bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative transcriptomics provides insight into the molecular basis of species diversification of section Trigonopedia (Cypripedium) on the Qinghai-Tibetan Plateau
Authors: Guo Yan-Yan , Zhang Yong-Qiang , Zhang Guo-Qiang , Huang Lai-Qiang , Liu Zhong-Jian 
Published: July 2018

AbstractDeceptive pollination is key to the species richness of Orchidaceae. However, the genetic basis of species diversification is still under study. SectionTrigonopediais a monophyletic clade of genusCypripediumdistributed in the southwest of China. The species of this section are pollinated by different flies. Pollinator differentiation makes sectionTrigonopediaan ideal group for studying the genetic basis underlying species diversification. Here, we sequenced the transcriptomes of eight species of the genusCypripedium, including six co-flowering species of sectionTrigonopediaand two species outside this section as an outgroup. We reconstructed the phylogeny of the section with the combined 1572 single-copy genes extracted from the eight species and produced a highly resolved tree of the section. Furthermore, we combined substitution rate estimation and differential expression analysis to identify candidate genes, including genes related to floral scent synthesis and environmental adaptation, involved in species differentiation. Field investigations showed that these species have adapted to different habitats. We propose that the species diversification in this section is initiated by floral scent differentiation, followed by habitat differentiation, finally leading to speciation. This study sheds novel light on the diversification of closely related orchid species in the Qinghai-Tibetan region.
Metabolic network-based predictions of toxicant-induced metabolite changes in the laboratory rat
Authors: Pannala Venkat R. , Wall Martha L. , Estes Shanea K. , Trenary Irina , O’Brien Tracy P. , Printz Richard L. , Vinnakota Kalyan C. , Reifman Jaques , Shiota Masakazu , Young Jamey D. , Wallqvist Anders 
Published: July 2018

AbstractIn order to provide timely treatment for organ damage initiated by therapeutic drugs or exposure to environmental toxicants, we first need to identify markers that provide an early diagnosis of potential adverse effects before permanent damage occurs. Specifically, the liver, as a primary organ prone to toxicants-induced injuries, lacks diagnostic markers that are specific and sensitive to the early onset of injury. Here, to identify plasma metabolites as markers of early toxicant-induced injury, we used a constraint-based modeling approach with a genome-scale network reconstruction of rat liver metabolism to incorporate perturbations of gene expression induced by acetaminophen, a known hepatotoxicant. A comparison of the model results against the global metabolic profiling data revealed that our approach satisfactorily predicted altered plasma metabolite levels as early as 5 h after exposure to 2 g/kg of acetaminophen, and that 10 h after treatment the predictions significantly improved when we integrated measured central carbon fluxes. Our approach is solely driven by gene expression and physiological boundary conditions, and does not rely on any toxicant-specific model component. As such, it provides a mechanistic model that serves as a first step in identifying a list of putative plasma metabolites that could change due to toxicant-induced perturbations.
Photobiomodulation of extracellular matrix enzymes in human nucleus pulposus cells as a potential treatment for intervertebral disk degeneration
Authors: Hwang Min Ho , Son Hyeong Guk , Lee Jae Won , Yoo Chang Min , Shin Jae Hee , Nam Hyo Geun , Lim Hyun Jung , Baek Seung Min , Park Jeong Hun , Kim Joo Han , Choi Hyuk 
Published: July 2018

AbstractIntervertebral disc (IVD) degeneration is associated with imbalances between catabolic and anabolic responses, regulated by extracellular matrix (ECM)-modifying enzymes such as matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors of metalloproteinases (TIMPs). Potential contributing factors, such as interleukin (IL)-1β and tumor necrosis factor (TNF)-α, derived from infiltrated, activated macrophages within IVD tissues, can trigger abnormal production of ECM-modifying enzymes and progression of IVD degeneration. Novel therapies for regulating ECM-modifying enzymes can prevent or ameliorate IVD degeneration. Photobiomodulation (PBM), known to regulate wound repair, exhibits regenerative potential by modulating biological molecules. This study examined the effects of PBM, administered at various wavelengths (630, 525, and 465 nm) and energy densities (16, 32, and 64 J/cm2), on the production of ECM-modifying enzymes in replicated degenerative IVD. Our results showed that PBM selectively inhibited the production of ECM-modifying enzymes in a dose- and wavelength-dependent manner, suggesting that it could be a novel tool for treating symptomatic IVD degeneration.
Update ESC-Leitlinie 2017: Duale Antiplättchentherapie
Authors: Massberg Steffen , Polzin Amin 
Published: July 2018

Was ist neu?
Risikostratifizierung der Dualen Plättcheninhibition (DAPT) Die neuen Leitlinien befassen sich mit grundlegenden Empfehlungen zu Form und Dauer der DAPT. Die Individualisierung der Therapie liegt deutlich im Fokus. Dabei wird geraten, mithilfe von Expertenteams bzw. Scores das individuelle Ischämie- bzw. Blutungsrisiko des jeweiligen Patienten einzuschätzen. In Abhängigkeit davon wird die Dauer einer DAPT festgelegt. Dabei wird hervorgehoben, dass die Entscheidung über die DAPT-Dauer dynamisch ist und in regelmäßigen Abständen reevaluiert werden sollte.
Duale Plättchenhemmung nach elektiver koronarer Stentimplantation Aufgrund der durch die neuen Stenttechnologien deutlich seltener auftretenden Stentthrombosen ist erstmals die Dauer der DAPT unabhängig vom Stenttyp (Bare-metal- oder Drug-eluting-Stent). Dabei ist eine Dauer von einem Monat bis zu 36 Monaten möglich. Damit hat sich die Sicht der DAPT von einer stentbezogenen auf eine systemische Behandlungsstrategie gewandelt.
Duale Plättchenhemmung im Rahmen eines akuten Koronarsyndroms In diesem Kontext wurden auch die Empfehlungen zur DAPT angepasst bei Patienten mit akutem Koronarsyndrom (ACS), die konservativ behandelt werden (inklusive Patienten mit Myokardinfarkt bei nicht okkludierten Koronararterien) und bei denjenigen, die mit einer Bypassoperation versorgt werden. In beiden Gruppen wird eine konsequente DAPT empfohlen. Deren Dauer richtet sich ebenfalls nach dem individuellen Blutungsrisiko des jeweiligen Patienten. Hinsichtlich des Starts einer DAPT bei Patienten mit Nicht-ST-Strecken-Hebungsinfarkt wird nun geraten, das Loading mit einem P2Y12-Hemmer (Ticagrelor oder Clopidogrel) bereits bei Diagnose durchzuführen, sofern eine Koronarangiografie angedacht ist.
Duale Plättchenhemmung bei Patienten mit Indikation zur dauerhaften Antikoagulation Ebenfalls gibt es Neuerungen der Empfehlungen zu Patienten mit Koronarintervention und zusätzlicher Indikation einer dauerhaften effektiven Antikoagulation bei Vorhofflimmern. Die Guidelines positionieren sich dahingehend, dass die Vorteile von oralen Nicht-Vitamin-K-Antikoagulanzien (NOAK) gegenüber Marcumar auch bei diesen Patienten Bestand haben könnten. Daher sei ein NOAK anstatt von Marcumar in Erwägung zu ziehen. Auch wird empfohlen, die Dauer der DAPT in Kombination mit oraler Antikoagulation (Triple-Therapie) in Abhängigkeit vom individuellen Ischämie- und Blutungsrisiko zu wählen. Dabei wird nun auch die Möglichkeit eingeräumt, eine Triple-Therapie lediglich periinterventionell anzuwenden und bereits bei Krankenhausentlassung auf ein duales Regime mit oraler Antikoagulation und einem Thrombozytenfunktionshemmer (Aspirin oder Clopidogrel) zu wechseln.
Interventionelle Bronchoskopie: was ist möglich und was ist sinnvoll?
Authors: Sarmand Nilab , Gompelmann Daniela 
Published: July 2018

Was ist neu?
Interventionelle Techniken bei Atemwegsstenosen Zu den interventionellen Techniken bei Atemwegsstenosen gehören nach wie vor die Ballondilatation, Kryotherapie, Lasertherapie, Argon-Plasma-Koagulation, Brachytherapie, fotodynamische Therapie und Stentimplantation. Die Auswahl der Therapieform wird in Abhängigkeit von Ausweitung und Entität des Tumors indiziert.
Endoskopische Lungenvolumenreduktion bei COPD Die endoskopische Lungenvolumenreduktion mittels Ventilimplantation oder Coilimplanation ist mittlerweile fester Bestandteil der COPD-Leitlinie. Endoskopische Thermoablation (BTVA) und polymerische Lungenvolumenreduktion (PLVR) sind weitere Therapieoptionen bei ausgewählten Patienten mit fortgeschrittenem Lungenemphysem.
Targeted Lung Denervation (TLD) Die TLD befindet sich für Patienten mit COPD und therapierefraktärem Asthma bronchiale in klinischer Untersuchung.
Thermoplastie bei Asthma bronchiale Die Thermoplastie ist das einzige etablierte endoskopische Verfahren bei therapierefraktärem Asthma bronchiale.
Kryospray-Therapie bei chronischer Bronchitis Für Patienten mit chronischer Bronchitis steht die Kryospray-Therapie zur Verfügung, deren Effektivität und Sicherheit ebenfalls im Rahmen von Studien überprüft wird.
In vitro Effects of Aprosulate sodium, a Novel Anticoagulant, On Platelet Activation: Possible Mechanism for Antiplatelet Action
Authors: Sugidachi Atsuhiro , Breiter Norbert , Ogawa Taketoshi , Asai Fumitoshi , Koike Hiroyuki 
Published: July 2018

SummaryAprosulate sodium, a bis-lactobionic acid amide derivative, is a novel synthetic polyanion with potent anticoagulant activities. In the present study, the effects of aprosulate on platelet aggregation were investigated in a plasma-free system. Aprosulate inhibited thrombin (0.03-0.3 U/ml)-induced aggregation in rat washed platelets in a concentration-dependent manner, with an IC50 value of 0.38 Μg/ml. In contrast, aprosulate, at up to 10 Μg/ml, did not affect collagen (1 Μg/ml) - or ADP (3 ΜM)-induced aggregation. In fura 2-loaded platelets, aprosulate (1-10 Μg/ml) inhibited intracellular Ca2+ mobilization induced by thrombin, but not that by ADP. Protamine, a highly basic protein, abolished aprosulate-mediated inhibition of thrombin-induced platelet aggregation, suggesting that the observed inhibition is primarily due to the negative charge contained on the aprosulate molecule. In human platelets, aprosulate inhibited thrombin-induced aggregation, but failed to inhibit platelet aggregation induced by SFLLRN, a synthetic tethered ligand of a thrombin receptor. Antiplatelet profiles of aprosulate were largely similar to those of heparin, although heparin inhibited both thrombin- and collagen-induced aggregation. These in vitro studies indicate that aprosulate is capable of inhibiting thrombin-induced platelet activation and that this effect is independent of its anticoagulant activity. These results suggest that the polyanionic feature of aprosulate plays an essential role in promoting its antiplatelet activities, and that a plausible mechanism to explain the observed inhibition conferred by this agent, would be one which involves blocking the platelet-thrombin interaction.
Transfusion Requirements Are Correlated with the Degree of Proteolysis of von Willebrand Factor during Orthotopic Liver Transplantation
Authors: Lattuada A , Mannucci P M , Chen C , Legnani C , Palareti G 
Published: July 2018

SummaryDuring orthotopic liver transplantation (OLT) excessive bleeding is the main cause of death and graft failure. The acute bleeding tendency that accompanies OLT, particularly during the anhepatic period and after reperfusion of the graft, is due to the depletion or functional abnormalities of several hemostasis components caused by the enhanced activity of enzymes such as plasmin, trypsin and leukocyte proteases. We surmised that enhanced proteolysis might also cause abnormalities of von Willebrand factor (vWF), and that these abnormalities are implicated in the bleeding tendency that develops during OLT. Therefore, the pattern of vWF proteolysis was studied with 16 patients with chronic liver disease, in serial blood samples obtained before OLT, during the anhepatic stage, after graft reperfusion and at the end of the surgical procedure. vWF became markedly degraded during the anhepatic and reperfusion stages, as shown by the partial loss of high molecular weight multimers, the relative decrease of the intact 225 kD subunit and the increase of the native proteolytic fragments of 176 and 140 kD. Novel proteolytic fragments also became detectable. Using monoclonal antibody epitope mapping, it could be demonstrated that some of the proteolytic fragments corresponded in apparent molecular mass to those produced in vitro by incubating purified vWF with plasmin or elastase, but other fragments could not be attributed to these proteases. During the anhepatic and reperfusion stages there was a significant correlation between the degree of vWF degradation and the total amount of blood components transfused to replace blood losses. To evaluate whether or not vWF degradation could be controlled by the administration of a broad-spectrum protease inhibitor such as aprotinin, 5 patients were given a bolus dose of 500,000 U before surgery followed by 100,000 U/h during surgery, 5 were given a 2,000,000 U bolus followed by 500,000 U/h, and no aprotinin was given to the remaining 6 patients. There were no differences in the patterns or degrees of vWF degradation between patients treated with aprotinin or not. In conclusion, there is a marked degradation of a key hemostasis protein during OLT. These alterations may be of clinical significance, because they are correlated with the transfusion requirements.
Dissociation of Antithrombotic Effect and Bleeding Time Prolongation in Rabbits by Inhibiting Tissue Factor Function
Authors: Himber Jacques , Kirchhofer Daniel , Riederer Markus , Tschopp Thomas B , Steiner Beat , Roux Sébastien P 
Published: July 2018

SummaryInhibition of the tissue factor/factor Vila (TF/F. Vila) complex attenuates thrombosis in different animal models of arterial thrombosis. However, it remains unclear to what extent the antithrombotic effects are associated with changes in hemostatic functions and how this compares with inhibition of thrombin, an enzyme acting at a later stage in the coagulation cascade. The antithrombotic and the antihemostatic effects of a monoclonal anti-TF antibody (AP-1) were compared in a model of arterial thrombosis to those of a direct thrombin inhibitor (napsagatran) and heparin. In anesthetized rabbits transient arterial thrombi were induced by mechanical damage to the subendothelium of a moderately stenosed carotid artery. Recurrent formation and dis lodgement of thrombi resulted in cyclic flow variations (CFVs) which were monitored over 2 hours. Rabbits received intravenously either a placebo (control), a monoclonal anti-rabbit TF antibody (AP-1, 05 mg/kg as an i.v. bolus repeated every 15 min, a specific low molecular weight thrombin inhibitor (napsagatran, 3 fxg/kg/min) or heparin (3 and 13 fig/kg/min). The effect of the inhibitors on the hemostatic system was studied in a separate set of rabbits by measuring template bleeding times (BT) in the ear arterioles, marginal ear vein and the nail cuticle of the foreleg. AP-1 and napsagatran showed a similar antithrombotic activity (78% and 80% abolition of the CFVs, respectively), whereas either low or high dose heparin was poorly effective (43 % and 40% inhibition of CFVs, respectively). At these antithrombotic doses and even at 4-fold higher dosage, AP-1 did not significantly alter the BT, whereas napsagatran and heparin prolonged the ear vessels and cuticle BT in a dose-dependent manner. These results suggest that in contrast to direct thrombin inhibition, the blockade of the TF/F. Vila function did not result in a concomitant prolongation of the bleeding time. Thus, dissociation of antithrombotic and antihemostatic effects indicates that inhibition of the coagulation system at its initial stage represents a promising approach for the development of new anticoagulants.
Haemophilia B in Female Twins Caused by a Point Mutation in one Factor IX Gene and Nonrandom Inactivation Patterns of the X-Chromosomes
Authors: Schröder Winnie , Wulff Karin , Wollina Karin , Herrmann Falko H 
Published: July 2018

SummaryHaemophilia B is a X-linked recessive bleeding disorder with an incidence of 1:25,000-30,000 male birth. Usually female carriers are clinically normal. Phenotypic expression of the disease in female carriers is extremely rare.We describe cytogenetically inconspicuous female identical twins both with factor IX levels below 2%, prolonged bleeding after venipuncture as well as haematomas after intramuscular injections. The father, suffering from a severe haemophilia B, is deceased. By sequencing one point mutation was characterized in heterozygote condition in the factor EX gene of the probands at nt 17678. This mutation leads to the substitution cystein 88 to tyrosine in the growth factor domain of the factor IX. Investigation of the X-chromosomal inactivation by comparison of methylation patterns of genomic DNA at locus DXS255 after digestion with Pst I and Pst I +Hha I and hybridisation with the probe M27β indicated a nonrandom pattern of X-chromosomal inactivation in the twins. In both girls, only the paternal X-chromosome was the active one leading to the phenotypic expression of haemophilia in the female carriers.
Elevating Endogenous Sphingosine-1-Phosphate (S1P) Levels Improves Endothelial Function and Ameliorates Atherosclerosis in Low Density Lipoprotein Receptor-Deficient (LDL-R−/−) Mice
Authors: Feuerborn Renata , Besser Manuela , Potì Francesco , Burkhardt Ralph , Weißen-Plenz Gabriele , Ceglarek Uta , Simoni Manuela , Proia Richard , Freise Hendrik , Nofer Jerzy-Roch 
Published: July 2018

Background Sphingosine-1-phosphate (S1P) is a bioactive lysosphingolipid and a constituent of high-density lipoprotein (HDL) exerting several atheroprotective effects in vitro. However, the few studies addressing anti-atherogenic effects of S1P in vivo have led to disparate results. We here examined atherosclerosis development in low-density lipoprotein receptor (LDL-R)-deficient (LDL-R−/−) mice with elevated endogenous S1P levels.
Methods and Results Sub-lethally irradiated LDL-R−/− mice were transplanted with bone marrow deficient in sphingosine kinase 2 (SphK2), which led to the elevation of S1P concentrations in erythrocytes, plasma and HDL by approximately 1.5- to 2.0-fold in SphK2−/−/LDL-R−/− mice. Afterwards, mice were fed a Western diet for 14 weeks. Elevation of endogenous S1P significantly reduced atherosclerotic lesion formation by approximately half without affecting the plasma lipid profile. Furthermore, the macrophage content of atherosclerotic lesions and lipopolysaccharide-induced monocyte recruitment to the peritoneal cavity were reduced in SphK2−/−/LDL-R−/− mice. Studies using intra-vital microscopy revealed that endogenous S1P lowered leukocyte adhesion to capillary wall and decreased endothelial permeability to fluorescently labelled LDL. Moreover, SphK2−/−/LDL-R−/− mice displayed decreased levels of vascular cell adhesion molecule 1 in atherosclerotic lesions and in plasma. Studies in vitro demonstrated reduced monocyte adhesion and transport across an endothelial layer exposed to increasing S1P concentrations, murine plasma enriched in S1P or plasma obtained from SphK2-deficient animals. In addition, decreased permeability to fluorescence-labelled dextran beads or LDL was observed in S1P-treated endothelial cells.
Conclusion We conclude that raising endogenous S1P levels exerts anti-atherogenic effects in LDL-R−/− mice that are mediated by favourable modulation of endothelial function.
Successful Treatment of Left Ventricular Perforation Occurring After Insertion of an Impella Device
Authors: Glazier James J. , Kaki Amir , Baciewicz Frank 
Published: July 2018

AbstractThe Impella device is a miniaturized ventricular assist device that is being increasingly used to increase the safety and efficacy of high-risk coronary interventions and to treat patients with acute myocardial infarction complicated by cardiogenic shock. The device has a miniaturized rotary pump mounted on a 9F catheter with a pigtail conformation. The pump draws blood from the left ventricular cavity and expels it into the ascending aorta and systemic circulation. We report a patient who, following insertion of an Impella device, developed angiographically documented left ventricular perforation with marked hemodynamic instability. Our successful management of this patient is described and potential mechanisms responsible for the perforation are discussed.
Identifying Asthma Exacerbation-Related Emergency Department Visit Using Electronic Medical Record and Claims Data
Authors: Sundaresan Agnes , Schneider Gargi , Reynolds Joy , Kirchner H. 
Published: July 2018

Background Asthma exacerbation leading to emergency department (ED) visit is prevalent, an indicator of poor control of asthma, and is a potentially preventable clinical outcome.
Objective We propose to utilize multiple data elements available in electronic medical records (EMRs) and claims database to create separate algorithms with high validity for clinical and research purposes to identify asthma exacerbation-related ED visit among the general population.
Methods We performed a retrospective study with inclusion criteria of patients aged 4 to 40 years, a visit to Geisinger ED from January 1, 2006, to October 28, 2013, with asthma on their problem list. Different electronic data elements including chief complaints, vitals, season, smoking, medication use, and discharge diagnoses were obtained to create the algorithm. A stratified random sample was generated to select the charts for review. Chart review was performed to classify patients with asthma-related ED visit, that is, the gold standard. Two reviewers performed the chart review and validation was done on a small subset.
Results There were 966 eligible ED visits in the EMR sample and 731 in the claims sample. Agreement between reviewers was 95.45% and kappa statistic was 0.91. Mean age of the EMR sample was 22 years, and mostly white (93%). Multiple models conventionally used in studies were evaluated and the final model chosen included principal diagnosis, bronchodilator, and steroid use for both algorithms, chief complaints for EMR, and secondary diagnosis for claims. Area under the curve was 0.93 (95% confidence interval: 0.91–0.94) and 0.94 (0.93–0.96), respectively, for EMR and claims data, with positive predictive value of > 94%. The algorithms are visually presented using nomograms.
Conclusion We were able to develop two separate algorithms for EMR and claims to identify asthma exacerbation-related ED visit with excellent diagnostic ability and varying discrimination threshold for clinical and research purposes.