bluuebunny/crossref_metadata_2025_split huggingface dataset:
From Natural to Artificial Antitumor Lipidic Alkynylcarbinols: Asymmetric Synthesis, Enzymatic Resolution, and Refined SARs
Authors: Génisson Yves , Maraval Valérie , Chauvin Remi , Listunov Dymytrii , Joly Etienne , Rullière Pauline , Gaspard Hafida , Bernardes-Génisson Vania 
Published: July 2018

Among acetylenic natural products, chiral lipidic alkynylcarbinol (LAC) metabolites, mostly extracted from marine sponges, have revealed a broad spectrum of biological activities, in particular, remarkable antitumor cytotoxicity. With reference to one of the simplest natural representatives, [(S)-eicos-(4E)-en-1-yn-3-ol], and a given cancer cell line (HCT116), combined extensive efforts in chemical synthesis (relying on the use of a large chemical toolbox) and biological analysis (in vitro tests), have provided systematic structure–activity relationships (SARs) where the initially selected four structural parameters appear as independent principal components: (i) and (ii) the sp/sp2 content and extent of the terminal and internal unsaturations adjacent to the carbinol center, (iii) the absolute configuration of the latter, (iv) the length of the n-aliphatic backbone. Two key criteria have also been established regarding the functional alkynylcarbinol pharmacophore: the alkynylcarbinol unit must be both secondary and terminal (i.e., substituted by a short ethynyl or ethenyl C2 group). This review is intended to provide a further illustration of the value of a simple rational approach for drug design, and to act as a benchmark for future optimization of LACs as antitumor agents.1	Introduction2	2C2-Unsaturated Pharmacophore Candidates2.1	Alkenylalkynylcarbinols (AACs)2.2	Dialkynylcarbinols (DACs or DACys)2.3	Alkynylalkenylcarbinols (iso-AACs) and Dialkenylcarbinols (DACes)2.4	Oxidation-Protected Dialkynylcarbinols and Dialkynylketones2.5	Fluorophore-Labeled Lipidic Dialkynylcarbinols3	C2/C3-Unsaturated Pharmacophore Candidates3.1	Cyclopropylalkynylcarbinols (CACs)3.2	Allenylalkynylcarbinols (AllACs)4	C2/C4- and 3C2-Unsaturated Pharmacophore Candidates4.1	Butadiynylalkynylcarbinols (BACs)4.2	Trialkynylcarbinols (TACs)5	Double-AC-Headed Pharmacophore Candidates6	Screening on the Lipidic Chain Length7	Conclusion
Electrical Aggregometry in Whole Blood from Human, Pig and Rabbit
Authors: Galvez Angel E , Badimon Lina , Badimon Juan-Jose , Fuster Valentin 
Published: July 2018

SummaryThe objective of this study was to characterize and standardize whole blood electrical aggregometry (WBEA) in the pig and rabbit, animal models extensively used in atherosclerosis research, and to compare their platelet response with that of man. Platelet aggregation was studied in blood (WBEA) and platelet rich plasma (optical aggregometry, OA). Dose response curves were obtained for ADP and collagen. The effect of hematocrit on WBEA was also evaluated. Aggregation with ADP and collagen using WBEA was more extensive with human than with pig or rabbit platelets. OA revealed similar differences among species but the time to reach maximal aggregation was markedly shorter. Using WBEA, the extent of aggregation was inversely related to the hematocrit. We conclude that WBEA is a useful technique that may be of particular importance in situations where hyper-lipidemic plasma prevents the use of OA, as occurs in some atherosclerosis research animal models.
Anticoagulant Activities of Pentosan Polysulphate (Hémoclar) Due to Release of Hepatic Triglyceride Lipase (HTGL)
Authors: Barrowcliffe T W , Gray E , Merton R E , Dawes J , Jennings C A , Hubbard A R , Thomas D P 
Published: July 2018

SummarySubcutaneous injections of 50 mg pentosan poly sulphate (Hemoclar) were given to normal volunteers and the effects on anti-Factor Xa activity, thrombin generation and lipase release measured. Concentrations of pentosan polysulphate were measured by a competitive binding assay and the mean peak level found to be 1.6 μg/ml. Anti-Xa clotting activity rose to 0.034 iu/ml and thrombin generation induced by lipid peroxides was inhibited by approximately 50%. Neither of these effects could be accounted for by the direct action of pentosan polysulphate at the concentrations measured. Pentosan poly sulphate was very effective in releasing lipase, approximately 70-80% of the total enzyme activity being due to hepatic triglyceride lipase (HTGL). In vitro addition of purified HTGL to plasma markedly enhanced anti-Xa clotting activity, and caused a 70% inhibition of lipid peroxide induced thrombin generation. Anti-Xa activity of postinjection plasma was increased rather than neutralised by addition of polybrene, and this effect could be mimicked by addition of polybrene to plasma containing pentosan polysulphate and purified HTGL. It is concluded that, when given in low doses subcutaneously, pentosan polysulphate acts as an indirect anticoagulant, its major effects being due to release of HTGL.
The Relation Between Platelet Reactivity and Coronary Angiographic Findings in Young Female Survivors of Acute Myocardial Infarction
Authors: Kutti Jack , Wadenvik Hans , Johansson Saga , Vilén Lars , Vedin Anders , Wilhelmsson Claes 
Published: July 2018

SummaryIn 31 women who had survived their first acute myocardial infarction (MI) studies of platelet reactivity were related to coronary angiographic findings. The results were compared to those obtained from 38 age-matched control women. According to the cardioangiographic findings the group of MI was subdivided into: 9 patients with 1-vessel disease (VD), 10 patients with 2-VD, and 5 patients with 3-VD; 7 subjects did not reveal significant coronary stenosis. When each of these 4 subgroups of MI-patients were compared with the control material significant difference with respect to PF4 was found only for subjects with 1-VD (20.0 ± 4.8 vs. 10.3 ± 0.6 ng/ml). As regards BTG the difference was significant for 1-VD and 2-VD patients (69 ± 12 and 59 ± 3, respectively vs. 40 ± 2 ng/ml). The cumulative frequency for secondary aggregation differed only as regards 1-VD patients (78 vs 40%).
Increased Procoagulant Response of Monocytes from Patients with Familial Mediterranean Fever
Authors: Courillon-Mallet Anne , Bevilacqua Michael , Wautier Jean-Luc , Dervichian Michel , Cattan Daniel , Caen Jacques 
Published: July 2018

SummaryFamilial Mediterranean Fever (FMF) is an inherited disease of unknown etiology characterized by recurrent inflammatory episodes. Circulating fibrin was found in patients with FMF in absence of clinical manifestation of thrombosis and was statistically less frequently observed in patients treated with colchicine. These results suggest a cellular dysfunction. Therefore, we examined the procoagulant activity (PCA) of isolated mononuclear leukocytes and purified monocytes from FMF patients (n = 20). No PCA was detectable on freshly-isolated monocytes. After several hours of culture, FMF monocytes contained more PCA than control cells and the difference was more marked after endotoxin stimulation. Data obtained with coagulation factor-deficient plasma and anti-human apoprotein III antiserum indicated that the enhanced PCA in FMF monocytes is thromboplastin-like. Lysozyme and interleukin 1 production by monocytes were similar in patients and controls. The increased monocyte PCA appears to be due to an intrinsic and selective higher responsiveness of monocytes.
Managing Adhesive Small Bowel Obstruction with Water-Soluble Contrast Should Be Protocolized: A Retrospective Analysis
Authors: Köstenbauer Jakob 
Published: July 2018

Aim Current literature emphasizes the effectiveness of computed tomography (CT) and water-soluble contrast agent, Gastrografin, in the investigation of adhesive small bowel obstruction (ASBO). As there is no management protocol for ASBO at our institution, the aim of this study was to determine the effect of imaging methods—CT, Gastrografin challenge (GC), or plain-film X-ray—on patient outcomes in a clinical setting.
Methods All 163 emergency presentations of ASBO during the study period between December 2010 and September 2012 were collected retrospectively. Cases were divided into three groups: CT with oral contrast, GC, or plain-film X-ray only. The primary outcome was time to theater.
Results Patients investigated with X-ray only were significantly less likely to require surgery (6% in plain-film X-ray vs. 35% and 20% in CT and GC, respectively; p = 0.003). In cases requiring surgery, GC was associated with a 24-hour longer time to imaging than CT (p < 0.001). The time to theater was 71:25 hours for GC versus 46:39 for CT (p = 0.039). There was no significant difference in bowel resection or complication rates.
Conclusion Patients undergoing water-soluble contrast studies were subjected to unnecessary delays in their clinical course. These delays are costly and avoidable. The development and implementation of an evidence-based protocol for the management of small bowel obstruction is strongly recommended. The lack of a protocol likely caused significant delays in Gastrografin administration, reducing its known benefits for clinical decision-making and length of stay.
Skull Base 3D Modeling of Rigid Buttress for Gasket-Seal Closure Using Operative Endoscopic Imaging: Cadaveric Feasibility
Authors: Shin James , Forbes Jonathan , Lehner Kurt , Tomasiewicz Hilarie , Schwartz Theodore H. , Phillips C. 
Published: July 2018

AbstractSurgical defect closure following endonasal transsphenoidal tumor resection is a critical component of procedural success. Three-dimensional (3D) modeling of relevant skull base anatomy during resection can potentially facilitate design of a custom rigid buttress for gasket-seal closure; however, access to conventional cross-sectional imaging intraoperatively is limited and cumbersome. Endoscopic imaging, by contrast, is always available. This work demonstrates the feasibility of 3D modeling of the visible skull base through structure-from-motion photogrammetric postprocessing techniques, providing a suitable template to design a gasket-seal buttress. Additionally, endoscopic 3D reconstruction of skull base surface anatomy may represent a more robust depiction of the surgical defect than is available by conventional 3D modeling with computed tomography, which suboptimally recapitulates very thin bones and mucosal surfaces typical of this regional anatomy.
Laufen für Einsteiger
Authors: Haas Hans-Josef 
Published: July 2018

ZusammenfassungEine physiotherapeutische Behandlungsserie führt oft dazu, dass der Patient beschließt, wieder mehr „für sich“ zu tun – z.B. laufen zu gehen. Beachtet er dabei ein paar Regeln, stehen die Chancen gut, dass aus der anfänglichen Schwärmerei eine Leidenschaft wird, die am Ende sogar von sportlichen Erfolgen gekrönt ist.
From object nominalization to object focus
Authors: Galucio Ana Vilacy , de Souza Nogueira Antônia Fernanda 
Published: July 2018

AbstractThis article proposes that the divergent pattern of verb argument marking found in object focus clauses in the Tuparian branch of the Tupian family comes from the reanalysis of an object nominalization in a cleft construction. Based on the distribution of free and bound person markers, the major alignment pattern can be characterized as nominative-absolutive in simple clauses, with free pronouns expressing the nominative, whereas bound person markers express the absolutive. However, object focus clauses show a distinct alignment pattern: the ergative, and not the absolutive, is indexed by the bound markers on the verb. We present arguments for identifying the object nominalization as the source of this grammar in the object focus clause, showing also how this reanalysis resulted in the nominalizer morpheme and the person markers gaining new functions.
Expletive negation is not expletive
Authors: Cépeda Paola 
Published: July 2018

Abstract
Spanish punctual hasta-clauses (‘until’) have been described as identical in meaning when containing or not an expletive negation, that is, a negative marker that apparently does not contribute to the sentence meaning. I show that the negation in the hasta-clause does in fact play a role in the meaning calculation. My proposal is that the semantic contribution of the so-called “expletive” negation is to negate that the eventuality in the main clause holds during the interval denoted in the hasta-clause; as a result, such eventuality is expected to hold after the eventuality in the hasta-clause is finished. The novelty of my analysis is the comparison of the aspect (specifically, the durativity component) of the eventualities expressed in the hasta-clause.
Prunasin production using engineered Escherichia coli expressing UGT85A47 from Japanese apricot and UDP-glucose biosynthetic enzyme genes
Authors: Yamaguchi Takuya , Asano Yasuhisa 
Published: July 2018

ABSTRACT
Japanese apricot, Prunus mume Sieb. et Zucc., biosynthesizes the l-phenylalanine-derived cyanogenic glucosides prunasin and amygdalin. Prunasin has biological properties such as anti-inflammation, but plant extraction and chemical synthesis are impractical. In this study, we identified and characterized UGT85A47 from Japanese apricot. Further, UGT85A47 was utilized for prunasin microbial production. Full-length cDNA encoding UGT85A47 was isolated from Japanese apricot after 5ʹ- and 3ʹ-RACE. Recombinant UGT85A47 stoichiometrically catalyzed UDP-glucose consumption and synthesis of prunasin and UDP from mandelonitrile. Escherichia coli C41(DE3) cells expressing UGT85A47 produced prunasin (0.64 g/L) from racemic mandelonitrile and glucose. In addition, co-expression of genes encoding UDP-glucose biosynthetic enzymes (phosphoglucomutase and UTP-glucose 1-phosphate uridiltransferase) and polyphosphate kinase clearly improved prunasin production up to 2.3 g/L. These results showed that our whole-cell biocatalytic system is significantly more efficient than the existing prunasin production systems, such as chemical synthesis.
The Functional Role of Large-scale Brain Network Coordination in Placebo-induced Anxiolysis
Authors: Meyer Benjamin , Yuen Kenneth S L , Saase Victor , Kalisch Raffael 
Published: July 2018

Abstract
Anxiety reduction through mere expectation of anxiolytic treatment effects (placebo anxiolysis) has enormous clinical importance. Recent behavioral and electrophysiological data suggest that placebo anxiolysis involves reduced vigilance and enhanced internalization of attention; however, the underlying neurobiological mechanisms are not yet clear. Given the fundamental function of intrinsic connectivity networks (ICNs) in basic cognitive processes, we investigated ICN activity patterns associated with externally and internally directed mental states under the influence of an anxiolytic placebo medication. Based on recent findings, we specifically analyzed the functional role of the rostral anterior cingulate cortex (rACC) in coordinating placebo-dependent cue-related (phasic) and cue-unrelated (sustained) network activity. Under placebo, we observed a down-regulation of the entire salience network (SN), particularly in response to threatening cues. The rACC exhibited enhanced cue-unrelated functional connectivity (FC) with the SN, which correlated with reductions in tonic arousal and anxiety. Hence, apart from the frequently reported modulation of aversive cue responses, the rACC appears to be crucially involved in exerting a tonically dampening control over salience-responsive structures. In line with a more internally directed mental state, we also found enhanced FC within the default mode network (DMN), again predicting reductions in anxiety under placebo.
Involvement of Phosphodiesterase 2A Activity in the Pathophysiology of Fragile X Syndrome
Authors: Maurin Thomas , Melancia Francesca , Jarjat Marielle , Castro Liliana , Costa Lara , Delhaye Sébastien , Khayachi Anouar , Castagnola Sara , Mota Elia , Di Giorgio Audrey , Servadio Michela , Drozd Malgorzata , Poupon Gwénola , Schiavi Sara , Sardone Lara , Azoulay Stéphane , Ciranna Lucia , Martin Stéphane , Vincent Pierre , Trezza Viviana , Bardoni Barbara 
Published: July 2018

Abstract
The fragile X mental retardation protein (FMRP) is an RNA-binding protein involved in translational regulation of mRNAs that play key roles in synaptic morphology and plasticity. The functional absence of FMRP causes the fragile X syndrome (FXS), the most common form of inherited intellectual disability and the most common monogenic cause of autism. No effective treatment is available for FXS. We recently identified the Phosphodiesterase 2A (Pde2a) mRNA as a prominent target of FMRP. PDE2A enzymatic activity is increased in the brain of Fmr1-KO mice, a recognized model of FXS, leading to decreased levels of cAMP and cGMP. Here, we pharmacologically inhibited PDE2A in Fmr1-KO mice and observed a rescue both of the maturity of dendritic spines and of the exaggerated hippocampal mGluR-dependent long-term depression. Remarkably, PDE2A blockade rescued the social and communicative deficits of both mouse and rat Fmr1-KO animals. Importantly, chronic inhibition of PDE2A in newborn Fmr1-KO mice followed by a washout interval, resulted in the rescue of the altered social behavior observed in adolescent mice. Altogether, these results reveal the key role of PDE2A in the physiopathology of FXS and suggest that its pharmacological inhibition represents a novel therapeutic approach for FXS.
Adenosine Receptor-Mediated Developmental Loss of Spike Timing-Dependent Depression in the Hippocampus
Authors: Pérez-Rodríguez Mikel , Arroyo-García Luis E , Prius-Mengual José , Andrade-Talavera Yuniesky , Armengol José A , Pérez-Villegas Eva M , Duque-Feria Paloma , Flores Gonzalo , Rodríguez-Moreno Antonio 
Published: July 2018

Abstract
Critical periods of synaptic plasticity facilitate the reordering and refining of neural connections during development, allowing the definitive synaptic circuits responsible for correct adult physiology to be established. Presynaptic spike timing-dependent long-term depression (t-LTD) exists in the hippocampus, which depends on the activation of NMDARs and that probably fulfills a role in synaptic refinement. This t-LTD is present until the third postnatal week in mice, disappearing in the fourth week of postnatal development. We were interested in the mechanisms underlying this maturation related loss of t-LTD and we found that at CA3–CA1 synapses, presynaptic NMDA receptors (pre-NMDARs) are tonically active between P13 and P21, mediating an increase in glutamate release during this critical period of plasticity. Conversely, at the end of this critical period (P22–P30) and coinciding with the loss of t-LTD, these pre-NMDARs are no longer tonically active. Using immunogold electron microscopy, we demonstrated the existence of pre-NMDARs at Schaffer collateral synaptic boutons, where a decrease in the number of pre-NMDARs during development coincides with the loss of both tonic pre-NMDAR activation and t-LTD. Interestingly, this t-LTD can be completely recovered by antagonizing adenosine type 1 receptors (A1R), which also recovers the tonic activation of pre-NMDARs at P22–P30. By contrast, the induction of t-LTD was prevented at P13–P21 by an agonist of A1R, as was tonic pre-NMDAR activation. Furthermore, we found that the adenosine that mediated the loss of t-LTD during the fourth week of development is supplied by astrocytes. These results provide direct evidence for the mechanism that closes the window of plasticity associated with t-LTD, revealing novel events probably involved in synaptic remodeling during development.
Acute kidney injury after transcatheter aortic valve implantation and mortality risk—long-term follow-up
Authors: Kliuk-Ben Bassat Orit , Finkelstein Ariel , Bazan Samuel , Halkin Amir , Herz Itzhak , Salzer Gotler Dalit , Ravid Dor , Hakakian Odelia , Keren Gad , Banai Shmuel , Arbel Yaron 
Published: July 2018

Abstract

Background
Acute kidney injury (AKI) complicating transcatheter aortic valve implantation (TAVI) is relatively frequent and associated with significant morbidity. Previous studies have shown a higher 30-day and 1-year mortality risk in patients with periprocedural AKI. Our aim was to identify the prognostic impact of periprocedural AKI on long-term follow-up.

Methods
This is a single-center prospective study evaluating patients undergoing TAVI for severe aortic stenosis. AKI was defined according to the Valve Academic Research Consortium 2 definition, as an absolute increase in serum creatinine ≥0.3 mg/dL or an increase &gt;50% within the first week following TAVI. Mortality data were compared between patients who developed AKI and those who did not. Logistic and Cox regressions were used for survival analysis.

Results
The final analysis included 1086 consecutive TAVI patients. AKI occurred in 201 patients (18.5%). During the follow-up period, 289 patients died. AKI was associated with an increased risk of 30-day mortality {4.5 versus 1.9% in the non-AKI group; hazard ratio [HR] 3.70 [95% confidence interval (CI) 1.35–10.13]}. Although 1-year mortality was higher in the AKI group in univariate analysis, it was not significant after a multivariate regression. AKI was a strong predictor of longer-term mortality [42.3 versus 22.7% for 7-year mortality; HR 1.71 (95% CI 1.30–2.25)]. In 189 of 201 patients we had data regarding recovery from AKI up to 30 days after discharge. In patients with recovery from AKI, the mortality rate was lower (38.2 versus 56.6% in the nonrecovery group; P = 0.022).

Conclusions
Periprocedural AKI following TAVI is a strong risk factor for short-term as well as long-term mortality (up to 7 years). Therefore more effort is needed to reduce this complication.
Increasing Rates of Invasive Group A Streptococcal Disease in Alberta, Canada; 2003–2017
Authors: Tyrrell Gregory J , Fathima Sumana , Kakulphimp Jocelyne , Bell Christopher 
Published: July 2018

Abstract

Background
We present an analysis of increasing rates of invasive group A streptococci (iGAS) over a 15-year period in Alberta, Canada.

Methods
From 2003 to 2017, the emm type of iGAS isolates was identified from patients with iGAS disease in Alberta. Demographic, clinical, and risk factor data were collected.

Results
A total of 3551 cases of iGAS were identified in Alberta by isolation of a GAS isolate from a sterile site. The age-standardized incidence rates of iGAS increased from 4.24/100 000 in 2003 to 10.24 in 2017. Rates (SD) were highest in those age &lt;1 (9.69) years and 60+ (11.15) years; 57.79% of the cases were male. Commonly identified risk factors included diabetes, hepatitis C, nonsurgical wounds, addiction, alcohol abuse, drug use, and homelessness. The overall age-standardized case fatality rate was 5.11%. The most common clinical presentation was septicemia/bacteremia (41.84%), followed by cellulitis (17.25%). The top 4 emm types from 2003–2017 were emm1, 28, 59, and 12. In 2017, the top 4 emm types (emm1, 74, 101, and 59) accounted for 46.60% of cases.

Conclusions
The incidence of iGAS disease in Alberta, Canada, has increased from 2003 to 2017. This increase has been driven not by a single emm type, but rather what has been observed is a collection of common and emerging emm types associated with disease. In addition, it is also likely that societal factors are playing important roles in this increase as risk factors associated with marginalized populations (addiction, alcohol abuse, and drug use) were found to have increased during the survey period.