bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Quality Improvement Intervention to Reduce Necrotizing Enterocolitis in premature infants with Probiotic Supplementation
Authors: Rolnitsky Asaph , Ng Eugene , Asztalos Elizabeth , Shama Yasmin , Karol Dalia , Findlater Carla , Garsch Maren , Dunn Michael 
Published: September 2019

Background:
Necrotizing Enterocolitis (NEC) is a severe intestinal inflammatory disease due to multifactorial causes that present in preterm infants. Compared with similar neonatal intensive care units, our NEC rate was increasing and prompted reduction by a quality improvement (QI) intervention.

Methods:
We aimed to reduce NEC rate by 30% by the end of 2016. We used the Institute of Healthcare Improvement model and typical QI tools, including teamwork, process organizing tools, and evidence-based review, to assist in our selection of supplementation of Lactobacillus reuteri probiotic. We used education, process mapping, process control statistics, and forcing mechanism to implement the changes. In addition to reducing NEC rates, our additional outcome measures were sepsis, mortality, sepsis evaluations, feeding intolerance, growth, days of both antimicrobials, and parenteral nutrition use. Process measures were compliance with probiotics supplementation policy and balancing measures were sepsis rates and feeding intolerance.

Results:
NEC rates decreased from 4.4% to the current 1.7%, and in a pre/post-intervention analysis, the results were significant in all patient subcategories. We did not demonstrate a reduction in mortality. No adverse events occurred. Feeding intolerance episodes and days nil-per-os decreased with no differences in growth at discharge. These results continued over 2 years, and this practice has already spread to several neonatal intensive care units in Ontario, Canada.

Conclusions:
We utilized QI methods and tools to implement a successful practice change of routine probiotic supplementation to reduce NEC rates in preterm infants. We suggest considering this intervention as a successful means to prevent this serious illness.
Novel delivery of cellular therapy to reduce ischaemia reperfusion injury in kidney transplantation
Authors: Thompson Emily R , Bates Lucy , Ibrahim Ibrahim K , Sewpaul Avinash , Stenberg Ben , McNeill Andrew , Figueiredo Rodrigo , Girdlestone Tom , Wilkins Georgina C , Irwin Ellen A , Tingle Samuel J , Scott William E , Lamos Henrique , Mellor Andrew L. , Roobrouck Valerie D. , Ting Anthony E. , Hosgood Sarah A , Nicholson Michael L , Fisher Andrew J , Ali Simi , Sheerin Neil S , Wilson Colin H 
Published: September 2019

AbstractEx-vivo normothermic machine perfusion (NMP) of donor kidneys prior to transplantation provides a platform for direct delivery of cellular therapeutics to optimise organ quality prior to transplantation. Multipotent Adult Progenitor Cells (MAPC®) possess potent immunomodulatory properties which could prove beneficial in minimising subsequent ischaemia reperfusion injury. We investigated the potential reconditioning capability of MAPC cells in kidney NMP.MethodsPairs (5) of human kidneys from the same donor were simultaneously perfused for 7 hours. The right or left kidney was randomly allocated to receive MAPC treatment. Serial samples of perfusate, urine and tissue biopsies were taken for comparison with the control paired kidney.ResultsMAPC-treated kidneys demonstrated improved urine output (p<0.01), decreased expression of the kidney injury biomarker NGAL (p<0.01), improved microvascular perfusion on contrast enhanced ultrasound (cortex p<0.05, medulla p<0.01), downregulation of IL-1β (p<0.05) and upregulation of IL-10 (p<0.05) and Indolamine-2, 3-dioxygenase (p<0.05). A mouse model of intraperitoneal chemotaxis demonstrated decreased neutrophil recruitment when stimulated with perfusate from MAPC-treated kidneys (p<0.01). Immunofluorescence revealed pre-labelled MAPC cells home to the perivascular space in the kidneys during NMP. MAPC therapy was not associated with detrimental physiological or embolic events.ConclusionWe report the first successful delivery of cellular therapy to a kidney during NMP. Kidneys treated with MAPC cells demonstrate improvement in clinically relevant functional parameters and injury biomarkers. This novel method of cell therapy delivery provides an exciting opportunity to recondition organs prior to clinical transplantation.One Sentence SummaryEx-vivo reconditioning of human kidneys using Multipotent Adult Progenitor Cell therapy delivered during normothermic machine perfusion.
Changes in association between school foods and child and adolescent dietary quality during implementation of the Healthy, Hunger-Free Kids Act of 2010
Authors: Berger Aaron T. , Widome Rachel , Erickson Darin J. , Laska Melissa N. , Harnack Lisa J. 
Published: September 2019

AbstractPurposeTo estimate the effect of Healthy, Hunger-Free Kids Act of 2010 (HHFKA) implementation on dietary quality of all US school-aged children and adolescents, and examine whether those effects differed by demographic group.MethodsWe used survey regression on 2007-2016 National Health and Nutrition Examination Survey (NHANES) data to estimate the proportion of energy intake from school foods and the association between school food intake and dietary quality, before and after HHFKA passage/implementation. To account for demographic changes in the US population over time, inverse probability weighting was employed. The product of the proportion of energy from school foods and the association between school food intake and dietary quality estimated the effect of HHFKA implementation on dietary quality.ResultsSchool food intake quantity remained stable during the study period. HHFKA implementation improved students’ dietary quality by 4.3 Healthy Eating Index-2010 (HEI) points (95% CI: 2.5, 6.1) on days when school foods were eaten, and by 1.3 HEI points (95% CI: 0.73, 1.8) averaged over all days annually.ConclusionsHHFKA implementation improved the total dietary quality of US school students. US students would benefit from eating school meals in the post-HHFKA era, and HHFKA regulations should not be relaxed.
Arfgef1 haploinsufficiency in mice alters neuronal endosome composition and decreases membrane surface postsynaptic GABAA receptors
Authors: Teoh JiaJie , Subramanian Narayan , Pero Maria Elena , Bartolini Francesca , Amador Ariadna , Kanber Ayla , Williams Damian , Petri Sabrina , Yang Mu , Allen Andrew S. , Beal Jules , Haut Sheryl R. , Frankel Wayne N. 
Published: September 2019

AbstractARFGEF1 encodes a guanine exchange factor involved in intracellular vesicle trafficking, and is a candidate gene for childhood genetic epilepsies. To model ARFGEF1 haploinsufficiency observed in a recent Lennox Gastaut Syndrome patient, we studied a frameshift mutation (Arfgef1fs) in mice. Arfgef1fs/+ pups exhibit signs of developmental delay, and Arfgef1fs/+ adults have a significantly decreased threshold to induced seizures but do not experience spontaneous seizures. Histologically, the Arfgef1fs/+ brain exhibits a disruption in the apical lining of the dentate gyrus and altered spine morphology of deep layer neurons. In primary hippocampal neuron culture, dendritic surface and synaptic but not total GABAA receptors (GABAAR) are reduced in Arfgef1fs/+ neurons with an accompanying decrease in GABAAR-containing recycling endosomes in cell body. Arfgef1fs/+ neurons also display differences in the relative ratio of Arf6+:Rab11+:TrfR+ recycling endosomes. Although the GABAAR-containing early endosomes in Arfgef1fs/+ neurons are comparable to wildtype, Arfgef1fs/+ neurons show an increase in GABAAR-containing lysosomes in dendrite and cell body. Together, the altered endosome composition and decreased neuronal surface GABAAR results suggests a mechanism whereby impaired neuronal inhibition leads to seizure susceptibility.HighlightsArfgef1fs/+ mice have lower seizure threshold but no spontaneous seizure.Arfgef1fs/+ neurons show reduced dendritic surface GABAAR.Arfgef1fs/+ neurons have decreased GABAAR-containing recycling endosome accompanied with an increase in GABAAR-containing lysosomes.
Causes and consequences of facultative sea crossing in a soaring migrant
Authors: Becciu Paolo , Rotics Shay , Horvitz Nir , Kaatz Michael , Fiedler Wolfgang , Zurell Damaris , Flack Andrea , Jeltsch Florian , Wikelski Martin , Nathan Ran , Sapir Nir 
Published: September 2019

AbstractStudying the causes and consequences of route selection in animal migration is important for understanding the evolution of migratory systems and how they may be affected by environmental factors at various spatial and temporal scales. One key decision during migration is whether to cross “high transport cost” areas, or to circumvent them. Soaring birds may face this choice when encountering waterbodies where convective updrafts are weak or scarce. Crossing these waterbodies requires flying using energetically costly flapping flight, while circumventing them over land permits energetically cheap soaring.We tested how several atmospheric factors (e.g., wind, thermal uplift) and geographic, seasonal and state-related factors (sex and age) affected route selection in migrating white storks (Ciconia ciconia). We used 196 GPS tracks of 70 individuals either crossing or circumventing the north-easternmost section of the Mediterranean Sea, over Iskenderun Bay in southern Turkey.We found that westward and southward winds promoted a cross-bay journey in spring and autumn, respectively, acting as tailwinds. Also, overall weaker winds promoted a sea crossing in spring. Sea crossing was associated with flapping flight and higher values of Overall Dynamic Body Acceleration (ODBA) and resulted in higher ground speed than travel over land.The combined environmental conditions and the effects of route selection on movement-related energy costs and speed were likely responsible for an increase in the time spent flying and distance travelled of migrating storks that decided to cross the bay during spring. Notably, daily travel distances of spring migrants crossing the bay were 60 kilometres longer than those of land-detouring birds, allowing them to reach their destination faster but likely incurring a higher energetic flight cost. No such benefit was found during autumn.Our findings confirm that atmospheric conditions can strongly affect bird route selection. Consequently, migration timing, speed and movement-related energy expenditure differed considerably between the two migratory seasons and the two route choices, highlighting a time-energy trade-off in the migration of white storks.
Alpha Activity Reflects the Magnitude of an Individual Bias in Human Perception
Authors: Grabot Laetitia , Kayser Christoph 
Published: September 2019

AbstractBiases in sensory perception can arise from both experimental manipulations and personal trait-like features. These idiosyncratic biases and their neural underpinnings are often overlooked in studies on the physiology underlying perception. A potential candidate mechanism reflecting such idiosyncratic biases could be spontaneous alpha band activity, a prominent brain rhythm known to influence perceptual reports in general. Using a temporal order judgement task, we here tested the hypothesis that alpha power reflects the overcoming of an idiosyncratic bias. Importantly, to understand the interplay between idiosyncratic biases and contextual (temporary) biases induced by experimental manipulations, we quantified this relation before and after temporal recalibration. Using EEG recordings in human participants (male and female), we find that pre-stimulus frontal alpha power correlates with the tendency to respond relative to an own idiosyncratic bias, with stronger alpha leading to responses matching the bias. In contrast, alpha power does not predict response correctness. These results also hold after temporal recalibration and are specific to the alpha band, suggesting that alpha band activity reflects, directly or indirectly, processes that help to overcome an individual’s momentary bias in perception. We propose that combined with established roles of parietal alpha in the encoding of sensory information frontal alpha reflects complementary mechanisms influencing perceptual decisions.Significance statementThe brain is a biased organ, frequently generating systematically distorted percepts of the world, leading each of us to evolve in our own subjective reality. However, such biases are often overlooked or considered noise when studying the neural mechanisms underlying perception. We show that spontaneous alpha band activity predicts the degree of biasedness of human choices in a time perception task, suggesting that alpha activity indexes processes needed to overcome an individual’s idiosyncratic bias. This result provides a window onto the neural underpinnings of subjective perception, and offers the possibility to quantify or manipulate such priors in future studies.
Density dependence on multiple spatial scales maintains spatial variation in both abundance and traits
Authors: van Benthem Koen J. , Wittmann Meike J. 
Published: September 2019

AbstractPopulation density affects fitness through various processes, such as mate finding and competition. The fitness of individuals in a population can in turn affect its density, making population density a key quantity linking ecological and evolutionary processes. Density effects are, however, rarely homogeneous. Different life-history processes can be affected by density over different spatial scales. In birds, for example, competition for food may depend on the number of birds nesting in the direct vicinity, while competition for nesting sites may occur over larger areas. Here we investigate how the effects of local density and of density in nearby patches can jointly affect the emergence of spatial variation in abundance as well as phenotypic diversification. We study a two-patch model that is described by coupled ordinary differential equations. The patches have no intrinsic differences: they both have the same fitness function that describes how an individual’s fitness depends on density in its own patch as well as the density in the other patch. We use a phase-space analysis, combined with a mathematical stability analysis to study the long-term behaviour of the system. Our results reveal that the mutual effect that the patches have on each other can lead to the emergence and long-term maintenance of a low and a high density patch. We then add traits and mutations to the model and show that different selection pressures in the high and low density patch can lead to diversification between these patches. Via eco-evolutionary feedbacks, this diversification can in turn lead to changes in the long-term population densities: under some parameter settings, both patches reach the same equilibrium density when mutations are absent, but different equilibrium densities when mutations are allowed. We thus show how, even in the absence of differences between patches, interactions between them can lead to differences in long-term population density, and potentially to trait diversification.
Mechanisms of distributed working memory in a large-scale network of macaque neocortex
Authors: Mejias Jorge F. , Wang Xiao-Jing 
Published: September 2019

AbstractTo elucidate the circuit mechanism of persistent neural activity underlying working memory that is distributed across multiple brain regions, we developed an anatomically constrained computational model of large-scale macaque cortex. We found that persistent activity may emerge from inter-areal reverberation, even in a regime where none of the isolated areas is capable of generating persistent activity. The persistent activity pattern along the cortical hierarchy indicates a robust bifurcation in space, characterized by a few association areas near dynamical criticality. A host of spatially distinct attractor states is found, potentially subserving various internal processes. The model yields testable predictions including the idea of counterstream inhibitory bias, and suggests experiments to differentiate local versus distributed mechanisms. Simulated lesion or optogenetic inactivation revealed that distributed activity patterns are resilient while dependent on a structural core. This work provides a theoretical framework for identifying large-scale brain mechanisms and computational principles of distributed cognitive processes.
Benchmarking analysis of deleterious SNP prediction tools on CYP2D6 enzyme
Authors: do Vale Ferreira Karla Cristina , Fialho Leonardo Ferreira , Franco Octávio Luiz , de Alencar Sérgio Amorim , Porto William Farias 
Published: September 2019

AbstractThe cytochrome P450 family is composed of hemeproteins involved in the metabolic transformation of endogenous and exogenous substances. The CYP2D6 enzyme is responsible for the metabolism of approximately 25% of clinically used drugs and is mainly expressed in the liver. The CYP2D6 gene is known to have a large number of Single Nucleotide Polymorphisms (SNPs) and the majority of them do not present clinical consequences. Nevertheless, these variations could modify the CYP2D6 enzyme’s function, resulting in poor metabolizing or ultra-extensive metabolizing phenotypes, when metabolism is slower or accelerated, respectively. Currently, there are several computational tools for predicting functional changes caused by genetic variations. Here, using 20 web servers, we evaluated the impact of 21 missense SNPs (6 neutral and 15 deleterious) previously validated by the literature. Only seven predictors presented sensitivity higher than 70%, while four showed specificity higher than 70% and only one reached the Matthews correlation coefficient of 0.39. Combinations of tools with greater sensitivity and specificity were made to improve the Matthews correlation coefficient, which increased the coefficient of five tools (Provean, FatHMM, SDM, PoPMuSiC and HotMuSiC). The results suggest that the most appropriate tool for CYP2D6 SNP prediction is FATHMM, which could aid in the classification of novel missense SNPs in this gene, providing the identification of mutations potentially associated with drug metabolism.
Mechanical and molecular parameters that influence the tendon differentiation potential of C3H10T1/2 cells in 2D- and 3D-culture systems
Authors: Gaut Ludovic , Bonnin Marie-Ange , Cacciapuoti Isabelle , Orpel Monika , Mericskay Mathias , Duprez Delphine 
Published: September 2019

AbstractOne of the main challenges in tendon field relies in the understanding of regulators of the tendon differentiation program. The optimum culture conditions that favor tendon cell differentiation are not identified. Mesenchymal stem cells present the ability to differentiate into multiple lineages in cultures under different cues ranging from chemical treatment to physical constraints. We analyzed the tendon differentiation potential of C3H10T1/2 cells, a murine cell line of mesenchymal stem cells, upon different 2D- and 3D-culture conditions. We observed that C3H10T1/2 cells cultured in 2D conditions on silicone substrate were more prone to tendon differentiation assessed with the expression of the tendon markersScx, Col1a1andTnmdas compared to cells cultured on plastic substrate. 3D fibrin environment was more favorable forScxandCol1a1expression compared to 2D-cultures. We also identified TGFβ2 as a negative regulator ofTnmdexpression in C3H10T1/2 cells in 2D- and 3D-cultures. Altogether, our results provide us with a better understanding of the culture conditions that promote tendon gene expression and identify mechanical and molecular parameters on which we could play to define the optimum culture conditions that favor tenogenic differentiation in mesenchymal stem cells.
Rest functional brain maturation during the first year of life
Authors: Lemaître Hervé , Augé Pierre , Saitovitch Ana , Vinçon-Leite Alice , Tacchella Jean-Marc , Fillon Ludovic , Calmon Raphael , Dangouloff-Ros Volodia , Lévy Raphaël , Grévent David , Brunelle Francis , Boddaert Nathalie , Zilbovicius Monica 
Published: September 2019

AbstractThe first year of life is a key period of brain development, characterized by dramatic structural and functional modifications. Here, we measured rest cerebral blood flow (CBF) modifications throughout babies’ first year of life using arterial spin labeling magnetic resonance imaging sequence in 52 infants, from 3 to 12 months of age. Overall, global rest CBF significantly increased during this age span. In addition, we found marked regional differences in local functional brain maturation. While primary sensorimotor cortices and insula showed early maturation, temporal and prefrontal region presented great rest CBF increase across the first year of life. Moreover, we highlighted a late and remarkably synchronous maturation of the prefrontal and posterior superior temporal cortices. These different patterns of regional cortical rest CBF modifications reflect a timetable of local functional brain maturation and are consistent with baby’s cognitive development within the first year of life.
Maternal care of heterozygous Dopamine Receptor D4 knockout mice: Differential susceptibility to early-life rearing conditions
Authors: Knop Jelle , van IJzendoorn Marinus H. , Bakermans-Kranenburg Marian J. , Joëls Marian , van der Veen Rixt 
Published: September 2019

AbstractThe differential susceptibility hypothesis proposes that individuals who are more susceptible to the negative effects of adverse rearing conditions may also benefit more from enriched environments. Evidence derived from human experiments suggests the lower efficacy dopamine receptor D4 (DRD4) 7-repeat as a main factor in exhibiting these for better and for worse characteristics. However, human studies lack the genetic and environmental control offered by animal experiments, complicating assessment of causal relations. To study differential susceptibility in an animal model, we exposed Drd4+/- mice and control litter mates to a limited nesting/bedding (LN), standard nesting (SN) or communal nesting (CN) rearing environment from postnatal day (P) 2-14. Puberty onset was examined from P24-P36 and adult females were assessed on maternal care towards their own offspring. In both males and females, LN reared mice showed a delay in puberty onset that was partly mediated by a reduction in body weight at weaning, irrespective of Drd4 genotype. During adulthood, LN reared females exhibited characteristics of poor maternal care, whereas dams reared in CN environments showed lower rates of unpredictability towards their own offspring. Differential susceptibility was observed only for licking/grooming levels of female offspring towards their litter; LN reared Drd4+/- mice exhibited the lowest and CN reared Drd4+/- mice the highest levels of licking/grooming. These results indicate that both genetic and early-environmental factors play an important role in shaping maternal care of the offspring for better and for worse.