bluuebunny/crossref_metadata_2025_split huggingface dataset:
Complementary effects of bevacizumab and MMC in the improvement of surgical outcome after glaucoma filtration surgery
Authors: Van Bergen Tine , Vandewalle Evelien , Moons Lieve , Stalmans Ingeborg 
Published: May 2015

AbstractPurposeTo determine the optimum administration route of bevacizumab after glaucoma filtering surgery (GFS) and to investigate whether a reduced dose of mitomycin‐C (MMC) in combination with bevacizumab could improve surgical outcome with a reduced incidence of side‐effects.MethodsPlasma levels of bevacizumab were determined via ELISA after intracameral (IC), subconjunctival (SC) and intravitreal (IV) injections in mice, subjected to a mouse model of GFS. Application of MMC was compared to bevacizumab (SC, 25 μg) and to the combined use of both adjuvants. Surgical sponges soaked in MMC 0.02% or 0.01% were exposed to the sclera for 1 or 2 min. Treatment outcome was studied by bleb investigation.ResultsThe three administration routes of bevacizumab equally improved surgical outcome. The VEGF antibody was detected at relatively high levels in plasma shortly after IV injection, whereas it was minimally absorbed after IC and SC injections. Both bevacizumab (SC) and MMC 0.02% (2 min) similarly increased bleb area. As compared to MMC, the combined injection with bevacizumab induced an additional effect on surgical outcome. Exposure of MMC 0.02% for 1 or 2 min together with bevacizumab equally improved surgical outcome, but 2 min application induced corneal toxicity. The combined use of bevacizumab and 1‐min MMC 0.01% also improved surgical outcome compared to monotherapy, although to a lesser extent than the combination with 1‐min MMC 0.02%.ConclusionsAdjunctive bevacizumab not only enhances the beneficial effect of MMC on surgical outcome, but also allows reducing the administration time of MMC 0.02%, thereby eliminating its toxic effects on the cornea.
Pharmacological actions of nobiletin in the modulation of platelet function
Authors: Vaiyapuri Sakthivel , Roweth Harvey , Ali Marfoua S , Unsworth Amanda J , Stainer Alexander R , Flora Gagan D , Crescente Marilena , Jones Chris I , Moraes Leonardo A , Gibbins Jonathan M 
Published: May 2015

Background and PurposeThe discovery that flavonoids are capable of inhibiting platelet function has led to their investigation as potential antithrombotic agents. However, despite the range of studies on the antiplatelet properties of flavonoids, little is known about the mechanisms by which flavonoids inhibit platelet function. In this study, we aimed to explore the pharmacological effects of a polymethoxy flavonoid, nobiletin, in the modulation of platelet function.Experimental ApproachThe ability of nobiletin to modulate platelet function was explored by using a range ofin vitroandin vivoexperimental approaches. Aggregation, dense granule secretion and spreading assays were performed using washed platelets. Fibrinogen binding, α‐granule secretion and calcium mobilization assays were performed using platelet‐rich plasma and whole blood was used in impedance aggregometry and thrombus formation experiments. The effect of nobiletinin vivowas assessed by measuring tail bleeding time usingC57BL/6 mice.Key ResultsNobiletin was shown to suppress a range of well‐established activatory mechanisms, including platelet aggregation, granule secretion, integrin modulation, calcium mobilization and thrombus formation. Nobiletin extended bleeding time in mice and reduced the phosphorylation ofPKB(Akt) andPLCγ2 within the collagen receptor (glycoproteinVI)‐stimulated pathway, in addition to increasing the levels of cGMPand phosphorylation of vasodilator‐stimulated phosphoprotein, a protein whose activity is associated with inhibitory cyclic nucleotide signalling.Conclusions and ImplicationsThis study provides insight into the underlying molecular mechanisms through which nobiletin modulates haemostasis and thrombus formation. Therefore, nobiletin may represent a potential antithrombotic agent of dietary origins.
The GPR 55 agonist, L‐α‐lysophosphatidylinositol, mediates ovarian carcinoma cell‐induced angiogenesis
Authors: Hofmann Nicole A , Yang Jiang , Trauger Sunia A , Nakayama Hironao , Huang Lan , Strunk Dirk , Moses Marsha A , Klagsbrun Michael , Bischoff Joyce , Graier Wolfgang F 
Published: May 2015

Background and PurposeHighly vascularized ovarian carcinoma secretes the putative endocannabinoid and GPR55 agonist, L‐α‐lysophosphatidylinositol (LPI), into the circulation. We aimed to assess the involvement of this agonist and its receptor in ovarian cancer angiogenesis.Experimental ApproachSecretion of LPI by three ovarian cancer cell lines (OVCAR‐3, OVCAR‐5 and COV‐362) was tested by mass spectrometry. Involvement of cancer cell‐derived LPI on angiogenesis was tested in the in vivo chicken chorioallantoic membrane (CAM) assay along with the assessment of the effect of LPI on proliferation, network formation, and migration of neonatal and adult human endothelial colony‐forming cells (ECFCs). Engagement of GPR55 was verified by using its pharmacological inhibitor CID16020046 and diminution of GPR55 expression by four different target‐specific siRNAs. To study underlying signal transduction, Western blot analysis was performed.Key ResultsOvarian carcinoma cell‐derived LPI stimulated angiogenesis in the CAM assay. Applied LPI stimulated proliferation, network formation, and migration of neonatal ECFCs in vitro and angiogenesis in the in vivo CAM. The pharmacological GPR55 inhibitor CID16020046 inhibited LPI‐stimulated ECFC proliferation, network formation and migration in vitro as well as ovarian carcinoma cell‐ and LPI‐induced angiogenesis in vivo. Four target‐specific siRNAs against GPR55 prevented these effects of LPI on angiogenesis. These pro‐angiogenic effects of LPI were transduced by GPR55‐dependent phosphorylation of ERK1/2 and p38 kinase.Conclusions and ImplicationsWe conclude that inhibiting the pro‐angiogenic LPI/GPR55 pathway appears a promising target against angiogenesis in ovarian carcinoma.
Racialized Mobility Transitions in Philadelphia: Connecting Urban Sustainability and Transport Justice
Authors: SHELLER MIMI 
Published: May 2015

AbstractNational level statistics show a decade‐long decline in the use of cars in the United States as well as other developed countries. This transition has been connected to growth in more sustainable forms of urban transport such as walking, bicycling, and increased use of transit, as well as changes in urban spatial planning. This article examines the recent trends toward more sustainable mobility in Philadelphia, in order to locate these cultural changes in a specific spatial, cultural, and racial context. The article raises the crucial yet often ignored issue of how urban spatial form and mobility regimes in post‐industrial cities like Philadelphia are highly inflected by racial space and racialized mobilities. It suggests that wider trends toward decreasing young white automobility in cities across the U.S. must be situated in relation to changing patterns of suburbanization of poverty, gentrification of city centers, and struggles over public transit access and investment. The specific case is analyzed in relation to multi‐level transition theories, cultural analysis of mobility frames and discourses, and the addition of local observation of everyday transport drawing on perspectives from mobilities research. A focus on racial space and transport inequality adds new insights to understanding the limits of any transition that may be taking place in the American automobility regime, and it expands how such transitions are being culturally framed and promoted.
Cyclists as Part of the City's Organism: Structural Stories on Cycling in Copenhagen
Authors: FREUDENDAL‐PEDERSEN MALENE 
Published: May 2015

AbstractThis article examines Copenhagen cyclists' emotional and “rational” stories about cycling in the city. Copenhagen is branded as a city of cyclists; nevertheless, the car still plays a dominant role in both policy and planning and thus everyday life. This shapes cyclists' stories as well as their praxis. This paper reveals how Copenhagen cyclists contest the role of the car but simultaneously support the automobile system that privileges cars over bikes through their narrations and praxis. This article employs the concept “structural stories” (Freudendal‐Pedersen 2009) to reveal how particular rationales are used to explain everyday actions and choices. Structural stories are understood and expressed as universal truths, and as such they create paths for mobilities praxis. The stories also reveal contradictions in the image of Copenhagen and the way that people actually live and move through the city. The article draws on empirical data compiled from several research projects on mobilities in Copenhagen between 2007 and 2013. It suggests ways to further engender cycling in the city.
New Disability Mobilities and Accessibilities in Urban India
Authors: FRIEDNER MICHELE , OSBORNE JAMIE 
Published: May 2015

AbstractThis article analyzes mobilities and accessibilities in urban India in relation to disability in India. The concept of disability has become a privileged site for the state and NGOs to situate development interventions and for corporations to engage in corporate social responsibility initiatives. These state, NGO, and corporate efforts are directed at a specific kind of disabled individual and are heavily based upon market logics. Utilizing data from disability‐related conferences held in New Delhi and Bangalore, and other initiatives developing in these cities for disabled people, this article critically examines new disability mobilities and accessibilities and argues that a new assemblage of state, NGO, and corporation is forming around disability and giving rise to a new “disability marketplace.” This article calls for analysts and activists working in the arena of disability to be more specific in their treatment of the concepts of mobility and accessibility, and more aware of the consequences of reifying the concept of disability.
Neoadjuvant chemoradiation for rectal cancer is not associated with higher rates of thromboembolism
Authors: Smart P. J. , Stocchi L. L. , Remzi F. H. 
Published: May 2015

AbstractAimThromboembolism (TE) is a leading cause of death amongst cancer patients. The effect of neoadjuvant chemoradiotherapy (nCRT) on the risk of TE in rectal cancer patients is unknown. The aim of this study was to determine whether nCRT was associated with an increased risk of TE in patients with rectal cancer, either during therapy or with subsequent treatment.MethodThis was a retrospective study from a prospectively maintained database at a tertiary referral centre. Participants included patients with rectal cancer treated between January 2000 and December 2013. The primary outcome was the rate of TE in patients with rectal cancer who had nCRT compared with those who did not.ResultsOne hundred and seventy‐one (7.8%) of 2181 rectal cancer patients developed TE. Patients who had nCRT did not have an increased incidence of TE compared with those who had surgery alone (81/946, 8.6% vs 94/1235, 7.6%, P = 0.42) after a median follow‐up of 95 months. Ten (1.1%) of 946 patients who received nCRT developed TE during or immediately after nCRT. Most TE events occurred in the 30‐day postoperative period (70 patients, 3.2%).ConclusionThe prevalence of TE in patients with rectal cancer was 7.8%, with most events occurring in within 30 days of surgery. Neoadjuvant chemoradiation was not associated with an increased risk of TE.
Factors predicting 30‐day readmission after laparoscopic colorectal cancer surgery within an enhanced recovery programme
Authors: Francis N. K. , Mason J. , Salib E. , Allanby L. , Messenger D. , Allison A. S. , Smart N. J. , Ockrim J. B. 
Published: May 2015

AbstractAimHospital readmission within 30 days of surgery has become a marker of poor quality patient care. This study aimed to investigate factors predictive of 30‐day readmission after laparoscopic colorectal cancer surgery within an enhanced recovery after surgery (ERAS) programme.MethodConsecutive patients undergoing laparoscopic surgery for colorectal cancer within an ERAS programme between 2002 and 2009 were included. Data were collected relating to patient demographics, neoadjuvant chemoradiotherapy, ERAS compliance, and operative and postoperative outcomes. A logistic regression model was used to identify factors associated with readmissions after adjusting for the potential effect of covariables simultaneously.ResultsIn all, 268 cancer patients underwent laparoscopic colorectal surgery (108 rectal resections), of whom 34 (12.7%) were readmitted due most commonly to bowel obstruction (29%) and surgical site infection (18%). The use of neoadjuvant therapy (odds ratio 4.49, 95% CI 1.41–14.35; P = 0.011) and ERAS compliance above 93% (odds ratio 0.38, 95% CI 0.18–0.84; P = 0.016) were independent predictors of readmission.ConclusionPoor ERAS compliance and preoperative chemoradiotherapy were significant predictors of readmission following laparoscopic colorectal cancer surgery. Further research is required to expand the scope of ERAS beyond hospital discharge.
Asymmetrical allocation ofJAK1mRNAduring spermatogonial stem cell division inXenopus laevis
Authors: Hyakutake Keiichiro , Kawasaki Toshihiro , Zhang JiDong , Kubota Hiroshi , Abe Sin‐Ichi , Takamune Kazufumi 
Published: May 2015

DuringXenopusspermatogenesis, each primary spermatogonium (PG), the largest single cell in the testis, undergoes mitotic divisions with a concomitant decrease in size to produce smaller differentiating spermatogonia. The spermatogonial stem cells (SSCs) occur in thisPGpopulation. Taking advantage of identifiable and isolatable properties ofXenopusSSCs, we examinedJAK1gene expression during the spermatogenesis because there have been reports on the important role ofJAK/STATpathway in regulating the status ofSSCs inDrosophilaand mouse. Surprisingly,in situhybridization revealed the presence ofJAK1mRNAin the differentiating spermatogonia and primary spermatocytes as well as somePGs. Inhibition ofJAK1 activity in the testis caused a decrease in percentage of BrdU‐incorporating spermatogonia, suggesting thatJAK1 was at least involved in regulation of spermatogonial proliferation. Interestingly, single cell reverse transcription–polymerase chain reaction (RT–PCR) clearly showed two different types ofSSCs:SSCs withJAK1mRNA(JAK1+) or withoutJAK1mRNA(JAK1−). SinceJAK1−SSClevel was increased by induction of testis regeneration, self‐renewingSSCs were thought to beJAK1−. In addition, we found barrel‐shapedPGs, in whichJAK1mRNAwas localized asymmetrically to one half of the cell. The stainability with propidium iodide and morphology of two nuclei in the barrel‐shapedPGwere similar to those ofPGnucleus. Based on the above observations, we propose the hypothesis thatJAK1+SSCis preparing for production ofPGs destined to differentiate (destinedPGs) and the accumulatedJAK1mRNAin theSSCis distributed exclusively into the destinedPGs through mitotic division.
Sex‐dependent modulation of age‐related cognitive decline by the L‐type calcium channel gene Cacna1c (Cav1.2)
Authors: Zanos Panos , Bhat Shambhu , Terrillion Chantelle E. , Smith Robert J. , Tonelli Leonardo H. , Gould Todd D. 
Published: May 2015

AbstractIncreased calcium influx through L‐type voltage‐gated calcium channels has been implicated in the neuronal dysfunction underlying age‐related memory declines. The present study aimed to test the specific role of Cacna1c (which encodes Cav1.2) in modulating age‐related memory dysfunction. Short‐term, spatial and contextual/emotional memory was evaluated in young and aged, wild‐type as well as mice with one functional copy of Cacna1c (haploinsufficient), using the novel object recognition, Y‐maze and passive avoidance tasks, respectively. Hippocampal expression of Cacna1c mRNA was measured by quantitative polymerase chain reaction. Ageing was associated with object recognition and contextual/emotional memory deficits, and a significant increase in hippocampal Cacna1c mRNA expression. Cacna1c haploinsufficiency was associated with decreased Cacna1c mRNA expression in both young and old animals. However, haploinsufficient mice did not manifest an age‐related increase in expression of this gene. Behaviourally, Cacna1c haploinsufficiency prevented object recognition deficits during ageing in both male and female mice. A significant correlation between higher Cacna1c levels and decreased object recognition performance was observed in both sexes. Also, a sex‐dependent protective role of decreased Cacna1c levels in contextual/emotional memory loss has been observed, specifically in male mice. These data provide evidence for an association between increased hippocampal Cacna1c expression and age‐related cognitive decline. Additionally, they indicate an interaction between the Cacna1c gene and sex in the modulation of age‐related contextual memory declines.
Lateralization of mesial temporal lobe epilepsy with chronic ambulatory electrocorticography
Authors: King‐Stephens David , Mirro Emily , Weber Peter B. , Laxer Kenneth D. , Van Ness Paul C. , Salanova Vicenta , Spencer David C. , Heck Christianne N. , Goldman Alica , Jobst Barbara , Shields Donald C. , Bergey Gregory K. , Eisenschenk Stephan , Worrell Gregory A. , Rossi Marvin A. , Gross Robert E. , Cole Andrew J. , Sperling Michael R. , Nair Dileep R. , Gwinn Ryder P. , Park Yong D. , Rutecki Paul A. , Fountain Nathan B. , Wharen Robert E. , Hirsch Lawrence J. , Miller Ian O. , Barkley Gregory L. , Edwards Jonathan C. , Geller Eric B. , Berg Michel J. , Sadler Toni L. , Sun Felice T. , Morrell Martha J. 
Published: May 2015

SummaryObjectivePatients with suspected mesial temporal lobe (MTL) epilepsy typically undergo inpatient video–electroencephalography (EEG) monitoring with scalp and/or intracranial electrodes for 1 to 2 weeks to localize and lateralize the seizure focus or foci. Chronic ambulatory electrocorticography (ECoG) in patients with MTL epilepsy may provide additional information about seizure lateralization. This analysis describes data obtained from chronic ambulatory ECoG in patients with suspected bilateral MTL epilepsy in order to assess the time required to determine the seizure lateralization and whether this information could influence treatment decisions.MethodsAmbulatory ECoG was reviewed in patients with suspected bilateral MTL epilepsy who were among a larger cohort with intractable epilepsy participating in a randomized controlled trial of responsive neurostimulation. Subjects were implanted with bilateral MTL leads and a cranially implanted neurostimulator programmed to detect abnormal interictal and ictal ECoG activity. ECoG data stored by the neurostimulator were reviewed to determine the lateralization of electrographic seizures and the interval of time until independent bilateral MTL electrographic seizures were recorded.ResultsEighty‐two subjects were implanted with bilateral MTL leads and followed for 4.7 years on average (median 4.9 years). Independent bilateral MTL electrographic seizures were recorded in 84%. The average time to record bilateral electrographic seizures in the ambulatory setting was 41.6 days (median 13 days, range 0–376 days). Sixteen percent had only unilateral electrographic seizures after an average of 4.6 years of recording.SignificanceAbout one third of the subjects implanted with bilateral MTL electrodes required >1 month of chronic ambulatory ECoG before the first contralateral MTL electrographic seizure was recorded. Some patients with suspected bilateral MTL seizures had only unilateral electrographic seizures. Chronic ambulatory ECoG in patients with suspected bilateral MTL seizures provides data in a naturalistic setting, may complement data from inpatient video‐EEG monitoring, and can contribute to treatment decisions.
Comparison of lacosamide concentrations in cerebrospinal fluid and serum in patients with epilepsy
Authors: May Theodor W. , Brandt Christian , Helmer Renate , Bien Christian G. , Cawello Willi 
Published: May 2015

SummaryObjectiveThis study was carried out to estimate the exposure of the central nervous system (CNS) to the antiepileptic drug (AED) lacosamide, under steady state conditions, in patients with epilepsy who take oral lacosamide alongside up to three other AEDs.MethodsTwenty‐seven serum and cerebral spinal fluid (CSF) samples were collected from 21 patients receiving lacosamide for the treatment of epilepsy (50–600 mg/day over two or three doses). This included 23 time‐matched pairs of serum and CSF samples from 19 patients. The concentration of lacosamide in each sample was determined using high‐performance liquid chromatography tandem mass spectrometry (HPLC‐MS/MS). Linear regression was used to characterize the relationship between the CSF‐to‐serum ratio of lacosamide concentration and the time since dosing, the daily lacosamide dose, or the daily dose normalized by volume of distribution (Vd, approximated to total body water), and between the drug concentrations in each compartment (CSF vs. serum).ResultsConcentrations of lacosamide in CSF (mean ± standard deviation [SD] 7.37 ± 3.73 μg/ml, range 1.24–14.95, n = 27) and serum (mean ± SD 8.16 ± 3.82 μg/ml, range 2.29–15.45, n = 27) samples showed a good correlation over the dose range investigated. The mean CSF‐to‐serum ratio of lacosamide concentrations was 0.897 ± 0.193 (range 0.492–1.254, n = 23 time‐matched pairs) and was independent of lacosamide dose.SignificanceDrug concentrations in the CSF are often used to indicate those in the brain interstitial fluid. In patients with epilepsy who follow a stable oral AED dosing regimen, lacosamide concentration in CSF is approximately 85% of that found in serum, suggesting that serum may be a valuable indicator of lacosamide concentration in the CNS.
Integrating plant litter quality, soil organic matter stabilization, and the carbon saturation concept
Authors: Castellano Michael J. , Mueller Kevin E. , Olk Daniel C. , Sawyer John E. , Six Johan 
Published: May 2015

AbstractLabile, ‘high‐quality’, plant litters are hypothesized to promote soil organic matter (SOM) stabilization in mineral soil fractions that are physicochemically protected from rapid mineralization. However, the effect of litter quality on SOM stabilization is inconsistent. High‐quality litters, characterized by high N concentrations, low C/N ratios, and low phenol/lignin concentrations, are not consistently stabilized in SOM with greater efficiency than ‘low‐quality’ litters characterized by low N concentrations, high C/N ratios, and high phenol/lignin concentrations. Here, we attempt to resolve these inconsistent results by developing a new conceptual model that links litter quality to the soil C saturation concept. Our model builds on the Microbial Efficiency‐Matrix Stabilization framework (Cotrufo et al., 2013) by suggesting the effect of litter quality on SOM stabilization is modulated by the extent of soil C saturation such that high‐quality litters are not always stabilized in SOM with greater efficiency than low‐quality litters.