bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aberrant pregnancy-associated plasma protein-A expression in breast cancers prognosticates clinical outcomes
Authors: Prithviraj Prashanth , Anaka Matthew , Thompson Erik W. , Sharma Revati , Walkiewicz Marzena , Tutuka Candani S. A. , Behren Andreas , Kannourakis George , Jayachandran Aparna 
Published: August 2020

AbstractElevated levels of pregnancy-associated plasma protein-A (PAPP-A) have been implicated in the pathogenesis of various malignancies, including breast cancers. Breast cancer is one of the most frequent carcinomas and is the second most common cancer type detected in women of child-bearing age. Throughout pregnancy PAPP-A is produced and secreted by the placental syncytiotrophoblast cells; co-incidentally pregnancy-associated breast cancers often have an aggressive clinical course. The components of the PAPP-A/IGF axis was assessed in a panel of breast cancer cell lines. Using neutralising antibodies the impact of PAPP-A/IGF axis on cell motility was evaluated. PAPP-A was expressed in four of the twelve breast cancer cell lines tested. Blocking PAPP-A and IGFBP4 with neutralising antibodies significantly decreased motiliy of MDA-MB-231 cells. Upregulation of PAPP-A expression in breast tumours resulted in a trend towards worse overall survival. Notably, PAPP-A expression also positively correlated with epithelial-to-mesenchymal transition markers. In conclusion, these results indicate that PAPP-A plays an important role in breast cancer progression and it may be a promising therapeutic target in breast cancer.
Real time monitoring of oxygen uptake of hepatocytes in a microreactor using optical microsensors
Authors: Gehre Christian , Flechner Marie , Kammerer Sarah , Küpper Jan-Heiner , Coleman Charles Dominic , Püschel Gerhard Paul , Uhlig Katja , Duschl Claus 
Published: August 2020

AbstractMost in vitro test systems for the assessment of toxicity are based on endpoint measurements and cannot contribute much to the establishment of mechanistic models, which are crucially important for further progress in this field. Hence, in recent years, much effort has been put into the development of methods that generate kinetic data. Real time measurements of the metabolic activity of cells based on the use of oxygen sensitive microsensor beads have been shown to provide access to the mode of action of compounds in hepatocytes. However, for fully exploiting this approach a detailed knowledge of the microenvironment of the cells is required. In this work, we investigate the cellular behaviour of three types of hepatocytes, HepG2 cells, HepG2-3A4 cells and primary mouse hepatocytes, towards their exposure to acetaminophen when the availability of oxygen for the cell is systematically varied. We show that the relative emergence of two modes of action, one NAPQI dependent and the other one transient and NAPQI independent, scale with expression level of CYP3A4. The transient cellular response associated to mitochondrial respiration is used to characterise the influence of the initial oxygen concentration in the wells before exposure to acetaminophen on the cell behaviour. A simple model is presented to describe the behaviour of the cells in this scenario. It demonstrates the level of control over the role of oxygen supply in these experiments. This is crucial for establishing this approach into a reliable and powerful method for the assessment of toxicity.
Rapid three-dimensional multiparametric MRI with quantitative transient-state imaging
Authors: Gómez Pedro A. , Cencini Matteo , Golbabaee Mohammad , Schulte Rolf F. , Pirkl Carolin , Horvath Izabela , Fallo Giada , Peretti Luca , Tosetti Michela , Menze Bjoern H. , Buonincontri Guido 
Published: August 2020

AbstractNovel methods for quantitative, transient-state multiparametric imaging are increasingly being demonstrated for assessment of disease and treatment efficacy. Here, we build on these by assessing the most common Non-Cartesian readout trajectories (2D/3D radials and spirals), demonstrating efficient anti-aliasing with a k-space view-sharing technique, and proposing novel methods for parameter inference with neural networks that incorporate the estimation of proton density. Our results show good agreement with gold standard and phantom references for all readout trajectories at 1.5 T and 3 T. Parameters inferred with the neural network were within 6.58% difference from the parameters inferred with a high-resolution dictionary. Concordance correlation coefficients were above 0.92 and the normalized root mean squared error ranged between 4.2 and 12.7% with respect to gold-standard phantom references for T1 and T2. In vivo acquisitions demonstrate sub-millimetric isotropic resolution in under five minutes with reconstruction and inference times < 7 min. Our 3D quantitative transient-state imaging approach could enable high-resolution multiparametric tissue quantification within clinically acceptable acquisition and reconstruction times.
A novel approach to genetic engineering of T-cell subsets by hematopoietic stem cell infection with a bicistronic lentivirus
Authors: Bogert N. V. , Furkel J. , Din S. , Braren I. , Eckstein V. , Müller J. A. , Uhlmann L. , Katus H. A. , Konstandin M. H. 
Published: August 2020

AbstractLentiviral modification of hematopoietic stem cells (HSCs) paved the way for in vivo experimentation and therapeutic approaches in patients with genetic disease. A disadvantage of this method is the use of a ubiquitous promoter leads not only to genetic modification of the leukocyte subset of interest e.g. T-cells, but also all other subsequent leukocyte progeny of the parent HSCs. To overcome this limitation we tested a bicistronic lentivirus, enabling subset specific modifications. Designed novel lentiviral constructs harbor a global promoter (mPGK) regulating mCherry for HSCs selection and a T-cell specific promoter upstream of eGFP. Two T-cell specific promoters were assessed: the distal Lck—(dLck) and the CD3δ-promoter. Transduced HSCs were FACS sorted by mCherry expression and transferred into sublethally irradiated C57/BL6 mice. Successful transplantation and T-cell specific expression of eGFP was monitored by peripheral blood assessment. Furthermore, recruitment response of lentiviral engineered leukocytes to the site of inflammation was tested in a peritonitis model without functional impairment. Our constructed lentivirus enables fast generation of subset specific leukocyte transgenesis as shown in T-cells in vivo and opens new opportunities to modify other HSCs derived subsets in the future.
Thermal analysis of a Gramme‐ring‐winding high‐speed permanent‐magnet motor for pulsed alternator using CFD
Authors: Wan Yuan , Li Qiang , Guo Jian , Cui Shumei 
Published: August 2020

Due to the merit of very‐short end turns, Gramme‐ring windings are widely used in high‐speed permanent‐magnet motors (HSPMMs). This study investigated the thermal issues of a 300 kW, 12,000 rpm Gramme‐ring‐winding HPSMM with housing water jacket and forced air cooling, based on the computational fluid dynamics (CFD) and numerical heat‐transfer calculations. The reasons that cause the overheat of the prototype in the experimental test are thoroughly analysed. The high wind resistance of air gap as the ventilation duct and the large interface gap between the stator lamination and housing water jacket is thought to be the main reasons. Then improvement of the ventilation structures is studied to decrease the wind resistance. Besides, the modification of water channels is also investigated to avoid the influence of a large interface gap on the water cooling performance. Finally, a new cooling structure, combining the slot ventilation ducts and inside water channels, is proposed for the HSPMM with Gramme‐ring windings. With the new cooling structure, the temperature rise of the motor is decreased, and the power density can be increased.
Improvements in cosmological constraints from breaking growth degeneracy
Authors: Perenon L. , Ilić S. , Maartens R. , de la Cruz-Dombriz A. 
Published: August 2020

Context. The key probes of the growth of a large-scale structure are its rate f and amplitude σ8. Redshift space distortions in the galaxy power spectrum allow us to measure only the combination fσ8, which can be used to constrain the standard cosmological model or alternatives. By using measurements of the galaxy-galaxy lensing cross-correlation spectrum or of the galaxy bispectrum, it is possible to break the fσ8 degeneracy and obtain separate estimates of f and σ8 from the same galaxy sample. Currently there are very few such separate measurements, but even this allows for improved constraints on cosmological models.
Aims. We explore how having a larger and more precise sample of such measurements in the future could constrain further cosmological models.
Methods. We considered what can be achieved by a future nominal sample that delivers an ∼1% constraint on f and σ8 separately, compared to the case with a similar precision on the combination fσ8.
Results. For the six cosmological parameters of ΛCDM, we find improvements of ∼5–50% on their constraints. For modified gravity models in the Horndeski class, the improvements on these standard parameters are ∼0–15%. However, the precision on the sum of neutrino masses improves by 65% and there is a significant increase in the precision on the background and perturbation Horndeski parameters.
Aktuelle Entwicklungen bei der Lebertransplantation – Wo stehen wir?
Authors: Aehling Niklas F. , Seehofer Daniel , Berg Thomas 
Published: August 2020

Was ist neu?Indikation zur Transplantation – aktuelle Entwicklungen Der Wandel in den Indikationen zur Transplantation setzt sich weiter fort, Hauptindikationen werden die Spätfolgen der nichtalkoholischen und alkoholassoziierten Lebererkrankungen und das hepatozelluläre Karzinom (HCC) sein. Zirrhosen auf dem Boden von Virushepatitiden spielen zunehmend eine untergeordnete Rolle.Ist die 6-Monats-Alkoholkarenz eine zwingende Voraussetzung für die Transplantation? Die Richtlinien der Bundesärztekammer fordern grundsätzlich eine Alkoholabstinenzperiode von 6 Monaten. Wissenschaftliche Daten zeigen, dass insbesondere Patienten mit Erstmanifestation einer akuten Alkoholhepatitis, die nicht auf die medikamentöse Therapie anspricht, in besonderer Weise von einer Transplantation profitieren können. Für diese Patienten kann eine individuelle Ausnahme für eine Transplantationslistung beantragt werden.Das hepatozelluläre Karzinom außerhalb der Mailand-Kriterien – Transplantation nach „Downstaging“ Zahlreiche Studien belegen, dass mithilfe effektiver „Downstaging“-Therapien und unter Berücksichtigung des Biomarkers AFP eine Subgruppe von Patienten mit initialem HCC außerhalb der Mailand-Kriterien definiert werden kann, die eine sehr günstige und der von Patienten innerhalb der Mailand-Kriterien vergleichbare postoperative Prognose besitzt.Zu krank für eine Transplantation? Das akut-auf-chronische Leberversagen (ACLF) Selbst Patienten mit dekompensierter Zirrhose mit Mehrorganversagen, wie es im Rahmen eines ACLF definiert ist, können erfolgreich und mit einer guten Langzeitprognose transplantiert werden. Das Zeitfenster, in welchem dies möglich ist, ist jedoch kurz.Spenderorganmangel – Verwendung HBV- und HCV-positiver Organe und neue Chancen durch die Maschinenperfusion Die Transplantation von Organen chronisch HCV- und HBV-infizierter Spender stellt durch die exzellenten Behandlungsmöglichkeiten bei diesen viralen Infektionen eine relevante Strategie zur Vergrößerung des Spenderpools dar. Zusätzlich gewinnt die Maschinenperfusion als neuartige Methode der Organkonservierung bzw. der Organaufbereitung an Bedeutung.
Impfen im Alter – Pflicht oder Kür?
Authors: Kwetkat Anja , Endres Anne-Sophie , Leischker Andreas , Heppner Hans Jürgen 
Published: August 2020

Aktuelle Entwicklungen Die Wirksamkeit von Impfungen ist durch die Immunseneszenz reduziert. Stärker immunogene Impfstoffe sind daher für Hochbetagte und Multimorbide von besonderer Bedeutung.
Ausblick Die in der Entwicklung befindlichen Impfstoffe – Pneumokokken-, Norovirus-, Clostridium-difficile-, Hepatitis-B-Vakzine – betreffen zum einen Erkrankungen, für die bisher keine Impfungen für Senioren zur Verfügung stehen (z. B. Norovirus-Infektion), zum anderen werden stärker immunogene Vakzine mit einer breiteren Wirksamkeit entwickelt (z. B. Pneumokokken-Vakzine).
Innovationsmanagement diagnostischer Geräte am Beispiel der Detektion zirkulierender Tumorzellen
Authors: Fleßa Steffen , Aichinger Heike , Bratan Tanja 
Published: August 2020

ZusammenfassungZielsetzung Diagnostik ist eine Grundvoraussetzung für die effektive und effiziente Behandlung komplexer Krankheiten. Dementsprechend ist die Entwicklung innovativer Diagnostiktechnik von der Entwicklung des Verfahrens bis zur Einführung in die Versorgung von großer Bedeutung für die Weiterentwicklung der Medizin. Allerdings wird der komplexe Prozess häufig nicht ganzheitlich gesehen, sodass insbesondere technische und ökonomische Aspekte getrennt betrachtet werden. In dieser Arbeit entwickeln wir ein Modell des Innovationsmanagements von Diagnostiktechnologie mit dem Ziel, den Innovationsprozess im Sinne einer integrativen Entwicklung zu verbessern.Methodik Der Prozess des Innovationsmanagements von Diagnostiktechnologie von der Produktidee bis zur Marktreife wird als Modell entwickelt, wobei die einzelnen Barrieren und Einflussfaktoren herausgearbeitet werden. Die Erkenntnisse werden anschließend am Beispiel eines Gerätes zur Detektion von zirkulierenden Tumorzellen diskutiert.Ergebnisse Der Innovationsprozess durchläuft verschiedene Phasen: von der Produktidee, der Entwicklung, der Zulassung, der Entgeltung bis zur Markteinführung. Bislang werden die ersten 3 Phasen überwiegend als technisches Problem angesehen, während die letzten beiden Phasen der Ökonomie vorbehalten sind. Ein effizientes Innovationsmanagement erfordert hingegen den Einsatz betriebswirtschaftlicher und gesundheitsökonomischer Elemente von Anfang an im Sinne einer integrativen Entwicklung.Schlussfolgerung Es stehen erprobte Instrumente des Innovationsmanagements und der gesundheitsökonomischen Evaluation zur Verfügung, die den Prozess von der Produktidee bis zur Markteinführung effizient und effektiv gestalten lassen. Eine entsprechende Listung der Instrumente ist hilfreich als Anregung für ein professionelles Innovationsmanagement diagnostischer Geräte.
Silibinin Inhibit Cell Migration through Downregulation of RAC1 Gene
Expression in Highly Metastatic Breast Cancer Cell Line
Authors: Lashgarian Hamed Esmaeil , Adamii Vahid , Ghorbanzadeh Vajihe , Chodari Leila , Kamali Fayze , Akbari Soheila , Dariushnejad Hassan 
Published: August 2020

Abstract
Background Triple negative breast cancer is the most invasive breast
cancer subtype and possesses poor prognosis and survival. Rho GTPase famil,
especially Rac1 participates in a number of signaling events in cells with
crucial roles in malignancy, migration and invasion of tumor cells.
Silibinin, a flavonoid antioxidant from milk thistle has attracted attention
in the recent decades for chemoprevention and chemotherapy of tumor cells.
In this study, the effect of silibinin on the migration capacity of
MDA-MB-231 cells, a highly metastatic human breast cancer cell line was
investigated by evaluation of Rac1 expression.
Method MTT wound healing and transwell assays were performed to
evaluate the effects of silibinin on proliferation and migration of
MDA-MB-231 cells. In addition, the influence of the silibinin on the
expression of Rac1mRNAs was assessed by RT-PCR.
Results Results indicated significant dose-dependent inhibitory effect
of silibinin on proliferation and migration of MDA-MB-231 cells. It
significantly inhibited the expression of Rac1 mRNA.
Conclusion In conclusion, the results demonstrate that the silibinin
can be used as an experimental therapeutic for the management of TNBC
metastatic cancer.
„Das ist auch unser Ziel, dass wir diese Patienten in ruhigem Fahrwasser behandeln“ – Palliativversorgung älterer Menschen mit lebensbegrenzenden Erkrankungen in der hausärztlichen Praxis: Eine qualitative Studie
Authors: Freihoff Silke , Tetzlaff Fabian , Schneider Nils , Stiel Stephanie , Müller-Mundt Gabriele 
Published: August 2020

Zusammenfassung
Hintergrund Praktische Erfahrungen und Studien untermauern die Relevanz der Palliativversorgung (PV) für ältere Menschen mit lebensbegrenzenden Erkrankungen. Ziel dieser Studie ist, die hausärztliche Versorgung älterer Menschen in der letzten Lebensphase zu untersuchen.
Methodik Als Teil der Ist-Analyse des Interventionsprojekts „Proaktive Palliativversorgung älterer Patienten in der letzten Lebensphase (ProPall, BMBF-01GY1710)“ wurden leitfadenorientierte Interviews mit Hausärzten geführt und inhaltsanalytisch ausgewertet.
Ergebnisse Im Frühjahr/Sommer 2018 wurden 15 Hausärzte aus 12 Praxen in 2 Regionen in Niedersachsen interviewt. Die Interviewanalyse zeigt, dass die Hausärzte eine umfassende Begleitung älterer Patienten als integralen Bestandteil ihrer Tätigkeit ansehen. Sie beschreiben ihre Rolle als Lotse im ,Dickicht der Medizin‘ und Begleiter bis zum Ende. Um ein ,ruhiges Sterben‘ im vertrauten Umfeld zu ermöglichen, ist es den Hausärzten wichtig, Leiden zu lindern, die Versorgung zu koordinieren und neben den Erkrankten auch ihre Angehörigen zu begleiten. Bedarf für PV schreiben die Hausärzte vorrangig Patienten mit Krebserkrankungen sowie im Endstadium nicht maligner chronischer Erkrankungen zu.
Schlussfolgerung Verstärkte Anstrengungen sind erforderlich, um insbesondere bei älteren Menschen mit lebenslimitierenden nicht onkologischen Erkrankungen PV frühzeitiger in die hausärztliche Versorgung zu integrieren.
In Vitro Whitening Effect of a Hydroxyapatite-Based Oral Care Gel
Authors: Sarembe Sandra , Enax Joachim , Morawietz Maria , Kiesow Andreas , Meyer Frederic 
Published: August 2020

Abstract
Objective Oral care formulations aim to prevent oral diseases such as dental caries and gingivitis. Additionally, desire for white teeth still exists across all age groups. It is known that most whitening toothpastes are highly abrasive and can be harmful to teeth and gingiva. Therefore, a gel formulation with biomimetic hydroxyapatite (HAP; Ca5[PO4]3[OH]) as active ingredient was developed. This formulation was tested with respect to its tooth whitening properties in an in vitro study.
Materials and Methods Enamel samples were allocated to either group (a) HAP gel, (b) whitening mouth rinse with phosphates, or (c) negative control (distilled water). Test products were applied by finger (a) or were rinsed (b, c) for 1, 3, and 9 (b and c only) cycles, respectively.
Results Color changes (ΔE) were measured spectrophotometrically. Group (a) showed a significant increase in color changes with respect to whitening after one cycle (mean ΔE = 5.4 [±2.66], p ≤ 0.006) and three cycles (mean ΔE = 11.2 [±3.11], p < 0.0001) compared to groups (b) and (c). For group (b), a significant increase in color change was measured after three (mean ΔE = 2.77 [±1.01], p = 0.02) and nine cycles (mean ΔE = 3.27 [±1.61], p = 0.006) compared to (c). Group (c) showed only minor and statistically insignificant color changes.
Conclusion This in vitro study demonstrated a significantly higher ad hoc whitening effect of the HAP gel compared to the mouth rinse and water after short-time application.
Intraamniotic Infection Rates after Intrauterine Pressure Catheter with and without Amnioinfusion
Authors: Mokhtari Neggin , Wang Tiffany , DiSciullo Alison , Iqbal Sara N. , Kawakita Tetsuya 
Published: August 2020

Objective This study aimed to examine the rates of intraamniotic infection between intrauterine pressure catheter with amnioinfusion and intrauterine pressure catheter alone.
Study Design This was a retrospective cohort study of all women who had an intrauterine pressure catheter placement during labor at a tertiary referral hospital from January 2016 to June 2018. Outcomes were compared between women who had an intrauterine pressure catheter with amnioinfusion and intrauterine pressure catheter placement alone. The primary outcome was the rate of intraamniotic infection. Secondary outcomes included postpartum endometritis, postpartum hemorrhage (blood loss of ≥1,000 mL), quantitative blood loss (mL), and cesarean delivery. Multivariable logistic regression analysis was performed to calculate adjusted odds ratios (aOR) and 95% confidence interval (95% CI), controlling for age, race, body mass index, gestational age, and length of time of rupture of membranes.
Results Of 1,268 women with an intrauterine pressure catheter, 298 (23.5%) also had an amnioinfusion. Women who had amnioinfusion through an intrauterine pressure catheter compared with those who had intrauterine pressure catheter alone had similar rates of intraamniotic infection (5.4 vs. 8.0%, crude p = 0.12, aOR 0.69; 95% CI 0.39–1.21), as well as secondary outcomes such as postpartum endometritis (3.0 vs. 2.5%, crude p = 0.61, aOR 1.12; 95% CI 0.49–2.53), postpartum hemorrhage (16.1 vs. 15.8%, crude p = 0.89, aOR 1.07; 95% CI 0.75–1.54), blood loss (479.5 vs. 500 mL, adjusted p = 0.89), and cesarean delivery (40.6 vs. 43.1%, crude p = 0.45, aOR 0.90; 95% CI 0.68–1.19).
Conclusion Amnioinfusion was not associated with increased odds of intraamniotic infection compared with intrauterine pressure catheter placement alone.
Key Points
An intimate dialog between race and gender at Women’s Suffrage Centennial
Authors: Yang Mimi 
Published: August 2020

AbstractWomen’s Suffrage Centennial has arrived in a culturally divisive time in the United States as well as in a high-stakes presidential election year. All this is accompanied with the emergence of Black Lives Matter movement on a global-scale in the wake of the African American man George Floyd’s death under the knees of white police officers. In an “I cannot breathe” America at a new cultural awakening moment, is the Centennial a divider or unifier for American women in 2020? This article aims to answer the question by revisiting the 14th and 15th Amendments to the Constitution and iconic figures like Elizabeth Cady Stanton, Susan B. Anthony, Frederick Douglass, W.E.B. DuBois, and Mary Church Terrell. In an interdisciplinary approach anchored in both historical and cultural studies, the article scrutinizes the split between the two visceral elements pertinent to cultural identity—gender and race—in Women’s Suffrage Movement, draws a pattern of their intersection, and maps out a “double consciousness” (to borrow W.E.B. DuBois’ term). The article argues that the women’s suffrage movement was indeed a gigantic step towards the American ideal of gender equality but it fell short of racial equality. There is a mixed legacy to embrace and to reevaluate at the same time. Therefore, Women’s Suffrage Centennial should not and cannot be a single-issue gender celebration, nor a one-size-fits-all symphony, but a landmark occasion for an intimate and nuanced dialog between gender and race. The article suggests that the Centennial should not only celebrate white American suffragists, but should be an opportunity to make a historic step to cross the color line that has cutoff African American women, as well as women of color from other races, ethnicities, and heritages from the power center.