bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intelligence quotient in paediatric sickle cell disease: a systematic review and meta‐analysis
Authors: Kawadler Jamie M , Clayden Jonathan D , Clark Chris A , Kirkham Fenella J 
Published: April 2016

AimSickle cell disease (SCD) is the commonest cause of childhood stroke worldwide. Magnetic resonance imaging (MRI) is routinely used to detect additional silent cerebral infarction (SCI), as IQ is lower in SCI as well as stroke. This review assesses the effect of infarction on IQ, and specifically whether, compared to healthy controls, IQ differences are seen in children with SCI with no apparent MRI abnormality.MethodA systematic review was conducted to include articles with an SCD paediatric population, MRI information, and Wechsler IQ. A meta‐analysis of 19 articles was performed to compare IQ in three groups: stroke vs SCI; SCI vs no SCI; and no SCI vs healthy controls.ResultsMean differences in IQ between all three groups were significant: stroke patients had lower IQ than patients with SCI by 10 points (six studies); patients with SCI had lower IQ than no patients with SCI by 6 points (17 studies); and no patients with SCI had lower IQ than healthy controls by 7 points (seven studies).InterpretationChildren with SCD and no apparent MRI abnormality have significantly lower IQ than healthy controls. In this chronic condition, other biological, socioeconomic, and environmental factors must play a significant role in cognition.
Transthoracic Echocardiography‐Guided Percutaneous Patent Ductus Arteriosus Occlusion: A New Strategy for Interventional Treatment
Authors: Pan Xiang‐Bin , Ouyang Wen‐Bin , Wang Shou‐Zheng , Liu Yao , Zhang Da‐Wei , Zhang Feng‐Wen , Pang Kun‐Jing , Zhang Zhe , Hu Sheng‐Shou 
Published: April 2016

IntroductionPercutaneous patent ductus arteriosus (PDA) occlusion has become the preferred therapeutic option, which uses fluoroscopy as the guidance. To reduce the x‐ray exposure, PDA occlusion using the Amplatzer Duct Occluder II (ADO II) under guidance of transthoracic echocardiography only was conducted. This single center study aims to access the safety and efficiency of this new strategy.Methods and ResultsFrom June 2013 to May 2015, 63 consecutive PDA patients underwent transthoracic echocardiography‐guided PDA occlusion through the femoral artery. Outpatient follow‐up was conducted at 1, 3, and 6 months, and yearly. Sixty‐two patients successfully underwent echocardiography‐guided percutaneous PDA occlusion. One patient was converted to minimally invasive transthoracic occlusion due to failure of delivery sheath passage through tortuous PDA. Mean procedure duration was 24.3 ± 7.0 minutes; ADO II diameter averaged 4.6 ± 0.9 mm; 8 cases showed traces of residual shunt immediately after operation which resolved after 24 hours; and mean hospital stay was 3.4 ± 0.5 days. There was no occluder migration, hemolysis, pericardial effusion, pulmonary branch or aortic stenosis at mean 13.5 ± 4.8 months follow‐up.ConclusionsThis study demonstrated that percutaneous PDA occlusion can be successfully performed under guidance of transthoracic echocardiography only and appears safe and effective while avoiding radiation and contrast agent use.
Influence of platelet and white blood cell counts on major thrombosis – analysis from a patient registry in essential thrombocythemia
Authors: Buxhofer‐Ausch Veronika , Steurer Michael , Sormann Siegfried , Schloegl Ernst , Schimetta Wolfgang , Gisslinger Bettina , Ruckser Reinhard , Gastl Günther , Gisslinger Heinz 
Published: April 2016

AbstractObjectivesAlthough guidelines recommend normalization of platelet counts as an appropriate endpoint for treatment in high‐risk essential thrombocythemia (ET), retrospective studies could not prove a correlation of diagnostic platelet counts with an increased thrombotic rate. There is, however, an increasing evidence that leukocytosis is an important risk factor for arterial thrombosis in myeloproliferative neoplasms.MethodsThis study considers the Austrian cohort of a European registry regarding the platelet‐lowering therapeutic anagrelide. Influence of platelet and white blood cell (WBC) counts on thrombotic risk was assessed.ResultsUsing the calculated cutoffs of 574.5 G/L for platelets and 8.48 G/L for WBC counts, respectively, the Cox regression analysis revealed a clear influence of elevated platelets (P = 0.008) and WBC counts (P = 0.011) on the occurrence of major thrombotic events. The time to a major thrombotic event was shortest (P < 0.001) and the frequency related to 100 patient‐years was highest (P = <0.001) when both platelet and WBC counts ranged above the calculated cutoffs.ConclusionOur data add evidence to the impact of platelet and WBC counts on thrombosis in ET. We suspect a particular interaction between platelets and WBC which might be based on a biological interplay depending on particular cell counts.
Lack of mGluR6‐related cascade elements leads to retrograde trans‐synaptic effects on rod photoreceptor synapses via matrix‐associated proteins
Authors: Tummala Shanti R. , Dhingra Anuradha , Fina Marie E. , Li Jian J. , Ramakrishnan Hariharasubramanian , Vardi Noga 
Published: April 2016

AbstractHeterotrimeric G‐proteins couple metabotropic receptors to downstream effectors. In retinal ON bipolar cells, Go couples the metabotropic receptor mGluR6 to the TRPM1 channel and closes it in the dark, thus hyperpolarizing the cell. Light, via GTPase‐activating proteins, deactivates Go, opens TRPM1 and depolarizes the cell. Go comprises Gαo1, Gβ3 and Gγ13; all are necessary for efficient coupling. In addition, Gβ3 contributes to trafficking of certain cascade proteins and to maintaining the synaptic structure. The goal of this study was to determine the role of Gαo1 in maintaining the cascade and synaptic integrity. Using mice lacking Gαo1, we quantified the immunostaining of certain mGluR6‐related components. Deleting Gαo1 greatly reduced staining for Gβ3, Gγ13, Gβ5, RGS11, RGS7 and R9AP. Deletion of Gαo1 did not affect mGluR6, TRPM1 or PCP2. In addition, deleting Gαo1 reduced the number of rod bipolar dendrites that invaginate the rod terminal, similar to the effect seen in the absence of mGluR6, Gβ3 or the matrix‐associated proteins, pikachurin, dystroglycan and dystrophin, which are localized presynaptically to the rod bipolar cell. We therefore tested mice lacking mGluR6, Gαo1 and Gβ3 for expression of these matrix‐associated proteins. In all three genotypes, staining intensity for these proteins was lower than in wild type, suggesting a retrograde trans‐synaptic effect. We propose that the mGluR6 macromolecular complex is connected to the presynaptic rod terminal via a protein chain that includes the matrix‐associated proteins. When a component of the macromolecular chain is missing, the chain may fall apart and loosen the dendritic tip adherence within the invagination.
Echo‐level compensation and delay tuning in the auditory cortex of the mustached bat
Authors: Macías Silvio , Mora Emanuel C. , Hechavarría Julio C. , Kössl Manfred 
Published: April 2016

AbstractDuring echolocation, bats continuously perform audio‐motor adjustments to optimize detection efficiency. It has been demonstrated that bats adjust the amplitude of their biosonar vocalizations (known as ‘pulses’) to stabilize the amplitude of the returning echo. Here, we investigated this echo‐level compensation behaviour by swinging mustached bats on a pendulum towards a reflective surface. In such a situation, the bats lower the amplitude of their emitted pulses to maintain the amplitude of incoming echoes at a constant level as they approach a target. We report that cortical auditory neurons that encode target distance have receptive fields that are optimized for dealing with echo‐level compensation. In most cortical delay‐tuned neurons, the echo amplitude eliciting the maximum response matches the echo amplitudes measured from the bats’ biosonar vocalizations while they are swung in a pendulum. In addition, neurons tuned to short target distances are maximally responsive to low pulse amplitudes while neurons tuned to long target distances respond maximally to high pulse amplitudes. Our results suggest that bats dynamically adjust biosonar pulse amplitude to match the encoding of target range and to keep the amplitude of the returning echo within the bounds of the cortical map of echo delays.
Amphetamine elevates nucleus accumbens dopamine via an action potential‐dependent mechanism that is modulated by endocannabinoids
Authors: Covey Dan P. , Bunner Kendra D. , Schuweiler Douglas R. , Cheer Joseph F. , Garris Paul A. 
Published: April 2016

AbstractThe reinforcing effects of abused drugs are mediated by their ability to elevate nucleus accumbens dopamine. Amphetamine (AMPH) was historically thought to increase dopamine by an action potential‐independent, non‐exocytotic type of release called efflux, involving reversal of dopamine transporter function and driven by vesicular dopamine depletion. Growing evidence suggests thatAMPHalso acts by an action potential‐dependent mechanism. Indeed, fast‐scan cyclic voltammetry demonstrates thatAMPHactivates dopamine transients, reward‐related phasic signals generated by burst firing of dopamine neurons and dependent on intact vesicular dopamine. Not established forAMPHbut indicating a shared mechanism, endocannabinoids facilitate this activation of dopamine transients by broad classes of abused drugs. Here, using fast‐scan cyclic voltammetry coupled to pharmacological manipulations in awake rats, we investigated the action potential and endocannabinoid dependence ofAMPH‐induced elevations in nucleus accumbens dopamine.AMPHincreased the frequency, amplitude and duration of transients, which were observed riding on top of slower dopamine increases. Surprisingly, silencing dopamine neuron firing abolished allAMPH‐induced dopamine elevations, identifying an action potential‐dependent origin. Blocking cannabinoid type 1 receptors preventedAMPHfrom increasing transient frequency, similar to reported effects on other abused drugs, but not from increasing transient duration and inhibiting dopamine uptake. Thus,AMPHelevates nucleus accumbens dopamine by eliciting transients via cannabinoid type 1 receptors and promoting the summation of temporally coincident transients, made more numerous, larger and wider byAMPH. Collectively, these findings are inconsistent withAMPHeliciting action potential‐independent dopamine efflux and vesicular dopamine depletion, and support endocannabinoids facilitating phasic dopamine signalling as a common action in drug reinforcement.
Characterization of neuromuscular synapse function abnormalities in multiple Duchenne muscular dystrophy mouse models
Authors: van der Pijl Elizabeth M. , van Putten Maaike , Niks Erik H. , Verschuuren Jan J. G. M. , Aartsma‐Rus Annemieke , Plomp Jaap J. 
Published: April 2016

AbstractDuchenne muscular dystrophy (DMD) is an X‐linked myopathy caused by dystrophin deficiency. Dystrophin is present intracellularly at the sarcolemma, connecting actin to the dystrophin‐associated glycoprotein complex. Interestingly, it is enriched postsynaptically at the neuromuscular junction (NMJ), but its synaptic function is largely unknown. Utrophin, a dystrophin homologue, is also concentrated at the NMJ, and upregulated in DMD. It is possible that the absence of dystrophin at NMJs in DMD causes neuromuscular transmission defects that aggravate muscle weakness. We studied NMJ function in mdx mice (lacking dystrophin) and wild type mice. In addition, mdx/utrn+/− and mdx/utrn−/− mice (lacking utrophin) were used to investigate influences of utrophin levels. The three Duchenne mouse models showed muscle weakness when comparatively tested in vivo, with mdx/utrn−/− mice being weakest. Ex vivo muscle contraction and electrophysiological studies showed a reduced safety factor of neuromuscular transmission in all models. NMJs had ~ 40% smaller miniature endplate potential amplitudes compared with wild type, indicating postsynaptic sensitivity loss for the neurotransmitter acetylcholine. However, nerve stimulation‐evoked endplate potential amplitudes were unchanged. Consequently, quantal content (i.e. the number of acetylcholine quanta released per nerve impulse) was considerably increased. Such a homeostatic compensatory increase in neurotransmitter release is also found at NMJs in myasthenia gravis, where autoantibodies reduce acetylcholine receptors. However, high‐rate nerve stimulation induced exaggerated endplate potential rundown. Study of NMJ morphology showed that fragmentation of acetylcholine receptor clusters occurred in all models, being most severe in mdx/utrn−/− mice. Overall, we showed mild ‘myasthenia‐like’ neuromuscular synaptic dysfunction in several Duchenne mouse models, which possibly affects muscle weakness and degeneration.
Altered cerebellar‐cerebral functional connectivity in benign adult familial myoclonic epilepsy
Authors: Long Lili , Zeng Ling‐Li , Song Yanmin , Shen Hui , Fang Peng , Zhang Linlin , Xu Lin , Gong Jian , Zhang Yun‐Ci , Zhang Yong , Zhou Pinting , Huang Sha , Chen Si , Xie Yuanyuan , Hu Dewen , Xiao Bo 
Published: April 2016

SummaryObjectiveThe pathogenesis of benign adult familial myoclonic epilepsy (BAFME) remains unknown, although cerebellar pathologic changes and brain hyperexcitability have been reported. We used resting‐state functional magnetic resonance imaging (fMRI) to examine the functional connectivity between the cerebellum and cerebrum in a Chinese family with BAFME for the first time.MethodsEleven adults with BAFME and 15 matched healthy controls underwent resting‐state blood oxygen level–dependent (BOLD) fMRI scanning. The cerebellar seeds, including the bilateral crus I, lobule VIII, lobule VIIb, and lobule IV&V, were defined a priori. Next, regional time courses were obtained for each individual by averaging the BOLD time series over all voxels in each seed region. Then, seed‐based functional connectivity z‐maps were produced by computing Pearson's correlation coefficients (converted to z‐scores by Fisher transformation) between each seed signal and the time series from all other voxels within the entire brain. Finally, a second‐level random‐effect two‐sample t‐test was performed on the individual z‐maps in a voxel‐wise manner.ResultsReduced functional connectivity of the right cerebellar crus I with the left middle frontal gyrus and right cerebellar lobule IX was observed in the default network of BAFME. Enhanced functional connectivity of the left cerebellar lobule VIII with the bilateral middle temporal gyri, right putamen, and left cerebellar crus I was found in the dorsal attention network of BAFME. Enhanced functional connectivity between the left cerebellar lobule VIIb and right frontal pole was found in the control network of BAFME.SignificanceAltered cerebellar‐cerebral functional connectivity may contribute to the understanding of the nosogenesis of BAFME and explain the cognitive dysfunction in this Chinese family with BAFME.
Comparison of IgG concentrations by radial immunodiffusion, electrophoretic gamma globulin concentrations and total globulins in neonatal foals
Authors: Tscheschlok L. , Venner M. , Howard J. 
Published: April 2016

SummaryReasons for performing studyFailure of transfer of passive immunity (FTPI) in foals is associated with a risk of infection and death. The current diagnostic gold standard is quantification of immunoglobulins using radial immunodiffusion (IgG‐RID). Routine diagnosis is often performed using semi‐quantitative tests. Concentrations of serum electrophoretic gamma globulins (EGG) and total globulins may be useful to assess FTPI, but few studies have investigated their use.ObjectivesTo assess agreement between IgG‐RID and EGG and evaluate the accuracy of total globulin concentration to diagnose FTPI based on both IgG‐RID and EGG.Study designProspective study.MethodsA total of 360 serum samples were harvested at 6–24 h post natum from 60 German Warmblood foals. Concentrations of EGG, IgG‐RID and total globulin (calculated from total proteins and albumin) were measured. Agreement between EGG and IgG‐RID was assessed using Bland–Altman plots and Passing–Bablok regression. The accuracy of total globulin concentration was assessed using rank correlation and ROC curve analysis.ResultsGood agreement was found with slightly lower EGG than IgG‐RID concentrations (Bland–Altman systemic bias ‐1.9 g/l) which was more pronounced at higher concentrations (regression equation: IgG‐RID = ‐0.78 + 1.28 × EGG). Correlations between total globulin concentration and EGG and total globulin concentration and IgG‐RID were 0.93 and 0.79, respectively. The area under the curve was 0.982 and 0.952 for EGG <4 and <8 g/l and 0.953 and 0.899 for IgG‐RID <4 and <8 g/l. Sensitivities and specificities of total globulin concentration in the diagnosis of FTPI were comparable to those of commonly used screening tests, but cut‐offs could be selected to achieve sensitivities of >95% with 71.2% (IgG‐RID) and 90.5% (EGG) specificity for <4 g/l and >90% with 66.0% (IgG‐RID) and 87.9% (EGG) specificity for <8 g/l.ConclusionsThere is good agreement between EGG and IgG‐RID, with slightly more conservative estimates of immunoglobulins obtained using EGG. Total globulins may be a useful and economic quantitative screening test with cut‐offs achieving high sensitivities, but analyser‐specific cut‐offs may be necessary.
Neutrophil apoptosis is delayed in an equine model of colitis: Implications for the development of systemic inflammatory response syndrome
Authors: Anderson S. L. , Singh B. 
Published: April 2016

SummaryBackgroundHorses that develop colitis invariably exhibit signs of a systemic inflammatory response syndrome (SIRS). A significant contributor to the development of SIRS in human subjects is delayed neutrophil apoptosis, but this has not been specifically studied in horses.ObjectivesTo determine the occurrence of ex vivo neutrophil apoptosis and its contribution to the development of SIRS in an equine colitis model.Study designExperiment using a colitis model.MethodsNeutrophils were isolated before and after the induction of colitis using an oligofructose overdose model, placed into culture for 12 h or 24 h with or without lipopolysaccharide (LPS) at various concentrations, and assessed for the occurrence of apoptosis using Annexin V and propidium iodide staining with flow cytometric quantification. Levels of caspase‐3, ‐8 and ‐9 activity were measured after 12 h of incubation in neutrophil lysates.ResultsEx vivo neutrophil apoptosis was significantly delayed in neutrophils isolated after the induction of colitis (12‐h incubation: P = 0.004; 24‐h incubation: P = 0.003) with concomitant reductions in caspase‐3, ‐8 and ‐9 activity (caspase‐3: P = 0.004; caspase‐8: P = 0.02; caspase‐9: P = 0.02). Neutrophils isolated after the induction of colitis were refractory to LPS‐delayed apoptosis. Neutrophil apoptosis was delayed with increasing cell concentration in vitro.Main limitationsThe main limitation of the study is the that the exact mechanism for delayed neutrophil apoptosis following the induction of colitis was not fully elucidated.ConclusionsThe data show that neutrophil apoptosis is delayed in horses following the induction of colitis as a result of interference with the intrinsic and extrinsic apoptotic pathways, which may contribute to the development of equine SIRS. Concurrent development of neutrophilia may contribute to a prolonged neutrophil lifespan through a concentration‐dependent delay in apoptosis.
Prevalence of liver fluke infection in Irish horses and assessment of a serological test for diagnosis of equine fasciolosis
Authors: Quigley A. , Sekiya M. , Egan S. , Wolfe A. , Negredo C. , Mulcahy G. 
Published: April 2016

SummaryBackgroundThere is little information on the prevalence of Fasciola hepatica infection in the horse population in Ireland or the potential impact of fluke infection on animal health.ObjectivesTo investigate F. hepatica infection in the Irish horse population and to assess the diagnostic potential of an indirect enzyme‐linked immunosorbent assay (ELISA) based on the F. hepatica recombinant cathepsin L1 (CL1) antigen.Study designCross‐sectional abattoir survey of horses for liver fluke status.MethodsAnimals (n = 200) were examined at an abattoir between May 2013 and April 2014. Horses were graded ante mortem for body condition score. Blood and faeces were collected and livers were examined post mortem by gross morphology. A cohort (n = 35) of livers were also examined histologically. Haematology and blood biochemistry, including serum liver enzyme activities, were measured and faeces were sedimented for egg counts. Serum was assayed by indirect ELISA using a recombinant CL1.ResultsThe prevalence of liver fluke infection was 9.5%. There was no correlation between liver fluke status and time of year, breed classification, age group, sex, body condition score, ante mortem assessment, strongyle infection status, serum liver enzyme activities or CL1 concentration. A comparison of the CL1 ELISA in horse sera compared with a reference standard diagnosis showed high specificity of 95.6% (95% confidence interval [CI] 91.5–98.0%), but low sensitivity of 42.1% (95% CI 20.2–66.5%).Main limitationsThis study is limited by its nature as an abattoir study, the relatively small number of animals examined (n = 200), and the absence of a known negative group of horses.ConclusionsBlood biomarkers are not good indicators of liver fluke infection and the CL1 ELISA is not a sensitive tool for diagnosis of fluke infection in the horse. The prevalence of F. hepatica in horses indicates that further research is required to assess the potential impact of liver fluke on equine liver health.
In situ characterization of humidity effect on the fatigue damage evolution of a cast aluminium alloy
Authors: Li Wenkai , Engler‐Pinto C.C. , Cui Haitao , Wen Weidong , Su Xuming 
Published: April 2016

AbstractIn this paper, the feedback signal of ultrasonic fatigue system was used to deduce the accumulated fatigue damage in situ using the ultrasonic nonlinearity parameter. It was observed that, compared with the decrease in resonant frequency, the ultrasonic nonlinearity parameter shows a greater sensitivity to fatigue damage evolution (i.e. crack initiation and propagation). Ultrasonic nonlinearity parameters obtained from tests conducted under various environmental humidity levels were monitored and analysed. Through changes in the ultrasonic nonlinearity parameter, it was concluded that both of the fatigue crack initiation life and crack propagation life were reduced by increasing the humidity levels.
The multiaxial weld root fatigue of butt welded joints subjected to uniaxial loading
Authors: Khurshid M. , Barsoum Z. , Barsoum I. , Däuwel T. 
Published: April 2016

AbstractIn this study, the fatigue strength of inclined butt welds subjected to a proportional multiaxial stress state generated by uniaxial loading is studied in nominal and local stress concepts. The local methodologies studied included principal stress hypothesis, von Mises stress hypothesis and modified Wöhler curve method. Nominal methodologies included modified Gough–Pollard interaction equation, the design equation in Eurocode3 and the interaction equation in DNV standard. Results are evaluated along with data published in relevant literature. It is observed that both local and nominal stress assessment methods are able to estimate multiaxial fatigue strength. No obvious difference in fatigue strength is observed in the nominal stress concept, but the notch stress concept is able to capture a decrease in fatigue strength in shear‐dominated joints. It is concluded that modified Wöhler curve method is a suitable tool for the evaluation of fatigue strength in joints dominated by both normal and shear stresses.