bluuebunny/crossref_metadata_2025_split huggingface dataset:
Very narrow coronal mass ejections producing solar energetic particles
Authors: Bronarska K. , Wheatland M. S. , Gopalswamy N. , Michalek G. 
Published: July 2018

Aims. Our main aim is to study the relationship between low-energy solar particles (energies below 1 MeV) and very narrow coronal mass ejections (“jets” with angular width ≤ 20°).
Methods. For this purpose, we considered 125 very narrow coronal mass ejections (CMEs) from 1999 to 2003 that are potentially associated with low-energy solar particles (LESPs). These events were chosen on the basis of their source location. We studied only very narrow CMEs at the western limb, which are expected to have good magnetic connectivity with Earth.
Results. We found 24 very narrow CMEs associated with energetic particles such as ions (protons and 3He), electrons, or both. We show that arrival times at Earth of energetic particles are consistent with onset times of the respective CMEs, and that in the same time intervals, there are no other potential sources of energetic particles. We also demonstrate statistical differences for the angular width distributions using the Kolmogorov–Smirnov test for angular widths for these 24 events. We consider a coherent sample of jets (mostly originating from boundaries of coronal holes) to identify properties of events that produce solar energetic particles (velocities, widths, and position angles). Our study presents a new approach and result: very narrow CMEs can generate low-energy particles in the vicinity of Earth without other activity on the Sun. The results could be very useful for space weather forecasting.
Update mHealth
Authors: Becker Stefan , Jahn Michael , Pramann Oliver , Hasenfuß Gerd , Budde Clemens , Halleck Fabian , Albrecht Urs-Vito 
Published: July 2018

ZusammenfassungIm Gesundheitswesen kommen immer mehr Apps auf den Markt und im klinischen Alltag zum Einsatz. Unabhängig davon, ob es sich um ein Medizinprodukt handelt oder
nicht, besteht bei einer Fehlfunktion im Schadensfall unter Umständen ein erhebliches Haftungsrisiko für den Arzt. Trifft man vor der Anwendung gezielte
Vorkehrungen, lässt sich dieses minimieren. Ein neues Filtersystem für Apps im Bereich der Inneren Medizin soll zudem für eine bessere Orientierung in den
App-Stores bieten.
Imaging of Sacral Stress and Insufficiency Fractures
Authors: Spiegl Ulrich , Schnake Klaus , Osterhoff Georg , Scheyerer Max , Ullrich Bernhard , Bula Philipp , Siekmann Holger 
Published: July 2018

ZusammenfassungSakrumfrakturen, die ohne adäquates Trauma entstanden sind, werden in Insuffizienzfrakturen und Stressfrakturen eingeteilt. Während Insuffizienzfrakturen bei physiologischer Belastung meist auf dem Boden einer relevanten Osteoporose entstehen, beruhen Stressfrakturen auf einer mechanischen Überlastung. Der vordere Beckenring ist regelmäßig beteiligt. Aufgrund des fehlenden bzw. niederenergetischen Unfallhergangs wird die korrekte Diagnose oft verspätet gestellt. Demzufolge war es das Ziel der AG Osteoporotische Frakturen der Sektion Wirbelsäule der DGOU, die einzelnen bildgebenden Verfahren zur korrekten, schnellen und kosteneffektiven Diagnostik vorzustellen. Zur Diagnosesicherung sollte neben der konventionell radiologischen Diagnostik zeitnah eine Schnittbildgebung in die Wege geleitet werden. Mittels CT kann die Frakturmorphologie am besten beurteilt werden, wodurch potenzielle Instabilitätszeichen der Verletzung erkannt werden können. Die MRT kann aufgrund der hohen Sensitivität bei fehlendem Frakturnachweis im CT, bei jungen Patienten und unklaren Situationen zusätzliche wichtige Informationen liefern. Im Falle einer Kontraindikation für das MRT stellen nuklearmedizinische Untersuchungen eine gute Alternative dar.
Maschinen statt Menschen
Authors: Alscher Mark Dominik 
Published: July 2018

ZusammenfassungDie Praxis der Medizin sieht sich aktuell großen Herausforderungen gegenüber. Insbesondere die Aspekte der „e-Health“ bieten einerseits Chancen, aber auch
Herausforderungen. Um Exzellenz in der Medizin zu erreichen, ist eine praktische Erfahrungsbasis von 10 000 Stunden notwendig. Heutzutage wird dies aufgrund
mehrerer Faktoren nicht mehr erreicht. Die Exzellenz in der Medizin, welche häufig auch auf Intuition beruht, wird damit verschwinden, wenn wir nicht durch
digitale Lösungen andere Möglichkeiten finden. Eine davon besteht in „Clinical-decision-support“-Systemen. In der Maschine-Mensch-Partnerschaft wird in naher
Zukunft die Exzellenz aufrecht zu erhalten sein.
Conjugate Alkynylation of Electrophilic Double Bonds. From Regioselectivity to Enantioselectivity
Authors: Blay Gonzalo , Pedro José , Sanz-Marco Amparo 
Published: July 2018

This review surveys the historical efforts addressed toward the development of the conjugate alkynylation reaction. The regio- and enantioselective conjugate alkynylation of electron-deficient double bonds, most commonly unsaturated carbonyl compounds, has been an elusive reaction for a long time. Intensive research during the last decades has resulted in the identification of a number of effective reagents and catalysts to perform this reaction. Non-stereoselective conjugate alkynylation of unsaturated carbonyl compounds was first achieved by using preformed alkynyl organometallics and later with terminal alkynes under catalytic conditions. These methods paved the way for the development of enantioselective procedures. After initial methods requiring stoichiometric amounts of chiral material, the findings by Corey on Ni-catalyzed addition of alkynylalanes and, particularly, by Carreira on Cu-catalyzed addition of terminal alkynes boosted the research on the development other asymmetric procedures catalyzed by Cu, Zn, Rh, Co, Ru and Pd complexes. The alkynylation of electrophilic alkenes conjugated with groups other than carbonyl and the alkynylation of extended conjugated systems are also discussed in the last part of this review.1	Introduction2	Non-Stereoselective Conjugate Alkynylation of α,β-Unsaturated Carbonyl Compounds3	Enantioselective Conjugate Alkynylation of α,β-Unsaturated Carbonyl Compounds4	Non-Stereoselective and Enantioselective Alkynylation of Other Electrophilic Alkenes5	γ-Alkynylation of α,β-Unsaturated Amides and δ-Alkynylation of Electrophilic Dienes6	Alternative Enantioselective Procedures7	Conclusion and Outlook
Buttocks Hard as Rocks: Not Wanted after Aortic Dissection Repair
Authors: Cameron-Gagné Maude , Bédard Luc , Lafrenière-Bessi Valérie , Lévesque Marie-Hélène , Dagenais François , Langevin Stéphan , Laflamme Maxime , Voisine Pierre , Jacques Frédéric 
Published: July 2018

AbstractThe authors report the case of a patient developing a gluteal compartment syndrome after DeBakey type I dissection repair. Prompt recognition and treatment led to successful results. The surgical approach to the gluteal compartment is described.
Epigenetics in Ascending Thoracic Aortic Aneurysm and Dissection
Authors: Boileau Adeline , Lindsay Mark , Michel Jean-Baptiste , Devaux Yvan 
Published: July 2018

AbstractThoracic aortic aneurysm (TAA) is an asymptomatic and progressive dilatation of the thoracic aorta. Ascending aortic dissection (AAD) is an acute intraparietal tear, occurring or not on a pre-existing dilatation. AAD is a condition associated with a poor prognosis and a high mortality rate. TAA and AAD share common etiology as monogenic diseases linked to transforming growth factor β signaling pathway, extracellular matrix defect, or smooth muscle cell protein mutations. They feature a complex pathogenesis including loss of smooth muscle cells, altered phenotype, and extracellular matrix degradation in aortic media layer. A better knowledge of the mechanisms responsible for TAA progression and AAD occurrence is needed to improve healthcare, nowadays mainly consisting of aortic open surgery or endovascular replacement. Recent breakthrough discoveries allowed a deeper characterization of the mechanisms of gene regulation. Since alteration in gene expression has been linked to TAA and AAD, it is conceivable that a better knowledge of the causes of this alteration may lead to novel theranostic approaches. In this review article, the authors will focus on epigenetic regulation of gene expression, including the role of histone methylation and acetylation, deoxyribonucleic acid methylation, and noncoding ribonucleic acids in the pathogenesis of TAA and AAD. They will provide a translational perspective, presenting recent data that motivate the evaluation of the potential of epigenetics to diagnose TAA and prevent AAD.
Protein C Osaka 10 with Aberrant Propeptide Processing: Loss of Anticoagulant Activity Due to an Amino Acid Substitution in the Protein C Precursor
Authors: Miyata Toshiyuki , Zheng Yan-Zhen , Sakata Toshiyuki , Kato Hisao 
Published: July 2018

SummaryWe studied the molecular basis of protein C deficiency in a family with a history of thromboembolic disease. An approximately 50% reduction in anticoagulant activity despite normal levels of protein C amidolytic activity and antigen was detected in plasma from the proband. All the exons and intron/exon junctions of the protein C gene were studied using a strategy that combined polymerase chain reaction amplification with DNA sequencing of the amplified fragments. We identified a C-to-A change at nucleotide number 1387 of the protein C gene in the proband and his mother, and this mutant was designated protein C Osaka 10. The C-to-A change resulted in the substitution of Ser for Arg at position -1, which is the processing protease cleavage site. The mutant protein C was partially purified from plasma of the patient’s mother using barium adsorption followed by ion-exchange column chromatography. It eluted at the same sodium chloride concentration as normal protein C, and thus γ-carboxylation of the mutant protein appeared to be normal. The apparent molecular weight of this mutant protein C was the same as that of the normal protein on immunoblotting. Amino-terminal sequence analysis showed that the light chain of the mutant protein C had an additional Ser at position -1. Thus, the loss of anticoagulant activity of protein C Osaka 10 can be explained by alteration of the conformation of the Gla domain by the additional Ser in the mutant molecule.
Studies on the Haemostatic Defect in a Complicated Syndrome
Authors: Stormorken H , Holmsen H , Sund R , Sakariassen K S , Hovig T , Jellum E , Solum N O 
Published: July 2018

SummaryThe Stormorken syndrome is a multifacetted syndrome including a bleeding tendency. No deviations were found in the coagulation- or fibrinolytic systems. Platelet number was low normal, and size abnormal, whereas EM findings were unremarkable. Survival time was half normal. Clot retraction was initially rapid, but clearly decreased, whereas prothrombin consumption was also initially rapid, but complete. Membrane GP’s were normal, so was AA metabolism, PI-cycle, granule storage and secretion, and c-AMP function, whereas 5-HT uptake and storage was decreased. Optical platelet aggregation was low normal with all physiological agonists. The only clearly abnormal finding was that coagulant activity was present on non stimulated platelets at the same level as kaolin-stimulated normal platelets. This indicated a platelet abnormality which should lead to a thrombogenic, not to a haemorrhagic trait. This paradox may have its origin in rheology, because when challenged with in vivo shear rates in an ex vivo perfusion chamber, platelet cohesion was abnormally low. Further studies to better delineate the membrane abnormality are underway.
Identification and Genetic Analysis of a Common Molecular Variant of Histidine-rich Glycoprotein with a Difference of 2KD in Apparent Molecular Weight
Authors: Hennis B C , van Boheemen P A , Wakabayashi S , Koide T , Hoffmann J J M L , Klevit P , Dooijewaard G , Jansen J G , Kluft C 
Published: July 2018

SummaryTwo forms of histidine-rich glycoprotein (HRG) were detected on SDS-PAGE by silver staining and immunoblotting after isolation of the protein from pooled plasma using immuno-affinity chromatography followed by chromatography with heparin-Sepharose. Both forms were single-chain molecules and the apparent molecular weights of form 1 and form 2 were 77 kD and 75 kD respectively. Mendelian inheritance of both HRG forms was observed in four families with 24 informative meioses, strongly suggesting that the two forms are encoded by different alleles. The frequency of form 1 and form 2 in a group of 36 individuals was 0.35 and 0.65 respectively.The difference between the two molecular variants was studied by direct sequence analysis of amplified exons of the HRG gene from 6 individuals who were homozygous either for form 1 or form 2. Five amino acid polymorphisms in three different exons were observed: Ile/Thr in exon 4; Pro/Ser in exon 5; His/Arg, Arg/Cys and Asn/Ile in exon 7. Analysis of these polymorphisms in 20 volunteers showed that only the Pro/Ser polymorphism at position 186 in exon 5 was coupled to the form of the HRG protein. Ser was found in form 1 and Pro in form 2. The presence of Ser at position 186 introduces a consensus sequence for a N-glycosylation site (Asn-X-Ser/Thr). By removing N-linked sugars with N-glycanase, it could be demonstrated that the difference between the two forms of HRG is caused by an extra carbohydrate group at Asn 184 in form 1.
Uptake, Internalization and Degradation of the Novel Plasminogen Activator Reteplase (BM 06.022) in the Rat
Authors: Kuiper J , van de Bilt H , Martin U , van Berkel Th J C 
Published: July 2018

SummaryThe catabolism of the novel plasminogen activator reteplase (BM 06.022) was described. For this purpose BM 06.022 was radiolabelled with l25I or with the accumulating label l25I-tyramine cellobiose (l25I-TC).BM 06.022 was injected at a pharmacological dose of 380 μg/kg b.w. and it was cleared from the plasma in a biphasic manner with a half-life of about 1 min in the α-phase and t1/2of 20-28 min in the β-phase. 28% and 72% of the injected dose was cleared in the α-phase and β-phase, respectively. Initially liver, kidneys, skin, bones, lungs, spleen, and muscles contributed mainly to the plasma clearance. Only liver and the kidneys, however, were responsible for the uptake and subsequent degradation of BM 06.022 and contributed for 75% to the catabolism of BM 06.022. BM 06.022 was degraded in the lysosomal compartment of both organs. Parenchymal liver cells were responsible for 70% of the liver uptake of BM 06.022. BM 06.022 associated rapidly to isolated rat parenchymal liver cells and was subsequently degraded in the lysosomal compartment of these cells. BM 06.022 bound with low-affinity to the parenchymal liver cells (550 nM) and the binding of BM 06.022 could be displaced by t-PA (IC50 5.6 nM), indicating that the low-density lipoprotein receptor-related protein (LRP) could be involved in the binding of BM 06.022. GST-RAP, which is an inhibitor of LRP, could in vivo significantly inhibit the uptake of BM 06.022 in the liver.It is concluded that BM 06.022 is metabolized primarily in the liver and the kidneys. These organs take up and degrade BM 06.022 in the lysosomes. The uptake mechanism of BM 06.022 in the kidneys is unknown, while LRP is responsible for a low-affinity binding and uptake of BM 06.022 in parenchymal liver cells.
Effects of an Epoxymethano Stable Analogue of Prostaglandin Endoperoxides (U-46619) on Human Platelets
Authors: di Minno G , Bertelé V , Bianchi L , Barbieri B , Cerletti C , Dejana E , de Gaetano G , Silver M J 
Published: July 2018

SummaryU-46619 is a stable epoxymethano analogue of cyclic endoperoxide PGH2. We studied platelet aggregation, 14C-5HT release, LDH extrusion and prostaglandin and thromboxane production induced by this compound in platelet-rich plasma samples from 15 healthy volunteers. Each subject was tested both before and 90 min after aspirin (500 mg) ingestion. The threshold aggregating concentration (TAC) of U-46619 ranged between 0.18 and 0.90 µM. Aggregation was maximal between 40 and 60 min after venipuncture and was concentration-dependent. At concentrations below the TAC, U-46619 induced primary reversible aggregation with minimal 14C-5HT release. At TAC or higher concentrations aggregation and release proceded as parallel events. Neither prostaglandin or thromboxane production nor LDH loss could be detected in any of the situations tested. Aspirin ingestion did not modify the pattern of platelet responses. In unstirred, not aggregated platelet samples 14C-5HT release by U-46619 occurred to a similar extent as in stirred, aggregated platelet samples. Addition to citrated PRP of 0.3 mM Na2 EDTA blocked both aggregation and release induced by U-46619. This compound, however, aggregated washed platelets resuspended in Ca++-free-tyrode-albumin containing fibrinogen. The mechanism by which U-46619 activates platelets differs from that of all other common aggregating agents.
Induction of Human Factor VIII Inhibitors in Rats by Immunization with Human Recombinant Factor VIII: a Small Animal Model for Humans with High Responder Inhibitor Phenotype
Authors: Jarvis M A , Levin L G , Harrison J A , DePianto D J , Suzuki C M , Ziaja C L , Brown J E , Jolly K W , Reisner H M , Abidgaard C F , Powell J S 
Published: July 2018

SummaryHemophilia A is a clotting disorder that is due to reduced or absent coagulation factor VIII (FVIII) activity. In approximately 25% of people with severe hemophilia A, standard treatment with intravenous plasma-derived or recombinant FVIII (rFVIII) induces anti-FVIII antibodies that inhibit FVIII activity (inhibitors). We describe the development of a rat model to study the formation of inhibitors. Immunization of rats with human rFVIII in adjuvant induced an anti-human rFVIII antibody response characteristic of an anti-FVIII inhibitor response in hemophilia A patients. The rats exhibited a rapid, polyclonal secondary antibody response to human rFVIII. These antibodies were reactive against epitopes located in the heavy and light chains. All the rFVIII-immunized rats developed antibodies against the FVIII C2 domain, a region of major reactivity in hemophilia A patients with inhibitors. Furthermore, competition ELISAs demonstrated that rat and human anti-FVIII antibodies recognized identical or overlapping epitopes of the FVIII molecule. The rat anti-FVIII antibodies also functioned as human FVIII inhibitors with titers ranging from 120 to 2048 Bethesda Units (B.U.). We propose that this rat model may be useful to investigate immune responses to FVIII and may lead to better therapies for FVIII inhibitors.
Retinoids Induce t-PA Synthesis by C6 Glioma Cells -Role in Tumoral Haemorrhagic Necrosis
Authors: Pernod Gilles , Amalfltano Guy , Le Magueresse Brigitte , Berger Francois , Polack Benolt , Kolodie Lucien 
Published: July 2018

SummaryTreatment of rat C6 glioma with high doses of 13 cis-retinoic acid (cRA) was responsible for death related to haemorrhagic necrosis localized to the tumor. Our aim was to explore this adverse effect of retinoid treatment. We show that cRA-treated C6 glioma at 25 mg/kg/day for 18 days exhibits in vivo an increased t-PA activity, which is responsible for a localized tumor fibrinolytic activity. Production of t-PA is supported by specific enhancement of gene expression, as was shown by the increase in t-PA mRNA (X 2.3). This production is a direct effect of cRA when treating the tumor, since tumor cells themself do not produce enough t-PA and treatment of control rats does not increase the t-PA level. t-PA production by rat C6 glioma is in vivo related to the specific synthesis of t-PA by the C6 cell-line. The stimulation of C6 cell-line by cRA in vitro is dose-dependent and reached a maximum for 3 and 30 |iM at the 72nd h. So cRA-treated C6 glioma cells produce t-PA which appears to be the major species associated with the fibrinolytic activity-induced intra-tumoral haemorrhage after exposure to retinoid treatment.
Platelet-derived Microvesicles in Thrombotic Thrombocytopenic Purpura and Hemolytic Uremic Syndrome
Authors: Galli Monica , Grassi Anna , Barbui Tiziano 
Published: July 2018

SummaryThrombotic thrombocytopenic purpura (TTP) and the related hemolytic uremic syndrome (HUS) are disorders characterized by thrombocytopenia, microangiopathic hemolytic anemia, a variable degree of impairment of renal function and fluctuating neurological symptoms, which are thought to be due to platelet activation and subsequent formation of thrombi in the microcirculation. Since platelet activation is accompanied by the generation of microvesicles (PMPs), we determined their presence in patients with TTP and HUS by flow cytometry. The analysis was performed in whole blood, using FITC-conjugated monoclonal antibodies (CD 42b and/or CD 61a). PMPs were discriminated from platelets on the basis of size and fluorescence profiles. Their levels in 21 normal controls ranged between 2.4% and 9.4% (mean ± SD: 5.2 ± 1.99%). No correlations were found with platelet number. PMPs were then evaluted in 13 patients with TTP and 2 cases of HUS. In all patients they were found higher than in controls, ranging from 11.0 to 91.1% (45.0 ± 26.0%; p = 0.0001 vs controls). PMPs were serially measured in patients with TTP: at diagnosis a correlation between PMPs and platelet number was found (R^2 = 0.669) and the time-course showed that the improvement of both microangiopathy and clinical manifestations of cerebral and renal involvement was accompanied by a progressive normalization of PMP levels and platelet count.PMP levels were measured also in patients suffering from other forms of thrombocytopenia: they were 17 patients with idiopathic thrombocytopenic purpura and 10 patients with acute leukemias and severe thrombocytopenia during the aplastic phase following chemotherapy. PMP ranges were: 2.0−79.6% (21.6 ± 20.8%; p = 0.001 vs controls) and 4.6−12.5% (8.8 ± 2.4%; p = 0.0001 vs controls), respectively. No correlations were found between platelet number and the absolute number of PMPs in these 2 groups of patients.These findings show that increased levels of PMPs may be found in peripheral thrombocytopenias and suggest that their presence may be clinically relevant, particularly in the microangiopathic forms.
Characterization Of The In Vitro “Factor VIII Bypassing Activity”
Authors: Aronson D L , Bagley J 
Published: July 2018

The in vitro correction of the prolonged APTT of hemophilic plasma has been ascribed to an uncharacterized entity “Factor VIII Bypassing Activity.” Such products also correct the prolonged APTT plasma deficient in Factor IX, Factor X and Factor XII, but not of Factor V deficient plasma. Correction of the APTT in Factor VIII deficient plasma by early stage coagulants such as Factor XIIa, Kallikrein and Factor IXa is minimal. These results indicate that this in vitro activity acts at the level of either the activation of Factor X or the activation of prothrombin.A coagulant has been prepared from serum by barium precipitation, heparin-agarose, DEAE cellulose and high pressure liquid chromatography (HPLC). The in vitro coagulant properties are similar to “activated” prothrombin complex (Autoplex) and the biologic and chemical properties are identical to activated Factor X.Infusion of the partially purified serum coagulant into normal dogs was well tolerated and, in contrast to Factor IX concentrates, gave no signs of DIC. Infusion into bleeding hemophilic dogs had no hemostatic effect. It is concluded that a major portion of the in vitro potency of activated prothrombin concentrates is due to activated Factor X, a material which when infused has no in vivo hemostatic effect.Acknowledgments - The authors gratefully acknowledge the studies of Dr. Henry Kingdon in hemophilic dogs.