge near the eastern slab edge, the AAN exhibits trench‐parallel fast‐velocity directions (FVDs), which may reflect along‐strike mantle flow. The FVDs in the subducting Pacific slab are nearly east‐west, which may indicate fossil anisotropy formed at the mid‐ocean ridge. A negative RAN is revealed within the subducting slab, which may be caused by the fast plate subduction with a steep dip angle. Trench‐normal FVDs of the AAN are revealed in the mantle below the Pacific slab, which may reflect mantle flow entrained by the subducting slab. A positive RAN is revealed in the mantle beneath the Yakutat slab, indicating that its shallow subduction flattens the mantle flow below the slab to be subhorizontal. Along‐strike FVDs of the AAN around the eastern slab edge may indicate the edge‐induced toroidal mantle flow.
Genetic and environmental influences on structural brain measures in twins with autism spectrum disorder
Authors: Hegarty John P. , Pegoraro Luiz F. L. , Lazzeroni Laura C. , Raman Mira M. , Hallmayer Joachim F. , Monterrey Julio C. , Cleveland Sue C. , Wolke Olga N. , Phillips Jennifer M. , Reiss Allan L. , Hardan Antonio Y. 
Published: January 2019

AbstractAtypical growth patterns of the brain have been previously reported in autism spectrum disorder (ASD) but these alterations are heterogeneous across individuals, which may be associated with the variable effects of genetic and environmental influences on brain development. Monozygotic (MZ) and dizygotic (DZ) twin pairs with and without ASD (aged 6–15 years) were recruited to participate in this study. T1-weighted MRIs (n = 164) were processed with FreeSurfer to evaluate structural brain measures. Intra-class correlations were examined within twin pairs and compared across diagnostic groups. ACE modeling was also completed. Structural brain measures, including cerebral and cerebellar gray matter (GM) and white matter (WM) volume, surface area, and cortical thickness, were primarily influenced by genetic factors in TD twins; however, mean curvature appeared to be primarily influenced by environmental factors. Similarly, genetic factors accounted for the majority of variation in brain size in twins with ASD, potentially to a larger extent regarding curvature and subcortical GM; however, there were also more environmental contributions in twins with ASD on some structural brain measures, such that cortical thickness and cerebellar WM volume were primarily influenced by environmental factors. These findings indicate potential neurobiological outcomes of the genetic and environmental risk factors that have been previously associated with ASD and, although preliminary, may help account for some of the previously outlined neurobiological heterogeneity across affected individuals. This is especially relevant regarding the role of genetic and environmental factors in the development of ASD, in which certain brain structures may be more sensitive to specific influences.
Activation of TGF-β signaling in an aortic aneurysm in a patient with Loeys-Dietz syndrome caused by a novel loss-of-function variant of TGFBR1
Authors: Hara Hironori , Takeda Norifumi , Fujiwara Takayuki , Yagi Hiroki , Maemura Sonoko , Kanaya Tsubasa , Nawata Kan , Morita Hiroyuki , Komuro Issei 
Published: January 2019

AbstractLoeys–Dietz syndrome (LDS) is caused by variants of transforming growth factor-β (TGF-β)-related genes and is characterized by aortic aneurysm and dissection. We report an LDS patient with a de novo missense variant of TGFBR1 [c.1126A>G, p.(Lys376Glu)] in which active TGF-β signaling was observed in the aorta, despite the in vitro demonstration that the loss-of-function mutation lies within the serine/threonine kinase domain. The mechanism underlying this TGF-β paradox in LDS aortopathy should be further investigated.
Antibiotic collateral sensitivity is contingent on the repeatability of evolution
Authors: Nichol Daniel , Rutter Joseph , Bryant Christopher , Hujer Andrea M. , Lek Sai , Adams Mark D. , Jeavons Peter , Anderson Alexander R. A. , Bonomo Robert A. , Scott Jacob G. 
Published: January 2019

AbstractAntibiotic resistance represents a growing health crisis that necessitates the immediate discovery of novel treatment strategies. One such strategy is the identification of collateral sensitivities, wherein evolution under a first drug induces susceptibility to a second. Here, we report that sequential drug regimens derived from in vitro evolution experiments may have overstated therapeutic benefit, predicting a collaterally sensitive response where cross-resistance ultimately occurs. We quantify the likelihood of this phenomenon by use of a mathematical model parametrised with combinatorially complete fitness landscapes for Escherichia coli. Through experimental evolution we then verify that a second drug can indeed stochastically exhibit either increased susceptibility or increased resistance when following a first. Genetic divergence is confirmed as the driver of this differential response through targeted and whole genome sequencing. Taken together, these results highlight that the success of evolutionarily-informed therapies is predicated on a rigorous probabilistic understanding of the contingencies that arise during the evolution of drug resistance.
Combining LOPIT with differential ultracentrifugation for high-resolution spatial proteomics
Authors: Geladaki Aikaterini , Kočevar Britovšek Nina , Breckels Lisa M. , Smith Tom S. , Vennard Owen L. , Mulvey Claire M. , Crook Oliver M. , Gatto Laurent , Lilley Kathryn S. 
Published: January 2019

AbstractThe study of protein localisation has greatly benefited from high-throughput methods utilising cellular fractionation and proteomic profiling. Hyperplexed Localisation of Organelle Proteins by Isotope Tagging (hyperLOPIT) is a well-established method in this area. It achieves high-resolution separation of organelles and subcellular compartments but is relatively time- and resource-intensive. As a simpler alternative, we here develop Localisation of Organelle Proteins by Isotope Tagging after Differential ultraCentrifugation (LOPIT-DC) and compare this method to the density gradient-based hyperLOPIT approach. We confirm that high-resolution maps can be obtained using differential centrifugation down to the suborganellar and protein complex level. HyperLOPIT and LOPIT-DC yield highly similar results, facilitating the identification of isoform-specific localisations and high-confidence localisation assignment for proteins in suborganellar structures, protein complexes and signalling pathways. By combining both approaches, we present a comprehensive high-resolution dataset of human protein localisations and deliver a flexible set of protocols for subcellular proteomics.
Lsd1 as a therapeutic target in Gfi1-activated medulloblastoma
Authors: Lee Catherine , Rudneva Vasilisa A. , Erkek Serap , Zapatka Marc , Chau Lianne Q. , Tacheva-Grigorova Silvia K. , Garancher Alexandra , Rusert Jessica M. , Aksoy Ozlem , Lea Robin , Mohammad Helai P. , Wang Jianxun , Weiss William A. , Grimes H. Leighton , Pfister Stefan M. , Northcott Paul A. , Wechsler-Reya Robert J. 
Published: January 2019

AbstractDrugs that modify the epigenome are powerful tools for treating cancer, but these drugs often have pleiotropic effects, and identifying patients who will benefit from them remains a major clinical challenge. Here we show that medulloblastomas driven by the transcription factor Gfi1 are exquisitely dependent on the enzyme lysine demethylase 1 (Kdm1a/Lsd1). We demonstrate that Lsd1 physically associates with Gfi1, and that these proteins cooperate to inhibit genes involved in neuronal commitment and differentiation. We also show that Lsd1 is essential for Gfi1-mediated transformation: Gfi1 proteins that cannot recruit Lsd1 are unable to drive tumorigenesis, and genetic ablation of Lsd1 markedly impairs tumor growth in vivo. Finally, pharmacological inhibitors of Lsd1 potently inhibit growth of Gfi1-driven tumors. These studies provide important insight into the mechanisms by which Gfi1 contributes to tumorigenesis, and identify Lsd1 inhibitors as promising therapeutic agents for Gfi1-driven medulloblastoma.
Assessment of HMGA2 and PLAG1 rearrangements in breast adenomyoepitheliomas
Authors: Pareja Fresia , Geyer Felipe C. , Brown David N. , Sebastião Ana P. Martins , Gularte-Mérida Rodrigo , Li Anqi , Edelweiss Marcia , Da Cruz Paula Arnaud , Selenica Pier , Wen Hannah Y. , Jungbluth Achim A. , Varga Zsuzsanna , Palazzo Juan , Rubin Brian P. , Ellis Ian O. , Brogi Edi , Rakha Emad A. , Weigelt Britta , Reis-Filho Jorge S. 
Published: January 2019

AbstractBreast adenomyoepitheliomas (AMEs) are rare epithelial-myoepithelial neoplasms that may occasionally produce myxochondroid matrix, akin to pleomorphic adenomas (PAs). Regardless of their anatomic location, PAs often harbor rearrangements involving HMGA2 or PLAG1. We have recently shown that the repertoire of somatic genetic alterations of AMEs varies according to their estrogen receptor (ER) status; whilst the majority of ER-positive AMEs display mutually exclusive PIK3CA or AKT1 hotspot mutations, up to 60% of ER-negative AMEs harbor concurrent HRAS Q61 hotspot mutations and mutations affecting either PIK3CA or PIK3R1. Here, we hypothesized that a subset of AMEs lacking these somatic genetic alterations could be underpinned by oncogenic fusion genes, in particular those involving HMGA2 or PLAG1. Therefore, we subjected 13 AMEs to RNA-sequencing for fusion discovery (n = 5) and/or fluorescence in situ hybridization (FISH) analysis for HMGA2 and PLAG1 rearrangements (n = 13). RNA-sequencing revealed an HMGA2-WIF1 fusion gene in an ER-positive AME lacking HRAS, PIK3CA and AKT1 somatic mutations. This fusion gene, which has been previously described in salivary gland PAs, results in a chimeric transcript composed of exons 1–5 of HMGA2 and exons 3–10 of WIF1. No additional in-frame fusion genes or HMGA2 or PLAG1 rearrangements were identified in the remaining AMEs analyzed. Our results demonstrate that a subset of AMEs lacking mutations affecting HRAS and PI3K pathway-related genes may harbor HMGA2-WIF1 fusion genes, suggesting that a subset of breast AMEs may be genetically related to PAs or that a subset of AMEs may originate in the context of a PA.
Teaching Medical Students Skills for Effective Communication With Patients Who Have Communication Disorders
Authors: Baylor Carolyn , Burns Michael , McDonough Karen , Mach Helen , Yorkston Kathryn 
Published: January 2019

Purpose
Patients with communication impairments including speech, language, cognition, or hearing disorders face many barriers to communication in health care settings. These patients report loss of autonomy in health care decision making, are at increased risk for medical errors, and are less satisfied with health care than patients without communication disorders. Although medical students receive training in effective patient–provider communication, most of this training assumes patients have intact communication abilities. Medical students and other health care providers are often unprepared to meet the communication needs of patients with communication disorders in health care encounters. The purpose of this study was to assess the impact of a curriculum for training medical students to communicate effectively with patients who have a range of communication disorders.

Method
Twenty-six 2nd-year medical students volunteered for assessments before and after a required workshop in a class. This workshop included instruction about different types of communication disorders and communication strategies, followed by practice with standardized patients portraying different communication disorders. Outcome measures included a knowledge test, ratings of self-efficacy, and evaluation of students' skills when interviewing standardized patients portraying aphasia and dysarthria.

Results
Medical students demonstrated significant improvements in knowledge, self-efficacy, and use of recommended communication techniques.

Conclusions
The curriculum appeared effective in changing medical students' knowledge and skills for working with patients with communication disorders. Equipping medical students to meet the needs of patients with communication disorders is 1 key element for improving the quality of health care for this patient population.
Stufentherapie der COPD
Authors: Watz Henrik , Kirsten Anne , Greulich Timm 
Published: January 2019

AbstractThe goal of pharmacologic therapy of stable chronic obstructive pulmonary disease (COPD) is to reduce symptoms, improve exercise intolerance and health-related quality of life, and to reduce exacerbations. Inhaled long-acting β2-agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) are equally effective for the symptomatic management of COPD. However, LAMAs are more effective than LABAs in the reduction of exacerbations. In patients with symptomatic COPD pharmacologic therapy is usually escalated using the fixed combination of LAMAs and LABAs (dual bronchodilation), which is also superior to LAMA monotherapy in the prevention of exacerbations. Adding inhaled corticosteroids (ICS) to LABA and LAMA (triple therapy) for a prevention of exacerbations results in a further reduction of exacerbations, especially in those patients with higher blood eosinophil counts. Non-pharmacologic management of COPD patients includes smoking cessation programs, vaccination, pulmonary rehabilitation, and strategies to improve or maintain their physical activity.
Sepsis-Update: evidenzbasierte Therapie
Authors: Martin Lukas , Bickenbach Johannes , Marx Gernot 
Published: January 2019

ZusammenfassungSepsis und septischer Schock stellen medizinische Notfälle dar, die einer kompetenten Früherkennung und eines entsprechenden sofortigen, zielgerichteten Managements bedürfen. Die Therapie der Sepsis und des septischen Schocks hat sich während der letzten Jahre kontinuierlich weiterentwickelt. Dieser Beitrag gibt einen Überblick über die aktuelle Evidenz der Therapie der Sepsis und des septischen Schocks und deren Umsetzung in die klinische Praxis.
Die Medizinisch-beruflich orientierte Rehabilitation (MBOR) in der Neurologie erfordert eine individualisierte Rehabilitandenidentifikation
Authors: Leniger Tobias , Heßling Andrea 
Published: January 2019

ZusammenfassungZur Erhöhung einer erfolgreichen beruflichen Wiedereingliederung nach akuter oder bei chronischer Erkrankung entwickelte die Deutsche Rentenversicherung die medizinisch-beruflich orientierte Rehabilitation (MBOR) als strategische Weiterentwicklung der herkömmlichen medizinischen Rehabilitation. Obwohl in einigen Indikationen bereits Überlegenheitsnachweise der MBOR gegenüber der herkömmlichen Rehabilitation hinsichtlich der beruflichen Wiedereingliederung vorliegen, gelang dies für die Neurologie bisher noch nicht. Aktuelle Studien zur MBOR in der Neurologie verweisen auf die Vielschichtigkeit klinisch anamnestischer Charakteristika der MBOR-Zielgruppe, die eine Definition einer besonderen beruflichen Problemlage (BBPL) als Zugangsvoraussetzung in die neurologische MBOR erschwert. Zudem beeinflussen die heterogenen Störungsbilder, die zahlreichen Komorbiditäten und die Rehabilitationsform (AHB, HV) eine BBPL-Identifikation maßgeblich. So identifizieren standardisierte BBPL-Screeninginstrumente mit dem Fokus auf sozialmedizinische Kriterien eine BBPL unzureichender als eine Individualanamnese. In der Neurologie empfiehlt sich trotz höheren Aufwands ein individualisiertes BBPL-Screening zur Beginn der Rehabilitationsmaßnahme.
Früher mobilisiert – früher entlassen?
Authors: Kluger Daniel 
Published: January 2019

ZusammenfassungAnhand dreier ausgewählter Studien geht Autor Daniel Kluger der Frage nach,
inwieweit sich Frühmobilisation auf die Krankenhausverweildauer von Patienten
auswirkt. Obwohl die drei Studien unterschiedliche Limitationen aufweisen,
deuten sie doch alle darauf hin, dass Frührehabilitation und -mobilisation zu
einer kürzeren Krankenhausaufenthaltsdauer führen können.
Pancreatic pseudocyst-portal vein fistula with refractory hepatic pseudocyst: Two cases treated with EUS cyst-gastrostomy and review of the literature
Authors: Eccles John , Wiebe Edward , D’Souza Pernilla , Sandha Gurpal 
Published: January 2019

Abstract
Background and study aims Pseudocysts are the most common pancreatic cystic lesions and they usually develop in association with pancreatitis of at least 4 weeks’ duration. Extra-pancreatic pseudocysts, although reported, are relatively uncommon. Secondary liver pseudocysts are recognized within the literature, and most patients described have required percutaneous or surgical drainage due to infection or symptoms. The mechanism of hepatic pseudocyst formation is not entirely clear but it is postulated that this phenomenon may occur through pseudocyst-portal vein fistulization. We describe two cases of patients presenting with pancreatic pseudocysts invading the portal venous system with embolization of pancreatic fluid to the liver and subsequent hepatic pseudocyst formation. Interestingly, liver pseudocyst resolution was incomplete with antibiotics and percutaneous drainage alone, and only occurred following endoscopic ultrasonography-guided pancreatic cyst-gastrostomy and metal stent insertion. We have reviewed the current literature on the diagnosis and management of pseudocyst-portal vein fistula formation and we believe that our cases represent the first published within the literature to describe this treatment approach.
Bone Metastases – Pathophysiology, Diagnostic Testing and Therapy (Part 2)
Authors: Koob Sebastian , Kehrer Michael , Strauss Andreas , Jacobs Cornelius , Wirtz Dieter Christian , Schmolders Jan 
Published: January 2019

AbstractThe second part of this review deals with the several options for the surgical therapy of bone metastases according to their anatomical site and the patientʼs individual prognosis. Although metastases to the bone – with few exceptions – are normally given palliative therapy, patients nowadays reach survival times of several months to years, depending on the underlying tumour entity. Scoring systems are suitable to estimate the patientʼs prognosis and fracture risk. The indication for operation has to be adapted to these parameters. In order to preserve a high quality of life, a limb saving procedure has to be aimed at. The options include the resection of the metastasis with stabilisation, the sole stabilisation of the affected bone, and wide resection with limb reconstruction using a modular tumor endoprosthesis. With todayʼs anaesthesiological peri- and intraoperative care, a vast number of surgical implants and bone augmentations are available. However, what is important is not the practicability of the procedure, but the oncological justification and patient-adapted selection of surgical therapy.