bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hyperglycaemia-induced methylglyoxal accumulation potentiates VEGF resistance of diabetic monocytes through the aberrant activation of tyrosine phosphatase SHP-2/SRC kinase signalling axis
Authors: Dorenkamp Marc , Müller Jörg P. , Shanmuganathan Kallipatti Sanjith , Schulten Henny , Müller Nicolle , Löffler Ivonne , Müller Ulrich A. , Wolf Gunter , Böhmer Frank-D. , Godfrey Rinesh , Waltenberger Johannes 
Published: September 2018

AbstractDiabetes mellitus (DM) is a major cardiovascular risk factor contributing to cardiovascular complications by inducing vascular cell dysfunction. Monocyte dysfunction could contribute to impaired arteriogenesis response in DM patients. DM monocytes show blunted chemotactic responses to arteriogenic stimuli, a condition termed as vascular endothelial growth factor (VEGF) resistance. We hypothesize that methylglyoxal (MG), a glucose metabolite, induces monocyte dysfunction and aimed to elucidate the underlying molecular mechanisms. Human monocytes exposed to MG or monocytes from DM patients or mice (db/db) showed VEGF-resistance secondary to a pro-migratory phenotype. Mechanistically, DM conditions or MG exposure resulted in the upregulation of the expression of SHP-2 phosphatase. This led to the enhanced activity of SHP-2 and aided an interaction with SRC kinase. SHP-2 dephosphorylated the inhibitory phosphorylation site of SRC leading to its abnormal activation and phosphorylation of cytoskeletal protein, paxillin. We demonstrated that MG-induced molecular changes could be reversed by pharmacological inhibitors of SHP-2 and SRC and by genetic depletion of SHP-2. Finally, a SHP-2 inhibitor completely reversed the dysfunction of monocytes isolated from DM patients and db/db mice. In conclusion, we identified SHP-2 as a hitherto unknown target for improving monocyte function in diabetes. This opens novel perspectives for treating diabetic complications associated with impaired monocyte function.
Study on heating mechanism of GRP rod in a composite insulator
Authors: Yuan Zhikang , Tu Youping , Jiang Han , Wang Cheng , Wang Cong 
Published: September 2018

An abnormal temperature rise of the composite insulator, which was reported as the early stage of decay‐like fracture of the composite insulator, has drawn the close attention of the operation and maintenance department of the power grid. In this study, the heating mechanism of GRP rod in composite insulator was studied. At first, the current, partial discharge and temperature rise of 30 mm‐length short GRP rods were tested in high and low humidity environment. According to the experimental results, the simulation model for the temperature rise of the GRP rod was established. It was proved that the temperature rise was caused by the volume current. At last, the circuit model of the GRP rod was set up and the contribution of polarisation loss and conduction loss to the temperature rise was discussed. It could be concluded that the power of temperature rise of the GRP rods was mainly supplied by polarisation loss and the invasion of moisture was the main reason for the increase of polarisation loss in high humidity. In low humidity environment, both polarisation loss and conduction loss would play an important role in temperature rise and the deterioration of the material was the main reason for the increase of the dielectric loss.
Highly accreting quasars: The SDSS low-redshift catalog
Authors: Negrete C. A. , Dultzin D. , Marziani P. , Esparza D. , Sulentic J. W. , del Olmo A. , Martínez-Aldama M. L. , García López A. , D’Onofrio M. , Bon N. , Bon E. 
Published: September 2018

Context. The most highly accreting quasars are of special interest in studies of the physics of active galactic nuclei (AGNs) and host galaxy evolution. Quasars accreting at high rates (L/LEdd ∼ 1) hold promise for use as “standard candles”: distance indicators detectable at very high redshift. However, their observational properties are still largely unknown.Aims. We seek to identify a significant number of extreme accretors. A large sample can clarify the main properties of quasars radiating nearL/LEdd ∼ 1 (in this paper they are designated as extreme Population A quasars or simply as extreme accretors) in theHβspectral range for redshift ≲0.8.Methods. We use selection criteria derived from four-dimensional Eigenvector 1 (4DE1) studies to identify and analyze spectra for a sample of 334 candidate sources identified from the SDSS DR7 database. The source spectra were chosen to show a ratioRFeIIbetween the FeII emission blend atλ4570 andHβ,RFeII> 1. Composite spectra were analyzed for systematic trends as a function of Fe IIstrength, line width, and[OIII]strength. We introduced tighter constraints on the signal-to-noise ratio (S/N) andRFeIIvalues that allowed us to isolate sources most likely to be extreme accretors.Results. We provide a database of detailed measurements. Analysis of the data allows us to confirm thatHβshows a Lorentzian function with a full width at half maximum (FWHM) ofHβ≤ 4000 km s−1. We find no evidence for a discontinuity at 2000 km s−1in the 4DE1, which could mean that the sources below this FWHM value do not belong to a different AGN class. Systematic[OIII]blue shifts, as well as a blueshifted component inHβare revealed. We interpret the blueshifts as related to the signature of outflowing gas from the quasar central engine. The FWHM ofHβis still affected by the blueshifted emission; however, the effect is non-negligible if the FWHMHβis used as a “virial broadening estimator” (VBE). We emphasize a strong effect of the viewing angle onHβbroadening, deriving a correction for those sources that shows major disagreement between virial and concordance cosmology luminosity values.Conclusions. The relatively large scatter between concordance cosmology and virial luminosity estimates can be reduced (by an order of magnitude) if a correction for orientation effects is included in the FWHMHβvalue; outflow and sample definition yield relatively minor effects.
Constraining the period of the ringed secondary companion to the young star J1407 with photographic plates
Authors: Mentel R. T. , Kenworthy M. A. , Cameron D. A. , Scott E. L. , Mellon S. N. , Hudec R. , Birkby J. L. , Mamajek E. E. , Schrimpf A. , Reichart D. E. , Haislip J. B. , Kouprianov V. V. , Hambsch F.-J. , Tan T.-G. , Hills K. , Grindlay J. E. , Rodriguez J. E. , Lund M. B. , Kuhn R. B. 
Published: September 2018

Context. The 16 Myr old star 1SWASP J140747.93-394542.6 (V1400 Cen) underwent a series of complex eclipses in May 2007, interpreted as the transit of a giant Hill sphere filling debris ring system around a secondary companion, J1407b. No other eclipses have since been detected, although other measurements have constrained but not uniquely determined the orbital period of J1407b. Finding another eclipse towards J1407 will help determine the orbital period of the system, the geometry of the proposed ring system and enable planning of further observations to characterize the material within these putative rings.
Aims. We carry out a search for other eclipses in photometric data of J1407 with the aim of constraining the orbital period of J1407b.
Methods. We present photometry from archival photographic plates from the Harvard DASCH survey, and Bamberg and Sonneberg Observatories, in order to place additional constraints on the orbital period of J1407b by searching for other dimming and eclipse events. Using a visual inspection of all 387 plates and a period-folding algorithm we performed a search for other eclipses in these data sets.
Results. We find no other deep eclipses in the data spanning from 1890 to 1990, nor in recent time-series photometry from 2012–2018.
Conclusions. We rule out a large fraction of putative orbital periods for J1407b from 5 to 20 yr. These limits are still marginally consistent with a large Hill sphere filling ring system surrounding a brown dwarf companion in a bound elliptical orbit about J1407. Issues with the stability of any rings combined with the lack of detection of another eclipse, suggests that J1407b may not be bound to J1407.
Outracing Lung Signal Decay – Potential of Ultrashort Echo Time MRI
Authors: Wielpütz Mark , Triphan Simon , Ohno Yoshiharu , Jobst Bertram , Kauczor Hans-Ulrich 
Published: September 2018

Background Magnetic resonance imaging (MRI) of the pulmonary parenchyma is generally hampered by multiple challenges related to patient respiratory- and circulation-related motion, low proton density and extremely fast signal decay due to the structure of the lungs evolved for gas exchange.
Methods Systematic literature database research as well as annual participation in conferences dedicated to pulmonary MRI for more than the past 20 years by at least one member of the author team.
Results and Conclusion The problem of motion has been addressed in the past by developments such as triggering, gating and parallel imaging. The second problem has, in part, turned out to be an advantage in those diseases that lead to an increase in lung substance and thus an increase in signal relative to the background. To reduce signal decay, ultrashort echo time (UTE) methods were developed to minimize the time between excitation and readout. Having been postulated a while ago, improved hardware and software now open up the possibility of achieving echo times shorter than 200 µs, increasing lung signal significantly by forestalling signal decay and more effectively using the few protons available. Such UTE techniques may not only improve structural imaging of the lung but also enhance functional imaging, including ventilation and perfusion imaging as well as quantitative parameter mapping. Because of accelerating progress in this field of lung MRI, the review at hand seeks to introduce some technical properties as well as to summarize the growing data from applications in humans and disease, which promise that UTE MRI will play an important role in the morphological and functional assessment of the lung in the near future.
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Consequences of the Adoption of the IADPSG versus Carpenter and Coustan Criteria to Diagnose Gestational Diabetes: A Before-After Comparison
Authors: Gariani Karim , Egloff Michael , Prati Sarah , Philippe Jacques , Boulvain Michel , Jornayvaz François R. 
Published: September 2018

Abstract
Aims To evaluate if the adoption of the International Association of Diabetes and Pregnancy Study Groups (IADPSG) diagnostic criteria for Gestational Diabetes Mellitus (GDM) led to changes in the management and in the occurrence of pregnancy complications.
Methods This was a retrospective study of women with GDM followed at a single university center, diagnosed in 2009–2010 using the Carpenter and Coustan criteria (period 1) and in 2012–2013 using the IADPSG criteria (period 2).
Results We included 286 women with GDM, 129 in period 1 and 157 in period 2. Age, body mass index and weight gain during pregnancy were similar. There were less women requiring insulin therapy in period 2 than in period 1 (43.3% versus 55.0% respectively, p=0.048), but no significant difference in the number of cesarean section, in babies born large for gestational age and in the occurrence of preeclampsia. There was less neonatal hypoglycemia (<2.5 mmol/l) in period 2 versus period 1 (7 versus 23 neonates respectively, p<0.001).
Conclusions When using the new IADPSG criteria, women with a less severe GDM are diagnosed, and fewer women require insulin. There was no difference in maternal outcomes, but less neonatal hypoglycemia during when using the IADPSG criteria.
Calibrated Automated Thrombinography (CAT), a Tool to Identify Patients at Risk of Bleeding during Anticoagulant Therapy: A Systematic Review
Authors: Zwaveling Suzanne , Bloemen Saartje , de Laat Bas , ten Cate Hugo , ten Cate-Hoek Arina 
Published: September 2018

Background Bleeding is a feared adverse event during anticoagulant treatment. In patients on vitamin K antagonists, most bleedings occur with the international normalized ratio (INR) in the therapeutic range. Currently, identification of high-risk patients via laboratory methods is not reliable. In this systematic review, we assessed the ability of calibrated automated thrombin generation (CAT-TG) to predict bleeding in patients on anticoagulant treatment.
Methods A systematic search was executed in three databases: Medline, Embase, and Cochrane.
Results Seven studies were included; two were of good methodological quality. One study showed that patients on warfarin with INRs in range (2–3) admitted for hemorrhage (n = 28), had lower CAT-TG levels (endogenous thrombin potential [ETP]: 333 ± 89 nM/min) than patients on warfarin admitted for other reasons (ETP: 436 ± 207 nM/min; p < 0.001). Another study found no difference in ETP or peak levels between bleeding and nonbleeding patients in PPP or PRP. When measured in whole blood, both levels were significantly lower in patients with bleeding compared with nonbleeding patients (median [interquartile range, IQR] ETP: 182.5 [157.2–2,847 nM/min] vs. median [IQR] ETP: 256.2 [194.9–344.2 nM/min]; p < 0.001) and median [IQR] peak: 23.9 [19.6–41.8 nM] vs. median [IQR] peak: 39.1 [24.9–53.2 nM]; p < 0.05). From the remaining studies, four suggested that CAT-TG is more sensitive in detecting hemostatic abnormalities than INR and one article found ETP and INR to be equally useful. However, insufficient data were provided to validate these conclusions.
Conclusion Studies investigating the direct association between decreased CAT-TG values and hemorrhagic events are rare. Therefore, the clinical consequences of low CAT-TG values remain to be further investigated.
An Assessment of the Effectiveness of Warfarin Therapy Monitoring Systems on Thrombophilic Patients in Zimbabwe
Authors: Maramba Aaron , Ncube Silenkosi , Mandisodza Arthur , Da Silva Marques Dayana , Matsikure Tsehay 
Published: September 2018

Introduction Thrombophilia describes conditions that predispose individuals to increased blood clotting and includes conditions such as deep vein thrombosis and pulmonary embolism. Thrombophilia is associated with high morbidity and mortality rates, and is commonly treated by warfarin anticoagulation. However, warfarin may cause both bleeding and clotting episodes if the therapy is not monitored and managed effectively.
Objectives The main objective of this study was to assess the effectiveness of warfarin monitoring systems on thrombophilic patients at a major hospital in Zimbabwe.
Material and Methods A clinical and laboratory prospective and retrospective study was performed on patients who had been on warfarin therapy for at least 1 year. Questionnaires were administered to participants on warfarin from outpatients clinics at Parirenyatwa Group of Hospitals. Their international normalized ratio (INR) results were also accessed from the laboratory information system and captured in the Epi info and Microsoft Excel for analysis.
Results Fifty questionnaires were administered and 47 (94%) participants responded adequately. Twenty-nine (61.1%) participants on warfarin were females. The majority of them were elderly and in the 31 to 40 age groups. Eighteen (38.3%) participants missed their medication at some point, while 12 (25.5%) had warfarin overdose. Sixteen (34%) and 11 (23.4%) admitted to taking alcohol and smoking, respectively, while on warfarin. Thirty-five (74.5%) did not change their medication nor were advised on the right diet. Thirty-four (72.3%) had appointments set after every month. Some participants indicated that they had symptoms of both clotting and bleeding. There were statistically significant differences (p < 0.0001) between INRs for 3 monthly intervals from the initiation of warfarin therapy.
Conclusion Women and the elderly formed the majority of the patients on warfarin, indicating gender and advanced age susceptibility to thrombophilia, respectively. The effectiveness of the warfarin monitoring systems appeared to be hampered by lack of a coordinated system that adequately monitors anticoagulant therapy in the country.
Bethesda Assay for Detecting Inhibitory Anti-ADAMTS13 Antibodies in Immune-Mediated Thrombotic Thrombocytopenic Purpura
Authors: Vendramin Chiara , Thomas Mari , Westwood John-Paul , Scully Marie 
Published: September 2018

AbstractA diagnosis of thrombotic thrombocytopenic purpura (TTP) is confirmed by a severe deficiency (<10%) of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) activity. Autoantibodies to ADAMTS13 can be detected with a simplified enzyme-linked immunosorbent assay (ELISA). An alternative methodology is a Bethesda assay, which has never been formally assessed in TTP. This study aimed to investigate the inhibitory anti-ADAMTS13 antibody assay and determine if the Bethesda assay is advantageous compared with the ELISA, measuring total immunoglobulin G (IgG) antibodies to ADAMTS 13. The Bethesda method determines the neutralizing activity of anti-ADAMTS13 antibodies in pooled normal plasma. We selected six immune-mediated TTP (iTTP) patients with ADAMTS13 activity levels <10% and strong ADAMTS13 inhibitors by 50:50 mixing studies and analyzed anti-ADAMTS13 antibodies using the Bethesda and ELISA assays. ADAMTS13 activity was stable at room temperature, while a time-dependent decrease in activity was detected in assay conditions of 37°C. Adding 5 mM Ca2+ to citrated plasma prevented loss of ADAMTS13 activity with time. There was time dependence to the antibody-mediated inactivation, after 2-hour incubation. Two of the iTTP patients had no detectable ADAMTS13 antibodies by the Bethesda assay, but had high titer of anti-ADAMTS13 antibodies and low ADAMTS13 antigen levels. The Bethesda assay can only detect anti-ADAMTS13 antibodies that functionally inhibit ADAMTS13. The anti-ADAMTS13 IgG ELISA instead allows the rapid identification of total IgG autoantibodies, detecting both inhibitory and noninhibitory antibodies.
Massive Left Atrial Thrombus in Two Patients with Heparin-Induced Thrombocytopenia Type II after Cardiac Surgery
Authors: Mandryk Yuriy , Czesla Markus , Mogilansky Christian , Stefkova Kristina , Drees Aloys , Massoudy Parwis 
Published: September 2018

AbstractHeparin-induced thrombocytopenia type II (HIT type II) can have devastating consequences in cardiac surgical patients. We report two cases of massive left atrial thrombus after mitral valve replacement and endocardial cryoablation in patients with HIT type II.
Translocatable voltage-gated Ca2+channel β subunits in α1–β complexes reveal competitive replacement yet no spontaneous dissociation
Authors: Yeon Jun-Hee , Park Cheon-Gyu , Hille Bertil , Suh Byung-Chang 
Published: September 2018

SignificanceVoltage-gated Ca2+(CaV) channels have an α1-α2δ core complexed with one of several alternative β subunits. Contradictory evidence says that, once bound, (i) a β subunit is permanently associated with the α1-α2δ core or (ii) that it is free to be exchanged for other β subunits. We designed rapamycin-translocatable CaVβ subunits that allow drug-induced sequestration of free β subunits to several organelle anchors. Sequestering free subunits does not dissociate bound subunits from channels except when the binding site is mutated to weaken the interaction. Nevertheless, our rapamycin constructs show that, when nontranslocatable β subunits are coexpressed with a translocatable subunit, sequestering the translocatable subunit changes the channel properties, revealing a quick replacement by the nontranslocatable subunit in the channel complex.
Exploring the free-energy landscape of GPCR activation
Authors: Alhadeff Raphael , Vorobyov Igor , Yoon Han Wool , Warshel Arieh 
Published: September 2018

Significance
Exploring the action of G-protein–coupled receptors (GPCRs) is a problem of major fundamental and practical importance. Hence, it is crucial to understand the free-energy landscape of the activation of a GPCR. However, at present it is practically impossible to explore this issue by all-atom simulations. The current work uses a coarse-grained (CG) model to explore the nature of the relevant landscape and the resulting GPCR activation. We explore the energetic determinants of the allosteric mechanism of GPCR activation, shedding light on the structure/activity relationship of the system. This advance can serve as a basis for further progress in understanding GPCRs and related systems. Furthermore, it demonstrates the utility of CG approaches in describing and analyzing large and complex biological systems.
Impact of Operating Room Etiquette Video on Medical Student Comfort in the Gynecologic OR
Authors: Melnyk Alexandra , Stuparich Mallory , Lee Jessica , Donnellan Nicole 
Published: September 2018

PURPOSE:
To assess if enhanced orientation to the gynecologic operating room (OR) by brief video intervention affects medical students' comfort and self-rated performance in the OR.

BACKGROUND:
A large percentage of third year medical education is spent in the OR, an environment that many students have never previously experienced. We identified a deficit in OR orientation in the clerkship, and made a brief video reviewing scrubbing technique, gowning/gloving, patient positioning, and skin preparation.

METHODS:
Third and fourth year medical students participating in the OBGYN clerkship at Magee-Womens Hospital were recruited during orientation. Participants completed a pre-test survey, self-assessments of daily OR performance and a posttest survey after their final exam. All students watched the video once during orientation and were provided online access to the video.

RESULTS:
We recruited 71 OBGYN clerkship students. Most students accessed the video one or zero times during the rotation. Students were divided into those with no prior surgical rotation experience and those with prior experience. Medical students demonstrated self-reported improvement in using personal protective equipment (PPE), gowning/gloving, full surgical scrub, and donning PPE with and without assistance (P<.0001). Students without previous experience demonstrated greater improvement than those with experience in using PPE (P=.0003), gowning/gloving, full surgical scrub, and donning with assistance (P<.0001).

DISCUSSION:
The majority of students reported improved comfort in the gynecologic OR by having access to the video. This video can be implemented as part of the clerkship curriculum, made available to surgical naïve students, and broadened for use in other surgical clerkships.