bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimizing Participation of Older Adults with Cognitive Deficits Post-stroke: Types of Help and Caregiver Burden
Authors: Viscogliosi Chantal , Desrosiers Johanne , Belleville Sylvie 
Published: February 2019

RÉSUMÉCette étude a examiné les types d’aide fournis par des proches aidants qui visaient à optimiser la participation de personnes aînées ayant des déficits cognitifs (personnes aidées) consécutifs à un accident vasculaire cérébral (AVC), et la façon dont ces types d’aide différaient selon le niveau de fardeau des proches aidants. Un devis longitudinal mixte a été utilisé. Douze proches aidants d’aînés ayant subi un AVC ont complété un questionnaire sur le fardeau du proche aidant et ont participé à des entrevues semi-structurées qui ont été réalisées trois semaines, trois mois et six mois suivant le congé de l’hôpital (soins aigus), de l’unité de réadaptation fonctionnelle intensive ou de l’hôpital de jour. Les personnes aidées ont passé des tests cognitifs et ont rempli un questionnaire sur la participation sociale. Les types d’aide fournis par les proches aidants ont différé selon la quantité d’aide apportée, selon le niveau de préoccupation associé au bien-être de la personne aidée et selon l’impact sur la vie sociale du proche aidant. Il est intéressant de constater que les types d’aide favorisant la participation, l’estime de soi et le maintien des capacités n’étaient pas associés à un impact négatif sur la vie sociale des proches aidants. Une meilleure compréhension des relations entre les différents types d’aide et le fardeau des proches aidants permettrait d’optimiser le soutien fourni pour la participation sociale d’aînés ayant subi un AVC sans augmenter le fardeau de leurs proches aidants.
Resident-Level Factors Associated with Hospitalization Rates for Newly Admitted Long-Term Care Residents in Canada: A Retrospective Cohort Study
Authors: McArthur Caitlin , Rostami Mehdi , Saarela Olli , Suria Mohammad Owais , Feng Cindy , Berg Katherine 
Published: February 2019

RÉSUMÉChez les résidents en soins de longue durée (SLD), l’hospitalisation peut amener des complications telles que le déclin fonctionnel. L’objectif de notre étude était d’examiner l’association entre les données démographiques et de santé et le taux d’hospitalisation des résidents nouvellement admis en SLD. Nous avons mené une étude de cohorte rétrospective incluant tous les centres de SLD de six provinces et d’un territoire du Canada, à l’aide des données de la RAI-MDS 2.0 et de la Discharge Abstract Database. Nous avons inclus les résidents nouvellement admis ayant eu une évaluation entre le 1er janvier et le 31 décembre 2013 (n = 37 998). Les résidents de sexe masculin avec une santé plus instable et une déficience fonctionnelle de modérée à grave présentaient des taux d’hospitalisation plus élevés, tandis que les résidents avec une déficience cognitive de modérée à grave avaient des taux moindres. Les résultats de notre étude pourraient contribuer à l’identification des résidents nouvellement admis qui seraient plus à risque d’hospitalisation et à l’élaboration de stratégies préventives plus ciblées, incluant la réadaptation, la planification préalable de soins, les soins palliatifs et les services gériatriques spécialisés.
Quantifying Uncertainty from Mass-Peak Overlaps in Atom Probe Microscopy
Authors: London Andrew J. 
Published: February 2019

AbstractThere are many sources of random and systematic error in composition quantification by atom probe microscopy, often, however, only statistical error is reported. Significantly larger errors can occur from the misidentification of ions and overlaps or interferences of peaks in the mass spectrum. These overlaps can be solved using maximum likelihood estimation (MLE), improving the accuracy of the result, but with an unknown effect on the precision. An analytical expression for the uncertainty of the MLE solution is presented and it is demonstrated to be much more accurate than the existing methods. In one example, the commonly used error estimate was five times too small.Literature results containing overlaps most likely underestimate composition uncertainty because of the complexity of correctly dealing with stochastic effects and error propagation. The uncertainty depends on the amount of overlapped intensity, for example being ten times worse for the CO/Fe overlap than the Cr/Fe overlap. Using the methods described here, accurate estimation of error, and the minimization of this could be achieved, providing a key milestone in quantitative atom probe. Accurate estimation of the composition uncertainty in the presence of overlaps is crucial for planning experiments and scientific interpretation of the measurements.
Fraction-specific post-treatment quality assurance for active breath-hold radiation therapy
Authors: Thiyagarajan Rajesh , Nambiraj Arunai , Manigandan Durai , Singaravelu Tamilseivan , Selvaraj Rajesh , Kataria Tejinder 
Published: February 2019

AbstractPurposeThe purpose of this study is to evaluate variation in the treatment hold pattern and quantify its dosimetric impact in breath-hold radiotherapy, using fraction-specific post-treatment quality assurance.Material and MethodsA patient with lung mets treated using intensity-modulated radiation therapy (IMRT) with active breath coordinator (ABC) was recruited for the study. Treatment beam hold conditions were recorded for all the 25 fractions. The linearity and reproducibility of the dosimetric system were measured. Variation in the dose output of unmodulated open beam with beam hold was studied. Patient-specific quality assurance (PSQA) was performed with and without beam hold, and the results were compared to quantify the dosimetric impact of beam hold.ResultsThere was a considerable amount of variation observed in the number of beam hold for the given field and the monitor unit at which the beam held. Linearity and reproducibility of the dosimetric system were found within the acceptable limits. The average difference over the 25 measurements was 0·044% (0·557 to −0·318%) with standard deviation of 0·248.ConclusionPatient comfort with the ABC system and responsiveness to the therapist communication help to maintain consistent breathing pattern, in turn consistent treatment delivery pattern. However, the magnitude of dosimetric error is much less than the acceptable limits recommended by IROC. The dosimetric error induced by the beam hold is over and above the dose difference observed in conventional PSQA.
Cross‐Shock Potential in Rippled Versus Planar Quasi‐Perpendicular Shocks Observed by MMS
Authors: Hanson E. L. M. , Agapitov O. V. , Mozer F. S. , Krasnoselskikh V. , Bale S. D. , Avanov L. , Khotyaintsev Y. , Giles B. 
Published: February 2019

AbstractThe unprecedented detail of measurements by the four Magnetospheric Multiscale (MMS) spacecraft enable deeper investigation of quasi‐perpendicular collisionless shocks. We compare shock normals, planarities, and Normal Incidence Frame cross‐shock potentials determined from electric field measurements and proxies, for a subcritical interplanetary shock and a supercritical bow shock. The subcritical shock's cross‐shock potential was 26±6 V. The shock scale was 33 km, too short to allow comparison with proxies from ion moments. Proxies from electron moments provided potential estimates of 40±5 V. Shock normals from magnetic field minimum variance analysis were nearly identical, indicating a planar front. The supercritical shock's cross‐shock potential was estimated to be from 290 to 440 V from the different spacecraft measurements, with shock scale 120 km. Reflected ions contaminated the ion‐based proxies upstream, whereas electron‐based proxies yielded reasonable estimates of 250±50 V. Shock normals from electric field maximum variance analysis differed, indicating a rippled front.
Desert Dust, Industrialization, and Agricultural Fires: Health Impacts of Outdoor Air Pollution in Africa
Authors: Bauer Susanne E. , Im Ulas , Mezuman Keren , Gao Chloe Y. 
Published: February 2019

AbstractThe African continent continuously experiences extreme aerosol load conditions, during which the World Health Organization clean air standard of 10 μg/m3 of PM2.5 mass is systematically exceeded. Africa holds the world largest source of desert dust emissions, undergoes strong industrial growth, and produces approximately a third of the Earth's biomass burning aerosol particles. Sub‐Saharan biomass burning is driven by agricultural practices, such as burning fields and bushes in the postharvest season for fertilization, land management, and pest control. Thus, these emissions are predominantly anthropogenic. Here we use global atmospheric composition, climate, and health models to simulate the chemical composition of the atmosphere and calculate the mortality rates for Africa by distinguishing between purely natural, industrial/domestic, and biomass burning emissions. Air quality‐related deaths in Africa rank within the top leading causes of death in Africa. Our results of ~780,000 premature deaths annually point to the extensive health impacts of natural emissions, high mortality rate caused by industrialization in Nigeria and South Africa, and a smaller extent by fire emissions in Central and West Africa. In Africa, 43,000 premature deaths are linked to biomass burning mainly driven by agriculture. Our results also show that natural sources, in particular windblown dust emissions, have large impacts on air quality and human health in Africa.
Dexmedetomidine inhibits astrocyte pyroptosis and subsequently protects the brain in in vitro and in vivo models of sepsis
Authors: Sun Yi-Bing , Zhao Hailin , Mu Dong-Liang , Zhang Wenwen , Cui Jiang , Wu Lingzhi , Alam Azeem , Wang Dong-Xin , Ma Daqing 
Published: February 2019

AbstractSepsis is life-threatening and often leads to acute brain damage. Dexmedetomidine, an α2-adrenoceptor agonist, has been reported to possess neuroprotective effects against various brain injury but underlying mechanisms remain elusive. In this study, in vitro and in vivo models of sepsis were used to explore the effects of dexmedetomidine on the inflammasome activity and its associated glia pyroptosis and neuronal death. In vitro, inflammasome activation and pyroptosis were found in astrocytes following lipopolysaccharide (LPS) exposure. Dexmedetomidine significantly alleviated astrocyte pyroptosis and inhibited histone release induced by LPS. In vivo, LPS treatment in rats promoted caspase-1 immunoreactivity in astrocytes and caused an increase in the release of pro-inflammatory cytokines of IL-1β and IL-18, resulting in neuronal injury, which was attenuated by dexmedetomidine; this neuroprotective effect was abolished by α2-adrenoceptor antagonist atipamezole. Dexmedetomidine significantly reduced the high mortality rate caused by LPS challenge. Our data demonstrated that dexmedetomidine may protect glia cells via reducing pyroptosis and subsequently protect neurons, all of which may preserve brain function and ultimately improve the outcome in sepsis.
PD-1-siRNA delivered by attenuated Salmonella enhances the antimelanoma effect of pimozide
Authors: Zhao Tiesuo , Wei Tian , Guo Jing , Wang Yangeng , Shi Xiangyi , Guo Sheng , Jia Xiaolong , Jia Huijie , Feng Zhiwei 
Published: February 2019

AbstractMelanoma is one of the most aggressive skin cancers worldwide. Although there has been much effort toward improving treatment options over the past few years, there remains an urgent need for effective therapy. Immunotherapy combined with chemotherapy has shown great promise in clinical trials. Here, we studied the cooperative effects of the small molecule drug pimozide, which has a therapeutic effect in melanoma, and RNA interference (RNAi) targeting PD-1, an important immune checkpoint molecule involved in tumor immune escape. PD-1 siRNA was delivered by attenuated Salmonella to melanoma-bearing mice in combination with pimozide. Our results demonstrated that the combination therapy had the optimal therapeutic effect on melanoma. The mechanisms underlying the efficacy involved the induction of apoptosis and an enhanced immune response. This study suggests that immunotherapy based on PD-1 inhibition combined with anticancer drugs could be a promising clinical strategy for the treatment of melanoma.
Engineered transfer RNAs for suppression of premature termination codons
Authors: Lueck John D. , Yoon Jae Seok , Perales-Puchalt Alfredo , Mackey Adam L. , Infield Daniel T. , Behlke Mark A. , Pope Marshall R. , Weiner David B. , Skach William R. , McCray Paul B. , Ahern Christopher A. 
Published: February 2019

AbstractPremature termination codons (PTCs) are responsible for 10–15% of all inherited disease. PTC suppression during translation offers a promising approach to treat a variety of genetic disorders, yet small molecules that promote PTC read-through have yielded mixed performance in clinical trials. Here we present a high-throughput, cell-based assay to identify anticodon engineered transfer RNAs (ACE-tRNA) which can effectively suppress in-frame PTCs and faithfully encode their cognate amino acid. In total, we identify ACE-tRNA with a high degree of suppression activity targeting the most common human disease-causing nonsense codons. Genome-wide transcriptome ribosome profiling of cells expressing ACE-tRNA at levels which repair PTC indicate that there are limited interactions with translation termination codons. These ACE-tRNAs display high suppression potency in mammalian cells, Xenopus oocytes and mice in vivo, producing PTC repair in multiple genes, including disease causing mutations within cystic fibrosis transmembrane conductance regulator (CFTR).
Underpinning heterogeneity in synaptic transmission by presynaptic ensembles of distinct morphological modules
Authors: Fekete Adam , Nakamura Yukihiro , Yang Yi-Mei , Herlitze Stefan , Mark Melanie D. , DiGregorio David A. , Wang Lu-Yang 
Published: February 2019

AbstractSynaptic heterogeneity is widely observed but its underpinnings remain elusive. We addressed this issue using mature calyx of Held synapses whose numbers of bouton-like swellings on stalks of the nerve terminals inversely correlate with release probability (Pr). We examined presynaptic Ca2+ currents and transients, topology of fluorescently tagged knock-in Ca2+ channels, and Ca2+ channel-synaptic vesicle (SV) coupling distance using Ca2+ chelator and inhibitor of septin cytomatrix in morphologically diverse synapses. We found that larger clusters of Ca2+ channels with tighter coupling distance to SVs elevate Pr in stalks, while smaller clusters with looser coupling distance lower Pr in swellings. Septin is a molecular determinant of the differences in coupling distance. Supported by numerical simulations, we propose that varying the ensemble of two morphological modules containing distinct Ca2+ channel-SV topographies diversifies Pr in the terminal, thereby establishing a morpho-functional continuum that expands the coding capacity within a single synapse population.
C. elegans collectively forms dynamical networks
Authors: Sugi Takuma , Ito Hiroshi , Nishimura Masaki , Nagai Ken H. 
Published: February 2019

AbstractUnderstanding physical rules underlying collective motions requires perturbation of controllable parameters in self-propelled particles. However, controlling parameters in animals is generally not easy, which makes collective behaviours of animals elusive. Here, we report an experimental system in which a conventional model animal, Caenorhabditis elegans, collectively forms dynamical networks of bundle-shaped aggregates. We investigate the dependence of our experimental system on various extrinsic parameters (material of substrate, ambient humidity and density of worms). Taking advantage of well-established C. elegans genetics, we also control intrinsic parameters (genetically determined motility) by mutations and by forced neural activation via optogenetics. Furthermore, we develop a minimal agent-based model that reproduces the dynamical network formation and its dependence on the parameters, suggesting that the key factors are alignment of worms after collision and smooth turning. Our findings imply that the concepts of active matter physics may help us to understand biological functions of animal groups.
A lipid gating mechanism for the channel-forming O antigen ABC transporter
Authors: Caffalette Christopher A. , Corey Robin A. , Sansom Mark S. P. , Stansfeld Phillip J. , Zimmer Jochen 
Published: February 2019

AbstractExtracellular glycan biosynthesis is a widespread microbial protection mechanism. In Gram-negative bacteria, the O antigen polysaccharide represents the variable region of outer membrane lipopolysaccharides. Fully assembled lipid-linked O antigens are translocated across the inner membrane by the WzmWzt ABC transporter for ligation to the lipopolysaccharide core, with the transporter forming a continuous transmembrane channel in a nucleotide-free state. Here, we report its structure in an ATP-bound conformation. Large structural changes within the nucleotide-binding and transmembrane regions push conserved hydrophobic residues at the substrate entry site towards the periplasm and provide a model for polysaccharide translocation. With ATP bound, the transporter forms a large transmembrane channel with openings toward the membrane and periplasm. The channel’s periplasmic exit is sealed by detergent molecules that block solvent permeation. Molecular dynamics simulation data suggest that, in a biological membrane, lipid molecules occupy this periplasmic exit and prevent water flux in the transporter’s resting state.
Flagellar cAMP signaling controls trypanosome progression through host tissues
Authors: Shaw Sebastian , DeMarco Stephanie F. , Rehmann Ruth , Wenzler Tanja , Florini Francesca , Roditi Isabel , Hill Kent L. 
Published: February 2019

AbstractThe unicellular parasiteTrypanosoma bruceiis transmitted between mammals by tsetse flies. Following the discovery that flagellar phosphodiesterase PDEB1 is required for trypanosomes to move in response to signals in vitro (social motility), we investigated its role in tsetse flies. Here we show that PDEB1 knockout parasites exhibit subtle changes in movement, reminiscent of bacterial chemotaxis mutants. Infecting flies with the knockout, followed by live confocal microscopy of fluorescent parasites within dual-labelled insect tissues, shows that PDEB1 is important for traversal of the peritrophic matrix, which separates the midgut lumen from the ectoperitrophic space. Without PDEB1, parasites are trapped in the lumen and cannot progress through the cycle. This demonstrates that the peritrophic matrix is a barrier that must be actively overcome and that the parasite’s flagellar cAMP signaling pathway facilitates this. Migration may depend on perception of chemotactic cues, which could stem from co-infecting parasites and/or the insect host.
Double helical conformation and extreme rigidity in a rodlike polyelectrolyte
Authors: Wang Ying , He Yadong , Yu Zhou , Gao Jianwei , ten Brinck Stephanie , Slebodnick Carla , Fahs Gregory B. , Zanelotti Curt J. , Hegde Maruti , Moore Robert B. , Ensing Bernd , Dingemans Theo J. , Qiao Rui , Madsen Louis A. 
Published: February 2019

AbstractThe ubiquitous biomacromolecule DNA has an axial rigidity persistence length of ~50 nm, driven by its elegant double helical structure. While double and multiple helix structures appear widely in nature, only rarely are these found in synthetic non-chiral macromolecules. Here we report a double helical conformation in the densely charged aromatic polyamide poly(2,2′-disulfonyl-4,4′-benzidine terephthalamide) or PBDT. This double helix macromolecule represents one of the most rigid simple molecular structures known, exhibiting an extremely high axial persistence length (~1 micrometer). We present X-ray diffraction, NMR spectroscopy, and molecular dynamics (MD) simulations that reveal and confirm the double helical conformation. The discovery of this extreme rigidity in combination with high charge density gives insight into the self-assembly of molecular ionic composites with high mechanical modulus (~ 1 GPa) yet with liquid-like ion motions inside, and provides fodder for formation of other 1D-reinforced composites.
MiR-135 suppresses glycolysis and promotes pancreatic cancer cell adaptation to metabolic stress by targeting phosphofructokinase-1
Authors: Yang Ying , Ishak Gabra Mari B. , Hanse Eric A. , Lowman Xazmin H. , Tran Thai Q. , Li Haiqing , Milman Neta , Liu Juan , Reid Michael A. , Locasale Jason W. , Gil Ziv , Kong Mei 
Published: February 2019

AbstractPancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human cancers. It thrives in a nutrient-poor environment; however, the mechanisms by which PDAC cells undergo metabolic reprogramming to adapt to metabolic stress are still poorly understood. Here, we show that microRNA-135 is significantly increased in PDAC patient samples compared to adjacent normal tissue. Mechanistically, miR-135 accumulates specifically in response to glutamine deprivation and requires ROS-dependent activation of mutant p53, which directly promotes miR-135 expression. Functionally, we found miR-135 targets phosphofructokinase-1 (PFK1) and inhibits aerobic glycolysis, thereby promoting the utilization of glucose to support the tricarboxylic acid (TCA) cycle. Consistently, miR-135 silencing sensitizes PDAC cells to glutamine deprivation and represses tumor growth in vivo. Together, these results identify a mechanism used by PDAC cells to survive the nutrient-poor tumor microenvironment, and also provide insight regarding the role of mutant p53 and miRNA in pancreatic cancer cell adaptation to metabolic stresses.
Morphologic determinant of tight junctions revealed by claudin-3 structures
Authors: Nakamura Shun , Irie Katsumasa , Tanaka Hiroo , Nishikawa Kouki , Suzuki Hiroshi , Saitoh Yasunori , Tamura Atsushi , Tsukita Sachiko , Fujiyoshi Yoshinori 
Published: February 2019

AbstractTight junction is a cell adhesion apparatus functioning as barrier and/or channel in the paracellular spaces of epithelia. Claudin is the major component of tight junction and polymerizes to form tight junction strands with various morphologies that may correlate with their functions. Here we present the crystal structure of mammalian claudin-3 at 3.6 Å resolution. The third transmembrane helix of claudin-3 is clearly bent compared with that of other subtypes. Structural analysis of additional two mutants with a single mutation representing other subtypes in the third helix indicates that this helix takes a bent or straight structure depending on the residue. The presence or absence of the helix bending changes the positions of residues related to claudin-claudin interactions and affects the morphology and adhesiveness of the tight junction strands. These results evoke a model for tight junction strand formation with different morphologies – straight or curvy strands – observed in native epithelia.