bluuebunny/crossref_metadata_2025_split huggingface dataset:
Familial Cancer Variant Prioritization Pipeline version 2 (FCVPPv2) applied to a papillary thyroid cancer family
Authors: Kumar Abhishek , Bandapalli Obul Reddy , Paramasivam Nagarajan , Giangiobbe Sara , Diquigiovanni Chiara , Bonora Elena , Eils Roland , Schlesner Matthias , Hemminki Kari , Försti Asta 
Published: July 2018

AbstractWhole-genome sequencing methods in familial cancer are useful to unravel rare clinically important cancer predisposing variants. Here, we present improvements in our pedigree-based familial cancer variant prioritization pipeline referred as FCVPPv2, including 12 tools for evaluating deleteriousness and 5 intolerance scores for missense variants. This pipeline is also capable of assessing non-coding regions by combining FANTOM5 data with sets of tools like Bedtools, ChromHMM, Miranda, SNPnexus and Targetscan. We tested this pipeline in a family with history of a papillary thyroid cancer. Only one variant causing an amino acid change G573R (dbSNP ID rs145736623, NM_019609.4:exon11:c.G1717A:p.G573R) in the carboxypeptidase gene CPXM1 survived our pipeline. This variant is located in a highly conserved region across vertebrates in the peptidase_M14 domain (Pfam ID PF00246). The CPXM1 gene may be involved in adipogenesis and extracellular matrix remodelling and it has been suggested to be a tumour suppressor in breast cancer. However, the presence of the variant in the ExAC database suggests it to be a rare polymorphism or a low-penetrance risk allele. Overall, our pipeline is a comprehensive approach for prediction of predisposing variants for high-risk cancer families, for which a functional characterization is a crucial step to confirm their role in cancer predisposition.
Chiral visible light metasurface patterned in monocrystalline silicon by focused ion beam
Authors: Gorkunov Maxim V. , Rogov Oleg Y. , Kondratov Alexey V. , Artemov Vladimir V. , Gainutdinov Radmir V. , Ezhov Alexander A. 
Published: July 2018

AbstractHigh refractive index makes silicon the optimal platform for dielectric metasurfaces capable of versatile control of light. Among various silicon modifications, its monocrystalline form has the weakest visible light absorption but requires a careful choice of the fabrication technique to avoid damage, contamination or amorphization. Presently prevailing chemical etching can shape thin silicon layers into two-dimensional patterns consisting of strips and posts with vertical walls and equal height. Here, the possibility to create silicon nanostructure of truly tree-dimensional shape by means of the focused ion beam lithography is explored, and a 300 nm thin film of monocrystalline epitaxial silicon on sapphire is patterned with a chiral nanoscale relief. It is demonstrated that exposing silicon to the ion beam causes a substantial drop of the visible transparency, which, however, is completely restored by annealing with oxidation of the damaged surface layer. As a result, the fabricated chiral metasurface combines high (50–80%) transmittance with the circular dichroism of up to 0.5 and the optical activity of up to 20° in the visible range. Being also remarkably durable, it possesses crystal-grade hardness, heat resistance up to 1000 °C and the inertness of glass.
Profiling of the TCRβ repertoire in non-model species using high-throughput sequencing
Authors: Migalska Magdalena , Sebastian Alvaro , Radwan Jacek 
Published: July 2018

AbstractIn recent years, immune repertoire profiling with high-throughput sequencing (HTS) has advanced our understanding of adaptive immunity. However, fast progress in the field applied mostly to human and mouse research, with only few studies devoted to other model vertebrates. We present the first in-depth characterization of the T-cell receptor (TCR) repertoire in a non-model mammal (bank vole,Myodes glareolus), widely used in ecological and evolutionary research. We used RNA from spleens, 5′RACE and HTS to describe V and J segments of TCRβ, qualitatively characterize preferential V–J segment usage and CDR3 length distribution. Overall orthology to murine genes was preserved, with 11 J and 37 V genes found in voles (although 3 V genes lacked a close orthologue). Further, we implemented unique molecular identifiers for quantitative analysis of CDR3 repertoire with stringent error correction. A conservative, lower bound estimation of the TCRβ repertoire was similar to that found for mice (1.7–2.3 × 105clonotypes). We hope that by providing an easy-to-follow molecular protocol and on-line bioinformatics tools that do not require reference sequences (AmpliTCR and AmpliCDR3), we will encourage HTS immune repertoire profiling in other non-model vertebrates, thus opening new research avenues in e.g. comparative immunology, ecology and evolutionary biology.
Inequality as information: Wealth homophily facilitates the evolution of cooperation
Authors: Johnson Tim , Smirnov Oleg 
Published: July 2018

AbstractFree-riding produces inequality in the prisoners’ dilemma: cooperators suffer costs that defectors avoid, thus putting them at a material disadvantage to their anti-social peers. This inequality, accordingly, conveys information about a social partner’s choices in past game play and raises the possibility that agents can use the aggregation of past payoffs—i.e. wealth—to identify a social partner who uses their same strategy. Building on these insights, we study a computational model in which agents can employ a strategy—when playing multiple one-shot prisoners’ dilemma games per generation—in which they view other agents’ summed payoffs from previous games, choose to enter a PD game with the agent whose summed payoffs most-closely approximate their own, and then always cooperate. Here we show that this strategy of wealth homophily—labelled COEQUALS (“CO-operate with EQUALS”)—can both invade an incumbent population of defectors and resist invasion. The strategy succeeds because wealth homophily leads agents to direct cooperation disproportionately toward others of their own type—a phenomenon known as “positive assortment”. These findings illuminate empirical evidence indicating that viewable inequality degrades cooperation and they show how a standard feature of evolutionary game models—viz. the aggregation of payoffs during a generation—can double as an information mechanism that facilitates positive assortment.
Efficient homology-directed gene editing by CRISPR/Cas9 in human stem and primary cells using tube electroporation
Authors: Xu Xiaoyun , Gao Dongbing , Wang Ping , Chen Jian , Ruan Jinxue , Xu Jie , Xia Xiaofeng 
Published: July 2018

AbstractCRISPR/Cas9 efficiently generates gene knock-out via nonhomologous end joining (NHEJ), but the efficiency of precise homology-directed repair (HDR) is substantially lower, especially in the hard-to-transfect human stem cells and primary cells. Herein we report a tube electroporation method that can effectively transfect human stem cells and primary cells with minimal cytotoxicity. When applied to genome editing using CRISPR/Cas9 along with single stranded DNA oligonucleotide (ssODN) template in human induced pluripotent stem cells (iPSCs), up to 42.1% HDR rate was achieved, drastically higher than many reported before. We demonstrated that the high HDR efficiency can be utilized to increase the gene ablation rate in cells relevant to clinical applications, by knocking-out β2-microglobulin (B2M) in primary human mesenchymal stem cells (MSCs, 37.3% to 80.2%), and programmed death-1 (PD-1) in primary human T cells (42.6% to 58.6%). Given the generality and efficiency, we expect that the method will have immediate impacts in cell research as well as immuno- and transplantation therapies.
Sensitivity of gravito-inertial modes to differential rotation in intermediate-mass main-sequence stars
Authors: Van Reeth T. , Mombarg J. S. G. , Mathis S. , Tkachenko A. , Fuller J. , Bowman D. M. , Buysschaert B. , Johnston C. , García Hernández A. , Goldstein J. , Townsend R. H. D. , Aerts C. 
Published: July 2018

Context. While rotation has a major impact on stellar structure and evolution, its effects are not well understood. Thanks to high-quality and long-time base photometric observations obtained with recent space missions, we are now able to study stellar rotation more precisely.Aims. We aim to constrain radial differential rotation profiles inγDoradus (γDor) stars, and to develop new theoretical seismic diagnosis for such stars with rapid and potentially non-uniform rotation.Methods. We have derived a new asymptotic description which accounts for the impact of weak differential near-core rotation on gravity-mode period spacings. The theoretical predictions are illustrated from pulsation computations with the code GYRE and compared with observations ofγDor stars. When possible, we also derived the surface rotation rates in these stars by detecting and analysing signatures of rotational modulation, and computed the core-to-surface rotation ratios.Results. Stellar rotation must be strongly differential before its effects on period spacing patterns can be detected, unless multiple period spacing patterns can be compared. Six stars in our sample exhibit a single unexplained period spacing pattern of retrograde modes. We hypothesise that these are Yanai modes. Finally, we find signatures of rotational spot modulation in the photometric data of eight targets.Conclusions. If only one period spacing pattern is detected and analysed for a star, it is difficult to detect differential rotation. A rigidly rotating model will often provide the best solution. Differential rotation can only be detected when multiple period spacing patterns have been found for a single star or its surface rotation rate is known as well. This is the case for eight of the stars in our sample, revealing surface-to-core rotation ratios between 0.95 and 1.05.
Kepler Object of Interest Network
Authors: Freudenthal J. , von Essen C. , Dreizler S. , Wedemeyer S. , Agol E. , Morris B. M. , Becker A. C. , Mallonn M. , Hoyer S. , Ofir A. , Tal-Or L. , Deeg H. J. , Herrero E. , Ribas I. , Khalafinejad S. , Hernández J. , Rodríguez S. M. M. 
Published: July 2018

Context. The Kepler Object of Interest Network (KOINet) is a multi-site network of telescopes around the globe organised to follow up transiting planet-candidate Kepler objects of interest (KOIs) with large transit timing variations (TTVs). Its main goal is to complete their TTV curves, as the Kepler telescope no longer observes the original Kepler field.
Aims. Combining Kepler and new ground-based transit data we improve the modelling of these systems. To this end, we have developed a photodynamical model, and we demonstrate its performance using the Kepler-9 system as an example.
Methods. Our comprehensive analysis combines the numerical integration of the system’s dynamics over the time span of the observations along with the transit light curve model. This provides a coherent description of all observations simultaneously. This model is coupled with a Markov chain Monte Carlo algorithm, allowing for the exploration of the model parameter space.
Results. Applied to the Kepler-9 long cadence data, short cadence data, and 13 new transit observations collected by KOINet between the years 2014 and 2017, our modelling provides well constrained predictions for the next transits and the system’s parameters. We have determined the densities of the planets Kepler-9b and 9c to the very precise values of ρb = 0.439 ± 0.023 g cm−3 and ρc = 0.322 ± 0.017 g cm−3. Our analysis reveals that Kepler-9c will stop transiting in about 30 yr due to strong dynamical interactions between Kepler-9b and 9c, near 2:1 resonance, leading to a periodic change in inclination.
Conclusions. Over the next 30 years, the inclination of Kepler-9c (-9b) will decrease (increase) slowly. This should be measurable by a substantial decrease (increase) in the transit duration, in as soon as a few years’ time. Observations that contradict this prediction might indicate the presence of additional objects in this system. If this prediction turns out to be accurate, this behaviour opens up a unique chance to scan the different latitudes of a star: high latitudes with planet c and low latitudes with planet b.
Empfehlungen zur Anwendung der indirekten und direkten Antikoagulanzien zur langfristigen Sekundärprophylaxe nach venösen Thromboembolien
Authors: Kroeger Knut , Pleye Jürgen , Pourhassan Siamak , Peter Jochen , Noppeney Thomas 
Published: July 2018

ZusammenfassungDie Dosierungen der direkten oralen Antikoagulanzien für die langfristige Erhaltungstherapie nach akuter tiefer Venenthrombose und Lungenembolie erfordern im Alltag häufig eine individuelle Entscheidung, da für die Präparate Apixaban und Rivaroxaban jeweils 2 Dosen zur Verfügung stehen, für die es keine festgelegten separaten Indikationsspektren gibt. Daher hat die Arbeitsgemeinschaft der niedergelassenen Gefäßchirurgen und Gefäßmediziner Deutschlands e. V. dieses Positionspapier entwickelt. Patienten mit einem klar identifizierbaren und passageren Triggerfaktor für die venöse Thromboembolie (z. B. Trauma, Operation, akute internistische Erkrankung, orale Kontrazeption, Schwangerschaft) oder einer isolierten Unterschenkelvenenthrombose haben ein geringes Rezidivrisiko und werden i. d. R. nicht dauerhaft antikoaguliert. Besteht eine hohes Rezidivrisiko bei fortbestehendem Triggerfaktor (z. B. fortbestehende aktive Tumorerkrankung, zweifelsfrei nachgewiesenes Antiphospholipidsyndrom sowie ein Gerinnungsinhibitormangel von Protein C, Protein S oder Antithrombin bei positiver Familienanamnese bez. venöser Thromboembolien [VTE], Erstereignis einer Lungenembolie, mehrfachen Rezidiven einer VTE) ist eine verlängerte Erhaltungstherapie indiziert, sofern nicht ein sehr hohes Blutungsrisiko dagegen spricht. Bei allen Patienten mit einer abgelaufenen VTE, bei denen man grundsätzlich die Antikoagulationsphase beenden würde, kann eine verlängerte Prophylaxe fortgeführt werden, da auch diese Patienten ein höheres Rezidivrisiko haben als ein Mensch, der noch nie eine VTE gehabt hat.
Alterations in Vascular Endothelial Cell-related Plasma Proteins In Thalassaemic Patients and their Correlation with Clinical Symptoms
Authors: Butthep P , Bunyaratvej A , Funahara Y , Kitaguchi H , Fucharoen S , Sato S , Bhamarapravati N 
Published: July 2018

SummaryAn increased level of plasma thrombomodulin (TM) in α- and β- thalassaemia was demonstrated using an enzyme-linked immunosorbent assay (ELISA). Nonsplenectomized patients with β-thalassaemia/ haemoglobin E (BE) had higher levels of TM than splenectomized cases (BE-S). Patients with leg ulcers (BE-LU) were found to have the highest increase in TM level. Appearance of larger platelets in all types of thalassaemic blood was observed indicating an increase in the number of younger platelets. These data indicate that injury of vascular endothelial cells is present in thalassaemic patients.
Tissue Factor Expression on Mesothelial Cells is Induced during in vitro Culture – Manipulation of Culture Conditions Creates Perspectives for Mesothelial Cells as a Source for Cell Seeding Procedures on Vascular Grafts
Authors: Verhagen Hence J M , Heijnen-Snyder Glenda J , Vink Tom , Pronk Apollo , Vroonhoven Theo J M V van , Eikelboom Bert C , Sixma Jan J , Groot Philip G de 
Published: July 2018

SummaryLining the luminal surface of prosthetic small diameter bypasses with endothelial cells (EC) will lower its thrombogenicity. Unfortunately, human EC are only scarcely available. Mesotheliai cells (MC) have antithrombotic properties in vivo and can be harvested in large numbers, from the omentum. Recent work demonstrated that the expression of tissue factor (TF) is induced in MC after isolation and culture. Different culture conditions were studied to suppress TF-expression.MC grown in pooled human serum (HS) are procoagulant (717 ± 119 pM factor Xa/min.105 cells). Replacing HS for fetal calf serum, precoating the surface with extracellular matrix and the addition of the xanthine-oxidase inhibitor allopurinol, inhibited TF expression by 90% (p <0.001). Allopurinol clearly reduced TF-mRNA levels.TF expression on cultured MC is an in-vitro effect due to culture conditions and the formation of oxygen free radicals. By reducing TF expression by 90%, we have established conditions in which MC are a good alternative for EC for seeding on synthetic grafts.
Factor V Leiden (FV R506Q) in Families with Inherited Antithrombin Deficiency
Authors: van Boven H H , Reitsma P H , Rosendaal F R , Bayston T A , Chowdhury V , Borg Jeanne-Yvonne , Bauer K A , Scharrer I , Conard J , Lane D A 
Published: July 2018

SummaryWe investigated the presence of the gene mutation of factor V, FV R506Q or factor V Leiden, responsible for activated protein C resistance, in DNA samples of 127 probands and 188 relatives from 128 families with antithrombin deficiency. The factor V mutation was identified in 18 families. Nine families were available to assess the mode of inheritance and the clinical relevance of combined defects.The factor V and antithrombin genes both map to chromosome 1. Segregation of the defects on opposite chromosomes was observed in three families. Co-segregation with both defects on the same chromosome was demonstrated in four families. In one family a de novo mutation of the antithrombin gene and in another a crossing-over event were the most likely explanations for the observed inheritance patterns.In six families with type I or II antithrombin deficiency (reactive site or pleiotropic effect), 11 of the 12 individuals with both antithrombin deficiency and the factor V mutation developed thrombosis. The median age of their first thrombotic episode was 16 years (range 0-19); this is low compared with a median age of onset of 26 years (range 20-49) in 15 of 30 carriers with only a defect in the antithrombin gene. One of five subjects with only factor V mutation experienced thrombosis at 40 years of age. In three families with type II heparin binding site deficiencies, two of six subjects with combined defects experienced thrombosis; one was homozygous for the heparin binding defect.Our results show that, when thrombosis occurs at a young age in antithrombin deficiency, the factor V mutation is a likely additional risk factor. Co-segregation of mutations in the antithrombin and factor V genes provides a molecular explanation for severe thrombosis in several generations. The findings support that combinations of genetic risk factors underly differences in thrombotic risk in families with thrombophilia.
Purification, Characterization and cDNA Cloning of a Novel Anticoagulant of the Intrinsic Pathway, (Prolixin-S), from Salivary Glands of the Blood Sucking Bug, Rhodnius prolixus
Authors: Sun Jianxin , Yamaguchi Masahiro , Yuda Masao , Miura Ken , Takeya Hiroyuki , Hirai Makoto , Matsuoka Hiroyuki , Ando Katsuhiko , Watanabe Takashi , Suzuki Koji , Chinzei Yasuo 
Published: July 2018

SummaryThe salivary glands of the blood sucking insect, Rhodnius prolixus, have an anticoagulant, prolixin-S, which was reported as a specific inhibitor of intrinsic coagulant pathway. Prolixin-S was purified from the salivary glands extract of Rhodnius prolixus by gel filtration and anion exchange HPLC by assaying prolongation of activated partial thromboplastin time (APTT). The isolated protein specifically inhibited factor IXa-catalyzed activation of factor X in the presence of Ca2+ and phospholipids irrespective of the presence or absence of factor Villa. The anticoagulant factor had red color and a specific absorbance peak at 402 nm and thus it was identified as a heme protein. A Rhodnius prolixus salivary gland cDNA library was prepared, screened with an antibody against prolixin-S and its complete cDNA sequence was determined. cDNA and deduced amino acid sequences showed that prolixin-S is a novel anticoagulant of 19,922 Da, which has no sequence homology with any other anticoagulant reported so far.
The Significance of Hypofibrinolysis for the Risk of Recurrence of Venous Thromboembolism
Authors: Schulman S , Wiman B ,   the Duration of Anticoagulation (DURAC) Trial Study Group
Published: July 2018

SummaryAn impaired fibrinolytic function has been described in several case-control studies of patients with venous thromboembolism (VTE). In the present study the correlations between some fibrinolytic compounds and future recurrent VTE were investigated. Blood samples for analysis of tissue-type plasminogen activator (t-PA) antigen before and after 10 min of venous occlusion (V.O.) and plasminogen activator inhibitor type 1 (PAI-1) activity were taken at 6 months after the first episode of VTE or the first recurrent VTE in 784 and 207 patients, respectively, who were anticoagulated for 1.5 or 6 months (first VTE) and 6 months or indefinitely (first recurrence). During a follow-up of 3-6 years from the event which qualified for inclusion there have been 177 recurrences. All initial and recurrent events were verified with objective diagnostic methods. Using cut off points of 10.0 ng/ml for t-PA antigen before V.O. and 30 AU/ml for PAI-1 in samples taken at rest, there were more patients above those levels in the groups with than without further recurrence (t-PA antigen, 50% versus 36%, p = 0.001; PAI-1, 18% versus 12%, p = 0.045). In the 495 patients, who received oral anticoagulation for 6 months, t-PA antigen at rest discriminated better, with 59% versus 34% of patients above 10 ng/ml in the groups with and without recurrence, respectively (p <0.001). The t-PA antigen levels after V.O. and the fibrinolytic capacity (t-PA antigen after V.O. minus t-PA antigen before V.O.) were distributed similarly in patients with and without new recurrences. There was a statistically significant positive correlation between age and t-PA antigen (p <0.001), and by analysis of covariance the difference between the groups with and without further recurrence regarding t-PA antigen disappeared.In conclusion, increased levels of PAI-1 and t-PA antigen in VTE-patients correlate with development of recurrent VTE within the next 3–6 years, but the value of these components in predicting future events for the individual patient is limited.