bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vascular Remodeling Process in Pulmonary Arterial Hypertension, with Focus on miR‐204 and miR‐126 (2013 Grover Conference Series)
Authors: Potus François , Graydon Colin , Provencher Steeve , Bonnet Sébastien 
Published: May 2014

Pulmonary arterial hypertension (PAH) is a vascular remodeling disease characterized primarily by increased proliferation and resistance to apoptosis in distal pulmonary arteries. Previous literature has demonstrated that the transcription factors NFAT (nuclear factor of activated T cells) and HIF‐1α (hypoxia inducible factor 1α) are extensively involved in the pathogenesis of this disease and, more recently, has implicated STAT3 (signal transducer and activator of transcription 3) in their activation. Novel research shows that miR‐204, a microRNA recently found to be notably downregulated through induction of PARP‐1 (poly [ADP‐ribose] polymerase 1) by excessive DNA damage in PAH, inhibits activation of STAT3. Contemporary research also indicates systemic impairment of skeletal muscle microcirculation in PAH and attributes this to a debilitated vascular endothelial growth factor pathway resulting from reduced miR‐126 expression in endothelial cells. In this review, we focus on recent research implicating miR‐204 and miR‐126 in vascular remodeling processes, data that allow a better understanding of PAH molecular pathways and constitute a new hope for future therapy.
SIBIS: a Bayesian model for inconsistent protein sequence estimation
Authors: Khenoussi Walyd , Vanhoutrève Renaud , Poch Olivier , Thompson Julie D. 
Published: May 2014

Motivation: The prediction of protein coding genes is a major challenge that depends on the quality of genome sequencing, the accuracy of the model used to elucidate the exonic structure of the genes and the complexity of the gene splicing process leading to different protein variants. As a consequence, today’s protein databases contain a huge amount of inconsistency, due to both natural variants and sequence prediction errors.
Results: We have developed a new method, called SIBIS, to detect such inconsistencies based on the evolutionary information in multiple sequence alignments. A Bayesian framework, combined with Dirichlet mixture models, is used to estimate the probability of observing specific amino acids and to detect inconsistent or erroneous sequence segments. We evaluated the performance of SIBIS on a reference set of protein sequences with experimentally validated errors and showed that the sensitivity is significantly higher than previous methods, with only a small loss of specificity. We also assessed a large set of human sequences from the UniProt database and found evidence of inconsistency in 48% of the previously uncharacterized sequences. We conclude that the integration of quality control methods like SIBIS in automatic analysis pipelines will be critical for the robust inference of structural, functional and phylogenetic information from these sequences.
Availability and implementation: Source code, implemented in C on a linux system, and the datasets of protein sequences are freely available for download at http://www.lbgi.fr/∼julie/SIBIS.
Contact: thompson@unistra.fr
Externally driven changes in the abundance of summer and winter flounder
Authors: Bell Richard J. , Hare Jonathan A. , Manderson John P. , Richardson David E. 
Published: May 2014

AbstractMarine organisms that utilize nearshore environments for major components of their life histories are subject to both local-scale forcing such as water quality and estuarine degradation as well as large-scale forcing such as fishing and decadal-scale climate variability. Large-scale forcing has the potential to synchronize the dynamics of subpopulations, while local-level forcing can produce asynchronous subpopulation trends. Summer flounder (Paralichthys dentatus) and winter flounder (Pseudopleuronectes americanus) are important commercial and recreational flatfish along the east coast of North America which spend their first year of life in coastal habitats. We found that the two exhibited significant within-species coherence in commercial landings and fisheries-independent surveys across the northeast shelf of the United States, suggesting large-scale external drivers. In laboratory studies, temperature has been found to be an important factor regulating survival during the egg, larva and settlement phases of both species. We reconstructed a 40-year time-series of coastal water temperature for the major spawning and nursery areas to examine changes in the thermally available habitat. Estimates of winter flounder abundance were negatively correlated with the winter water temperature, but not with fishing mortality. Summer flounder abundance, by contrast, was negatively correlated with fishing mortality, but exhibited no link with temperature. In addition, time-varying stock–recruitment relationships indicated that stock productivity declined for winter flounder over time, while summer flounder productivity has varied without a trend. While both species declined in the 1980s and early 1990s due to heavy fishing pressure, the reduction in fishing over the last two decades has led to rebuilding of the summer flounder stock and an expansion of its age structure. Declining productivity due to warming estuarine conditions has kept the winter flounder stock at low levels despite low fishing pressure. The two stocks illustrate the importance of controlling fishing mortality in the management of natural marine resources while also accounting for changes in productivity due to climate variability and change.
Fold Rise in Antibody Titers by Measured by Glycoprotein-Based Enzyme-Linked Immunosorbent Assay Is an Excellent Correlate of Protection for a Herpes Zoster Vaccine, Demonstrated via the Vaccine Efficacy Curve
Authors: Gilbert Peter B. , Gabriel Erin E. , Miao Xiaopeng , Li Xiaoming , Su Shu-Chih , Parrino Janie , Chan Ivan S. F. 
Published: May 2014

Abstract
Background.  The phase III Zostavax Efficacy and Safety Trial of 1 dose of licensed zoster vaccine (ZV; Zostavax; Merck) in 50–59-year-olds showed approximately 70% vaccine efficacy (VE) to reduce the incidence of herpes zoster (HZ). An objective of the trial was to assess immune response biomarkers measuring antibodies to varicella zoster virus (VZV) by glycoprotein-based enzyme-linked immunosorbent assay as correlates of protection (CoPs) against HZ.
Methods.  The principal stratification vaccine efficacy curve framework for statistically evaluating immune response biomarkers as CoPs was applied. The VE curve describes how VE against the clinical end point (HZ) varies across participant subgroups defined by biomarker readout measuring vaccine-induced immune response. The VE curve was estimated using several subgroup definitions.
Results.  The fold rise in VZV antibody titers from the time before immunization to 6 weeks after immunization was an excellent CoP, with VE increasing sharply with fold rise: VE was estimated at 0% for the subgroup with no rise and at 90% for the subgroup with 5.26-fold rise. In contrast, VZV antibody titers measured 6 weeks after immunization did not predict VE, with similar estimated VEs across titer subgroups.
Conclusions.  The analysis illustrates the value of the VE curve framework for assessing immune response biomarkers as CoPs in vaccine efficacy trials.
Clinical Trials Registration.  NCT00534248.
Axiomatization and Measurement of Quasi-Hyperbolic Discounting *
Authors: Montiel Olea José Luis , Strzalecki Tomasz 
Published: May 2014

AbstractThis article provides an axiomatic characterization of quasi-hyperbolic discounting and a more general class of semi-hyperbolic preferences. We impose consistency restrictions directly on the intertemporal trade-offs by relying on what we call “annuity compensations.” Our axiomatization leads naturally to an experimental design that disentangles discounting from the elasticity of intertemporal substitution. In a pilot experiment we use the partial identification approach to estimate bounds for the distributions of discount factors in the subject pool. Consistent with previous studies, we find evidence for both present and future bias.
Characterization of thrombogenic, endothelial and inflammatory markers in supraventricular tachycardia: a study in patients with structurally normal hearts
Authors: Schultz Carlee D , Rangneker Geetanjali , Lim Han S , Fraudeau Angelique , Young Glenn , Roberts‐Thomson Kurt , John Bobby , Worthley Matthew , Sanders Prashanthan , Willoughby Scott R 
Published: May 2014

SummaryPatients with atrial fibrillation (AF) are at an increased risk of thromboembolism and stroke primarily from the development of thrombi within the left atrium. Pathological changes in blood constituents and atrial endothelial damage promote left atrial thrombus formation. It is not known whether factors predisposing to left atrial thrombus formation in AF are disease specific or also evident within the normal heart. The present study examined whether there are differences in platelet reactivity, endothelial function and inflammation in blood samples obtained from intracardiac and peripheral sites in subjects within structurally normal hearts. Sixteen patients with diagnosed left‐sided supraventricular tachycardia (SVT) undergoing a routine elective electrophysiological study and ablation were investigated. Blood samples were taken simultaneously from the femoral vein, right atrium and left atrium, immediately following trans‐septal puncture and prior to heparin bolus administration. Between peripheral and atrial sample sites, patients with SVT showed no change in platelet reactivity or aggregation (P‐selectin (CD62P) P = 0.91; platelet‐derived soluble CD40 ligand P = 0.9), thrombus formation (thrombin–antithrombin complex; P = 0.55), endothelial function (von Willebrand factor P = 0.75; asymmetric dimethylarginine (ADMA) P = 0.97; nitric oxide P = 0.61), or inflammation (vascular cell adhesion molecule‐1 P = 0.59; intercellular adhesion molecule‐1 (ICAM‐1) P = 0.69). However, SVT patients had lower ADMA and ICAM‐1 levels than AF patients. The present study demonstrates, for the first time, that SVT subjects with structurally normal hearts have consistent haemostatic function between atrial and peripheral sites. These results suggest that the atria of SVT patients do not contain predisposing thrombogenic, endothelial or inflammatory factors that promote and/or initiate thrombus formation.
Efficacy of metformin‐based oral antidiabetic drugs is not inferior to insulin glargine in newly diagnosed type 2 diabetic patients with severe hyperglycemia after short‐term intensive insulin therapy
Authors: Cheng Qingfeng , Yang Shumin , Zhao Changhong , Wang Zhihong , Feng Zhengping , Li Rong , Ye Peng , Zhang Suhua , Deng Huacong , Zhou Bo , Long Jian , Gong Lilin , Qing Hua , Luo Cheng , Li Qifu 
Published: May 2014

AbstractBackgroundInsulin therapy should be strongly considered in newly diagnosed type 2 diabetic (T2D) patients with severe hyperglycemia. However, whether insulin be continued or patients switched to an oral antidiabetic drug (OAD) after short‐term intensive insulin therapy (ITT) is not clear.MethodsAfter ITT for 10–14 days, 47 patients were randomized into either a glargine (n = 21) or metformin‐based OAD (n = 26) group for a 6‐month intervention. After these 6 months, patients in the glargine group were switched to metformin‐based OAD therapy, whereas treatment in the OAD group was unchanged. Patients were followed‐up for another 6 months.ResultsAt the end of the 6‐month intervention, HbA1c was similarly reduced in both the glargine (from 11.81 ± 1.70% to 6.48 ± 0.79%; P < 0.001) and OAD (from 11.71 ± 1.89% to 6.16 ± 0.52%; P < 0.001) groups. At the end of 12 months, HbA1c was at comparable and near optimal levels in both groups. Similar increases were seen in homeostatic model assessment of β‐cell function in the two groups after 6 months. There were no significant differences between the two groups in insulin sensitivity improvement, hypoglycemic episodes, weight change, treatment satisfaction and quality of life after the 6‐month intervention.ConclusionsThe effects of metformin‐based OAD therapy on glycemic control and improvements in β‐cell function are not inferior to glargine in newly diagnosed T2D patients with severe hyperglycemia after short‐term ITT. Considering the superiority of metformin in terms of safety, cost, and convenience, metformin‐based OAD therapy is strongly recommended for these patients.
Endospore‐enriched sequencing approach reveals unprecedented diversity of Firmicutes in sediments
Authors: Wunderlin Tina , Junier Thomas , Roussel‐Delif Ludovic , Jeanneret Nicole , Junier Pilar 
Published: May 2014

SummaryWe present a method for the physical isolation of endospores from environmental samples allowing the specific targeting of endospore‐forming bacteria for sequencing (endospore‐enriched community). The efficiency of the method was tested on lake sediment samples. After 16S rRNA gene amplicon sequencing, the composition in the endospore‐enriched community was compared with the community from untreated control samples (whole community). In the whole community, Firmicutes had a relative abundance of 8% and 19% in the two different lake sediments. In contrast, in the endospore‐enriched community, Firmicutes abundance increased to 90.6% and 83.9%, respectively, confirming the efficiency of the endospore enrichment. The relative abundance of other microbial groups that form spore‐like resisting states (i.e. actinobacteria, cyanobacteria and myxococcales) was below 2% in the endospore‐enriched community, indicating that the method is adapted to true endospores. Representatives from two out of the three known classes of Firmicutes (Bacilli and Clostridia) were detected and supposedly asporogenic groups (e.g. Ethanoligenes and Trichococcus) could be detected. The method presented here is a leap forward for ecological studies of endospore‐forming Firmicutes. It can be applied to other types of samples in order to reveal the diversity and metabolic potential of this bacterial group in the environment.
Pazopanib diminishes non‐small cell lung cancer (NSCLC) growth and metastases in vivo
Authors: Zhao Honglin , Yang Fan , Shen Wang , Wang Yuli , Li Xuebing , You Jiacong , Zhou Qinghua 
Published: May 2014

AbstractBackgroundAnti‐angiogenesis has been demonstrated to have a critical role in lung cancer pathogenesis. Here, we characterized the effect of the small‐molecule angiogenesis inhibitor pazopanib on non‐small cell lung cancer (NSCLC) cells.MethodsNSCLC cells were tested for viability and migration after incubation with varying concentrations of pazopanib. Further, the phosphorylation status of extracellular signal‐regulated kinase, protein kinase B, and MEK were assessed in vitro. For in vivo testing, mice grafted with NSCLC cell lines L9981 and A549 were treated orally with pazopanib.ResultsPazopanib inhibits signaling pathways in tumor cells, thus blocking NSCLC cell growth and migration in vitro and inducing tumor cell arrest at G0/G1 phase. We show that pazopanib could inhibit tumor cell growth, decrease metastases, and prolong survival in two mouse xenograft models of human NSCLC.ConclusionThese preclinical studies of pazopanib show the possibility of clinical application and, ultimately, improvement in patient outcome.
Active management of the third stage of labor with and without controlled cord traction: a systematic review and meta‐analysis of randomized controlled trials
Authors: Du Yongming , Ye Man , Zheng Feiyun 
Published: May 2014

AbstractObjectiveTo determine the specific effect of controlled cord traction in the third stage of labor in the prevention of postpartum hemorrhage.Data sourcesWe searched PubMed, Scopus and Web of Science (inception to 30 October 2013).Study selectionRandomized controlled trials comparing controlled cord traction with hands‐off management in the third stage of labor were included.ResultsFive randomized controlled trials involving a total of 30 532 participants were eligible. No significant difference was found between controlled cord traction and hands‐off management groups with respect to the incidence of severe postpartum hemorrhage (relative risk 0.91, 95% confidence interval 0.77–1.08), need for blood transfusion (relative risk 0.96, 95% confidence interval 0.69–1.33) or therapeutic uterotonics (relative risk 0.94, 95% confidence interval 0.88–1.01). However, controlled cord traction reduced the incidence of postpartum hemorrhage in general (relative risk 0.93, 95% confidence interval 0.87–0.99; number‐needed‐to‐treat 111, 95% confidence interval 61–666), as well manual removal of the placenta (relative risk 0.70, 95% confidence interval 0.58–0.84) and duration of the third stage of labor (mean difference −3.20, 95% confidence interval −3.21 to −3.19).ConclusionsControlled cord traction appears to reduce the risk of any postpartum hemorrhage in a general sense, as well as manual removal of the placenta and the duration of the third stage of labor. However, the reduction in the occurrence of severe postpartum hemorrhage, need for additional uterotonics and blood transfusion is not statistically significant.
Teaching laparoscopic radical prostatectomy during the primary surgeon's early learning curve – analysis of our first 207 cases
Authors: Luke Serge , Delprado Warick , Louie‐Johnsun Mark 
Published: May 2014

ObjectiveTo assess the feasibility of introducing laparoscopic radical prostatectomy (LRP) training during the primary surgeon's early learning curve in a regional Australian centre.Patients and methodsFrom a prospective single surgeon database perioperative, oncological and functional outcome data was collected from the first 207 consecutive patients who underwent LRP immediately after a 12‐month LRP Fellowship in a high‐volume centre by the primary surgeon (M.L.J.). A training case was defined as the successful completion of at least two of 10 steps by a training Fellow. Perioperative and oncological outcomes were compared in training and non‐training cohorts and overall learning curve was assessed by comparing consecutive 50‐patient cohorts.ResultsIn all, 31% of cases were training cases with a median (range) of 7 (2–10) steps of 10 steps performed by the training Fellow. Operative times were significantly longer in training cases (mean 269 vs 209 min; P < 0.001). There was no statistically significant difference in perioperative outcomes of length of stay (2.7 vs 2.6 days), transfusion rates (3.1% vs 2.1%), major complication (Clavien >3a) rates (1.6% vs 2.1%) or positive surgical margins (PSMs: pT2 2.8% vs 15.3% and pT3 52.0% vs 45.1%) between training and non‐training groups, respectively. Overall, there were two open conversions (1.0%).ConclusionDespite the challenging learning curve, LRP training can be commenced safely with a stepwise modular approach, even when the primary surgeon is in their early learning curve. Perioperative outcomes including PSMs and major complications were unaffected by trainee involvement.
Evolution of shockwave lithotripsy (SWL) technique: a 25‐year single centre experience of >5000 patients
Authors: Jagtap Jitendra , Mishra Shashikant , Bhattu Amit , Ganpule Arvind , Sabnis Ravindra , Desai Mahesh 
Published: May 2014

ObjectiveTo assess the impact of various treatment optimisation strategies in shockwave lithotripsy (SWL) used at a single centre over the last 25 years.Patients and MethodsIn all, 5017 patients treated between 1989 and 2013 were reviewed and divided into groups A, B, C and D for the treatment periods of 1989–1994 (1561 patients), 1995–2000 (1741), 2001–2006 (1039) and 2007–2013 (676), respectively. The Sonolith 3000 (A and B) and Dornier compact delta lithotripters (C and D) were used. Refinements included frequent re‐localisation, limiting maximum shocks and booster therapy in group B and Hounsfield unit estimation, power ramping and improved coupling in group D. Parameters reviewed were annual SWL utilisation, stone and treatment data, retreatment, auxiliary procedures, complications and stone‐free rate (SFR).ResultsThe SFR with Dornier compact delta was significantly higher than that of the Sonolith 3000 (P < 0.001). The SFR improved significantly from 77.58%, 81.28%, 82.58% to 88.02% in groups A, B, C, and D, respectively (P < 0.001). There was a concomitant decrease in repeat SWL (re‐treatment rate: A, 48.7%; B, 33.4%; C, 15.8%; and D, 10.1%; P < 0.001) and complication rates (A, 8%; B, 6.4%; C, 4.9%; and D, 1.6%; P < 0.001). This led to a rise in the efficiency quotient (EQ) in groups A–D from 50.41, 58.94, 68.78 to 77.06 (P < 0.001).The auxiliary procedure rates were similar in all groups (P = 0.62).ConclusionIn conclusion, improvement in the EQ together with a concomitant decrease in complication rate can be achieved with optimum patient selection and use of various treatment optimising strategies.
Dysregulation of the suppressor of cytokine signalling 3–signal transducer and activator of transcription-3 pathway in the aetiopathogenesis of Sjögren's syndrome
Authors: Vartoukian S R , Tilakaratne W M , Seoudi N , Bombardieri M , Bergmeier L , Tappuni A R , Fortune F 
Published: May 2014

Summary
The suppressor of cytokine signalling 3 (SOCS3) negatively regulates the Janus kinase (JAK)/signal transducer and activator of transcription-3 (STAT-3)/interleukin (IL)-17 pathway. The proinflammatory cytokine IL-17 is over-expressed in Sjögren's syndrome (SS) and is a key factor in its pathogenesis. We hypothesized that IL-17 over-expression in SS results from ineffective regulation by SOCS3. The expression of SOCS3 was analysed in peripheral blood mononuclear cells (PBMC) from SS cases, sicca controls (SC) and healthy controls (HC) and tissue samples from SS, SC and healthy salivary glands (HSG). PBMC and salivary gland tissue from SS and controls were dual-immunostained for SOCS3 and IL-17. IL-6-stimulated PBMC from SS and controls were evaluated for time-dependent STAT-3 activation and SOCS3 induction, and for IL-17 expression. Immunoblotting revealed greater levels of SOCS3 in PBMC from SS than SC (P = 0·017) or HC (P &lt; 0·001). Similarly, the proportion of salivary-gland tissue cells staining for SOCS3 was significantly higher in SS than SC (P = 0·029) or HSG (P = 0·021). The cells in PBMC/salivary gland samples from controls predominantly expressed either SOCS3 or IL-17. However, there was a high frequency of SOCS3/IL-17 co-expression within cells of SS samples. IL-6-stimulation of PBMC from SS cases revealed prolonged activation of STAT-3 with reduced negative regulation by SOCS3, and enhanced expression of IL-17. This study showed that SOCS3 expression is up-regulated in SS. However, the absence in SS of the normal inverse relationship between SOCS3 and pSTAT-3/IL-17 indicates a functional disturbance in this signalling cascade. Consequently, a reduction in function, rather than a reduction in expression of SOCS3 accounts for the unregulated expression of IL-17 in SS, and may play a crucial role in aetiopathogenesis.