bluuebunny/crossref_metadata_2025_split huggingface dataset:
SNAI1 recruits HDAC1 to suppress SNAI2 transcription during epithelial to mesenchymal transition
Authors: Sundararajan Vignesh , Tan Ming , Tan Tuan Zea , Ye Jieru , Thiery Jean Paul , Huang Ruby Yun-Ju 
Published: June 2019

AbstractAberrant activation of epithelial to mesenchymal transition (EMT) associated factors were highly correlated with increased mortality in cancer patients. SNAIL family of transcriptional repressors comprised of three members, each of which were essentially associated with gastrulation and neural crest formation. Among which, SNAI1 and SNAI2 were efficiently induced during EMT and their expressions were correlated with poor clinical outcome in patients with breast, colon and ovarian carcinoma. In an ovarian cancer cell lines panel, we identified that SNAI1 and SNAI2 expressions were mutually exclusive, where SNAI1 predominantly represses SNAI2 expression. Detailed analysis of SNAI2 promoter region revealed that SNAI1 binds to two E-box sequences that mediated transcriptional repression. Through epigenetic inhibitor treatments, we identified that inhibition of histone deacetylase (HDAC) activity in SNAI1 overexpressing cells partially rescued SNAI2 expression. Importantly, we demonstrated a significant deacetylation of histone H3 and significant enrichments of HDAC1 and HDAC2 corepressors in both E-box regions of SNAI2 promoter. Our results suggested that SNAI1 repression on SNAI2 expression was predominantly mediated through the recruitment of the histone deacetylation machinery. Utilization of HDAC inhibitors would require additional profiling of SNAI1 activity and combined targeting of SNAI1 and HDACs might render efficient cancer treatment.
Characterization of a recently detected halogenated aminorex derivative: para-fluoro-4-methylaminorex (4′F-4-MAR)
Authors: Fabregat-Safont D. , Carbón X. , Ventura M. , Fornís I. , Hernández F. , Ibáñez M. 
Published: June 2019

AbstractDespite the fact that 33% of the new psychoactive substances seized in 2015 were synthetic cathinones, the number of these derivatives has been decreasing in the last years, probably as a consequence of the unfavourable effects reported by users. Thus, the list of possible cathinone analogues is expected to get shorter, and it is likely that the same moiety changes applied for the preparation of synthetic cathinones will be applied in the near future to other stimulants in the search for favourable alternatives to controlled substances. This is evidenced by the increase in newly reported substances belonging to stimulant classes other than cathinones. One of the possible candidates for a new backbone from which to base new stimulants is aminorex, which is classified as a Schedule I substance by the Drug Enforcement Administration. Three derivatives have been reported until now: 4-methylaminorex or 4-MAR (also categorized as a Schedule I substance), para-methyl-4-methylaminorex (4,4′-DMAR) and 3′,4′-methylenedioxy-4-methylaminorex (MDMAR). Recently, the new halogenated 4-MAR derivative, para-fluoro-4-methylaminorex, characterised in this work (and abbreviated as pF-4-methylaminorex or 4′F-4-MAR) was detected by the Slovenian police. In the present work, 4′F-4-MAR has been characterized by high resolution mass spectrometry and nuclear magnetic resonance in a sample obtained from an anonymous consumer. This research shows that the same modifications applied for the preparation of synthetic cathinones are being used to prepare new stimulants based on the aminorex backbone.
Mechanism of nitrite-dependent NO synthesis by human sulfite oxidase
Authors: Bender Daniel , Tobias Kaczmarek Alexander , Niks Dimitri , Hille Russ , Schwarz Guenter 
Published: June 2019

Abstract
In addition to nitric oxide (NO) synthases, molybdenum-dependent enzymes have been reported to reduce nitrite to produce NO. Here, we report the stoichiometric reduction in nitrite to NO by human sulfite oxidase (SO), a mitochondrial intermembrane space enzyme primarily involved in cysteine catabolism. Kinetic and spectroscopic studies provide evidence for direct nitrite coordination at the molybdenum center followed by an inner shell electron transfer mechanism. In the presence of the physiological electron acceptor cytochrome c, we were able to close the catalytic cycle of sulfite-dependent nitrite reduction thus leading to steady-state NO synthesis, a finding that strongly supports a physiological relevance of SO-dependent NO formation. By engineering SO variants with reduced intramolecular electron transfer rate, we were able to increase NO generation efficacy by one order of magnitude, providing a mechanistic tool to tune NO synthesis by SO.
Turbulent power distribution in the local interstellar medium
Authors: Kalberla P. M. W. , Haud U. 
Published: June 2019

Context. The interstellar medium (ISM) on all scales is full of structures that can be used as tracers of processes that feed turbulence.
Aims. We used H I survey data to derive global properties of the angular power distribution of the local ISM.
Methods. HI4PI observations on an nside = 1024 HEALPix grid and Gaussian components representing three phases, the cold, warm, and unstable lukewarm neutral medium (CNM, WNM, and LNM), were used for velocities |vLSR|≤ 25 km s−1. For high latitudes |b| > 20° we generated apodized maps. After beam deconvolution we fitted angular power spectra.
Results. Power spectra for observed column densities are exceptionally well defined and straight in log-log presentation with 3D power law indices γ ≥−3 for the local gas. For intermediate velocity clouds (IVCs) we derive γ = −2.6 and for high velocity clouds (HVCs) γ = −2.0. Single-phase power distributions for the CNM, LNM, and WNM are highly correlated and shallow with γ ~−2.5 for multipoles l ≤ 100. Excess power from cold filamentary structures is observed at larger multipoles. The steepest single-channel power spectra for the CNM are found at velocities with large CNM and low WNM phase fractions.
Conclusions. The phase space distribution in the local ISM is configured by phase transitions and needs to be described with three distinct different phases, being highly correlated but having distributions with different properties. Phase transitions cause locally hierarchical structures in phase space. The CNM is structured on small scales and is restricted in position-velocity space. The LNM as an interface to the WNM envelops the CNM. It extends to larger scales than the CNM and covers a wider range of velocities. Correlations between the phases are self-similar in velocity.
Identification of newly developed advanced schistosomiasis with MALDI-TOF mass spectrometry and ClinProTools analysis
Authors: Huang Yuzheng , Xu Yongliang , Huang Yi , Sun Fang , Tian Haisong , Hu Nannan , Shi Liang , Hua Haiyong 
Published: June 2019

Cases of newly developed advanced schistosomiasis (NDAS) have occurred in areas where schistosomiasis transmission has been blocked for more than 25 years. The causes and pathogenesis of NDAS are still unknown. Diagnosis of NDAS relies on historical investigation and clinical symptoms, such as liver fibrosis, hepatic ascites and abnormal biochemical indexes in serum. It is important but difficult at this stage to develop a new tool for early screening and rapid diagnosis. In this study, serum peptides from thirty patients with NDAS and thirty healthy controls were captured with weak cation exchange magnetic beads, and subjected to MALDI-TOF mass spectrometry and ClinProTools analysis. Eleven peaks with m/z 924, 2661, 2953, 2991, 3241, 3884, 5337, 5905, 5943, 7766 and 9289 were decreased and three peaks with m/z 1945, 2082 and 4282 were increased in the NDAS group. The proteomic detection pattern (PDP) was established with 14 different peptide peaks, and its sensitivity and specificity were investigated with a blind test. The peptide mass fingerprints of sera from 50 NDAS patients and 100 healthy controls were double-blind subjected to the PDP method, and 50 patients and 92 healthy controls were classified as NDAS and healthy separately, which showed 100% sensitivity and 92% specificity. Our results showed that the PDP could be a new and useful method to detect NDAS.
50 Jahre Universitäts-Hautklinik am Biederstein in München
Authors: Eberlein B. , Darsow U. , Eyerich K. , Konstantinow A. , Posch C. , Volz T. , Zink A. , Brockow K. , Hein R. , Köberle M. , Möckel S. , Schnopp N. , Biedermann T. 
Published: June 2019

ZusammenfassungDie Klinik und Poliklinik für Dermatologie und Allergologie am Biederstein der Technischen Universität München (TUM) wurde 1969 in Betrieb genommen und feiert daher im Jahr 2019 ihr 50-jähriges Bestehen. Die Ursprünge dieser Klink gehen aber wie an vielen Orten auf ältere Versorgungsstrukturen zurück. Anlässlich des 50-jährigen Bestehens soll dieser Artikel die Entwicklung und aktuelle Ausrichtung der Klinik illustrieren und dabei auch die Wertschätzung für unsere Vorgänger ausdrücken, die sich auf den verschiedenen Positionen für unsere Patienten eingesetzt und so die Basis für eine erfolgreiche Klinik in Krankenversorgung, Forschung und Lehre geschaffen haben. Die Klinik und Poliklinik für Dermatologie und Allergologie am Biederstein gehört zum Universitätsklinikum, dem Klinikum rechts der Isar, der Technischen Universität München (TUM), sie selbst liegt jedoch links der Isar, im schönen Schwabing unweit des Englischen Gartens. Sie ist eine von 3 Hautkliniken in München, die im Rahmen der Münchner Dermatologischen Gesellschaft (MDG e. V.) regelmäßig Fortbildungen ausrichten. Die MDG am Biederstein wird sich im Jahr 2019 neben der Fortbildung auch dem Jubiläum dieser Klinik widmen.Die Klinik als universitäre Einrichtung umfasst den Bereich medizinische Versorgung mit 74 Betten auf 4 Stationen, einen ambulanten Bereich mit einer großen Poliklinik für Allgemein- und Privatpatienten (jährlich mehr als 60 000 Patientenbesuche), den Bereich Forschung mit verschiedenen Forschungsgruppen und großen Laboratorien sowie den Bereich Lehre, Weiter- und Fortbildung. Ein Schwerpunkt in der klinischen Versorgung und in der Forschung war bereits zur Zeit der Gründung der Klinik 1969 die Allergologie. Weiterhin bestehen Schwerpunkte im Bereich der entzündlichen Hauterkrankungen, der Dermatoonkologie, der Dermatoinfektiologie, der Dermatochirurgie und der Wundversorgung. Die Klinik hat das Comprehensive Allergy Center der Technischen Universität München (ACTUM) und EU-Exzellenz-Zentrum für Allergie auf den Weg gebracht und ist Teil der Krebszentren Comprehensive Cancer Center München der Technischen Universität München (CCC MünchenTUM) und des Comprehensive Cancer Center München (CCCM). Pro Semester werden etwa 450 Studenten im Rahmen von Vorlesungen, Seminaren und Praktika betreut. Neben Kongressen wie der Jahrestagung der Arbeitsgemeinschaft Dermatologische Forschung (ADF) im Jahr 2019 oder der European Society for Dermatological Research (ESDR) im Jahre 2016 richten die Klinik und der Lehrstuhl regelmäßige Fortbildungsveranstaltungen im Rahmen des Biedersteiner Symposiums, des Biedersteiner Kolloquiums und der MDG aus.
Soja in der veganen Ernährung – Lifestyleprodukte mit Gefahrenpotenzial für Birkenpollenallergiker?
Authors: Oesterlin C. , Kugler C. , Darsow U. , Biedermann T. , Brockow K. 
Published: June 2019

ZusammenfassungBei 10 % aller Birkenpollenallergiker wurden allergische Reaktionen auf die Sojabohne nachgewiesen. Typischerweise manifestieren diese sich in Form eines milden oralen Allergiesyndroms. Wir stellen 4 Patienten (1 Mann, 3 Frauen, 50 – 72 Jahre) mit primärer Birkenpollenallergie aus unserer Allergieabteilung vor, bei denen sich jedoch nach Verzehr von Sojamilch/-drink schwere allergische Reaktionen bis hin zur Anaphylaxie entwickelten. Diese Patienten litten unter einer Rhinoconjunctivitis allergica im Frühjahr und zusätzlichen pollenassoziierten Nahrungsmittelallergien. Haut-Pricktestungen auf Sojaprodukte waren positiv. Bei 3 von 4 Patienten war die Sojaallergie lediglich durch spezifische IgE-Antikörper auf das birkenpollenhomologe PR-10-Protein Gly m 4 nachweisbar, jedoch nicht auf den Sojagesamtextrakt (< 0,35 KU/l). Bei einer Patientin, die Sojaprodukte bisher immer vertragen hatte, wurde die Sojaallergie erst durch orale Provokationstestung nachgewiesen. Es handelt sich bei allen Patienten um eine sekundäre birkenpollenassoziierte Sojaanaphylaxie nach Einnahme großer Mengen an geringgradig verarbeiteten Sojaprodukten (Sojadrink). Diese stellt für Birkenpollenallergiker mit IgE-vermittelten Allergien sowohl auf das Birkenpollenallergen Bet v 1 als auch auf das homologe Gly m 4 in der Sojabohne aufgrund einer Kreuzreaktion ein Risiko dar.
Onkologische Therapiekonzepte bei systemischer Metastasierung des kolorektalen Karzinoms
Authors: Modest Dominik Paul , von Bergwelt-Baildon Michael 
Published: June 2019

ZusammenfassungDie onkologische Therapieführung des metastasierten Darmkrebs (mKRK) erfolgt in enger Kooperation mit anderen Fachdisziplinen, insbesondere der Chirurgie. Trotz Metastasierung können durch interdisziplinäre Behandlungen hier Langzeitverläufe ermöglicht werden, auch wenn die Erkrankung in der Mehrzahl der Fälle (unabhängig vom Behandlungspfad) nicht geheilt werden kann. Die rein onkologische Systemtherapie stützt sich derzeit vor allem auf Chemotherapiekombinationen und monoklonale Antikörper gegen VEGF (Vascular endothelial Growth Factor) und EGFR (Epidermal Growth Factor Receptor), die zu unterschiedlichen Regimen zusammengesetzt werden. Für die EGFR-Antikörper besteht mit den verschiedenen RAS-Mutationen ein negativer prädiktiver Biomarker, der aktuell durch die Beachtung der Primärtumorseite ergänzt wird. In späteren Therapielinien eröffnet sich derzeit die Möglichkeit einer personalisierten Therapie von Subgruppen. Hier sind insbesondere Patienten mit BRAF-V600E-Mutation (BRAF-inhibitorbasierte Kombinationen), Her2-positivem mKRK und Patienten mit MSI-H-Tumor (Checkpointinhibitoren) zu nennen.
Personalisierte Medizin bei Nierenzelltumoren
Authors: Junker Kerstin , Zeuschner Philip 
Published: June 2019

ZusammenfassungDie Entdeckung von immer kleineren Tumoren durch den umfassenden Einsatz von bildgebenden Verfahren, die Erweiterung der operativen Techniken und der systemischen Therapieoptionen fordern auch für Nierentumorpatienten eine Individualisierung der Therapie. Essenzielle Voraussetzung ist dabei die Kenntnis der Tumorbiologie, da sie eine differenzierte Diagnostik, individuelle Prognosebewertung und Therapiewahl, basierend auf Biomarkern, und die Entwicklung von neuen Therapiestrategien ermöglicht.Nierenzelltumore werden aktuell in 16 histologische Subtypen unterschieden, die durch spezifische genetische Veränderungen charakterisiert sind. Aufgrund ihrer unterschiedlichen Aggressivität ist die Kenntnis der Subtypen sowohl für die Therapieentscheidung als auch für die Nachsorge wichtig. Molekulare Marker können bei der Differenzialdiagnose eingesetzt werden. Molekulare Signaturen werden zukünftig aber auch wesentlich zur Prognosedifferenzierung innerhalb der Subtypen beitragen, wie für das klarzellige Nierenzellkarzinom bereits gezeigt wurde. Dies wird zur Entwicklung differenzierter Nachsorgeprotokolle und zu einer genaueren Selektion der Patienten für adjuvante Therapien führen. Für metastasierte Patienten stehen immer mehr medikamentöse Therapien zur Verfügung, die zielgerichtet in bestimmte zelluläre Signal- oder Kommunikationswege eingreifen. Auch wenn bisher noch keine validen prädiktiven Biomarker verfügbar sind, liegen vielversprechende Daten zu molekularen Signaturen in Korrelation mit dem Ansprechen auf Tyrosinkinaseinhibitoren oder Checkpointinhibitoren vor, die in Zukunft wesentlich besser als die klinischen Scores eine individuelle Therapiewahl ermöglichen werden.Zur Überführung der vielversprechenden Biomarker in die klinische Praxis sind nun prospektive multizentrische Studien erforderlich. Die Berücksichtigung von bereits vorhandenen Erkenntnissen aus der Tumorbiologie der verschiedenen NZK-Entitäten sowohl bez. der veränderten Signalwege in den Tumorzellen selbst als auch der Rolle des Mikromilieus einschließlich der Immunzellen ist eine essenzielle Voraussetzung für eine weitere Verbesserung von Diagnostik und Therapie.
Lung Diseases in Inflammatory Myopathies
Authors: Barba Thomas , Mainbourg Sabine , Nasser Mouhamad , Lega Jean-Christophe , Cottin Vincent 
Published: June 2019

AbstractLung involvement is the leading cause of mortality in inflammatory myopathy. A careful assessment of clinical and serologic manifestations especially myositis-associated autoantibodies allows precise classification of the different phenotypes of inflammatory myopathy and stratification of the risk of lung involvement. About three out of four patients with inflammatory myopathy develop interstitial lung disease (ILD), which represents the main cause of morbidity and mortality. In patients with a confirmed diagnosis of inflammatory myopathy, the approach to the diagnosis of ILD includes assessment of clinical and functional severity, evaluation of the high-resolution computed tomography pattern of disease, which often suggests nonspecific interstitial pneumonia or organizing pneumonia. Bronchoalveolar lavage to rule out infection is often performed; however, video-assisted thoracoscopic lung biopsy is now generally discouraged, unless malignancy is suspected. The so-called antisynthetase syndrome characterized by the combination of mechanics' hands, Raynaud' phenomenon, myositis often mild or absent, and presence of one of the anti-tRNA synthetase antibodies is associated with a 70% risk of ILD, especially in subjects with antibodies other than anti-Jo1 antibodies (i.e., anti-PL7 or -PL12 antibodies). Treatment depends on both severity and progression of ILD, often including a combination of corticosteroids and immunosuppressive therapy. Rituximab-based regimen has showed promising results in retrospective studies for the management of refractory or rapidly progressive forms of ILD. Clinical trials are ongoing to evaluate the actual efficacy of this strategy on mortality related to lung disease. Secondary pulmonary complications of inflammatory myopathy include opportunistic infections, aspiration pneumonia, pneumomediastinum, ventilatory failure due to diaphragmatic muscular weakness, drug-induced pneumonitis, and rarely pulmonary hypertension.
Ontology-Based Interactive Visualization of Patient-Generated Research Questions
Authors: Borland David , Christopherson Laura , Schmitt Charles 
Published: June 2019

Background Crohn's disease and colitis are chronic conditions that affect every facet of patients' lives (e.g., social interaction, family, work, diet, and sleep). Thus, treatment consists largely of disease management. The University of North Carolina at Chapel Hill chapter of the Crohn's and Colitis Foundation—IBD Partners—has created an interactive website that, in addition to providing helpful information and disease management tools, provides a discussion forum for patients to talk about their experiences and suggest new lines of research into Crohn's disease and colitis.
Objectives The primary objective of this work is to enable researchers to more effectively browse the forum content. Researchers wish to identify important/popular patient-suggested research topics, appreciate the full breadth of the research topics, and see connections between them, in order to more effectively prioritize research agendas.
Methods To help structure the forum content we have developed an ontology describing the major themes in the discussion forum. We have also created a prototype interactive visualization tool that leverages the ontology to help researchers identify common themes and related patient-generated research topics via linked views of (1) the ontology, (2) a research topic overview clustered by relevant ontology terms, and (3) a detailed view of the discussion forum content.
Results We discuss visualizations and interactions enabled by the visualization tool, provide an example scenario using the tool, and discuss limitations and future work based on feedback from potential users.
Conclusion The integration of a user-community specific ontology with an interactive visualization tool is a promising approach for enabling researchers to more effectively study user-generated research questions.
Head Circumference Growth Is Enhanced by SMOFlipid in Preterm Neonates
Authors: Bin-Nun Alona , Kassirer Yair , Mimouni Francis B. , Shchors Irina , Hammerman Cathy 
Published: June 2019

Abstract
Background Suboptimal fat intake during the early postnatal weeks significantly affects brain growth and maturation. Studies to date have focused on the quantity rather than the quality of fat intake.
Objective We hypothesized that early nutrition of premature neonates should also include optimization of the type of fat intake, and thus those receiving SMOFlipid, a balanced multicomponent lipid emulsion, would have improved head growth as measured by head circumference (HC) at discharge.
Study Design We retrospectively reviewed HC in infants weighing <1,500 g who were hospitalized for two or more weeks during a 20-month period, in which all preterm infants received fat as Lipofundin, and the following 20-month period, in which all such infants received SMOFlipid.Lipids were dosed up to 3 g/kg/day and reduced as enteral nutrition progressed. Parenteral fish oil (Omegaven) was permitted as rescue therapy during both periods.
Results Period 2 infants had better head growth (0.79 [0.69,0.90] vs. 0.75 [0.64,0.86] cm/week; p = 0.0158). More infants reached discharge with an HC of ≥50 percentile (51 vs. 31%; p = 0.0007), and fewer infants had an HC of ≤3 percentile (11 vs. 14%; p = 0.023). Median length of stay was reduced by more than 1 week.A multivariable regression was performed using the weekly increase in HC as the dependent variable, and the time epoch, birth weight, gestational age, hospitalization days, and gender as independent variables. Only the time epoch and days of hospitalization were significant (both p < 0.0001).
Conclusion Our data offer preliminary evidence of improved brain growth in those receiving a balanced lipid emulsion as compared with a soybean oil emulsion.
Multifrequency source for pumping CPT-resonances based on an external cavity diode laser
Authors: Isakova A.A. , Golovin N.N. , Savinov K.N. , Dmitriev A.K. 
Published: June 2019

Abstract
We report the results of studying operation regimes for an external-cavity diode laser in which the intermode interval corresponds to the clock transition frequency under modulation of the injection current by an rf oscillator, which provides multifrequency pumping of CPT-resonances.
Stable random lasing in CdSSe micropowders
Authors: Leanenia M.S. , Nagorny A.V. , Urmanov B.D. , Shulenkova V.A. , Yablonskii G.P. 
Published: June 2019

Abstract
The random lasing in CdS micropowder in the green region (near 520 nm) at room temperature under optical pumping by pulsed Nd3+ : YAG and N2 lasers at wavelengths of 355 and 337 nm, respectively, is studied. The influence of fluctuations of pump pulse output energy on the random lasing action in CdS micropowder is determined. It is shown that the use of a pump laser with highly stable output power and high spatial beam uniformity (in particular, an N2 laser) provides stable random lasing in CdSSe micropowders. The lasing is characterised by the presence of a clear structure of narrow lines in the spectrum and stability of their position during pulsed operation at a repetition rate of 700 Hz at wavelengths of 525, 570, 600, and 650 nm with thresholds in the range of 1100 – 1600 kW cm−2.
Toward Resolved Simulations of Burning Fronts in Thermonuclear X-ray Bursts
Authors: Zingale M. , Eiden K. , Cavecchi Y. , Harpole A. , Bell J. B. , Chang M. , Hawke I. , Katz M. P. , Malone C. M. , Nonaka A. J. , Willcox D. E. , Zhang W. 
Published: June 2019

Abstract
We discuss the challenges of modeling X-ray bursts in multi-dimensions, review the different calculations done to date, and discuss our new set of ongoing simulations. We also describe algorithmic improvements that may help in the future to offset some of the expense of these simulations, and describe what may be possible with exascale computing.