bluuebunny/crossref_metadata_2025_split huggingface dataset:
A retrospective study of clinical signs and epidemiology of chronic valve disease in a group of 207 Dachshunds in Poland
Authors: Garncarz Magdalena , Parzeniecka-Jaworska Marta , Jank Michał , Łój Magdalena 
Published: July 2013

Abstract

Background
Chronic mitral valve disease is frequently seen in the Dachshund. Dachshunds (n=207) made up 11.73% of the dogs admitted to the Cardiology Service at the Small Animal Clinic, Warsaw University of Life Sciences, Poland (first visits only).

Results
Of these, 35 dogs had no clinically detectable heart disease while 172 had chronic valve disease with the mitral valve affected most often (130 dogs), both mitral and tricuspid valves infrequently (39 dogs) and rarely the tricuspid valve (3 dogs). Males were affected more frequently than females and the average age of dogs with chronic valve disease was 11.9 years for females and 11.3 years for males. A majority of the diseased Dachshunds were classified as ISACHC 2 (79), followed by ISACHC 1 (60). Most frequent clinical signs noted by owners included coughing, exercise intolerance, dyspnea and tachypnea. Heart murmurs were generally louder with increased disease severity; however there were 20 dogs in the ISACHC 1 group with no audible heart murmurs. The most frequent electrocardiographic abnormalities included an increased P wave and QRS complex duration, increased R wave amplitude and tachycardia. With increased disease severity, echocardiography revealed an increase in heart size. A higher ISACHC class was related to increased heart size (based on echocardiography) and increased percentage of patients exhibiting enlargement of both left atrium and left ventricle (based on radiography).

Conclusions
The Dachshund is often affected by chronic mitral valvular disease with a late onset of associated clinical signs and few cardiac complications.
Coumestrol from the national cancer Institute’s natural product library is a novel inhibitor of protein kinase CK2
Authors: Liu Shu , Hsieh David , Yang Yi-Lin , Xu Zhidong , Peto Csaba , Jablons David M , You Liang 
Published: July 2013

Abstract

Background
Casein kinase 2 (CK2) is involved in various cellular events such as proliferation, apoptosis, and the cell cycle. CK2 overexpression is associated with multiple human cancers and may therefore be a promising target for cancer therapy. To identity novel classes of inhibitors for CK2, we screened a natural product library obtained from National Cancer Institute.

Methods
The quantitative luminescent kinase assay ADP-Glo™ was used to screen CK2 inhibitors from the natural product library. The same assay was used to determine cell-free dose-dependent response of CK2 inhibitors and conduct a kinetic study. Docking was performed to predict the binding patterns of selected CK2 inhibitors. Western blot analysis was used to evaluate Akt phosphorylation specific to CK2 and apoptosis effect. The cell viability assay CellTiter-Glo® was used to evaluate the inhibition effects of CK2 inhibitors on cancer cells.

Results
We identified coumestrol as a novel reversible ATP competitive CK2 inhibitor with an IC50 value of 228 nM. Coumestrol is a plant-derived compound that belongs to the class of phytoestrogens, natural compounds that mimic the biological activity of estrogens. In our study, coumestrol showed high selectivity among 13 kinases. The hydrogen bonds formed between coumestrol and the amino acids in the ATP binding site were first reviewed by a molecular docking study that suggested a possible interaction of coumestrol with the hinge region of ATP site of CK2. In addition, coumestrol inhibited cancer cell growth partially through down-regulation of CK2-specific Akt phosphorylation. Finally, coumestrol exerted strong inhibition effects on the growth of three cancer cell lines.

Conclusion
Our study shows that coumestrol, a novel ATP competitive and cell permeable CK2 inhibitor with submicromolar IC50, had inhibition effects on the growth of three cancer cell lines and may represent a promising class of CK2 inhibitors.
Tau pathology induces loss of GABAergic interneurons leading to altered synaptic plasticity and behavioral impairments
Authors: Levenga Josien , Krishnamurthy Pavan , Rajamohamedsait Hameetha , Wong Helen , Franke Thomas F , Cain Peter , Sigurdsson Einar M , Hoeffer Charles A 
Published: July 2013

Abstract

Background
Tau is a microtubule stabilizing protein and is mainly expressed in neurons. Tau aggregation into oligomers and tangles is considered an important pathological event in tauopathies, such as frontotemporal dementia (FTD) and Alzheimer’s disease (AD). Tauopathies are also associated with deficits in synaptic plasticity such as long-term potentiation (LTP), but the specific role of tau in the manifestation of these deficiencies is not well-understood. We examined long lasting forms of synaptic plasticity in JNPL3 (BL6) mice expressing mutant tau that is identified in some inherited FTDs.

Results
We found that aged (>12 months) JNPL3 (BL6) mice exhibit enhanced hippocampal late-phase (L-LTP), while young JNPL3 (BL6) mice (age 6 months) displayed normal L-LTP. This enhanced L-LTP in aged JNPL3 (BL6) mice was rescued with the GABAAR agonist, zolpidem, suggesting a loss of GABAergic function. Indeed, we found that mutant mice displayed a reduction in hippocampal GABAergic interneurons. Finally, we also found that expression of mutant tau led to severe sensorimotor-gating and hippocampus-dependent memory deficits in the aged JNPL3 (BL6) mice.

Conclusions
We show for the first time that hippocampal GABAergic function is impaired by pathological tau protein, leading to altered synaptic plasticity and severe memory deficits. Increased understanding of the molecular mechanisms underlying the synaptic failure in AD and FTD is critical to identifying targets for therapies to restore cognitive deficiencies associated with tauopathies.
High positive end-expiratory pressure: only a dam against oedema formation?
Authors: Protti Alessandro , Andreis Davide T , Iapichino Giacomo E , Monti Massimo , Comini Beatrice , Milesi Marta , Zani Loredana , Gatti Stefano , Lombardi Luciano , Gattinoni Luciano 
Published: July 2013

Abstract
Introduction
Healthy piglets ventilated with no positive end-expiratory pressure (PEEP) and with tidal volume (VT) close to inspiratory capacity (IC) develop fatal pulmonary oedema within 36 h. In contrast, those ventilated with high PEEP and low VT, resulting in the same volume of gas inflated (close to IC), do not. If the real threat to the blood-gas barrier is lung overinflation, then a similar damage will occur with the two settings. If PEEP only hydrostatically counteracts fluid filtration, then its removal will lead to oedema formation, thus revealing the deleterious effects of overinflation.

Methods
Following baseline lung computed tomography (CT), five healthy piglets were ventilated with high PEEP (volume of gas around 75% of IC) and low VT (25% of IC) for 36 h. PEEP was then suddenly zeroed and low VT was maintained for 18 h. Oedema was diagnosed if final lung weight (measured on a balance following autopsy) exceeded the initial one (CT).

Results
Animals were ventilated with PEEP 18 ± 1 cmH2O (volume of gas 875 ± 178 ml, 89 ± 7% of IC) and VT 213 ± 10 ml (22 ± 5% of IC) for the first 36 h, and with no PEEP and VT 213 ± 10 ml for the last 18 h. On average, final lung weight was not higher, and actually it was even lower, than the initial one (284 ± 62 vs. 347 ± 36 g; P = 0.01).

Conclusions
High PEEP (and low VT) do not merely impede fluid extravasation but rather preserve the integrity of the blood-gas barrier in healthy lungs.
Comparison of the predictive performance of the BIG, TRISS, and PS09 score in anadult trauma population derived from multiple international trauma registries
Authors: Brockamp Thomas , Maegele Marc , Gaarder Christine , Goslings J Carel , Cohen Mitchell J , Lefering Rolf , Joosse Pieter , Naess Paal A , Skaga Nils O , Groat Tahnee , Eaglestone Simon , Borgman Matthew A , Spinella Philip C , Schreiber Martin A , Brohi Karim 
Published: July 2013

Abstract
Background
The BIG score (Admission base deficit (B), International normalized ratio (I), andGlasgow Coma Scale (G)) has been shown to predict mortality on admission inpediatric trauma patients. The objective of this study was to assess itsperformance in predicting mortality in an adult trauma population, and to compareit with the existing Trauma and Injury Severity Score (TRISS) and probability ofsurvival (PS09) score.

Materials and methods
A retrospective analysis using data collected between 2005 and 2010 from seventrauma centers and registries in Europe and the United States of America wasperformed. We compared the BIG score with TRISS and PS09 scores in a population ofblunt and penetrating trauma patients. We then assessed the discrimination abilityof all scores via receiver operating characteristic (ROC) curves and compared theexpected mortality rate (precision) of all scores with the observed mortalityrate.

Results
In total, 12,206 datasets were retrieved to validate the BIG score. The mean ISSwas 15 ± 11, and the mean 30-day mortality rate was 4.8%. With an AUROC of0.892 (95% confidence interval (CI): 0.879 to 0.906), the BIG score performed wellin an adult population. TRISS had an area under ROC (AUROC) of 0.922 (0.913 to0.932) and the PS09 score of 0.825 (0.915 to 0.934). On a penetrating-traumapopulation, the BIG score had an AUROC result of 0.920 (0.898 to 0.942) comparedwith the PS09 score (AUROC of 0.921; 0.902 to 0.939) and TRISS (0.929; 0.912 to0.947).

Conclusions
The BIG score is a good predictor of mortality in the adult trauma population. Itperformed well compared with TRISS and the PS09 score, although it hassignificantly less discriminative ability. In a penetrating-trauma population, theBIG score performed better than in a population with blunt trauma. The BIG scorehas the advantage of being available shortly after admission and may be used topredict clinical prognosis or as a research tool to risk stratify trauma patientsinto clinical trials.
High-frequency oscillation and tracheal gas insufflation in patients with severe acute respiratory distress syndrome and traumatic brain injury: an interventional physiological study
Authors: Vrettou Charikleia S , Zakynthinos Spyros G , Malachias Sotirios , Mentzelopoulos Spyros D 
Published: July 2013

Abstract
Introduction
In acute respiratory distress syndrome (ARDS), combined high-frequency oscillation (HFO) and tracheal gas insufflation (TGI) improves gas exchange compared with conventional mechanical ventilation (CMV). We evaluated the effect of HFO-TGI on PaO2/fractional inspired O2 (FiO2) and PaCO2, systemic hemodynamics, intracranial pressure (ICP), and cerebral perfusion pressure (CPP) in patients with traumatic brain injury (TBI) and concurrent severe ARDS.

Methods
We studied 13 TBI/ARDS patients requiring anesthesia, hyperosmolar therapy, and ventilation with moderate-to-high CMV-tidal volumes for ICP control. Patients had PaO2/FiO2 <100 mm Hg at end-expiratory pressure ≥10 cm H2O. Patients received consecutive, daily, 12-hour rescue sessions of HFO-TGI interspersed with 12-hour periods of CMV. HFO-TGI was discontinued when the post-HFO-TGI PaO2/FiO2 exceeded 100 mm Hg for >12 hours. Arterial/central-venous blood gases, hemodynamics, and ICP were recorded before, during (every 4 hours), and after HFO-TGI, and were analyzed by using repeated measures analysis of variance. Respiratory mechanics were assessed before and after HFO-TGI.

Results
Each patient received three to four HFO-TGI sessions (total sessions, n = 43). Pre-HFO-TGI PaO2/FiO2 (mean ± standard deviation (SD): 83.2 ± 15.5 mm Hg) increased on average by approximately 130% to163% during HFO-TGI (P < 0.01) and remained improved by approximately 73% after HFO-TGI (P < 0.01). Pre-HFO-TGI CMV plateau pressure (30.4 ± 4.5 cm H2O) and respiratory compliance (37.8 ± 9.2 ml/cm H2O), respectively, improved on average by approximately 7.5% and 20% after HFO-TGI (P < 0.01 for both). During HFO-TGI, systemic hemodynamics remained unchanged. Transient improvements were observed after 4 hours of HFO-TGI versus pre-HFO-TGI CMV in PaCO2 (37.7 ± 9.9 versus 41.2 ± 10.8 mm Hg; P < 0.01), ICP (17.2 ± 5.4 versus 19.7 ± 5.9 mm Hg; P < 0.05), and CPP (77.2 ± 14.6 versus 71.9 ± 14.8 mm Hg; P < 0.05).

Conclusions
In TBI/ARDS patients, HFO-TGI may improve oxygenation and respiratory mechanics, without adversely affecting PaCO2, hemodynamics, or ICP. These findings support the use of HFO-TGI as a rescue ventilatory strategy in patients with severe TBI and imminent oxygenation failure due to severe ARDS.
REAPR: a universal tool for genome assembly evaluation
Authors: Hunt Martin , Kikuchi Taisei , Sanders Mandy , Newbold Chris , Berriman Matthew , Otto Thomas D 
Published: July 2013

AbstractMethods to reliably assess the accuracy of genome sequence data are lacking. Currently completeness is only described qualitatively and mis-assemblies are overlooked. Here we present REAPR, a tool that precisely identifies errors in genome assemblies without the need for a reference sequence. We have validated REAPR on complete genomes or de novo assemblies from bacteria, malaria and Caenorhabditis elegans, and demonstrate that 86% and 82% of the human and mouse reference genomes are error-free, respectively. When applied to an ongoing genome project, REAPR provides corrected assembly statistics allowing the quantitative comparison of multiple assemblies. REAPR is available at http://www.sanger.ac.uk/resources/software/reapr/.
Variants in exons and in transcription factors affect gene expression in trans
Authors: Kreimer Anat , Pe'er Itsik 
Published: July 2013

Abstract
Background
In recent years many genetic variants (eSNPs) have been reported as associated with expression of transcripts in trans. However, the causal variants and regulatory mechanisms through which they act remain mostly unknown. In this paper we follow two kinds of usual suspects: SNPs that alter coding regions or transcription factors, identifiable by sequencing data with transcriptional profiles in the same cohort. We show these interpretable genomic regions are enriched for eSNP association signals, thereby naturally defining source-target gene pairs. We map these pairs onto a protein-protein interaction (PPI) network and study their topological properties.

Results
For exonic eSNP sources, we report source-target proximity and high target degree within the PPI network. These pairs are more likely to be co-expressed and the eSNPs tend to have a cis effect, modulating the expression of the source gene. In contrast, transcription factor source-target pairs are not observed to have such properties, but instead a transcription factor source tends to assemble into units of defined functional roles along with its gene targets, and to share with them the same functional cluster of the PPI network.

Conclusions
Our results suggest two modes of trans regulation: transcription factor variation frequently acts via a modular regulation mechanism, with multiple targets that share a function with the transcription factor source. Notwithstanding, exon variation often acts by a local cis effect, delineating shorter paths of interacting proteins across functional clusters of the PPI network.
Subcortical connectivity in dementia with Lewy bodies and Alzheimer's disease
Authors: Kenny Eva R. , O'Brien John T. , Firbank Michael J. , Blamire Andrew M. 
Published: July 2013

BackgroundResting-state functional magnetic resonance imaging (fMRI) can be used to measure correlations in spontaneous low-frequency fluctuations in the blood oxygen level-dependent (BOLD) signal which represent functional connectivity between key brain areas.AimsTo investigate functional connectivity with regions hypothesised to be differentially affected in dementia with Lewy bodies (DLB) compared with Alzheimer's disease and controls.MethodFifteen participants with probable DLB, 16 with probable Alzheimer's disease and 16 controls were scanned in the resting-state using a 3T scanner. The BOLD signal time-series of fluctuations in seed regions were correlated with all other voxels to measure functional connectivity.ResultsParticipants with DLB and Alzheimer's disease showed greater caudate and thalamic connectivity compared with controls. Those with DLB showed greater putamen connectivity compared with those with Alzheimer's disease and the controls. No regions showed less connectivity in DLB or Alzheimer's disease v. controls, or in DLB v. Alzheimer's disease.ConclusionsAltered connectivity in DLB and Alzheimer's disease provides new insights into the neurobiology of these disorders and may aid in earlier diagnosis.
Interleukin-10 regulates progenitor differentiation and modulates neurogenesis on adult brain
Authors: Perez-Asensio Fernando J. , Perpiñá Unai , Planas Anna M. , Pozas Esther 
Published: July 2013

The adult subventricular zone (SVZ) is the main neurogenic niche in normal adult brain of mice and rats. The adult SVZ contains neural stem cells (NSCs) that mainly differentiate into committed neuroblasts. The new generated neuroblasts accumulate in dorsal SVZ where they further differentiate and initiate a long migration pathway to their final destination the olfactory bulb (OB).
In here we report a new role for Interleukin 10 (IL-10) different from its well known anti-inflammatory properties. We reveal that IL-10 receptor is expressed in Nestin+ progenitors restricted to the dorsal SVZ in adult brain. Through IL-10 gain models we observed that IL-10 maintains neural progenitors in an undifferentiated stage by keeping progenitors in active cycle and up-regulating the presence of pro-neural genes markers (Nestin, Sox genes, Musashi, Mash1) in detriment of neuronal gene expression (Numb, DCX, TUBB3). On top, IL-10 reduces neuronal differentiation and finally impairs endogenous neurogenesis. Consistently, in the absence of IL-10 in vivo neuronal differentiation among SVZ progenitors is enhanced and the incorporation of new neurons in the adult OB is increased.
Thus, our results provide the first evidence that IL-10 acts as a growth factor on SVZ progenitors and regulates adult neurogenesis in adult normal brain.
Comparison of the 99th percentiles of three troponin I assays in a large reference population
Authors: Petersmann Astrid , Ittermann Till , Fries Cornelia , Lubenow Norbert , Kohlmann Thomas , Kallner Anders , Greinacher Andreas , Nauck Matthias 
Published: July 2013

Abstract

Background: The IFCC Task Force on Clinical Applications of Cardiac Biomarkers suggests comparing several contemporary sensitive troponin assays in the same, sufficiently large reference population.

Methods: Three contemporary sensitive assays were used to measure troponin I concentration in samples from a uniquely large healthy population (2404 individuals) and in a sub-group with tighter inclusion criteria of 908 individuals. The 99th percentiles were calculated using quantile regression which takes the entire population into account.

Results: The 99th percentile for the ARCHITECT STAT Troponin I assay was 21 ng/L, 31 ng/L for the ADVIA Centaur Troponin I-Ultra assay and 28 ng/L for the Dimension Vista cTnI assay. Significantly higher values were found in males than in women only in the Dimension Vista cTnI assay and in the subgroup for the ARCHITECT STAT Troponin I assay.

Conclusions: Quantile regression provides a tool to accurately estimate the 99th percentile and establish a continuous function of the relation between the 99th percentile and the age and gender. There was no age dependency demonstrated. A gender difference was found in one assay but inconclusive in another and not demonstrated in a third.
The order of draw: myth or science?
Authors: Salvagno Gianluca , Lima-Oliveira Gabriel , Brocco Giorgio , Danese Elisa , Guidi Gian Cesare , Lippi Giuseppe 
Published: July 2013

Abstract

Background: The potential for cross-contamination of additives among evacuated blood tubes has led to the development of the order of draw. This practice, however, is mainly based on scarce, anecdotal, and mostly outdated literature data. Therefore, the goal of this investigation was to definitely establish whether or not the indication of a specific order of draw is still justified.

Methods: The study population consisted of 57 outpatients referred to the outpatient oral anticoagulant (OA) clinic of the Academic Hospital of Verona and 58 healthy volunteers enrolled from the laboratory personnel. In OA outpatients, one serum tube was collected immediately after needle insertion, followed by a buffered sodium citrate tube and another serum tube. In the healthy volunteers, one serum tube was collected immediately after needle insertion, followed by a potassium-ethylenediaminetetraacetic acid (K2-EDTA) tube and another serum tube. After separation, the serum was tested for potassium, sodium, calcium, magnesium, and phosphorus in the first and second serum tubes.

Results: No significant difference could be observed between the first and the second serum tubes for any of the parameters. The bias calculated with Bland-Altman plots did not achieve statistical significance when the serum tube was collected after either a K2-EDTA or a sodium citrate tube.

Conclusions: According to our data, revision of national and supranational recommendations on blood collection by venipuncture should consider that the order of draw exerts a negligible effect on sample quality, and this aspect should no longer be considered a quality criterion when evaluating the performance of phlebotomists.
Synthesis and antimicrobial activities of some novel thiophene containing azo compounds
Authors: Fondjo Emmanuel Sopbué , Tsemeugne Joseph , De Dieu Tamokou Jean , Djintchui Arnaud Ngongang , Kuiate Jules Roger , Sondengam Beibam Luc 
Published: July 2013

Abstract
A series of new thienylazothiophenes were prepared by coupling reactions of diazotized thienocoumarins with their corresponding free amines. The structures of the products 3–7 were assigned on the basis of their elemental and spectroscopic data. The HMBC and HSQC techniques were used in some cases to ascertain the structural assignments. The antimicrobial screenings of compounds 3–7 along with substituted 2-aminothiophenes 1a,b were performed against three bacteria and three fungal species and their activities compared to those of nystatin, gentamycin and ciprofloxacin used as reference drugs. It was found that the antimicrobial activities of the tested new hybrid compounds were in some cases equal or better than those of the reference drugs.
Preeclampsia is caused by continuous sympathetic center excitation due to an enlarged pregnant uterus
Authors: Maeda Kazuo 
Published: July 2013

Abstract

Aims: To deduce the origin of preeclampsia characterized by hypertension and proteinuraia on the basis of results from animal studies and its therapeutic strategies.

Methods: Sympathetic and parasympathetic zones of female non-pregnant rabbit brain were stimulated electrically with Kurotu’s electrodes. Systolic blood pressure, urine volume, and proteinuria were evaluated before and after the stimulation of autonomic zones.

Results: Excitation, hypertension, urine reduction, cloudy urine, and proteinuria were observed following stimulation of the sympathetic zone. A stable state, low blood pressure, increased urine volume, and no proteinuria were observed following stimulation of the parasympathetic zone.

Conclusion: Hypertension and proteinuria in preeclampsia are caused by continuous stimulation of the sympathetic nervous center in the hypothalamus through the innervation between the enlarged uterus and hypothalamus in the latter stages of pregnancy or in a complete hydatidiform mole. Future studies are needed to address the potential of pharmacological suppression of an overactive sympathetic nerve system.