bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine learning detection of obstructive hypertrophic cardiomyopathy using a wearable biosensor
Authors: Green Eric M. , van Mourik Reinier , Wolfus Charles , Heitner Stephen B. , Dur Onur , Semigran Marc J. 
Published: June 2019

AbstractHypertrophic cardiomyopathy (HCM) is a heritable disease of heart muscle that increases the risk for heart failure, stroke, and sudden death, even in asymptomatic patients. With only 10–20% of affected people currently diagnosed, there is an unmet need for an effective screening tool outside of the clinical setting. Photoplethysmography uses a noninvasive optical sensor incorporated in commercial smart watches to detect blood volume changes at the skin surface. In this study, we obtained photoplethysmography recordings and echocardiograms from 19 HCM patients with left ventricular outflow tract obstruction (oHCM) and a control cohort of 64 healthy volunteers. Automated analysis showed a significant difference in oHCM patients for 38/42 morphometric pulse wave features, including measures of systolic ejection time, rate of rise during systole, and respiratory variation. We developed a machine learning classifier that achieved a C-statistic for oHCM detection of 0.99 (95% CI: 0.99–1.0). With further development, this approach could provide a noninvasive and widely available screening tool for obstructive HCM.
Dual Ca2+-dependent gates in human Bestrophin1 underlie disease-causing mechanisms of gain-of-function mutations
Authors: Ji Changyi , Kittredge Alec , Hopiavuori Austin , Ward Nancy , Chen Shoudeng , Fukuda Yohta , Zhang Yu , Yang Tingting 
Published: June 2019

AbstractMutations of human BEST1, encoding a Ca2+-activated Cl− channel (hBest1), cause macular degenerative disorders. Best1 homolog structures reveal an evolutionarily conserved channel architecture highlighted by two landmark restrictions (named the “neck” and “aperture”, respectively) in the ion conducting pathway, suggesting a unique dual-switch gating mechanism, which, however, has not been characterized well. Using patch clamp and crystallography, we demonstrate that both the neck and aperture in hBest1 are Ca2+-dependent gates essential for preventing channel leakage resulting from Ca2+-independent, spontaneous gate opening. Importantly, three patient-derived mutations (D203A, I205T and Y236C) lead to Ca2+-independent leakage and elevated Ca2+-dependent anion currents due to enhanced opening of the gates. Moreover, we identify a network of residues critically involved in gate operation. Together, our results suggest an indispensable role of the neck and aperture of hBest1 for channel gating, and uncover disease-causing mechanisms of hBest1 gain-of-function mutations.
Melting and re-entrant melting of polydisperse hard disks
Authors: Sampedro Ruiz Pablo , Lei Qun-li , Ni Ran 
Published: June 2019

AbstractBecause of long-wavelength fluctuations, the nature of solids and phase transitions in 2D are different from those in 3D systems, and have been heavily debated in past decades, in which the focus was on the existence of hexatic phase. Here, by using large scale computer simulations, we investigate the melting transition in 2D systems of polydisperse hard disks. We find that, with increasing the particle size polydispersity, the melting transition can be qualitatively changed from the recently proposed two-stage process to the Kosterlitz-Thouless-Halperin-Nelson-Young scenario with significantly enlarged stability range for hexatic phase. Moreover, re-entrant melting transitions are found in high density systems of polydisperse hard disks, which were proven impossible in 3D polydisperse hard-sphere systems. These suggest a new fundamental difference between phase transitions in polydisperse systems in 2D and 3D.
Quantitative analysis of isolated boulder fields on comet 67P/Churyumov-Gerasimenko
Authors: Cambianica P. , Cremonese G. , Naletto G. , Lucchetti A. , Pajola M. , Penasa L. , Simioni E. , Massironi M. , Ferrari S. , Bodewits D. , La Forgia F. , Sierks H. , Lamy P. L. , Rodrigo R. , Koschny D. , Davidsson B. , Barucci M. A. , Bertaux J.-L. , Bertini I. , Da Deppo V. , Debei S. , De Cecco M. , Deller J. , Fornasier S. , Fulle M. , Gutiérrez P. J. , Güttler C. , Ip W.-H. , Keller H. U. , Lara L. M. , Lazzarin M. , Lin Z.-Y. , López-Moreno J. J. , Marzari F. , Mottola S. , Shi X. , Scholten F. , Toth I. , Tubiana C. , Vincent J.-B. 
Published: June 2019

Aims.We provide a detailed quantitative analysis of isolated boulder fields situated in three different regions of comet 67P/Churyumov-Gerasimenko: Imhotep, Hapi, and Hatmehit. This is done to supply a useful method for analyzing the morphology of the boulders and to characterize the regions themselves.Methods.We used OSIRIS Narrow Angle Camera images with a spatial scale smaller than 2 m px−1and analyzed the size-frequency distribution and the cumulative fractional area per boulder population. In addition, we correlated shape parameters, such as circularity and solidity, with both the spatial and the size-frequency distribution of the three populations.Results.We identified 11 811 boulders in the Imhotep, Hapi, and Hatmehit regions. We found that the Hatmehit and Imhotep areas show power indices in the range of −2.3/−2.7. These values could represent a transition between gravitational events caused by thermal weathering and sublimation, and material formed during collapses that has undergone sublimation. The Hapi area is characterized by a lower power index (−1.2/−1.7), suggesting that those boulders have a different origin. They can be the result of material formed during gravitational events and collapses that has undergone continuous fragmentation. We calculated the cumulative fractional area (CFA) in order to investigate how the area is covered by boulders as a function of their sizes. The Hatmehit and Imhotep regions show a CFA that is well fit by a power law. In contrast, the Hapi area does not show the same trend. We analyzed the fractal distributions, finding that the populations seem to be fractal at all dimensions, except for the Hapi distribution, which shows a possible fractal behavior for small dimensions only. Finally, the average values of the shape parameters reveal solid and roundish boulders in all populations we studied.
The physical and chemical structure of Sagittarius B2
Authors: Schwörer A. , Sánchez-Monge Á. , Schilke P. , Möller T. , Ginsburg A. , Meng F. , Schmiedeke A. , Müller H. S. P. , Lis D. , Qin S.-L. 
Published: June 2019

Context.Sagittarius B2 (north) is a chemically rich, high-mass star-forming region located within the giant molecular cloud complex Sgr B2 in the central molecular zone of our Galaxy. Dust continuum emission at 242 GHz, obtained at high angular resolution with the Atacama Large Millimeter Array (ALMA), reveals that it has a filamentary structure on scales of 0.1 pc.Aims.We aim to characterize the filamentary structure of Sgr B2(N) and its kinematic properties using multiple molecular dense gas tracers.Methods.We have used an unbiased, spectral line-survey that covers the frequency range from 211 to 275 GHz and obtained with ALMA (angular resolution of 0.′′4, or 3300 au) to study the small-scale structure of the dense gas in Sgr B2(N). In order to derive the kinematic properties of the gas in a chemically line-rich source like Sgr B2(N), we have developed a python-based tool that stacks all the detected line transitions of any molecular species. This allows us to increase the signal-to-noise ratio (S/N) of our observations and average out line blending effects, which are common in line-rich regions.Results.A filamentary network is visible in Sgr B2(N) in the emission maps of the molecular species CH3OCHO, CH3OCH3, CH3OH and H2CS. In total, eight filaments are found that converge to the central hub (with a mass of 2000M⊙, assuming a temperature of 250 K) and extending for about 0.1 pc (up to 0.5 pc). The spatial structure, together with the presence of the massive central region, suggest that these filaments may be associated with accretion processes, transporting material from the outer regions to the central dense hub. We derive velocity gradients along the filaments of about 20–100 km s−1pc−1, which are 10–100 times larger than those typically found on larger scales (~1 pc) in other star-forming regions. The mass accretion rates of individual filaments are ≾0.05M⊙yr−1, which result in a total accretion rate of 0.16M⊙yr−1. Some filaments harbor dense cores that are likely forming stars and stellar clusters. We determine an empirical relation between the luminosity and stellar mass of the clusters. The stellar content of these dense cores is on the order of 50% of the total mass. The timescales required for the dense cores to collapse and form stars, exhausting their gas content, are compared with the timescale of their accretion process onto the central hub. We conclude that the cores may merge in the center when already forming stellar clusters but still containing a significant amount of gas, resulting in a “damp” merger.Conclusions.The high density and mass of the central region, combined with the presence of converging filaments with high mass, high accretion rates and embedded dense cores already forming stars, suggest that Sgr B2(N) may have the potential to evolve into a super stellar cluster.
Stress verstehen und bewältigen
Authors: Richter Yvonne 
Published: June 2019

ZusammenfassungDas Arbeitsaufkommen im OP steigt – und mit ihm der Stress. Deshalb befragte
unsere Autorin im Rahmen ihrer Facharbeit Mitarbeiter im Zentral-OP der
Universitätsklinik Erlangen, welche Stressoren sie im Arbeitsalltag am stärksten
belasten. Außerdem entwickelte sie einen Gesundheitszirkel, mit dem die
Auswirkungen der Stressoren reduziert werden können.
Wahre Schönheit kommt von innen
Authors: Wolf Gunther 
Published: June 2019

ZusammenfassungPersonalmanager beklagen zunehmende Schwierigkeiten bei der Beschaffung von gut
ausgebildetem Operationspersonal. So ergreifen immer mehr Krankenhausleitungen
vielfältige Maßnahmen, um die bestehende Belegschaft fest an das Haus zu binden.
Doch viel nützt nicht immer viel: Nur, wenn die Mitarbeiterbindungsmaßnahmen
strukturiert und systematisch umgesetzt werden, tragen diese Früchte. Wie geht
man am besten vor? Unser Autor gibt direkt umsetzbare Tipps – für
Geschäftsführungen, Personalmanager und Führungskräfte.
Zirkulierende Tumorzellen, zirkulierende Tumor-DNA und zirkulierende microRNA beim metastasierten Mammakarzinom – oder: Welche Rolle spielt die Liquid Biopsy beim Brustkrebs?
Authors: Polasik Arkadius , Tzschaschel Marie , Schochter Fabienne , Gregorio Amelie de , Krause Sabrina , Friedl Thomas W.P. , Rack Brigitte , Hartkopf Andreas , Fasching Peter A. , Schneeweiss Andreas , Müller Volkmar , Huober Jens , Janni Wolfgang , Fehm Tanja 
Published: June 2019

ZusammenfassungDie Streuung von Tumorzellen und Entstehung solider Metastasen findet sowohl über das Lymph- als auch das Blutsystem statt. Der Nachweis zirkulierender Tumorzellen (CTCs) und der zirkulierenden Tumor-DNA (ctDNA) im venösen Blut ist sowohl beim frühen als auch beim metastasierten Mammakarzinom möglich. Ihre prognostische Relevanz wurde bereits mehrfach bewiesen. Dabei ist die repetitive Untersuchung der CTCs bzw. ctDNA im Sinne einer regelmäßigen „liquid biopsy“ jederzeit und problemlos möglich. Durch die zusätzlichen molekularen Analysen ist es möglich, Tumorcharakteristika und ihre Heterogenität, die mit möglichen Resistenzen einhergehen, zu definieren. Dies ermöglicht den Einsatz einer personalisierten und zielgerichteten Therapie, um neben einem verlängerten Gesamtüberleben auch die Verbesserung der Lebensqualität zu erreichen.
Factor V Leiden (Arg506Gln), a Confounding Genetic Risk Factor but not Mandatory for the Occurrence of Venous Thromboembolism in Homozygotes and Obligate Heterozygotes for Cystathionine β-synthase Deficiency
Authors: Yap S. , O’Donnell K. A. , O’Neill C. , Mayne P. D. , Thornton P. , Naughten E. 
Published: June 2019

SummaryThrombosis is the major cause of morbidity and mortality in individuals with untreated classical homocystinuria (HCU) due to cystathionine β-synthase deficiency and characterised by severe hyperhomocysteinaemia. In addition, mild and moderate hyperhomocysteinaemia and Factor V Leiden (FVL; Arg506Gln) have recently been identified as thrombotic risk factors. FVL, which renders resistance to activated Protein C, is the most common inherited genetic risk factor for thrombosis with a high allelic frequency amongst Caucasians. As thrombophilia is a multigenic disorder, 26 individuals with HCU (median age 17.6 years, range 3.5-32.8 years) and 36 obligate heterozygotes (median age 51.5 years, range 34-74 years) were screened for FVL. All the HCU individuals received treatment, except one, within 6 weeks of birth for those who were diagnosed at birth through the national newborn screening programme (n = 20) and at the time of diagnosis for those late detected (n = 5, mean age of starting treatment 4.9 years, range 1.4-11 years). All had been free from venous thrombosis, except one HCU individual and one HCU obligate heterozygote. Neither of the two individuals with venous thrombosis carried FVL. Two independent individuals with HCU (male 14.8 years; female 18.2 years) were heterozygous for FVL (allelic frequency 3.8%) and three independent HCU obligate heterozygotes (males 40 and 45.8 years; female 45.6 years) were also heterozygous for FVL (allelic frequency 4.16%). The findings in this small group suggest that FVL is not a mandatory but a significant confounding risk factor for the occurrence of thrombosis in HCU individuals and additional contributing factors may be required for thrombosis to occur in HCU obligate heterozygotes with FVL heterozygosity. Our data also suggest that treatment of HCU not only reduces the thrombotic risk in patients with isolated HCU but also in those with the additional FVL heterozygosity.
Venous Thromboembolic Disease and the Prothrombin, Methylene Tetrahydrofolate Reductase and Factor V Genes
Authors: Alhenc-Gelas Martine , Arnaud Emmanuel , Nicaud Viviane , Aubry Marie-Laurence , Fiessinger Jean-Noël , Aiach Martine , Emmerich Joseph 
Published: June 2019

SummaryThe prevalence of the A20210 allele of the prothrombin (PT) gene and the T677 allele of the methylene tetrahydrofolate reductase (MTHFR) gene was determined in 205 patients with venous thromboembolism (VTE) and in 398 healthy subjects of similar age and sex distribution. We also determined the frequency of these two candidate risk alleles in subjects carrying the factor V (FV) Q506 allele, to identify a possible interaction. Forty patients (19.5%) and 14 control subjects (3.5%) were heterozygous for the FV R506Q mutation. Twenty-one patients (10.2%) and 11 controls (2.8%) were heterozygous for the PT A20210 allele (odds ratio (OR) 4.02, 95% confidence interval (CI): 1.90-8.50, p <0.001). This confirmed that the PT A20210 allele was a risk factor for VTE in our population. Among the FV Q506 allele carriers, 9 patients (22.5%) and no control also had the PT gene G20210A mutation. The absence of the combined abnormality in the control group made it impossible to calculate the relevant ORs but the lower bound of the 95% CI was 3.94, suggesting that individuals bearing the two mutations have a higher risk than those with a single mutation. Twenty-six patients (12.7%) and 49 controls (12.3%) were homozygous for the MTHFR T677 allele (OR 1.04, 95% CI: 0.62-1.72, not significant). Four patients and 1 control were also heterozygous for the FV R506Q mutation (OR 9.33, 95% CI: 1.03-84.23). However, the ORs for carriers of the FV R506Q mutation were not significantly influenced by MTHFR gene C677T homozygosity.
Activated Protein C Resistance (FV:Q506) and Pregnancy
Authors: Lindqvist Pelle G. , Svensson Peter J. , Maršál Karel , Grennert Lars , Luterkort Marie , Dahlbäck Björn 
Published: June 2019

SummaryActivated protein C (APC) resistance, due to a point mutation in the factor V gene (FV:Q506), is a major risk factor for venous thromboembolism. To determine the prevalence of APC resistance in a large series of pregnant women, and to elucidate its obstetric consequences, we performed a prospective study in Malmö, Sweden, comprising 2,480 women enrolled in early pregnancy. The presence of APC resistance (the FV:Q506 allele) was determined. The women were interviewed about their medical histories including venous thromboembolic events (VTE) in relatives. The outcome variables were the VTE rate, intrapartum blood loss, and the prevalence of selected pregnancy complications such as fetal loss, pre-eclampsia, and intrauterine growth retardation.The overall prevalence of APC resistance was 11% (270/2480). The APC-resistant subgroup did not differ significantly from the non-APC-resistant subgroup in terms of pregnancy complications, but was characterized by an 8-fold higher risk of VTE (3/270 vs. 3/2210), a lower rate of profuse intrapartum haemorrhage (3.7% vs. 7.9%) (p = 0.02), and less intrapartum blood loss (340 ml vs. 361 ml) (p = 0.04). Despite the high prevalence of APC resistance in this series of gravidae (11%), its presence was unrelated to adverse pregnancy outcome apart from an 8-fold increased risk of VTE.
Fibrinogen, Factor VII and PAI-1 Genotypes and the Risk of Coronary and Peripheral Atherosclerosis: Edinburgh Artery Study
Authors: Lee A. J. , Fowkes F. G. R. , Lowe G. D. O. , Connor J. M. , Rumley A. 
Published: June 2019

SummaryThere are now many epidemiological studies that have shown a relationship between haemostatic factors and subsequent risk of both coronary and peripheral arterial disease. However, there is less information on the association between genetic variation in these factors and the risks of coronary and peripheral arterial disease. As part of the five-year follow-up of the Edinburgh Artery Study, polymorphisms of the fibrinogen (-455G/A), factor VII (R/Q353) and PAI-1 (HindIII) genes were measured in men and women aged 60-79 years, together with their plasma levels. Using widely accepted criteria, 88 subjects were identified as having peripheral arterial disease (PAD), 195 having coronary artery disease (CAD) and 423 subjects comprised a “healthy” group. The -455AA genotype of the fibrinogen gene was found to be more frequent among those subjects with PAD. This genotype also showed the highest plasma fibrinogen levels in both disease groups and in the healthy group. Using logistic regression, after adjustment for age, sex, smoking and plasma level, the -455AA genotype was associated with over twice the risk of PAD compared with the -455GG genotype, the odds ratio reaching marginal significance (p″0.10). Combining those with genotype -455AA with the heterozygotes in order to increase the power of the study resulted in a more significant multiple-adjusted risk of PAD (p″0.05). These data provide evidence that a polymorphism of the β fibrinogen gene is associated with an increased risk of peripheral atherosclerosis.
Tissue Factor Reduction and Tissue Factor Pathway Inhibitor Release after Heparin Administration
Authors: Gori A. M. , Pepe G. , Attanasio M. , Falciani M. , Abbate R. , Prisco D. , Fedi S. , Giusti B. , Brunelli T. , Comeglio P. , Gensini G. F. , Neri Serneri G. G. 
Published: June 2019

SummaryElevated plasma levels of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) and large amounts of monocyte procoagulant activity (PCA) have been documented in unstable angina (UA) patients. In in vitro experiments heparin is able to blunt monocyte TF production by inhibiting TF and cytokine gene expression by stimulated cells and after in vivo administration it reduces adverse ischemic outcomes in UA patients. TF and TFPI plasma levels and monocyte PCA have been investigated in 28 refractory UA patients before and during anticoagulant subcutaneous heparin administration (thrice daily weight- and PTT-adjusted for 3 days) followed by 5000 IU × 3 for 5 days. After 2-day treatment, immediately prior to the heparin injection, TF and TFPI plasma levels [(median and range): 239 pg/ml, 130-385 pg/ ml and 120 ng/ml, 80-287 ng/ml] were lower in comparison to baseline samples (254.5 pg/ml, 134.6-380 pg/ml and 135.5 ng/ml, 74-306 ng/ml). Four h after the heparin injection TF furtherly decreased (176.5 pg/ml, 87.5-321 pg/ml; -32.5%, p<0.001) and TFPI increased (240.5 ng/ml, 140-450 ng/ml; +67%, p<0.0001).After 7-day treatment, before the injection of heparin, TF and TFPI plasma levels (200 pg/ml, 128-325 pg/ml and 115 ng/ml, 70-252 ng/ml) significantly decreased (p<0.05) in comparison to the pre-treatment values. On the morning of the 8th day, 4 h after the injection of heparin TF plasma levels and monocytes PCA significantly decreased (156.5 pg/ml, 74-259 pg/ml and from 180 U/105 monocytes, 109-582 U/105 monocytes to 86.1 U/105 monocytes, 28-320 U/105 monocytes; - 38% and -55% respectively) and TFPI increased (235.6 ng/ml, 152-423 ng/ ml; +70%, p<0.001). In conclusion, heparin treatment is associated with a decrease of high TF plasma levels and monocyte procoagulant activity in UA patients. These actions of heparin may play a role in determining the antithrombotic and antiinflammatory properties of this drug.
Phospholipase A2 Enzymes Regulate αIIbβ3-mediated, but not FcγRII Receptor-mediated, pp125FAK Phosphorylation in Platelets
Authors: Haimovich Beatrice , Ji Ping , Ginalis Ernest , Kramer Ruth , Greco Ralph 
Published: June 2019

SummaryThe αIIbβ3 integrin and FcγRII receptors mediate, respectively, platelet adhesion and spreading on fibrinogen and immunoglobulin (IgG) coated surfaces. Platelet adhesion to fibrinogen resulted in a partial conversion of the faster to the slower migrating (phosphorylated) form of Ca+2-sensitive cytosolic phospholipase A2 (cPLA2) but failed to trigger arachidonic acid (AA) release. Full mobility shift of cPLA2 and a massive release of AA release were stimulated by platelet adhesion to IgG or addition of thrombin to the fibrinogen adherent platelets. IgG and thrombin induced AA production were blocked by methyl arachidonyl fluorophosphonate (MAFP), an irreversible inhibitor of cPLA2 and the Ca+2-independent phospholipase A2 (iPLA2). In contrast, bromoenol lactone (BEL), a specific inhibitor of iPLA2 had no effect on the release of AA. MAFP and BEL prevented pp125FAK phosphorylation and platelet spreading on fibrinogen having no effect on pp125FAK phosphorylation or platelet spreading on immobilized IgG. We conclude that αIIbβ3-mediated pp125FAK phosphorylation and platelet spreading on fibrinogen are regulated by PLA2 enzymes.Abbreviations: cPLA2, cytosolic calcium-dependent phospholipase A2; iPLA2, calcium-independent phospholipase A2; BSA, bovine serum albumin; mAB, monoclonal antibody; MAFP, methyl arachidonyl fluorophosphonate; pp125FAK, focal adhesion kinase; BEL, bromoenol lactone; AA, arachidonic acid.