bluuebunny/crossref_metadata_2025_split huggingface dataset:
Amiloride Analogs as ASIC1a Inhibitors
Authors: Leng Tian‐Dong , Si Hong‐Fang , Li Jun , Yang Tao , Zhu Mengyuan , Wang Binghe , Simon Roger P. , Xiong Zhi‐Gang 
Published: February 2016

SummaryBackgroundASIC1a, the predominant acid‐sensing ion channels (ASICs), is implicated in neurological disorders including stroke, traumatic spinal cord injury, and ALS. Potent ASIC1a inhibitors should have promising therapeutic potential for ASIC1a‐related diseases.AimsWe examined the inhibitory effects of a number of amiloride analogs on ASIC1a currents, aimed at understanding the structure–activity relationship and identifying potent ASIC1a inhibitors for stroke intervention.MethodsWhole‐cell patch‐clamp techniques and a mouse model of middle cerebral artery occlusion (MCAO)‐induced focal ischemia were used. Surflex‐Dock was used to dock the analogs into the pocket with default parameters.ResultsAmiloride and its analogs inhibit ASIC1a currents expressed in Chinese hamster ovary cells with a potency rank order of benzamil > phenamil > 5‐(N,N‐dimethyl)amiloride (DMA) > amiloride > 5‐(N,N‐hexamethylene)amiloride (HMA) ≥ 5‐(N‐methyl‐N‐isopropyl)amiloride (MIA) > 5‐(N‐ethyl‐N‐isopropyl)amiloride (EIPA). In addition, amiloride and its analogs inhibit ASIC currents in cortical neurons with the same potency rank order. In mice, benzamil and EIPA decreased MCAO‐induced infarct volume. Similar to its effect on the ASIC current, benzamil showed a much higher potency than EIPA.ConclusionAddition of a benzyl group to the terminal guanidinyl group resulted in enhanced inhibitory activity on ASIC1a. On the other hand, the bulky groups added to the 5‐amino residues slightly decreased the activity. Among the tested amiloride analogs, benzamil is the most potent ASIC1a inhibitor.
Spinal Cord Stimulation and Augmentative Control Strategies for Leg Movement after Spinal Paralysis in Humans
Authors: Minassian Karen , Hofstoetter Ursula S. 
Published: February 2016

SummarySevere spinal cord injury is a devastating condition, tearing apart long white matter tracts and causing paralysis and disability of body functions below the lesion. But caudal to most injuries, the majority of neurons forming the distributed propriospinal system, the localized gray matter spinal interneuronal circuitry, and spinal motoneuron populations are spared. Epidural spinal cord stimulation can gain access to this neural circuitry. This review focuses on the capability of the human lumbar spinal cord to generate stereotyped motor output underlying standing and stepping, as well as full weight‐bearing standing and rhythmic muscle activation during assisted treadmill stepping in paralyzed individuals in response to spinal cord stimulation. By enhancing the excitability state of the spinal circuitry, the stimulation can have an enabling effect upon otherwise “silent” translesional volitional motor control. Strategies for achieving functional movement in patients with severe injuries based on minimal translesional intentional control, task‐specific proprioceptive feedback, and next‐generation spinal cord stimulation systems will be reviewed. The role of spinal cord stimulation can go well beyond the immediate generation of motor output. With recently developed training paradigms, it can become a major rehabilitation approach in spinal cord injury for augmenting and steering trans‐ and sublesional plasticity for lasting therapeutic benefits.
Metonymy as Referential Dependency: Psycholinguistic and Neurolinguistic Arguments for a Unified Linguistic Treatment
Authors: Piñango Maria M. , Zhang Muye , Foster‐Hanson Emily , Negishi Michiro , Lacadie Cheryl , Constable R. Todd 
Published: February 2016

AbstractWe examine metonymy at psycho‐ and neurolinguistic levels, seeking to adjudicate between two possible processing implementations (one‐ vs. two‐mechanism). We compare highly conventionalized systematic metonymy (producer‐for‐product: “All freshmen read O'Connell”) to lesser‐conventionalized circumstantial metonymy (“[a waitress says to another:] ‘Table 2 asked for more coffee.”’). Whereas these two metonymy types differ in terms of contextual demands, they each reveal a similar dependency between the named and intended conceptual entities (e.g., Jackendoff, 1997; Nunberg, 1979, 1995). We reason that if each metonymy yields a distinct processing time course and substantially non‐overlapping preferential localization pattern, it would not only support a two‐mechanism view (one lexical, one pragmatic) but would suggest that conventionalization acts as a linguistic categorizer. By contrast, a similar behavior in time course and localization would support a one‐mechanism view and the inference that conventionalization acts instead as a modulator of contextual felicitousness, and that differences in interpretation introduced by conventionalization are of degree, not of kind. Results from three paradigms: self‐paced reading (SPR), event‐related potentials (ERP), and functional magnetic resonance imaging (fMRI), reveal the following: no main effect by condition (metonymy vs. matched literal control) for either metonymy type immediately after the metonymy trigger, and a main effect for only the Circumstantial metonymy one word post‐trigger (SPR); a N400 effect across metonymy types and a late positivity for Circumstantial metonymy (ERP); and a highly overlapping activation connecting the left ventrolateral prefrontal cortex and the left dorsolateral prefrontal cortex (fMRI). Altogether, the pattern observed does not reach the threshold required to justify a two‐mechanism system. Instead, the pattern is more naturally (and conservatively) understood as resulting from the implementation of a generalized referential dependency mechanism, modulated by degree of context dependence/conventionalization, thus supporting architectures of language whereby “lexical” and “pragmatic” meaning relations are encoded along a cline of contextual underspecification.
Information‐Theoretic Measures Predict the Human Judgment of Rhythm Complexity
Authors: de Fleurian Remi , Blackwell Tim , Ben‐Tal Oded , Müllensiefen Daniel 
Published: February 2016

AbstractTo formalize the human judgment of rhythm complexity, we used five measures from information theory and algorithmic complexity to measure the complexity of 48 artificially generated rhythmic sequences. We compared these measurements to human prediction accuracy and easiness judgments obtained from a listening experiment, in which 32 participants guessed the last beat of each sequence. We also investigated the modulating effects of musical expertise and general pattern identification ability. Entropy rate and Kolmogorov complexity were correlated with prediction accuracy, and highly correlated with easiness judgments. A logistic regression showed main effects of musical training, entropy rate, and Kolmogorov complexity, and an interaction between musical training and both entropy rate and Kolmogorov complexity. These results indicate that information‐theoretic concepts capture some salient features of the human judgment of rhythm complexity, and they confirm the influence of musical expertise on complexity judgments.
Mapping the impact of alien species on marine ecosystems: the Mediterranean Sea case study
Authors: Katsanevakis Stelios , Tempera Fernando , Teixeira Heliana 
Published: February 2016

AbstractAimTo develop a standardized, quantitative method for mapping cumulative impacts of invasive alien species on marine ecosystems.LocationThe methodology is applied in the Mediterranean Sea but is widely applicable.MethodsA conservative additive model was developed to account for the Cumulative IMPacts of invasive ALien species (CIMPAL) on marine ecosystems. According to this model, cumulative impact scores are estimated on the basis of the distributions of invasive species and ecosystems, and both the reported magnitude of ecological impacts and the strength of such evidence. In the Mediterranean Sea case study, the magnitude of impact was estimated for every combination of 60 invasive species and 13 habitats, for every 10 × 10 km cell of the basin. Invasive species were ranked based on their contribution to the cumulative impact score across the Mediterranean.ResultsThe CIMPAL index showed strong spatial heterogeneity. Spatial patterns varied depending on the pathway of initial introduction of the invasive species in the Mediterranean Sea. Species introduced by shipping gave the highest impact scores and impacted a much larger area than those introduced by aquaculture and the Suez Canal. Overall, invasive macroalgae had the highest impact among all taxonomic groups. These results represent the current best estimate of the spatial variation in impacts of invasive alien species on ecosystems, in the Mediterranean Sea.Main ConclusionsA framework for mapping cumulative impacts of invasive alien species was developed. The application of this framework in the Mediterranean Sea provided a baseline that can be built upon with future improved information. Such analysis allows the identification of hotspots of highly impacted areas, and prioritization of sites, pathways and species for management actions.
Clinical characteristics and neurodevelopmental outcomes of children with tuberculous meningitis and hydrocephalus
Authors: Rohlwink Ursula K , Donald Kirsty , Gavine Bronwyn , Padayachy Llewellyn , Wilmshurst Jo M , Fieggen Graham A , Figaji Anthony A 
Published: February 2016

AimTuberculous meningitis (TBM) is a lethal and commonly occurring form of extra‐pulmonary tuberculosis in children, often complicated by hydrocephalus which worsens outcome. Despite high mortality and morbidity, little data on the impact on neurodevelopment exists. We examined the clinical characteristics, and clinical and neurodevelopmental outcomes of TBM and hydrocephalus.MethodDemographic and clinical data (laboratory and radiological findings) were prospectively collected on children treated for probable and definite TBM with hydrocephalus. At 6 months, clinical outcome was assessed using the Paediatric Cerebral Performance Category Scale and neurodevelopmental outcome was assessed with the Griffiths Mental Development Scale – Extended Version.ResultsForty‐four patients (median age 3y 3mo, range 3mo–13y 1mo, [SD 3y 5mo]) were enrolled. The mortality rate was 16%, three patients (6.8%) were in a persistent vegetative state, two were severely disabled (4.5%), and 11 (25%) suffered mild–moderate disability. All cases demonstrated neurodevelopmental deficits relative to controls. Multiple or large infarcts were prognostic of poor outcome.InterpretationNeurological and neurodevelopmental deficits are common after paediatric TBM with hydrocephalus, and appear to be related to ongoing cerebral ischaemia and consequent infarction. The impact of TBM on these children is multidimensional and presents short‐ and long‐term challenges.
Effect of chenodeoxycholic acid and the bile acid sequestrant colesevelam on glucagon‐like peptide‐1 secretion
Authors: Hansen M. , Scheltema M. J. , Sonne D. P. , Hansen J. S. , Sperling M. , Rehfeld J. F. , Holst J. J. , Vilsbøll T. , Knop F. K. 
Published: February 2016

AimTo evaluate the effects of the primary human bile acid, chenodeoxycholic acid (CDCA), and the bile acid sequestrant (BAS) colesevelam, instilled into the stomach, on plasma levels of glucagon‐like peptide‐1 (GLP‐1), glucose‐dependent insulinotropic polypeptide, glucose, insulin, C‐peptide, glucagon, cholecystokinin and gastrin, as well as on gastric emptying, gallbladder volume, appetite and food intake.MethodsOn four separate days, nine patients with type 2 diabetes, and 10 matched healthy control subjects received bolus instillations of (i) CDCA, (ii) colesevelam, (iii) CDCA + colesevelam or (iv) placebo. At baseline and for 180 min after instillation, blood was sampled.ResultsIn both the type 2 diabetes group and the healthy control group, CDCA elicited an increase in GLP‐1 levels compared with colesevelam, CDCA + colesevelam and placebo, respectively (p < 0.05). The interventions did not affect plasma glucose, insulin or C‐peptide concentrations in any of the groups. CDCA elicited a small increase in plasma insulin : glucose ratio compared with colesevelam, CDCA + colesevelam and placebo in both groups. Compared with colesevelam, CDCA + colesevelam and placebo, respectively, CDCA increased glucagon and delayed gastric emptying in both groups.ConclusionsCDCA increased GLP‐1 and glucagon secretion, and delayed gastric emptying. We speculate that bile acid‐induced activation of TGR5 on L cells increases GLP‐1 secretion, which, in turn, may result in amplification of glucose‐stimulated insulin secretion. Furthermore our data suggest that colesevelam does not have an acute effect on GLP‐1 secretion in humans.
Opening the Black Box of Developmental Experiments: Behavioural Mechanisms Underlying Long‐Term Effects of Early Social Experience
Authors: Taborsky Barbara 
Published: February 2016

AbstractTypically, animals spend a considerable portion of their time with social interactions involving mates, offspring, competitors and group members. The social performance during these interactions can strongly depend on the social environment individuals have experienced early in life. Despite a considerable number of experiments investigating long‐term effects of the early social environment, our understanding of the behavioural mechanisms mediating these effects is still limited, mainly for two reasons. (1) Only in few experimental studies have researchers actually observed and quantified the behaviour of their study animals during the social treatment. (2) Even if differences in social interactions between social rearing treatments are reported, these differences might not be causally linked to any observed long‐term effects later in life. The aim of this review was to investigate whether behavioural records of animals during the experimental manipulation of their social environment can help (1) identifying behavioural mechanisms involved in a long‐term effect and (2) obtaining a better understanding of the long‐term consequences of early manipulations. First, I review studies that manipulated the social environment at an early stage of the ontogeny, observed the social interactions and behaviour during the social experience phase and subsequently tested the performance in social and non‐social behavioural tasks at a later life stage. In all reviewed studies, treatment differences were reported both in social interactions during the social experience phase and in social and/or non‐social behaviours later in life. Second, I discuss four classes of behavioural mechanisms that can cause the reported long‐term effects of social experience, namely learning by experience, social learning, sensory stimulation and social cueing. I conclude that social interactions during the social experience phase should always be recorded for at least two reasons. Knowledge about how the social interactions differ between rearing treatments (1) permits researchers to formulate hypotheses about candidate mechanisms causing long‐term effects on behaviour and (2) can help to interpret unexpected outcomes of developmental experiments. Finally, I propose that as a crucial ultimate step towards understanding effects of the early social environment, we should develop targeted experiments testing for the causality of identified candidate mechanism.
Evaluation of a wireless activity monitoring system to quantify locomotor activity in horses in experimental settings
Authors: Fries M. , Montavon S. , Spadavecchia C. , Levionnois O. L. 
Published: February 2016

SummaryReasons for performing studyMethods of evaluating locomotor activity can be useful in efforts to quantify behavioural activity in horses objectively.ObjectivesTo evaluate whether an accelerometric device would be adequate to quantify locomotor activity and step frequency in horses, and to distinguish between different levels of activity and different gaits.Study designObservational study in an experimental setting.MethodsDual‐mode (activity and step count) piezo–electric accelerometric devices were placed at each of 4 locations (head, withers, forelimb and hindlimb) in each of 6 horses performing different controlled activities including grazing, walking at different speeds, trotting and cantering. Both the activity count and step count were recorded and compared by the various activities. Statistical analyses included analysis of variance for repeated measures, receiver operating characteristic curves, Bland–Altman analysis and linear regression.ResultsThe accelerometric device was able to quantify locomotor activity at each of the 4 locations investigated and to distinguish between gaits and speeds. The activity count recorded by the accelerometer placed on the hindlimb was the most accurate, displaying a clear discrimination between the different levels of activity and a linear correlation to speed. The accelerometer placed on the head was the only one to distinguish specifically grazing behaviour from standing. The accelerometer placed on the withers was unable to differentiate different gaits and activity levels. The step count function measured at the hindlimb was reliable but the count was doubled at the walk.ConclusionsThe dual‐mode accelerometric device was sufficiently accurate to quantify and compare locomotor activity in horses moving at different speeds and gaits. Positioning the device on the hindlimb allowed for the most accurate results. The step count function can be useful but must be manually corrected, especially at the walk.
Detecting signatures of competition from observational data: a combined approach using DNA barcoding, diversity partitioning and checkerboards at small spatial scales
Authors: Bringloe Trevor T. , Adamowicz Sarah J. , Harvey Vivian F. I. , Jackson John K. , Cottenie Karl 
Published: February 2016

Summary

Competitive interactions are assumed to play a role in governing species distributions but are difficult to infer using observational data. In addition, morphological identification may overlook species, obscuring patterns of competitive exclusion. To address these limitations, we showcase a molecular (DNA barcoding) approach to species‐unit delineation and sample stream insect communities at small spatial scales where environmental filtering and dispersal limitations are minimised.

Rocks from riffles were sampled for stream insects, in particular caddisfly (Trichoptera), beetle (Coleoptera) and blackfly (Simuliidae) larvae from filterer and grazer guilds at White Clay Creek, Pennsylvania, U.S.A. (20 June, 2013). Additive partitioning of species diversity was used to establish at which spatial scale(s) variation in the distribution of species occurs; this informed us of the spatial scale at which to conduct checkerboard analyses, which tested for signatures of species segregations (e.g. competitive exclusion).

Only a small portion of the total species diversity occurred at the smallest spatial level (mean = 30% on individual rocks). Distributional variation in species was greatest at the kilometre scale (where beta‐diversity was 37% and 41% for filterers and grazers respectively). At the scale of White Clay Creek sampled (c. 3 km extent), species of filterers showed a strong tendency to segregate on individual rocks, while grazers showed random structure approaching aggregation.

This study demonstrates a potential approach to assessing the role of competition in structuring communities using observational data and highlights the importance of accurate species units for analysis (e.g. DNA barcoding). Using a combination of analyses, we were able to link patterns of segregation to competitive interactions among stream insect species in a filterer guild, while determining these interactions were not important in a grazer guild.
Patient involvement in the development of patient‐reported outcome measures: a scoping review
Authors: Wiering Bianca , de Boer Dolf , Delnoij Diana 
Published: February 2016

AbstractBackgroundPatient‐reported outcome measures (PROMs) measure patients’ perspectives on health outcomes and are increasingly used in health care. To capture the patient's perspective, it is essential that patients are involved inPROMdevelopmentObjectiveThis article reviews in what ways and to what extent patients are involved inPROMdevelopment and whether patient involvement has increased over time.Search strategyLiterature was searched inPubMed,EMBASE,MEDLINEand the Cochrane Methodology Register.Inclusion criteriaStudies were included if they described a newPROMdevelopment.Data extractionBasic information and information regarding patient involvement in development phases was recorded.Main resultsA total of 189 studies, describing the development of 193PROMs, were included. MostPROMs were meant for chronic disease patients (n= 59) and measured quality of life (n= 28). In 25.9% of thePROMdevelopment studies, no patients were involved. Patients were mostly involved during item development (58.5%), closely followed by testing for comprehensibility (50.8%), while patient involvement in determining which outcome to measure was minimal (10.9%). Some patient involvement took place in the development of mostPROMs, but in only 6.7% patients were involved in all aspects of the development. Patient involvement did not increase with time.ConclusionsAlthough patient involvement inPROMdevelopment is essential to develop valid patient‐centredPROMs, patients are not always involved. When patients are involved, their level of involvement varies considerably. These variations suggest that further attention to building and/or disseminating consensus on requirements for patient involvement inPROMdevelopment is necessary.
Infection‐related and ‐unrelated malignancies, HIV and the aging population
Authors: Shepherd L , Borges ÁH , Ledergerber B , Domingo P , Castagna A , Rockstroh J , Knysz B , Tomazic J , Karpov I , Kirk O , Lundgren J , Mocroft A ,   EuroSIDA in EuroCOORD
Published: February 2016

ObjectivesHIV‐positive people have increased risk of infection‐related malignancies (IRMs) and infection‐unrelated malignancies (IURMs). The aim of the study was to determine the impact of aging on future IRM and IURM incidence.MethodsPeople enrolled in EuroSIDA and followed from the latest of the first visit or 1 January 2001 until the last visit or death were included in the study. Poisson regression was used to investigate the impact of aging on the incidence of IRMs and IURMs, adjusting for demographic, clinical and laboratory confounders. Linear exponential smoothing models forecasted future incidence.ResultsA total of 15 648 people contributed 95 033 person‐years of follow‐up, of whom 610 developed 643 malignancies [IRMs: 388 (60%); IURMs: 255 (40%)]. After adjustment, a higher IRM incidence was associated with a lower CD4 count [adjusted incidence rate ratio (aIRR) CD4 count < 200 cells/μL: 3.77; 95% confidence interval (CI) 2.59, 5.51; compared with ≥ 500 cells/μL], independent of age, while a CD4 count < 200 cells/μL was associated with IURMs in people aged < 50 years only (aIRR: 2.51; 95% CI 1.40–4.54). Smoking was associated with IURMs (aIRR: 1.75; 95% CI 1.23, 2.49) compared with never smokers in people aged ≥ 50 years only, and not with IRMs. The incidences of both IURMs and IRMs increased with older age. It was projected that the incidence of IRMs would decrease by 29% over a 5‐year period from 3.1 (95% CI 1.5–5.9) per 1000 person‐years in 2011, whereas the IURM incidence would increase by 44% from 4.1 (95% CI 2.2–7.2) per 1000 person‐years over the same period.ConclusionsDemographic and HIV‐related risk factors for IURMs (aging and smoking) and IRMs (immunodeficiency and ongoing viral replication) differ markedly and the contribution from IURMs relative to IRMs will continue to increase as a result of aging of the HIV‐infected population, high smoking and lung cancer prevalence and a low prevalence of untreated HIV infection. These findings suggest the need for targeted preventive measures and evaluation of the cost−benefit of screening for IURMs in HIV‐infected populations.