bluuebunny/crossref_metadata_2025_split huggingface dataset:
S-Phase Kinase-associated Protein-2 Rejuvenates Senescent Endothelial Progenitor Cells and Induces Angiogenesis in Vivo
Authors: Wang Hsueh-Hsiao , Lee Yi-Nan , Su Cheng-Huang , Shu Kuo-Tung , Liu Wen-Ting , Hsieh Chin-Ling , Yeh Hung-I , Wu Yih-Jer 
Published: April 2020

AbstractCell cycle slowdown or arrest is a prominent feature of cellular senescence. S-phase kinase-associated protein-2 (Skp2), an F-box subunit of SCFSkp2 ubiquitin ligase, is a key regulator of G1/S transition. We investigated whether Skp2 plays a role in the regulation of endothelial progenitor cell (EPC) senescence, which is closely associated with aging-related vasculopathy. Replication-induced senescent EPCs demonstrated more pronounced senescence markers and lower Skp2 levels in comparison with those of their younger counterparts. Depletion of Skp2 induced increases in senescence-associated β-galactosidase (SA-βGal) activity and a reduction of telomere length and generated a senescent bioenergetics profile, whereas adenoviral-mediated Skp2 expression reversed the relevant senescence. EPCs isolated from older rats displayed a reduced proliferation rate and increased SA-βGal activity, both of which were significantly reversed by Skp2 ectopic expression. In addition to reversing senescence, Skp2 also rescued the angiogenic activity of senescent EPCs in the ischemic hind limbs of nude mice. The results revealed that ectopic expression of Skp2 has the potential to rejuvenate senescent EPCs and rescue their angiogenic activity and thus may be pivotal in the development of novel strategies to manage aging-related vascular disease.
An intact C-terminal end of albumin is required for its long half-life in humans
Authors: Nilsen Jeannette , Trabjerg Esben , Grevys Algirdas , Azevedo Claudia , Brennan Stephen O. , Stensland Maria , Wilson John , Sand Kine Marita Knudsen , Bern Malin , Dalhus Bjørn , Roopenian Derry C. , Sandlie Inger , Rand Kasper Dyrberg , Andersen Jan Terje 
Published: April 2020

AbstractAlbumin has an average plasma half-life of three weeks and is thus an attractive carrier to improve the pharmacokinetics of fused therapeutics. The half-life is regulated by FcRn, a cellular receptor that protects against intracellular degradation. To tailor-design the therapeutic use of albumin, it is crucial to understand how structural alterations in albumin affect FcRn binding and transport properties. In the blood, the last C-terminal residue (L585) of albumin may be enzymatically cleaved. Here we demonstrate that removal of the L585 residue causes structural stabilization in regions of the principal FcRn binding domain and reduces receptor binding. In line with this, a short half-life of only 3.5 days was measured for cleaved albumin lacking L585 in a patient with acute pancreatitis. Thus, we reveal the structural requirement of an intact C-terminal end of albumin for a long plasma half-life, which has implications for design of albumin-based therapeutics.
Domain sliding of two Staphylococcus aureus N-acetylglucosaminidases enables their substrate-binding prior to its catalysis
Authors: Pintar Sara , Borišek Jure , Usenik Aleksandra , Perdih Andrej , Turk Dušan 
Published: April 2020

AbstractTo achieve productive binding, enzymes and substrates must align their geometries to complement each other along an entire substrate binding site, which may require enzyme flexibility. In pursuit of novel drug targets for the human pathogenS. aureus, we studied peptidoglycan N-acetylglucosaminidases, whose structures are composed of two domains forming a V-shaped active site cleft. Combined insights from crystal structures supported by site-directed mutagenesis, modeling, and molecular dynamics enabled us to elucidate the substrate binding mechanism of SagB and AtlA-gl. This mechanism requires domain sliding from the open form observed in their crystal structures, leading to polysaccharide substrate binding in the closed form, which can enzymatically process the bound substrate. We suggest that these two hydrolases must exhibit unusual extents of flexibility to cleave the rigid structure of a bacterial cell wall.
Genome-wide association study of Buruli ulcer in rural Benin highlights role of two LncRNAs and the autophagy pathway
Authors: Manry Jeremy , Vincent Quentin B. , Johnson Christian , Chrabieh Maya , Lorenzo Lazaro , Theodorou Ioannis , Ardant Marie-Françoise , Marion Estelle , Chauty Annick , Marsollier Laurent , Abel Laurent , Alcaïs Alexandre 
Published: April 2020

AbstractBuruli ulcer, caused byMycobacterium ulceransand characterized by devastating necrotizing skin lesions, is the third mycobacterial disease worldwide. The role of host genetics in susceptibility to Buruli ulcer has long been suggested. We conduct the first genome-wide association study of Buruli ulcer on a sample of 1524 well characterized patients and controls from rural Benin. Two-stage analyses identify two variants located within LncRNA genes: rs9814705 inENSG00000240095.1(P = 2.85 × 10−7; odds ratio = 1.80 [1.43–2.27]), and rs76647377 inLINC01622(P = 9.85 × 10−8; hazard ratio = 0.41 [0.28–0.60]). Furthermore, we replicate the protective effect of allele G of a missense variant located inATG16L1, previously shown to decrease bacterial autophagy (rs2241880,P = 0.003; odds ratio = 0.31 [0.14–0.68]). Our results suggest LncRNAs and the autophagy pathway as critical factors in the development of Buruli ulcer.
Mechanical stimulation induced osteogenic differentiation of BMSCs through TWIST/E2A/p21 axis
Authors: Guo Qingyuan , Liu Ying , Sun Renhao , Yang Fang , Qiao Pengyan , Zhang Rong , Song Ling , E Lingling , Liu Hongchen 
Published: April 2020

AbstractThe relationship between mechanical force and alveolar bone remodeling is an important issue in orthodontics because tooth movement is dependent on the response of bone tissue to the mechanical force induced by the appliances used. Mechanical cyclical stretch plays an essential role in the cell osteogenic differentiation involved in bone remodeling. However, the underlying mechanisms are unclear, particularly the molecular pathways regulated by mechanical stimulation. In the present study, we reported a dynamic change of p21 level in response to mechanical cyclical stretch, and shRNA-p21 in bone marrow mesenchymal stem cells (BMSCs) induced osteogenic differentiation. The mechanism was mediated through TWIST/E2A/p21 axis. These results supported the mechanical stimulation-induced osteogenic differentiation is negatively regulated by p21.
Properties of OB star−black hole systems derived from detailed binary evolution models
Authors: Langer N. , Schürmann C. , Stoll K. , Marchant P. , Lennon D. J. , Mahy L. , de Mink S. E. , Quast M. , Riedel W. , Sana H. , Schneider P. , Schootemeijer A. , Wang C. , Almeida L. A. , Bestenlehner J. M. , Bodensteiner J. , Castro N. , Clark S. , Crowther P. A. , Dufton P. , Evans C. J. , Fossati L. , Gräfener G. , Grassitelli L. , Grin N. , Hastings B. , Herrero A. , de Koter A. , Menon A. , Patrick L. , Puls J. , Renzo M. , Sander A. A. C. , Schneider F. R. N. , Sen K. , Shenar T. , Simón-Días S. , Tauris T. M. , Tramper F. , Vink J. S. , Xu X.-T. 
Published: April 2020

Context. The recent gravitational wave measurements have demonstrated the existence of stellar mass black hole binaries. It is essential for our understanding of massive star evolution to identify the contribution of binary evolution to the formation of double black holes.
Aims. A promising way to progress is investigating the progenitors of double black hole systems and comparing predictions with local massive star samples, such as the population in 30 Doradus in the Large Magellanic Cloud (LMC).
Methods. With this purpose in mind, we analysed a large grid of detailed binary evolution models at LMC metallicity with initial primary masses between 10 and 40 M⊙, and identified the model systems that potentially evolve into a binary consisting of a black hole and a massive main-sequence star. We then derived the observable properties of such systems, as well as peculiarities of the OB star component.
Results. We find that ∼3% of the LMC late-O and early-B stars in binaries are expected to possess a black hole companion when stars with a final helium core mass above 6.6 M⊙ are assumed to form black holes. While the vast majority of them may be X-ray quiet, our models suggest that these black holes may be identified in spectroscopic binaries, either by large amplitude radial velocity variations (≳50 km s−1) and simultaneous nitrogen surface enrichment, or through a moderate radial velocity (≳10 km s−1) and simultaneous rapid rotation of the OB star. The predicted mass ratios are such that main-sequence companions can be excluded in most cases. A comparison to the observed OB+WR binaries in the LMC, Be and X-ray binaries, and known massive black hole binaries supports our conclusion.
Conclusions. We expect spectroscopic observations to be able to test key assumptions in our models, with important implications for massive star evolution in general and for the formation of double black hole mergers in particular.
Erkrankungen des Tränenapparats, Teil 2: Grundlagen der Therapie
Authors: Heichel Jens , Struck Hans-Gert , Viestenz Arne , Glien Alexander , Plontke Stefan 
Published: April 2020

AbstractThe tearing eye (epiphora) is deemed to be the leading symptome of efferent tear duct stenosis. Nevertheless, epiphora might be caused by ocular surface pathologies or even intraocular diseases. A distinguished anamnesis and sufficient clinical examination is most meaningful for the differential diagnostic distinction. Therapy is based on pathologic changes. In case of ocular surface disease, a suitable tear substitution and antiinflammatory approach is mandatory. Multifarious triggers have to be considered as well. Addressing tear film distribution, suitable oculoplastic surgery is required. Efferent tear duct stenosis necessitates surgical treatment as the level of suffering is often very high and acute exacerbations may develop. Besides recanalization, anastomosing techniques represent the available therapeutic principles. Possible surgical approaches offer a great variety and many influencing factors navigate therapy decisions. This part of the review comments on the most important therapeutic approaches for lacrimal apparatus diseases.
Barrett-Screening: rationale, aktuelle Konzepte und Perspektiven
Authors: Weismüller Josef , Thieme René , Hoffmeister Albrecht , Weismüller Tobias , Gockel Ines 
Published: April 2020

ZusammenfassungDer Barrett-Ösophagus (BE) stellt den wichtigsten Risikofaktor für das ösophageale Adenokarzinom dar. Derzeit ist kein hinreichend effizientes Screening-Programm verfügbar, um in der Gesamtpopulation Patienten mit einem hohen Risiko für ein ösophageales Adenokarzinom auf dem Boden eines Barrett-Ösophagus zu identifizieren. Das aktuelle endoskopische Screening zielt auf symptomatische Refluxpatienten, aus denen sich aber nur ein Teil der Risikopatienten rekrutiert. Derzeit werden verschiedene neue Verfahren untersucht, die die Effektivität des Screenings deutlich erhöhen könnten.Selektive Literaturrecherche in MEDLINE/PubMed unter Berücksichtigung deutscher und internationaler Leitlinien.Alternative Screening-Verfahren könnten 2-stufig angelegt sein: Zunächst die Identifikation von Personen „at risk“ über eine Erfassung geeigneter biologischer Marker, dann deren gezielte endoskopisch-bioptische Abklärung, Risikostratifikation, Überwachung (Surveillance) und ggf. Therapie. Neue diagnostische Methoden wie der Cytosponge® in Kombination mit einer Auswertung von Markern für Barrett-Schleimhaut könnten einen wesentlichen Fortschritt darstellen.Barrett-Karzinome zeigen nach wie vor eine zunehmende Inzidenz und eine (trotz therapeutischer Fortschritte) ungünstige Prognose, wobei aber Patienten mit Barrett-Frühkarzinomen eine gute Prognose hinsichtlich Langzeitüberleben aufweisen. Eine verbesserte Früherkennung ist dringend wünschenswert, da bisher die meisten Patienten erst im fortgeschrittenen Stadium endoskopisch diagnostiziert werden, was eine kurative Therapie erschwert. Nur eine effiziente frühzeitige Identifizierung von Risikopatienten mit Barrett-Ösophagus durch ein praktikables Screening-Programm auf Populationsebene wird zur Verbesserung der Prognose beitragen können.
„Die einzige Art, gegen die Pest zu kämpfen, ist die
Ehrlichkeit“ (A. Camus)
Authors: Singer Dominique 
Published: April 2020

Liebe Leserinnen und Leser,in dem 1947 erschienenen Roman „Die Pest“ des franko-algerischen
Literaturnobelpreisträgers Albert Camus spricht der Arzt Bernard Rieux,
indem er jede Art von „Heldentum“ im Kampf gegen die Seuche von sich
weist, die Worte: „… la seule façon de lutter contre la
peste, c‘est l’honnêteté“. Eine
Aussage, die sich angesichts der aktuellen Coronavirus-Pandemie in geradezu
bedrückender Weise bestätigt. Haben wir es doch auch heute mit einer
Reihe von „Unbedachtheiten“ zu tun, die das Ausmaß der Krise
begünstigt haben.
Gastrointestinal Ultrasound (GIUS) in Intestinal Emergencies – An EFSUMB Position Paper
Authors: Hollerweger Alois , Maconi Giovanni , Ripolles Tomas , Nylund Kim , Higginson Antony , Serra Carla , Dietrich Christoph F. , Dirks Klaus , Gilja Odd Helge 
Published: April 2020

AbstractAn interdisciplinary group of European experts summarizes the value of gastrointestinal ultrasound (GIUS) in the management of three time-critical causes of acute abdomen: bowel obstruction, gastrointestinal perforation and acute ischemic bowel disease. Based on an extensive literature review, statements for a targeted diagnostic strategy in these intestinal emergencies are presented. GIUS is best established in case of small bowel obstruction. Metanalyses and prospective studies showed a sensitivity and specificity comparable to that of computed tomography (CT) and superior to plain X-ray. GIUS may save time and radiation exposure and has the advantage of displaying bowel function directly. Gastrointestinal perforation is more challenging for less experienced investigators. Although GIUS in experienced hands has a relatively high sensitivity to establish a correct diagnosis, CT is the most sensitive method in this situation. The spectrum of intestinal ischemia ranges from self-limited ischemic colitis to fatal intestinal infarction. In acute arterial mesenteric ischemia, GIUS may provide information, but prompt CT angiography is the gold standard. On the other end of the spectrum, ischemic colitis shows typical ultrasound features that allow correct diagnosis. GIUS here has a diagnostic performance similar to CT and helps to differentiate mild from severe ischemic colitis.
Influence of Antagonist Material on Fatigue and Fracture Resistance of Zirconia Crowns
Authors: Nawafleh Noor , Bibars Abdel Raheem , Al Twal Elina , Öchsner Andreas 
Published: April 2020

Abstract
Objective This study investigates the influence of the most commonly used indenter materials on fatigue survival and fracture resistance of zirconia crowns.
Materials and Methods A total of 40 zirconia crowns were prepared using computer-aided design (CAD)/computer-aided manufacturing (CAM) technology: 30 crowns were divided into three experimental groups of 10 specimens and the last 10 specimens acted as the control group. The experimental groups were subjected to chewing simulation with simultaneous thermocycling. Three indenter materials (steatite ceramic, stainless steel, and tungsten carbide) with identical diameter were used to load the specimens. All crowns were then subjected to single load to fracture test in universal testing machine. Load was applied vertically with a crosshead speed of 1 mm/min until failure, and fracture load was recorded.
Statistical Analysis Normal distribution of data was confirmed using the Shapiro–Wilk test. Descriptive statistics including means and standard deviations were determined for all groups. Differences between groups were tested using Dunnett’s test and paired sample t-test.
Results Chewing simulation for 1.2 million cycles resulted in 100% survival. The highest mean fracture load was recorded for the control group and the lowest one was for the group fatigued with stainless steel indenter. Chewing simulation statistically significantly (p < 0.05) reduced the mean fracture load of the crowns fatigued with stainless steel and steatite ceramic indenter. However, the mean fracture load for the crowns fatigued with tungsten carbide was not significantly different from that of the control group.
Conclusion Steatite ceramic and stainless steel indenters produced close results and significantly reduced fracture load of zirconia crowns. However, tungsten carbide indenter caused nonsignificant reduction in the fracture load of zirconia crowns.
Unfolding Various Concepts of Junctional Epithelium
Authors: Puvvalla Bhavana , A. Suchetha , Mundinamanae Darshan B. , M. Apoorva S. , Bhat Divya 
Published: April 2020

AbstractThe Gingival epithelium comprises of three different areas based on their anatomical and functional points of view 1) the oral or outer epithelium (OGE), 2) Sulcular epithelium (SE) and 3) Junctional epithelium (JE). The junctional epithelium may be regarded as the most interesting structure of the gingiva. The formation of junctional epithelium in the implant/mucosal interface can be considered as the first barrier of defense against oral micro flora. Any kind of disruption of this barrier will lead to initiation and progression of progression of periodontal disease. Hence, in this review we made an attempt to wrap various concepts of junctional epithelium formation, its role in disease progression and its relation to the implant surface.
Effectiveness of Video Assisted Teaching Program on Knowledge Regarding Prevention and Management of Laryngitis among Primary School Teachers of Selected Primary Schools at Hassan
Authors: B. Mamatha , S. Damayanthi 
Published: April 2020

Abstract
Background: Teaching is a profession where teachers are exposed to use their voice excessively in many situations which impose the risk for developing morbidity caused to larynx, among them the most common is laryngitis. However, I felt that there was great need for educating primary school teachers on Prevention and Management of Laryngitis.
Objectives: To find the effectiveness of Video Assisted Teaching Program (VATP) on Knowledge regarding Prevention and Management of Laryngitis among Primary School Teachers.
Materials and methods: Quasi-experimental research design was adopted for the study with purposive sampling technique to select the sample (N=60) with n=30 in experimental group and control group of primary school teachers respectively. A structured knowledge questionnaire was used to assess the Knowledge; VATP was administered only to experimental group to find its effectiveness in comparison with control group. The findings of the study revealed deficit in knowledge of primary school teachers before administration of VATP.
Results: The mean percentage knowledge score of post-test (79.80 %) was higher than the pretest (39.30%). The calculated paired 't' value is greater than the table value (0.05, 29df) = 2.045. It showed a significant difference between mean pre and post- test knowledge scores among experimental group. The mean percentage of knowledge scores in post-test (79.80%) among experimental group was higher than the post-test (39.80%) among control group. The 2 calculated unpaired 't' value is greater than the table value (0.05,58df) = 1.96. Calculated ÷ values showed significant association between post-test knowledge scores of respondents with their selected demographic variables.
Conclusion: VATP was effective in increasing the knowledge of primary school teachers on Prevention and Management of Laryngitis.
Trapped in the prison of the mind: Notions of climate-induced (im)mobility decision-making and wellbeing from an urban informal settlement in Bangladesh
Authors: Ayeb-Karlsson Sonja , Kniveton Dominic , Cannon Terry 
Published: April 2020

AbstractThe concept of Trapped Populations has until date mainly referred to people ‘trapped’ in environmentally high-risk rural areas due to economic constraints. This article attempts to widen our understanding of the concept by investigating climate-induced socio-psychological immobility and its link to Internally Displaced People’s (IDPs) wellbeing in a slum of Dhaka. People migrated here due to environmental changes back on Bhola Island and named the settlement Bhola Slum after their home. In this way, many found themselves ‘immobile’ after having been mobile—unable to move back home, and unable to move to other parts of Dhaka, Bangladesh, or beyond. The analysis incorporates the emotional and psychosocial aspects of the diverse immobility states. Mind and emotion are vital to better understand people’s (im)mobility decision-making and wellbeing status. The study applies an innovative and interdisciplinary methodological approach combining Q-methodology and discourse analysis (DA). This mixed-method illustrates a replicable approach to capture the complex state of climate-induced (im)mobility and its interlinkages to people’s wellbeing. People reported facing non-economic losses due to the move, such as identity, honour, sense of belonging and mental health. These psychosocial processes helped explain why some people ended up ‘trapped’ or immobile. The psychosocial constraints paralysed them mentally, as well as geographically. More empirical evidence on how climate change influences people’s wellbeing and mental health will be important to provide us with insights in how to best support vulnerable people having faced climatic impacts, and build more sustainable climate policy frameworks.
Production of styrene oxide from styrene by a recombinant Escherichia coli with enhanced AcrAB-TolC efflux pump level in an aqueous-organic solvent two-phase system
Authors: Doukyu Noriyuki , Iida Shinichiro 
Published: April 2020

Abstract
The AcrAB-TolC efflux pump is involved in the organic solvent tolerance of Escherichia coli. Most E. coli strains are highly sensitive to organic solvents such as n-hexane and cyclohexane. Here, a recombinant E. coli transformed with an expression plasmid containing acrAB and tolC became tolerant to n-hexane and cyclohexane. The levels of AcrA, AcrB, and TolC in the recombinant increased by 3- to 5-fold compared to those in the control strain without the plasmid for acrAB or tolC. To investigate the usability of the recombinant as a biocatalyst in an aqueous-organic solvent two-phase system, we further introduced xylMA xylene monooxygenase genes from Pseudomonas putida mt-2 into the recombinant and examined the production of styrene oxide from styrene. The resulting recombinant produced 1.8 mg and 1.0 mg styrene oxide mL−1 of medium in a medium overlaid with a 25% volume of n-hexane and cyclohexane containing 10% (wt vol−1) styrene, respectively.
Variation theory as a lens for interpreting and guiding physics students’ use of digital learning environments
Authors: Euler Elias , Gregorcic Bor , Linder Cedric 
Published: April 2020

Abstract
In this paper, we examine the implementation of a digital learning environment—namely, the physics software, Algodoo—which is less-constrained in its design than the digital learning environments typically used in physics education. Through an analysis of a case study, we explore a teaching arrangement wherein physics teachers responsively guide small groups of students as they use less-constrained DLEs in a mostly self-directed manner. Our analysis leads to practical recommendations for physics teachers in terms of (1) how to glean useful information about students’ existing physics knowledge through observation and (2) how to responsively intervene so as to productively guide students toward the learning of particular physics content. These recommendations stem from our use of the variation theory of learning as a lens for physics students’ use of digital learning environments.