bluuebunny/crossref_metadata_2025_split huggingface dataset:
Urinary Exosomes from Bladder Cancer Patients Show a Residual Cancer Phenotype despite Complete Pathological Downstaging
Authors: Hiltbrunner Stefanie , Mints Michael , Eldh Maria , Rosenblatt Robert , Holmström Benny , Alamdari Farhood , Johansson Markus , Veerman Rosanne E. , Winqvist Ola , Sherif Amir , Gabrielsson Susanne 
Published: April 2020

AbstractInvasive urinary bladder cancer shows high recurrence rates after cystectomy even with apparent complete downstaging at cystectomy. Exosomes are nano-sized vesicles important in cell-cell communication, which have been hypothesized to contribute to cancer dissemination and recurrence. The aim of this study was to investigate if pro-carcinogenic exosomes could be detected in urine from histologically downstaged bladder cancer patients. 13 Patients were included in this study. Paired ureter and urine samples from nine patients underwent mass spectrometry, while samples from the remaining patients were used for exosome characterization. At cystectomy, exosomes were isolated from bladder and ureter urine, whereafter quantitative proteome profiling was performed. Urinary exosomes clustered based on whether they came from the bladder, with tumour contact, or the ureters, without tumour contact, even though all came from completely downstaged patients. Proteins overexpressed in exosomes derived from bladder urine contained several oncogenes and were mainly associated with tumour metabolism pathways. Although patients were histologically tumour-free at cystectomy, the bladder urine contained exosomes with a carcinogenic metabolic profile. This suggests a continuous release of exosomes from the bladder, which may promote recurrence at distant sites through metabolic rewiring, even after apparent complete downstaging. These exosomes, coming from either undetected cancer cells or partly transformed cells, are likely to increase the risk of metastasis and encourages cystectomy even in completely downstaged patients.
Urban Particles Elevated Streptococcus pneumoniae Biofilms, Colonization of the Human Middle Ear Epithelial Cells, Mouse Nasopharynx and Transit to the Middle Ear and Lungs
Authors: Yadav Mukesh Kumar , Go Yoon Young , Jun Indong , Chae Sung-Won , Song Jae-Jun 
Published: April 2020

AbstractAir-pollutants containing toxic particulate matters (PM) deposit in the respiratory tract and increases microbial infections. However, the mechanism by which this occurs is not well understood. This study evaluated the effect of urban particles (UP) on Streptococcus pneumoniae (pneumococcus) in vitro biofilm formation, colonization of human middle ear epithelium cells (HMEECs) as well as mouse nasal cavity and its transition to the middle ear and lungs. The in vitro biofilms and planktonic growth of S. pneumoniae were evaluated in metal ion free medium in the presence of UP. Biofilms were quantified by crystal violet (CV) microplate assay, colony forming unit (cfu) counts and resazurin staining. Biofilm structures were analyzed using a scanning electron microscope (SEM) and confocal microscopy (CM). Gene expressions of biofilms were evaluated using real time RT-PCR. Effects of UP exposure on S. pneumoniae colonization to HMEECs were evaluated using fluorescent in-situ hybridization (FISH), cell viability was detected using the Ezcyto kit, apoptosis in HMEECs were evaluated using Annexin-V/PI based cytometry analysis and reactive oxygen species (ROS) production were evaluated using the Oxiselect kit. Alteration of HMEECs gene expressions on UP exposure or pneumococci colonization was evaluated using microarray. In vivo colonization of pneumococci in the presence of UP and transition to middle ear and lungs were evaluated using an intranasal mice colonization model. The UP exposure significantly increased (*p < 0.05) pneumococcal in vitro biofilms and planktonic growth. In the presence of UP, pneumococci formed organized biofilms with a matrix, while in absence of UP bacteria were unable to form biofilms. The luxS, ply, lytA, comA, comB and ciaR genes involved in bacterial pathogenesis, biofilm formation and quorum sensing were up-regulated in pneumococci biofilms grown in the presence of UP. The HMEECs viability was significantly decreased (p < 0.05) and bacteria colonization was significantly elevated (p < 0.05) in co-treatment (UP + S. pneumoniae) when compared to single treatment. Similarly, increased apoptosis and ROS production were detected in HMEECs treated with UP + pneumococci. The microarray analysis of HMEECs revealed that the genes involve in apoptosis and cell death, inflammation, and immune response, were up-regulated in co-treatment and were unchanged or expressed in less fold in single treatments of UP or S. pneumoniae. The in vivo study showed an increased pneumococcal colonization of the nasopharynx in the presence of UP and a higher transition of bacteria to the middle ear and lungs in the presence of UP. The UP exposure elevated S. pneumoniae in vitro biofilm and colonization of HMEECs, and in vivo mouse nasopharyngeal colonization, and increased dissemination to mouse middle ear and lungs.
Network-based metabolic characterization of renal cell carcinoma
Authors: Pandey Nishtha , Lanke Vinay , Vinod P. K. 
Published: April 2020

AbstractAn emerging hallmark of cancer is metabolic reprogramming, which presents opportunities for cancer diagnosis and treatment based on metabolism. We performed a comprehensive metabolic network analysis of major renal cell carcinoma (RCC) subtypes including clear cell, papillary and chromophobe by integrating transcriptomic data with the human genome-scale metabolic model to understand the coordination of metabolic pathways in cancer cells. We identified metabolic alterations of each subtype with respect to tumor-adjacent normal samples and compared them to understand the differences between subtypes. We found that genes of amino acid metabolism and redox homeostasis are significantly altered in RCC subtypes. Chromophobe showed metabolic divergence compared to other subtypes with upregulation of genes involved in glutamine anaplerosis and aspartate biosynthesis. A difference in transcriptional regulation involving HIF1A is observed between subtypes. We identified E2F1 and FOXM1 as other major transcriptional activators of metabolic genes in RCC. Further, the co-expression pattern of metabolic genes in each patient showed the variations in metabolism within RCC subtypes. We also found that co-expression modules of each subtype have tumor stage-specific behavior, which may have clinical implications.
CXXC5 as an unmethylated CpG dinucleotide binding protein contributes to estrogen-mediated cellular proliferation
Authors: Ayaz Gamze , Razizadeh Negin , Yaşar Pelin , Kars Gizem , Kahraman Deniz Cansen , Saatci Özge , Şahin Özgür , Çetin-Atalay Rengül , Muyan Mesut 
Published: April 2020

AbstractEvidence suggests that the CXXC type zinc finger (ZF-CXXC) protein 5 (CXXC5) is a critical regulator/integrator of various signaling pathways that include the estrogen (E2)-estrogen receptor α (ERα). Due to its ZF-CXXC domain, CXXC5 is considered to be a member of the ZF-CXXC family, which binds to unmethylated CpG dinucleotides of DNA and through enzymatic activities for DNA methylation and/or chromatin modifications generates a chromatin state critical for gene expressions. Structural/functional features of CXXC5 remain largely unknown. CXXC5, suggested as transcription and/or epigenetic factor, participates in cellular proliferation, differentiation, and death. To explore the role of CXXC5 in E2-ERα mediated cellular events, we verified by generating a recombinant protein that CXXC5 is indeed an unmethylated CpG binder. We uncovered that CXXC5, although lacks a transcription activation/repression function, participates in E2-driven cellular proliferation by modulating the expression of distinct and mutual genes also regulated by E2. Furthermore, we found that the overexpression ofCXXC5, which correlates with mRNA and protein levels of ERα, associates with poor prognosis in ER-positive breast cancer patients. Thus, CXXC5 as an unmethylated CpG binder contributes to E2-mediated gene expressions that result in the regulation of cellular proliferation and may contribute to ER-positive breast cancer progression.
Long-term exposure to nanoplastics reduces life-time in Daphnia magna
Authors: Kelpsiene Egle , Torstensson Oscar , Ekvall Mikael T. , Hansson Lars-Anders , Cedervall Tommy 
Published: April 2020

AbstractPlastics are widely used in todays society leading to an accelerating amount of plastic waste entering natural ecosystems. Over time these waste products degrade to micro- and, eventually, nanoplastic particles. Therefore, the break-down of plastics may become a critical threat to aquatic ecosystems and several short term studies have demonstrated acute toxicity of nanoplastics on aquatic organisms. However, our knowledge about effects of chronic or life-time exposure on freshwater invertebrates remains elusive. Here, we demonstrate results from life-time exposure (103 days) of a common freshwater invertebrate, Daphnia magna, exposed to sub-lethal concentrations of polystyrene nanoparticles. 53 nm positively charged aminated polystyrene particles were lethal at concentration of 0.32 mg/L which is two magnitudes lower than previously used concentrations in short-term (24 h) tests. At this concentration the life-time of individuals was shortened almost three times. Negatively charged carboxylated 26 and 62 nm polystyrene particles, previously demonstrated to be non-toxic at 25 and 50 mg/L concentrations in short-term tests, were toxic to D. magna at all concentrations used in our long-term study. Although total reproductive output was not significantly affected at increasing concentrations of polystyrene nanoparticles, there was a decreasing trend in the number of offspring over their life-time. Hence, in order to understand how the potential future environmental problem of nanoplastic particles may affect biota, long-term or life-time studies resembling environmental concentrations should be performed in order to provide information for predictions of future scenarios in natural aquatic environments.
Tungsten Diselenide Top-gate Transistors with Multilayer Antimonene Electrodes: Gate Stacks and Epitaxially Grown 2D Material Heterostructures
Authors: Zhang Yu-Wei , Li Jun-Yan , Wu Chao-Hsin , Chang Chiao-Yun , Chang Shu-Wei , Shih Min-Hsiung , Lin Shih-Yen 
Published: April 2020

AbstractWe have demonstrated that with e-beam deposition of a thin Al2O3 layer before atomic layer deposition, a uniform Al2O3 film can be obtained on WSe2/sapphire samples. Device performances are observed for WSe2 top-gate transistors by using oxide stacks as the gate dielectric. By using thermal evaporation, epitaxially grown multilayer antimonene can be prepared on both MoS2 and WSe2 surfaces. With multilayer antimonene as the contact metal, a significant increase in drain currents and ON/OFF ratios is observed for the device, which indicates that high contact resistance between metal/2D material interfaces is a critical issue for 2D devices. The observation of multilayer antimonene grown on different 2D material surfaces has demonstrated less dependence on the substrate lattice constant of the unique van der Waals epitaxy for 2D materials. The results have also demonstrated that stacking 2D materials with different materials plays an important role in the practical applications of 2D devices.
Probing the magnetospheric accretion region of the young pre-transitional disk system DoAr 44 using VLTI/GRAVITY
Authors: Bouvier J. , Perraut K. , Le Bouquin J.-B. , Duvert G. , Dougados C. , Brandner W. , Benisty M. , Berger J.-P. , Alécian E. 
Published: April 2020

Context. Young stellar objects are thought to accrete material from their circumstellar disks through their strong stellar magnetospheres.
Aims. We aim to directly probe the magnetospheric accretion region on a scale of a few 0.01 au in a young stellar system using long-baseline optical interferometry.
Methods. We observed the pre-transitional disk system DoAr 44 with VLTI/GRAVITY on two consecutive nights in the K-band. We computed interferometric visibilities and phases in the continuum and in the Brγ line in order to constrain the extent and geometry of the emitting regions.
Results. We resolve the continuum emission of the inner dusty disk and measure a half-flux radius of 0.14 au. We derive the inclination and position angle of the inner disk, which provides direct evidence that the inner and outer disks are misaligned in this pre-transitional system. This may account for the shadows previously detected in the outer disk. We show that Brγ emission arises from an even more compact region than the inner disk, with an upper limit of 0.047 au (~5 R⋆). Differential phase measurements between the Brγ line and the continuum allow us to measure the astrometric displacement of the Brγ line-emitting region relative to the continuum on a scale of a few tens of microarcsec, corresponding to a fraction of the stellar radius.
Conclusions. Our results can be accounted for by a simple geometric model where the Brγ line emission arises from a compact region interior to the inner disk edge, on a scale of a few stellar radii, fully consistent with the concept of magnetospheric accretion process in low-mass young stellar systems.
The quest for AMS of 182Hf – why poor gas gives pure beams
Authors: Martschini Martin , Lachner Johannes , Merchel Silke , Priller Alfred , Steier Peter , Wallner Anton , Wieser Alexander , Golser Robin 
Published: April 2020

The long-lived radioisotope 182Hf (T1/2 = 8.9 Ma) is of high astrophysical interest as its potential abundance in environmental archives would provide insight into recent r-process nucleosynthesis in the vicinity of our solar system. Despite substantial efforts, it could not be measured at natural abundances with conventional AMS so far due to strong isobaric interference from stable 182W. Equally important is an increase in ion source efficiency for the anions of interest.
The new Ion Laser InterAction Mass Spectrometry (ILIAMS) technique at VERA tackles the problem of elemental selectivity in AMS with a novel approach. It achieves near-complete suppression of isobar contaminants via selective laser photodetachment of decelerated anion beams in a gas-filled radio-frequency quadrupole (RFQ) ion cooler. The technique exploits differences in electron affinities (EA) within elemental or molecular isobaric systems neutralizing anions with EAs smaller than the photon energy. Alternatively, these differences in EA can also facilitate anion separation via chemical reactions with the buffer gas.
We present first results with this approach on AMS-detection of 182Hf. With He +O2 mixtures as buffer gas in the RFQ, suppression of 182WF5− vs 180HfF 5− by >105 has been demonstrated. Mass analysis of the ejected anion beam identified the formation of oxyfluorides as an important reaction channel. The overall Hf-detection efficiency at VERA presently is 1.4% and the W-corrected blank value is 182Hf/180Hf = (3.4 ± 2.1)×10−14. In addition, a survey of different sample materials for highest negative ion yields of HfF 5− with Cs-sputtering has been conducted.
Is Exercise a Match for Cold Exposure? Common Molecular Framework for
Adipose Tissue Browning
Authors: Martin Alexandra R. , Chung Soonkyu , Koehler Karsten 
Published: April 2020

AbstractExercise is commonly utilized for weight loss, yet research has focused less
on specific modifications to adipose tissue metabolism. White adipose tissue
(WAT) is the storage form of fat, whereas brown adipose tissue (BAT) is a
thermogenic tissue whose uncoupling increases energy expenditure. The most
established BAT activator is cold exposure, which also transforms WAT into
“beige cells” that express uncoupling protein 1 (UCP1).
Preliminary evidence in rodents suggests exercise elicits similar effects.
The purpose of this review is to parallel and examine differences between
exercise and cold exposure on BAT activation and beige induction. Like cold
exposure, exercise stimulates the sympathetic nervous system and activates
molecular pathways responsible for BAT/beige activation, including
upregulation of BAT activation markers (UCP1, proliferator-activated
receptor-gamma coactivator-1α) and stimulation of endocrine
activators (fibroblast growth factor-21, irisin, and natriuretic peptides).
Further, certain BAT activators are altered exclusively by exercise
(interleukin-6, lactate). Markers of BAT activation increase from both cold
exposure and exercise, whereas effects in WAT are compartment-specific.
Stimulation of endocrine activators depends on numerous factors, including
stimulus intensity and duration. Evidence of these analogous, albeit not
mirrored, mechanisms is demonstrated by increases in adipose activity in
rodents, while effects remain challenging to quantify in humans.
Salt Appetite and its Effects on Cardiovascular Risk in Primary
Aldosteronism
Authors: Adolf Christian , Schneider Holger , Heinrich Daniel A. , Handgriff Laura , Reincke Martin 
Published: April 2020

AbstractFirst described in 1955 by Jerome W. Conn, primary aldosteronism (PA) today is
well established as a relevant cause of secondary hypertension and accounts for
about 5–10 % of hypertensives. The importance of considering PA
is based on its deleterious target organ damage far beyond the effect of
elevated blood pressure and on PA being a potentially curable form of
hypertension. Aside the established contributory role of high dietary salt
intake to arterial hypertension and cardiovascular disease, high salt intake is
mandatory for aldosterone-mediated deleterious effects on target-organ damage in
patients with primary aldosteronism. Consequently, counselling patients on the
need to reduce salt intake represents a major component in the treatment of PA
to minimize cardiovascular damage. Unfortunately, in PA patients salt intake is
high and far beyond the target values of 5 g per day, recommended by the
World Health Organization. Insufficient patient motivation for lifestyle
interventions can be further complicated by enhancing effects of aldosterone on
salt appetite, via central and gustatory pathways. In this context, treatment
for PA by adrenalectomy results in a spontaneous decrease in dietary salt intake
and might therefore provide further reduction of cardiovascular risk in PA than
specific medical treatment alone. Furthermore, there is evidence from clinical
studies that even after sufficient treatment of PA dietary salt intake remains a
relevant prognostic factor for cardiovascular risk. This review will focus on
the synergistic benefits derived from both blockade of aldosterone-mediated
effects and reduction in dietary salt intake on cardiovascular risk.
Die kultursensible Therapiebeziehung: Ein Konzept für die Aus-, Fort- und Weiterbildung von Psychotherapeutinnen und Psychotherapeuten
Authors: Haller Julia , Hillebrecht Jennifer , Bengel Jürgen 
Published: April 2020

ZusammenfassungBereits 2002 wurde im Rahmen der Sonnenberger Leitlinien die Entwicklung von Fortbildungsprogrammen für Psychotherapeuten im Sinne der interkulturellen Öffnung des psychosozialen Versorgungssystems gefordert [1]. Bislang mangelt es jedoch an evaluierten, zugänglichen (veröffentlichten) Fortbildungskonzepten zur Förderung inter- bzw. transkultureller Kompetenzen von Psychotherapeuten im deutschsprachigen Raum. Der vorliegende Beitrag stellt ein Fortbildungskonzept für ärztliche und psychologische Psychotherapeuten sowie für Psychologen in Ausbildung vor, das auf den Leitlinien für Trainings inter-/transkultureller Kompetenz in der Aus-, Fort- und Weiterbildung von Psychotherapeuten [2] basiert. Das Konzept legt einen besonderen Fokus auf die Reflexion eigener kulturell geprägter Werte sowie auf Wissensinhalte und Fertigkeiten, die den Aufbau einer therapeutischen Beziehung im interkulturellen Setting erleichtern. Es werden Hinweise zur praktischen Implementierung gegeben, die Lesern die Umsetzung des Konzepts als Lehrende erleichtern.
COMP-Ang-1 Improves Glucose Uptake in db/db
Mice with Type 2 Diabetes
Authors: Baum Petra , Paeschke Sabine , Klöting Nora , Blüher Matthias , Kern Matthias , Serke Heike , Nowicki Marcin , Kosacka Joanna 
Published: April 2020

AbstractCartilage oligomeric matrix protein (COMP)-Angiopoietin-1 is a potent
angiopoietin-1 (Ang-1) variant that possesses therapeutic potential in
angiogenesis and vascular endothelial dysfunction. Noteworthy, we have shown
that COMP-Ang-1 improves hyperglycemia and neuroregeneration in
ob/ob mice. However, the mechanism of the antidiabetic
effect of COMP-Ang-1 is completely unknown. Therefore, we elucidated the
diabetes protective molecular mechanisms of COMP-Ang-1 in diabetic
db/db mouse model. COMP-Ang-1
(0.5 ng/g body weight) or aqueous NaCl solution was injected
intraperitoneally per day in 21 consecutive days into 3-month old, male
db/db mice (n=10 per group). Blood glucose and
HbA1c levels were determined at baseline and 21 days after COMP-Ang-1 or NaCl
treatment. The effect of COMP-Ang-1 on glucose uptake was investigated by
euglycemic-hyperinsulinemic clamp studies and key genes of glucose metabolism
were studied by Western blot analysis. Our findings indicate that COMP-Ang-1
improves glucose metabolism in a tissue specific manner by regulating
HIF-1α transcriptional genes of GLUT-1 expression.
Medizinisch-beruflich orientierte Rehabilitation bei Rehabilitanden mit muskuloskelettalen Erkrankungen: eine Propensity-Score-Analyse
Authors: Fauser David , Vogel Martin , Bethge Matthias 
Published: April 2020

Zusammenfassung
Ziel der Studie Die medizinisch-beruflich orientierte Rehabilitation ist ein multimodales interdisziplinär durchgeführtes Programm, das Diskrepanzen von arbeitsplatzbezogenen Fähigkeiten und Anforderungen zu verringern sucht, um berufliche Teilhabechancen von Personen mit ungünstiger Erwerbsprognose zu verbessern. Die Studie untersuchte die Teilhabeeffekte eines in der regulären Versorgung implementierten medizinisch-beruflich orientierten Rehabilitationsprogramms im Vergleich zur herkömmlichen medizinischen Rehabilitation bei Rehabilitanden mit Muskel-Skelett-Erkrankungen.
Methodik Die Daten wurden 2014 und 2015 erhoben und anhand einer As-treated-Analyse ausgewertet. Mittels Propensity-Score-Matching wurden die Ergebnisse von Teilnehmenden einer medizinische-beruflich orientierten Rehabilitation (Interventionsgruppe, IG) mit denen von vergleichbaren Teilnehmenden einer herkömmlichen medizinischen Rehabilitation (Kontrollgruppe, KG) verglichen. Primäres Zielkriterium war die Rate sozialversicherungspflichtiger Beschäftigung ein Jahr nach Rehabilitationsende. Die Behandlungseffekte wurden mit logistischen Modellen überprüft und absolute Risikodifferenzen (ARR) berechnet.
Ergebnisse Ein Jahr nach Rehabilitationsende wurden die Daten von 312 Rehabilitanden analysiert (156 in der IG). Mittels Propensity-Score-Matching konnten Stichproben mit balancierten Stichprobenmerkmalen generiert werden. Der Anteil sozialversicherungspflichtig beschäftigter Rehabilitanden in der IG war um rund 11 Prozentpunkte höher als in der KG (ARR=0,11; 95% KI: 0,02–0,20; p=0,020).
Schlussfolgerung Die medizinisch-beruflich orientierte Rehabilitation führt im Vergleich zur herkömmlichen medizinischen Rehabilitation zu deutlich höheren Beschäftigungsraten nach einem Jahr.