bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prestroke antiplatelet therapy and early prognosis in stroke patients: the Dijon Stroke Registry
Authors: Béjot Y. , Aboa‐Eboulé C. , de Maistre E. , Jacquin A. , Troisgros O. , Hervieu M. , Osseby G. V. , Rouaud O. , Giroud M. 
Published: December 2012

Background and purposePrevious antiplatelet therapy (APT) in cardiovascular prevention is common in patients with first‐ever stroke. We aimed to evaluate the prognostic value of APT on early outcome in stroke patients.MethodsAll first‐ever strokes from 1985 to 2011 were identified from the population‐based Stroke Registry of Dijon, France. Demographic features, risk factors, prestroke treatments and clinical information were recorded. Multivariate analyses were performed to evaluate the associations between pre‐admission APT and both severe handicap at discharge, and mortality at 1 month and 1 year.ResultsAmong the 4275 patients, 870 (20.4%) were previously treated with APT. Severe handicap at discharge was noted in 233 (26.8%) APT users and in 974 (28.7%) non‐users. Prestroke APT use was associated with lower odds of severe handicap at discharge [adjusted odds ratio (OR): 0.79; 95% confidence interval (CI): 063–1.00; P = 0.046], non‐significant better survival at 1 month [adjusted hazard ratio (HR): 0.87; 95% CI: 0.70–1.09; P = 0.222] and no effect on 1‐year mortality (HR: 0.94; 95% CI 0.80–1.10; P = 0.429). In stratum‐specific analyses, APT was associated with a lower risk of 1‐month mortality in patients with cardioembolic ischaemic stroke (HR: 0.65; 95% CI: 0.43–0.98; P = 0.040).ConclusionsAPT before stroke was associated with less severe handicap at discharge, with no significant protective effect for mortality at 1 month except in patients with cardioembolic stroke. No protective effect of APT was observed for mortality at 1 year. Further studies are needed to understand the mechanisms underlying the distinct effects of prior APT observed across the ischaemic stroke subtypes.
Cost‐effectiveness of onabotulinumtoxinA for the treatment of wrist and hand disability due to upper‐limb post‐stroke spasticity in Scotland
Authors: Doan Q. V. , Gillard P. , Brashear A. , Halperin M. , Hayward E. , Varon S. , Lu Z. J. 
Published: December 2012

Background and purposeThe objective was to evaluate the cost‐effectiveness of treating upper‐limb post‐stroke spasticity (ULPSS) with usual care (UC) plus onabotulinumtoxinA versus UC alone in Scotland.MethodsWe developed a model to simulate costs and quality‐adjusted life years (QALYs) gained from treating ULPSS. Efficacy data and health utilities were taken from clinical trials. Unit costs were taken from published Scottish sources. We compared UC plus onabotulinumtoxinA and UC alone in three scenarios: (i) a scenario from the National Health Service perspective, which included differences in onabotulinumtoxinA use, specialist visits and day‐hospital visits; (ii) a scenario that only included differences in onabotulinumtoxinA use and specialist visits; and (iii) a scenario from a societal perspective that included differences in onabotulinumtoxinA use, specialist visits and caregiver burden.ResultsIn the first scenario, the model predicted that UC plus onabotulinumtoxinA produced 0.107 QALYs at an additional cost of £1099 compared with UC alone over 5 years, resulting in an incremental cost‐effectiveness ratio (ICER) of £10 271/QALY. In the second scenario, the ICER increased to £27 134/QALY. In the third scenario (societal perspective), UC plus onabotulinumtoxinA produced lower total cost and higher QALYs, and therefore was superior to UC alone.ConclusionsBased on a model, UC plus onabotulinumtoxinA improved disability, which translated into greater QALYs but also increased direct medical costs compared with UC alone; however, the resulting ICER can be considered cost‐effective. Moreover, UC plus onabotulinumtoxinA can be cost‐saving if reduction in caregiver burden was included. OnabotulinumtoxinA offers value for money in the management of ULPSS in Scotland.
Collateral circulation on perfusion‐computed tomography‐source images predicts the response to stroke intravenous thrombolysis
Authors: Calleja A. I. , Cortijo E. , García‐Bermejo P. , Gómez R. D. , Pérez‐Fernández S. , del Monte J. M. , Muñoz M. F. , Fernández‐Herranz R. , Arenillas J. F. 
Published: December 2012

Background and purposePerfusion‐computed tomography‐source images (PCT‐SI) may allow a dynamic assessment of leptomeningeal collateral arteries (LMC) filling and emptying in middle cerebral artery (MCA) ischaemic stroke. We described a regional LMC scale on PCT‐SI and hypothesized that a higher collateral score would predict a better response to intravenous (iv) thrombolysis.MethodsWe studied consecutive ischaemic stroke patients with an acute MCA occlusion documented by transcranial Doppler/transcranial color‐coded duplex, treated with iv thrombolysis who underwent PCT prior to treatment. Readers evaluated PCT‐SI in a blinded fashion to assess LMC within the hypoperfused MCA territory. LMC scored as follows: 0, absence of vessels; 1, collateral supply filling ≤ 50%; 2, between> 50% and < 100%; 3, equal or more prominent when compared with the unaffected hemisphere. The scale was divided into good (scores 2–3) vs. poor (scores 0–1) collaterals. The predetermined primary end‐point was a good 3‐month functional outcome, while early neurological recovery, transcranial duplex‐assessed 24‐h MCA recanalization, 24‐h hypodensity volume and hemorrhagic transformation were considered secondary end‐points.ResultsFifty‐four patients were included (55.5% women, median NIHSS 10), and 4‐13‐23‐14 patients had LMC score (LMCs) of 0‐1‐2‐3, respectively. The probability of a good long‐term outcome augmented gradually with increasing LMCs: (0) 0%; (1) 15.4%; (2) 65.2%; (3) 64.3%, P = 0.004. Good‐LMCs was independently associated with a good outcome [OR 21.02 (95% CI 2.23–197.75), P = 0.008]. Patients with good LMCs had better early neurological recovery (P = 0.001), smaller hypodensity volumes (P < 0.001) and a clear trend towards a higher recanalization rate.ConclusionsA higher degree of LMC assessed by PCT‐SI predicts good response to iv thrombolysis in MCA ischaemic stroke patients.
A Common Marking Technique Affects Tadpole Behavior and Risk of Predation
Authors: Carlson Bradley E. , Langkilde Tracy 
Published: December 2012

AbstractIn many studies, it is necessary for researchers to mark individual animals for later identification. It is often assumed in the interpretation of these studies that marks have no effects on the biology of the animals. This assumption is insufficiently tested, and, when it is, coarse assessments of negative effects are often used, such as survival and growth under simplified laboratory conditions. We examined the consequences of a common larval amphibian marking technique (staining with methylene blue) for wood frog tadpole behavior and survival in an ecologically realistic scenario (predation). We measured a number of tadpole behavioral variables, under baseline conditions and in the presence of olfactory cues of a predator, for marked and unmarked tadpoles. We then exposed pairs of tadpoles (one marked and one unmarked) to one of two predators and tested for the effects of marking on the susceptibility of tadpoles to predation. We found that marking suppressed the increase in movement rate that typically occurred in (unmarked) tadpoles in the presence of predator cues. Marked tadpoles were significantly more likely to be captured by predators, an effect that could not be attributed to this difference in movement rate. These results raise concern about the use of this staining method and highlight the need for studies involving marked animals to thoroughly address any relevant effects the marks may have on the biology of the subjects.
Pathological and clinical features associated with palmar/plantar osteochondral disease of the metacarpo/metatarsophalangeal joint in Thoroughbred racehorses
Authors: Pinchbeck G. L. , Clegg P. D. , Boyde A. , Riggs C. M. 
Published: December 2012

SummaryReasons for performing studyPalmar/plantar osteochondral disease (POD) of the metacarpo/metatarsophalangeal (Mc/MtPh) joints is common in Thoroughbred racehorses, but there is little information on predilection sites, associated pathologies and clinical signs.ObjectivesTo describe the distribution of POD at post mortem examination and to examine the association of POD with other pathologies and clinical histories.MethodsThe Mc/MtPh joints of 102 Thoroughbred racehorses were examined post mortem. Gross pathology of associated osteochondral elements, suspensory ligament and flexor tendons was recorded. Clinical data were extracted from computerised records. Relationships between all Mc/MtPh joint pathologies, clinical data and grade of POD in each condyle were determined using multilevel, ordinal logistic regression models.ResultsPalmar/plantar osteochondral disease was recorded (grade 1–3 in at least one condyle) in 80.4% (95% confidence interval 71–88) of horses. The grade of POD was significantly higher in the forelimb, where the medial condyle had higher grades, than in the hindlimb, where the POD grade was higher in the lateral condyle. There was a significant positive relationship between POD grade and multiple other joint pathologies, whereas grades of linear fissures had a negative relationship with grade of POD. There was no relationship between grade of POD and tendon and suspensory ligament gross pathology, although horses with a history of tendon injury had significantly lower POD grades. Horses that had a clinical history of a Mc/MtPh joint problem had higher POD grades. In addition, horses that had been retired from racing for more than 2 months at the date of death had significantly lower POD grades.Conclusions and potential relevancePalmar/plantar osteochondral disease has specific predilection sites. Horses with a clinical history of Mc/MtPh‐associated lameness had higher POD grades, whereas those with a history of superficial digital flexor tendon injury and retired horses had lower grades. The progression of POD and its ability to heal requires further evaluation.
Ultrasound features of arytenoid chondritis in Thoroughbred horses
Authors: Garrett K. S. , Embertson R. M. , Woodie J. B. , Cheetham J. 
Published: December 2012

SummaryReasons for performing studyLaryngeal ultrasonography can provide valuable information when considering a diagnosis of arytenoid chondritis, but specific ultrasonographic parameters have not been defined.ObjectivesTo compare ultrasonographic findings of the arytenoid cartilages in horses with endoscopically diagnosed arytenoid chondritis with ultrasonographic findings of the arytenoid cartilages in normal horses.MethodsUltrasound images of the larynx were obtained at the level of the arytenoid cartilages in horses with endoscopically diagnosed arytenoid chondritis and horses with normal arytenoid cartilage structure and function. Information obtained from the ultrasound examination included arytenoid cartilage cross‐sectional area, arytenoid cartilage echogenicity and arytenoid cartilage shape. Comparisons were performed between affected and unaffected arytenoid cartilages. For horses with multiple examinations, relationships between time point and arytenoid cartilage cross‐sectional area were determined.ResultsChondritic arytenoid cartilages were significantly larger and had abnormal shape and echogenicity when compared with normal arytenoid cartilages (P<0.001). For horses with multiple examinations, no significant changes were identified in arytenoid cartilage size over time.ConclusionsChondritic arytenoid cartilages are increased in size and have abnormal echogenicity and contour in comparison with normal arytenoid cartilages when assessed using laryngeal ultrasonography. Once enlarged, the cartilage does not appear to return to normal size after the infection and/or inflammation has resolved.Potential relevanceUltrasonography is a valuable diagnostic modality when investigating cases of possible arytenoid chondritis or abnormal arytenoid cartilage movement. It has additional benefit in determining the extent of disease when medial masses are present on the surface of arytenoid cartilages, aiding in surgical decision making.
Horse‐, training‐ and race‐level risk factors for palmar/plantar osteochondral disease in the racing Thoroughbred
Authors: Pinchbeck G. L. , Clegg P. D. , Boyde A. , Barr E. D. , Riggs C. M. 
Published: December 2012

SummaryReasons for performing studyPalmar/plantar osteochondral disease (POD) is a common, debilitating condition in Thoroughbred racehorses; however, training‐ and racing‐related factors associated with this disease are unknown.ObjectivesTo determine horse‐, racing‐ and training‐related risk factors for POD. The general hypotheses were that early training and racing, and increased intensity of racing and training, lead to increased severity of POD.MethodsThe metacarpo/metatarsophalangeal joints of 164 Thoroughbred racehorses were examined at post mortem and graded for third metacarpal and metatarsal POD. The relationships between training‐ and racing‐related factors and grade of POD in each condyle were determined using multilevel, multivariable, ordinal logistic regression models.ResultsA total of 1288 condyles were graded. Factors associated with higher grades of POD were the total lifetime number of races, an increase in gallop sessions in the previous season, racing before import to Hong Kong and an increase in the number of short (8–16 weeks) between‐race intervals per season. Horses in their first racing season were more likely to have lower POD grades, while horses that had a long between‐race interval (greater than 16 weeks) in the season prior to euthanasia were also more likely to have lower POD grades. Lower POD grades were significantly more likely as days since last race increased up to 400 days. Age at first race was not significantly associated with grade of POD.Conclusions and potential relevanceCumulative racing exposure and training intensity in the previous season were associated with higher grades of POD, supporting the hypothesis that the disease is due to repetitive loading. Longer between‐race intervals and increased time since racing were associated with lower POD grades, which may indicate that lesions heal. Further work is required to enable optimisation of racing and training programmes to reduce the frequency and severity of this disease.
Genetic alterations in RAS‐regulated pathway in acral lentiginous melanoma
Authors: Puig‐Butillé Joan A. , Badenas Celia , Ogbah Zighereda , Carrera Cristina , Aguilera Paula , Malvehy Josep , Puig Susana 
Published: December 2012

AbstractStudies integrating clinicopathological and genetic features have revealed distinct patterns of genomic aberrations in Melanoma. Distributions of BRAF or NRAS mutations and gains of several oncogenes differ among melanoma subgroups, while 9p21 deletions are found in all melanoma subtypes. In the study, status of genes involved in cell cycle progression and apoptosis was evaluated in a panel of 17 frozen primary acral melanomas. NRAS mutations were found in 17% of the tumors. In contrast, BRAF mutations were not found. Gains of AURKA gene (20q13.3) were detected in 37.5% of samples, gains of CCND1 gene (11q13) or TERT gene (5p15.33) in 31.2% and gains of NRAS gene (1p13.2) in 25%. Alterations in 9p21 were identified in 69% of tumors. Gains of 11q13 and 20q13 were mutually exclusive, and 1p13.2 gain was associated with 5p15.33. Our findings showed that alterations in RAS‐related pathways are present in 87.5% of acral lentiginous melanomas.
Self‐trimerization of ExsD limits inhibition of the Pseudomonas aeruginosa transcriptional activator ExsA in vitro
Authors: Bernhards Robert C. , Marsden Anne E. , Esher Shannon K. , Yahr Timothy L. , Schubot Florian D. 
Published: December 2012

The opportunistic pathogen Pseudomonas aeruginosa ranks among the leading causes of nosocomial infection. The type III secretion system (T3SS) aids acute Pseudomonas aeruginosa infection by injecting potent cytotoxins into host cells to suppress the host's innate immune response. Expression of all T3SS‐related genes is strictly dependent on the transcription factor ExsA. Consequently, ExsA and the biological processes that regulate ExsA function are of great biomedical interest. The present study focused on the ExsA–ExsC–ExsD–ExsE signaling cascade, which ties host cell contact to the upregulation of T3SS gene expression. Prior to T3SS induction, the antiactivator protein ExsD binds to ExsA and blocks ExsA‐dependent transcription by interfering with ExsA dimerization and promoter interactions. Upon host cell contact, ExsD is sequestered by the T3SS chaperone ExsC, resulting in the release of ExsA and upregulation of the T3SS. Previous studies have shown that the ExsD–ExsA interactions are not freely reversible. Because independently folded ExsD and ExsA were not found to interact, it has been hypothesized that folding intermediates of the two proteins form the complex. Here, we demonstrate, for the first time, that ExsD alone is sufficient to inhibit ExsA‐dependent transcription in vitro and that no other cellular factors are required. More significantly, we show that independently folded ExsD and ExsA are capable of interacting, but only at 37 °C and not at 30 °C. Guided by the crystal structure of ExsD, we designed a monomeric variant of the protein, and demonstrated that ExsD trimerization prevents ExsD from inhibiting ExsA‐dependent transcription at 30 °C. We propose that this unique mechanism plays an important role in T3SS regulation.Structured digital abstract
ExsD and ExsD bind by molecular sieving (View interaction).
ExsA physically interacts with ExsA by protein complementation assay (View interaction).
Evaluation of cell‐free protein synthesis for the crystallization of membrane proteins – a case study on a member of the glutamate transporter family from Staphylothermus marinus
Authors: Jaehme Michael , Michel Hartmut 
Published: December 2012

Cell‐free in vitro synthesis of proteins using coupled transcription/translation is considered to be a powerful alternative to the use of traditional cell‐based expression systems. Recently, promising developments have been reported applying cell‐free production to membrane proteins for structural biology and in particular for NMR spectroscopy. However, the general applicability of this system to produce large amounts of stable, functional and homogeneous membrane proteins as required for X‐ray crystallography remains to be determined. Here, we present a systematic study comparing structural and functional properties of membrane proteins produced using Escherichia coli derived in vitro and in vivo expression systems. The function of the target membrane protein, a previously uncharacterized bacterial glutamate transporter homolog from Staphylothermus marinus, was analyzed using ligand binding and transport assays. In addition, the protein structure was investigated with respect to its overall fold and oligomeric state in different detergents. We found that the protein synthesized in vitro is highly stable and monodisperse. However, in contrast to the protein produced using an in vivo system, it was not able to assemble into the native trimeric state nor to bind substrate. We thus conclude that cell‐free expression systems can compromise folding and function of such complex secondary active transporters. The expression product has to be carefully characterized prior to biophysical investigations like crystallography of membrane proteins.Structured digital abstract
GltSM and GltSM bind by molecular sieving (View interaction)
GltSM and GltSM bind by cross-linking study (View interaction)
Unraveling the function of the two Entner–Doudoroff branches in the thermoacidophilic Crenarchaeon Sulfolobus solfataricus P2
Authors: Kouril Theresa , Wieloch Patricia , Reimann Julia , Wagner Michaela , Zaparty Melanie , Albers Sonja‐Verena , Schomburg Dietmar , Ruoff Peter , Siebers Bettina 
Published: December 2012

Sulfolobus solfataricus P2 is a thermoacidophilic archaeon that metabolizes glucose and galactose via an unusual branched Entner–Doudoroff (ED) pathway, which is characterized by a non‐phosphorylative (np) and a semi‐phosphorylative (sp) branch. However, so far the physiological significance of the two pathway branches is unknown. In order to address these questions two key enzymes of the branched ED pathway, the class II glycerate kinase (GK) of the np‐ED branch and the 2‐keto‐3‐deoxygluconate kinase (KDGK) of the sp‐ED branch in S. solfataricus, were investigated. GK was recombinantly purified and characterized with respect to its kinetic properties. Mg2+ dependent Sso‐GK (glycerate + ATP → 2‐phosphoglycerate + ADP) showed unusual regulatory properties, i.e. substrate inhibition and cooperativity by d‐glycerate and ATP, and a substrate‐inhibition model was established fitting closely to the experimental data. Furthermore, deletion of the sp‐ED key enzyme KDGK in S. solfataricus PBL2025 resulted in a similar growth phenotype on glucose as substrate compared with the wild‐type. In contrast, the mutant showed strongly increased concentrations of np‐ED intermediates whereas the hexose and pentose phosphates as well as trehalose were decreased. Together the results indicate (a) that the np‐ED pathway is able to compensate for the missing sp‐ED branch in glucose catabolism, (b) that in addition to its catabolic function the sp‐ED pathway has an additional although not essential role in providing sugar phosphates for anabolism/gluconeogenesis and (c) that GK, with its unusual regulatory properties, seems to play a major role in controlling the flux between the glycolytic np‐ED and the glycolytic/gluconeogenetic sp‐ED pathway.DatabaseThe amino acid sequence data of GK of S. solfataricus P2 is available in the UniProt Protein Database under the accession number Q7LXP1 (http://www.uniprot.org/uniprot/Q7LXP1).
Detecting nonlinear response of spring phenology to climate change by Bayesian analysis
Authors: Pope Katherine S. , Dose Volker , Da Silva David , Brown Patrick H. , Leslie Charles A. , DeJong Theodore M. 
Published: December 2012

AbstractThe impact of climate change on the advancement of plant phenological events has been heavily studied in the last decade. Although the majority of spring plant phenological events have been trending earlier, this is not universally true. Recent work has suggested that species that are not advancing in their spring phenological behavior are responding more to lack of winter chill than increased spring heat. One way to test this hypothesis is by evaluating the behavior of a species known to have a moderate to high chilling requirement and examining how it is responding to increased warming. This study used a 60‐year data set for timing of leaf‐out and male flowering of walnut (Juglans regia) cultivar ‘Payne’ to examine this issue. The spring phenological behavior of ‘Payne’ walnut differed depending on bud type. The vegetative buds, which have a higher chilling requirement, trended toward earlier leaf‐out until about 1994, when they shifted to later leaf‐out. The date of male bud pollen shedding advanced over the course of the whole record. Our findings suggest that many species which have exhibited earlier bud break are responding to warmer spring temperatures, but may shift into responding more to winter temperatures (lack of adequate chilling) as warming continues.